Oxaloacetate is an important metabolic intermediate in the energy pathway of the mitochondria. Recent case studies support the use of oxaloacetate as a nutritional supplement to help regulate blood glucose levels, potentially support longevity and protect the brain.

Can you get similar beneficial results from a nutritional supplement as you can from a water fast (previously discussed in episode 16 and episode 28)? Oxaloacetate supplements (also discussed in this episode with Bob Troia) are currently being studied for their use in improving blood sugar regulation and potential anti-aging properties.

…through the clinical trial that was done. We know that 100mg [of oxaloacetate] was effective in reducing fasting glucose levels in diabetics.
– Alan Cash

Alan Cash is a physicist who has spent years researching the effects of oxaloacetate. Through his efforts and travels he has seen great success for terminally ill patients and more who use oxaloacetate to supplement their health. Cash helped stabilize the molecule so that it could be used as a nutritional supplement and continues to advocate and study its use so that more research and clinical trials can continue to support its use.

In this interview we get into the nuts and bolts of how oxaloacetate works, the current studies underway, and some different ways you can use it depending on what benefits you are seeking.

The episode highlights, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know what you think in the comments!

itunes quantified body

What You’ll Learn

  • The implementation of a calorie restriction diet may work to consistently increase your lifespan and reduce any age related diseases (6:19).
  • Calorie restriction seems to affect the energy pathway of the cell (9:20).
  • We can essentially “bio-hack” our systems by tricking the cells into thinking that the NAD to NADH ratio is high so that fat production is reduced (12:50).
  • Human trials have shown that calorie restriction reduces fasting glucose levels and atherosclerosis (13:46).
  • Reducing age related diseases will increase the average lifespan and increase the maximum lifespan for every cell in the body (14:32).
  • Oxaloacetate is an important metabolite involved in one of the energy pathways in the mitochondria, the power house of a cell (16:20).
  • Oxaloacetate is used in the Kreb’s cycle to oxidize NADH to NAD (17:09).
  • A human clinical trial in the 60’s demonstrated that the use of oxaloacetate as a nutritional supplement reduced Type 2 Diabetes symptoms (20:00).
  • As the dosage increases from the minimum 100 mg other system processes occur, such as the reduction of high glutamate levels, which is one of the damaging factors for closed head injury/stroke victims (22:33).
  • A medical food called CRONaxal contains a large dose of oxaloacetate which, when used in conjunction with chemotherapy, can reduce tumor size and sometimes stop tumor growth completely in patients with brain cancer (26:07).
  • Fasting/a calorie restricted diet is another technique that has been shown to slow brain tumor growth (27:53).
  • Some cancer patients have already seen results with oxaloacetate supplementation and calorie restriction diets, however these are just individual cases and not clinical trials (28:46).
  • Recently, clinical trials have begun to study oxaloacetate as a treatment for different conditions such as mitochondrial dysfunction, Parkinson’s disease, and Alzheimer’s disease (30:13).
  • Oxaloacetate may also work well to reduce inflammation and increase neurogenesis in the brain (32:30).
  • Oxaloacetate may also become an important supplement for athletes who encounter severe head injuries during their sport (34:30).
  • Long term potentiation, the restoration of the ability to learn, may improve for patients after a stroke or closed head injury if oxaloacetate is used in combination with acetyl-l-carnitine (36:18).
  • Alan Cash spent years proving to the FDA that there do not seem to be any negative effects found with taking large doses of oxaloacetate (38:35).
  • So overall, oxaloacetate has an immediate pharmacological effect on the glutamate in the brain and a long term genomic effect on the mitochondria (46:30).
  • When trying your own experiment, take a daily fasting glucose level for a couple weeks to see the normal variability and then follow with oxaloacetate supplementation along with daily reading of your glucose levels (48:06).
  • The biomarkers Alan Cash tracks on a routine basis to monitor and improve his health, longevity and performance (55:29)
  • Alan Cash’s one biggest recommendation on using body data to improve your health, longevity and performance (58:49).

Alan Cash

  • Terra Biological: Alan Cash’s company which produces the stable form of oxaloacetate.
  • Oxaloacetate supplementation increases lifespan of C. elegans: The original study published by Alan Cash on PubMed.
  • : you can contact Alan Cash with questions using this email address.

Tools & Tactics

Supplements & Drugs

Oxaloacetate is available in a few versions in the market today – all of these come from Alan Cash’s company since he developed the proprietary method to thermally stabilize it and as such make it usable. A number of studies on Oxaloacetate were mentioned in this interview – see the complete PubMed list here.

  • benaGene Oxaloacetate: The nutritional supplement (100mg) version of Oxaloacetate to promote longevity and glucose regulation.
  • CRONaxal Oxaloacetate: This version of oxaloacetate is a medical food (containing oxaloacetate) which, when used with other treatments such as chemotherapy, has been shown to significantly improve outcomes and quality of life for cancer patients.
  • Aging Formula Oxaloacetate: Dave Asprey’s supplement is the same as the benaGene version of Oxaloacetate.
  • Acetyl-l-Carnitine: Mentioned with respect to a study where a combination of oxaloacetate and acetyl-l-carnitine reduced long term potentiation impairment in rats.
  • Metformin: A drug which is used to improve blood sugar regulation in diabetes. Researchers are looking at its wider applications as a knock on effect from improving blood sugar regulation to cancer and aging.

Diet & Nutrition

  • Calorie restriction: this dietary regimen involves a significant decrease in daily calorie intake and has been shown to slow the aging process as described in this review article. You can learn more about the potential benefits and the arguments against the anti-aging benefits of calorie restriction in episode 14 with Aubrey De Grey.
  • Fasting: The fasts referred to in this episode were complete water fasts that were also being used in combination with oxaloacetate in order to attempt to “stack” the effects and get better outcomes. The examples given were case studies of cancer patients (no clinical trials have been completed as yet). For more information on fasting as a possible cancer treatment see episode 16, and episode 28 on our water fasting self-experiment.
  • Calorie Restricted Ketogenic Diets: In a similar light to above, the anecdotal cases discussed for cancer were patients use of ketogenic diets (that put you into ketone metabolism, by restricting carbs and protein, and emphasizing fat) which were also calorie restricted. This involves stacking two nutritional strategies: ketogenic diets have been shown to be therapeutic for some conditions like alzheimers and blood sugar regulation related problems as has calorie restriction in general. Then some of these cases were also combining the use of oxaloacetate, again to try to stack the effects from these three tactics to further improve outcomes. See episode 7 for complete details on using ketogenic diets as a tactic to improve health.

Tracking

Biomarkers

  • Blood Glucose Levels (mg/dL): A measure of the level of glucose in the blood at one point in time. Fasting blood glucose levels are specifically taken when you have not eaten for at least 8 hours and optimally would be between 75 and 85 mg/dL. Health concerns with blood sugar regulation such as diabetes risk start to rise over 92 mg/dL. After taking oxaloacetate for many weeks Alan Cash suggests that your fasting blood glucose should vary less when compared with any control levels. These levels can be measured at home using a glucose monitor and glucose testing strips (an explanation for the use of glucose monitors can be found in this episode).

Other People, Books & Resources

People

  • Hans Adolf Krebs: Krebs is best known for his discovery of the citric acid cycle, or Kreb’s cycle, which is the main energy pathway of a cell.
  • Dominic D’Agostino: Well known for his work with ketogenic diets and performance.

Organizations

  • Calorie Restriction Society: This organization is dedicated to the understanding of the calorie restriction diet by researching, advocating, and promoting the diet through regular conferences, research studies, and forums.

Other

  • Kreb’s Cycle: oxaloacetate is one of the components involved in this energy pathway in the mitochondria of a cell.
  • NAD/NADH: the effects of oxaloacetate in the Kreb’s cycle changes the ratio of NAD and NADH in the mitochondria which in turn affects the energy available to the cell.
  • Orphan Drug Act: This law passed in the US in 1983 has provided more opportunities for researchers and physicians to pursue drug development for rare, or “orphan”, disorders.
  • Calorie restriction PubMed results

Full Interview Transcript

Click Here to Read Transcript

[Damien Blenkinsopp]:Alan, thank you so much for joining the show today.

[Alan Cash]: Oh, thanks. It’s always a thrill to talk about oxaloacetate.

[Damien Blenkinsopp]: First of all, I’d just like to get a bit of background story as to why you got interested in this at first. What’s the story, basically, behind how you got interested in oxaloacetate, and started getting involved with it?

[Alan Cash]: That’s a pretty weird story.

It turns out I had a brain condition where nerves sometimes grow very close to arteries. I had an artery that wrapped around my nerve. Every time my heart beat it acted like a little saw and eventually cut in through the myelin sheath that surrounds the nerve and protects the nerve, and went directly into a nerve bundle that was a major nerve bundle in my neck. And the result was instantaneous pain.

I found out that I was very lucky; I was able to get it corrected. They just went into the back of my head and followed the nerve until they could find where it crossed over, and they untangled it and put in a piece of Teflon. So now I don’t stick, but the pain is 100% gone, which is really nice. A miracle of modern science, because it was pretty terrible.

In looking up this condition, I found that it was really a condition of aging. As we grow older, your arteries get about 10 to 15 percent longer, even though we’re not getting 10 to 15 percent longer. So they have to fold over, go someplace, and it was just bad luck that it folded over next to this nerve.

As a physicist I thought I’d look into aging and see, whats the current state of what we can do about aging. And thankfully at that time there was a lot going on with the basic fundamentals of aging and trying to understand this, and looking at all the data that’s out there. That’s what physicists do; we take a huge amount of data and see where the kernels of truth are. We try to think of E=MC2, or F=MA, how much that describes about the universe.

And looking at the aging literature, the thing that stood out the most is almost nothing works, which is disappointing. The one thing we did find that worked consistently throughout the animal kingdom was calorie restriction. That was discovered back in 1934 in Cornell University.

It’s not just the diet. It’s essentially establishing a baseline of what you’d eat if you had all the food available, and then backing off that baseline anywhere from 25 to 40 percent. And when you do that consistently over a long period of time, we see several things. One, we see an increase in lifespan. Not just average lifespan of the group, but the maximal lifespan is also increased.

For small animals that live short times, that could be anywhere from 25 to 50 percent increases. In primates, we’ve seen an increase in lifespan of about 10 to 18 percent, depending upon the test. So we’re thinking in humans, we’ll probably see something in that range if you calorie restrict your whole life.

The other things we see though are a reduction in age related diseases, such as cancer. Our animal models indicate that incidence of cancer is 55 percent less in animals that calorie restrict. And that’s one of the most effective methods we have of preventing cancer, that we know of.

Incidence of neurodegenerative diseases such as Parkinson’s and Alzheimer’s are either reduced or greatly delayed. Incidences of any kind of autoimmune type issue, or inflammation issues. So it’s very, very powerful this concept of calorie restriction, and it wasn’t until just recently that we figured out molecular pathways of why it’s working.

[Damien Blenkinsopp]: So, in terms of the actual mechanisms for what’s going on in the body when we calorie restrict, what happens? What is it that creates these benefits and these changes in our biology, versus disease, and longevity in general?

[Alan Cash]: We’ve been looking at that for a long time as a question, and some of the things that we looked at were does it matter if it’s the calorie restriction with fats, or does it matter if it’s just carbohydrates or proteins. And what we’ve seen is it’s pretty much across the board ‘calories’.

There are various diets out there – there’s a new diet every week it seems like – that looks at restricting one form or another of calories, or fats, or proteins, or even specific components of proteins. But what we’ve seen in general in calorie restriction is it’s the number of calories.

So, based on that it seems like it’s an energy proposition, and looking at the energy pathways there’s been focus on the ratio of two compounds that are pretty much the same. Nicotinamide adenine dinucleotide, or NAD, and it’s reduced version NADH. So that ratio, which is also known as the redox of the cell, is looking at the energy of the cell. And when we have a very high NAD to NADH ratio, we see effects very similar to calorie restriction.

[Damien Blenkinsopp]: So in terms of what that’s actually doing, do we understand why the changes in NADH create this change in our biology?

[Alan Cash]: You know we’ve been able to trace this, and what we see is increasing the NAD to NADH ratio – and you can do that through a variety of ways – but that increase is measured by a protein called AMP protein-activated kinase, or AMPK. What AMPK does is it monitors, essentially, the NAD and NADH ratio, or the redox of the cell.

Think of it as a see-saw, so with AMPK as the fulcrum of the see-saw and NAD on one side and NADH on the other side. When the see-saw is in one position, AMPK will then act with other proteins that translate to the nucleus and turn on genes. When the see-saw is in a different position, AMPK will work with other proteins that translate to the nucleus and turn on different genes.

So let me give you a specific example. If you’ve had a lot to eat, your NAD to NADH ratio will be low. And AMPK will turn on genes that help with fat storage and production, because you’ve got all this extra energy, so hey let’s store some of it. So it will actually start producing proteins that deal with fat storage and synthesis.

On the other hand, if the see-saw is in the different position, if you haven’t had a lot to eat, there’s no point in storing fat. And so your genes will not be making these proteins that assist in making fat production. So how can we use that information?

For instance, when we trick the cells into thinking that the NAD to NADH ratio is high – or that the animal hasn’t had a lot to eat even if it has – we can slow down the rate of fat production, which could be interesting for people on diets. What we see is that you still gain some fat, but you just don’t gain it as fast.

So, biochemically, there are reasons why when you go on a diet and you lose all that weight, and you stop the diet and you rebound back very quickly. We can slow down the rate of rebound if we can keep the NAD to NADH ratio up high, because then the genes that are produced that create and store fat aren’t being produced. So there’s some really neat tricks that we can use to bio-hack into our systems that are existing systems.

[Damien Blenkinsopp]: Yeah, yeah. There are quite a few potential benefits to calorie restriction. We’ve come across some of these before. We’ve spoken with Dr. Thomas Seyfried about purposefully doing fasting for this kind of work as well.

What are kind of list the main big areas which people have seen this impact, like diabetes. What have you seen in your area, areas where people are meaningfully impacting this area with calorific restriction?

[Alan Cash]: We’ve actually done human trials in calorie restriction, and what we see is a reduction in fasting glucose levels. We also see a reduction in atherosclerosis, which, considering heart disease is the number one killer in America, if we can reduce that you’re going to have people living longer. That alone is huge.

[Damien Blenkinsopp]: So that just begs the question, when people are doing these estimates of longevity, is it because you’re reducing the risk of many of the kind of diseases that kill us – like cancer and neurological disorders, and heart disease – that people are living longer, and therefore you’re getting a higher longevity score? Or are they kind of separate topics?

[Alan Cash]: It’s both, actually.

Reducing these diseases is going to bring up the average increase in survival. So that would give you your average increase in lifespan. But there are certain people who don’t get these diseases, and they live a long time. But calorie restriction has been able to increase the maximal amount of lifespan. So that’s making every cell in your body live longer.

And we see that in our animal tests. For instance we started off working with these little worms called C elegans, which are used a lot in research because we understand, somewhat, the genetics of them. And one of the interesting things about these worms is once they go into adulthood, they don’t produce any more cells. That’s it.

They only live for about 30 days, but they live with the cells that they have. So if we can extend their lifespan, it means that we’re allowing each of their cells to live longer, and to be functional for longer. And when we increase the NAD to NADH ratio in C elegens, we see up to a 50 percent increase in lifespan.

So, as I said, it’s both. It’s eliminating a lot of these diseases that are associated with aging. I mean, think of all the diseases that you get when your old that you don’t get when you’re seven years old.

[Damien Blenkinsopp]: So, I’m sure you’re aware of Aubrey de Grey? We had him on the podcast previously talking about his seven areas of aging, which are basically diseases of aging. So he’s looking at it from that perspective. So, in terms of oxaloacetate, which is the mechanism you were using to generate that, where does it actually come from? What is it?

[Alan Cash]: Well, it’s a human metabolite. It’s in something called the Krebs cycle, which is what gives us power in our little mitochondria. So, mitochondria can be thought of like a little power plant. Glucose is the fuel for the power plant.

So the more mitochondria you have, the more power plants you have, but you have to also have the fuel, the glucose, to up-regulate that. So oxaloacetate is one of those critical components within the mitochondria. So it’s in every cell of your body already.

Now, when we give it to animals, the reason we started looking at oxaloacetate is in looking at our energy pathways, oxaloacetate can break down into malate, which is another metabolite. It’s found in excess in apples. And as part of that reaction, it takes NADH and turns it into NAD.

[Damien Blenkinsopp]: So it takes it from reduced into the oxidized form?

[Alan Cash]: Yes, and so in doing that, because you’re taking something from the denominator and putting it in the numerator, it changes the ratio very rapidly. The first person who measured this ratio change was Krebs himself, back in the 60’s. He added oxaloacetate to the cells and he saw a 900 percent increase in the NAD to NADH ratio in two minutes. So, huge changes with this human metabolite oxaloacetate.

Now, oxaloacetate has got some problems. It’s not very stable, it’s highly energetic. Commercially it’s available through chemical suppliers, but you have to store it at -20 degrees Celsius. If you want to make popsicles out of it, you could probably do that. But putting it into a usable supplement has been very difficult, and that’s why you don’t see it very often.

We came up with a method to thermally stabilize it so that it can be stored at room temperature for a period of up to two years without degrading. And that’s how we were able to introduce this into the market.

[Damien Blenkinsopp]: Great. So, in terms of where it comes from, in my understanding it’s also something that is part of foods. So there are foods which have oxaloacetate in it, so it’s basically a nutrient that’s found in the environment?

[Alan Cash]: Yes. Absolutely. Although it’s only found in very, very small amounts. There are some foods that have higher amounts of oxaloacetate, and these are foods that typically have higher amounts of mitochondria.

So, for example, pigeon breast has a lot of oxaloacetate in it because you need tremendous amounts of mitochondria to power flight. That’s what one of the most energy intensive things out there, is flying around. But you need about 18 to 20 pigeons breast to get the amount of oxaloacetate that we see as the minimum for seeing some of the gene expression changes we want to accomplish. So it takes a lot of pigeons.

[Damien Blenkinsopp]: So you’ve determined the minimum effective dose, which is around how much?

[Alan Cash]: So far – and this is from a human clinical trial – one of the side effects of calorie restriction in primates is it eliminates Type 2 diabetes, which is a good thing. And it turns out they, in trying to mimic calorie restriction – which is what we’re trying to do is turn on the same molecular pathways – we looked at oxaloacetate, and there was a clinical trial that was done back in the 60’s in Japan.

This was published, and it showed that oxaloacetate reduced fasting glucose levels in diabetics. So, we knew that this is one of the side effects of the calorie restricted metabolic state, and we could look at, in humans, what is the most effective dose.

And what we found is they did a range in this clinical trial of 100mg to 1000mg. There were no side effects in the 45 day trial. 100 percent of the people saw a reduction in their fasting glucose levels, which was good because they were all diabetics. We couldn’t understand why this wasn’t commercialized back in the 60’s.

So I actually flew to Japan to interview the department that was responsible for this clinical trial. The conversation went something like this, “Hi. I’m Alan Cash, your department produced this paper on oxaloacetate working in diabetics to reduce fasting glucose levels. Where’s the follow-on work?”

They said, “Well there is no follow-on work.” And I said, “Well why not?” They said, “Well because it’s a natural ingredient.” And I said, “Yeah it’s not only natural, it’s a human ingredient. So toxicity is extremely low.” And they said, “Yes, but we can’t get a patent on it.” And that was pretty much the end of the conversation.

So, as far as knowing the dosing and what’s effective, we already have a clinical trial showing where the minimum effect is, which is 100mg, which is where we set our sights to put out a nutritional supplement.

[Damien Blenkinsopp]: Yeah.

So, was there any advantage for the people, if we take the most extreme example, the people taking 1000mg in that study, was there any advantage to it? Did it impact blood sugar regulation differently?

[Alan Cash]: Yeah, well actually, as the dosage increases, we start looking at other reactions that oxaloacetate are involved in. And one of the main other reactions is the combination of oxaloacetate with glutamate. So, oxaloacetate and glutamate link together and that reduces glutamate levels in the brain.

Now that can be important for certain people. For instance, in a closed head injury, 20 percent of the damage to your brain is caused by the actual strike to the head, the damage to the tissue. 80 percent of the damage is caused by the aftereffects. And those after effects are in your brain it releases something called a glutamate storm.

Glutamate is one of those essential brain chemicals that you need to function properly, but if you get too much of it it excites the neurons to the point where they die. So this glutamate storm is responsible for about 80 percent of the damage.

And what they’ve been able to show now with oxaloacetate is primarily in tests over in Europe – the Weizmann institute out of Israel is doing a lot of this work, and there’s also some people in Hungary and Spain that are doing quite a bit of work with oxaloacetate. But they’re able to show that oxaloacetate, if you can get it to a stroke victim or a closed head injury victim within two hours, 80 percent of the damage is eliminated.

[Damien Blenkinsopp]: Wow. What, do they just take a small dose, or what does it have to be?

[Alan Cash]: No, you’ve got to take a lot, because you have to get it into your bloodstream, and if you take, let’s say, two 100mg capsules of oxaloacetate we’ve seen the data in the bloodsteam, only about five percent gets through. The rest of it is used up in the liver and intestines. That’s not a bad thing, because you want to keep those things healthy. But to get it so that it starts reducing glutamate levels in the brain you want to increase it’s supply in the bloodstream, and so you’ve got to take a lot.

[Damien Blenkinsopp]: So, basically after that is it always five percent? If I take 1000mg, is it just going to be 15mg?

[Alan Cash]: We don’t know. There may be a point where you start overloading the liver and more passes through. I can tell you that we have a medical food that is directed towards people with brain cancer, because if we can reduce the glutamate levels in the brain we see better results.

[Damien Blenkinsopp]: Because people, just to get back to it, is it that people with brain cancer tend to die from glutamate toxicity? Is that one of the main mechanism for their death? Or is it acting on other dimensions?

[Alan Cash]: Well, one of the main predictors of survival is the amount of glutamate that’s produced because what the tumor does is it produces tremendous amounts of glutamate, and it kills the surrounding tissues so that the tumor can grow into that area. So, if you can stop that, you don’t kill the tumor, you just stop it growing.

And this is essentially what we’re seeing with the product called CRONaxal, which is a medical food [that] is a high, high dosage oxaloacetate. So you may take the equivalent of 30 to 60 capsules of the nutritional supplement per day, and we’re seeing in animal tests a 237 percent increase in survival.

So FDA gave us an Orphan Drug designation for oxaloacetate for brain cancer. In the actual human work, we’re just doing case studies right now, but in the 17 case studies that we have MRI data on, the oxaloacetate was in conjunction with chemotherapy. So you use them together, it was able to stop tumor growth, or reduce tumor size, in 88 percent of those patients.

[Damien Blenkinsopp]: Wow, so that’s pretty great statistics there.

[Alan Cash]: Yeah, considering some of these people with glioblastoma, their tumors were growing at a rate of 80 percent per month. You can do the math there, it’s not a great equation.

And we were able to bring that growth rate to, in one guy’s case – he was 42 years old, two kids, a nice guy – we were able to bring that growth rate to zero for eight months. That’s very significant when chemotherapy alone only increases survival by a month and a half.

[Damien Blenkinsopp]: Wow, right. So, you were also saying earlier, we were just discussing you looking at combining oxaloacetate with fasting. We spoke to Dr. Thomas Seyfried about this recently, and you may be seeing potentially better results with that? Or it might be–

[Alan Cash]: Well what we’ve seen so far, fasting is one of the techniques used in brain cancer to slow or retard the growth of the tumor. It’s one of the few things that has been shown to work, especially a calorie restricted ketogenic diet, where you eat more fats.

And the thinking behind that is that you reduce glucose levels tremendously with the ketogenic diet, and glucose is one of the things that feed the tumor. Now, the other thing that feeds the tumor, according to Dr. Seyfried, could be glutamate. And so if we can reduce glutamate levels also with oxaloacetate, we may see some impressive results.

And we’re already starting to see that in anecdotal cases in patients. We had one young man who had a slow growing brain tumor that’s been able to stop it’s growth with a combination of calorie restriction and oxaloacetate supplementation with our CRONaxal product for a period of two years now.

[Damien Blenkinsopp]: Wow. And so is he taking around 6000…

[Alan Cash]: No, his tumor is slower growing, so he’s taking about the equivalent of 10 capsules a day.

We’ve also had recently a woman with Stage 4 breast cancer. Her latest report from her PET scan and her MRI data, they can no longer find the tumor, or tumors; she had like four of them. And all she was doing was calorie restriction and about 10 capsules of oxaloacetate.

There’s some real promise here, but it’s very early on. We don’t have the clinical trial data that supports this in a statistically significant manner, we just have individual cases. Although those individual cases are stunning, it would not be prudent to rely upon those cases.

[Damien Blenkinsopp]: Right. Well, have you got any plans to have any clinical trials? Was that something that might be occurring soon in that area?

[Alan Cash]: Yeah, well we’re actually in clinical trial for a variety of conditions. One is mitochondrial dysfunction. There are certain people that are born with genetic defects that affect the mitochondria.

We have one infant that’s been on oxaloacetate now for nine months that is showing normal development, whereas normally with this type of defect we would expect the infant to have passed away six months ago. So that’s pretty interesting.

We’re also in clinical trial for Parkinson’s disease because anecdotally we’ve seen some interesting cases where the oxaloacetate has reduced the symptoms of Parkinson’s disease. And lastly, we’re in clinical trial for Alzheimer’s disease, so we’ll see how those all play out.

We’re getting ready to start some clinical trial work in pediatric brain cancer, because if we can get away from doing chemotherapy, it’s just a whole better quality of life.

[Damien Blenkinsopp]: It sounds like one of the main mechanisms. So if you’re looking at Alzheimer’s disease, they also use ketogenic diets, and so it’s obvious that the glutamate is helping, but do you think it’s also the aspect of improving blood sugar regulation is potentially helping in all these diseases as well? Is that one of the factors?

[Alan Cash]: It certainly could be a factor. We just published a paper in human molecular genetics that showed that oxaloacetate increased the amount of glucose that the cells could uptake in the brain, it increased the number of mitochondria in the brain. So we not only built more power plants, but we’re now having a way to fuel those power plants.

The interesting thing is that oxaloacetate is also a ketone. So you don’t necessarily need glucose to fire off all those neurons in the brain, you can actually use oxaloacetate as a power source. So, the other things we’ve seen with oxaloacetate in the brain in animal models is a reduction in inflammation, and probably most exciting is we’ve seen a doubling of the number of new neurons that are produced.

Ten years ago we used to think that the number of brain cells you have is static, that those brain cells that you lost in college are forever gone by imbibing in too much alcohol, but now what we’re seeing is that there’s an area of the brain called the hippocampus which continues to produce new neurons. And as we age, this function decreases. So our ability to repair our brains decreases.

Well oxaloacetate in animal models doubled that rate of production, and not only did it double the rate of new neurons, but the length of the connections between the neurons was also doubled. So, if you think about, well if a neuron can connect to a neuron that’s further away you get more interesting connections, more interesting abilities to have different variables.

It makes your brain more plastic, is what we say. And oxaloacetate has been able to show both that increase in neurons and the length of the neurons. So it’s pretty exciting work.

[Damien Blenkinsopp]: Yeah, so brain injuries – you were talking about brain injuries before – I guess a lot of us think about brain injuries as a big thing, like maybe a car crash or something, you have a big serious brain injury. But now they are also looking at athletes, for instance in football where they’ve been heading the ball and areas like that, and they’re seeing there’s a lot of damage.

So could this potentially be a tool for sports? If you’re playing in football, would it make sense to be taking this stuff whenever you’re going to a match, or something like that, to reduce the kind of damage you’re getting each time you’re heading the ball, and so on?

[Alan Cash]: I think so. I mean, my daughters play volleyball at a very high level – one’s at Pepperdine, and the other is going to be at Hofstra next year – and occasionally they get hit in the head with a volleyball. They’re middle blockers, they go up, and they just get slammed in the face. So I always have a bottle of oxaloacetate in their gym bag, and if they get hit in the head they’re told to take 10 capsules right away and to continue taking 10 capsules for the next week or so.

I don’t want to suggest that you should use oxaloacetate for any kind of disease. Mostly it’s a nutritional supplement, there is the medical food also that’s specific for brain cancer. And I just want to make that clarification that the work really hasn’t been done in clinical trial.

Now, over in Europe they are working on that. They’ve done a lot of animal studies, and the interesting thing they’ve found is that if they can get oxaloacetate into these animals that have been hit on the head with a hammer within two hours, it reduces the amount of brain damage they experience by 80 percent. They’re looking at a lot of things in Europe, and it’s very, very exciting work.

[Damien Blenkinsopp]: Yeah, it seems like this is a really interesting molecule, because it seems to be having an impact in a lot of different things. Of course, it’s all early stages of research, like you say, but it seems to have quite a lot of potential.

I saw another study where they had combined oxaloacetate with acetyl-l-carnitine and they were looking at that. Could you talk a little bit about that? I believe it was long-term potentiation it was impacting.

[Alan Cash]: Yeah, long-term potentiation is a measure of how plastic your brain is, how well you can still learn. And when they go into the brain of animal models and give them a stroke, an artificial stroke, and then measure long term potentiation, the levels drop significantly.

When they use oxaloacetate or a combination of oxaloacetate and acetyl-l-carnitine, they saw 100 percent restoration of the brain’s ability to learn again, in very short order. And this could be very important for people with stroke, closed head injuries, that type of thing.

But again, this is early work, it’s been done in animals, it’s been very successful in animals. And both oxaloacetate and acetyl-l-carnitine have very low toxicity profiles, so the risks are low there, but we still need to do this in clinical trial and make sure that there are no unexpected results in humans.

[Damien Blenkinsopp]: Right. Yeah, so ALCAR or acetyl-l-carnitine, a lot of people I know have been taking it for a very long time. So in terms of toxicity for oxaloacetate, as you said there was the trials where you had 1000mg per day. Has anything above that been tested? Because it sounds like with some people you’re actually giving 10,000 or more in specific cases.

So, in terms of toxicity, is there any evidence to say that it could be harmful in any way if someone overdoses, or potentially someone in a specific situation?

One thing I was just thinking about while you were talking was in terms of glutamate, you say it helps to deactivate glutamate. In some people who are normal and have normal levels of glutamate, could that impact them in any way in terms of their brain performance, memory, things like that?

[Alan Cash]: That was a multiple question, and let me address them one at a time.

[Damien Blenkinsopp]: I’m sorry.

[Alan Cash]: As far as toxicity, in order to bring the supplement into the United States we had to prove to the FDA safety because this is considered a new dietary ingredient, even though it’s in just about every food we eat but not at the levels that we’re giving it to people at. So we had to prove safety, and we spent quite a bit of money and three years of my life proving safety to the FDA.

One of the things we had to do is feed animals as much oxaloacetate as we could stuff into them to see at what point in time 50 percent of the animals would die. And what we found out is we got up to about 5000mg per kilogram of body weight in animals, and we still couldn’t get any of them to die.

[Damien Blenkinsopp]: Did you get any negative reaction at all?

[Alan Cash]: We couldn’t find one. Now, what we are seeing in humans, especially in some of these people with brain cancer that are taking the equivalent of about 60 capsules a day, we do see an increase in burping.

[Damien Blenkinsopp]: That’s interesting. It’s kind of random.

[Alan Cash]: Yeah, well it relaxes the upper sphincter muscle in the stomach, and we see an increase in burping in some of the people.

[Damien Blenkinsopp]: That’s interesting.

[Alan Cash]: But that’s about all we’ve seen so far. So, from a toxicity standpoint, this appears to be a very safe molecule.

[Damien Blenkinsopp]: Well, that’s great. Do you remember the multi-part question, or shall I repeat it?

[Alan Cash]: Yeah, the second part was what if you take a lot of this and you’re just a normal person, what would you expect to see? Some of the things we’ve seen are really interesting.

We have an R&D project where we’ve developed an oxaloacetate tablet that goes under your tongue. And so we deliver a lot more oxaloacetate to the bloodstream, which preferentially reacts with glutamate. And what we see with that tablet is an increase in the ability to [unclear 40:04] because if you can turn down glutamate levels a little bit in your brain, you don’t have some of that repetitive cycling of questions, you’re able to focus more, you’re able to pay attention better.

It’s kind of like, the way I can explain it, it’s like you’ve been meditating for a half an hour, so you have this incredible focus but it’s not jittery. Like if you have 10 cups of coffee you can also have more attention, but your whole body is shaky. This is more, you’re very relaxed, and you just have that increased ability to focus. It’s pretty cool.

[Damien Blenkinsopp]: It sounds like you’ve been testing it yourself.

[Alan Cash]: Yeah I test it always on myself, because if I’m ever going to give it to somebody else you’ve got to feel confident enough in it’s effects to try it on yourself first.

[Damien Blenkinsopp]: Yeah. You know, it would be nice to hear, how do you use oxaloacetate yourself? Do you have some kind of routine, or what do you do with it?

[Alan Cash]: Yes, I use it primarily for anti-aging, because I’m after that [00:41:11 – 00:41:14:17 audio error repeated “we see an increase in burping in some of the people.”] I take like three caps a day, which is a little bit more than our recommended one cap a day, but I get it for free, so what the heck, right.

I’ve also started working with this sublingual dose whenever I’m tired. Like if I have to drive somewhere and it’s late I take one and immediately I’m awake and my focus is there. Or if I’m in a conference and its 4 o’clock on the third day of the conference I find that it helps quite a bit. So that’s how I use it.

A lot of athletes are using this now because we’ve been able to measure a decrease in fatigue and an increase in endurance. We don’t see an increase in strength, just an increase in endurance. So a lot of endurance sport people take one to two capsules about 15 minutes before competition, with about 100 to 200 calories.

[Damien Blenkinsopp]: So it sounds very quick acting, in terms of you’ve take it in and within a very short period it’s going to have that impact. Are you talking about it feeding the mitochondria, basically?

I mean, you spoke earlier about it basically being like a ketone. Do you think that’s the mechanism there, or is it because it’s stimulating the mitochondria somehow?

[Alan Cash]: Well there’s been some work out of UCSD showing that oxaloacetate activates pyruvate decarboxylase and allows the citric acid cycle to process faster. So you get more ATP production, which would tie with the endurance effect.

We’ve been able to measure the endurance effect almost immediately, and we published that in the Journal of Sports Medicine. We saw about a 10 percent increase in endurance. And you think, you know, 10 percent is not all that much, but in a lot of athletic competitions 10 percent is huge.

So that’s the short term effect, and that actually only lasts about two hours. And then if you want it again, you have to reapply.

[Damien Blenkinsopp]: Yeah. So a marathon runner would be dosing every couple of hours?

[Alan Cash]: Yeah, about every two hours.

The second effect though is longer term. We’ve seen that oxaloacetate supplementation increases the number of mitochondria, or the mitochondrial density in the cell. So it produces more of the power plants so that when you feed it more glucose, you can turn it into fuel faster.

But that takes typically, you know, anywhere from two to six weeks to see the effect on that. And you have to take it daily. What we’re doing is we’re increasing that NAD to NADH ratio, which then activates AMPK, and chronic AMPK activation has been shown to start the process of mitochondrial biogenesis, or producing more mitochondria.

[Damien Blenkinsopp]: Is there any reason we want that activated? Anything you know of like in the research, where it says like chronic activation of AMPK could lead to any downsides?

I have another question, just to kind of give you a bit of context to that. Is it worth cycling oxaloacetate? So having a month on, or a couple of months on, a couple of months off, or anything like that?

[Alan Cash]: Yeah, a lot of supplements that deal with stressing your cells in order to get an effect they work better if you cycle them. For instance, echinacea. Echinacea works because it’s an irritant. So you turn on your stress response and get a response, but if you take it all the time, your body gets used to it.

Oxaloacetate doesn’t work as a stresser, it works to turn on genes and turn on the development of more mitochondria. So no you want to take it all the time.

[Damien Blenkinsopp]: Great, and so we were discussing earlier, I was just asking you about potentially doing a lot of experiments with oxaloacetate, and you were saying that for most of the effects it’s really this aggregated, this cumulative effect.

We want to be using it for between two and six weeks before we see the effects. And then, if we stop it’s probably going to take that amount of time before those effects disappear. But they will disappear, so it’s something that you really kind of have to take on an on-going basis.

[Alan Cash]: Yeah, yeah. Because it’s, well there are two effects. One is a pharmacological effect, like for instance the reduction of glutamate in the brain. That happens almost immediately, so some people when they take this they get that feeling of peace because they’re just reducing their excitatory chemical in their brain.

