Today’s episode takes a look at Methylation, it’s role and importance for many body functions, how it can enhance our quality of life and performance when running properly, or expose us to greater health risks like heart disease or cancer when it doesn’t.
Addressing methylation SNPs (genetic mutations that we all have some of to varying degrees) and related biochemical imbalances personally made a very big impact to the quality of my life, eliminating issues like migraine headaches, improving sleep, and enhancing my quality of life and productivity by smoothing out “mood dips and bumps”, and helping heal my body from chronic disease.
If you’ve listened to our other episodes you’ll have noticed that many of the guests have referred to methylation in some way. Because it affects so many people in so many ways, this is a topic that while not mainstream yet, is going to become increasingly so over over the next years. It has only just started.
Enter today’s guest, Dr. Ben Lynch. He is one of the people who has led the way in researching and helping both physicians and consumers understand methylation and how it is affecting them.
Dr Lynch is well known for his work and insights into treating methylation defects which has been his focus since 2011. He has done some incredibly detailed work in mapping out the various methylation pathways, how environmental and lifestyle factors affect them and how they can be supported. And as a result he is a highlight appearance at the conferences on topics related to methylation – which are growing in number and breadth.
His background is in environmental medicine and biochemistry and he has a doctorate in naturopathic medicine. He has worked with 100s of people with methylation defects, notably have started with the MTHFR gene (also “known as MotherFucker” gene because of the risk defects represent for cardiovascular health).
Besides insights into methylation, Ben makes some excellent points on how and when biomarker data is useful, what the most impactful actions are that we can take and optimizing methylation. I thoroughly enjoyed it and I hope you do too.
The show notes, biomarkers, lab test and links to everything else mentioned are below. Enjoy the show and let me know what you think in the comments)!
- Methylation’s role in the body as a balancer of all the body’s functions.
- How it drives detoxification via its production of SAMe (S-Adenosyl-Methionine) with links to Homocysteine and Glutathione.
- The role of methylation as a deactivator of genes in the body and how under-methylation can cause a cascade of gene regulation problems turning genes on that typically aren’t.
- Food, water and stress as the primary factors influencing the quality of our methylation.
- Creatine – making up 70% of SAMe’s use, thus methylation, and its importance in athletic performance.
- How epigenetics trump genetics with examples of the Agouti mice and the queen bee with completely different health, function and role outcomes.
- The issues with therapies of supplements or foods targeting specific genetic SNPs and why they are unlikely to work.
- Typical methylation related health issues like insomnia, anxiety, chemical sensitivity, digestive issues and fatigue.
- Methylation’s role in mitochondria health and output via its production of Adenosine for the mitochondria’s use.
- Measuring homocysteine, a recently popular metric for cardiovascular disease, and how it isn’t as straightforward as having high levels and supplementing to reduce them.
- The range of labs and biomarkers related to methylation and what can be effecting methylation that Ben likes to look at.
- Ben’s use of biomarkers and his strategy for making sure that values across tests are relevant and prevent a useful picture to identify issues or make clear assessments.
- How eating sufficient protein can influence your dopamine and serotonin balance.
- A look at the future of methylation and other areas: How Ben would like to see IT and applications get developed to predicts methylation biochemistry in connection with genetics and other biomarkers he’s looking forward to using and other important areas of development.
- Ben’s current work looking into how supplements don’t work with certain cases to avoid creating the negative symptoms they sometimes drive with, in particular, people who are sicker.
- The biomarkers and things Ben keeps track of for monitoring his own personal health and fitness.
Give some love to Ben on Twitter to thank him for the advice in this interview.
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Dr. Ben Lynch
- Connecting with Dr. Ben Lynch: You can connect with Dr. Ben in several places including his DrBenLynch.com (personal site), MTHFR.net (information on methylation and MTHFR specifically) and Seeking Health (his supplement company).
- MTHFR Basics: This book by Dr. Lynch provides an introduction into MTHFR.
- Methylation Pathways Planner: You can download Dr. Ben Lynch’s map of the Folate and Methionine cycle and an 80 minute video training on folate metabolism.
Biomarkers in this Episode
- MTHFR SNPs: Absolutely recommends getting tested for this via 23andme or other service, especially if you are planning pregnancy.
- Red Blood Cell (RBC) Magnesium: The RBC Magnesium test is more often used for identifying magnesium deficiency as it provides a better evaluation than the serum magnesium, which can be high despite body magnesium deficiencies (very common in the population).
- Serum Ferritin: The standard measure for iron in the body, most people’s levels, in particular men’s are too high. Ben discussed his wife’s inability to raise her serum ferritin because of pathogens in her gut sequestering it.
- Iron Panel: Besides serum ferritin, other iron markers can offer insights into the functioning of iron metabolism. Iron panels often include serum iron, serum ferritin, TIBC (Total Iron Binding Capacity), Transferrin Saturation and UIBC. Chris Kresser has a good presentation covering the use of these iron biomarkers here.
- Homocysteine: Ben discussed how it can be a useful value if it’s high, but if it’s low it’s not necessarily predictive of health risk factors. He also noted how it varies between children and younger adults versus older adults.
- S-Adenyl-Homocysteine (SAH): The precursor to homocysteine. Ben sees it as a more useful test than homocysteine for diagnostic of methylation issues.
- Lactate: Lactate elevation is an indicator of mitochondrial damage. Blood lactate is more accurate, but urinary lactate is more available via labs.
- Lipid peroxidation: Ben referred to these markers generally. We looked at each of the specific lipid peroxidation markers in episode 4 on measuring oxidative stress.
- Plasma Ammonia: Blood plasma levels of ammonia that are elevated can be an indicator of mitochondrial damage.
Biomarkers of mitochondrial function
Ben mentioned several markers you can use as proxies for mitochondrial health and damage.
Lab Tests and Apps from this Episode
- 23andMe Genetic Testing: The largest genetic testing service for consumers. You can download or connect your data from 23andme to better understand it with targeted applications looking at specific sets of genes. While health analysis data is no longer provided in 23andMe itself, you can simply download the data and use it with other gene analytics services.
- MTHFR Support Variant Report generation system: This online application allows you to upload your 23andme data to it to get additional information about a wide variety of areas of your body including eye health, detox, tongue tie/cleft palate, methylation, allergy/mold, IgE, IgA, IgG, clotting disorders, thyroid, celiacs/gluten intolerance, mitochondrial function and sulfonotransferase genes.
- Genetic Genie: Similar as above, an online application that allows you to upload, or connect, your 23andme data to it to get analysis of your detoxification and methylation SNPs (Single-Nucleotide Polymorphisms).
- Doctor’s Data Adenosine Profile: Dr. Ben noted that he has been talking about getting Doctor’s Data to provide an Adenosine profile (not yet available).
- Doctor’s Data’s Methylation Profile Plasma: A limited methylation profile that just covers the methionine cycle. Ben noted the usefulness of the SAM, SAH and SAM/SAH ratio in particular.
- Health Diagnostics Research Institute – Methylation Pathways Panel: The most complete profile of methylation biochemistry currently available on the market – mostly used by Dr. Ben, notes that time lag of delivery of results is a bit slow.
- ION (Individual Optimal Nutrition) Panel @ Genova Diagnostics: Ben uses this as a good place to start when looking for issues and things to optimize.