But the other effect is a genomic effect, and while your genes start producing these proteins right away it takes a while for the proteins to be enough in number that we see measurable effects. We can see those effects in typically four to six weeks.

For instance, blood glucose levels would be one that we’ve been able to trace that down to activating AMPK, which is the same thing that the diabetic drug Metformin does but through a different pathway, and the up-regulation of a gene called FOXO3A, which deals with glucose stability. But that takes time, it takes usually four to six weeks.

[Damien Blenkinsopp]: So, for the people at home, if they were going to design their own little experiment, it would be basically measuring blood glucose stability, is that the main, is it the variant which is reduced, or is it actually lowered in general?

[Alan Cash]: One experiment that they could try is start off with a baseline. Go to the drugstore, get a glucose meter and some little paper strips, and take your fasting glucose levels for maybe a couple of weeks. You see the variability, because even in fasting glucose levels, you’re going to see the levels bounce all over the place.

And then start oxaloacetate supplementation, one or two capsules a day for a month, and take your daily glucose levels. You won’t see much change for about three weeks, and then what we typically see is a slight reduction – in non-diabetics – in fasting glucose levels.

And more importantly, a reduction in the swing. So you don’t see as high a high, and as low a low. And that reduction is typically on the order of 50 to 60 percent, so you have better glucose regulation. And in normal people, that’s not a bad thing.

[Damien Blenkinsopp]: Right. Just if we’re talking in terms of performance, just throughout the day I think people’s performance goes up and down. Some of the reasons people try new diets such as Paleo and Ketogenic and so on is to try and even out their blood sugar a bit more so they don’t have these typical dips people get after lunch when they need another shot of caffeine to get through the afternoon.

So I’m sure probably you can see how that could impact their performance in that way. That would be interesting.

[Alan Cash]: Yeah. Absolutely.

[Damien Blenkinsopp]: So how would you recommend someone takes oxaloacetate? Would it just be 100mg one capsule? Would it be in the morning, once daily?

What would be the recommended way to try this out, for someone who is just normal and healthy, and they’re just more interested in the long term benefits, and so on.

[Alan Cash]: For the long term benefits, we looked at the minimum amount that you could take – I believe in small measures for big effects – the minimum amount over time, and we know that through the clinical trial that was done. We know that 100mg was effective in reducing fasting glucose levels in diabetics. We’re turning on those genes that we want to turn on.

So, one capsule a day. It doesn’t matter if you take it in the morning or the evening, what does matter is that you take it every day, because we’re trying to increase that NAD to NADH ratio and keep it pretty steady, so that we continuously activate AMPK. And that continual activation is what turns on the genes and gives us the gene expression that we want to see to see extended lifespans.

[Damien Blenkinsopp]: Great, great, thank you. Are there any situations where you would recommended people – because you’re taking 300mg yourself, and obviously you don’t have the costs that other people would have – but are there other situations where you would think it would be interesting for people to take a slightly larger dose?

[Alan Cash]: Yeah, but I really can’t recommend that, as I’m not a physician, I’m a physicist.

[Damien Blenkinsopp]: Right, right. We’re getting outside of the nutritional realm again.

[Alan Cash]: Yeah, and that [can] be a dangerous thing for us to do.

[Damien Blenkinsopp]: Absolutely.

[Alan Cash]: Definitely our CRONaxal medical food for [treating] cancer, they would take a lot more oxaloacetate.

[Damien Blenkinsopp]: Great, great. If someone wanted to learn more about the topic of caloric restriction and oxaloacetate, where would you say, are there any books or presentations or is there any other resources people could look up that would help them to learn more about this?

[Alan Cash]: Absolutely. There’s quite a bit in PubMed, so they could go to www.pubmed.com, or .gov, and just type in ‘oxaloacetate’ and ‘calorie restriction’. We’ve got some papers in there that we’ve published.

And they can also look at oxaloacetate and other things like Parkinson’s, Alzheimer’s, cancer, you know, if they’re interested in that, and see what animal data there is out there right now. There’s not a lot of human clinical work done yet.

We’re in the middle of some of that ourselves. They can also email me. My email address is acash@benagene.org. I typically get back to people in a couple of days with questions.

[Damien Blenkinsopp]: Great, and I can attest to that, because we’ve been in contact before and I know you make yourself very much available, and that’s really appreciated.

Are there other ways that people could connect with you? I don’t know if you are on Twitter. You have a website, of course, which is benagene.com?

[Alan Cash]: Yeah, we have a website benagene.com. There’s not a lot of information on that because the FDA discourages that. For instance, we can’t legally put any animal data on our site, even though I consider humans animals. I think it’s relevant, but the FDA does not.

[Damien Blenkinsopp]: Right, right. Of course. So, is there anyone besides yourself that you’d recommend to learn about this topic? I don’t know, calorie restriction, longevity. Is there any interesting stuff you’ve read over the years, or have you referred people’s work?

[Alan Cash]: There’s tremendous amounts of data on calorie restriction. And there’s a society, the Calorie Restriction Society, where these people have been restricting their own calories for years, seeing tremendous results, especially in reducing atherosclerosis. In human clinical trial we’ve seen a major drop in atherosclerosis and blood pressure.

[Damien Blenkinsopp]: Do you know if that’s reflected by the CRP? The C-reactive Protein biomarker? Because you spoke about inflammation earlier, I wasn’t sure if that was that marker or another one.

[Alan Cash]: I’ve seen a decrease in inflammation in our studies really through the M4 pathway. I don’t know if C-reactive protein levels are down. We did have a case where due to a genetic dysfunction an 11 year old girl, she was in critical care, her CRP levels were up around 20,000.

[Damien Blenkinsopp]: Wow.

[Alan Cash]: Yeah, yeah. She was…

[Damien Blenkinsopp]: That’s insane.

[Alan Cash]: Yeah. Yeah. She was eating herself alive, essentially. And she was in critical care. They tried just about everything. And this was work done out of University of California San Diego Mitochondria Dysfunction Department. They’re doing some breakthrough work there.

They ended up giving her some oxaloacetate and in two days her CRP levels dropped to zero, and she was released from the hospital and went home. Once again, that’s a case of one person and specific genetic anomaly.

[Damien Blenkinsopp]: Yeah, yeah. Interesting. That’s pretty impressive.

In terms of your own personal approach to data and body data – because we’re always talking about data on this show in terms of our biologies and so on – do you track any metrics or biomarkers for your own body on a routine basis?

[Alan Cash]: Glucose levels. And for a guy, I’m 57 years old, my blood glucose levels are typically in the low 80s, which is pretty good. That’s about the only thing I track regularly. I mean I track my weight, which is very stable. I don’t count the number of hours I exercise or anything like that. I should.

[Damien Blenkinsopp]: I guess. Have you tracked your blood sugar over time? Before you started taking oxaloacetate, or is it since, so you probably wouldn’t see the effects? I’m just wondering if it would be a cumulative effect from you having taking it, I assume, for years now.

[Alan Cash]: I have been taking it since about 2007, which is when we introduced it into the Canadian market. Basically it just dropped. Initially I was up in the upper 80s to low 90s, and over time I’m just pretty much consistently in the low 80s now.

[Damien Blenkinsopp]: So you have seen some kind of steady decline, or did it decline when the genes turned on and then it stayed there?

[Alan Cash]: It pretty much declined when the genes turned on and stayed there, yeah.

Now there’s ways to lower it even further if I went to a ketogenic diet. I know some people who have been doing this, like Dominic D’Agostino. I think his blood glucose levels are down in the 40s.

[Damien Blenkinsopp]: Wow.

[Alan Cash]: Yeah. But he does a very strict ketogenic diet, and he’s feeding his cells with ketones instead of glucose.

[Damien Blenkinsopp]: Yeah, so I was interested – just before we started the interview – also in just cancer prevention, so we had Thomas Seyfried on here and he recommended a five day water fast twice a year.

So it would be interesting to combine that with the oxaloacetate. It might have a potentially beneficial upside, you know, combining those two rather than doing them separately.

[Alan Cash]: Yeah, we’re seeing that in patients now. Hopefully we’ll be able to get some funding for some clinical trials to combine calorie restriction with oxaloacetate in some of these patients. To take the science from our animal data, which is very promising, but it’s not human data. And so hopefully we can continue our research and help some people here.

[Damien Blenkinsopp]: Yeah. I’m guessing it takes quite a while to get these clinical trials going. Would you expect this to be done over the next 10 years? Is there anything that could help you with that, in terms of getting funders, or what could help to push that along faster?

[Alan Cash]: We’ve taken the unusual step in brain cancer of making oxaloacetate available for a disease through the Orphan Drug Act in the US. So this allows for various medical conditions that have scientific basis to be used for a specific disease. In this case, we’re using it for brain cancer, which is an orphan disease.

So that’s helping get the word out, get some anecdotal cases, which I’ve discussed with you a little bit, and increase the interest in getting a clinical trial out there. We’ll see how that all evolves.

[Damien Blenkinsopp]: Great, great. Thank you. Well, one last question Alan. What would be your number one recommendation to someone trying to use data, in some way, to make better decisions about their health and performance, or their longevity?

[Alan Cash]: I think that’s a great place to start. You know the benefits of calorie restriction, and so just counting calories and reducing calories where you can would be one strategy of using data to improve your health. If you keep track of that information.

Keeping track of blood glucose levels, because having lower glucose levels rather than higher glucose levels is going to positively affect your health. The amount of time you exercise.

One of the ways we’ve seen to increase the NAD to NADH ratio is chronic exercise. So calorie restriction is one way, chronic exercise is another way. A drug such as Metformin can increase your NAD to NADH ratio, or activating AMPK anyway.

And oxaloacetate as a nutritional supplement over the long term. So there are quite a few ways that you can use data and monitor your data to positively affect your health.

[Damien Blenkinsopp]: Alan, thank you so much for your time today. It’s been really amazing having you on the show with all of these interesting stories about these case studies about the work that you’ve been doing.

[Alan Cash]: Yes, and just as, again, as a disclaimer, we don’t want to recommend this nutritional supplement, which we manufacture, called Benagene, which you can get at www.benagene.com, for any disease.

Not to diagnose, treat, prevent, or cure any disease. It’s primarily, we developed this to keep healthy people healthy.

[Damien Blenkinsopp]: Great. And I take it myself too, so I’m kind of following in your footsteps there.

Well Alan thanks again for your time today, and I look forward to talking to you again soon.

[Alan Cash]: Alright, thank you very much.

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Mitochondria, the power plants of our body, get damaged through aging and other stressors. Lipid Replacement Therapy (LRT) is a tool being used to repair part of this damage to mitochondrial membranes, and can help people recover and optimize their energy levels.

The mitochondria is often described as the “powerhouse” of the cell and it supplies the energy the body needs to function properly and efficiently.

Previously, we have discussed mitochondria as related to cancer, in episode 16 with Dr. Thomas Seyfried and in episode 3 where Dr. Terry Wahls described mitochondrial health and the link to autoimmune disorders.

This episode will focus on mitochondrial function and the symptoms we experience when our mitochondria have sustained damage from either environmental factors, natural aging, or other exposures. Often this leads to general fatigue, cognitive decline, or physical decline and the effects can be seen in patients who suffer from chronic fatigue illnesses, neurodegenerative disorders, cancer and various other diseases.

Lipid Replacement Therapy (LRT) has been shown to repair the mitochondrial membrane damage and improve symptoms for many patients suffering from these chronic diseases and other natural aging symptoms.

One of the things we’ve done with the aging process is we’ve taken people that were fatigued, 90 years old plus, we’ve improved their mitochondrial function to a 30 year old. And they’ve gained all kinds of function in the process. Mental function, physical function, you name it.
– Garth Nicolson PhD

Today’s guest is Dr. Garth Nicolson who is an extremely accomplished research scientist best known for his work with Gulf War Syndrome, and Lipid Replacement Therapy (LRT). He is the president, founder, chief scientific officer, and researcher at The Institute for Molecular Medicine in Huntington Beach, CA where he conducts most of his current research.

He was the leading authority serving the United States House of Representatives on the study of the cause, treatment and prevention of Gulf War Syndrome on suspicion of biological warfare. For his service he was conferred honorary Colonel of the US Army Special Forces and honorary US Navy SEAL.

He has published over 600 peer reviewed research papers and served on the editorial boards of 30 scientific journals. In 2003 he introduced LRT and its benefits for the first time, shedding light on the importance of mitochondrial function and repair of damaged membranes and its benefits for aging, cancer and chronic disease states.

The episode highlights, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know what you think in the comments!

itunes quantified body

What You’ll Learn

  • Mitochondrial function decline is the underlying problem in many chronic diseases (6:43).
  • Mitochondria are the powerhouse of the cell providing energy – like a battery – which fuels the cell’s function (7:43).
  • Oxidative damage to the lipid membrane of the mitochondria is the most universal cause of damage (8:38).
  • Damage to the lipid membrane harms the phospholipid molecules causing “leakiness” across the membrane (11:30).
  • If you don’t produce enough energy in a cell, you lose the function of that cell (13:15).
  • Damage to the energy process in a system can occur during aging, chronic illness, viral/bacterial infection, toxic exposure, etc. (13:55).
  • Some patients have restored their endocrine systems by repairing their mitochondria in some way (15:53).
  • Chronic fatigue illnesses (chronic fatigue syndrome, fibromyalgia, etc.) are directly related to loss of mitochondrial function, which is mostly true for many other diseases as well, such as cancer and neurodegenerative disorders (16:45).
  • Much of the mitochondrial function decline occurs because of the natural aging process (18:46).
  • For instance, improving the function of a 90 year old, fatigued patient greatly improves mental and physical functions for the patient (19:01).
  • Repairing the mitochondrial function for patients who have any of these diseases is not a cure-all, however it is a step in the right direction and definitely supports the overall recovery for the patient (21:21).
  • Dr. Nicolson discusses the importance of lipid replacement therapy (LRT) as a way to replace damaged membrane phospholipids to improve mitochondrial function (22:48).
  • LRT also functions to detox and repair chemically damaged cells as the lipids delivered to the system can soak any chemicals out from the membranes and remove them from the body (27:11).
  • Dr. Nicolson works with populations who have had particular exposures however everyone has been exposed to various chemicals throughout their lifetime (31:05).
  • Using both LRT and infrared saunas can speed up the long, slow process of detoxification and recovery (32:47).
  • LRT can reduce the symptoms of detoxification and recovery; for example LRT used in conjunction with chemotherapy for cancer patients helps the patient manage the side effects of the cancer treatments (34:50).
  • Patients generally see improvement of symptoms between 10 days and 3 months after the start of LRT but when therapy is removed the mitochondrial function declines again and symptoms return (36:39).
  • Mitochondrial function can be measured directly by testing the mitochondrial membranes in the white blood cells (38:38).
  • LRT is becoming more popular especially with naturopathic doctors and individual people as you do not need a prescription to obtain these natural supplements (40:37).
  • An increased dose of lipids is crucial for patients with severe chemical damage or mitochondrial damage so luckily no one has reported negative side effects yet as lipids are natural substances of the body anyways (44:37)!
  • Cholesterol markers and homocysteine levels have been shown to improve when using LRT (45:48).
  • LRT is proving to be effective as an anti-aging treatment, a therapy for various diseases processes, and as a co-treatment option for cancer patients to reduce negative side effects and fatigue related to traditional therapies (46:29).
  • LRT works well at improving energy systems however dosages, etc. do have to be optimized to work with each person’s unique system (50:26).
  • LRT is a lifelong solution and a long term treatment because we are constantly exposed to new toxins, infections, and traumas throughout our lives (52:17).
  • The minimum supplement needed for LRT is NT factor lipids. (55:32).

Garth Nicolson PhD

Tools & Tactics

Interventions

  • Lipid Replacement Therapy (LRT): Used to restore and repair mitochondria function by replacing damaged lipids in the membrane and restoring the mitochondria’s ability to produce energy for the cell. (See relevant lipid supplements below).
  • Infrared Sauna: Used to remove fat soluble toxins in particular from the body. Garth Nicolson recommends using this along side LRT to help with the removal of chemicals from the cells, which tends to improve results.

Supplements

  • NT Factor EnergyLipids: NT Factor is the lipid based supplement that is the main component used in LRT. There are a variety of products including this one, which contain NT Factor. Read more about these on NTFactor.com, as recommended for use by Dr. Nicolson.
  • NT Factor Energy Wafers: The specific NT Factor product that is “child friendly”, as the wafers easily dissolve in the mouth and do not need to be swallowed.
  • ATP Fuel: In addition to NT Factor, this supplement also contains NADH and coenzyme Q10 which also aid in the energy production cycle in a cell.

Tracking

Biomarkers

  • Cholesterol: A cholesterol panel covers a number of markers related to lipoproteins (such as HDL and LDL) in the blood. LDL and HDL are standard markers used to track cardiovascular risk. Dr. Nicolson has seen LDL drop and HDL increase with use of LRT – which typically indicates improvement and lower cardiovascular risk.
  • Homocysteine: A marker often used to assess cardiovascular risk. Higher values relate to increase cardio risk. This marker is often related to methylation SNPs like MTHFR as discussed in episode 5 with Ben Lynch. Dr. Nicolson has seen homocysteine levels drop with LRT also.
  • Mitochondrial Membrane Potential: An approach to assessing the health and functioning of a cell’s mitochondria by looking at it’s potential or voltage. In the same way as with a battery, if it is functioning, the outer membrane of mitochondria has an electric output and thus a voltage.

Lab Tests, Devices and Apps

  • Inner Mitochondrial Membrane Potential via Rhodamine 123: The status and functioning of the mitochondria are assessed via analysis of mitochondria inside white blood cells with the dye rhodamine 123 and a fluorescence microscope (see study here). The test provides a quantitative fluorescence value indicating the health of the mitochondria and integrity of the membrane. This test is not easily accessible and is used for research purposes.

Other People, Books & Resources

Organizations

Full Interview Transcript

Click Here to Read Transcript
[Damien Blenkinsopp]: Garth, thank you so much for joining us on the show.

[Garth Nicolson]: Well it’s a pleasure to be on your program.

[Damien Blenkinsopp]: To start off with, I was really interested to find out how you first started working with mitochondrial function. Where it first came up for you, and you started taking an interest in it.

[Garth Nicolson]: Well this really goes back to our work on Gulf War veterans. And from that we did work on civilians with Chronic Fatigue Syndrome, Fibromyalgia Syndrome and related fatiguing illnesses. And one of the underlying problems in all of these – and it turns out any chronic disease – is mitochondrial function. There’s just not enough energy around to provide all the necessary high energy molecules in a cell to perform all the functions necessary.

Then you get into energy deficits, and if the energy deficits are systemic, well you can have a chronic condition with lack of energy, lack of mental alertness, all kinds of other additional problems. Because basically every cell requires energy to perform. And some cells, such as the nervous system, require a lot of it – six times what most cells require – and so they’re particularly sensitive to losses in energy function.

[Damien Blenkinsopp]: It sounds like there’s a wide variety of symptoms that could be reflecting some kind of mitochondrial function damage, or interruption. Is that the case? Is it quite a wide variety of symptoms?

[Garth Nicolson]: There are a wide variety of symptoms associated with loss of mitochondrial function. And as I mentioned before, the mitochondria provide energy to your cells. In fact, almost all the energy is provided by mitochondrial function in our cells.

If you’re breathing oxygen, you’re using that oxygen to provide it to mitochondria, so they can convert it to energy, along with other molecules that they use in the process called Electron Transport System. And it’s a complicated conversion system which converts, essentially, stores that you have in your cells to high energy molecules that you need for doing a number of different functions.

Now in different clinical conditions, we find that these people have given signs and symptoms, but often they’re also related to mitochondrial function, because a lot of these problems arise when there isn’t enough energy left for cells to perform their functions necessary, and consequently this can have profound effects.

[Damien Blenkinsopp]: Right, and what kinds of damage can interfere with mitochondrial function?

[Garth Nicolson]: Well there are a variety of different types of damage. We’ve concentrated on damage to the lipid membrane of the mitochondria, because this turns out to be the most sensitive form of damage, or the most universal form of damage that we find in mitochondria. They’re particularly sensitive to oxidative damage.

And oxidative damage can occur, for example, during infection, during high performance issues, if you get run down – for example, physically, mentally, you name it – or because of infections or other damages, disease associated damages, mitochondrial function suffers. And in order to recover from all of these, you do have to have mitochondrial function available, because you can’t repair and recover without it.

[Damien Blenkinsopp]: So are we all constantly repairing the lipid membranes, as you are talking about? Is this a constant? Because when you mentioned, for instance, high performance, could that be someone like an athlete, or someone who’s heavily into fitness? Are they constantly causing this type of damage with oxidative stress, which then has to be repaired?

[Garth Nicolson]: Well, that’s true, but it’s also true during aging, for example, where our membranes normally get damaged during aging processes. And mitochondrial membranes are particularly sensitive to aging, and as we age, they get more damaged. And so if you look at a 90 year old, many of these 90 plus year old people have lost almost half their mitochondrial function.

And a lot of that is due to accumulated damage in the mitochondria, and a lot of the damage is due to the damage to the mitochondrial membrane. And the inner mitochondrial membrane is integral to our production of energy, and if that’s damaged, they become leaky, and lose function, and they can’t maintain the trans-membrane potential, the electrical potential across the inner mitochondrial membrane, which is absolutely necessary to produce high energy molecules.

[Damien Blenkinsopp]: Right, right. Well to take a step back, when you’re talking about trans-membrane, what’s the function of the membrane in terms of generating electricity? Because basically the mitochondria are a bit like our power cells, you know our batteries, which feed our cells and the rest of our body with energy. But how do they do that, and what’s the role of the membrane in that process?

[Garth Nicolson]: Well I always liken mitochondria to the little batteries inside our cells. And like any battery, it has to be insulated to selectively permit a trans-membrane potential across different membranes in our mitochondria. It’s a biological membrane instead of a synthetic membrane that we have in batteries, but it provides the same kind of insulation necessary to separate electrical charges.

And so when this separation of electrical charges occurs, you can make a battery out of it. Essentially that battery drives the production of high energy molecules in the mitochondria just as it does in a normal battery.

[Damien Blenkinsopp]: Great. And what types of damage are we talking about when we’re talking about this membrane getting damaged?

[Garth Nicolson]: Well there’s certain molecules in the membrane. It can be the phospholipids that make up the matrix of the membrane. But when they’re damaged, there can be enhanced leakiness across the membrane. So it’s like you get a leakiness if you take the insulation off a battery it will leak, and you’ll lose the charge of the battery.

The same thing in the mitochondria. If they become leaky, and the inner membrane becomes leaky, you can lose the trans-membrane potential, and then you can’t form the high energy molecules. There are also some critical lipid molecules, like cardiolipin, that are exquisitely sensitive, in fact, to oxidative damage. And when they’re damaged, this results in loss of function. So these different types of things are very important, the direct function and the trans-membrane potential.

[Damien Blenkinsopp]: So these are different types of fat molecules that we need in the membrane for it to function optimally. And it’s kind of like holes have been punched in the surface of the membrane, and molecules have been knocked out of it? Is that a way to look at it?

[Garth Nicolson]: It’s a little more subtle than that. When oxidative damage occurs, think of the lipid chains that are going into the membrane, into the hydrophobic matrix of the membrane, you can think of kinks getting in those chains after they’ve been oxidatively damaged. And those kinks mean that the lipids can’t fit together as well, and there’s a certain rate of leakiness across the membrane.

[Damien Blenkinsopp]: Great. Is this something anyone should be concerned about, in terms of the type of damage? You just referred to a 90 year old, the damage that’s gone on to them.

What kind if symptoms could someone think of if, maybe they don’t have a chronic disease like some of the ones you referred to, but are there other indicators that potentially they have some aspect of mitochondrial damage, in terms of some symptoms they could look out for which might identify that?

You were referring to, like brain fog, or other symptoms. Are there obvious ones, or is it always very different, and it’s kind of difficult to differentiate this to other things that might be going on?

[Garth Nicolson]: Well, obviously a number of different factors can cause problems with your central nervous system, for example, your peripheral nerves and other systems of your cells, but one of the things that can happen is that if the energy systems inside the cells get run down, they don’t function as well. It’s as simple as that.

So if you don’t produce enough energy in your cells, your cells can’t function as well. So all the different functions that cells do, of course the nervous system, the function is to transmit nerve impulses, if they’re not functioning properly then the nerve impulses can’t be transmitted properly. And so that leads to a loss of function.

Now this can occur when people get run down. And they can get run down for a variety of reasons. They can lose their energy stores, for example, or they can have them damaged through the mitochondrial damage that I was talking about. Some of this occurs naturally, and it’s reversed by rebuilding things like the membrane as it’s damaged.

And if there’s some process that prevents that rebuilding of the membrane, then this will persist. For example, during infection we know that a variety of different types of infections – viral, bacterial and so on – cause an increase in the what are called reactive oxygen species, or ROS. And these damage the membranes of the cell, and in particular they can damage the inner mitochondrial membrane and cause loss of function.

So these are things that can happen. So it can happen during infection, it can happen during aging, it can happen during a chronic illness. It can happen when you get run down, for example, or you have exposures of various types that are toxic. So under a variety of different conditions you can have damage done to your mitochondria, which means loss of function, and your body cannot repair itself as well without that energy that’s necessary to do it.

[Damien Blenkinsopp]: Great. And I guess an important differentiation I just wanted to point out here is a lot of people talk about adrenal fatigue, and if one of the symptoms is fatigue, basically having low energy – which I guess would be one of the outputs of mitochondrial damage – how do you differentiate it, or is it possible to differentiate it, to something which someone would diagnose as adrenal fatigue? Or how do you look at that?

[Garth Nicolson]: Well they go hand in hand, because for the adrenal gland to function, it requires energy. So if there’s an energy deficit in the adrenal gland, then that’s not producing the correct hormones and everything that your body needs. Cytokines and so on. So this sends up the deficit, and this can cause a problem. So they’re inter-related.

[Damien Blenkinsopp]: Right, right. And it sounds like you’d think mitochondrial damage might be a pre-cursor to adrenal fatigue, often.

[Garth Nicolson]: It could be a pre-cursor to adrenal fatigue. And so we’ve seen people that have managed to repair their endocrine systems by repairing their mitochondria. So at least we know, and at least in some patients, that’s reversible.

Now in other patients they may have either genetic defects, or toxic exposures, or something like that, that’s damaging specifically those particular adrenal glands. So that’s a different issue. But we do know that these things are inter-related. If you don’t have the energy, you can’t repair.

[Damien Blenkinsopp]: So you’ve worked, in your clinical studies and your patient population, you’ve worked with Gulf War illness and Chronic Fatigue Syndrome and some others. Could you give us a brief explanation, for the audience, what are the issues that these people have? How critical are they, what kind of situation are they in? Before we talk about the lipid replacement therapy and what it was able to do.

[Garth Nicolson]: Well there’s quite a bit of variation on the signs and symptoms of people with chronic illnesses, and a variety of different sorts. We started working with what are called Fatiguing illnesses, because Chronic Fatigue is the hallmark of those illnesses, and that’s directly related to mitochondrial function. So that was a good place to start.

A lot of other diseases, mitochondrial function may be thought of as a side issue; although it’s important it may not be the primary clinical manifestation of the disease process. Nonetheless, it’s still important [for] practically any chronic illness.

If you take something like a neurodegenerative disease, for example, mitochondrial function is intimately tied up with neurodegeneration. You cannot repair your nervous system if you don’t have the energy available to do it. So if mitochondrial function goes down, you’re particularly susceptible to neural damage. And to have that process going on, it can exacerbate it.

So this is one of the things that we are trying to work with, how to improve mitochondrial function, how to help people with a variety of chronic illnesses.

So we started with the fatiguing illnesses, and Gulf War Illnesses are really one of the fatiguing illnesses, but Chronic Fatigue Syndrome is another one, Fibromyalgia syndrome is another. Fibromyalgia syndrome is a little different because it’s also characterized by widespread pain, in part, we think, that’s due to mitochondrial function problems as well. The nervous system not operating properly. But there are some other factors as well.

So all these issues have as an underlying commonality loss of mitochondrial function. In a variety of different diseases, that’s true. And it’s true in infections, it’s true in toxic exposures, it’s true in a wide variety of different diseases. Cancer, you name it, practically every disease you can think of has a problem with mitochondrial function. They can’t keep up the repair process.

[Damien Blenkinsopp]: Are there other, beyond the ones we’ve already discussed, are there other types of patient populations, or other use cases you’ve looked at for lipid replacement therapy? You mentioned anti-aging as well. Have you worked with people for that area also?

[Garth Nicolson]: Exactly. Well, anti-aging is probably the normal manifestation of mitochondrial functions. I mentioned as you age you lose mitochondrial function naturally. And there’s an increase in the oxidative damage that occurs in all of our cells, so we need to reverse that process.

And so, one of the things we’ve done with the aging process is we’ve taken people that were fatigued, 90 years old plus, we’ve improved their mitochondrial function to a 30 year old. And they’ve gained all kinds of function in the process. Mental function, physical function, you name it. Every system that seems to be important improves.

[Damien Blenkinsopp]: In terms of the studies you’ve done, are these all based on studies, or is some of this based on patient population, other studies? Because I’ve seen some of your presentations, looking at your studies and work on the fatigue cases and the Gulf War Syndrome. So are all of the studies basically based on those patient populations versus the anti-aging, or have you also done studies on anti-aging also?

[Garth Nicolson]: Well we’ve done some studies where we’ve included older people in our studies, and that’s where we see the anti-aging effect. So with those older cohorts of patients – well they really are, they’re subjects, not patients, because their main problem is they’re elderly and they have fatigue issues. So we can’t categorize them as a disease process, because it’s a natural process of aging.

So they are fatigue subjects. So they have chronic fatigue, but they don’t have a disease called Chronic Fatigue syndrome, or Myalgic Encephalopathy, or something like that. They have fatigue problems. So we work with people like that as well.

We’ve also worked with cancer patients, we’ve worked with people with chemical exposures, we’ve worked with people with infections. For example, there are a wide variety of chronic infections that we work with, like Lyme disease, mycoplasma infection, so on and so forth. Were, again, in the chronic disease process, it’s always an issue. Mitochondrial function is always an issue.

[Damien Blenkinsopp]: Right. Would you say it’s going to be helpful in most situations to have some kind of lipid replacement therapy as a support for your mitochondria? In terms of the disease process, to give an idea, what kind of results do you get from people? Can you get people back to resolution? Or is this basically managing symptoms, managing the damage of mitochondria, kind of therapy?

[Garth Nicolson]: Well it depends on the situation. If we take normal, healthy people that can get run down for one reason or another, yes we can bring them completely back by repairing their mitochondrial function.

If you take people that are in a disease process, usually these processes are much more complex than just mitochondrial function. Mitochondria being one part of the problem that they have. And we can repair that part, but there are other elements that have to be taken care of as well. For example, if you take somebody with a neurodegenerative disease, does just repairing their mitochondria reverse the process? No. There’s some other elements that are involved.

Does it help? Yes, it seems to help people with cognitive loss and so on and so forth. But it doesn’t reverse it or completely cure the problem. That would be a pretty simplistic approach to these complex, multi-factorial issues. But, we do know that this is an important element in all of these processes.

[Damien Blenkinsopp]: Do you feel like it provides a support to get people to recovery? That it’s an important ingredient in your practice? You feel like it helps people to recover by giving them that mitochondria energy, thus supporting things like the immune system, and other systems of the body?

[Garth Nicolson]: Absolutely. If you’re talking about the immune system, for example, it requires energy to function. So if your energy goes down, your system might be less capable. So, it’s absolutely important there.

And it’s absolutely important for any type of recovery, because what is recovery? Generally it’s repairing our cellular processes and our system processes, our organ processes, and that requires energy. That just doesn’t happen naturally without energy.

[Damien Blenkinsopp]: Okay, so let’s get kind of concrete here, for the audience listening at home. What is lipid replacement therapy? What does that actually involve, what do people do when they’re taking lipid replacement therapy?

[Garth Nicolson]: Well this is a particular type of lipid, this is not just the normal gross lipids that people might think of. These are very particular membrane lipids, so these are lipids that make up the membranes of all our cells. And of course as I mentioned before the membrane is an integral part of the mitochondria, but they’re also an integral part of other organelles within the cell.

Membranes, in fact, are absolutely essential for the function of all of our cells. And they get damaged, they get run down, we have to replace the molecules and the membrane occasionally. And some of the most sensitive molecules are the lipid molecules, because they’re very sensitive to oxidative damage, which can occur in any disease process, infection, or whatever.

So this is something that has to be replaced. And we came up with this idea, well we need to replace the membrane lipids, which are primarily a class of lipids called glycerophospholipids, that don’t need a lot of other things. That’s what we need to help repair the, more or less the matrix of the membrane.

So if we supply that in purified form, undamaged form – which is very important – then we should be able to help repair this process, because we have natural systems in our body to replace these lipids as they’re damaged. Because we evolved with the mechanism to help repair and replenish our membranes.
The problem is we can’t keep with the damage, and that’s when the disease process can occur. So to help it along, if we provide the lipids, well we can help that process.

Now people say well, you can buy all kinds of different stuff at the store. Well, the reason it doesn’t do it is a lot of those lipids are already damaged, they’re already oxidized, they’re not the right kind of lipids, and so on. So they’re not very helpful. And even a lot of supplements that people buy in the store are not very helpful, because even if they have lipids they’re not the right kind of lipids, or they’re already damaged, or they’re damaged during the shelf-life.

These are very sensitive issues, which we’ve tried to overcome with the products that are designed to survive and provide our bodies with exactly the right lipids that we need to repair our membranes and restore function.

[Damien Blenkinsopp]: So, would it be correct to, because you provide these in pill form. So is it these are things we can get from food, but we get them in very low quantities, so it’s like having a very high dose of the reduced form? The active form versus the oxidized form of these lipids?

[Garth Nicolson]: Well that’s part of it, but a lot of the lipids are damaged already by the time we take then in in the foods, and unfortunately, our transport systems, they can’t readily acknowledge a damaged lipid from a properly pristine, undamaged lipid. And so a lot of these things might get transported in as well. Or at least they’re transported in, too much of it is transported in if it’s damaged.

So we kind of flood the system with undamaged lipids, and that helps the whole process move very smoothly. It also helps remove the damaged lipids, which is one thing we’re working on now, is how to take people who are chemically damaged – and I can talk about that later – help them remove those damaged chemicals from their bodies.

And it turns out that the replacement therapy can help do that, because it’s an energy driven process, so it helps provide energy, but it also is very dependent upon moving what we call hydrophobic molecules out of the cells. And the lipids that we provide have a very important part of their structure, a hydrophobic part of their structure, which helps remove these molecules.

So if they’re present in quite a bit of excess it can help remove these damaging chemicals from our system. And that’s one thing we’re working on right now.

[Damien Blenkinsopp]: That sounds very interesting. We’ve spoken about detoxification before. So, just to take a step back, when you say chemically damaged people, what kind of things has happened to these people?

[Garth Nicolson]: Well often people with chemical damage due to illness could be anything from herbicides, for example, to very industrial chemicals, and so on and so forth. Often damaging chemicals are chemicals that we would classify as hydrophobic chemicals. That is, they don’t like water. They like fat, essentially.

So they concentrate in our membranes, they concentrate in the fatty parts of our cells and lipid droplets, and so on. And they can remain there indefinitely. And they can bleed out very slowly and cause problems with the cellular mechanisms. So to get rid of these, we need a system to remove them.

But the system that we have for detoxification is an energy dependent system, at least one of the most important ones. So by providing mitochondrial energy, that helps in that process. But it also helps remove them because, it turns out, the lipids that we provide kind of soak up these molecules, because it will bind to the lipids and it helps them be excreted from our cells and from our system, so they naturally come out in the GI system.

[Damien Blenkinsopp]: So that sounds like the new molecules that you’re providing are basically replacing the ones which have absorbed the toxins, the chemicals, the fat soluble chemicals, and are thereby displacing them and allowing the body to remove them.

[Garth Nicolson]: Well that’s basically it, but it’s providing a different store, or different storehouse for these chemicals to move into, but a storehouse that we can eliminate. And that’s the important thing is to do that.

One of the mechanisms for moving chemicals that’s most important for these very damaging chemicals that concentrate in our cells is that there are enzymatic mechanisms, to conjugate the offending chemicals with other hydrophobic molecules within the cells, to make them more easily removable.