- CDSA (Comprehensive Digestive Stool Analysis) or CSA (Comprehensive Stool Analysis): CDSAs / CSAs aim to cover a range of markers via a stool sample related to types of bacteria, to parasitology to digestive markers. Several labs run these tests with differing sets of analysis. Ben mentioned CDSA @ Genova Diagnostics, CSA @ Doctor’s Data and biohealth (this latter he found to be insensitive, not finding what he had found in other tests).
- Mitochondrial Functional Profile: Acumen Labs’ mitochondria profile was mentioned by both Ben and Damien. The profile is used in research and clinically by Dr. Sarah Myhill.
- Spectracell’s Micronutrient Test: Ben gave this test as an example of intracellular assessment of nutrients level, being better than traditional blood, serum or plasma levels. The spectracell looks at the nutrient levels in lymphocytes, a type of white blood cell.
- TMG (TriMethylGlycine): A supplement used in connection with methylation supports, and in particular can help lower high levels of homocysteine.
- B-Complex: Another methylation support in the form of a B-complex combining B12, B6 and methylfolate. The Thorne version contains the active forms.
- Creatine Monohydrate: As one of the most expensive molecules biochemically to exit from methylation, it can be helpful to support with creatine.
Other People, Resources and Books
- The Biology of Belief by Bruce H. Lipton PhD: Ben recommended this as a good read on epigenetics.
- NOVA – The Tale of Two Mice: Example of the important role epigenetics plays in producing our phenotype (our actual gene expression).
- Diagnosis and Treatment of Chronic Fatigue Syndrome: it’s mitochondria, not hypochondria by Dr. Sarah Myhill: Ben mentioned this book and specifically Dr. Myhill’s explanation of RBC Magnesium and D-Ribose in relation to mitochondria. Dr. Myhill is a researcher and doctor working in the area of mitochondria primarily in relation to Chronic Fatigue Syndrome (CFS). Learn more about her at her personal site here.
- Could it be B12? An Epidemic of Misdiagnoses: Book mentioned by Ben on B12 and reference ranges, written by Sally M. Pacholok and Jeffrey J. Stuart. This was one of the first books to highlight the many health issues that vitamin B12 deficiency can cause, and how to test effectively for B12 levels.
- Stop the Thyroid Madness II: How Thyroid Experts Are Challenging Ineffective Treatments and Improving the Lives of Patients: Chapter 12 of this book discusses MTHFR, methylation and its relationship with thyroid disorders.
- Episode 3 with Terry Wahls: Damien mentioned Dr. Terry Wahls in connection with work on mitochondria who appeared recently on The Quantified Body.
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Full Interview Transcript
[Damien Blenkinsopp]: Dr. Lynch, thank you very much for being on the show.
[Dr. Ben Lynch]: Yeah, thank you Damien.
[Damien Blenkinsopp]: First of all, I want to jump in to look at the area of methylation and how it relates to our health, performance, and longevity. What are the links with these objectives we have today?
[Dr. Ben Lynch]: With methylation?
[Damien Blenkinsopp]: Yeah, how does methylation impact our health, our performance, our longevity, our whole being, essentially.
[Dr. Ben Lynch]: Well it is central. It is absolutely central. So the mitochondria are the engines of the car and it seems that methylation seems to balance how everything works. So methylation is needed to create certain things in the body. So it creates SAMe, and a lot of us know what SAMe is.
SAMe is a primary methyl-donor which goes around the body and helps makes our neurotransmitters. It gets rid of them and it helps make a compound called phosphocholine for our cell membranes. Then we have quite a bit of methylation around. The body will say okay, we have got too much, and it will speed up one enzyme to help make glutathione and it will make creatine so our kidneys and our muscles will be happy.
So you can see a lot of issues with low creatine in people. It balances our immune system, it helps make immune cells, it supports creatine and CoQ10 formation, which are pretty important. It is very central. It helps regulate genes, turning them on and off. In fact, most of our genes are turned off and if we have low methylation then some of these genes will turn on and they will stay on and then we know what happens from that. The cancer can ensue. So those are some of them and there are probably some other major ones that I am not remember offhand.
[Damien Blenkinsopp]: Yeah, that is great. So does it play a role in detoxification?
[Dr. Ben Lynch]: Yes it does because methylation is a very small role if you look in the toxicology textbook. And when I read that I was kind of disheartened and sad. But at the same time when there is a lot of SAMe around, then SAMe will help promote the enzyme which takes homocysteine and moves it into glutathione. So homocysteine, which some people call ‘the evil marker’ on labs, if it is too low that is a problem and if it is too high that is a problem.
So we need to make sure there is adequate homocysteine because homocysteine will actually move into glutathione production. That in itself is a pretty direct connection between a major thing for a xenobiotic detoxification and glutathione is the mothership for that.
[Damien Blenkinsopp]: So to let the people at home visualize what methylation is, would you call it – is it like a biochemical process where the enzymes are many biochemical processes taking place through a whole line of enzymes which are required for the body? How would you explain it in a simple way or how would you tend to explain that?
[Dr. Ben Lynch]: I would say that methylation is a process by which there is a carbon with three hydrogens, which as a methyl group will bind and dock to certain thing. And it will bind to neurotransmitters. It will bind to chemicals, it will bind to DNA, but it seems the biggest methyl donor of the body is again [inaudible – 00:06:05]-methionine. And so what that SAMe does – methylation is a long, complicated process and there are multiple methyl donors.
Choline is one, SAMe is another one, methylfolate, glycine, and all of these are methyl donors because the body creates redundancy. Basically these methyl groups, as you said, will support various enzymes in the body and then these enzymes are proteins which do work. If these enzymes are malfunctioning due to various toxins in the environment or nutrient deficiencies, then these enzymes won’t be able to do work. And if you back up even one step further, where do enzymes come from?
Enzymes come from genes so if these genes are not functioning very well then they will not be able to make their end product. And so everybody knows about the MTHFR gene defect, making methylfolate needs that MTHFR enzyme, and that MTHFR gene to work so it can go in and do its job.
In summary, I would say that methylation is the process by which genes will produce an end-product which will then have a certain of functions and sometimes a singular function. And there are hundreds and hundreds and possibly even thousands of functions that are going on in our body that are due to methylation and I know that there are hundreds. There could be more than that. You need to also understand too that it is much bigger than that because think of a pyramidal shape – at the top of the pyramid you might have MTHFR and it is just one gene, but the downstream effect of that one gene will form a base of that pyramid. So the impact of that one gene not working is really broad.
[Damien Blenkinsopp]: Yeah, that can cascade down pretty quickly.
[Dr. Ben Lynch]: That’s right.
[Damien Blenkinsopp]: So what are the biggest methylation challenges that you see? Or the most common ones?
[Dr. Ben Lynch]: Stress, food, intake, and water I would say are the biggest ones. And I say that because if you work as a physician, you work with patients. And if you can modify their diet and their lifestyle alone then their methylation will balance very, very well. Of course, there are other things too like toxins in the environment, lead, and yeast overgrowth producing acetaldehyde and alcohol intake, those are other big ones. But I would say food, water and stress.
Stress is a big one because glucocorticoids, cortisol stimulate methylation. So you are saying well, that is good. It is good, but if you have ongoing stress you are pushing methylation all the time, which then means you need to be able to produce more methyl donors. And if you are eating McDonald’s or you are eating inappropriately and you are not eating your leafy greens or your grass-fed meats then your methylation is going to suffer.