Well when that happens, if we have somebody’s undergoing lipid replacement therapy, there are a lot of these lipid droplets around and lipid carriers around, which could help soak these conjugated chemicals up and remove them from our systems.

So it’s a process, it’s a very slow and steady process of removal. It doesn’t, of course, happen over night, but it’s a natural system for removal of damaging offending chemicals from our bodies. And this just takes it to a maximum advantage by providing some of the things necessary for it to operate in the first place.

[Damien Blenkinsopp]: So out of interest, because we’ve spoken quite a bit about detoxification, and also the kinds of tests involved in measuring things like mercury, lead, and other toxins. Are you able to test these chemicals in fats and see the change, and how long does it take? Does it take a month, two months?

[Garth Nicolson]: Again, we’re not talking about heavy metals, because that’s a different process of removal. We’re talking about chemicals that partition themselves into the fatty portions of your cells. Well these chemicals, and they could be, for example, herbicides or any number of different chemicals.

[Garth Nicolson]: Yeah, a lot of the chemicals that damage our cells are very hydrophobic, and they partition into the fats of the cell, the fat systems and the membranes of the cell. They have to be removed or eventually they’ll interfere with the function. That removal process is slow. It does not happen over night.

So it’s a very slow process of bleeding them out and removing them from the stores, and so on and so forth. So one of the first things that you can see, for example, if you give somebody lipid replacement therapy, is you might actually see an increase in the number of these chemicals that are being excreted, that are being at least mobilized as well.

So there may be an increase in the blood levels of these, because they’re being brought out of the cells and being transported to the brush border cells in the intestines, and then secreted there. But again, there are a number of different mechanisms, this being just one of them.

[Damien Blenkinsopp]: I’m guessing this is a new area, it sounds like you’re more focused on this recently?

[Garth Nicolson]: This is a very new area of ours that we planned to get very focused on because it’s so important, so necessary to help these people, many of whom have been damaged for decades without much help at all.

[Damien Blenkinsopp]: So just out of interest, are there any specific exposures? And is it people working in factories, or is it people who have detoxification systems which aren’t functioning, or perhaps they have some methylation or other issues, which they’ve lived a pretty normal life, compared to most people. It’s not like they’ve been in any specific situation which could have exposed them to more chemicals.

What kind of populations are you dealing with here?

[Garth Nicolson]: We work with the populations that are sick in general, although a variety of different individuals may be exposed to chemicals, because they are all over the place in our modern environment. And people will have tremendous variation in their sensitivities to these chemicals.

So you may have somebody that’s been normally and naturally exposed who’s becoming sick because of it, and other people not at all. Because there’s such a range of sensitivities to these.

So we’ve worked with people who’ve had specific exposure. For example Vietnam war veterans who’ve had exposure to Agent Orange, which is a particularly nasty chemical that takes a long time to remove from the body. Or Gulf War veterans that are exposed to petrochemicals in the forms of fumes, and exhausts, and oil fires, and so on and so forth, during the first Gulf War, and some during the second Gulf War.

So these are people that have had chemical exposures above and beyond the normal types of exposures that we might see. But in the industrial environment that we’re in, there are a lot of people that get exposed to various chemicals.

If you work in the petrol-chemical industry, for example, you could be exposed fairly easily, and it may not cause any problems with you but there are other individuals who have severe problems because of it.

So again, there’s a wide range of different sensitivities to these different chemicals that are seemingly in our population.

[Damien Blenkinsopp]: Great. I just want to bring it up, because I know a lot of people talk about infrared saunas, and saunas in general when it comes to fat detoxing from the fat soluble toxins like the ones we’re talking about. So, do you have a viewpoint on that, on the effectiveness of infrared sauna? Is it something you’ve ever gotten involved with, and could you compare it to your process?

[Garth Nicolson]: We’ve looked a bit into that, and yes the use of infrared saunas to actually bring the chemicals out in your sweat, which is what it really does. But if you do these at least a minimum two times a week, you’ll slowly start to deplete some of the chemicals from your body.

What we found is if you add our lipid replacement therapy on top of that, you can accelerate the process of removing the chemicals from your body that way. So again, this can be an adjunct to a variety of very well established methods for detoxification.

[Damien Blenkinsopp]: Great. Have you seen complete recoveries, or to what degree have people recovered from their health? Because we’re talking about people that are quite sick.

[Garth Nicolson]: Well, we’re in the beginning process of this right now. So this long term goal of ours, but again, this is just the beginning, and we’re seeing some responses. We’re seeing people that are feeling better, getting better. But again, it’s a long, slow process for recovery.

And again, there may be other types of damage along the way that we discover that these individuals have. Most of these chronic illnesses are multi-factorial. There’s not just one problem, generally these people have a number of problems, this being one of them. But this is something that we can approach.

[Damien Blenkinsopp]: Absolutely. So it sounds like an on-going process of a year. We’re talking really long term, just to give people an idea.

[Garth Nicolson]: We’re talking long term. Particularly when it comes to removing offending chemicals from your body, it’s a long term process. Same thing with removal of heavy metals from your body, it’s not a short term process.

It can take years to remove heavy metals from your body, and the same thing is true with chemicals that build up in your body. It can take a long time to really get rid of them. And in fact, if you mobilize them too quickly, you can really make people feel sick in the process. So it’s better to do it naturally and slowly.

[Damien Blenkinsopp]: So, I’m glad you brought this up, because we’ve spoken about these kind of topics quite often on the podcast before. It’s nice to get that. Is there anything you have to do in terms of supporting them?

Because you mentioned that some people can get sick if it comes up too fast. Is there anything else that you do for them while you’re using the lipid replacement therapy to support detox, or as long as you go at a reasonable rate, which I imagine is a reasonable dose?

[Garth Nicolson]: What we have found is that lipid replacement therapy actually reduces the symptoms of detoxification, reduces the symptoms, for example, of cancer chemotherapy. So it is very significant in our studies with the cancer patients. They’ve showed really quite a dramatic decrease in the side effects due to chemotherapy, because it causes a lot of damage to our normal systems, and the lipid replacement therapy helps repair those normal systems.

So you get a reduction in the associate problems, very adverse events that occur during cancer therapies. So, you could figure that is, again, when you’re repairing the normal mechanisms of the cells, the tissues, and this helps the overall process.

[Damien Blenkinsopp]: Right, right. So you’re saying a lot of the symptoms people have when they’re going to a detoxification process, or, as you’re saying, chemotherapy or exposure to other toxins or when they’re ill, is due to mitochondrial damage, right?

So when you’re supporting the mitochondria with lipid replacement therapy, it helps to manage the symptoms as well in that process and reduce them, because there’s not as much damage going on.

[Garth Nicolson]: Well it does, and not only that, it helps accessory systems as well, because a lot of the signs and symptoms that we see that are associated with damage are release of chemical messengers like cytokines, that cause all kinds of problems in the body, and so on.

And damaged tissues can initiate this whole process. So if you reduce the damage, you can reduce these accessory damage response systems from exacerbating the signs and symptoms in these patients.

[Damien Blenkinsopp]: Great. One thing I wanted to kind of make clear to people, what kind of results, because when I was watching some of your clinical studies you were looking at. Over the few months you were giving lipid replacement therapy, could you talk about what kind of impacts it generally has on the people?

If we’re talking about say the chronic fatigue, or in the Gulf Syndrome cases, the ones I saw, what kind of time-lines did you walk through in your clinical studies? And also, it was interesting what happens when you stopped the therapy.

[Garth Nicolson]: This is a process that takes time. You don’t repair your mitochondria overnight. It takes days to weeks. The process can begin fairly soon after you take the lipid replacement, but it takes time to fully repair the mitochondria.

And we’ve seen, again, that it can take, depending upon the different formulations of lipids, anywhere from 10 days to three months, depending on the formulation, depending on the patient type, to reach an equilibrium of repair. And these people see a maximum benefit in that time. But they do see benefit fairly, fairly soon.

[Damien Blenkinsopp]: And then what happens when you stop the therapy? Depending on the condition. So when it’s in a chronic condition, like Chronic Fatigue Syndrome, or Gulf Syndrome, where they have some kind of infection or some underlying cause, then what happens when you stop the therapy?

[Garth Nicolson]: Well then it slowly returns back. As the mitochondria get damaged again, it will slowly go back to the way it was before you started the therapy. And one of the trials that we did was called a cross-over trial, where we take patients, and they’re on part placebo and part the lipid replacement therapy, but they don’t know when they get it.

And what we found was when they get the lipid replacement therapy, they improved. They had reductions in fatigue with 35 to 45%, enhancement of mitochondrial function was a little bit less than that in terms of percentage, but very significant. But when we switched them to placebo, it slowly started to go back again.

[Damien Blenkinsopp]: Yeah.

[Garth Nicolson]: And they wondered what was going on, because it wasn’t having the same effect. So we could prove that it was in fact the lipid replacement therapy that was giving them the benefit, not a placebo effect.

[Damien Blenkinsopp]: Great, thank you very much for that. And so, what were you using to assess mitochondrial function in terms of tests?

[Garth Nicolson]: Well what we do is we take a blood sample from patients, we isolate the white blood cells which have mitochondria – the red blood cells do not have mitochondria – and we can measure the mitochondrial function directly.

And what we’ve done actually, more recently, is we’ve measured the membrane potential of the inner mitochondrial membrane using a special redox dye, called rhodamine 123, and see that fluorescent dye in the mitochondria. If the mitochondria are fully functioning, they will reduce that dye and it will fluoresce.

And if they’re not functioning, they can’t reduce it, and the mitochondria won’t fluoresce. So you can see it visually in a microscope and you can quantitate the fluorescence so we can get a quantitative value.

[Damien Blenkinsopp]: Great, great. So this is your own lab tests that you developed for this purpose?

[Garth Nicolson]: Well other people really developed the tests, we just adapted it to what we were doing.

[Damien Blenkinsopp]: Great. Well I guess what I wanted to say is it’s a pretty unique [test], like we wouldn’t expect to find it outside of research, apart from potentially your practice, and some other specific areas.

[Garth Nicolson]: This is a very specific research type of test, and you won’t find it in your normal doctors office, that’s for sure. Because it requires some complicated machinery, like a cell sorter and fluorescent tools, fluorescent light sources, and so on and so forth. So, it’s a bit complicated, but it works in a research environment.

[Damien Blenkinsopp]: So it’s not something you use on your patient population, I guess it’s cost prohibitive. It sounds like quite complex.

[Garth Nicolson]: Well it is, and speed is very important. So you have to have a very fresh sample. Often if you’re not doing the test immediately or soon, you could get variable results. So to get the best results, speed is very important. So, generally you have to have this complicated equipment on hand to do it. And the technical expertise to do it.

[Damien Blenkinsopp]: So, how well accepted is lipid replacement therapy? We’ve spoken with functional medicine doctors here, and we’ve looked at functional medicine quite a bit, contemporary medicine is there of course also, and in the research studies.

Is there a lot of support for it right now, or is it still something quite niche that basically there’s not very many people using?

[Garth Nicolson]: Well more and more are using it, because more and more people are finding out about it. And we published some 28 papers on this process. So, it’s well-known in the literature. We published a number of reviews on it now.

Less known in the general population of physicians, more in the naturopathic medicine areas, mainly because I get around and talk to these people, and then they get informed that way, through conferences and so on. So it’s becoming more and more well-known, and even people outside the medical area will find out about it through broadcasts like yours, for example.

They can buy this stuff over the counter, it’s not something they need their physician’s prescription for. These are natural supplements. It’s the lipids that are in our membranes all along. So, it’s not a drug, it’s not anything but what’s there. We just have to provide it in a way that’s not damaged.

[Damien Blenkinsopp]: Well so I’ve got to ask you the question, are you using lipid replacement therapy yourself?

[Garth Nicolson]: Absolutely.

[Damien Blenkinsopp]: Okay. How long have you been using it?

[Garth Nicolson]: Well, I’ve been using it for years now. It was very effective for me in terms of reduction of fatigue. And for example, recently I got an influenza virus, unfortunately. It kind of knocked me down, and this helped the repair process. I recovered much more quickly than normal, and so I think it’s very useful for that.

[Damien Blenkinsopp]: What kind of dose are you taking? Let’s talk about practicals here. Because I’m taking ATP Fuel, for example, because I’ve had my own issues and it was recommended to me. And your research was recommended to me, so that’s kind of where I came into it.

So I’ve been taking that for a while, the ATP Fuel. And you have the NT Factor, which is a part of that. Is that actually your company who supplies that, or is that another company?

[Garth Nicolson]: I’m in a non-profit organization. We’re not really a company, but we do consult with companies like Researched Nutritionals that makes the ATP Fuel, [and] Nutritional Therapeutics in New York which makes the NT Factor, the lipids.

In fact, the Researched Nutritionals uses the NT factor product in their own product. They add some other things as well. So, ATP Fuel is an excellent product for these chemical exposure patients. In fact, I’ve just been going back and forth with the President of Research Nutritionals because we need to increase the amount of NT Factor, which is the lipids, to that product to really help these individuals.

So what we found is that more of the NT Factor is actually better. You might want to supplement your ATP Fuel with some NT Factor Lipid Wafers. By the way this is an excellent product.

We use these with children, for example, that have autism spectrum disorders, and these children have mitochondrial function problems. They readily take these wafers, and they don’t take pills. You can’t get them to take a pill.

[Damien Blenkinsopp]: Right, right.

[Garth Nicolson]: But these wafers are very tasty, and they’re creamy, they melt in your mouth because they’re lipids. So they like these creamy things, and so we have no problem with the compliance, even with difficult cases like these autistic children.

These are things that we work with on a daily basis, and we’re trying to improve our products as we go. Recently we found that although ATP Fuel is a really good product, I’m saying for the chemically exposed individuals that we need to increase the amount of NT Factor with the lipids in that product.

[Damien Blenkinsopp]: So just for the audience, the ATP Fuel has co-enzyme 10 and NADH added to it. Obviously, say that the dose of the lipids, which you say is the most important, this is kind of the innovation here, the lipid replacement therapy.

[Garth Nicolson]: That seems to be the most important thing because if you leave that out, it’s not very effective. If you put it in, it’s very effective. So it is a combination, but it’s a critical part of that combination.

[Damien Blenkinsopp]: Let’s just talk downsides here. Are there any downsides you know to this, and are there any safety issues? I just want to make that clear in terms of, maybe if you overdose it. You’re talking about increasing a dose for chemically exposed people. Is there any downside or risk to taking a lot of this?

[Garth Nicolson]: We’ve never seen any safety issues with the NT Factor lipids. As a matter of fact, we’ve given approximately 40,000,000 doses of this to patients without any recorded evidence of a real side effect.

And the reason for that is these are natural molecules that are in our cells and our systems all along. So we’re not giving our systems anything that’s different. We’re not giving them a drug, we’re not giving them something that they don’t see all the time anyway. I don’t know that it has any toxicity.

There are some studies that had been done in animals, where they’ve been given tremendous doses, without any effect at all. And we’ve had patients that have been on, oh, up to several grams per day of the NT Factor lipids without any [negative], as a matter of fact more positive effects. Their blood lipids had more normalized, they’ve had a lot of really positive things happen to them.

[Damien Blenkinsopp]: So that’s interesting. What kind of quantitative changes have you seen in terms of, are you talking about cholesterol markers?

[Garth Nicolson]: Yes.

[Damien Blenkinsopp]: Have those changed as well?

[Garth Nicolson]: Cholesterol markers and bad and good lipids. For example, lipoproteins, we’ve seen a move in the right direction. We’ve seen reductions in a product that’s associated with Heart Disease, homocysteine.

We’ve seen in elderly patients a reduction over time in homocysteine levels, which are directly related to coronary, artery disease and heart attack. So these are some of the beneficial things that we’ve seen in patients taking this long term.

[Damien Blenkinsopp]: Great, great, thank you for that. So, are there things that you’re looking for in the next five or ten years, where you think there’s going to be some more changes or innovation? Or is there anything you’re kind of excited about the opportunity of this, to help more people or to improve it?

[Garth Nicolson]: Well we’re doing an anti-aging study right now, which I’m very excited about. It’s actually going on in Uruguay. A colleague of mine who is there is a specialist on sperm function, and he takes care of men with fertility problems. But as we age, our sperm function declines, and that’s what I’m interested in as a test model for anti-aging.

So far what we’ve seen is that even in vitro, if you take sperm they have a certain lifetime. So if you take older men they have less of a lifetime, that is they can be for a while, but then they start losing motility more rapidly than younger men. But if we put in the NT Factor in it, we can help restore the function of the sperm even from older men.

So the next step is that we’re going to go from these in vitro experiments, which are very interesting, sperm motility, to in vivo experiments where we look at actual men with fertility problems that have functional problems with their sperm motility, and see if we can help repair that process.

But in terms of it’s anti-aging, which is what I’m really looking for, long range, this is an interesting model to look at. So whenever we have systems that undergo slow degeneration, like sperm function over time, if we can reverse that process, that means that we’re having an anti-aging effect, and it’s very clear, it’s very specific, and very quantitative effect. And so that’s one of the systems that we’re looking at, and I’m very excited about.

And we also have a number of different diseases processes that we’re very interested in, and we’re trying to intervene and see if we can help. Neurodegenerative diseases is one thing I’m very interested in. That’s obviously a very long term and slow process to eventually recruit patients in that area.

Another thing is reducing the adverse effects of cancer in cancer therapy. So there are two aspects of this. If some person has cancer, often they have what’s known as cancer associated fatigue, in the absence of any therapy. And of course the NT Factor will help patients with that.

We’ve seen a 30% reduction in that fatigue with patients with long-term cancer, that have had cancer associated fatigue. But it’s really reducing the side effects of cancer therapy that is most interesting, because we’ve seen reductions in side effects to chemotherapy that are really dramatic. So there’s reductions, for example, not only in fatigue but in vomiting, and malaise, and a number of other side effects – headaches, for example, and so on – associated with chemotherapy.

I think the reason for that is we’re helping repair the normal systems very rapidly in these patients after their burst of chemotherapy. So you might ask, well does this interfere with the therapy? And the answer is no, because it turns out there’s a window of therapy which is very short for the cancer, but it’s very long for the normal systems.

So these chemotherapeutic drugs attack the cancer very quickly, but then they have lingering effects on our normal systems for months, literally, after the therapy is over. So, what this does is the NT Factor helps reverse that process of damage after the therapy.

[Damien Blenkinsopp]: It sounds like you’re saying that there’s no risk of them providing a protective effect to the cancer cells themselves, provided that you introduce a timing?

[Garth Nicolson]: Well what we do is we put it in after the therapy. Because we know the damage to the cancer cells occurs very quickly. Generally, within hours after the therapy is administered. Whereas the damage to the normal systems occurs for weeks, or even months later. So we allow the therapy to occur and then next day, the following day, we start the lipid replacement to help repair the normal systems.

[Damien Blenkinsopp]: This is really interesting work. You must be really excited about all of these projects you’ve been working on.

[Garth Nicolson]: There’s something new every day!

[Damien Blenkinsopp]: And luckily you have lipid replacement therapy to keep your energy up, so you can keep focused on them all.

[Garth Nicolson]: Well I’m taking it, and so far it’s been a real help. I know that personally. But every individual will have to see what’s optimal for them. Some people will find they have to take a bit more of the lipid replacement than other people, and that may have to do with their transport systems that bring these lipids into their bodies and cells, and everybody’s different in that regard as well.

So, the same thing with detoxification. We have systems in place to help detoxify us, but it’s working so poorly for most people, or their systems are swamped out with these dangerous chemicals and they can’t keep up with the damage, and so this helps accelerate the removal of chemicals.

And also, we know that’s an energy dependent process. So it helps rebuild the energy systems that are necessary for detoxification. Because detoxification just doesn’t occur naturally, it requires energy.

So if you don’t have the cellular energy necessary, you can give them all kinds of different things, and you’re not going to see much improvement, or at least you could see much better improvement if you repair their energy systems at the same time. So I think for any detoxification, mitochondrial repair is really important, because it really helps accelerate the detoxification process.

[Damien Blenkinsopp]: Great, great, thank you. There is a cost side of this kind of therapy.

So, in terms of monitoring, how do you assess whether someone should remain on the treatment? Is it purely based on symptoms resolution, or whatever they’re trying to achieve, or do you have any markers? You brought up the homocysteine, for example. So if they had raised homocysteine and it leveled out, you could say, okay now I can take you off the therapy, because you’ve got to that critical [point].

[Garth Nicolson]: Well, actually, here’s the problem that we have in the modern environment. We don’t stop people from being exposed. We don’t stop people from getting sick, we don’t stop people from getting into automobile accidents, or whatever. We can’t do that, but what we can help them do is repair once it occurs.

We can help repair and accelerate the healing process due to trauma. We can help the healing process due to infection. We can help the process due to long term treatment of a chronic condition. All of that means that this is a long term solution, not a quick fix. And that’s why I’m taking this for the rest of my life.

And I put my father on it when he was 92, and he had much better cognition, he had less fatigue issues, and was more ambulatory, and clearer thinking, and so on and so forth. And he lived another eight or nine years. He was a coronary patient and he was on his last legs when he started.

So I think it’s never too soon. Just like it’s never too soon to stop smoking, it’s never too soon to start taking lipid replacement therapy. And yes, you may have to take it for the rest of your life if you want the benefit.

[Damien Blenkinsopp]: Well, I think I’m certainly going to stay on it. And I’m very glad to have you on the show to spread the information about this. It’s been very useful to me.

In terms of other people who, besides yourself, you would recommend to talk to about mitochondria, or lipid replacement therapy. Is there anyone else who’s done work which you would reference which is interesting, that have done a lot of work in this area?

[Garth Nicolson]: People can go to our publications, because they can see what we’ve cited in terms of the references, and the groups, and so on. Yes, there are other people working on different aspects of it. For example, there are some groups in Europe that are using intravenous lipids – similar type but not the same – and they’re getting very good results with that.

We prefer the oral supplements because obviously you can’t go in every day for an intravenous lipid replacement therapy. So, we prefer people take it orally, because we know we have the mechanism in our brush border cells lining our guts to bring these lipids in naturally, because they’re essential lipids. So, this is a very natural process that we’re supplementing, essentially.

And I think people need to find out about this. The ATP Fuel that you mentioned is primarily available through physicians and naturopaths, and professional health people, but there are also a lot of people out there maybe listening that want to know where can I get this stuff on my own.

And there’s a website called NTFactor.com, where they can buy all these products over the counter, because they’re just natural supplements. And so, that’s where they can go, NTfactor.com to find these lipids replacement therapy products, and find out more about it. And they can go to our website, the Institute for Molecular Medicine, which is www.immed.org. It’s like a media .org, and they can see the scientific results and the clinical trials.

[Damien Blenkinsopp]: Great, thank you so much. We’re going to put all of this in the show notes so people have all the references to everything we’ve spoken about today. Would you recommend they take the straight version of NT Factor? Because there’s these different combinations of things.

[Garth Nicolson]: Well it depends on what people want to do, and it also depends in a lot of cases on what people could afford if they’re buying supplements and stuff. The minimum thing they need is the NT Factor lipids.

Now, the more complex formulations like the one you’re taking cost more because they have a lot of other ingredients that are very costly. But if they want the initial punch, they need to take at a minimum the NT Factor lipids.

[Damien Blenkinsopp]: I see, that sounds like the big lever.

So Garth, thank you so much for your time today. Just on a personal note, are there any data metrics that you track for yourself? Either on a routine basis or a once yearly basis for your health, longevity, or performance?

[Garth Nicolson]: Well of course we look routinely at membrane lipids, for example, in our blood. We look at things like homocysteine and so on – and my levels are very low. I find that I feel better on NT Factor and, by the way, I have gone on a trip recently and I forgot to take it along, and I suffered because of it.

[Damien Blenkinsopp]: Oh no.

[Garth Nicolson ]: I feel very strongly about taking it on a daily basis. So I’ve seen it in myself. I mean I know that I can recover much faster from travel associated problems, for example, from illnesses and so on and so forth if I take the NT Factor.

And that’s what other people reported back to us as well, it’s not just my own personal results. We get a lot of feedback from a lot of people who are taking this, and now tens of millions of doses have been given to patients and subjects and so on, in various forms, and so far we haven’t had any complaints. And that’s a good news.

[Damien Blenkinsopp]: Its great news, it’s amazing news. Thank you very much for your time today, Garth. Its been great to have you on the show.

[Garth Nicolson]: Sure. Thanks for having me.

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How well are you aging? We look at an attempt to make an aging biomarker index accessible to consumers that tracks their true biological age and provides feedback recommendations to improve how they age.

In this episode we take another look at longevity through the lens of aging biomarkers. This time taking a look at some of the most well research-supported biomarkers to predict how well we are aging. Or more to the point, how badly we may be aging, and get some early warning indicators, about having to intervene to assure we avoid shortening our lifespan.

Specifically we look at InnerAge, a new panel of aging biomarkers developed by the consumer blood testing service InsideTracker.

The panel provides an index estimating longevity based on a combination of biomarkers, and based on the results, makes recommendations to improve your longevity (AKA put the biomarkers back in the optimum zone, reducing the associated risks of shortened lifespan).


“…for each of those biomarkers, we have an intervention that you can take in order to optimize your InnerAge, and it’s very important for us to take markers that you can [have an impact on]. For example, we are not taking a marker of a disease like BRCA1 or other markers that show whether you have cancer or not, as you cannot do an intervention for that.”

– Gil Blander, PhD

Today’s guest is Gil Blander, the founder, president and chief scientific officer of InsideTracker. Gil has 18 years of experience in systems biology, computational biology, aging, metabolism and caloric restriction research.

During his career he has worked at MIT, the Weizmann Institute, and several systems-biology and computational biology companies. In this interview he walks us through the new aging panel, InnerAge, and the research and thinking behind why the company chose each of the biomarkers in the panel.

The episode highlights, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know what you think in the comments!

itunes quantified body

What You’ll Learn

  • Gil’s interest in biomarkers arose at the age of 12 when the death of a close family member made him think about age and longevity. (5:12).
  • Gil founded InsideTracker, with the aim of having a way of doing a monthly health check-up with optimal values for various biomarkers that are tailored to each individual (8:06).
  • When we look at biomarkers in the blood, they can show us where we are in terms of health and based on that, we can find optimal zones for each biomarker. (9:30).
  • The team of scientists and two year research process it took to cut down the aging biomarkers from hundreds to the top five (12:55).
  • How InnerAge uses an algorithm to estimate your chronological age, and recommend interventions based on your biomarker results (17:06).
  • Examples of some of the interventions including food supplements, exercise and lifestyle changes used to push biomarker values back into their optimum zones and reduce risk of shortened lifespan. (18:58).
  • Other biomarkers included in InnerAge are vitamin D, testosterone for males, CRP (22:35).
  • Why testosterone was included for men in the panel and why they have used different optimum ranges according to age and fitness activity (23:03).
  • InsideTracker is building its own database with information from athletic populations that do primarily strength or primarily endurance training. They are mining the database to determine optimal biomarker levels for each population. The benchmarking tool can be used to tell you how you compare with the rest of the population For example, a large percentage of the population has low vitamin D levels, but InsideTracker can tell you what percentage of the population shares those levels (25:47).
  • For benchmark levels of the biomarkers, InsideTracker shows the optimal range, which is their range, the normal range, which is what is used by the diagnostic companies and out of normal. For some biomarkers, even more ranges are shown (28:55).
  • An interesting biomarker not included in the panel is cholesterol. There are no scientific papers that have shown the correlation between cholesterol, or LDL and longevity. New guidelines by the American Heart association state that cholesterol is not as important as was once thought (30:00).
  • Cholesterol is a building block of testosterone, so if cholesterol is low it will be harder to make testosterone. If you have good metabolism, you can metabolize cholesterol (31:50).
  • CRP is another biomarker included in the InnerAge panel to capture the inflammation dimension of aging. (32:38).
  • InsideTracker should be used repeatedly so that you can see the trends in your values. Samples should be taken at least a couple of times a year for average users (35:09).
  • Other scientists working on aging is Nir Barzilai from New York City and Cynthia Kenyon from UCSF (37:29).
  • Currently, InsideTracker is developing an app that will help you maintain weight, biomarkers and activity (41:46).
  • InsideTracker uses LabCorp request to send samples, but it also uses home kits. They hope that in the future, home kits will improve. (42:18).
  • Theranos’ innovation in finger prick blood samples for a wide range of blood tests. (44:20).
  • Gil Blander’s own personal routines for tracking his own biometrics with InsideTracker and other tools, and the current devices and other services he uses.

Thank Gil Blander, PhD on Twitter for this interview.
Click Here to let him know you enjoyed the show!

Gil Blander, PhD

The Tracking

Biomarkers

  • Fasting Glucose: One of the most commonly used biomarkers. It is used as an indicator of blood sugar regulation and can be indicative of longevity as blood sugar disregulation lies behind many common health issues such as diabetes and obesity. Gil mentions that while blood glucose should be between 65 and 99 for everybody, his aim was to find optimal levels for different populations.
  • Total Testosterone: Low testosterone has also been linked to depression and decreased cognitive ability. Since testosterone levels decline with age, it can be used as a biomarker of aging. Gil Blander included testosterone as one of the biomarkers in the InnerAge panel.
  • Vitamin D (25 Hydroxy Vitamin D): Also referred to as Vitamin D 25-OH. InnerAge panel includes vitamin D as a marker of longevity. This is measured in ng/mL and InnerAge uses ranges of between 40 and 50 ng/ml depending on your profile.
  • Total Cholesterol: Has long been thought to contribute to cardiovascular disease. However, re-evaluation of scientific evidence has shown that cholesterol is not harmful for most people. Cholesterol is a building block for steroid hormones, such as testosterone and estrogen and is an integral part of cell membranes. Since recent scientific data do not support the idea that high cholesterol causes heart disease, Gil Blander has decided not to include it in the InnerAge panel.
  • High Sensitivity C-Reactive Protein (hs-CRP): We’ve discussed this common biomarker of inflammation often on the show. As a general rule, the closer your marker comes back to 0, the better. InnerAge includes CRP in its panel because they implicate higher inflammation as a dimension of aging. Gil Blander notes that because exercise increases inflammation, the test should not be taken for approximately one week after vigorous exercise.
  • Alanine Amino Transferase (ALT): This biomarker of liver function is also included in the InnerAge panel. Normally, levels of ALT in blood are low, but increase if there is liver damage, which may be chronic and ongoing. The Liver is looked at for longevity in this case as its role in detoxification is considered an important predictor of health and longevity.

Lab Tests, Devices and Apps

  • HRV from ithlete: This is an app for iPhone and Android that tracks HRV. It can be used to maximize athletic performance and maintain good health. Gil Blander uses this to track his HRV, as does Damien.
  • MyFitnessPal: This is an app that is used to track nutritional intake. It can be used to track intake of calories, macronutrients and micronutrients as well as energy expenditure. Gil Blander uses MyFitnessPal to track his food intake
  • Nutrino: Nutrino is a “virtual nutritionist” app that connects to wearable devices like Whitings and Fitbit and makes personal meal recommendations. It includes information on what to eat and when to eat it. Gil Blander uses it to track his nutrition.
  • Withings WS-50 Smart Body Analyzer: Gil Blander uses this scale to track his weight and store the data daily.
  • Fit Bit Charge: FitBit is a wearable tracker used by Gil Blander. It monitors physical activity and sleep quality.

Other People, Books & Resources

People

  • Simon Wegerif: was mentioned in the context of his interview on QBP and his app and HRV platform ithlete.
  • Lenny Guarente, PhD: One of the leading researchers on aging and is considered to be the father of the new aging research.
  • David Sinclair, PhD: David Sinclair is a professor of genetics at Harvard Medical School is one of the leaders of aging research. He is also involved in the biotech community and has started several companies.
  • Bob Troia: Bob Troia is known for his n=1 experiments in self-tracking and biohacking. He was a guest on episode 22 of QBP and is a user of InsideTracker.
  • Nir Barzilai: Nir is one of the scientists involved in developing the InnerAge. He is the director of the Institute of Aging Research at the Albert Einstein College of Medicine. He is studying the effects of the environment, especially nutrition, on extending the lifespan.
  • Cynthia Kenyon: Cynthia Kenyon is a professor of biochemistry and biophysics at UCSF and is one of the scientists who has helped develop InnerAge. She is one of the pioneers of research in genetics of aging.

Organizations

  • LabCorp: Laboratory Corporation of America provides lab testing and services. InsideTracker currently uses LabCorp for its lab processing.
  • Theranos: A lab testing service that tests on very small amounts of blood, taken from the fingertip. Their tests promise to be a lot more affordable, convenient and faster than tests from traditional labs.

Full Interview Transcript

Click Here to Read Transcript

[Damien Blenkinsopp]: Hi Gil, thank you so much for joining us today on the Quantified podcast.

[Gil Blander]: Thank you so much for inviting me. It’s a great pleasure
and I already listened to a few of your guests and I really appreciate it because the
quality is very good.

[Damien Blenkinsopp]: Thank you, that’s a great compliment coming from
you. As we’re going to see, you’ve been pretty busy yourself doing some good stuff.
So, could you share first why you got involved with your interest area—what is the
story about why you do what you do at InsideTracker today?

[Gil Blander]: It’s a great question. Apparently everyone is asking me this
question. My scientific journey started at the age of 12 when one of my closest relatives
passed away, triggering my quest and a thirst for knowledge in our body age. Basically,
at that time I decided that instead of being a physician or physicist, what I wanted to do,
I decided to become a biologist. The reason for that is that one of my relatives passed
away and I started to realize that I’m not immortal anymore, and I realized that one day I will be gone. I wanted to live forever; I wanted to stop the clock; I wanted to try to delay the aging-related diseases. So that basically pushed me to become a scientist and to focus and to have my lifetime goal in aging research.

So I’ll fast-forward a few years: I decided to study biology, graduated from Tel Aviv
University with an undergraduate in biology, PhD from the Weizmann Institute of
Science studying aging, and then I came here to MIT in Cambridge, Massachusetts,
and I joined the best lab that studied aging in the world. I studied aging there for five
years, published a lot of interesting papers, did very cool research, but very early when I arrived here to Cambridge, I started to be exposed to what we call “the Kendall square
environment.” There are hundreds of start-ups in biotech, pharmaceutical, and high-tech. I started to be exposed to them and I started to talk with a lot of founders. I started to do some partnerships with them and I very soon realized that I will contribute much more to humanity if I would start my own company than to be a professor in the academia that publishes a paper once a year and maybe five people will read the paper. I realized that that should be my next step.

Even having realized that, it took me some time because I really like the work in the lab
and I did a very cool experiment. So after five years at the MIT, I left MIT and I joined a
couple of biotech companies and worked there just in order to learn and understand the
industry. Also, I really wanted to learn more about systems biology. So I spent a couple
of years there and then, during that time, I was exposed to two other PhD scientists that were really intrigued by the aging process as well, but also were trying to change the equation between healthcare—basically that the healthcare is taking care of the sick and not of the healthy.

We came at that time with the basic of InsideTracker. The basic is very simple. First of
all, all of us are a machine and like a machine, we need to take care of ourselves.
Today, we are not taking care of ourselves. If you look at that, you go to the physician
mainly when the machine or “us” is broken down. When we are breaking down then we
go to the physician. So we decided to find a way to have once a month to have a
check-up that we can basically check ourselves, find what is not completely optimized
with ourselves, then intervene, and then have our body good for a few more months.
I really like the analogy of the car: so every 5000 miles, you take the car to the
technician. The technician plugs a computer into the car, the computer tells the
technician exactly what should be done in order to make the car good for another 5000
miles, should he replace oil or the oil filter and so on. The technician does that and then
the car is good for another 5000 miles. There is a lot of research that shows that since
the time that this routine schedule of maintenance for the car was introduced, in the
80s, the lifespan of the car increased from around 100,000 miles on average to around
200,000 miles on average.

So we said let’s do something similar. We cannot obviously plug a computer into our
body, but we can plug a needle into our vein and extract the liquid gold that we have in
our veins, called blood. Then when we extract the blood, we can look at the biomarkers
that show where you are staying and based on that, you can find optimal zones for each biomarker. I can give you an example; let’s look at the most boring, maybe, biomarker that you know, which is glucose. For all of us, the optimal zone is between 65 to 99. It doesn’t matter if you’re male or female, young or old, Olympian or couch potato, someone that is obese or someone that has a BMI of less than 15; all of us should be between 65 to 99.