So if you are under chronic stress and you are eating carbs to make you happy, you are not getting the proteins and the leafy greens and you are going to be in big trouble. Then it also goes back to our water levels here in the America that are pretty high in arsenic. And then so is our chicken because they use antibiotics laced with arsenic. And when they feed those chickens before they are butchered these chickens get bioaccumulation of arsenic throughout their life and then we eat that chicken. And then we eat another chicken and another chicken.
So our bioaccumulation of arsenic goes up. And then you have got arsenic in rice, which is a big issue. And then greens as well. So our bioaccumulation of arsenic is a really big deal in the United States and I think it is commonly missed. And arsenic is a real tough one to eliminate because it requires both glutathione and SAMe in order to get it out of the body. So our primary methyl donor and our primary antioxidant or detoxification compound need to be in their prime in order to get arsenic out of the body. And if you just have one or the other then arsenic transforms into a more brutal marker because our body will transform it into something more toxic.
So just the basic lifestyle being calm I think is really important. And another thing too I want to add to that really quickly about stress is not only does cortisol increase our methylation cycles but what neurotransmitters increase from being stressed? We have got norepi and epi. So these things also require methylation to get rid of. So if the norepinephrine increases then we need SAMe to convert norepinephrine to epinephrine, so again that is very catabolic.
And stress in itself is also very depleting of things like magnesium. And then also our adrenals might get shot and we might not be able to function very well and aldosterone levels might drop, so now we are peeing out sodium and other minerals that we actually need. So it is a big deal. So stress is a big one.
[Damien Blenkinsopp]: Right, so when you are talking about stress that is both emotion and physical. So it could be things you are doing like training?
[Dr. Ben Lynch]: Yes, excellent point – training and overtraining is a huge problem. I was a collegiate athlete at University of Washington. I did crew there and I wish I wish I knew about this. I would have been a way better athlete. But anyhow, creatine is a major user of SAMe and the more muscle mass that you have the more it takes for your body to make that creatine because your muscles will use up creatine.
So if you’re methylation is deficient and you are a bodybuilder then I know a lot of bodybuilders that supplement with creatine, which is great, but some of it is garbage. There are definitely inferior forms of creatine out there. But if you are eating grass fed meats and you are eating your veggies and not overtraining then creatine by itself is very important. They say that creatine and phosphocholine consume the majority of your SAMe in the body. I think creatine is about 70% of SAMe’s use.
[Damien Blenkinsopp]: Great. In terms of genetic defects we hear about the MTHFR and other snips – how big of a role are they and how important is this in the population compared to the other factors you have spoken about?
[Dr. Ben Lynch]: Well I would say that genetic factors are important but not nearly as important as the lifestyle and diet. So the epigenetics are what control the genetics. the epigenetics are the things that are around the outside of the actual gene itself – just our environment and our perception of the environment as Bruce Lipton so beautifully explains in his videos or in his book, the biology of belief. The epigenetics are so far more important than the genetics themselves. Do you ever watch that video, A Tale Of Two Mice, from NOVA?
[Damien Blenkinsopp]: I haven’t seen that.
[Dr. Ben Lynch]: Yeah, so you’re listeners need to see that. If you Google ‘NOVA A Tale Of Two Mice,’ you will see a perfect example of what I am talking about because these mice – I won’t get into too much detail. There are these mice and they are genetical. They are called agouti mice and they are genetically predisposed to cancer, cardiovascular disease, and diabetes. They are genetically predispositioned for this.
This means they will go through live and get it if their lifestyle and diet are going to be a mess. And so what they did is this mouse had little baby pups, mice pups. The pups were divided equally and they were genetically identical because they came from the same mom. They were absolutely genetically identical. They were divided in half and one group of these mice got methyl donors with their chow and the other group just got their standard chow.
Now they also had some BPA in there and that was another experiment because BPA messes up your methylation. But anyhow, the baby rats who were fed the methyl donors and the rat chow did not go on in life and get diabetes, cardiovascular risk, or cancer and their fur was a lot healthier. The other rats went on and they got basically everything under the sun. So that is a perfect example of epigenetics.
And another one that I like to talk about too is the queen bee. So the queen bee is genetically identical to the other worker bees but the epigenetics of them are totally different because the queen bee was nurtured and she was fed the royal jelly and all that. So that is another living example of how epigenetics is more important than genetics.
[Damien Blenkinsopp]: Great, thanks for making that point. I remember the rat and mouse from your Chicago presentation, actually. So is it worth us getting genetics tested for to identify snips in MTHFR and other area or do you think it is more worthwhile working on lifestyle first and then maybe later if we still have some problems looking at the testing?
The other question I have is doesn’t everyone have snips in some of the methylation process? We were just talking about how it has got hundreds of working parts to it. So isn’t everyone who has got some snips in part of the chain that is taking place in our body – we are pretty much all going around a bit and some of us are healthy and some of us are not so healthy. So like you said, is it more about the epigenetics side of it?
[Dr. Ben Lynch]: Well it definitely is but you have to take every situation in context for that specific individual. So while genetic testing is useful, and that is how evolution occurs – we evolve through mutations and these mutations can be hopefully selected and be an improvement for something in the future. So not all mutations are bad.
They have their various functions and even MTHFR has its benefits. But I would say if the person is going along and they are doing well, not going to doctors and not on various medications, they are just humming along and they are young and pretty confident in their health and how they are feeling and there is not much family risk, they look at their family and their family has a long life of good health and history, then I say it is not that big of an issue.
Now if you are born from a family that dies early, your parents are dying in their 50s or 60s, then you might want to be taking a moment, even if you are healthy because a lot of athletes, as you know, might look and appear healthy but the next thing they know they are in a wheelchair or they are dead. And they say this guy had super high risk for cardiovascular disease. Or he had the [inaudible – 00:00:16] genes and he had Alzheimer’s risk and his cholesterol was not normal but if you look at the cholesterol subfractions he was a mess. So sometimes you can just test for those things or you can look at the genetics, or you can do both.
Now, I am all about disease prevention and optimizing lifestyles, especially in unborn children. So if someone is looking to get pregnant then I absolutely recommend genetic testing through 23andMe and then running it through MTHFRsupport.com, with which I have no affiliation. Or these other things like genetic genie. The reason I say this is because there are specific genes which do mess up your methylation and it is good to know which ones they are. And then with proper education you can bypass these things. Also, if you look through history and see your family line was anxious, they had bipolar, they had breast cancer or various cancers, then again I think it is important to do genetic testing just so you can see which genes are the issue. And if you know which ones are the issue that you can focus more on that.
So it has its places in both sides where you can and you can’t. But it also depends on where you are mentally. If you think the genetic testing is going to scare you more than benefit you then I wouldn’t do it right away. I would maybe start with MTHFR and work on that or work on all the diet and lifestyle things so you can be less stressed out and then order the genetic testing under some false name if insurance kind of concerns you in the future.
[Damien Blenkinsopp]: I would like to talk about what is going to have an impact – so with some tests you can get a test but you can’t really take much action after that. So there is not that much benefit. It is nice to hear you talking about getting your lifestyle fixed first. That is probably going to have a big impact and if you want to refine things, maybe some testing will help you get a bit further. Is that the way you look at it?