We said that that’s wrong; let’s find an optimal zone for each of us based on age,
gender, ethnicity, and athletic activity, and other criteria. Let’s find an optimal zone that
is matched, and then find whether you are within your optimal zone, above or below. If
you are not in your optimal zone, we can subscribe you an intervention that includes
food, supplements, exercise, and lifestyle changes, that basically will help you to bring
yourself to the optimal zone, and when you bring yourself to the optimal zone there is a
good chance that you will optimize your health, your performance, and hopefully, your
longevity.

So that’s basically the background of InsideTracker. I just want to say that all of our
recommendations, the zones, everything, is extracted from peer-reviewed scientific
literature. We have a team of scientists that do that, so we are looking at it very
seriously and taking it very seriously.

[Damien Blenkinsopp]: What are the most common use cases you have
today? You mentioned a few different things like athletes. What are your clients today?
What are they mostly using it for?

[Gil Blander]: We have three main segments of clients: we call them the
train, the gain, and the pain. The train is, as you said, is an athlete: someone that wants
to shave two minutes off his marathon time; someone that wants to play at the fourth
quarter; someone that wants, basically, to approve his athletic performance. The gain is
an interesting segment. People—that are more like me—that are trying to reach to their
forties, trying to stay in their peak performance, trying to reach the afternoon and have
enough energy and enough patience to play with their kids; people that are trying to
perform better in their work, so a lot of executives; those are the gain population. The
pain are people that are sick.

Currently we are mainly trying to serve the train and the gain, because we feel like the
pain, which are sick, have already someone taking care of them—that’s the physician,
and wishing that the physician is doing a good job. We also don’t want to get into all the
regulation—when you are sick, there is more regulation. We are trying to have a proof
of concept or to show to the train and the gain that we can help them a lot, and maybe
in the future, we’ll go also for the pain, but currently, the main customer segment that
we are trying to approach are the train and the gain.

[Damien Blenkinsopp]: Thank you very much for that. You have just
created this new panel, which is called InnerAge, and it’s specifically targeted at aging,
whereas the rest of your platform, as I understand, is a bit more general. When you
were looking at the criteria for selecting biomarkers, how did you go about that? What
kind of criteria were you looking for in order to select the biomarkers that you’ve put
into that panel?

[Gil Blander]: First of all, we built a team of scientists, and actually we
recruited new scientists and we work with our scientific advisory board. I want to
mention that two of those scientific advisors that we have, one of them is Professor
Lenny Guarente from MIT, who is considered to be the father of new aging research
era and is by far considered to be the initiator of the aging research in the world and
considered to be one of the five top researchers of aging in the world.

Another scientist is Professor David Sinclair from Harvard Medical School. He actually did his postdoc at the lab of Lenny Guarente. Now he’s also considered to be one of the leaders of aging research. He’s also extremely involved in the biotech community; he’s started a lot of companies, and one of them called Sirtris—which use what they call resveratol (which I assume that you’ve heard of), a small molecule that is in high concentrations in red wine and has been shown in a lot of studies to increase longevity—was sold to a big pharmaceutical company a few years ago for $720 million. So both David Sinclair and Lenny Guarente help us to do that.

As to your question, we basically spent almost two years looking at hundreds of
biomarkers and trying to see what is the effect of those biomarkers on aging or
longevity. Basically, we were trying to pinpoint, looking at the scientific publications,
which are the five that are the most related to longevity.

[Damien Blenkinsopp]: So, just to take a step back—when you’re talking
about longevity and aging, are we referring to mortality here? Some people when they
think about aging, they’re thinking about their skin and how they look and things like
that. Are we talking about longevity in terms of how long we’re going to live, or is it
other aspects also?

[Gil Blander]: It’s a good question, and the answer is yes. I can give you
again the example of glucose, which is one of the markers that we have in the
InnerAge. We looked at the data and we found a lot of data that showed, not surprisingly, that when your glucose is high, you might compromise your longevity. But
we were looking for better data and we found it in the scientific publication that was
published based on the Framingham Heart Study. I don’t know if you’ve heard about it?

[Damien Blenkinsopp]: Of course, yeah.

[Gil Blander]: It’s basically a study that was done here in Massachusetts,
in a small lake town next to Boston. They followed up the population of this town for
tens of years and measured some biomarkers. What they found is that there is a strong
correlation for the level of glucose at a certain age and your final longevity. Let me give
you an example: if you are 40-years-old or 35-years-old and your fasting blood glucose
today is 70, you have a good chance to reach your 90s; if your glucose is a bit higher,
let’s say 80, you have a better chance to live to your 80s; and if your glucose is in the
90s, you have a better chance to live to your 70s; but if it’s 100 plus, you have a better
chance to live only to your 60s. So based on that, we took the data, we compiled it, and
then you can basically take a person and say, this person’s age is 40, his glucose is X,
so basically based on the glucose, the predicted longevity will be 80. He’s now only 40
so he has, just by the glucose, 40 more years to live.

Now we’re looking at a few other markers, so each of them show us what the effect is,
then we compile it all together using an algorithm and that’s what we show you as the
InnerAge. We show it to you in comparison to your chronological age, meaning what is
your age today.

[Damien Blenkinsopp]: So it’s an estimate of your longevity based on an
average person? The trendline I guess you’re showing is chronological age against this
biological age, and it’s showing it against, say an average 80-year-old or if you’re doing
better than the average, maybe you’re going to live to 100?

[Gil Blander]: Yes, so it uses the average but also, I want to say that it
shows what is happening with you today. It doesn’t say, and we’re not trying to say that
if you’re a 40-year-old male and your InnerAge is 30, we’re not trying to claim that you
will live 10 more years than what you’re supposed to or than the average. What we are
saying is that if you continue to stay like that, you have a chance to live ten years less
or ten years more. So that’s a very important point.

What is also very important is that for each of those biomarkers, we have an intervention that you can take in order to optimize your InnerAge, and it’s very important for us to take markers that you can intervene. For example, we are not taking a marker of a disease like BRCA1 or other markers that show whether you have cancer or not, and you cannot do an intervention for that.

[Damien Blenkinsopp]: Right. We don’t have any ideas about what exact
tool we could use to change the fact that, apart from having surgery and having your
breast removed in that case, but there’s no specific intervention that you have linked to
those. So you stick to things that are actionable, which is great; that’s what we like to
hear on this show.

[Gil Blander]: They are actionable and more than that, they are simple
interventions. So it’s a food supplement, exercise, lifestyle changes, so similar to Inside
Tracker but a bit more simple. And the simplicity comes with the next feature that we
have in InnerAge, which we called “focus foods.” So focus foods are basically nutrient-
heavy foods that will help you to optimize all the biomarkers that are related to InnerAge that are not optimized for you. So basically, focus foods are foods that are personalized just for you based on the level of the biomarkers that you have and they will help you to optimize all the biomarkers that are not optimized just for you.

For those foods, you don’t need to change completely your routine. What you need to
do is pick a couple of them and start to integrate them into your diet. So for example, if
you need to consume more oatmeal, eat it every day; that’s it. You don’t need to
change completely your behavior. Or if you need to eat strawberries, just try to integrate strawberries. Don’t change all your diet. So what we’re trying to do here is very simple because, as you know, it’s very hard for us to change our diet completely. You have a lot of influence on your diet, you are at home or at the office, you are commuting, you are travelling—it’s not easy. But when you have only a few food items that you need to incorporate all the time, it’s much easier to do that.

[Damien Blenkinsopp]: Could you give us an example—you gave us a
blood glucose example—as to what kind of recommendations the tool would make: I’m
40-years-old and my blood sugar is currently at 95. My fasting blood sugar I guess
we’re talking about.

[Gil Blander]: First of all is nutrition. To optimize your blood glucose, it’s
very important to consume foods that are rich in fiber because the fiber helps our body
to absorb the glucose and then the level of the fasting blood glucose decreases, and
that has been shown to increase your longevity. So one thing that it’s very important to
do is to try and consume more food that is high in fiber. Another thing that it’s good to do is to exercise more. Again, depending on the person; if you are a professional athlete, don’t exercise more. But if you are not, exercise more. Also maintain a healthy weight. There is a lot of data that shows in the literature that if you are overweight, you tend to have higher blood glucose. So there are a lot of interventions like that.

Each of our users receives the intervention based on this information. So if you have a
high BMI or you are heavy, you will receive the intervention of lose weight. But if you
are not, you won’t receive it. Or if you are exercising five times a day, you won’t receive
a recommendation to exercise more. But if you are not exercising at all, you will receive
it. So there are a lot of interventions that are personalized and coming to you based on
your profile and based on what will help you to optimize yourself.

I just want to add that we are also taking into consideration your dietary preferences. So you can tell us that you are on the Paleo Diet; you can tell us that you are a bachelor, live in town and don’t know how to cook; you can tell us that you are gluten-free; so we have a list of a few kinds of dietary requirements that you just need to click and then the algorithm will provide to you the food that is good for you and will help you to optimize yourself.

[Damien Blenkinsopp]: Which other biomarkers have you looked at for the
InnerAge panel? Which other ones have you included today?

[Gil Blander]: We discussed the glucose, we also added vitamin D, we
added testosterone for males, we added CRP, which is a marker of inflammation, and
ALT, which is a marker of liver function.

[Damien Blenkinsopp]: Vitamin D, a lot of people talk about that today, so
that’s common about the benefits to the immune system and so on. Testosterone, I
think, is not so obvious for a lot of people—what’s the issue with testosterone? Why’s
that important when it comes to aging for men?

[Gil Blander]: That’s a great question. What we have seen, and I assume
that you’ve heard about it, that the level of testosterone is decreased by 1-2% every
year when we are getting old. Testosterone is important for our muscle tone, it’s
important for our sex drive, it’s important for our mood. So it’s very important to maintain a healthy testosterone in order to maintain the health and longevity.

What you eluded in your question is, is testosterone as important as glucose? and my answer is definitely not. So each of the biomarkers that we included has its own value or its own weight. So, if you ask me if you have low testosterone and have a high glucose, what is more important to take care of? I would say definitely start with your glucose, and then move to the testosterone. But the testosterone is also very important and there is a lot of data in the scientific literature that shows that.

[Damien Blenkinsopp]: I believe there’s a lot of research on strength and
muscle: the higher the levels of muscle you have going on older in life, the better your
longevity chances. So that correlates also with the testosterone.

In terms of testosterone, what kind of ranges are you looking at? Because there are
obviously the lab ranges we often talk about here—you have the LabCorp range for
example—which isn’t necessarily, and I imagine is probably, not the same as the range
you’re looking at, so what kind of reference range are you looking to get people into?

[Gil Blander]: As I mentioned before, we have what we call the optimal
range or optimal zone, and that’s calculated exactly based on the papers, like I told you
before, looking at the population of thousands or hundreds of people and seeing what is the level of testosterone at specific ages. Then we can from that come with an optimal zone based on your age, based on your gender—obviously, because males and females are completed different—also based on your athletic activity. Those ranges come in based on all the demographic information and then we subscribe to you the optimal zone that is good for you. Your optimal zone might be completely different for a person completely similar to you but in a different age or ethnicity or so on.

[Damien Blenkinsopp]: That’s interesting. Do you look at the difference
between someone who’s doing endurance training versus heavy-weight training, the
different approaches?

[Gil Blander]: Yes, we are extracting the information that we can from
the peer-reviewed scientific literature. For some of them we have data, so we are doing
that; for some others, we don’t. Basically, we are trying to extract the most that we can,
but I want to admit that we don’t have everything because not everything is published in
the scientific literature. In order to try to fill the holes of that, we are building our own
database and we are mining the database. We have a lot of athletic active population
who are doing either strength or endurance, so we are starting to extract information
from there and then help our customers to compare themselves more to their peers
than compared to a couch potato doing nothing.

[Damien Blenkinsopp]: Great, I understand. So I’m guessing it’s early stages
in terms of mining the information from the client base. When do you expect to bring in
the first bits of information from that and analysis to help improve the tool?

[Gil Blander]: We are actually doing that already. We have what we call
a benchmarking tool that shows how you stand compared to InsideTracker
community. So for example, we can see that a high percentage of our community have
a low vitamin D. But you want to know whether it’s 5% or 20% or 40%, so we are
showing and sharing it with our community. They like it a lot because sometimes people say, “Oh, I have low D but it’s 50% of the population. It’s not so bad.” So some people like to see, “Oh, everyone’s having this issue so I’m not…”

[Damien Blenkinsopp]: Right, yeah, it’s not so bad.

[Gil Blander]: “… I’m not going to die tomorrow.”

[Damien Blenkinsopp]: Are you able to tunnel down and say, it’s athletes
like me, say I’ve put into your system that I’m an athlete and I’m eating Paleo, would it
be able to position me compared to that population, or is it early stages for that still?

[Gil Blander]: We are doing it currently just for specific customers; we
are basically tailoring it for them. We have what we call an InsideTracker Pro, which
we’re working with some professional athletes, teams, some gym chains, and others.
For them, we are doing what we call a tailoring solution for them. But we don’t supply
that yet for the person that comes to our website. We are working on that and we hope
to have it soon.

[Damien Blenkinsopp]: In terms of the number of users you need to make
this really useful, how many users do you have today and how many would you think
would be important to have to really make lots of statistical analysis? I guess you have
ideas about doing data mining and a lot more exciting and intricate things.

[Gil Blander]: We have many thousands of users. Obviously I cannot
expose the number. I have a statistician on the staff that helps us to analyze and to
evaluate each of them, so basically we are doing rigorous scientific work and statistic
work, and based on that we decide whether we have enough power to share it with our
users.

[Damien Blenkinsopp]: In terms of the benchmarks you’re using, we’ve
already discussed that they’re different to the lab reference ranges, so when I go into
the system would it also show me for instance the normal reference ranges and how
yours are different? Or will people just get your reference ranges? So that they can
compare—say they’ve had tests outside of your system in other places before, when
they’ve been given other numbers.

[Gil Blander]: Yes, it’s a good question. We are showing base, what we
call the normal and out-of-normal, and then we are showing the optimal. For some
biomarkers, we are showing even more ranges. I can give you an example of
cholesterol. There is an optimal, then you have a normal, then you have a near-normal,
you have high, and you have very high. So, sometimes it’s more complex than just
optimal, normal, and the out-of-normal. But in most of the biomarkers, you see the
optimal, which is our range, you see the normal, which is the range of the diagnostic
companies, and then you see the out-of-normal, which is out of the diagnostic
companies. Most of the time, our optimal range is consumed by the normal so it’s a
subset of the normal.

[Damien Blenkinsopp]: Right, I understand. So out-of-normal range means
the standard labs like LabCorp or based on the research and so on; thank you. Which
other biomarkers did you look at that you decided not to include in your panel?

[Gil Blander]: In the InnerAge panel?

[Damien Blenkinsopp]: In the InnerAge one, yes.

[Gil Blander]: One interesting biomarker is cholesterol, which when we
started to work on that I was sure that cholesterol would be part of the panel. I asked the
scientist that worked on this marker after a couple of weeks that he was working on
that, “Okay, show me the papers.” He said, “Gil, I cannot find any papers.” So I told him,
“Are you kidding me?” Well, you have cholesterol, you have statins, and you have
lipidol, and a business of, I don’t know, ten billion dollars. So I told him, “You know what,
I will spend.” I spent four weeks on that and I couldn’t find anything. You could find old
papers but old and new papers haven’t shown a strong correlation between cholesterol,
or LDL, and longevity.

Very interestingly, exactly a year ago, the new guidelines of the American Heart
Association came out, and basically said that cholesterol is not as important as it used to
be. It is important if you are overweight, if you have high inflammation, if you are not
athletically active, if you have a family history of high cholesterol, or if you have blood
pressure, but someone that doesn’t have most of those, it’s not as important as it used
to be. That was a big surprise for me, but apparently we came to the same conclusion
that other agencies or all the scientific community came to, so that was a very big
surprise.

[Damien Blenkinsopp]: There is definitely a lot of movement going on
around the cholesterol markers. One interesting thing with that in relation to your
testosterone is I found it’s easier to get my testosterone raised when I have higher
cholesterol. So I think if you’re on a lower cholesterol diet, it can be more difficult to
raise your testosterone, which you’ve included in your panel.

[Gil Blander]: Yeah, it makes a lot of sense because if you look at that,
testosterone is a derivative of cholesterol. So basically, cholesterol is one of the building
blocks of testosterone. So when you have low building blocks, it’s harder to build the
building. Actually, a couple of weeks ago, another news about cholesterol came out,
and what they’re saying now is that cholesterol is not evil. You can eat cholesterol as
much as you want if you have a good metabolism and your body can metabolize the
cholesterol. It’s not like everyone needs to run away from cholesterol. Again, don’t eat it
like crazy, don’t eat 50 eggs a day, but if you eat one or two eggs a day, you should be
all set, other than someone that has all the risk factors that we discussed.

[Damien Blenkinsopp]: You’ve included CRP. The reason everyone was
focused on cholesterol was for heart disease, but it turns out that hs-CRP is a better
marker, correct? Is that why you’ve included it?

[Gil Blander]: Yes, but CRP is not only for that. CRP is basically a
marker of inflammation and it’s related to cardiovascular diseases, but it’s also related to
a lot of other diseases, including cancer, and even diabetes. So, CRP is a marker of
inflammation, and inflammation is more and more considered to be a big, big problem,
not only for after athletic activity that your inflammation is increased but also for the
average population. Definitely inflammation is very important.

[Damien Blenkinsopp]: As you just mentioned, with athletic activity the
marker would go up, so I guess your tool comes in pretty useful in this situation because
you’re looking at those different populations and saying what’s normal for them.

[Gil Blander]: Exactly. It’s normal that your inflammation will go up after
athletic activity. For example, after a marathon run, I would suspect that your CRP
would be high. But it’s not normal that it would stay high for a week after that. So what
we are doing is we are asking our users to test themselves at a certain time when they
haven’t been running a marathon the day before, or maybe haven’t been highly
athletically active for a week before, and do it also after a day of rest. Then, if your
inflammation is high, that means you have some issue. It could be that you over-
exercise, could be that you have some injury, and it helps us and it helps our users to
pinpoint what the issues are that they have.

[Damien Blenkinsopp]: Great. It sounds like you’ve put a lot of controls in
there. Have you done the same thing with blood glucose? I’m just curious because we
had someone else on the show before, Bob Troia, “Quantified Bob,” and he’d been
tracking his fasting blood glucose daily and I was quite surprised to see how much it
went up and down most days. He was doing football practice some evenings, so he had
some correlation differences between the mornings after the night he’d been in football
practice and exercising versus a normal day when he hadn’t been exercising the day
before.

[Gil Blander]: Yes. First of all, I know Bob very well; he’s a user of
InsiderTracker and he’s a very interesting person. I completely agree with you. A blood
glucose, even fasting blood glucose, can change based on what you have done the
night before. What we are reaching or trying to do with our user or trying to explain to
everyone, it’s not only one time point and InsideTracker is not a tool that you should use
once. You should use it and use it again and again and again, and then when you start
to use it again and again, you see where is your field—Is it running between 80 to 90? Is
it running between 90 to 110? Or is it jumping all over? And usually it should be more or
less flat. And you can also start to see the trend if during the aging process or when you
are becoming older and older, you’re starting to see a trend of increasing it. So I
completely agree with what Bob has showed, but what we are trying to do here is not
looking at one point, not even two points, in order to see a trend you need to have at
least a few points.

[Damien Blenkinsopp]: How often do you recommend people take the
blood samples for the tool?

[Gil Blander]: We recommend that you do it at least a couple of times a
year. We have some users that are doing it four times a year; we have some athletes
that are doing it even once a month in order to really keep them in top performance, but
the average users that we have are doing it around twice a year.

[Damien Blenkinsopp]: Okay. That sounds about similar to me, actually—
what I do—so I’m glad to hear that I’m average in terms of how often I do these panels.
To learn more about InnerAge and any resources of our aging that you’ve come across,
first of all, where can we get information on InnerAge itself?

[Gil Blander]: Everyone can come to our website, it’s insidetracker.com,
and there we have a link to a page that we developed that shows what is InnerAge, an
explanation about focus foods, an explanation about the science, why those
biomarkers, and about the scientists who developed it. We developed a lot of
information for that because we know that it’s the cutting-edge and people need a lot of
information to understand what we are doing, so we devoted a page with a lot of
downloads that you can read PDF after PDF and spend maybe a full afternoon learning
about InnerAge.

[Damien Blenkinsopp]: So you’ve mentioned the scientists you’re working
with on this tool. Is there anyone else you would recommend to get more information
about aging, or are there any references like books or particular presentations that you
found useful in your research?

[Gil Blander]: Yeah, there are a lot of good scientists that are studying
aging. I mentioned Lenny Guarente and David Sinclair. There are a few other leading
scientists that are studying aging. One of them, which is a very interesting person, his
name is Nir Barzilai, located in New York City, and he’s studying mainly long-lived
humans and trying to see what are the changes in their genome and their proteome
compared to the average human, so that’s an interesting person to look at.

Another very interesting scientist is Cynthia Kenyon, who is from UCSF in San Francisco. She’s
focused mainly on the insulin pathway, which is very related to glucose—insulin and
glucose. She started with the model organism slow worms, and now she’s also working
on other model organisms. So I think that if you are looking at, or your audience will
look at those four, you can find a lot of very interesting information.

[Damien Blenkinsopp]: Great, thank you very much for that. What would
be the best ways to connect with you personally? And you on Twitter, Facebook?
Where do people connect to you? Where are you most active?

[Gil Blander]: I actually like Twitter a lot so I’m on Twitter. They can find
me, it’s GBlander1 and they can find me there. If someone has any questions, they can
contact us via our website. On our website there is contactus@insidetracker.com and I
would be more than happy to talk with them.

[Damien Blenkinsopp]: Great, thank you, Gil. I just wanted to learn a little
bit about you before you go, are you using your tool every month? What are you doing
in terms of tracking your biology at the moment?

[Gil Blander]: It’s a great question. I’m using the tool at least four times a
year. There are some months that I’m maybe testing every day. There was one day
that I was testing myself like four times because I’m all the time trying to find new tools.
So we are using home kits and different labs, and often my arm is completely dotted
with blood stains.

On top of that I used to use other Quantified Self tools. I used in the past the HRV from
Ithlete, which you interviewed Simon, and I think that it’s a great tool for the athletically
active population. Currently what I’m testing every day, or all the time, is my activity,
and my weight. I’m trying to use some other tools, so we’re trying to develop now a new
nutrition tool for our users, so obviously I’m using some nutrition applications,
MyFitnessPal, Nutrino, and others. So I’m using a lot of different tools but in the day-to-
day and in the last year, I measure my weight every day by Withings, which is a
European company, which have a great wireless scale. And I’m measuring my activity
using Fitbit, but I did test it from the 23andme to measure my genome, so I’m trying,
because I’m working on that, I’m trying a lot of different tools.

[Damien Blenkinsopp]: It sounds like you’ve got involved in a lot of them. Is
there any key insight; what have you learnt about yourself so far? Is there one important
thing that you’ve learnt from these activities?

[Gil Blander]: Yeah, I leant about myself that data is the key for me. For
example, when I’m measuring my weight, every day I’m measuring it here in the office,
after that I make a decision, should I eat that or should I eat that? Because it’s showing
me every day whether my weight went up or went down. So I succeed to maintain my
weight more or less stable. When I’ve seen that my weight is too high, I use some tools
to see if it’s helped me to decrease it. For example, I did an experiment when my weight
went up after the holidays. I started to log my food in MyFitnessPal and I lost like eight
pounds in a week and a half. The issue is that you cannot continue with it forever
because it’s very time consuming and annoying to add what you ate every day. So it’s a
good intervention but it’s for the short-term.

What we are trying to develop here in InsideTracker currently is find a tool that will
help you to maintain your weight, maintain your biomarkers, maintain your activity,
which is more seamless, and it’s not easy. We have a team of scientists, exercise
physiologists, coaches, and nutritionists who are trying to do that. But it’s definitely not
easy.

[Damien Blenkinsopp]: Yeah, great. Well keep me updated if you’re
coming out with something interesting; that would be great. So one thing you did
mention right there, which I forgot to mention, is I think that InsideTracker, currently
you use LabCorp request to get people’s samples. So you give them some requisition
forms and the person runs down to LabCorp and it gets sent to you, but you said you’re
also using home kits. Is that something that’s going to change in the future or is that just
for you in experimentation?

[Gil Blander]: No we have home kits. So if someone wants to use the
home kits, we have them; we are using home kits. The problem with the home kits is
that we tested a lot of vendors and most of them haven’t had the precision of the
measuring of the biomarkers to be good enough for us. Because we are giving you an
optimal zone, you should have the precision. So we came with two vendors that are
precise enough, but the number of biomarkers is limited. So for one of them we have
only five biomarkers; the other we have seven. But we are still using it because some
people are too lazy to go to the lab, some others don’t live in the U.S., and currently the
lab availability is only in the U.S., so they can use our advanced home kit and we are
sending it all over the world. So because of those reasons we are still using the home
kits.

We also hope that in the future, the quality, the precision of those home kits will be
better, then we could use more and more biomarkers. I really hope, and I think that it
will happen that in the next five years, we won’t need to go to the lab at all, we can use
our iPhone. Basically we are saying that you can bleed on your iPhone, spit on your
iPhone, pee on your iPhone, and then receive a lot of information, so that’s our goal. I
think that it will happen and what is nice about InsideTracker is that we are a
technology diagnostic. We don’t care where the information comes from; what we care
about is the quality of the information because we are running it via our analytic and
then providing to you the ranges and the recommendations. So as soon as the
technology will be good enough, we will integrate it.

[Damien Blenkinsopp]: I’m sure you are aware of Theranos and what
they’re doing. I don’t know if you know, but would you think that their services would be
accurate enough for you when they get to market? Or do you think they’re still focused
on being in or out of normal range and it’s not necessarily sharp enough for you?

[Gil Blander]: Theranos is very interesting. What is interesting is that
instead of taking the blood from the vein, you take it from the finger like the home kits
that we’re using. What is also interesting is the volume: because you’re taking it from the
tip of your finger, you cannot extract a milliliter; you are talking about microliters. What
is also interesting, that they promise, is that you can do it on time. So you receive the
information immediately, while when you do it at the lab it takes a couple of days, and
when you do it with the home kit it might take a couple of weeks. What is happening
with this—at least today, and I don’t know, I hope it will improve—is that even though
that they have a machine that can do it in place, they are sending it to a central lab. So
basically you go to one of the clinics of Walgreens. Currently only in…

[Damien Blenkinsopp]: I think it’s Arizona.

[Gil Blander]: Only in Arizona.

[Damien Blenkinsopp]: There’s one in San Francisco I think, as well.

[Gil Blander]: There should be one in Palo Alto, yeah. So you prick your
finger, they fill a small vial, and then they courier it to the lab. The lab do their analysis
and then you receive the result, I assume a day later, I’m not sure I haven’t tested it. So
you lose the value of the immediate response, that we don’t have, but it sounds like (at
least what they claim is) it’s accurate, which is great. Also, another advantage that they
have is the price: their price, at least the sticker price—what they show on their
website—is much lower than the price that a biophysician would do it, which is great
value. But again, it’s only available in Arizona; it’s not immediate. I think that it’s still an
intermediate solution. So it’s nice progress but it’s not the end product. The end product
will be the…

[Damien Blenkinsopp]: The iPhone.

[Gil Blander]: … your iPhone, yeah.

[Damien Blenkinsopp]: Thanks for the commentary on that because it’s
hard to know actually what’s going on and how far the progress. So it’s still in a trial
stage, Theranos.

[Gil Blander]: I assume so but my knowledge is the same as your
knowledge. I don’t have any internal knowledge about that.

[Damien Blenkinsopp]: Great, thank you. Well Gil, thank you so much for
answering all our questions today. You’ve given us some great insights into how you’ve
constructed your aging panel there.

[Gil Blander]: Thank you so much and I’m looking forward to really cool
entrepreneurs in your future podcast.

Leave a Reply

Today’s episode is about practical tools that we can use to improve our biology and how we can track those results to make sure we are getting the right answers. This episode can serve as an important source of information about N=1 experiments and biohacking.

N=1 experiments involve a single subject and they are entirely capable of providing statistical inferences about the efficacy or side-effects of treatments specifically on that subject alone. The aim of this episode is to provide very practical tips that are really accessible to you. Some of the topics covered are the Bulletproof diet, intermittent fasting, and the impact of oxaloacetate supplements.

“So we could run the same experiment…and your results can be different from mine, but it doesn’t mean that either are wrong, it just means that we’re all individuals. Our results apply to ourselves and we [need to approach it in] a different way in terms of how we want to improve or optimize something.”
– Bob Troia

Bob Troia’s quest for self knowledge, betterment, and optimization inspired his own self-tracking, biohacking, and n=1 experiments. Some of Bob’s experiments have included glucose hacking and tracking, telomere analysis, bulletproof diet (cholesterol/bloodwork), and central nervous system (CNS) training. He has had the opportunity to give several Quantified Self talks on his glucose tracking experiments. 

Bob is also a successful tech entrepreneur, and is currently working on a new venture, HuMend, which is developing a solution to treat musculoskeletal injuries using 3D printing technology. Bob holds a Bachelor of Science degree from Pennsylvania State University in Agricultural and Biological Engineering.

The show notes, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know what you think in the comments!

itunes quantified body

Show Notes

  • Bob’s interest in quantified self and biohacking results from trying to uncover and understand what makes him tick and how to optimize and improve it. (Time 5:58)
  • N=1 experiments are implemented on one person. They are not scientifically applicable to the whole population. (Time 8:00)
  • One of Bob’s earliest n=1 experiments involved a paleo-like diet called the Bulletproof diet. (Time: 9:00)
  • There are a number of online services that can facilitate your bloodwork testing. (Time 12:55).
  • There is a big difference between traditional and functional medicine. The normal ranges for traditional medicine may not be applicable to individuals based on their unique genetic composition. Services such as InsideTracker and WellnessFX may give you a “range” for your results, but you may need a functional medical practitioner to further investigate the details. (Time 14:00).
  • Part of a low white blood cell count is not that your immune system isn’t kicking up; it’s that it’s being suppressed. (21:00).
  • An underactive thyroid is linked to elevated LDLs. Bob was introduced to some programs that support thyroid and adrenal functions, and that was a shortcut which led to improving numbers such as total cholesterol, LDL, and testosterone. (28:00)
  • Bob’s recommendation is to find a medical practitioner with more of a functional medicine background. (29:50)
  • Another of Bob’s recommendations is to find a medical practitioner who has an investigative mindset.(31:16)
  • Bob sees the philosophy of “Quantified Self” evolving into “Quantified Team.” (33:00)
  • Bob gets testing every three months. He is still investigating having more short-term testing, for instance on a monthly basis. (37:00)
  • The biomarkers Bob tracks on a routine basis range from basic panels, cholesterol markers, glucose, nutrients like calcium, magnesium, vitamin D, white blood cells, C-reactive protein, and an MDL test that can check for chronic infections. (38:00)
  • As part of a longevity strategy and to maintain optimal glucose levels, Bob recommends a supplement called oxaloacetate. (48:00)
  • Other recommendations include the Calm app and binaural beats (Holosync) as tools for meditation. (54:30).
  • Bob’s biggest recommendation is to prevent your data from becoming a hindrance. It is ultimately more about how you feel. People have the tendency to over think it, instead of just starting to do it.  (1:34:20)

Thank Bob Troia on Twitter for this interview.
Click Here to let him know you enjoyed the show!

Bob Troia

  • quantifiedbob.com: Bob Troia’s personal self-tracking, biohacking, n=1 experiments, and Quantified Self tools and resources.
  • Bob on Twitter @QuantifiedBob

The Tracking

Biomarkers

  • Cortisol to DHEA Ratio: Cortisol is a stress hormone and DHEA is a precursor to testosterone and estrogen. Both are produced by the adrenal glands. Since they work in an opposing manner, they are more efficiently measured as a ratio. A normal ratio is approximately 5:1 to 6:1. An abnormal ratio indicates a problem with the adrenal glands.
  • hs-CRP (high sensitivity C-Reactive Protein): A marker of inflammation. The hs-CRP test accurately measures low levels of C-reactive protein to identify low but persistent levels of inflammation which is an indicator for cardiovascular disease (CVD), overtraining and other systemic inflammation issues. In a previous episode (episode 19), Dr. Garry Gordon notes hs-CRP may or may not be a sensitive enough marker of inflammation as it depends on the location and type of inflammation. Also, C-reactive protein is discussed previously in Episode 7 for tracking CVD risk.
  • Fasting glucose: Fasting glucose is one of the clinical markers for blood sugar regulation and can indicate a progression toward diabetes. In order to establish a baseline, Bob performed a fasting glucose measurement with eight hours of fasting before each morning.
  • HRV (Heart Rate Variability): HRV is one biomarker that is a good indicator for overall health and fitness. A high HRV shows that the parasympathetic response is dominant, and vice versa for a low HRV. A high HRV score – greater variability in the time gap between heart beats – is a good thing because it indicates a healthy, fit, well­-rested heart. Damien has found it beneficial to take his HRV readings every morning because a dip could be an indicator of additional stress load. We’ve covered HRV in many episodes (see here)
  • Telomere length: Telomeres are the protective DNA structures at the ends of chromosomes. Over time these protective structures shorten and degrade, as a result of the aging process in general for instance. By measuring telomere length, we’re able to identify how short they are against benchmarks, such as the societal norm, or sub-groups, for a typical age and gender, and use as a proxy for the aging process and how we are faring against it.
  • LDL (Low Density Lipoprotein): The traditional measure of ‘bad cholesterol’ that many doctors still use to evaluate cardiovascular risk, but for which research has now determined not to be the best predictor of cardiovascular risk. However, LDL is also associated with other risks can be a useful marker in general – such as an underactive thyroid as mentioned by Bob in this episode.

Lab Tests, Devices and Apps

  • InsideTracker: InsideTracker is a personalized health analytics company with a platform that tracks and analyzes key biochemical and physiological markers, and applies sophisticated algorithms and large scientific databases to determine personalized optimal zones for each marker.
  • WellnessFX: WellnessFX is a platform that visualizes your blood test results over time, as well as detailed descriptions of each biomarker for an easy interpretation of your overall health. WellnessFX also offers personalized consultations with licensed health practitioners for even more insight into your health.
  • 23andMe genetic testing: A service that provides a DNA kit for collecting samples and analyzing DNA.
  • MDL (Medical Diagnostics Laboratories) testing: A one vial test that can expose different pathogens. Bob referred to this test as one that extends more than the traditional panel and can indicate the presence of chronic diseases.
  • LabCorp: Laboratory Corporation of America provides lab testing and services, with expertise in esoteric testing, genomics, and clinical and anatomic pathology.
  • DirectLabs: DirectLabs offers blood chemistry tests directly to you online at extremely discounted prices with results available in as little as 24 hours for most tests.
  • GeneticGenie: Shows your free methylation and/or detoxification profile after sending a saliva sample to 23andMe genetic testing.
  • Promethease: Compares a person’s DNA data with entries in SNPedia, a public wiki on human genetics. Also can use data imported from 23andMe.
  • TeloMe: A company that offers saliva-based telomere length testing and analysis.

The Tools & Tactics

Diets and Nutrition

  • Intermittent Fasting: Involves consuming most of your calories during a very small window, typically 6 hours and fasting the remainder of the day.
  • Paleo Diet A diet that mimics the nutrition of early hunter-gatherers, and consists of all lean meats and fish, fresh fruits, and nonstarchy vegetables.
  • Bulletproof Diet: A diet that involves skipping breakfast, not counting calories, eating high levels of healthy saturated fat, working out and sleeping less, and adding smart supplements.
  • Holosync: A form of audio technology that is said to induce brain wave patterns such as those of deep meditation.

Supplements

  • Oxaloacetate: Oxaloacetate, the common name for the molecule 3-carboxy-3-oxopropanoic acid and synonymous with oxaloacetic acid (depending on acidity.  is an intermediate of the Kreb’s cycle and the stage immediately prior to the formation of  pyruvate (viapyruvate carboxylase) and immediately after the NAD+-consuming conversion from L-malate (via malate dehydrogenase). It is thought to help with glucose metabolism and reduce variability as well as promote longevity due to being an intermediate of the Kreb’s cycle of energy production.

Tech

  • Muse Calm: A consumer EEG device and app that is designed to help you meditate effectively. Damien refers to his use of this.