[Dr. Ben Lynch]: Yeah, and I always tell doctors this because they come to conferences and they hear this term, methylation, and they see all these complicated pathways. And I say, ‘Look, you guys are already doing this.’ Diet and lifestyle are absolutely number one – food, water, sleep, loved ones around you, and getting some form of exercise. And breathing fresh air and all these things are so, so important and the basis of not having a toxic environment around you too.
So all those things sound very simple but in our current modern lifestyle we are not conducive to any of it. They are plugged into their phones all the time and so on. So the basic lifestyle is so, so important. And I cannot tell you how many patients I have worked with that have these genetic defects and that have gotten better with just the absolute basics. If you focus on the snips and you treat the snips, the genetic mutations or polymorphisms as a more appropriate term.
If you focus on these genetic variations and you give meds or supplements or even foods that target these specific genetic variations and you miss the big picture, you are going to be chasing your tail and you are not going to be going anywhere. So you have got to do all the basic groundwork first and I cannot stand when I see these genetic tests come back and there are long recommendations of a whole bunch of nutrients to take.
That just outright pisses me off to be honest and it is very self-centered and very incorrect because these patients will never get better because they are taking supplements or meds or certain lifestyle things that are targeted to their genes, and that isn’t right. You have got to do big picture.
[Damien Blenkinsopp]: That is great. Thank you for that clarification. I think one of the things is that we don’t hear about methylation that much and it is still kind of a new topic. So what kind of chronic health issues or symptoms do you think methylation can be related to that people don’t typically think of?
[Dr. Ben Lynch]: Anxiety, insomnia would be another one, fatigue, depression, addictive disorders, generalized fatigue, skin issues, digestive issues in terms of if you have ulcerative colitis or Crohn’s and obviously there is big picture there too, but methylation is a major component of that as well. Chemical sensitivity.
[Damien Blenkinsopp]: You have quite a long list. I guess the point is that it is kind of there and it is this big important part that you have been talking about but there is not a lot of information about it there and it links with that yet.
[Dr. Ben Lynch]: I think the best way to summarize that question and keep it as simple as possible is methylation has its fingers in every symptom out there. That is really it in a nutshell. It might not be a direct effect but it is definitely an indirect effect. So I would say whatever symptom is out there, methylation is playing a role somehow. So while it might not be the primary treatment thing to go after it is definitely something that needs to be looked at in every patient, no matter the symptoms or the condition.
It needs to be optimized all the time and it is constantly shifting. Methylation reactions are occurring in every single cell of your body every single millisecond. It changes based upon how you are feeling, if you are stressed out, if you are overtraining. If you are overtraining and running say, a marathon, and you are burning through all this ATP and your muscles are using a bunch of creatine and you are not re-supplementing yourself, then you might be depressed and fatigued after. And you are like, ‘Why the hell am I depressed? I just ran a marathon and I won the damn thing, but I’m so depressed.’ So it is connected to everything.
[Damien Blenkinsopp]: How do you think methylation relates to mitochondria and oxidative stress in the body? I am aware of problems with mitochondria and oxidative stress causing chronic disease as well now. So how does methylation relate to those two things?
[Dr. Ben Lynch]: From my understanding right now it is an indirect thing. And I am trying to put the pieces together more succinctly so I can explain it better. When you methylate there are leftover things and when your SAMe does its job of making creatine, then after it makes the creatine it makes adenosylhomocysteine and that homocysteine then will convert into adenosine. And we know what ATP is, adenosine triphosphate.
So methylation does form adenosine through its end reactions and it helps make this adenosine and while it is not the primary formation of ATP it is a big player because if your adenosine levels get built up for various reasons due to deficiencies in B6 or Kreb cycle intermediates – or end-products there like NADH, your adenosine if it gets too high will shift your metabolism. And we have shifts in metabolism in order to protect us. So if we are running we are primarily, in the first few minutes, we are probably mostly going through aerobic energy.
There are pyruvates going to acetyl-COA and it is making our NADH. But after a while our muscles are going to be running out of those primary – it is going to be running out of acetyl-COA and there is going to be adenosine building up. And then as that adenosine builds up it will be shifting pyruvate into lactate. And that is good, we need that anaerobic shift because our body can only fuel so much glycogen in the muscles and then that shift in metabolism occurs so we can run off of lactate.
The problem is that some of these people are running off lactate all the time. And if their adenosine levels are high because their methylation cycle is inhibited that is a serious problem. If your adenosine levels are high that is going to lead into metabolic disorders, diabetes, high cholesterol, fatty livers, and the end result of this is going to be cancer and death. So a long-term metabolic shift that is due to elevated adenosine, which comes from methylation, is a serious issue. And it is not looked at and getting tests and doctors to even know what adenosine is is a big problem.
There are very few labs that look at pyruvate levels or adenosine levels. They do look at lactate, and lactate is a very important marker to look at, but if you have fatty liver or your GGT or ALT or AST levels in your liver enzymes are elevated then your adenosine is up and you have got to fix that, now. And I think that adenosine is a huge marker. And I have been working with doctor data for the last few months. As you saw at Chicago I was beating them up during that conference. And they are coming out with adenosine on their methylation profile at some point here so I am very excited for that.
[Damien Blenkinsopp]: Great, and obviously I want to talk about some of the testing and the metrics and so on. Where would you start? If you have a patient would it be like a 23andMe genetics test or would it be something more like a methylation profile from the doctor data that you were just talking about?
[Dr. Ben Lynch]: Well when you say where would I start, do you mean where would I start initially?
[Damien Blenkinsopp]: Let’s say we have been working on lifestyle and these things are fixed but we still have some problems where some things are not optimum. Are there certain tests you tend to go to first because you find them the most useful? Biomarkers that you are looking for because they help elucidate the situation more quickly or tell you a lot more? They are a lot more actionable.
[Dr. Ben Lynch]: 23andMe I will get if I am struggling. So I will order 23andMe and it takes about a month or month-and-a-half to get. Once we get that done I will send them to Genetic Genie or MTHFR Support. And I like MTHFR Support report better because there are some genes that I told them to get that are on the report now, like GAMT for creatine for example, or phosphocholine production or vitamin A production.
[Damien Blenkinsopp]: So just for the guys at home, they have to download their data from 23andMe in a file and then upload it into these other sites, right?
[Dr. Ben Lynch]: That’s right, and if you go to those websites they will walk you through it. There are diagrams and maybe even a small video of how to do that. I know there is on MTHFR Support, the basic instructions, and it is very easy. But yes, you are right. Money is an issue and unfortunately it is for a lot of people.
I will do that 23andMe and I will just base everything off of signs and symptoms. And once you get good at it you can see these pathways in your head. But if you are not good at it you can see these pathways in your head. But if you are not good at it initially then I would be getting that methylation profile from doctor’s data and that is important to run but again you have to understand how to interpret it. And on [inaudible – 00:25:59] there is an article on there along with a podcast in the learning center about methylation profile analysis.
And I give a walkthrough of an actual test that I interpreted and discuss why these markers are the way they are. And I give various recommendations and that is a good thing to look at. So I would say with the methylation pathway I like organic acids a lot.