Other People, Books & Resources

People

  • Dave Asprey: Dave Asprey, Founder and CEO of bulletproof, was mentioned by the guest as someone whose talks on the principles and logic of the “bulletproof” diet attracted him to the paleo-like diet.
  • Jimmy Moore: Jimmy Moore, a previous guest, is an expert on measuring ketones and optimizing ketogenic diets. Moore also spoke about intermittent fasting during his episode.
  • William J. Walsh: Walsh was a previous guest (episode 2) who is an expert on brain-related disorders. He was mentioned in this episode as helping to do certain labs that help assess micronutrient deficiencies or differences that are out of functional ranges including vitamin B6.
  • Ray Kurzweil: An American author, computer scientist, inventor, and futurist. Author of the books on longevity and extending lifespan Fantastic Voyage: Live Long Enough to Live Forever and Transcend: Nine Steps to Living Well Forever. Ray is mentioned in this episode as one of the proponents of solving a problem before going to sleep.
  • Aubrey de Grey: Chief Science Officer for the SENS Research Foundation, a not-for-profit organization funding research into longevity around the world. Aubrey de Grey is featured in episode 14.
  • Tim Ferriss: An American author, entrepreneur, angel investor, and public speaker. The Four Hour Body, authored by Tim Ferriss, is one of the early books that helped Bob.

Full Interview Transcript

Click Here to Read Transcript

[Damien Blenkinsopp]: Hello Bob, thanks so much for coming on the show.

[Bob Troia]: Thanks for having me.

[Damien Blenkinsopp]: How did you get into all of this Quantified Self (QS), biohacking, n=1 experiments? Is this something you’ve been doing for a while? Give us a quick background on what led you to this.

[Bob Troia]: Sure. I’m very different to some of your past guests, in that I’m more like your typical listener. I’m not an expert in a certain field; I’m an entrepreneur who’s been working with emerging technology for about the last twenty years and I just naturally had this curious mind. Even back in the time I was a little kid, it was always about taking things apart and figuring out how things work or putting them back together in a different way.
For me, going back to my teenage years and into college, I was an athlete, so I was always tracking aspects of workouts and training and diet, trying to figure out what had an effect on certain performances and just general improvements, whether it’s trying to gain weight or strength or run faster.
As I got older, out of college and began joining the workforce in the real world, I never got too out of shape, in terms of putting on tons of weight or anything like that, but I definitely wanted to get back into a better shape and I experimented with different diets and training, and again, I was logging a lot of these meals, workouts, and just trying to understand those effects.
So really you went from tracking for performance to getting back to a certain state, and now as you get older, you’re really looking to do it from the standpoint of longevity and maintenance. Because, for example, I had a program I did fifteen years ago where I gained a bunch of muscle and put on some weight, but it was just from a lifestyle perspective, I couldn’t maintain it from playing other sports.
But from a QS perspective, I was always tracking everything, whether it was notebooks, spreadsheets, etc., and about maybe five years ago I found a group of folks—I’m in New York City—like-minded people who were starting a meet-up around Quantified Self. I had never really heard the term before, but when I got together with these folks and they were exchanging stories, I was like, “Oh, these are my people.” I didn’t realize there were other people doing things similar to me in terms of trying to really track and understand and then optimize areas of their life. And so, for me, it really opened the door to this and from the standpoint of, even though we were doing this ourselves, our own n=1 experiments and tracking, when you’re meeting with other people, you can share tips and advice and stories and you can really connect around that.
So you have Quantified Self and then you’ve got biohacking, and they’re very similar but they’re also different in ways. So biohacking, there are people who might be in that school of thought who aren’t necessarily Quantified Self people. They’re just looking to somehow manipulate or get an advantage or optimize a biological impact, whereas Quantified Self people might be tracking non-physical elements of their lives. I found those groups sort of overlap, and for me, it was through some of the conferences that were out there, meeting people—whether it’s the first Quantified Self conference or there’ve been several biohacking conferences.
My interest in this has purely been from really trying to uncover and understand what makes me tick and then figure out ways to optimize and improve it. I’m no smarter, faster, more intelligent than anyone out there, definitely not. I’m still dealing with a number of issues like lingering infections and health issues, but I think it’s trying to achieve that state of being optimal is just something we can all strive for, whether or not we can actually get to it.

[Damien Blenkinsopp]: Yeah, absolutely. And how old are you? Just to give a bit of context.

[Bob Troia]: I’m just going into my forties.

[Damien Blenkinsopp]: Ok, cool. That’s pretty much the same place as I am. That’s interesting. So, just to give you a background in terms of your education and your work because I think that may have an influence.
I came from a business background and a lot of finance, and then management consulting, which is a lot of analytics, so I was doing a lot of this stuff in my work. And just like you, it naturally filtered in to fitness and then it started evolving into longevity and also into health issues when I got some health issues. So I’m just wondering how that compares to your background and if you think it influenced it, maybe your studies or your career? Because some people at home may be thinking, “Well I don’t have a degree in maths,” or “I don’t have an education in consulting or analytics,” or anything, but I think anyone pretty much from any kind of background can get into this stuff and at Quantified Self meetings you see a big variety of different people.

[Bob Troia]: Yes, so my background: I went to a school of engineering, so I definitely have a technical background. I’ve been programming since I was nine or ten years old just writing my old programs. Back in those days, you had to kind of make your own games, they didn’t really exist. So I have a technical background, that helps me from the standpoint of I can figure out a way to solve something, but I don’t have a data analytics background by any means.
From a scientific background we talk about experiments, and there’s a debate about the experiments we’re doing and are they following traditional experimental design? How accurate is the data? And I think when we’re talking about our own experiments, you have to sort of say, “Well look, I’m trying to structure this and control it in a certain way but it’s for me, I’m not trying to release this in an academic paper.”

[Damien Blenkinsopp]: Let’s take a step back, n=1 experiments, I’m not sure if we’ve brought up the term before on the actual podcast, but basically, it’s an experiment just on one person. It doesn’t mean that it’s scientifically applicable to the whole population as in the experiments and studies that are typically done. They’re trying to extrapolate things to say they apply to more than one person and they can be used, but with an n=1 experiment, you’re just trying to see what works for you.
Is that how you’d sum it up or would you look at it a bit differently?

[Bob Troia]: Exactly. So we could run the same experiment, for example, and your results can be different from mine, but it doesn’t mean that either are wrong, it just means that we’re all individuals. Our results apply to ourselves and we go after a different way in terms of how we want to improve or optimize something.

[Damien Blenkinsopp]: So, the reason I contacted you is you’ve already done a lot of different, interesting experiments, basically, and you’ve put those up on your blog, so I wanted to talk about a few of those.
Where would you like to start? Which one was your first major experiment? Was it the diet or the blood glucose?

[Bob Troia]: Yes, my entry point into Quantified Self and biohacking was starting a blog to essentially just share the information I was collecting. I thought maybe it could help other people or inspire them, get feedback on what I was doing.
One of the early experiments I was running was around diet. I hate to use the word “diet” because I wasn’t trying to lose weight. Again, being an entrepreneur, a CEO of a company, and being very active, playing sports, and working out, I got to a point a couple of years ago where I just was basically exhausted; I was broken down. Even though physically I was in shape, I was being successful in my work, everything was great, I couldn’t figure out why I just wanted to curl up in a ball on the weekend and do nothing.
And so I was looking at my diet, what I thought was a healthy diet, meaning there was lots of protein through like chicken, and low-fat, and lots of pasta and carbohydrates and all that, and it was working for me, but as I delved into looking at different diets—and this was when the Paleo movement was taking off and people were looking at rethinking the traditional food pyramid and saying, really you need to incorporate more healthy saturated fats and quality proteins—and so, for me, that was the kind of beginnings of that experiment.
I actually posted about it before I’d even started. I was like, “I’m going to try this and I’m going to post about my first 30 days.” Because you’re not going to see huge changes, but I think even just seeing how you feel as a result of making a minor change, and if it didn’t work, I would just have stopped and done something else.

[Damien Blenkinsopp]: So you set a period of 30 days and you selected a diet. How did you go about choosing the diet? Was it just one you were drawn to or were you looking for something specific, very different from the diet you currently have? I don’t really like the word “diet” either; I think we should really call it nutrition, which is more about what it’s about. But that’s where it is; everyone says diet. How did you go about selecting a diet and the period of 30 days?

[Bob Troia]: In terms of the diet, I was researching, again, the Paleo movement and let’s call it nutritional plans related to the Paleo movement, and I happened to come across the Bulletproof diet—one that I think a lot of people are talking about these days—which is the sort of tweaked version of a Paleo diet.
I’d encountered Dave through various conferences and he himself was running a podcast, so he was talking a lot about the principles behind the diet and the logic behind certain choices and how you structure it all. For me, that’s what attracted me, it was sort of mapped out, there was a lot of information that he had put together and again, it’s similar to a Paleo diet, and I said, “Okay, well let’s look at it. How am I going to change what I’m eating in terms of incorporating protein and protein sources?”
So we’re talking about grass-fed, grass-finished beef and lamb; getting adequate seafood; cutting out sugars and pretty much all grains; no gluten; which interestingly, I realized through blood testing—I had an allergen test and it showed that apparently I was allergic to wheat and barley, not chronically in a bad way, but there was an allergic reaction that kind of went up there, and beer is something that’s my favorite thing in the world.
So just even having to start making changes about what I was eating, people thought I was punishing myself, but I was like, “No. I’m eating this big, great, awesome steak and I’m having butter on it and I’m eating tons of veggies and oils.” So the diet itself, that’s the nutritional side of it, and then there’s also exercise and how do you support that.
Going to the gym six days a week, working out for 2 hours a day, can also contribute to being exhausted. I know you’ve done podcasts on HRV and things like overtraining, that’s very common and so by changing a workout program as well, to something that’s more high-intensity but shorter, you can get a lot of the benefits out of it.

[Damien Blenkinsopp]: Did you do both of these things at the same time? And did you do some kind of control before? Did you take your blood markers before based on your initial diet, which was what you were talking about before, the kind of low-fat chicken, whole pastas? I guess I’d call it the typical body builder’s diet, it sounded a bit like it.

[Bob Troia]: Yeah, I had been getting regular bloodwork prior to doing this so I had some data, not like every month or three months, it was six or twelve months, but I had a good baseline.

[Damien Blenkinsopp]: Where did you get this data from? Where did you go to get your labs? How did you do that, did you do it through your doctor or some service?

[Bob Troia]: A little of everything. The older bloodwork was tied to past doctor visits, physicals; they weren’t as comprehensive but they had some of the basic markers in there. Before I started with the diet, I did a round of bloodwork. There are a number of online services that facilitate your blood testing. You can basically go online and buy this sort of package, then they will set up an appointment. Depending on what state you live in, some of it you can do from home, so you can mail it in; some you go to a lab and they draw it and send it to them.
I used a service called Inside Tracker early on, so that was, I think, for some of the before bloodwork.

[Damien Blenkinsopp]: So that’s very similar to Wellness FX, which is the other well-known one. I think those are the two major ones in the U.S. There’s just a new one in the U.K. that’s trying to follow the same example. But, basically, they’re self-service labs, which try to give you a bit of package of advice with it as well? But you don’t necessarily have to buy that package of advice.

[Bob Troia]: Yes, it will take your results, and when you go to look at them online, they’ll give you suggestions. For example, if a marker is out of optimal range, it will say, “You might want to consider eating more leafy greens,” or some dietary choices.

[Damien Blenkinsopp]: So what’s good about those services is they give you those ranges, which are a bit more functional generally than others. Compared to the standard—if you go to LabCorp or some of the standard things—the ranges they give are probably wider in most cases. Is that what you’ve experienced? I don’t know if Wellness FX try to keep it a little bit tighter.

[Bob Troia]: Yeah, and that’s the big difference between when you talk about traditional medicine and functional medicine. The reference ranges are typically built around our population, which is a generally unhealthy population. So you might be in the optimal range for the general population, but you’re not really… So something like a vitamin D level, you might be considered in range, but a functional doctor might say, “No, you want to be way higher than that.”
The reference range is to some degree—Inside Tracker, Wellness FX—if you’re switching to like a Paleo diet, you might see your total cholesterol number jump up and it will kind of go in the red, but a functional doctor will be like, “That’s not important. What we actually want to look at is your LDL cholesterol and, in particular, the particle size analysis of it.”

[Damien Blenkinsopp]: So this is where even when you do have a service like Wellness FX or Inside Tracker, where they’re trying to provide this online information and support for your understanding of the markers, it’s not necessarily going to give you the best responses. There are, basically, more complex situations like you’ve brought up, where you can have high cholesterol and it’s not an issue at all; it’s just based on the type of diet you’re having, but in other scenarios it might be a problem. I’m sure Inside Tracker is the same, like Wellness FX, is like, “Uh, your LDL is too high,” but in its own conditions, it’s not necessarily so. So this is where it becomes really helpful if you have a functional medicine practitioner working with you or someone who’s aware of this stuff.

[Bob Troia]: Exactly, and I also think—not to single out those services—any service that’s providing just a syloid [check 0:15:39] snapshot of your overall lifestyle health, they don’t have access to all the information. They can show your bloodwork, but they don’t have like for example your genetic information, in 23andMe or something, so maybe there’s an issue there that’s genetic versus tied to a diet. Or having access to other bloodwork is great, but I support it with other types of testing that maybe will be something that was picked up through a saliva or urine or a stool test. So when you have all the information together, and that’s what your doctor will be able to look at with you, versus a service that only has one silo of information.

[Damien Blenkinsopp]: So when you started this, was there anything out of range or something that you focused on from the beginning in your results before you even changed your diet? Or was everything kind of standard and normal?

[Bob Troia]: Well no. Maybe I didn’t go back to the earlier bloodwork and notice it too badly, but when I put it all and tried to look at it side-by-side, things like testosterone were way down, really low.

[Damien Blenkinsopp]: What kind of level were you at?

[Bob Troia]: The 400s.

[Damien Blenkinsopp]: So is that the bottom of the normal reference range?

[Bob Troia]: Yeah, even lower. I probably had it tested and it even dropped below that, but it was considered very low. I think some of the reference ranges I’ve seen, they want you over 600; it just depends on what service you’re using.
I was noticing that my white blood cell count was consistently low, really low. My doctor—I had in my lab results, it showed the white blood cell count and usually they bold something if it’s out of range, to notify you like, “Hey, this is out of range”; it was in red and it said something like, “Bring it to the doctor’s attention,”—he was like, “okay, I’ve never seen that before.” And so that was something that we can talk further about.

[Damien Blenkinsopp]: I had a very similar situation that came up. My white blood cells were basically depressed, but they weren’t crazy out of range; they weren’t acutely problematic. My experience was that traditional doctors didn’t know what to make of that and it was basically, “Well your immune system isn’t responding as well as it should for some reason,” which isn’t so defined. I don’t think, in traditional medicine, if it’s slightly out of range—I don’t know how much you were, if you were just under the reference range or something?

[Bob Troia]: No, it was pretty low. Basically, under 2.

[Damien Blenkinsopp]: Yeah, that is pretty low, pretty severe. It’s interesting because did you discover this stuff when you started testing? Or did you feel like, you said you were feeling exhausted, but it doesn’t sound like you felt like you were sick or anything like that?

[Bob Troia]: Yeah, that’s one of those things where I’m a person who’s never sick, I don’t miss work, I had to function at a certain level every day; essentially, what I was doing was I was getting through life almost with like a parking brake on. When you actually look at the information and see how it can change with time, so a lot of it, you sort of uncover it, but yeah, you might feel great.
I felt good until I was hitting those moments of just exhaustion. On a day-to-day level, I think otherwise—like emotionally and everything else—I felt fine. It was this exhaustion, which we can talk a bit later about, things like addressing thyroid and adrenal problems, which can really tie into that.
But just to get back to the story on the diet, so I did it for 30 days. I got my results and my total cholesterol went up about 100 points; my HDL, which is good cholesterol, went up, it was actually really high which is great; and triglycerides stayed in a pretty good range.
The doctor I was working with at the time kind of looked at it, we did some other testing—this doctor is actually someone who had some background working with people who are eating these sorts of diets and Paleo—but even there he was like, “Well, it’s a bit out of range but we’ll do some additional testing.” They thought the cause was purely that it was a fat malabsorption issue, meaning you’re eating all these saturated fats and your body needs to be able to process them and quit them out, if they stay in your body and float around, it will elevate your LDL.

[Damien Blenkinsopp]: So what was funny about that was when I started the Bulletproof diet—I’ve been following pretty much the Bulletproof diet, with some modifications here and there but mostly that, for about three years now—and I got exactly the same LDL number as you. Mine jumped to 232 and I went to see a traditional doctor to get my results in Bangkok and he was like, “You’ve got to stop eating saturated fat,” and that’s the traditional line on it.
So you had a doctor who understood a bit more about what those kinds of levels can mean. But it actually did freak me out a little bit when it went up to 232, I don’t know how you felt about it?

[Bob Troia]: I wasn’t too worried because I was expecting that to happen and then when we actually went in, this doctor knew to do a more detailed LDL test. There are different types of LDL in your body: there are these larger particles, which can float around your body, they’re not going to cause any issues; and the smaller LDL particles. When you hear about people having heart issues and just chronic heart disease and all that, it’s because these little particles are getting wedged inside of your veins and arteries. So when you look at the LDL particle size analysis, for me, it was completely the large fluffy ones, so it was actually not an issue.
But, when we looked at the white blood cell count, this doctor sent me to a phlebotomist, who’s a blood specialist, and we did a whole bunch of other blood tests. This was a renowned doctor and he looked at the results and saw it was low and started asking me questions about, have you been working around solvents and chemicals?
Part of a low white blood cell count is not that your immune system isn’t kicking up; it’s that it’s being suppressed. There could be something at play that’s keeping your immune system from activating, so when you think about it, well why was I never getting sick? Because being sick is an expression of your immune system kicking into action?

[Damien Blenkinsopp]: Yeah, this is interesting. I think this is something that a lot of people don’t understand. Let’s explain this a bit.

[Bob Troia]: I know people, it’s the wintertime, and they’re always sick, they’ve got a cold or the flu. I never got colds or the flu or anything, and I’ve always thought of it as being a sign of resilience. But really what it was doing is my body just isn’t mounting any response to anything.

[Damien Blenkinsopp]: So if your body’s not fighting, you don’t get any inflammation, you don’t get all the symptoms because there’s no war going on, basically, where there should be a war going on with you trying to beat the thing down.
I went through exactly the same thing, and I haven’t really been sick for a very long time also. But we’re talking about it being a negative, which most people think, “Wow, it’s great that you never get sick.” Do you get sick now? Have you started to get sick yet?

[Bob Troia]: No.

[Damien Blenkinsopp]: I mean, me neither, but I think it’s a good thing. I think it has something to do with all the stuff I’m doing to keep things at bay, although— maybe we could talk about it—I think you were taking reishi, we could talk about that a little later; maybe you’ve noticed some of the stuff I did.
So anyway, you went through this process and after the 30-day diet, was LDL the only thing that changed or was there a whole bunch of other stuff as well?

[Bob Troia]: Definitely there was a difference in testosterone level; it jumped up. There were other reference markers, things like C-reactive protein, which is an indicator of inflammation—I’ve always had it pretty low; that remained low. There wasn’t anything else that was too out of range, other than the white blood cell count after that and the cholesterol numbers changing. And there are a number of ratios. I had done some research and found you can do things like the HDL to total cholesterol ratio, or triglycerides to HDL, or HDL to LDL, and you’ll get a ratio. They’ve figured out certain ranges that if each ratio is below a certain amount, your risk for things like heart disease or other ways of being a predictor of those types of things can be diminished. In those cases, I was in the green for everything. So, even though my total cholesterol and LDL went up, my HDL had gone up so high and my triglycerides were low enough that the ratios were actually good ratios.

[Damien Blenkinsopp]: I think what you’re illustrating is that when someone goes and gets a bunch of these labs or something, sometimes if we find something out of range, if it’s an LDL or triglycerides or something like that, that’s kind of like the first step. Because after that that’s going to be like, “Okay, this is something to look into,” and then you look into more detail of that. So there are different types of LDL, as you were explaining earlier, or there are ratios of triglycerides, which are more important. So, often when we have something out of range, it’s really like a starting point versus a final point.

[Bob Troia]: And then to follow up on that testing, that doctor basically was saying that I had some fat malabsorption issues, so we did some follow-up tests, some stool tests basically, and it did show that there was a fat malabsorption issue happening.
Then we did some microbiology work on it, as well, which shows you your gut flora, certain bacteria that could be good bacteria or bad bacteria in your gut. It showed that, for example there’s a good species of bacteria you often see in probiotics, lactobacillus; I had like none, which basically allows for some other bad bacteria to maybe grow or thrive in your gut.
So you had to then start going back through time, and I’m like, “Well, I probably didn’t receive any probiotics back in the day.” Maybe ten years ago I had been bitten by a tick that I was getting treated for. I didn’t have chronic Lyme disease symptoms, but I spotted the bite mark and I went to a doctor right away and basically, he gave me a bunch of antibiotics to treat it. But those are the types of things that can just wipe out all your gut flora because antibiotics get rid of the good stuff and the bad stuff.

[Damien Blenkinsopp]: So, you decided after this 30-day test to continue with the same diet, the Bulletproof diet?

[Bob Troia]: Yeah, exactly. So I was like, “Okay, I like how I’m feeling, even just in 30 days. Let’s keep doing it.” Basically, I think it’s been a little over a year and a half, almost two years now since that first post when I was about to start it, so I’ve got a lot more history now, I’ve gone down that rabbit hole of looking at different issues and seeing what’s linked to what.
Because what they started uncovering was, we’re looking at things like cholesterol and elevated cholesterol and other things like might show up in bloodwork, but really there was combination of things happening, and it wasn’t diet related. Diet almost uncovered it; the diet didn’t cause it.
Related to some chronic infections that were lingering, as well as some thyroid/adrenal issues, so talking about things like energy and being exhausted, it wasn’t necessarily chronic fatigue but there are tests that can show your body’s response, and like I said, everything is connected to each other. So you kind of go down this path where you start with the bloodwork on the macro-level, and now you’re working your way towards like, “Okay, if we could fix this one thing, that’s going to help ten things.”

[Damien Blenkinsopp]: Yeah. So I’m sure all of the people at home are like, “Wow, that sounds like a lot of different stuff and it’s complicated, and how do you figure out that you have to look at all these things” if you want to either resolve health symptoms or improve your performance?
Just take a step back here, since you went on this journey—so it’s about one a half years ago, maybe a bit more—how do you feel in comparison to when you started?

[Bob Troia]: I feel great. I used that analogy earlier: you always think you feel okay or you have moments where maybe you didn’t feel great, but you still feel like generally, “I’m okay, I’m not getting sick.” And as you remedy some of these issues, you realize that you kind of had that parking brake on, you were getting by. If you were able to be achieving things at that level with those conditions, once you take that parking brake off you just feel even more amazing.

[Damien Blenkinsopp]: I’ve got a very similar story to tell. It’s like I didn’t realize my full potential, pretty much the whole of my life because there were some lingering issues all the way through. As you work through this stuff, you realize that your performance, your functionality, just your general well-being can be potentially at a much higher level than you’ve been used to and you’ve accepted this lower standard, and you don’t realize that you can really feel really great and really operate at a really high level if you get there.
I feel way, way better after—I was talking to you just before about—taking steps up; you fix one thing and it takes you a step up in terms of energy or whatever is lacking for you, and every time you fix one thing it takes you up that other step, and slowly you get more and more out of life and out of performance and everything.
So, in terms of the diet now—you’ve been doing it one and a half years—has that really worked for you? Has that changed other things? You were talking about testosterone; have there been any benefits that you’ve noticed or that have been recorded? And how often have you been tracking your progress with that?

[Bob Troia]: We fast-forward now let’s say a year and a half from when I started, again, we talked about the initial 30-days or so and seeing things like total cholesterol going up a hundred points or so and LDL. After the year and a half, I did a round of follow-up work and my numbers actually went down to levels that were lower than before I even started the diet. Things like total cholesterol and LDL; my HDL still was higher, and testosterone was almost double from before I started.

[Damien Blenkinsopp]: So these are all positive changes by the sounds of it.

[Bob Troia]: Exactly, and this was really due to introducing some program around thyroid and adrenal support because an underactive thyroid has been linked to elevated LDL. It’s almost like that’s a shortcut that I had to spend a year and a half trying to get to because we had to try out and figure out a bunch of different things.
My doctor was basically, “Okay, here’s what we’re going to do. We’re going to support your thyroid while we deal with these chronic infections because it’s putting too much stress on your body and we need to support your adrenals and thyroid,” and sure enough, those numbers went right up.

[Damien Blenkinsopp]: We were talking about this just before the show and how important it is: you found a doctor that could work with the things that you had uncovered. You got these tests that weren’t kind of right and you wanted to explore them and find how to fix them and work on them, probably in quite a bit of detail. You sound like a guy who is really interested in performance and stuff, and you were trying to optimize.
That isn’t normally what doctors are there for, and so most of them would be like, “Well, I don’t normally work on this stuff.” So how did you go about finding a doctor that had the same mindset as you and was going to work with you on the way you wanted to with this?

[Bob Troia]: Yeah, it was a long process. When I first got into the biohacking side of things and looking at getting some of those tests and data, I was working with my local primary care physician, just someone local, and I could do some of the testing but the person wasn’t necessarily experienced in digging into those numbers; they just knew reference ranges. Then I moved on to another doctor.
Through research I was trying to find people with more of a functional medicine background. I know you’ve done some interviews around functional medicine, but it’s basically going from treating the symptoms to treating the causes or identifying the causes. So I found someone that was local, and when I first started doing some of this bloodwork and some of this testing, he was good at identifying certain things, but I think there was a point where that was it, he couldn’t really dig deeper.
Then, just by talking with other people I know and introductions, I came across another doctor who within a 15-minute phone call was like, “Okay, I’ve seen this ten times before. We’re going to test for these things, I’m pretty sure that this is the issue at play,” and sure enough, more just because that person was so used to seeing that.
And what’s great, even with a functional doctor, is they don’t have to be in your town. My doctor is in Austin and I’m in New York. We set up Skype calls every month; we can do a lot of this stuff virtually. We still see each other a couple of times a year face-to-face, if we run into each other at a conference or something like that, but it’s been great.

[Damien Blenkinsopp]: Yeah, I’m the same. I work with several doctors on different issues based on their expertise, so it’s kind of bringing the point that you just referred to, is when they get something and they’re like, “Oh, that looks like something I’ve seen before.” If you have an initial discussion with a doctor and they can get that feeling for it, that’s really good.
The other thing I look for is someone who’s got this investigative mindset because—if you’ve got some just small issues and you’re not sure what they are and there’s no clear answer, or you’re trying to improve your performance or energy levels and you’re not sure what’s there—if there’s not a straight answer, you need someone who’s going to try to sift through the data, have a bit of an investigative approach to it, and maybe even go and check out some research or something.
So I’ve got a bunch of friends who’ve come across problems in their lives and they’ve eventually found a doctor who’s got a bit more of a detective, investigative mindset and will go and do homework and look around and look at different tests until they find an answer, which isn’t necessarily everyone’s mindset when they’re looking at this. I don’t know if you’ve come across that kind of mindset before with someone you’ve worked with?

[Bob Troia]: From the standpoint of having a different experience with different tests?

[Damien Blenkinsopp]: Yeah, just having “I don’t know what the answer is right now,” but let’s investigate and just keep working on it until we find some kind of answer. Because I think the reality is, the world of biology is really complex. A lot of the terms we’ve brought up today and a lot of the things you’ve been talking about, it can be really, really complex to uncover little things that are holding you back in different ways. So it’s a bit like a maze and a puzzle sometimes that you’ve got to solve.
If you just look at the straight tests sometimes, you’re not going to get any clear answer. We were talking earlier about stool tests and I’ve probably done about ten stool tests right now, and sometimes an answer comes out. So sometimes you need someone to look through and dig through the data and keep going for a while, rather than relying on something they’ve seen before.
Whereas you brought up the example where if you find someone who’s had direct experience with your specific problem, I find it’s a kind of specialized approach. If you look at the business world of consulting for instance, they have specialized consultants versus general consultants, and the general consultants are problem solvers, they go in there and investigate, they’re like detectives; whereas the specialized guys really know their stuff really well.
I kind of see the world of doctors as a bit similar. You can find the general guy who’s going to investigate, maybe he’s a functional medicine doctor and he’s just going to keep investigating and looking at stuff, and he’s going to figure it out by problem solving; whereas the guy who will really be specialized in one area will really know it really well and he’s seen 500 different patients, or perhaps they’re athletes, trying to achieve the same goal and helping them with that.

[Bob Troia]: Yeah, where I see everything with Quantified Self going ultimately, is this concept of a “quantified team.” You’ll have your doctor, and your doctor can look at data and give you some information; you’ll have someone who can analyze data, like we were talking earlier, we’re not all data scientists. We can collect this information and have it, but to do correlations and really in-depth analysis, most of us don’t know where to start with that.
Having almost a coach or an interpreter of that information can sit between you with your doctor, or if you’re an athlete or something you can articulate that with other coaches etc., and I do see this idea of almost like a team. Instead of it just being you and your doctor, you’re going to have a group of people that will all work together to be that sort of team, but I think they each bring a different skill set to the table.

[Damien Blenkinsopp]: Yeah, that’s a great way to put it, I hadn’t heard that before, but that really is a great way to put it and it will be interesting how that takes place. I guess I kind of already have some kind of team going, I don’t know about you, but I hadn’t thought about it like that. I guess that’s just the way it’s evolving naturally.
Okay, it sounds like you were just frustrated that you weren’t solving things and you kept on looking and meeting people, and it was more like networking that you managed to meet someone that was relevant to you.

[Bob Troia]: Yeah, in my case it was. For me, I also have a really strong personal interest in understanding how human physiology works. So I’m sitting there reading books, consuming information; I’m not a scientist, I’m not a doctor, but I like to be able to understand. If someone shows me the lab tests, the doctor is going to explain things to me but I want to understand it at a deeper level. That’s just my curious nature. I think a lot of folks probably don’t want to dig that deep, but that’s just an interest of mine.

[Damien Blenkinsopp]: I’m the same way. For me, I kind of see it as my responsibility and, depending on what you want to get out of your body and your life, I see it as a really good investment of time. The more you understand your biology…
When I think back to four years, five years ago, and I was already working on fitness stuff like you and optimizing it with numbers and stuff, but now I have so much control over my body, just all sorts of functions that I didn’t realize that you could control; I thought they were things that just happened. We were talking about energy dips; I have my own adrenal fatigue documented that I’m working with. But when you learn a few tricks and things, even if you do have adrenal fatigue and you’re working on recovering from that, you can actually avoid those periods of exhaustion—which I guess some of your exhaustion you talked about before was either thyroid or adrenal related?

[Bob Troia]: Yes. You were talking about a certain test you take; it’s like a saliva test that, over the course of 24 hours, you basically can plot a curve to show your cortisol and DHEA response. I had a similar situation where it was showing my cortisol levels were actually pretty close to what the reference should have been, it mapped pretty closely, but when you looked at the ratio of cortisol to DHEA, it was completely out of whack. It rings an alarm saying, “Okay, there’s something going on with adrenals here,” and supporting it.

[Damien Blenkinsopp]: I found that a really valuable test and I feel like everyone should do it, especially driven entrepreneurs, anyone who’s just working too hard, basically. Too many hours a week or too stressed, and I think that’s pretty much everyone these days. It seems like everyone is stressed that I talk to, they don’t sleep enough and they work too hard, and often they’re working the weekends or the evenings as well, or in the mornings, if they can fit it in.
So when you think about all of that, I think a lot of people could maybe check that test out and they might find that there’s something they can do there to improve their energy levels and so on.

[Bob Troia]: Yeah, and with regards to the diet, I was also incorporating intermittent fasting. Essentially consuming all of my meals in a six-hour window each day.

[Damien Blenkinsopp]: Just out of interest, we’ve talked a little bit about intermittent fasting with Jimmy Moore a little bit when we were talking about ketosis, but which hours of the day do you choose to eat at and why?

[Bob Troia]: My window for intermittent fasting is probably I’d say between 13:00 and 19:00 or noon and 18:00; it depends. You try to time it so that you start right after your workout, but the way I was doing it was you sort of cheat because in the morning if you do a sort of special coffee, which I’m sure you’ve talked about before, with butter and MCT oil, because you’re getting fats in your body, you’re getting the calories but you’re still in ketosis.
But with regards to intermittent fasting, if you had adrenal/thyroid issues, you should not be doing it. I’ve had to cut it down to a day where it was on a weekend or a day I wasn’t working out because it is stressful on the body, and for me it was like, why add the stress that you don’t need right now until you’ve fixed the other issues?

[Damien Blenkinsopp]: I think that’s an important thing because intermittent fasting has become a bit of a trend. It seems very much in fashion these days, but for some people it’s not right for, or at least not right to be doing every day. Like you could do it from time-to-time, but doing too much of it, like you said, depending on where you’re at, can be a bit problematic as can the type of training that you did.
I was just wondering, how often do you get your blood labs done now? I guess you started to do it more routinely when you started the diet and everything, but how often do you do them? And which markers are you keeping an eye on primarily?

[Bob Troia]: I would say in terms of ongoing testing, every three months. If I’m addressing something more short-term, I can test on a monthly basis, but I would say three months is my good window because if I’m addressing something, that’s usually enough time to get an update and see where my markers are at.
In terms of what I’m checking, so those can range from basic panels, where you’re doing like we talked about, cholesterol markers, glucose, nutrients like calcium, magnesium, vitamin D, all those sorts of micronutrients, then getting into things like white blood cells, [and] C-reactive protein; that’s more of a traditional panel.
When I’ve had to dig deeper, I would do these additional tests. One is called an MDL test, where they can check for chronic infections and stuff, but it’s all done through bloodwork, so you can dig a little deeper. The main issue is these tests cost money. You either need a good insurance plan or you have some way to get those costs down.

[Damien Blenkinsopp]: So is that what you recommend? For you, three months is about right cost-benefit for those sorts of labs?

[Bob Troia]: Yeah, and I think you could basically, there are these at-home services that we were trying to launch that you could draw it every day if you want. Maybe there is a case where you are trying to do a before and after of something, but to go to a lab and do a full panel, for the average person, I think even six months is fine. But if you’re trying to deal with any issues or you need an update, I think for me, three months is a pretty good window.
Also, some of the testings, so Wellness FX or Inside Tracker, they have certain panels and for even the most expensive panel of the highest n=1 they have, there’s a limit to what they can provide. So what I’ve found through my doctor was by him ordering some of the tests, we can do much more comprehensive panels.

[Damien Blenkinsopp]: Had you been using Inside Tracker for those basic blood markers most of the time? What have you been doing for the routine tests you do?

[Bob Troia]: The routines had been on and off with Inside Tracker. I don’t know if you talked about the weird laws that exist in this country about all these testing services?

[Damien Blenkinsopp]: The weird laws that exist everywhere.

[Bob Troia]: So for example, with Inside Tracker, I was using that for the basic panels and when I needed to do some additional things, they would send me to a LabCorp facility, which is like a big chain of laboratories—you go there and they can do it all. In New York State, they can’t do it.
So there are rules about what they can and can’t do. I couldn’t just go there and set up the appointment; my doctor, however, could arrange and say, “Go to this lab,” and he could actually negotiate lower prices for certain things. So you might see on your bill that this bloodwork cost 2500 dollars, but you’re going to pay 100 dollars or something out of pocket, and suddenly you hit your insurance thresholds.
My point is, it’s tough because I love the convenience of those types of services, and it’s just that I happen to live in a state where it’s really difficult.

[Damien Blenkinsopp]: So New York is a bit more difficult. As far as I know, I think there’s one other state. New York always comes up as a specific state where this self testing is more complicated. There are also a bunch of other services you can use, like DirectLabs and other self-service websites that basically you can hit up and order testing. In fact, I found most tests these days I can order.
But as you say, sometimes it’s worth either you working with a functional doctor or someone from your kind of team and he’ll be ordering them for you. There is a cost-benefit to that often, I think, versus ordering them directly. And of course, he’s going to be checking them and looking at them, and he’s got his experience looking at tons and tons of tests of these types and he’s also probably got a mountain of data in all of the tests he’s stacked up over time, which I found this kind of thing is really valuable as we’ve talked about before.
But it is changing and that’s one of the things we’re going to look at in this podcast. Things do change over time and all these new services start coming out more and more.
So in terms of intermittent fasting, that’s something you cut down to fit with your personal situation, where it kind of comes back to an n=1 experiment thing, where it’s really a personal thing and what suits you. How did you know to change that? Was it because of one of your tests? Or was it a feeling and then you looked at it?