[Damien Blenkinsopp]: So you said that methylation – because the doctor’s data panel is called methylation profile, is it? Or is it the pathway? Because there is another company I know you have mentioned before and I have used before also, this Health Diagnostics. They used to be called [inaudible – 00:26:31] Diagnostics.
[Dr. Ben Lynch]: Yeah, I love their test. The problem is the turnaround time is pretty bad. But it might be hit or miss and I did hear from someone that if you call them for results and tell them to email the results it might speed up the return of the results by about three weeks. So that is worth mentioning, Health Diagnostics Research Institute. I think it is HDRI-USA.com or HDRI-Labs.com, something like that.
[Damien Blenkinsopp]: Yeah, we will put the links I am sure.
[Dr. Ben Lynch]: Okay, great. Their methylation test is the best out there right now. There is no question.
[Damien Blenkinsopp]: So what do you like about that versus the doctor’s data one then, for example? What helps you?
[Dr. Ben Lynch]: Well doctor’s data is basically – even Dr. [inaudible – 00:27:12] has stated that the methylation profile with doctor’s data is basically just a methionine cycle and it touches the transsulfuration cycle just a tiny bit. But we have no idea what is going on in the folate pathway. And the folate pathway is a significant pathway that leads into the methionine cycle and if we don’t know what is going on there, we don’t know why these markers are doing what they are doing in the methionine cycle. So you have to assume and assuming is not good. You want to know.
So the Health Diagnostics Research Institute will give all the folate derivatives, which is useful to the primary ones which is very useful. They don’t give the B12 in there, which I think would be nice, but you don’t really need it because if you see methylfolate as elevated and tetrahydrofolate is low, then you can know right there that there is a methionine synthase block of some sort, whether it is B12 or oxidative stress, lead, or yeast overgrowth or what have you. So I would say that Health Diagnostics is better in that regard.
They also look at adenosine. And adenosine isn’t in the methionine cycle but it is a beautiful marker once you understand how to use it. Again, I am still learning but I am getting better at it and I believe I know how to reduce it now. I know caffeine reduces adenosine, which is very interesting.
[Damien Blenkinsopp]: That is good news.
[Dr. Ben Lynch]: Yeah, for those coffee drinkers. I am not saying go and suck down coffee by the gallon, but –
[Damien Blenkinsopp]: Don’t quit your daily coffee.
[Dr. Ben Lynch]: Yeah, I mean a little bit of caffeine can be good, especially with D-ribose. I think some people, too, not to deviate too much but this is something I have recently learned, where if people aren’t doing very well in terms of they are getting post workout fatigue or soreness, that D-ribose is something beautiful. D-ribose is really important for producing ATP and it is very demanding to produce in the body.
So D-ribose and a little bit of caffeine, part of exercising, might keep that adenosine level low and then you might be able to use aerobic metabolism for a longer period of time before you shift into that lactic acid build up, the lactate. You might be increasing endurance that way. When it comes down to labs, if I am going to order labs what I would really like to do is just – they are expensive but you spend the money up front. Because if you order labs and one day you order the CBC and Chem and you get your serum ferritin and all that in there, your basic labs and you get those back and you find some things and you work on that.
Then you still have some symptoms and you order the CDSA and you look at the digestive function and you find some things there and you work on that and you say, you know, we still have some issues and you get the organic acids and you find that you are low in B12 or something else. And if you keep doing these labs this way then you are not connecting them. And the beautiful thing is if you order all those labs at once you can lay them out on your desk and you can stare at them with this built-in pathway planner which you have the privilege of staring at it in Chicago.
[Damien Blenkinsopp]: It’s huge, just for the readers. It’s huge.
[Dr. Ben Lynch]: Yeah, so I have got a whole new updated one so I will get you a new copy of that, Damien, for your listeners. So if you do all these tests at once and you look at it with the pathway planner then you can see how everything interacts and why maybe the CBC is bad because of this and this and this.
Or maybe why their methylation profile is bad, because of that and this and that. And you can see the underlying causes and you can say okay, look, now we know we have a pathogen in your gut and you are anemic and your iron levels are low, and your magnesium levels are low and your homocysteine is high. And your tetrahydrofolate is high and your yeast overgrowth is high and now we can say we have all this data and we can know why all these things are abnormal now, and the underlying causes are this, this, and this.
And so you work on those main underlying causes and you make such fast headway in the patient. It is an initial investment but the speed in which your patient can get better is tenfold because you are not chasing things. Now, mind you if the patient is under 30, or 30 and younger, and their main complaints are not that serious then would I do all this testing?
No, I would probably do most things empirical, meaning I just go for the lifestyle and dietary changes without looking at some labs but if it is the first, if they haven’t had labs done for years, then I would go ahead and do all this testing too. So it depends on if they have already had some baseline testing done. If they have never had baseline testing done then it needs to get done.
[Damien Blenkinsopp]: Right, so when you say baseline it sounds like you are doing – how many tests are you doing? Stool tests, urine tests, the methylation – ?
[Dr. Ben Lynch]: Yes, and I will get you that list too for your listeners. I have a list and I do what is called a roundtable for doctors. So I am going to Japan this fall and prior to going I am making them do all these different tests. And then what we are going to do is they are going to share their patients that are struggling to get better. And then I have a list of tests that I told them to get.
And so I will just get you that list if you like. Ion Panel by Genova is pretty good. The Ion panel looks at fatty acids. It looks at organic acids, it looks at amino acids. It looks at lipid peroxidation. So if you were to order just one test to keep it simple then the ion panel with the CBC chem panel would be something to look at. It is not perfect, no test is perfect. They all have holes, which is why I have a laundry list. But I think the Ion panel by Genova is definitely a good start.
[Damien Blenkinsopp]: So I guess one of the main points there is a lot of these tests are about biochemicals and they are not long-term markers that are changing over time and they are connected to each other. So unless you get the whole picture, like you are doing, then if you work on some problems with the CDSA then the methylation test you get could be different and it might not fit with the problems you have identified in the first place? You are looking in the wrong direction. Is it because the biochemicals are moving around too much?
[Dr. Ben Lynch]: That’s right and not only are they moving around too much, but why are they moving around? So if you order that methylation profile in 23andme because you are a doctor that specializes in methylation – and this is a big problem too, because methylation is not the tool. It is another tool.
If the patient comes in, they come to you because you are the methylation expert and you to MTHFR and the 23andme and the methylation profile and you just work on those things, and then you could be missing the underlying picture of why their methylation is wrong in the first place. And I cannot tell you as a physician – I would slap myself in the face multiple times for missing screening for pathogens.
And screening for pathogens is so hugely important because we are so susceptible to them now because of this stress and the lifestyle that we have and the likelihood of us having a pathogen is so high whether you have symptoms or not. And if you don’t have symptoms that is because you are supporting it through your lifestyle and diet or supplements or meds trying to mask the destruction that pathogen is doing on you.
So my point on this is that if you order the methylation test or your CBC and you get the things back and you work on that you might be missing the underlying picture of arsenic exposure or perhaps there is no pathogen there and maybe there is lead or mercury or maybe there are mercury amalgams in their teeth or root canals that were done that were festing anaerobic bacteria. That is why it is important to do all of these tests first so that you can see how all these things are.
And I have recently learned too is that some doctors already know this stuff but it just takes forever to link everything – but iron. I had my wife, for example, her serum ferritin just doesn’t go up. It just will not climb and her RBC magnesium too is just chronically low. And I have very good nutrients to work with this with all the cofactors and everything it is still low. Like, what the hell. And so RBC magnesium – I was reading this book and I don’t remember the title but it is by Dr. Myhill and it is her new one.
She talks about RBC magnesium being chronically low in people possibly because at rest I need to find a research citation to see if she is right or not but she says at rest 40% of ATP is utilized for moving minerals back and forth between the cell membrane. It’s like holy God, that’s big. So 40% of ATP at rest, not at exercise but at rest, is to move sodium and calcium and calcium and magnesium across the cell membrane. That’s big so magnesium has to be pumped in and so does potassium.
Potassium is a huge component that I think most people are deficient in. But my point here is RBC magnesium, I mentioned ribose earlier and this is also from Myhill, that she thinks that if people are chronically low on RBC and red blood cell magnesium it might be because their D-ribose levels are too low because their ATP levels are too low. And I give my wive ribose and I recommend it to her, but is she compliant? Sometimes. And the serum ferritin is low I believe because pathogenic bacteria in the gut, which we have recently found from the CDSA by doctor’s data is she has some pathogens in the gut and they suck up iron like crazy.
So why we are taking these nutrients, these high-quality nutrients – the pathogens in the gut are taking them all. And if you have yeast overgrowth in the gut then these things the yeast are using, your B1 and magnesium, to make acetaldehyde which is then converting to ethanol, which is disrupting your methylation cycle. So the gut is so central too – and I would do the ion panel with the CDSA probably first, and I like the RBC.
[Damien Blenkinsopp]: So the CDSA is the doctor’s data stool test?
[Dr. Ben Lynch]: I like that one.
[Damien Blenkinsopp]: Versus say metametrics or some of the other ones?
[Dr. Ben Lynch]: Yeah, there are a lot of them out there. I think Genova’s is getting better. I didn’t like Genova’s for a long time and I think GI stool effects was not very good. I like doctor’s data. I ran another one and I think I ran Biohealth and it came back with basically nothing so that everything looked fine. I did it for my whole family and I didn’t trust it, no way. And so I did the doctor’s data and it came back with all this useful data, so it is very important that you order the right test too.
[Damien Blenkinsopp]: So are there any methylation or other tests you have done which you didn’t find useful, whether it is for accuracy reasons that you didn’t trust or other reasons?
[Dr. Ben Lynch]: Well I would have to think about that one for a while.
[Damien Blenkinsopp]: I think you mentioned in a presentation homocysteine and it is in all of the main labs like LabCorp and Quest and so on, and it is obviously something that lots of people are getting tested now. How do you find that test, for example?
[Dr. Ben Lynch]: Well homocysteine is good if it is high, so if it is high it is useful and you know there is some type of blockage going on. And when I say it is high I am not talking about the standard range. I am talking higher than seven in an adult. Now, in kids homocysteine levels tend to be lower. And I think they are lower so normal in a kid say under 14 or so, shooting from the hip, I have it somehow in the forum of [inaudible – 00:38:20] and I need to remember the range is here and it is important. But anyhow younger kids have younger homocysteine levels.
So they might come back at five and he is like oh, that is too low, I need to work it up. No, they naturally run low and they naturally run low, probably because methylation cycles is humming along super quick because of their growth. So the younger you are the more methylation you burn through because you are growing. Look at autism, their methylation cycles are messed up and these kids are hurting big time.
But with homocysteine, my point here is that homocysteine is a good marker of a tie and the problem is that it is extremely rudimentary and we don’t know why it is high. So it is important to know why it is high but at least it is high. So doctor’s might take some action and get some B12, B6, TMG, methylfolate and so on, but the problem is if it comes back low, as you saw Dr. [inaudible – 00:39:06] lectured on about homocysteine and S-adenosylhomocysteine in the cardiovascular risk patients, because there is research out there that says look, homocysteine levels are not correlated with cardiovascular risk and you say well BS because all these other papers look at homocysteine and it is related to cardiovascular disease.
But some of these papers that are actually published are legit and they say homocysteine isn’t. But now if you look at S-adenosylhomocysteine, S-adenosylhomocysteine levels can be elevated while the homocysteine levels are normal and they are correlated. So those two things will be correlated to cardiovascular disease. So homocysteine, before you get to homocysteine is S-adenosylhomocysteine. I think while your listeners are listening to this show they should have this pathway popped up so they can follow me along a little bit but S-adenosylhomocysteine is above homocysteine and that pathway is bidirectional. SAW goes to homocysteine but homocysteine also goes back to SAW, so it goes two ways. So that is important to know, that homocysteine goes back to SAW preferentially.
So if you are to draw and write homocysteine on your piece of paper and homocysteine is your left hand and SAW is your right hand – there is going to be a bigger, heavier arrowhead moving from left to right from homocysteine to SAW than there is from SAW to homocysteine. So the pathway to moving back from homocysteine to SAW is fatter and now if your SAW is elevated your adenosine can get elevated. And if your adenosine gets elevated then it is metabolic syndrome, it is diabetes, and so on.
So you are absolutely right that homocysteine is very rudimentary and that is why methylation’s profile by doctor’s data is not as good as Health Diagnostics but at least it does look at SAM SAW and the ratio.
[Damien Blenkinsopp]: So that is right, the SAM SAW and the ratio, that is what you find useful in that one.
[Dr. Ben Lynch]: That’s right.
[Damien Blenkinsopp]: So another thing you just mentioned is some of the reference ranges are a bit different. Is that in a lot of the tests? Some of these tests are a bit young as well, like the methylation pathways from [inaudible 00:41:12] Diagnostics or [inaudible 00:41:14], as you said. Now, I am not sure how much data they actually have in a database to establish what a reference range is and what kind of populations – so how do you go about looking at reference ranges?
[Dr. Ben Lynch]: You have to remember that just like you said earlier a lab test is a snapshot in time. So I am going to answer your question here and I am a little bit delayed, so if I get too off track you can hit me on the head and I will get back to the answer. But in short a lab test is a snapshot in time.
So if you are stressed out and you are stuck in traffic to get to the lab test and somebody cuts you off or there is construction and now you’re late and the doctor is bitching you out for being late or the kids are screaming in the back of your car and then you draw your blood for the methylation test – it might make some impact. And then if the doctors don’t handle – or the lab tech doesn’t handle your sample properly, there can be some issues there.
Then it finally gets to the lab and maybe it gets lost in transit or maybe it is sitting in the back of the FedEx truck for a couple of extra days and that sample gets messed up. Maybe it doesn’t and say everything now is still on the way just fine and there are no hiccups, and then the sample gets processed in the lab and is done by humans – humans can sometimes make errors like adding too much reagent, being tired and not writing things down properly, or maybe the computer isn’t reset or reconfigured every morning and then didn’t do it properly that day.
They put the results on a beautiful PDF that looks fantastic and they have these little ranges on there and you get the results back and you are like, ‘What the hell? This doesn’t look right.’ You always need to look at the lab as a piece of paper and you need to match that to how your patient is at the moment. So if the lab comes back one way and your patient is completely the opposite, maybe the lab is right. But most likely I would say this is possibly a lab error.