[Bob Troia]: No, and in that case, actually, intermittent fasting worked great for me in terms of body composition and I was able to confine my meals into that window and still get everything I needed to eat. It was more just after talking with my doctor, we said, “Hey, let’s do everything we can to support your thyroid and adrenals. Let’s take as much stress as we can take off your body.” And so we decided to cut back the intermittent fasting just for the sake of let’s just remove a potential stressor.

[Damien Blenkinsopp]: It sounds like a great idea, so that’s some of the stuff I do as well, try to reduce all stress. So, that’s intermittent fasting. One of the other interesting things you’ve played about was blood glucose.

[Bob Troia]: Yeah, I was one of the early 23andMe customers, so I know that now if you sign up for them to get your genetic testing done, they don’t give you access to these research and tests that can say you’re more likely to develop this condition or have this response to this medication.

[Damien Blenkinsopp]: So, just to be clear on that because I bought in the early days like you, so I still have the health interface. I think the difference is just the interface they present to you; they don’t present the information summarized about your health, is that correct?

[Bob Troia]: Well I thought they ran into some FDA issues where they can only show people their ancestry information now.

[Damien Blenkinsopp]: I think it’s in terms of display but you can still download your whole…

[Bob Troia]: Yeah, you can download your raw data, but there’s no interpretation of it.

[Damien Blenkinsopp]: That’s right. Basically, we see a health panel because we got in early and they’d already shown it to us so they’re still allowed to show it to us, or I guess they promised us so they made some deal with the FDA that they’re allowed to keep showing us it. But they’re not changing it; it’s just what we saw from the start.
And then you guys, if you do download the data, then you can run it through some open source tools, but they’re not as nice and summarized, you have to do a lot more work with those if you want to get to some of your health issues.

[Bob Troia]: I’ve used Promethease, is one, and Genetic Genie.

[Damien Blenkinsopp]: Genetic Genie is a bit more simple actually, but Promethease is a lot of detail and a lot of work to get through it. Did you find it the same?

[Bob Troia]: Yeah. I thought the Genetic Genie was interesting though because it got more into a methylation analysis, which was for me kind of an interesting set of data that I wasn’t getting from anywhere else.

[Damien Blenkinsopp]: But you can get that from Promethease. You get everything basically from Promethease because it’s a bigger open source thing. The Genetic Genie guys are focused on a few different issues like detox and methylation, so they’re looking at specific panels. And there’s another website Ben Lynch mentioned, which looks at specific panels like that.
Anyway, so there are ways you can use this data from 23andMe and you can get different sets of health issues looked at by going to different sites basically, and putting your diet in there. So the data is still there if you want it; it just takes a bit more work than it used to.
In terms of the blood glucose, you found an issue that you wanted to look at?

[Bob Troia]: So going back to the blood glucose, my 23andMe data showed I had an elevated risk for Type 2 diabetes. It was about a 10% higher probability, meaning the average person has I think 26%, so it’s already a pretty high likelihood, and mine was 36%, and I know I have a few members in the family, like uncles and grandparents, that have developed it over the years. So I just got interested in looking at my glucose response and wanted to understand the effects on glucose and what affects me, and I’m going to take whatever proactive steps I can because I don’t want to develop it at any point in my life. So really this experiment just started as, let me just understand my blood sugar.
I went and bought a 12 dollar blood glucose meter, I ordered it off of Amazon, and you get the test strips and you prick your finger every morning. It’s a little meter that just says your blood sugar level. So I would do what’s called a fasting glucose measurement, that’s basically, I think you have eight hours of fasting before. Every morning, the first thing as soon as I wake up, I would just take a reading. I started establishing a baseline just to understand and get some basic levels.
I was reading up about different supplements and things people have been taking to better regulate glucose, both stabilizing it—so you have less swing of fasting glucose—but also overall, just bringing it down. My fasting glucose was around 85 mg per deciliter which is considered okay, but when you see these organizations like Life Extension Foundation, they actually want people down and closer to 75 – 78.

[Damien Blenkinsopp]: Jimmy Moore, when he was on, he was saying that his is pretty low, it’s around 80 and that’s where he keeps it. So when I looked at your data, what I found was interesting is that’s the blood test you got initially, 85 was it to start off with? And then when you started tracking it, what did you see? Because I was really surprised. I didn’t know that it worked like this when I saw your numbers.

[Bob Troia]: I did a 30-day baseline and in some days, I’d wake up and it could be 80 or so, and then there were other days where I would wake up and it could be about 105, there’s a bit of a swing.

[Damien Blenkinsopp]: Do you think that’s the accuracy of the device? Did you look into it? Because I didn’t expect big swings like that. When I’ve had my tests done in the past, which is just the three-month routine like you, I will have 85 and then maybe there were some times where it was 95, and I’d be like, “Oh, I don’t like that. I don’t like the fact that it’s up there.” But it seems from your data, that it’s actually swinging up and down every day. Is that normal or was that the device? Or is that just kind of how we are generally?

[Bob Troia]: I think in terms of the device, I did a bunch of research and listen, none of these are going to be completely accurate. I think the one I chose was probably within 5% accuracy. Because when you think about it, who are the people who are using these devices? They’re people who have diabetes, typically, so their glucose is so high that whether it shows them that they’re at 160 mg per deciliter or 150, they’re still too high. So the lower ranges that we’re talking about, you know, 5% is still okay, but some of these meters can be 10% or more.
And to your point, yeah I think that if you’re not controlling it consistently each time in terms of I take it almost the same time in the morning and I’m taking the sample from the same location, I’m not squeezing my finger too hard because if you squeeze the blood out of a little prick you give your finger, that can affect it. So I took a baseline and then I started supplementing.
I came across this supplement called oxaloacetate and it’s all natural, it’s part of the Krebs cycle, which is a whole cycle of conversion going into vitamin C, and it’s found in a lot of plants. It’s concentrated into a pill form so you take one every morning. I took one every morning, and over the course of the next 30 days I kept doing those fasting glucose readings, and I actually saw, “Wow, it actually reduced that swing that we’re just talking about. It condensed and the overall trend went down.” So it actually stabilized and lowered, which is really cool.

[Damien Blenkinsopp]: So why do you find this cool? Because I guess we’ve got to take a little step back. We talked about blood regulation with Jimmy Moore, but what kind of benefits were you looking for from this, yourself? Is it because of your genetic profile that you were basically managing your risk as you saw it? Is that what you feel the benefit is for you?

[Bob Troia]: I think long-term, it’s part of a longevity strategy. I can say very easily that today my glucose was in what’s already considered a good range, but it wasn’t optimal. I was trying to understand not just how could I bring it down into an optimal range but also what things affected it. Because once you’ve collected all this data, you can then look at other aspects of your life and go, “What affects these values?”
So for example, plotting your values on a chart over time is one thing, but if I average out what does Monday look like versus Friday, there’s a difference. Monday’s the beginning of the work week, more stressful; Friday’s end of the week; Saturday’s the weekend. For me, I could see it just very visually, there were these trends. I also noticed that if I exercise—I play a lot of soccer—and if I have a soccer match—I usually play in the evenings—the next day, no matter what, even if I went out with the team and had drinks or did whatever, my value the next day goes way lower. I only uncovered that by taking other data from other areas of my life or looking at my calendar and going, “Huh, that’s pretty interesting.”

[Damien Blenkinsopp]: Well you said you’ve got this detective mindset. How did you go about that? Was it you were looking for ideas?

[Bob Troia]: Yeah, because you have the data—now you have this repository of these values—and now you’re trying to figure out ways to correlate it with other areas of your life. For example, I was looking at exercise. I decided to look at my calendar and I superimposed dates that I had to travel cross country, like fly, and guess what? During those windows of time, I was taking measurements throughout the entire process, it definitely spiked. So travel for me is stressful, it actually took a few days to get back to those pre-existing baselines.

[Damien Blenkinsopp]: Wow, because that’s a big deal. And travel is something we say is stressful but it’s not often we hear some data on it. This proves that travel is stressful for you. But that sounds like a pretty clear case for you. An n=1 experiment you could probably say that you are going to be stressed next time and you can kind of prepare for it.

[Bob Troia]: And then with the experiment, I then stopped taking that supplement for example and just kept taking markers for another 30 days and I tried to replicate it, and when I replicated it—the beauty of these n=1 experiments are you often fail or maybe you set up to prove a theory and you fail but you learn something different so it’s not a failure per se—it didn’t work.
What I realized was it was a combination of things. It was last winter, we had gotten a bunch of snow in New York so our soccer season had basically gotten cancelled because we play outdoors all year round and the field is covered in ice and snow and so they were like no games. So that exercise that I was getting, I wasn’t getting. Also I had changed my commute from going into an office and having to walk to the subway and walk to the office, to working from home for a period of time.
So I actually then looked at my step data, not that I ever bothered tracking steps or looking at my step data for a health related reason, but I did notice that my activity was actually decreasing. So what does that say? The low hanging takeaway there is: if I exercise my glucose will go down, which is probably a “No, duh,” kind of thing but for me, it just showed the direct benefit, a short-term and a long-term trend.

[Damien Blenkinsopp]: You’re just making me think of something, and we’ve kind of touched on this before in podcasts, but when you were shown that direct benefit, it makes it clearer for you and it makes you more motivated to act upon it. Now you feel like you’ve got this extra additional motivation—tell me if this isn’t you, just me projecting—but I feel when I understand something a lot clearer, when I’ve seen the data, then it’s a lot easier for me to keep up that habit because I understand it to a clearer point of view.

[Bob Troia]: Absolutely. I think part of the folks like us who are doing all of this, I guess we’re like these A-type personalities and we’re trying to not only understand all this but we want to reduce this to the most simple terms, like what’s the one thing I can do to get to the same result? It’s not about creating more headaches, you’re trying to optimize and gain more time in your life, not take up more trying to do all this tracking.

[Damien Blenkinsopp]: Exactly, yeah let’s talk about it because it probably sounds like a lot of work. Do you feel like it’s a lot of work? Could you talk a little bit about how much time it takes to get the labs or track things or analyze it?

[Bob Troia]: I would say what takes the most time is probably the analysis, just sitting down with the data, because like you said, you have to have this sort of detective mindset often times because you have information until it makes itself clear to you in some way or you want to test out a theory. Most of the things I’ve done are almost in retrospect, where I collected information already and then I’m trying to figure something out versus I’m constructing an experiment and these are the variables. I’m pretty bad at that; I’m almost better at the reverse—here are the results; let’s figure out what created that result and go backwards.
From a time perspective, I think even collecting information, so going for a lab test and getting your blood drawn takes a few minutes; it’s not that big of a deal. For most of my data, I’ll wear a device on my wrist that’s collecting a lot of passive biometric information all day. I think the goal is to not create a lot of burdensome things on yourself.
I know there are a lot of people who track all the meals they eat, like they use MyFitnessPal or something, and they know a lot about the meals and track their calories, and I’ll do that every once in a while for a few days, just as a gut check. I’m not going to do it every day, it takes too much time. For me, it’s a headache. I eat consistently so I’m not too worried about it. Once I do a gut check or a sanity check, I know its okay.
But I think that’s the problem, I think a lot of people feel like this becomes so burdensome and takes up so much time, I think you have to pick your battles. There are certain things that you want to do every day and if it takes you a minute to do it, that’s great. Other things are being done passively, so you’re collecting that data and it’s just a matter of finding the time to sit down and analyze it.

[Damien Blenkinsopp]: There are very few things I do. I saw you noted on your blog, I think, you’re interested in meditation and you were looking at doing some—I don’t know if you’ve done any yet.
I’ve been using Calm for a few months now, I got it in September or something, and so I try to do that every day. I’ve, over time, been able to improve my scores with this EEG device, basically it’s a consumer EEG device and it’s got an app which shows you when you’re in one state versus another. I found it useful because I want to meditate anyway, but going back to what you were saying, I want to make sure I’m spending my time productively, and for me, the extra effort of tracking it has a huge impact in terms of improving my meditation.
Meditation is different for different people, but for me, I’ve been experimenting with binaural beats, which I think you mentioned too, the Holosync one, and I found that’s working for me. But I like to know stuff is working for me before I commit to it and I put that extra energy in it, so I did a few experiments and it seems to be working for me so I’m sticking with it. I’m just trying to give people a mindset in terms of time like you were saying.
But if something doesn’t seem to be working, you just kind of drop it, and then the stuff that does work, you’ll keep it because it’s beneficial. So some of this just kind of works out itself: you’ll keep the stuff that is beneficial, so it’s worth the time. Like I take my HRV readings every morning because when I see a dip, I know there’s some kind of problem coming or I should chill out for a day if I don’t want to get really tired or something.
The things that are beneficial I think you find that they stick and you make the time for them automatically, and the things that aren’t, you just kind of work them out of your routine. Is that similar to the way you found it? Or how have you gone about it?

[Bob Troia]: Exactly the same. I think there are certain tasks you can do that take up very little time. Like I had a little routine in the morning, when I wake up I’d do a handful of things or before I go to sleep, but then there are other things I’ve done where whether it was a piece of technology or I was trying to understand myself better, but once I did the analysis or once I gathered data, I have a box full of devices, you throw it out and you’re like, “Great, that was useful.” I think people get hung up on the gear a lot of time, and I think often you can figure out solutions that don’t require the technology per se. You could take a spreadsheet and something like little body fat calipers can give you a body fat measure and you don’t need a 200 dollar scale to do that.

[Damien Blenkinsopp]: That’s right and there’s all this excitement around the devices and everything at the moment; all the companies are investing in it. Of course because that’s what the market is, but so far, there aren’t any crazy, awesome devices yet; there are a few interesting ones here and there and it’s a thing in progress.
I’ve done some of the similar ones to you, I had the Basis watch. I wore it for a year, it broke and then I didn’t buy a new one because, honestly, I didn’t do that much with the data. It would be kind of nice to know my activity levels just to check that I’m keeping up and it’s a nice convenient way just to know that. Do you still use your Basis watch?

[Bob Troia]: Yeah, I have it on right now, and for me I was looking for something that gathered the metrics, and I felt it had the most robust set of data, even though they didn’t give you the data. We can talk a bit about it—I figured out a way to get to the data and I wrote a script. Given my technology background, I was able to write some code. I put it up on an open source website that people can use to download their Basis data.

[Damien Blenkinsopp]: Yeah thank you for that. I think that’s how I first found you, actually, because I was looking trying to get my data and I found your website, and I was like, “Oh, thank God someone’s solved this.”

[Bob Troia]: For something like that, that’s just passively collecting so I might not look at some of those numbers for a few months. Like right now, I’m actually about to go over all of my sleep data from 2014 and I’m going to do an analysis on looking at trends—how is my sleep by day of week or different sleep stages. I’m going to factor in when I look at things that happened in my life and did it affect my sleep. I don’t know what the answers are going to be, I’m not going into it with any preconceptions so that’s almost for me it’s going to be more like developing more self-awareness. I might be like, “Well look, I have this many sleep cycles but I don’t remember my dreams. What’s going on there? Why am I not remembering dreams?”

[Damien Blenkinsopp]: Has that been happening to you lately? Because I’ve had that a year and I’ve only just recently come across information that’s been helping me to figure it out.

[Bob Troia]: I have no problems sleeping. I’m actually a solid sleeper—I get eight hours a night—I have friends who are jealous of me, but does it mean I have quality sleep? I think it’s good, but for me, with dreaming, it could just be as simple as I started keeping a notebook next to the bed. As soon as I wake up in the morning I would try to think, and it was really hard for like the first week. And then maybe after a week, in the morning I’ll remember some minor detail of one dream, but then in the afternoon, other things will start coming back to me. So you have to almost train yourself.

[Damien Blenkinsopp]: So in your case, it was trainable? You could basically get your dreams back and it was a focus on dreams?

[Bob Troia]: I almost think it has a little bit of intent when you go to sleep of putting yourself in that mindset of you want to dream and then waking up and just being able to recall that information; it’s almost like an attention thing. It’s no different than you’re talking and I’m tuning you out.

[Damien Blenkinsopp]: That’s interesting. So the information I came across was a little bit different. It was through Tess actually. We had this guy called William J. Walsh—I don’t know if you’ve come across him before—on the podcast on episode 2. He does these labs that help you to assess basically micronutrient deficiencies or differences that are out of his functional ranges, and mine came up out of range. One of the things that it shows is an imbalance of B6, and when you have an imbalance of B6 then you tend to stop dreaming. So I think once I’ve rectified mine, it might kind of fix itself. But it’s interesting; I might try the experiment myself with the intent thing to see if that helps as well.

[Bob Troia]: Yeah, let me know how it works. Again, it’s something that I’ve started probably since the beginning of this year. I’ve just been more aware of trying to develop, but I think there will be value in it regardless, and it’s not something that really takes any money or time. You just need a pen and a notebook.

[Damien Blenkinsopp]: I’ve always loved that idea of trying to think of a problem you need to solve before going to sleep. I think Ray Kurzweil does this and he’s one of the guys who says he always does that. Just solving things in your dreams is a great way to do stuff efficiently that you wanted to do.
Coming back down to the practicalities; you’ve been doing this for quite a while now, what are the biggest time wasters you’ve found in the experimentation process about learning about stuff that works for you and what doesn’t, basically, and collecting data? Have you found that there are things that you were doing that are time wasters and you decided not to do them anymore? Or what have you learned about n=1 experiments? What do you do today that might be different to when you started out?

[Bob Troia]: Obviously on the testing side of things, I wish someone had given me the shortcuts and said, “Do this, this, and this.” I have a lot of people come to me asking, “Just give me a list of five things I need to do.” It’s often not that easy because we are all different, so it’s not like it’s a clear linear path; it’s very branched.
For me, it would have been if someone early on could have identified some of the issues, it would have saved me a lot of trial and error just trying to uncover. That was probably why I started doing a lot of it myself in terms of trying to understand it better.
Time wasters, this is more just from the standpoint of looking at your data, everybody wants this hub: “Upload all your data and we’ll be the place for you to access all your information.” The problem is, for most people, like we said earlier, we’re not data scientists; we don’t know how to run correlations, we don’t understand all that. And so, you’re uploading your data to these places but then what? It’s just there.
Or I look at it from the standpoint of, if it can’t collect all of my data it’s useless to me. Take Wellness FX, they might be like “Okay, you can manually input all of your blood lab tests in here,” but maybe I’ve got some additional fields or something in it that it doesn’t support. Well now it’s not my complete record, so now I’m like, this isn’t really valid for me. I feel like I’ve wasted some time going through the process of getting data and massaging it and uploading it to certain places to try to have this hub. So I’ve had to do a lot on my own, make my own little ways of gathering it.

[Damien Blenkinsopp]: Do you use Excel?

[Bob Troia]: Yeah, and I’ve got things imported into databases so I can run correlations against it.

[Damien Blenkinsopp]: But I guess for the people at home, they should stick with even a Google Docs spreadsheet, anyone can use that; it’s very similar to Excel. I have a huge monstrous Excel, which is scary. A database would probably be a better way to do it if I could get my head round that.

[Bob Troia]: Spreadsheets are a perfect way to get certain data. Pretty much anything you collect you can import into an Excel doc or a Google Doc and then chart it and do whatever you need to do with it.
But in terms of time wasters—well it’s not so much time but it’s almost like a money waster I’d call it—there are a couple of things. There’s the shelf-life of a lot of this technology and tools. You buy this new cool gadget or whatever, and it’s like planned obsolescence. You know in a year it’s going to be outdated or someone’s going to come out with something new, or you just wanted to be the first one to have this shiny object.
I got a device that analyzes your posture throughout the day, and it was fun, I did it, it kind of showed me some insight on understanding that better, but at some point I’m like, “I’m done. I’ve used it. I’m done with it. I’m not going to wear this every day.” It happened with the Zeo sleep tracking, they were an EEG-based sleep monitor. The problem with their business was more from a consumer issue, where people were buying the product because they had sleep problems and the device said, “Yes, you have a sleep problem,” but it didn’t really give them a solution so people were like, “Well, thanks.” There’s that level of things and then I’ve also been burned a number of times on these crowd-funding campaigns with companies, and it’s not so much it’s their fault that they were doing anything shady…

[Damien Blenkinsopp]: It’s the nature of it. It’s like a pre-startup situation.

[Bob Troia]: Yeah, and so my policy now is literally I’ll just wait for the thing to come out because you know what, you’re still going to get it if it’s out.

[Damien Blenkinsopp]: So just to outline what you’re talking about; what are the issues that come up when you’re buying those things?

[Bob Troia]: I think there are a number of issues. Like you said, they’re startups typically, so if they’re developing a product, they probably have no experience building a piece of hardware, so they don’t realize all the issues that can happen along that process from manufacturing to distribution, so when they say we’re going to ship in March and it’s January, they probably mean March the following year. Nothing ships on time.
I’ve also had issues where there was a blood testing service that was coming out that was doing blood spot tests, so you have these little index cards and you can put a drop of blood on it and you can send them in at any time you want. I bought the top of the line pack because it gave me three years of blood tests and they started letting us send in our samples and they were collecting them, so I wasn’t doing other bloodwork because I was sending them monthly samples. And then they got into trouble with the FDA, who were basically “You cannot operate,” and so the company has just been in limbo.
There was another company—did you ever talk about telomeres?

[Damien Blenkinsopp]: Actually, I did want to talk to you about that. We touched on it with—do you know Aubrey de Grey? We talked about it a little bit. It hasn’t been published on my podcast, but by the time this comes out it will have been, so it’s kind of time travelling here. He’s been on and we talked about that, and he was pretty pessimistic about the use of this, but I’d love to hear your experience with the practical experience of that because I was wanting to get mine tested, and I think I still will just to see where they’re at compared to the norm.

[Bob Troia]: So a telomere is basically if you look at your DNA strands—just to give an analogy, it’s the one I’ve always been given—if you think of a pair of shoelaces and at the end of your shoelaces there’s a little plastic tip. Think of your DNA strands as having those little plastic tips but as you get older, they’ll fray and eventually fall apart and then your strands will shorten. So it’s kind of a sign or a marker of aging, because at some point your cells can only divide so many times and then they just die.

[Damien Blenkinsopp]: It’s the idea of this countdown. You know those little countdown timers that start at a hundred or something and then it chips away one each time, and when it gets to a certain level you don’t have any life. It’s like losing lives on a videogame.

[Bob Troia]: Exactly, you see the health wearing down. But in this case, this company was providing a service where you basically spit into a tube, you mail it in, and through your saliva they do a telomere analysis.

[Damien Blenkinsopp]: Which company was that?

[Bob Troia]: They were called TeloMe.

[Damien Blenkinsopp]: You say TeloMe; are they not here anymore? Or are they still here?

[Bob Troia]: They’re here—well I’ll get to that part—but basically, there’s a parent company that was more clinical, they would do testing more for labs and all that, and this was a consumer initiative they were doing. So the idea was you would spit in this test-tube, mail it in, and then you get a report and it shows you the analysis of certain telomeres that they’ve identified and it says where you sit in a reference range. So I got my results, the problem is, they can only compare me to other people who have used their service.

[Damien Blenkinsopp]: And who has used this service?

[Bob Troia]: That’s the thing. So I wrote them back, they sent me my results and I was like, “Uh, these don’t look too good. So you’ve got me compared to my age range, well how many people have you had so far that are my age range?” And they were like, “I think five or six.” I’m like, “Great. So you’re giving me results on a small sample size.”

[Damien Blenkinsopp]: Are the markers they’re using—this is something I’m always interested in—that have a lot of research behind them? So you can at least go and look at the studies, or they should be giving you the information of those studies, “In the studies this is shown to be good in healthy populations and bad in people with cancer,” or whatever, some kind of data on it.

[Bob Troia]: Well again, this was a case where I crowd-funded this initiative, which got me like a three-test pack. The idea was that I was going to do an experiment. I was going to send in my sample, do some things, wait a few months, and send in another sample to see if I was able to change the expression, or the markers of aging. When I went back to do it, I found out that the company no longer existed. Well the parent company still exists, they can’t operate in the U.S. though, [and] they got shut down by the FDA. So I was like, “Give me my money back,” and they don’t respond to you. They’re in Europe doing their thing but they won’t acknowledge or give you any information about the testing service.

[Damien Blenkinsopp]: I guess it’s not even the cutting edge, it’s a bit of the bleeding edge of all of these labs. Because the FDA is still figuring out what it’s going to do with stuff and what it’s going to allow, and as you’ve pointed out, already three companies have been told they’re not allowed to do stuff at least for the moment until they figure more things out.
There’s a lot of that going on and so I find sometimes a test will be available and then it’s not available and then it’s available again. That’s happened to me on several occasions, where a place I’ve got a test initially isn’t available there anymore and I have to go somewhere else to get it. It’s kind of like the bleeding edge right now, and if you’re going to get into the more specialized stuff, like telomeres or stuff like that, it’s going to take some navigation, I guess, and expect some of these problems.

[Bob Troia]: Like I said, I don’t necessarily fault the companies all the time because they’ve run into some regulation or things like that, but I guess from my standpoint it’s like you are gambling. Funding these initiatives, they may come out some day, but it’s often not going to be what they were positioning themselves as, whether they pivoted or did something different.

[Damien Blenkinsopp]: We should look at crowdfunding as a bit of a gamble because it’s a pre-startup, it may not come out. And the thing I’ve had it there’s often a huge delay. I think I’ve bought a couple of things and it just took about six months to a year longer than I thought. I got Biomine Basis when they first went to crowdfunding. I don’t know if Basis was crowdfunding or if it was just pre-orders, anyway, it was a pre-order and it took about a year and a half to get it. It was a long time but I got it eventually, and maybe it wasn’t exactly what I wanted.
I think now the way I look at it is it really is the bleeding edge and if you want to play around with some of this stuff, I guess at the moment you’ve just got to consider that’s going to happen a lot. You’ve got to do more due diligence.
We were talking about the markers and the lab tests, the surprise you had with the telomeres, and I think that’s a pretty key thing because you could be getting useless data as well.

[Bob Troia]: Absolutely, and they wouldn’t have told me that unless I asked them, and I think with regards to crowdfunding, I’ve met a lot of great people in the space of QS and biohacking, and if it’s a company that I think is working on something cool and I’m happy to support them. But when there’s something where it’s a new technology or a new service, and it’s almost like do you want to be the first, but does it mean being the first today? You make that payment or crowdfunding donation and then you’re like, “Alright well I’ll see you in a year and a half.” I’d rather just be like I’ll wait a year and a half and then I’ll pay 20 dollars more for it.

[Damien Blenkinsopp]: That’s what I’m doing now. Every time I catch myself going to click on a crowdfund, I’m like, “Look, why don’t you just wait. You can buy it in a year when it’s actually there.” That’s kind of the way I’m looking at it these days, I think it’s from us tried and tested people. I don’t know if everyone’s going to start feeling in that way soon.
There was one called the Omega I was pretty excited about, I don’t know if you saw that one. I don’t think it’s come out yet still because it tracks a few more things.

[Bob Troia]: There was also one called Angel Sensor, which basically is creating a wearable, like a wrist-worn, almost like a Basis, but the entire platform is open source. So it has a bunch of sensors and then you can build your own apps. You can just grab the raw data, and so I was like, “Wow, this is cool,” so I crowdfunded it, and apparently, they were sending out some updates a few months ago about it but I think it’s one of those things were they’re like, “Oh we will be coming out in March,” and then they’re like “We will be coming out in July.” So I think it’s ongoing to come out at some point, but I crowdfunded that over a year ago, maybe a year and a half ago.

[Damien Blenkinsopp]: I guess the other way we could look at it is, this area is going to grow and we’re helping it. If we contribute to crowdfunders, we’re helping it happen faster. Eventually these wrinkles and bleeding edge is going to start calming down as bigger companies get more involved and the environment gets better for these devices as the market grows and so on, and we’re kind of helping to fund for the startup if we’re contributing to these crowdfund campaigns and so on.

[Bob Troia]: Absolutely, and even from a technology standpoint, like you said, it’s moving along so fast. This is what we call planned obsolescence. You buy something now that you already know in a year it’s going to be smaller and better and faster, so you just want to have access to it.
The analogy I use, I’m a musician, so people have home studios and they’re into music and musical equipment, and they can go down this same kind of rabbit hole where they’re buying more gear, more expensive things, they’re like, “If I get that microphone, I’m going to sound so much better,” and I see that happening with biohacking. I see this new gadget comes out or a new tool and they think it’s going to make them better in a certain way. But ultimately, it’s up to them and their behavior that’s going to affect it. So I think sometimes we get too caught up in just the bright lights and shiny things. I think there’s always a simpler way to do it.

[Damien Blenkinsopp]: And even the lab tests, there’s like tons and tons of lab tests you can get down and they can be really specific and complicated, and sometimes it just takes the most basic ones to figure stuff out. And lab tests can start really racking up if you get into specialty tests; you can be paying thousands of dollars just for one lab, so you have to be careful. That’s what I’ve learnt over time as well, I’ve spent a fortune in specialist labs and sometimes I was tracking them too frequently and things like this. We were talking about the cost-benefit earlier; I had to really learn how to spend my money wisely when it comes to those things.
So in terms of other people that you would recommend to talk about practicalities, is there anyone else you’ve come across like you that’s done a lot of this stuff in real life? Or other people that you’ve learnt a lot from in this area who you think would be great people to talk to?

[Bob Troia]: I’ve come across and met so many awesome people over the last few years. Are you talking more about people that have some sort of public presence?

[Damien Blenkinsopp]: Yeah, someone other people could connect with them and find their stuff.

[Bob Troia]: The first place to look would be just going to the Quantified Self website, quantifiedself.com and they tend to show meet-ups from all around the world and they film them, and so you’ll see lots of great talks. Those will typically then link out to that person like they have a blog or a website or something where you can get more information on it.
When I got started in all this, I think some of the early folks that I was reading, folks like Tim Ferriss, Four Hour Body was a big thing for me to kind of start peeling back the layers of the onion.

[Damien Blenkinsopp]: Tim Ferriss is a good guy to follow. He still talks about different stuff he’s doing here and there.

[Bob Troia]: I know he’s got a podcast that deals with a lot of other things, but I was talking more around when I started reading that book, and a lot of people that are out there doing podcasts, they’re branching out into other areas. If you’re talking just on the biohacking/QS side, there’s one guy who basically does nothing but talk about HRV. He’s done all sorts of n=1 experiments around understanding himself through how is HRV affected based on other parts of his life.

[Damien Blenkinsopp]: That sounds cool. Do you know his name? Or we’ll put it in the show notes afterwards.

[Bob Troia]: Yeah, quantlafont.com. I’d have to look up the spelling of that. There’s another guy, [unclear 1:13:16] in New York, he’s got a blog called Measured Me. He’s blogged on and off over the past few years and the thing you’ll see is that different people tend to focus on certain areas, so I think he’s more into tracking mood and understanding emotions and those types of things versus other people that might be getting more into the biohacking, getting into data from the physiology standpoint of things.
In terms of others, are you looking for specific names of blogs?

[Damien Blenkinsopp]: Whatever comes to mind. If those are the ones you’ve come across or if you have other examples that might be useful to the audience basically, if they’re interested to learn more about this kind of stuff.

[Bob Troia]: I think a great resource for understanding this more is quantifiedself.com. They have forums as a community and a Facebook group. I know Bulletproof Executives, so if you go to bulletproofexec.com.

[Damien Blenkinsopp]: So he’s been talking about his diet and his coffee today for example.

[Bob Troia]: Yeah, but there’s a really, really active forum there that’s all broken up by anything you could think of. If you want to talk about any little sub-topic of biohacking, there’s going to be some conversations in there because the community itself is aggregated there. So beyond coffee, you can get some really great conversations there. And those are like the main places. I think look for meetups in your city or nearby; connect with other people that are like-minded. That for me has been the greatest. When you meet people face-to-face, you build those relationships.

[Damien Blenkinsopp]: And there’s a conference, you mentioned you’ve been to a few conferences. So you went to Quantified Self and did you go to the Bulletproof one?

[Bob Troia]: Yeah. Quantified Self tend to do two conferences a year. They do one usually in the Bay Area—I think there’s one this May—and they’ll do one in the fall in Europe, usually in Amsterdam, so that happens twice a year. And then the Bulletproof biohacking conference just happened a few months ago in L.A. I’ve been to the first one was a couple of years ago where there was a group of maybe 30 or 40 people, it was really small, and this year it was probably like 400 or 500 people. To me, it’s not that more people are into it. I think everyone’s always been into this stuff, I think they’re just finding each other.

[Damien Blenkinsopp]: Yeah it does seem like that and when you were talking about the forum on the bulletproofexec site, there is a lot. I was looking at it a couple of days ago and there are some really heavy post threads, with 10,000 posts or threads. There’s a lot of information in there now; it’s been going for a few years so like you said, there’s a lot of information and you can connect with a lot of different people there as well. But I found, like you, that conferences I can interact more with people face-to-face. It’s a great way to meet people into this stuff as well.
So you did mention your routines, I wanted to ask you if you have some kind of daily routine about tracking metrics, like first thing in the morning or in the evening? Or is there anything you do every day which you find useful in terms of tracking data or doing any of this stuff?

[Bob Troia]: I would say on a daily basis the trick is to allow as much of it to be passive as possible, so things like having some devices collecting biometric data or having something in my home that can measure my indoor environment passively, just those types of things are happening so I can always go back. Even just your smartphone is tracking my position so I can actually map out where I’ve travelled throughout the day. I’m just collecting that data, whether or not I use it.
But in terms of the morning routine, today for example, I woke up, and the first thing I’m doing is part of my thyroid program is I have to check my morning temperature every morning, so I have a thermometer right next to my bed. So as soon as I wake up I pop in the thermometer. I actually was using an old-school, non-mercury thermometer, it was like a glass one, but now I’ve moved to this Kinsa, which hooks to your smartphone and it takes it really fast so instead of having that thermometer in your mouth for five minutes, you can just do it in thirty seconds.
I do that, I get my temperature done; it’s already in my phone, I don’t have to write it down anywhere.

[Damien Blenkinsopp]: Wow, that’s a nice little hack, I didn’t know you could do that.

[Bob Troia]: It’s pretty cool. And then if I’m doing something like we talked about HRV, so while I’m lying in bed, I have a dresser next to my bed and have my Polar chest strap and my phone’s already there, I put on the chest strap and do a three-minute reading. We talked about HRV, you want to see where you are in relation to your baseline.

[Damien Blenkinsopp]: Do you do the standing or the lying down?

[Bob Troia]: Lying down. When I wake up in the morning I try not to even shift. If I’m under the blankets or over the blankets, I don’t change it, I don’t’ want to affect it. And then I’ll get out of bed and I’ll weigh myself because I have scales in the bathroom. Again, I have one of those wireless scales so automatically the data is uploaded and you don’t have to think about it.
Then if I’m doing any glucose related tracking like I’m in a window where I was like, “Okay, this is the month I’m going to track again,” I’ll take a quick reading right then. And then throughout the day, I guess depending on my schedule, in terms of what I would track, if I had blocked out time on a given day to work on any kind of mind-training, so it could be things like space repetition or dual n-back, there are pieces of software that help improve short-term memory or recall, I’ll use tools and do that for maybe 30 minutes. The trick is just finding the time to do that.

[Damien Blenkinsopp]: So me personally, I’ve gone through phases of n-back and also the luminosity; right now for instance, I don’t do either. Have you done these in phases like you’ll do for them for a while and then other times you’re not doing them? Or is it just a constant ongoing thing that you’re doing?

[Bob Troia]: I would say more with the dual n-back. Space repitition it comes down to what I’m studying with it. One of the things I’m actually working on right now, it’s more of a long-term experiment, [and] I’m trying to get better at playing poker. I’m trying to come up with ways of memorization techniques and try to become better at it. I’ve been going through a lot of exercises and reading these books and doing these tests. Take away any of the actual active playing cards, you have to build your working memory up.

[Damien Blenkinsopp]: That’s pretty cool. I’ve actually been looking at that stuff recently myself and starting to work on it. Like minds.

[Bob Troia]: For example, if you go to the gym or you’re working out, you might just be tracking your heart rate. My workout itself, it’s still for me either a notebook and a pen just writing down what am I doing today, or I type it into my phone.