Now, getting back to the ranges, I know for a fact that the Health Diagnostic Research Institute – their lab values for that methylation test was they tested 100 medical students. Now, when I was in medical school I was the sickest I had ever been in my life. I was tired, I was just run ragged and med school is the toughest thing I have ever done in my life besides rowing for UW. And I would say how healthy were these medical students? Were they drinking? Were they not?
Using the word ‘healthy’ medical students is such an oxymoron to me. So that is where those lab values came from, those ranges. So you have to keep that in mind. The ranges on all lab tests are coming from the population to some degree. So in our population as a whole it is pretty sick. I don’t know the historical thing but there is a really good book out there. Do you know it, Damien? It is about homocysteine. I think it is called – could it be your B12 levels? Or is it your B12?
[Damien Blenkinsopp]: Yeah, that was one of the first ones.
[Dr. Ben Lynch]: And that is a pretty good little read. It is pretty basic and it is pretty good to read and he talks about, or I believe – or she – the ranges of homocysteine and how they have historically elevated. And look at arsenic – George W. Bush, Jr. increased arsenic levels that are “safe.” So the safety level of arsenic now has been inflated over time. So the ranges – you are going to really have to take those with a grain of salt and again match it with your patient.
And I know some doctors can really dial in where they like the ranges and it would be so great if doctors could share their data, saying I find from my clinical experience that this range is the ideal one. But for some reason they latch on to these things and they keep that information private, and I don’t know why. But yeah, so homocysteine I believe a lot of them say it is greater than 11 for an adult and some even say if it is greater than 15, and that is way too high. I would say 7 is ideal, or 9 you have definitely have some work to do.
[Damien Blenkinsopp]: Yeah, and coming back to when we spoke a couple of times about supplements and we spoke a couple of times about supplements and we spoke about people using supplements to lower homocysteine. So some people have done some work on their methylation and some of them have been taking supplements, the B vitamins, the folates, and other supplements for their methylation and they will feel better.
But as you were talking about earlier the underlying condition – they basically have to take these supplements all the time now to keep themselves going. Is that a good idea? You were talking about continuing to look for the pathogen or whatever causes it. Are there dangers from supplementing? Or do you think it is a good idea to control symptoms for a while if you are still trying to figure things out and you should always be aiming to get off of them?
[Dr. Ben Lynch]: Palliation is removing the symptoms and the irritation of whatever is causing disturbance in your patient or yourself quick – that is what drugs do fast, super fast, unless they are causing other issues. I call it drive-thru medicine. You go to your doctor and say, ‘I’ve got a headache,’ and they prescribe headaches.
And maybe your ergonomics at work are not right or maybe you are not drinking enough water or maybe you are drinking aspartame or you are sucking down caffeine all the time – there are a million reasons for headaches. But if you are taking an aspirin and the body is saying, ‘Hey, listen to me and fix it,’ and you tell it to shut up, I am taking an aspirin – now, you are telling it to shut up too if you are taking methyl donors and you are not addressing the alcohol intake that you are drinking every night if you are drinking beers and wines and whiskeys and vodkas all the time.
You have a job as a real estate agent and you are celebrating house closings all the time with your patients. Then yeah, it is a social thing and it is fun to have your wine but if your methylation is not appropriate or you have yeast overgrowth in your gut that is inhibiting your methylation or you have got lead toxicity.
If you order the lab tests and you see your methylation is messed up due to the lead and you know you have elevated lead – or say you don’t know you have elevated lead but you are bypassing it with these methyl donors, these methyl donors only do so much. But the lead is still causing oxidative stress. It is still blocking other pathways that have no relation to methylation. And so while some pathways are being bypassed, others aren’t. So it is a big deal to address the underlying cause.
Let me give you a brief example here. I had a friend of mine who was drinking not a lot but he would have a few beers every night. He would wake up tired and his kidneys were sore and he was getting kind of sick of it and he asked what to do. I told him to quit drinking and he just kind of looked at me and laughed. So I said all right, take some B vitamins.
So he took the B vitamins for a while and that helped but after a while it didn’t and I said, ‘Well, now I know about methylated B vitamins, so take the methylated B vitamins. So he started taking those and he wrote to me and goes, ‘Thanks man, now I can drink even more and I wake up in the morning feeling fine.’ I was like that really defeated the purpose. But now he is making more but he feels fine.
Then I told him that drinking was a mitochondrial toxin that was affecting his mitochondria and that leads to a big issue. And that got him because he was a former athlete too and he likes to be fit. So as soon as I told him that alcohol is a mitochondrial toxin he went, ‘Oh crap,’ and he stopped drinking pretty darn fast.
But he kept going on these methylated B vitamins and he was just taking additional methylated folate and B12 as well. And he was starting to get really irritable and angry. Before he was just fine and then he just kept taking it. And he didn’t tell me this and we would talk about what I was doing these days and talking about niacin and if people took too much.
So one day he was driving down the highway and he had auditory hallucinations. The radio was off but he was hearing the radio. He kept cool because he knew it wasn’t him. He knew something was wrong and I remember Ben telling me that this could happen. So he stopped the methyl folate and he started taking niacin and everything was normalized. And then he stopped taking the methyl folate at all. He just stopped taking it. And he reduced the methylated B and he became fine.
So my point is that he had this environmental trigger that his body had to handle, which was alcohol and acetaldehyde. So his body was using all these methylated nutrients to clean up that garbage but as soon as that garbage was no longer coming in, too much of that nutrient now was causing other things. So he stopped it and lowered his dosages significantly. So I usually tell people before they reach for a supplement bottle to understand what it does and if they need it or not.
[Damien Blenkinsopp]: There are a lot of these polymorphisms. Are there any situations where you have a polymorphism in your methylation process where you may have to take a supplement for a long period or maybe forever?
[Dr. Ben Lynch]: Yeah. I don’t know what that is yet but I would say let’s look at a couple real quick. With MTHFR if you have the 677 homozygous variant then your ability to make methylfolate is reduced by about 70% to 80%. So you are making about 20% of methyl folate compared to the standard person who has no MTHFR.
Now, if you are eating a lot of leafy greens in general and you are also eating grass fed meat and you are not that stressed out and you are leading basically a perfect life then you might not need methylated folate. I think those with MTHFR 677 might need some methylated folate to some degree pretty much the rest of their life but if they are getting it through their uncooked leafy greens and they are definitely eating quite a bit then I think they are going to be good through that.
Now, there is a paper I talked about that is on the video at MTHFR.net – a lot of the information there is dated but it is still pretty accurate. That video there is free and I show the polymorphisms in various populations like the Chinese, Indians, Hispanics, and so on, that have a very, very high rate of – Italians, too – that have a super high rate of MTHFR.
Now at the end of that video I talk about neural tube defects in Mexico and the United States being related to folate. Then they did another study that looked at neural tube defects and MTHFR, Hispanics, and the Americans and those were all directly related. The researchers also looked at Italians in MTHFR and neural tube defects, and there was no correlation.
So the neural tube defects in Italy, these people with their lifestyle seems very protective, even despite the MTHFR polymorphism over there. So they eat a lot of salads and they drink a bit of wine that is a little bit as good, and not too much not. And their lifestyle is a lot less hectic than us Americans and we chase this American dream which is just a complete nightmare for people. So the American dream is the American nightmare – I think it should be renamed.