[Damien Blenkinsopp]: So are you still doing the Body By Science? We had Doug McGuff on a while back and I saw you were doing that as well. Are you still doing that or are you doing something a bit different now?

[Bob Troia]: So I started off doing the Body By Science type of workouts, and then through that and through meeting folks in the biohacking space, I got connected with these folks that are doing a different type of training that’s built off what’s called isoextremes, which is essentially mostly body weight-type exercises where you’re pulling into a position. So the idea would be you have to do a wall sit where you basically go against a wall and you get down to a squat and you’ve got to hold yourself there for five minutes. But what you’re really doing though is you’re trying to pull yourself down not hold yourself up, and so there are a whole bunch of workouts around that. It’s more neurological training.

[Damien Blenkinsopp]: It sounds like you’re really intensely holding the muscles. It’s really intense effort.

[Bob Troia]: We could have a whole other conversation about that stuff because it also involves an electronic modality that you basically hook up these electrodes that are in very specific positions in certain polarities that allow your muscles to lengthen while you’re doing these exercises. Basically what you’re doing is you’re training your muscles but you’re also training your nervous system. Over time, it has a lot of impacts, everything from reaction time and speed, not just the physical benefits.

[Damien Blenkinsopp]: I find all of that stuff awesome.

[Bob Troia]: To me, that’s more like the bleeding edge stuff because I actually go to the gym with this stuff and people look at me. I always have someone coming up to me like, “What is that?” I have to explain it and eventually you start seeing the same people there so then they leave you alone, but you always get these funny looks.

[Damien Blenkinsopp]: One time I was in Bangkok and I was doing this specific exercise, and I actually came from the Body By Science guys, which was a very slow pull-up of one minute—I don’t know if you saw that before. Anyway, I was doing this one minute pull-up and this guy came up to me at the start and he starts asking me, “What are you doing?” I was in the middle of my exercise and it takes a lot of effort because it’s really intense, and he wouldn’t leave me alone, he was like, “Tell me what you’re doing,” literally for the whole minute. Afterwards I was like, “Man, seriously I’m exercising. I know it looks kind of different but…” So it does look different, and it does get people asking what the hell are you doing, you’re looking a bit strange in the gym.

[Bob Troia]: Yeah, I was doing an exercise where I was doing, imagine doing a curl, like you have a curl bar, and let’s assume you’re at the top position, you have to slowly lower it from the top position down all the way to the bottom but you have to do it over the course of five minutes. So people are looking at you like, “What the heck?”

[Damien Blenkinsopp]: Yeah, exactly, and it’s so hard. That’s very similar to what I was talking about. It’s really, really hard in terms of mental. That’s what I love about those things, like you were talking about the neuromuscular part, it’s really charging your mental capacity and you learn to push yourself way beyond where you start from and it’s just a mental game at first I find, and so they’ve looked into benefits of concentration and things like that once you learn to push yourself further than you thought you could go.
This has been such a great practical chat. I think this is the most practical chat we’ve ever had in terms of real life stuff and people doing it every day, so it’s great to hear about your routine. Also, just because that’s really useful to people like how could I implement this in my daily life.
If you were to give someone one recommendation that you think would be useful to them in their use of data to make better decisions about their bodies, health, performance, longevity; what would that one thing be?

[Bob Troia]: The biggest recommendation, I would say, don’t let it become a hindrance, meaning I think it’s ultimately how you feel. Its one thing to say I have a goal and I’m trying to achieve something, how do I get there. But if you’re going the opposite way and trying to understand your current state and what got you to that current state, I think as we talked about, figure out is there a way to do it without it becoming a burden. It’s like say even exercise; there’s no such thing as bad exercise, technically, as long as you don’t hurt yourself. So I think people can over think it, instead of just starting to do it.
I think if you’re just looking to improve your health or longevity, those are very different things, so I could give you a tip that’s diet-based where I would say, “Cut out sugar,” or something, but I think, for me, it’s more like the mental state you’re in to do it. These are people that have already made the decision they want to do this so start off and don’t let it become a hindrance; don’t try to do 20 things at once.
That’s a big answer but I was talking more like I think there’s a lot of information out there; I think you have to assess where you’re at and what your goal is. I think health is a very general thing, everybody wants that longevity, but there might be some people who are looking for a performance-based performance versus other people who are more focused on longevity.

[Damien Blenkinsopp]: So I guess what you’re saying is try and focus on what’s really important to you to start with to keep it simpler.

[Bob Troia]: Yeah I think people might even be coming at this not from the standpoint of “Something’s wrong with me and I need to fix it.” There might be people who are just “I like where I’m at and I want to be better.” And I think that mental state, I think you’re still striving to become better but I think you’re just coming at it from a different angle.

[Damien Blenkinsopp]: And the beauty of this is I think it’s really like this long slope. When you think of it as black and white, unhealthy healthy, but it’s really not; it’s this long slope and I think all of us can do better. You can push yourself up further to be better and you can be quite good like you’re saying.

[Bob Troia]: And I think people they’ll see something that doesn’t look quite in line, and instead of freaking out or stressing themselves out, if they feel okay I think ultimately that’s the gut check you always have to take: How do you feel? It could be physical, it could be mental, maybe your stress is due to things like your job or relationships or friendships, so the things that are outside of that, and so actually your biohack itself might be “Improve your relationships.”

[Damien Blenkinsopp]: Yeah, exactly. Great point. Okay Bob, so where would we find you? Where’s your blog? And is there anywhere else you’re hanging out online where we can find you and learn what you’re up to?

[Bob Troia]: Yeah, I detail all these happenings on my blog, at quantifiedbob.com. I have a Facebook page, a Twitter account, all under Quantified Bob, Google + as well, if you’re into that.

[Damien Blenkinsopp]: Where are you most active? Would it be the Twitter?

[Bob Troia]: Yeah, Twitter is the most active. And if you ever want to connect to my real life persona, myself, it’s just bobtroia.com. I tend to keep more of this stuff on the other account just to separate. That way, there are people who care about this that don’t care about my business stuff. But it’s very clear that I’m the same person but I just split my conversations up.

[Damien Blenkinsopp]: That’s cool. It seems like you’re a pretty diverse person—fitness, music, entrepreneur, tech—all this stuff going on.
Bob, it’s been great to have you on the show with all this practical information. It’s great for the audience at home. Thank you so much for making the time for it.

[Bob Troia]: Great, thanks so much for having me.

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Is Heart Rate Variability the best biomarker of the time to track our longevity? In this episode we look at why HRV may be the best way to track how well you are aging and the bets being placed on it in Silicon Valley to drive innovation in anti-aging and longevity research.

Previously we’ve looked at using HRV for training and recovery, stress management, and tracking hormesis. If you are new to biohacking, HRV is an easy economical way to start tracking. All one needs is a heart rate strap and phone app.

The activity around HRV in Silicon Valley originates from The Palo Alto Longevity Prize – a one million dollar life science competition to “hack the code” that regulates our health and lifespan. The prize is using HRV as a proxy measurement for longevity, so teams will compete against each other to find tools and tactics to increase the HRV metric – and thereby potential longevity.

“Whenever you want to nurture innovation, you need to have metrics… The reason HRV was chosen was… one, we have decades worth of heart rate variability data…. there is good cohort data, population level data, that suggests that declining HRV is also due to a chronologic age…. [and] unlike most biomarkers in health, HRV can be measured continuously, contextually. You can measure it for 24 hours.”

– Dr. Joon Yun

Today’s interview is with the man behind the Palo Alto Longevity Prize, Dr. Joon Yun. Dr. Yun is managing partner and president of Palo Alto Investors,LLC, which oversees 1.8 billion dollars in assets invested in healthcare. Dr. Joon Yun is board certified in Radiology, was clinically trained at Stanford and received his M. D. from Duke Medical School. He has published numerous scientific articles, and has a column in Forbes magazine. Recently, he agreed to sponsor the Palo Alto Longevity Prize by donating 1 million dollars to this life-science competition.

The show notes, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know what you think in the comments!

itunes quantified body

Show Notes

  • By the mid 40’s there are both subjective (able to be felt) examples and objective (not felt) examples of homeostatic capacity loss. (3:46).
  • Prior to middle life, the body’s homeostatic capacity is able to return to baseline (5:00).
  • Aging can be thought of as a decline in the body’s ability to get back to homeostasis due to an erosion of homeostatic capacity (5:27).
  • The healthcare system is centered on returning homeostasis and not homeostatic capacity (5:41).
  • The goal of the Palo Alto Prize is target and nurture ways to improve and restore homeostatic capacity, instead of restoring homeostasis (6:10).
  • There is some overlap in hormesis and homeostatic capacity (9:20).
  • Challenges to the body can increase homeostatic capacity (9:53).
  • The final perimeters of the Palo Alto Prize were announced at the end of 2014 (10:29).
  • Millions of people succumb to aging or aging-related issues. Thus, the sooner we start, the more people can benefit (11:19).
  • This is the first prize Dr. Joon Yun has sponsored (12:09).
  • Despite the innumerable traits of homeostatic capacity happening on the physiological level, there are existing biomarkers that represent proxies of homeostatic capacity (12:51).
  • Practical reason for why HRV was chosen as a biomarker include: (1) ability to be measured continuously (this is a unique feature compared to other health biomarkers); (2) ability to be measured contextually; and (3) ability to be measured non-invasively. Globally, there are numerous devices available to help measure HRV, thus providing an opportunity for a range of teams to apply for the prize (15:34).
  • Orthostatic hypotension was another biomarker considered (16:50).
  • Too rapid heart rate response or insufficient heart rate response during cardiac stress testing may indicate dysfunction in certain areas (18:05).
  • The data from orthostatic hypotension, cardiac stress testing, and heart rate decline after exercise are strong relative to other areas of homeostatic capacity assessment (19:05).
  • The goal of the project is to gather more data and develop more biomarkers of homeostatic capacity (19:14).
  • The definition (or standard) of HRV to be used in awarding the Palo Alto Prize will be determined by a team of experts (19:45).
  • Dr. Joon Yun does not track biomarkers on a routine basis (20:51).
  • Dr. Joon Yun’s single most important recommendation is exercise to improve your health, longevity and performance (23:37).

Thank Dr. Joon Yun on Twitter for this interview.
Click Here to let him know you enjoyed the show!

Dr. Joon Yun

The Tracking

Biomarkers

  • Heart Rate Variability (HRV): measurement of how one’s heart rate varies over time. Dr. Joon Yun describes HRV as a proxy for autonomic capacity, which itself is a surrogate of overall homeostatic capacity. Additionally, HRV can be taken continuously and non-invasively. Please check out other episodes for details on how to track HRV and optimum ranges.
  • Orthostatic Hypotension: measures the ability of the body to recalibrate blood pressure when moving from a lying to sitting position or a sitting to standing position. In aging, it has been associatively observed that the body’s ability to adapt to rapid changes in blood pressure deteriorates. Therefore, this is one way to infer homeostatic capacity and is another biomarker considered for the prize.
  • Heart Rate Recovery: measures autonomic capacity by looking at heart rate behavior after exercise. Looking at this decline over a certain time period gives insight into the function of the heart when compared with a normal curve.
  • RMSSD (Root Mean Square of the Successive Differences): the industry standard for measuring and calculating HRV. Discussed in more details in Episode 1 & Episode 6.
  • lnRMSSDx20 (RMSSD with natural log and multiple of 20 applied): applications have begun using this measure. This is RMSSD scaled to an index of 100 for easier use. Discussed in more details in Episode 1 & Episode 6.

Terms

  • Homeostatic capacity: a network of traits in our bodies to achieve homeostasis. It is the body’s ability to “self-tune” or, in response to stressors, its capability to self-stabilize. This capacity or trait is inborn: when we are young, the feeling of health feels like “nothing”. Once it begins to decline in midlife, we become aware of it. For instance, we notice an inability to tolerate hot or cold weather or that the recovery from a late night takes longer that it use to. There are also changes not necessarily felt, such as homeostatic capacity returning elevated blood pressure to base levels.

Lab Tests, Devices and Apps

  • Cardiac Stress Test: this test is an assessment of the body’s response to an exercise heart rate challenge. Dr. Joon Yun describes this as a test, common in standard practice, that can be viewed as a “homeostatic capacity test”.

Other People, Books & Resources

People

  • Edward J. Calabrese Ph.D.: Dr. Joon Yun first heard about the idea of hormesis from him.
  • Aubrey de Grey: a link to Aubrey de Grey’s published work. He was also mentioned in this episode by Dr. Joon Yun in reference to the Methuselah prize. We talked to Aubrey de Grey about his framework to increase longevity in Episode 14.

Organizations

  • Methuselah Mouse Prize (MPrize): started in 2003, this prize was designed to accelerate the development of life extension therapies. In 2009, the MPrize for both longevity and rejuvenation were awarded. Currently, $1.4 million is available for awarding to researchers who can top previous winners’ performances.

Full Interview Transcript

Transcript - Click Here to Read
[Damien Blenkinsopp]: Yeah, it’s great to have you here.

So, you’re involved in this big project called the Palo Alto Longevity Prize. Could you give us a run down. What is the vision behind that, and why have you put this together now?

[Dr. Joon Yun]: The vision of the Palo Alto Prize is to nurture innovation that improves the homeostatic capacity as a gateway into promoting healthy longevity, and health span.

[Damien Blenkinsopp]: Right, so, I think a lot of people aren’t exactly sure what homeostatic capacity is. So how would you describe that, and why is it particularly this homeostatic capacity that you’re linking to longevity?

[Dr. Joon Yun]: Most people are familiar with the word homeostasis. So think of homeostatic capacity as a network of traits in our body that enable us to achieve homeostasis.

Now homeostatic capacity is something that’s endowed by nature. It’s been shaped by evolution. And you can think about it as robustness, resilience, coping mechanism, dynamic range, anti-fragility. These are all kind of similar concepts. But the basic notion is that we have an incredible set of traits that enables our bodies to self tune.

One of the ironic things about homeostatic capacity is that we don’t really realize we have it until we start losing it, typically in mid-life, where all the sudden you start to feel things that you didn’t feel before. At nighttime, it’s a little too dark, the sun shines a little too bright during the day. [When] riding a roller coaster, you may come out of it nauseous, because your body doesn’t re-calibrate. Altitude sickness starts emerging around then. The bouncing back from injury or jet lag, or a late night.

All these things are suggestive ways that we start to experience the loss of something that we didn’t have. That we didn’t used to feel. The loss of something that we didn’t feel when we were younger.

In fact, when we’re 12 years old, another way to define health is the feeling of nothing. When we’re young and we’re healthy, what we feel is nothing. It’s when we start feeling something that we realize something’s going on.

[Damien Blenkinsopp]: Right, right. So in a sense, this is balance, and you’re just feeling well without any negative symptoms, or negative feelings, I guess.

[Dr. Joon Yun]: Yes. So you can think about homeostatic capacity as your body’s ability to self tune, and get back into balance or homeostasis. But think about all the things that happen…well.

So we’ve described the things that are subjective that you can experience. There’s also a lot of objective things that you can’t feel, but start to emerge by the middle of life, again that’s defined by the mid-forties.

When we’re young and our blood pressure’s high, or our blood sugar is high, the body has the homeostatic capacity to return those numbers to a normal baseline. But as we age, a lot of those numbers no longer return to baseline. They remain high.

And we call those situations diseases like hyper-tension and diabetes. The thing about a lot of the diseases of aging as reflections of the body’s declining intrinsic ability to get back to homeostasis because of potential underlying and inevitable erosion of homeostatic capacity.

Now what we do in the health care system today, we provide an external mechanism called the health care system, we trying now here in the US to help the body get back to homeostasis. But because we’re trying to restore homeostasis, and not necessarily focused on restoring homeostatic capacity, the inevitable loss of homeostatic capacity continues manifesting in increasing features of aging. And in the long run the health care system can no longer help the person make the homeostasis, and then death ensues.

So the gambit of the prize is to target and nurture innovations that improve homeostatic capacity. That we restore homeostatic capacity instead of restoring homeostasis, to see if this could be a gateway into improving health, and sustain health, and longevity could be an outcome of that.

[Damien Blenkinsopp]: Great. So this is an area you feel is undervalued, under-utilized, and currently when it comes to health and health care, and it’s something you want to promote.

What is the kind of vision behind the prize? For instance, we had an interview with Aubrey de Grey recently, and he’s talking about extending lifespan considerably. Would you put it along those kind of lines, or is it more kind of making sure that we live to our prime years 80 years old, 90 years old, 100 years and we live really well, versus having the current diseases which plague a lot of people these days?

[Dr. Joon Yun]: Well it’s really about promoting health. Longevity might be an outcome, but there’s a difference between something being an outcome and a goal.

Our goal is to improve health, and helping longevity may be a consequence of that. So I do think that the target is a little it different. And I also think that the target, the homeostatic capacity, is different than homeostasis.

To give you the example of high blood pressure. Think about high blood pressure or hyper-tension as it’s called medically as the lab error reported by the body of the blood pressure being too high. And the way we fix this is in the modern medical system is we give patients drugs that normalize that blood pressure. Meaning, return it back to a number associated with homeostasis.

But because we are externally providing that capacity, when you miss your dose of drug, or when you come off a drug, in many cases your baseline has progressed, and may be even worse. Because the one thing your body knows how to do is to homeostasis against all the external challenges. The more it sees blood pressure lowering drugs, in many ways the body rebounds. It’s called toxic phalasis.

And this is a challenge with most pharmaceuticals that the body remodels against the drug. So when you come off the drug, your lag error can even be worse. You can have rebound hyper-tension, something called addiction decompensation.

The way nature addresses high blood pressure is by exercising. Meaning the natural way to treat hyper-tension is to leverage your homeostatic capacity as a way to lower your blood pressure. Meaning, when we exercise, we’re actually increasing our blood pressure by challenging it. And in this sense, the homeostatic capacity can be stronger. And so the baseline blood pressure actually gets lower the more times you raise it. So it’s almost a mirror image of what we’re doing with the medical system today.

And when we think about the diffuse benefits of aging in, really, all those views of aging, including longevity itself, it’s generally suggested that using homeostatic capacity as a treatment for aging, rather than tools of homeostasis, may actually work in terms of expanding health for society and expanding longevity.

[Damien Blenkinsopp]: Great, great. Thanks. We’ve spoken about hormesis quite a few times on the podcast before. Would you say it’s related to hormesis? When you were talking about exercise, it sounded very similar to the kind of hormetic discussions we’ve spoken about. So are homeostasis and hormesis linked?

[Dr. Joon Yun]: Some people may find some overlapping ideas. Hormesis I first learned of it through some some great body by Ed Calabrese, out in the East Coast. My understanding of it is that it’s the notion that at different ends of the curve your going to have differences in response.

I guess there’s some relation to it, although I think the mechanism attributed to hormesis has been debated out there. But the notion that challenges to the body that, many challenges to the body can actually paradoxically induce competitory strength, or induction of homeostatic capacity. But I do think that there’s some overlap in the ideas.

[Damien Blenkinsopp]: Great, great. Thanks for that. Helps to situate our audience better.

Okay, so coming back to the Palo Alto Longevity Prize. Is there a specific reason why you decided to do it this year, and could you explain a bit more about the background? So you already have many teams participating in this challenge. Have they got any rules around defining the participation? So, have you said that there’s any restrictions to what they can do in order to compete? Or is it kind of very, very broad?

[Dr. Joon Yun]: The Palo Alto Longevity Prize is run by a team, including some of the scientific experts and industry experts in health care, and they’re the ones who convened to determine both the criteria, and they’ll represent the independent judging panel as well. And those final parameters will be announced to the public sometime this year. And there they’re accepting public comments.

Remember this is a new area, homeostatic capacity. It’s kind of a new word, although I think it is a phrase the scientific community understands, and it can embrace, and can develop innovations around. So we’re in the early stages of all that.

As to why do it this year? Well, we know that every year we wait, there’s enormous amounts of suffering that goes on around the planet associated with age and loss of life. And so we know that every week we wait, a million people have succumbed to aging or aging associated conditions. So, we think this is a very significant time, and the sooner we start, the better.

We do think that this is going to take some time, and maybe a series of prizes, with a lot of different starts. And we think it will be a long journey, but the earlier we start, the more people can benefit from improved health.

[Damien Blenkinsopp]: Great, thank you very much. I understand that you’ve put your money, or is it Palo Alto Investors that have put the money in for the prize to stimulate? We’re seeing a lot more prizes now, as a method for stimulating innovation in other industries. I think this is the first one that’s tried to do it in health care, and certainly longevity. Or have you seen other ones before?

[Dr. Joon Yun]: I think there have been other prizes before. The [inaudible 11:56] Prize, Aubrey de Grey, the Methuselah Prize. I’m new to prizes. I’m the sponsor of the prize, and I learned about prizes with some of the experts in the prize community.

And one of the things I like about it is that it mirrors how evolution works, Darwinian evolution works. There’s a niche, there’s a diversity of options that compete for the niche, and there’s a winner.

[Damien Blenkinsopp]: Great. Coming back to the rules of the prize, you’ve decided to focus the prize on using heart rate variability, HRV, which we’ve covered quite often in this podcast before. Why did you decide that this was the biomarker you were going to use for the focus of the prize?

[Dr. Joon Yun]: Exactly. So whenever you want to nurture innovation, you need to have metrics. And homeostatic capacity is a new phrase, and there are some existing biomarkers or diagnostic tests that could represent proxies of homeostatic capacity.

But homeostatic capacity is a diffuse network of many, many innumerable traits. Such as physiological level, tissue level, systems level, molecular level, cellular level. It’s a composition and the inter-relationship between all of them. It’s a composite that reflects an overall organismic homeostatic capacity. So the challenge is how do you take and define biomarkers that represent copies that affect the surrogates for homeostatic capacity?

The reason HRV was chosen was, first of all, it represent a… Well, so HRV is heart rate variability. It is a biomarker of autonomic capacity, which itself is a surrogate of overall homeostatic capacity. So it’s just one variable that happens to have a number of features that make it interesting.

Number one, we have decades worth of heart rate variability data. It’s been in clinical use since 1963 to monitor fetal stress. And when HRV goes low, it’s one of the criteria for determining fetal stress and associated infant-fetal mortality. So it’s notable that it’s not used in the post-natal life, adulthood. I mean there are very few labs around the world that actually monitor HRV in patients as they get older.

And there is good cohort data, population level data, that suggests that declining HRV is also due to a chronologic age. And many of the diseases of aging are also associated with aberration in heart rate variability. None of this is established in a causal way, but the degree of association of HRV decline with some features of aging suggest that it might be an interesting biomarker.

But there’s some additional practical reasons why HRV was chosen. Unlike most biomarkers in health, HRV can be measured continuously, contextually. You can measure it for 24 hours. Most biomarkers, as you know, are done through blood tests, body fluid samples. You only get a snap shot in time. And given the dynamism of the system, most biomarkers have a tremendous amount of variation, even in a 24 hour cycle.

So the fact that [with] most biomarkers, it’s impractical to get continuous monitoring, and you can’t detect changing patterns, and changing dynamism over 24 hour life cycle, as well as in a very different context, make it less useful than HRV, which can be measured non-invasively, continuously.

There’s also a global footprint of devices, including consumer devices, that help measure HRV. What that does is opens up the aperture in terms of the breadth of teams that can apply for the prize. If we make the biomarkers too narrow, it limits the number of labs and groups around the world who might have an innovative idea on the intervention side to be able to process their innovation.

So there is a tradeoff between specificity of a biomarker for homeostatic capacity versus this practically of the diversity of options that we may be able to solicit. So, HRV, again, there’s been empirical association with aging. Mechanistically because it’s associated with autonomic capacity it is a feature of homeostatic capacity. It’s global footprint, non-invasive, continuous monitoring, and relatively inexpensive to obtain, unlike some biomarkers that are proprietary, it’s pretty costless.

[Damien Blenkinsopp]: Great, thank you for that. Are there any other biomarkers that you looked at, and you considered for measuring homeostatic capacity?

[Dr. Joon Yun]: Absolutely. There’s only a small subset of modern diagnostic tests that actually assess homeostatic capacity. And you can think of a lot, well, actually get an annual checkup, but indirect proxies. But more direct proxies, more direct surrogates, really require tests themselves be dynamic.

So, an example of another potential surrogate is orthostatic hypo-tension. So it’s your ability of the cardiovascular system to recalibrate blood pressure from a sitting to a standing position, or lying to a sitting position. When we’re young, we have tremendous real time system dynamism that allows us to adjust to quite the rapid demand. And you really don’t have much else raising your blood pressure.

But as we get older, it’s observed that the body’s ability to adapt to those change in conditions deteriorates. So it’s associated with aging, and that’s one way to infer that there’s declining homeostatic capacity. And this may help explain why as you get older there’s one of the contributors to syncope, one of the contributors to declining ability to perform a lot of more strenuous physical tasks.

You can also start to think about the cardiac stress test as an example of a homeostatic capacity test. This is one of the ones that is more standard practice out there for the medicine of today. Essentially, one of the things we’re measuring is the body’s heart rate response to an exercise challenge.

And in some cases the heart rate response is too rapid. So that could reflect some dysfunction in the Diego Connor Response. And in some cases the heart rate increase is insufficient. So, BP is reflective of a system that is less dynamic than it used to be. And these things are associated in a lot of, on toward clinical outcomes in the long haul.

Anything where the heart rate declines after exercise. And one of the things we look for is does the heart rate return to normal, does it look like a normal heart? Does it happen in a normal amount of time? Because as we age and our intrinsically homeostatic capacity declines in which case this is a non-capacity there is abnormal return to normal as well.

So these are small subsets of the overall diagnosis landscape used in clinical medicines today, that we think already reflect homeostatic capacity. But those things require, there’s a higher burden in terms of throughput to asses innovation, and the tests themselves require more involvement.

And furthermore, the data in those areas are strong, although there are many others, but we certainly need more data across the spectrum. So one of the hopes for the competition is that we help promote the idea, that we gather more, and develop more biomarkers for homeostatic capacity.

[Damien Blenkinsopp]: Alright, great. Great, I didn’t realize that was part of the project. Have you defined the exact standard? Because there’s a few different standards of HRV out there.

One of the ones we’ve discussed quite a lot is is the natural log, RMSSD, which is multiplied by 20 and used by a lot of consumer devices at the moment. Have you defined that as yet, or are you going to be defining that at one stage as a criteria for use in the project?

[Dr. Joon Yun]: Yeah, we’re deferring that to a team of experts that have, they did the exact same topic. So, I’ll leave it up to them

[Damien Blenkinsopp]: Great, great. How can people get involved in the Palo Alto Longevity Prize? I understand there’s already 15 teams which have signed up? Maybe there’s a few more already. What’s the timeline before, for instance, you stop accepting new teams, and then for the other steps of the project?

[Dr. Joon Yun]: Yeah, you know, I don’t have that information at my fingertips. Again, all of that, the process is being managed by the production team. And I’m a sponsor of the prize. So for those details I’ll have to refer you to the team.

[Damien Blenkinsopp]: In terms of your own personal use of biomarkers, are there things that you use, or you track on a routine basis for your own health, longevity, or performance?

[Dr. Joon Yun]: You know, I actually haven’t. I haven’t thought about this project relative to my own health yet. It’s something that I probably will consider. But no, I’m not doing any personal tracking right now.

[Damien Blenkinsopp]: Maybe that’s because you’re really healthy and your homeostasis is pretty good, so you know you don’t feel out of sync, and the need to do it.

[Dr. Joon Yun]: Oh no, I definitely feel it. But yeah, these are early days, and I think a lot more science has to happen. And I think, I think we will learn about it, if nothing else, from this process.

[Damien Blenkinsopp]: Great, great. If someone is interested in getting involved in this, perhaps putting together a team, should they just go to the website for the Palo Alto Longevity Prize, or I understand it’s still available for signing up, as a project team. So would that be the best place to go?

[Dr. Joon Yun]: Yeah, I think the best way to engage is to read through the website. And I believe all the details are there, at the paloaltoprize.org. I believe all the teams have signed up through the website process.

[Damien Blenkinsopp]: Do you know if there’s other ways people can participate beyond just putting together a team?

[Dr. Joon Yun]: I don’t know, I don’t know. Again, I will defer that to the team, the way the public can engage.

[Damien Blenkinsopp]: Great, great. What do you think will happen in the next five or ten years in this area? Have you got some kind of vision or hopes, or are there any things that you’re excited about? The opportunities that are going to occur in this area, biomarkers or longevity, in the next five or ten years?

[Dr. Joon Yun]: I do hold out some hope that there’s a small chance that there are some major breakthroughs coming. And you can sense that even in talking with teams. Scientists tend to be pretty conservative, and also for reasons of competitiveness they tend to under-share hypotheses and preliminary data. And after you hear enough of these really intriguing, unique ideas, you realize that the scientific field is more advanced than the public realizes.

And one of those things that prizes are trying to accomplish prizes such as ours and the initiative such as ours is to accelerate those ideas and actions. So it’s possible that there’s some major breakthroughs that are possible in the five year time frame.

The thing that we know for sure, is that we’ll learn a ton, and the idea to create new paths and new avenues of research that give us more shots on goal in terms of improving people’s health.

[Damien Blenkinsopp]: Great, great. Thanks for that. Do you have one biggest recommendation or insight that you’ve used some kind of data, or you’ve learned about your biology when it comes to health, longevity, and performance, that would be a recommendation for other people when they’re using data?

You’ve mentioned a few things as we’ve gone through this talk about why you selected HRV, for instance. And what would be your one biggest recommendation for using data effectively to improve health, longevity, or performance?

[Dr. Joon Yun]: Well, for now I like HRV because it’s affordable, and it’s also accessible from a technology perspective. And I think the access is growing throughout the world. I like the convenience factor. It’s more practical.

Most other biomarkers, I think the distribution isn’t as broad, and the effect is not at real time. And in terms of in lifestyle habits that, in a way that also match to improving someone’s health…. exercise is still my favorite. And there’s good data suggesting exercise improves the measures of HRV.

We also know that our improvement of HRV as well as exercise itself is also with the amelioration of the stages of aging. So, based on what is known today, I think that’s probably the most practical thing that a person can do to enhance their health.

[Damien Blenkinsopp]: Great Joon, yeah. Exercise is very important. Thank you so much for your time today. I really appreciate it, I know you’re a very busy man. We’ll put together some information on the project, some of those references, in the show notes so everyone can get access to that. Is there anything else that you’d like to share about the project that we haven’t covered already?

[Dr. Joon Yun]: No, that’s great Damien. I appreciate your time, and thank you for having me on your show.

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A walk-through of a practical framework designed to achieve what most of us believe is impossible – completely eliminate aging. Learn about the 7 ways we age, and how scientists are trying to design tools to repair each one of them.

Today is our first episode on aging. Longevity is a subject close to my heart, and I’ve been following the career of this episode’s guest for many years.

Dr. Aubrey de Grey is a visionary and general strategist in the field of longevity and anti-aging. He applies the concepts of planning, investment, and risk management to the science of aging so that we get there as soon as possible, within our lifetimes. The basis of his plan is the seven “Strategies for Engineered Negligible Senescence” that offer a practical route to longer life.

“[The] seven major categories… was really the big breakthrough that allowed me to see that the repair of damage was not only the most promising approach to combating aging with medicine, it was actually a feasible approach that could realistically be implemented within a matter of decades.”
– Dr. Aubrey de Grey, PhD

Dr. de Grey may be the greatest activist for longevity of our time. He’s the Chief Science Officer for the SENS Research Foundation, a not-for-profit organization funding research into longevity around the world. He’s authored two books; Ending Aging: The Rejuvenation Breakthroughs that Could Reverse Human Aging in our Lifetime in 2008 and The Mitochondrial Free-Radical Theory of Aging, for which he received his PhD in 1999.

In today’s interview we examine popular longevity strategies such as caloric restriction and telomerase therapies, as well as those covered by his own research. His viewpoints on these topics contrast greatly to those you may see in the press, and offer important insights into whether we should make use of these existing strategies.

The show notes, biomarkers, and links to the apps, devices and labs and everything else mentioned are below. Enjoy the show and let me know what you think in the comments!

itunes quantified body

Show Notes

  • Aging as a medical problem versus “Aging as a disease” (3:55).
  • The relationship of aging to illness (4:35).
  • The difference between “diseases of old age” and general illness (6:51).
  • The relationship between aging and cellular damage (7:51).
  • How the “seven categories of aging damage” make the longevity problem solvable (9:28).
  • The roadmap to the end of aging (“Bridging”) (12 :12).
  • The roadmap to the end of aging (“Longevity escape velocity”) (14:16).
  • Are we waiting for expansions in biotechnology to achieve better longevity? (15:00).
  • Dr. de Grey’s and SENS’ research resources (16:13).
  • Mitochondrial damage as it relates to aging (17:48).
  • Changes in mitochondrial theory since Dr. de Grey’s first book (19:22).
  • The uncertainty as to whether mitochondrial disease affects aging (20:35).
  • The indirect route by which mitochondria may affect health (21:24).
  • Mitochondrial damage and the “metabolic theory of cancer” (24:09).
  • How current trends, such as calorie restriction, fit into the SENS theory (26:51).
  • Intermittent fasting versus long term calorie restriction (30:21).
  • How telomeres and telomerase affect aging (31:20).
  • The balance between telomerase and cancer (32:58).
  • Do telomeres really effect cell function and aging? (36:04).
  • The difficulty in finding biomarkers valuable for tracking physiological age (36:54).
  • The difference between useful biomarkers and transitory blood metabolites (40:02).
  • What can be done, today, to increase longevity? (41:13).
  • Managing longevity by managing an individual’s health risk factors (43:23).
  • More about the SENS Research Foundation and the Methuselah Foundation (45:45).
  • What biomarkers does Dr. de Grey, personally, track? (50:28).
  • The Palo Alto Longevity Competition (53:13).

Thank Dr. Aubrey de Grey on Twitter for this interview.
Click Here to let him know you enjoyed the show or what you’ve learned from it.

Dr. Aubrey de Grey, PhD & S.E.N.S.

Aubrey de Grey

S.E.N.S. Research Foundation

  • SENS Research Foundation: Foundation for the research of “Strategies for Engineered Negligible Senescence” (SENS) founded by Dr. de Grey as an offshoot of The Methuselah Foundation.
  • SENS’ tax deductible donation page: SENS is a U.S. 501-C3 tax-exempt nonprofit organization, which can also accept tax deductible donations from citizens of the UK and most of mainland Europe. By donating, you’ll be in good company. Peter Thiel, the billionaire entrepreneur, VC and co-founder of paypal, donated $3.5 million to its activities.

The Tracking

Biomarkers & Frameworks

  • 7 Types of Aging Damage Framework: The framework Aubrey discussed in this episode which he has developed as the foundation of the plan to end aging.
  • Insulin: Probably the best indicator for overall metabolic function and health. Blood insulin levels begin to rise when muscle cells (primarily) become insulin resistant, meaning they are not taking up glucose properly. Insulin resistance is a precursor to diabetes.
  • Triglycerides: An indicator of general metabolic health. The seven types of aging damage are based on the inevitable damage arising from the metabolisms of life, and maintaining general health is a factor in keeping this damage in check.
  • Homocysteine: Dr. de Grey tracks his homocysteine levels only because it’s been slightly elevated in his personal history, and not because he feels it’s a general biomarker for aging. This is a great example of personalizing your biomarker monitoring plan.
  • Telomere length and Telomerase: While Dr. de Grey did not feel telomere length or telomerase levels were valuable as an indicator of aging, he did discuss their potential value for the function of high-turnover cells as well as the possible cancer risk associated with telomere extension.

Lab Tests, Devices and Apps

  • 23andMe genetic testing: Dr. de Grey discussed the value of understanding one’s personal health risks and predispositions via genetic testing.

Other People, Resources and Books

People

Organizations

  • Methuselah Foundation: The Methuselah Foundation was co-founded by Dave Gobel and Aubrey de Grey in 2003 to shed light on the processes of aging and finds ways to extend healthy life.
  • The Palo Alto Longevity Prize: The Palo Alto Longevity Prize is a $1 million life science competition dedicated to ending aging. Aubrey de Grey is on the board of advisors.
  • Moscow Institute of Physics and Technology: Doctor Aubrey de Grey is an Adjunct Professor at the Moscow Institute of Physics and Technology (MIPT). According to his onsite bio, “[MIPT], better known as ‘Phystech’, is one of the best educational and research institutions in Europe, attracting the most talented students from all over Russia in the field of physics and mathematics.”

Full Interview Transcript

Transcript - Click Here to Read

[Damien Blenkinsopp]: Aubrey, thank you very much for coming on the show.

[Aubrey de Grey]: My pleasure, thank you for having me.

[Damien Blenkinsopp]: So, aging is a disease. Obviously this isn’t what everyone thinks today, so why would you describe aging as a disease?

[Aubrey de Grey]: Well, it is actually because that is a controversial use of terminology I don’t tend to do that. I tend to try to sidestep the ambiguity of the terminology, first of all, and cut to the chase. So let’s say whether or not we choose to call aging a disease, what we can certainly say is that it is a medical problem. It is bad for you. It makes your body and your head work less well, and eventually it kills you. And that is what I call a medical problem.

[Damien Blenkinsopp]: Okay, fine. When you are looking at it from this perspective, are there things in previous interviews where I have seen. When we are young we can die and we can get injured from certain things. And when we age, when we are older in our 40s and 50s, we tend to get other health conditions which you could say are linked to aging. Are there certain conditions where you could say that if we didn’t age, we wouldn’t have to put up with these health or functionality restrictions?

[Aubrey de Grey]: Actually, yeah. And actually let me elaborate on that by referencing your first question about the age. I think the big problem with telemetry, with the use of the word ‘disease’ is not so much that we don’t call aging a disease. The problem is that we do call things like Alzheimer’s disease and cancer and atherosclerosis – we call them diseases. That is the mistake and the reason it is the mistake is because actually the difference between those things and the things that we rightly call diseases like infections is a much bigger difference, both in terms of the symptoms and the progression of the symptoms and the ways that we might be able to treat them. That is a much bigger difference than the difference between both of these, on the one hand. And the aspect with aging that we don’t call a disease – like declining function of the immune system or a loss of muscle or gaining of fat or whatever.

I think that if we are looking truly accurate and instructive, useful classification, if you like, of the various ways in which we can get sick then a much better one is to say that aging conflicts with everything that goes wrong with the body or the mind, predominantly for those people who were born a long time ago. And diseases are things that can affect young people just as much as older people.

[Damien Blenkinsopp]: Right, so the distinction – just to give some examples to the audience, would it be things like Alzheimer’s, Parkinson’s, even multiple sclerosis? I don’t think people tend to get that before the age of 30, for instance. Cardiovascular disease – would all of these kind of things be linked into that area?

[Aubrey de Grey]: Kind of, yeah. Certainly multiple sclerosis a bit of a gray area, whether you would really call it an aspect of aging – not just because it happens rather earlier than the other diseases you listed, but also because it certainly doesn’t happen to everybody. Whereas the diseases of old age, the commonest ones – whether it is cardiovascular disease, cancers, Alzheimer’s, these things tend to affect everybody at more or less the same age. Of course, some people die of one thing and some people die of another thing, but the only real reason for that is because of small differences in the rates at which different people accumulate the damage that results in these diseases. But most people who die of cancer die with Alzheimer’s in some level or other. Most people who die of atherosclerosis die with cancer. It is just that it hasn’t got so far along.

[Damien Blenkinsopp]: Right, so in your book The End of Aging, you describe the seven causes of aging. Would all of these be classified – would it be correct to call them some type of damage to the body?

[Aubrey de Grey]: I would call them damage, yes. In fact this is another kind of terminology question. I would say really that the best way to define the use of the word damage, in relation to aging, is that we would say that damage consists of exactly those changes to the structure and composition of the body at the molecular and cellular level that on the one hand arise as side effects of being alive in the first place, side effects of the stuff that the body does to keep us alive from one day to the next. On the other hand, they accumulate throughout life. They get progressively more and more abundant and eventually they get more abundant than the amount that the body is set up to tolerate, so that means they start to impair and eventually completely eliminate their physiological function.

[Damien Blenkinsopp]: Right, so there are clearly changes which take place because of aging, because of the processes that are going on as we are living.

[Aubrey de Grey]: I would say that they are aging, it is not so much by aging or they think they are aging, but the nature of aging is the changes in molecular and cellular structure.

[Damien Blenkinsopp]: Right. That is a nice way to put it because most of us think of aging as what we are looking at outside the body – the wrinkles and when you are looking at people you can see that aging. but in a respect we could say that the actual things you have defined and are changing within the body would be aging. so could you please outline what those are and which ones are the most important for you or if they are all the same? What is this kind of framework that you have and which ones are you most focused on currently?

[Aubrey de Grey]: The classification – there are seven major categories. It was really the big breakthrough that allowed me to see that the repair of damage was not only the most promising approach to combating aging with medicine, it was actually a feasible approach that could realistically be implemented within a matter of decades. If you have got 1,000 different things to deal with, then 1,000 different therapies are going to take a long time to develop. Well, if you can classify them into a much more manageable number of categories, such that within each category you are basically doing the same treatment for every example within the category and then the whole thing becomes much more feasible-looking, and that is exactly what I was able to do. So the categories are very simple things like having progressively-fewer cells in a particular organ or tissue because cells are dying and not being automatically replaced by the division of other cell. Or we accumulate molecular waste products in the cell because the cell is creating this waste product as a byproduct of something it needs to do. And the cell does not have any machinery either to break it down or to excrete it, so it accumulates.

Now, in each of these things we can look at and we can point to particular diseases and disabilities of old age that are predominantly caused by one or another of these things, so that is what we work on. And yes, we feel that all seven of these categories of damage are equally important. Certainly – well, there is one exception I guess, which is mitochondrial mutations where we can’t 100% certainly say it matters as much as the others. Actually, it might matter more than many of the others, we don’t know. But all the others we can say they matter pretty much equally as much because we can go into a particular nature, age, relation, or [pathology 00:11:42] and kill people at more or less the same age driven by that damage.

[Damien Blenkinsopp]: I see, so you are saying that pathology can be linked to each of these aging processes?

[Aubrey de Grey]: Yes, for example, molecular garbage inside the cell I just mentioned, that is definitely the reason we get heart disease, atherosclerosis – molecular garbage outside the cell is a major cause of heart disease in certain areas. Cell loss is the major cause of Parkinson’s disease, and so on.

[Damien Blenkinsopp]: Great. Thanks for that clarification. So you have outlined a roadmap to basically end aging and you have brought to light two concepts that I understand there are like bridges and there is something called longevity escape philosophy. Did you explain how these are eventually going to end aging or stop us from having to go through this process of aging?

[Aubrey de Grey]: Sure. So first of all, let me talk about bridges. That is actually not my terminology – that comes mainly from [Ray Kurzweil 00:12:40] who has often pointed out that there is a certain amount that we can do today to postpone the ill health of old age, and that is good. That is all very well. But there is actually more. Maybe we will be able, some of us anyway, to postpone the ill health of old age today with methods already available well enough to still be around in time for therapies that are not yet developed, because they haven’t yet been developed. If that can be done then of course we get an additional amount of life and we may be around for the next generation therapy, and so on.

And that concept – well, he normally talked about three major failures – what we can do today, what we might be able to do in the next couple of decades with our technology, and then what we might be able to do in decades after that using more of the non-biological solutions such as nanotechnology. And that is a fine way of putting it. Certainly the biotechnological approaches that he favored are pretty much identical to the ones I favor. And nanotechnology is certainly not an area in which I can claim much expertise, but I think he is more or less on the mark there, as well.

There are some where we part, actually, Ray and myself, as to how beneficial for most people what things are today, things that you can do already. And I think that [Bridge 1 00:12:40] as he calls it may not be much of a bridge, but by large the concept – we stand together on this concept. So the longevity escape philosophy, which you mentioned, is indeed from a phrase that I invented. And here I am not splitting the process of getting from here to indefinite longevity into that particular number of phases, like three – I am just saying that once we get a certain way along this process we are safe because we will be improving the quality and comprehensiveness of these therapies fast enough to stay one step ahead of the problem, essentially be repairing the damage that we couldn’t yet repair well enough that the overall abundance of damage will at no point reach a level that exceeds what the bod is set up to tolerate.

[Damien Blenkinsopp]: Right, and this relies on the concept that medical technology and biotechnology will be advancing exponentially?

[Aubrey de Grey]: Oh not at all and this is something which – and again I talk a lot with respect to I owe to information technology that we can see there is an accelerating track where progress is made at a faster rate as time goes on. In the case of longevity escape philosophy that may well happen, but the key point is it does not need to happen. In fact, if we are able to say 20 years from now or 30 years from now to reach this point where people are eventually not getting older, they are getting repaired as fast as they are aging, then it turns out that thereafter we can actually proceed at only that same pace and perhaps even slow down a little bit and will still be doing well enough simply because the rate at which the damage we cannot yet repair is accumulating will diminish as the types of damage that we can’t yet repair become fewer and fewer.

[Damien Blenkinsopp]: Great. Thank you for those clarifications. So what, for you, is the first and most important step? Right now are you really focusing – because you do funding of research and you kind of prioritize things – are you kind of prioritizing any of these steps in particular? Are you are trying to spread your investments so that you kind of manage the risk?

[Aubrey de Grey]: Very much the last, we are spreading. We have our fingers in all of these fires because we feel it is pretty stupid if we focused on some of them and then the other ones didn’t get done by us or by anybody else and people carry on dying on schedule even though most of the problems have been fixed. So we need to make sure, especially for the areas which are least fashionable, are being most severely neglected by other people, that it is vital for us to move forward. In fact, that is the only criteria that we use that really does determine what we choose to work on and not to work on. So the real manifestation of it is that we do very little work in stem cells. Stem cell work is very limited simply because so many other people are already working in that area. It is very burgeoning, very fashionable. So our work effort would be a bit of a drop in the ocean where we are the leading group working in many of the other areas.

[Damien Blenkinsopp]: Great, so basically you are choosing the least fashionable topics so that other things get pushed on it? And we actually do need to fix all of these problems. I mean, that is your assumption – in order to extend life and create longevity?

[Aubrey de Grey]: That’s right. I don’t think it is even an assumption, I think we know it.

[Damien Blenkinsopp]: Okay, great, great. So one of your other books looks specifically at mitochondrial mutations and the free radical theory of disease. Why did you specifically write a book about that topic?

[Aubrey de Grey]: Great question. So that was a long time ago. That book was published in 1999 and it is actually the only other book I have written. I have only written two books total. It was simply the first area that I got interested in when I decided I wanted to work on aging, whether it being to do something about it. Of course, I started out knowing nothing about that subject. In fact, I didn’t know all that much biology. I had been a computer scientist for my research career until that point. So I had a lot to learn. And obviously you learn some things before other things just by random chance. I ended up gravitating into the area of mitochondrial mutations as my main focus before I got interested in the other things.

So for the first few years of my career in gerontology in the late 90s, that was what I was working on and that was where I published my first half dozen papers or so. And my very first paper came to the attention of a publisher who did low print run academic books and said – anyway, what I wrote, so he said that he liked what I did and asked if I could go on writing a book, so I said all right, and that was the result. So the material in there covers pretty much my first three or four years or gerontology research. And it actually was also the [inaudible 00:19:08] idea was cemented to the University of Cambridge and I got the PHD for it.

[Damien Blenkinsopp]: Great. So would everything you wrote in there still be valid today or are there things you have discovered which you would change, some of that?

[Aubrey de Grey]: So the fantastic thing is that more or less everything is actually still true. There have been, of course, some minor discoveries that have changed things, but the broad sway of what I was writing there is certainly still true with one big exception. That big exception is exactly the exception that you like to have – namely, as time has gone on, new techniques, new ideas, and new discoveries have been made that essentially provide shortcuts – they have made the job of fixing this problem easier. And that is true also for the book that I wrote for ending aging, which is not nearly half as long ago as I wrote the mitochondrial and free radical theory book. So, they are pretty good, the lead idea of standing the test of time so well – the seven point plan that we work on is pretty much identical to what I was describing more than ten years ago or 12 years ago. So that is really circumstantial, but nevertheless quite strong evidence that we are on the right line, that there is more to this robustly standing the test of time.

[Damien Blenkinsopp]: Well congratulations because that is not an easy feat given how everything is changing so fast in biology and so on. So you have talked a bit about – one thing you mentioned earlier was except for when you are talking about the seven different areas and causes of aging, you said that mitochondrial damage may or may not be one of the most important ones. Why is there that area of uncertainty around mitochondria specifically?

[Aubrey de Grey]: Simply because there is no one major pathology we can point to where we can say clearly that there is a chain of events from this particular type of damage to that particular pathology. In the case of every other – the other six types of damage, we can point to a particular pathology and say that it is established. It is not even a hypothesis, it is actually known and absolutely agreed that the main driver of that pathology is a lifelong accumulation of that particular type of damage.

[Damien Blenkinsopp]: Great. So is that because we need to do more research to understand properly this mechanism in mitochondrial damage so we can say that we understand it less than the others?

[Aubrey de Grey]: I don’t think so, actually. I think the reason is the actual fact of the biology, rather than our understanding of the biology. I think it is possible that mitochondrial mutations simply don’t matter very much in aging, but it is more likely that they do matter but only by a very indirect route. And if it is indirect then it may be very placebic and it is something that affects pretty much all aspects of aging but in a subtle manner. So if you look at my book in 1999, you will see that there is some discussion of a rather elaborate mechanism – in fact, it is so elaborate that a lot of people just didn’t like it because it was too elaborate, which basically says that if mitochondrial mutations are accumulating even to relatively low levels, they may be able to be disproportionately toxic by essentially damaging molecules in the blood stream. And if they do that then those molecules can get into other cells and spread the damage around and kind of amplify it. This model is still very much a hypothesis and it has by no means been shown to be true, but it hasn’t been shown to be false either. And in fact bits of it, occasionally here and there, end up acquiring little bits of supporting data. There was a paper actually put out in [inaudible 00:22:54] just a few weeks ago, which was the first one to support one little technical detail of that hypothesis which previously had been completely controversial.

[Damien Blenkinsopp]: Great, great. It seems to me that mitochondria have become quite fashionable lately, just from my perspective. I don’t know if you would agree with that, when you are talking about the least fashionable versus the quite fashionable. There are a lot of supplements that tend to target more mitochondria and the word just tends to come up a lot more.

[Aubrey de Grey]: So yes, in a general sense mitochondria are very fashionable. Lots of people work on them. They have the major pre-eminent conferences on mitochondria that are bigger than ever, and so on. But the particular question of how we might be able to restore health to cells that have been taken over by mitochondrial mutation, that is obviously a very, very narrow area within mitochondriology and that is not fashionable at all. We don’t know, but we think it’s because people think it can’t be done. It’s a nature of science that people work on, things that they think they can succeed on and get published and promote and those things. And that means the hardest things often don’t get worked on at all.

[Damien Blenkinsopp]: Right, absolutely. So like Dr. Thomas Seyfried is well-known for his ideas around mitochondrial and metabolism and cancer. Do your ideas connect with his or are they different?

[Aubrey de Grey]: I don’t actually know that name. Tell me about this guy and his ideas.

[Damien Blenkinsopp]: With the metabolic theory of cancer?

[Aubrey de Grey]: Okay, there are various metabolic theories of cancer, but go on – tell me the ideas a little bit and I will tell you what I think of them.

[Damien Blenkinsopp]: Well, the idea is basically about free radical damage of the MT DNA and once that is damaged the mitochondria are not functioning so they are not giving sufficient energy to the cells. The idea is that from there the cells start behaving in a different manner, which includes cancer.

[Aubrey de Grey]: All right, so certainly stated that simplistically that theory is not correct. Variations of it –

[Damien Blenkinsopp]: I am sure I am not doing it justice at all.

[Aubrey de Grey]: Variations on that idea may have some validity. Certainly we see in aging that normal cells that are not cancerous at all accumulate mitochondrial mutations. Only a small minority of cells do that, but the ones that do get completely taken over by that mutation. In cancer we don’t see those same mutations. We do see some mutations sometimes and certainly one thing that we see much more ubiquitously is a depression of mitochondrial function even in the absence of any actual mutations. So the [inaudible 00:25:36] and we certainly have a number of theories out there that describe how cancer cells may obtain some kind of advantage then and protect themselves from the immune system, for example, by doing things like that or reducing their oxidative metabolism. So if that is the general theory that is being put forward, then yes, there is a certain amount of validity to it. But the thing that counts is that there are an awful lot of ways this can occur. There are an awful lot of ways that cancer health can discover to escape the normal controls that stop cells from dividing when they shouldn’t. So they have to do a bunch of things like breaking down the intracellular matrix, they have to ignore the signals that tell them not to divide, they have to ignore signals that tell them to die. They have to, as I say, resist the attack from the immune system. All of these things are really hard and any cancer that has reached a size where it has come to the notice of the clinician it has already jumped through a million hoops. So there are a lot of different ways to be that way.

[Damien Blenkinsopp]: Great, thank you. So today we have a lot of things in the press – there are a lot of products and there is a fair amount of research around topics which supposedly could help to give us longevity. Some of these are caloric restriction and linked to that fasting, autophagy, mitophagy and then we have the telomeres, telomerase and some others. For any of these things that are available today, and we can stop and look at them separately, I understand that you feel that none of them are actually targeting any of the seven areas, or any of the seven causes of disease sufficiently to actually extend our life. So could you talk a little bit about why you feel that is? Perhaps you want to tackle the biggest one, which is caloric restriction, for example?

[Aubrey de Grey]: Yes, by and large the simple approaches that we have today are not even hypothesized to actually repair damage the way that science is trying to do. So the best that could be said about these things, the proponents will say, is that they may slow down the subsequent accumulation of more damage. So that is still good. That means you are postponing the age at which the damage reaches an abundance that is insupportable, but of course the later you start the older you are when you start doing it. And then even if it works, the less benefit you are going to get because you have already accumulated all the damage at the original rates. So that is bad enough, but yeah. So you can say I am also very pessimistic about the ability of the approaches even to slow down the accumulation of damage by a meaningful amount. In very short-lived species calorie restriction is very effective. We can certainly increase the lifespan of a mouse from let’s say two-and-a-half years to three-and-a-half years using calorie restrictions, and that is pretty impressive. But if we go further down the evolutionary chain and we ask about small invertebrates like worms, for example, that normally live only a few weeks, it turns out that calorie restriction can do a great deal more. You can multiply the longevity of a worm by a factor of maybe three or four by calorie restriction.

The unfortunate thing is that this correlation, this inverse correlation between the natural span of the species and the extent to which that lifespan can be multiplied by calorie restriction works the other way as well. So 20 years ago people did a calorie restriction experiment on dogs and they only got a 10% increase in lifespan instead of the 40% that you might get in mice. And more recently we had a couple of experiments that on for more than 20 year looking at monkeys under calorie restriction. They finally reported and they got less than 10% – in fact, one of them was basically faster. So it is not looking too good. The worst of it is that this is what we should have expected because it actually was predicted by evolutionary theory – especially simply because long famines are not so frequent as short famines. We are unlikely to have the ability – to have evolved the ability – to respond to long famines in a manner that would increase our evolutionary fitness whereas short famines we experience frequently enough irrespective of how long the actual lifespan is that it makes sense to have that ability.

[Damien Blenkinsopp]: That’s great. And of course, currently the more fashionable topic around caloric restriction and fasting is intermittent fasting, which is typically anything between 18 and 24 hours for most people. Do you have a different view of that and the idea of this, which is activation of autophagy which can help to clear up some of the cellular garbage?

[Aubrey de Grey]: No, it is absolutely the same. The kinds of metabolic changes and expression changes that are induced are basically identical, and a good approximation – whether you have continuous calorie restriction or intermittent fasting or whether you use drugs that essentially trick the body into thinking it is on calorie restriction when it isn’t like [rapamycin 00:30:59] or whether you use genetic modifications in model organisms that trick the body in that way, by turning on the same pathway. It is no surprise. All of these things are turning on the same response, they are just turning it on in different ways. So of course you are going to get the same response.

[Damien Blenkinsopp]: Great, thank you very much. So the other big area – I guess you could tell me if you see this as the other big area because you do a lot of these interviews and you probably get the same kind of rejections. I think the other big area is telomeres and telomerase, which has become very fashionable now. And I understand that of course you think that isn’t an area that is going to help us?

[Aubrey de Grey]: Sure, so the telomere is a critical part of the cell and the organism and we definitely need to understand how it changes with aging and the extent to which those changes are good or bad. But we definitely cannot say at this point that the changes we see during aging are uniformly bad and therefore the thing to do would be to stop those changes from happening. The reason we can’t say that is because it seems that large animals, or large mammals and certainly humans, have made use of the telomere as a kind of way to get a tradeoff – get the best of both worlds between two important aspects of aging. One of them being the inability of the cell to – well, let me back up and say it a little differently.

One of them being the increasing inability of cells to divide and the other being the increasing tendency of cells to get into a state where they divide when we wish they didn’t. Most of our cells, let’s remember, do not divide – or if they do, they only divide fairly rarely, on demand. Like, for example, skin cells – the bottom layer of the skin that divide like crazy when you have a cut, to close the wound. It is only a small proportion of our cells, a few cell types, the stem cells of rapidly renewing tissues like blood which divide regularly. Those are the only cells that have a potential problem of telomere shortening.

Telomere shortening is something that happens when cells divide because of the nature of DNA replication and eventually when cells have divided enough they end up getting telomeres that are so short that bad things happen in the cell. I won’t take the time to go into what bad things, but the cell basically gets unhappy.

So cells that divide rapidly need to compensate for this and they have an enzyme called telomerase which does so. They certainly don’t need that capacity because they don’t divide often enough. They just don’t make the same amount of telomerase. Now, most people believe that the reason why they don’t make it is so that if they mutate, or become cancerous, then the cancer will not be able to grow large enough to kill us because that will require enough cell division that the telomeres will get short and bad things will happen to the cancer cells and the cancer will just wither away. So the question is if we want to do better than what evolution has done, how do we address this tradeoff?

One way might be to make most of our cells create more telomerase, more of this enzyme. That would allow cells in the blood, for example, to divide more than they currently do. And that would be interesting because it might make the blood continue to work better and the gut continue to work better, and so on, but it would run the risk of exacerbating cancer. The alternative is to go the exact opposite direction to bear down on to telomerase and make it less of it. That might be a really good way to suppress cancer but it might exacerbate the more degenerative aspects in that it makes our blood age faster, for example. We simply don’t know which of these factors is going to better because really it is not just which of those things you do, it is also how you cope with the side effects that you are creating. You are going to make one or other sides of the equation worse, you have got to find some secondary therapy to alleviate that and we of course don’t know yet.

So a number of people are working on the telomerase stimulation side of the equation, going to rescue the aging of dividing cells by giving more telomerase and then trying to find some other way to deal with any cancer problems that might arise. And we are going the other way and saying we are still with cancer by suppressing telomerase and left the other cells to deal with the cell division problems that might arise.

[Damien Blenkinsopp]: Right. And that seems to be because cancer is one of the most sure things which is actually going to kill us versus the other side of the equation, which you are saying is more of a functional impact rather than a kind of end of life kind of impact?

[Aubrey de Grey]: Well, I wouldn’t quite put it like that. I mean, there is still the big question of the extent to which telomere shortening really contributes to the pathologies of old age, so definitely telomeres get shorter in the blood in older people, but nobody has really been able to show they get so short they cause loss of function. So we actually may not need to worry about that in a currently normal lifetime But for sure, if we were to suppress telomerate in the manner that I have been talking as an anti cancer therapy, then we would create a problem even if the problem doesn’t already exist.

[Damien Blenkinsopp]: Right – when we are dealing with really complex problems it has been shown that can often be the case for therapies. So a key thing we talk about in this podcast is any aspects of quantification and with respect to longevity I am wondering if there is anything that you feel that is worth monitoring to track how we are aging? Now, currently it is fashionable with telomeres to measure the telomeres and they have indexes which say your telomeres versus someone else your age are above average or below average in terms of how many you have left, basically. Are there any biomarkers that you feel can validly track the progress of aging and perhaps how it varies between different people based on their lifestyles, their genetics, or any other factors that might be affecting the rate at which they age?

[Aubrey de Grey]: That is a really tough question. They don’t actually age, the Natural Institute of Health paid a huge amount of money several years ago, many years ago now, into a long-term study trying to identify biomarkers of aging that were really reliable and it was basically completely unsuccessful. They basically found nothing. Now, people haven’t given up on this but the reason they haven’t given up is the complexity. Essentially there are a couple other things you can die of, so how do you put aside whether one means by a biomarker of aging. Well, you have to define that some how, its another way of saying the predictor of how long you are going to live, what your remaining longevity is, or that you will remain in healthy longevity, but then you have to define health and it gets a little bit fuzzy as well. So it is actually quite hard to even define what you mean by biomarker of aging, but even once you have gotten past that difficulty, because there are so many different things that go wrong you don’t expect to have one simple or even fairly simple number that says something like this.

You expect, one would think, that as you get older you are as old as your weakest link. So you are going to expect that you would want to measure a lot of things and each of them points to a probability of getting a severe case of this or that type of age-related pathology in this or that amount of time. And certainly some things are more influential than others. These things affect each other and we may be able to point to things that are a bit more indicative overall of the probability of death or disease of all types in old age. But it is a very – it is not an exact science, put it like that. I have been lucky enough to have my biological age tested, which I have been able to do maybe four times now over the past decade or more. The test I have been able to get done on me involved measuring probably 150 different things in my blood as well as all manner of physiological and cognitive tests. There is no one number that comes out of that, really. There is no one useful number. The only thing that really usually comes out of it is what to pay most attention to, what seems to be changing more rapidly or seems to be problematic levels or that of other people of your own chronological age, those sorts of things.

[Damien Blenkinsopp]: Right, so there are 130 markers. Would many of those fit within your seven areas of damage and kind of be related to that?

[Aubrey de Grey]: Oh certainly. Certainly not now because the things that one measures in the blood aren’t metabolized. These are small molecules that are constantly being ingested into the body or synthesized by the body or destroyed by the body or excreted from the body. The blood stream is just this pipeline, right? It is just this network of roads that take things from one place to another and particularly it shortens molecules whereas the seven types of damage that I talk about, types of molecules or cells, the molecular or cellular changes that accumulate over time. So in other words, yes, the concentration of a particular small molecule in the blood may change but that is because of subtle changes in the set point, in the equilibrium between synthesis and destruction or ingestion and excretion of those molecules, which are kind of readouts of the level of damage elsewhere – maybe of the activity of enzymes or the activities or numbers of certain cells, for example. But they are not the damage itself, they are readouts of the damage.

[Damien Blenkinsopp]: Okay, great. So if we wanted to live longer today – I mean, I know one answer which we are going to definitely come up with at the end which we need to talk about, like helping you fund the different areas because you see that as the most important to targeting these areas that we are not really looking at – but for the people at home who are concerned about their longevity, what would be the best strategy for them in terms of thinking about their own health?

[Aubrey de Grey]: I wish I had a better answer to this, I really do. Certainly I know that there are some people – if you are an unlucky person, so Ray Kurzweil – come back to Ray Kurzweil again because of course he is well-known as someone who thinks that one can make a big difference to one’s longevity using supplements and so on. He probably is making a substantial difference to his own longevity that way, but that is because his own longevity by default was probably going to be rather shorter than average. He has a lot of cardiovascular disease in his family, he came down with type 2 diabetes in his 30s, which is pretty unusual even though it is not unheard of. And he has been able to really completely fix that using his regime that he developed himself and I totally applaud that. What I can’t do is say that this would apply to people who are already doing okay, especially those doing better than average, like me. Only if you are somehow unlucky, we have simple ways that may be able to somewhat normalize your rate of aging. Now, of course, on top of that, there is the fact that there are plenty of ways to substantially shorten your longevity by smoking or getting seriously overweight or eating a very poor diet, for example, but you didn’t need me to tell you that. I bet your mother told you.

So unfortunately over and above that, as things stand, we cannot point to anything that can appreciably help most people. And that of course is why I always say the only thing you can really do is buy more time – not by extending the time that you stay healthy but by reducing the time before therapy had come along that would actually do much more than anything that exists today.

[Damien Blenkinsopp]: Right. So I will kind of run by you the way I think about this and see if you have ideas on this, to see if this is a decent idea or not. The way I talk to my friends and stuff when they ask me these kinds of questions is I say that basically you want to manage your biggest risks, right? So if you were talking about Ray Kurzweil has cardiovascular risk in his family. For instance, you had a 23&Me or other set of genetic tests which point out that with some probability you have – for instance, I have a higher risk of lung cancer than most people and a couple of other things in my profile and people have different risks. So I suggest they look at that and then potentially they look for the biomarkers related to that on an ongoing basis rather than the genetic longer-term risk. And they monitor that and they also look into the things that can reduce that specific health risk and to reduce the risk and to limit the risk of them actually getting that biggest risk. So it is kind of plugging the biggest gaps they have of shortening their lifespan. I am just wondering if you think that is a reasonable approach?

[Aubrey de Grey]: For sure. I think in general for most people if you have got a risk factor that puts you at risk of being considerably shorter length than average, then you are going to know about it as a consequence of the kinds of metabolic tests I was talking about. But there can certainly be exceptions to that, things that truly don’t really affect your health as measured in normal ways, so that is all they do. Like suddenly some of them bite you in the backside. So that is the kind of thing that 23&me analysis might lower. But one also has got to be extremely careful in evaluating that kind of data because ultimately it arises from basic science. It arises from people studying particular genetic variations in the population and identifying correlations between those variants and the instance of this or that to these. And those studies are notoriously difficult to do and they have a notoriously low level of reproducibility because different populations are different and because sample sizes are limited, and so on and so forth.

[Damien Blenkinsopp]: Thank you. I always appreciate your answers because they provide a different context and perspective to everyone else so it is always very interesting to get that feedback. Let’s talk a little bit about SENS organization and what you’re up to there because this is your vision basically for making it happen. So you have different activities – and I also want to know a little bit about the [Methuselah Foundation 00:45:56] which you were formerly part of. And I understand that has some similar activities although it is going about it in a different way.

[Aubrey de Grey]: Sure, and let me actually start with the Methuselah Foundation because that makes more sense chronologically. The Methuselah Foundation is a charity, a 501-C3, that was created by myself and a businessman from Virginia named David Gobel in 2002, late 2002. Our goal was, of course, was to hasten the defeat of ageing but we didn’t have any money. So we started out creating a prize pot creating competitions in which we encouraged people to give up money that would go into a prize box and that the competition would be to beat the prevailing world record for mouse longevity. So with all you had to do the mouse that lived longer than any mouse had ever lived before. And of course we weren’t saying how things would be done and we set things up so that even a small improvement would be enough to win some proportion of the prize box. And it worked.

Basically our goal was to raise the profile of longevity research to get the word out and to get people more interested in the possibility of developing medicine to postpone ill health of old age. Well, we were bringing all this money in and right about 2005 or so we had enough money that we felt we could spend some of the prize pot in advance on actually pursuing specific research projects. So that is what we started to do and then things started going pretty well in that regard. But then we had a problem which we started to recognize in about 2008, which was that if you are a research organization you have got to obviously impress people with your competence and you have got your feet on the ground and everything like that and you are doing the right stuff. Well, if you are a PR organization, to get people motivated and so on, then you want to be the opposite – you want to be very popular, sensational, and glitzy. So we felt that it would actually serve the mission better if these two themes of our activities were between two different organizations, which would thereby be able to have very different styles, discourse, and styles of communication. So that is why we created the SENS Research Foundation, which was started in 2009.

SENS Research, of course, is also a charity – a 501-C3 so anyone can get tax back. And because this is going out internationally I should probably mention that we have a subsidiary in the UK which is able to take tax-deductible donations not only for UK citizens but also from most of mainland Europe. And if anyone wants to know about that they can contact us on the website and we will tell them more.

[Damien Blenkinsopp]: Thanks. We will put all the links in the show notes.

[Aubrey de Grey]: Excellent, thank you so much. So we created the SENS Research Foundation and it has been a truly, and the Methuselah Foundation and all the assets that have been given us research into the new foundation, so both foundations have been made in parallel since that time and I think we have both done pretty well and it is pretty good. So SENS Research Foundation, to go into a bit more detail – we are headquartered in Mountain View, California, just a little south of San Francisco. We have about 5,000 square feet of space in a facility, most of which is lab space. We have a variety of projects going on here. We actually have more than two-thirds of our research budget is not in our facility but rather in five university labs, again most in the USA, but some elsewhere. We have on outside Cambridge, Biotechnology Institute, and these projects are focused on all of the various areas of research there that SENS describes.

[Damien Blenkinsopp]: Yes, and I don’t think we have actually said what SENS stands for – Strategies for Engineered Negligible Senescence.

[Aubrey de Grey]: That’s right. We don’t often try to spell that out because it is a bit of a tongue twister. The name originally arose because of – well, basically historical reasons within gerontology. The phrase ‘negligible senescence’ already had a particular technical meaning and it seemed like a good place to start. But it is a bit of a tongue twister so we don’t bother to get people to remember that anymore.

[Damien Blenkinsopp]: Great, thanks. I will put links to all of those, of course, in the show notes. One last thing I just want to ask you, Aubrey, is from a personal stance you have said every few years you are going to test 130 markers or so of your own. Are there any specific things that you feel are important for you to personally track about your body for longevity, health, or performance?

[Aubrey de Grey]: Well, yeah. I mean, I think that first of all, coming back to something that we were talking about earlier, if any one marker is out of whack, you know, it seems like it is really telling a much more pessimistic story than the rest, then you have certainly got to try to ask yourself why, ask yourself whether it really is an outlier, whether it actually has that much impact given everything else as people say, things like that – but it is definitely not something that would be a good idea to ignore. So my one outlier the past couple of times I have done this kind of thing has been homocysteine, and I have no – I am not really sure why my homocysteine level is unusually high because everything else that it is supposed to interact with has not – but it is still something that I pay attention to.

From that, I can certainly say that there are certain things that are really at the nexus of metabolism, things that really if they are extremely good then you will be pretty safe, pretty much with whatever else is happening. Insulin is the best one. And of course, insulin is the hormone that mediates the absorption of sugar after you eat a sugar-rich meal so that the overall concentration of sugar in the bloodstream is maintained at as constant a level as possible. And the precursor of diabetes, type 2 diabetes, is something called insulin resistance, where the cells that take up sugar in response to insulin, which are mainly muscle cells, start to be a little sluggish about it and to only respond when they are given a large amount of insulin. So if your insulin is high, then even if your glucose tolerance, as it’s called, your ability to normalize your glucose in the blood is still good, then the indication is that it won’t be good for very long. Whereas glucose tolerance is good and also your insulin is really low then that says that you are in the best possible state. I would say if you have one thing, that would be it.

Perhaps another one would be triglycerides, whether it is a type of fat which seems to be good to have very little of in your blood stream and again, I am pleased to say that I do.

[Damien Blenkinsopp]: Thank you very much because those are basically the biggest diseases that we have today, like metabolic syndrome, so those are good markers for that. I guess one of the confusions with biomarkers we are always facing is that we are not sure if it is the end point. So one last question I did have for you was on a Palo Alto longevity prize. I am not sure if you know about that?

[Aubrey de Grey]: I certainly do and I am invited to it.

[Damien Blenkinsopp]: Oh, great. Because I understand they are running a competition or they have been running a competition for heart rate variability in connection with longevity.

[Aubrey de Grey]: That’s right, yes. So, businessman in the Bay Area in Joon Yun has put up a million dollars as a prize fund for progress against aging. It is divided, actually, into two separate prizes. One of them is looking specifically at heart rate variability, as you say, but the other one is a bit more general. It is looking at what they call homeostatic control or something like that. I forget the exact terminology. But the point here is that the competition is for the attempt to actually extend longevity [inaudible 00:54:06] in this manner. And I think this is great. I mean, the heart rate variability aspect is a bit unusual for people who have not really bought into the idea that this could be a real fulcrum of aging but it might be. And we think it is great to encourage research in any area that hasn’t been terribly well looked at. The main thing is simply putting a million dollars on the table as a great way to get people pretty excited, and a lot of people are paying attention now, especially since in the Bay Area there is a lot of identity of people interested in longevity in general. It’s a great way for a research foundation to be located. So yes, I absolutely applaud them for doing this.

[Damien Blenkinsopp]: Great to hear you are part of that also because we had heard of that from one of our previous guests. Aubrey, thank you so much for your time today. I love to hear all your different ideas of course because you are working at a very high level compared to most people, so you have this perspective that stands back a bit, which can be very helpful to people. Thank you so much for your time and have a great day.

[Aubrey de Grey]: Thank you, and to you. Bye.

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