Then if you look at another gene – GAMT of creatine, I think people with the GAMT polymorphism may benefit from taking creatine and some form of creatine or at least eating meat. If you are a vegetarian and you have GAMT then you are probably going to be in trouble.
[Damien Blenkinsopp]: That is interesting that sometimes it can inform your lifestyle choices as well.
[Dr. Ben Lynch]: Yeah, and vegetarians and vegans – I was a vegetarian for a while and I felt terrible. Looking at my genes I think I could understand why, plus I didn’t know how to be a vegetarian properly. I was a carbitarian and I didn’t eat properly. I think if you are a vegetarian and you know how to eat very well and you are supplementing with choline, creatine, phosphocholine and B12 then I think you can be okay.
But some of the most ill people I have worked with are vegans and vegetarians and I would say the majority of women that have had recurrent miscarriage or can’t get pregnant were vegans and vegetarians. So in most pregnant women whether they are vegans or vegetarians or not, most pregnant women are deficient in choline. And most cancer patients are deficient in choline as well. So choline is a very, very important nutrient and that comes from meat, plain and simple.
[Damien Blenkinsopp]: And our friend, liver, in particular.
[Dr. Ben Lynch]: And our friend liver, yeah.
[Damien Blenkinsopp]: Great, thank you for all of those insights. I want to round off with a couple of questions a bit more about where you see things going over the longer term. So in the next five or ten years with this whole area of methylation, where would you hope it would go? What kind of things are you excited about in this area?
[Dr. Ben Lynch]: Well I am most excited about disease prevention with it and I think if it is utilized properly, meaning still focusing on lifestyle and diet and the basics, I think if there is a company like 23andMe that provides very clinically relevant polymorphisms and not a million polymorphisms that may mean nothing – but reducing it down to one 8.5 by 11 report of genetic polymorphisms that are very clinically relevant, that have been researched, that can bypass through lifestyle, diet, and nutrients, I think that would be very useful.
Right now there are a lot of polymorphisms that are published that may or may not have any clinical relevance. And I think that the 23andMe has – even with MTHFRsupport or Genetic Genie I think there are variants on that test report that are bogus, meaning no clinical relevance. I would like to see variations that are clinically relevant with actionable steps and understanding how to take action on them in simple, systematic ways and not so complex and convoluted – which I know some of my presentations can be.
I am trying to simplify things and would would be really cool too is to have some type of computer program that looks at all the polymorphisms that individual has along with their lab markers that are off, their diet, lifestyle, heavy metal exposures, and so on. You plug all that information into a database and the computer program will spit out some generalized recommendations for the physician to evaluate such pathogens or heavy metal screening or some certain things to look for, or nutrients that they absolutely must be taking and nutrients and meds that they absolutely should be avoiding.
So computerizing this I think would make it a lot more actionable. And also with prenatal screening, I think every person now should be taking some type of genetic screening that are actionable. There are things out there called Counsyl that looks at genetics that cause issues in the fetus during development. And why that test is useful – it also scares the hell out of the future parents, and having fear while you are pregnant is definitely no good because fear also messes up your methylation and a bunch of other pathways and blood flow to the baby.
So if you order a test which has actionable things that they can do through diet and lifestyle and the mother knows that and so does the father, because the father’s genetics are also significantly important for the baby’s development too, then I think that is the way to go. So I think that, in a nutshell, for disease prevention is important. And also mitochondrial disorders are really severe and you see a lot of early death in people who have mitochondrial dysfunction.
And as you may remember from the Chicago conference I talked about maternally-inherited mitochondrial disorders, because mitochondria is basically inherited from the mother. If you see a list of diseases that are all down from the mother’s side of the family or the women’s side of the family then it is probably a mitochondrial disorder and if you do any genetic testing on that you might be able to support the mitochondria immediately through NADH, COQ 10, glutathione, and so on. So again, I think disease prevention automation and specific targeted recommendations is where I would like to see it.
[Damien Blenkinsopp]: Yeah, in terms of tests is there anything that you see missing? I know mitochondrial tests, for example, you mentioned Sarah Myhill and I know she has a test she is doing, but I don’t know many other tests. Are there any other tests you feel would be useful to be available or are hard to access or they need further development?
[Dr. Ben Lynch]: Yeah, tons of them. And I would love to see this stuff on one panel and I have notes on these things trying to get other labs to look at it. So Acumen Labs, that is over in Wales or UK, Myhill promotes and works with a lot. Again, a test like this – not to spend too much time on it, but they were looking at a snapshot of ATP, ATP’s realization, and so on. And some of those tests look at causation too so I would say those are good tests. But would I necessarily order those? If they are not too expensive, yeah, and if they are expensive, no.
The reason why is because if I see lactate elevated on a patient, lactate is a very readily-available marker. So if lactate is elevated then I know immediately that the mitochondria in this patient are suffering, along with lipid peroxidation. If lipid peroxidation is elevated then we know their cell membranes are getting damaged. And if their cell membranes are damaged, then their mitochondria will be damaged.
I want to give you the markers now that are already available. So lactate, lipid peroxidation are great. Ammonia elevation is also a marker of mitochondrial dysfunction because mitochondria process ammonia, for the most part. So if that is elevated then we know the mitochondria are not working very well and creatinine is a great one for that as is general mitochondrial support. And so looking at –
[Damien Blenkinsopp]: You mentioned that it was difficult to access. Is that urine?
[Dr. Ben Lynch]: I don’t know, I don’t know what is better. I think blood lactate can be either, but I know urinary lactate is available. And I don’t know about pyruvate. And now looking at B12 – B12 is a nightmare. There are really no tests – well, I shouldn’t say that. Holotranscobalamin and methylmalonic acid are pretty good for B12.
You can look for macrocytic anemias too, elevated MCH, MCV, but those can be missed because you could have normalized MCV, MCH and still have a masked anemia because of folate, so a masked B12 anemia, I should say. So you want to be looking at methylmalonic acid and you want to be looking at holotranscobalamin, but the issue with B12 is if there is low glutathione reading about this now I have a bunch of papers on it actually, but glutathione is needed to carry B12 around and so if the patient has low glutathione their B12 levels may look elevated on the lab tests and serum cobalamin.
So serum levels of pretty much anything are not that useful. You want to look at intracellular and if it is an intracellular nutrient. And we know that B12 has to get into the cell. So if you see a serum folate and serum cobalamin elevated and your red blood cell, B12, and folate, I know Spectracell looks at T-lymphocyte testing for B12 and folates and that is intracellular, so that can be really useful for people.
Now to answer your question about tests that I want to see in the future, if you want to see oxidation, I want to see oxidized biopterin and reduced biopterin. These labs are looking at biopterin but they are not telling you if it oxidized or reduced. And if your biopterin levels are oxidized – say your biopterin levels are normal, but your patient still is having neurological symptoms or cardiovascular symptoms or they are having some type of mental or emotional imbalance.
Biopterin is really critical for this because biopterin recycles and helps revert your tryptophan and serotonin and tyrosine into dopamine and your arginine into nitric oxide for your cardiovascular systems. So with these things if you have oxidized biopterin and your biopterin levels are normal then this is going to be an issue so oxidative stress – if you measure oxidative stress this is why I also recommend looking at multiple tests at once, not just one at a time.
This is a beautiful reason why. So if their B12 levels are elevated and their folate levels are elevated in their serum – if their biopterin levels are normal but their oxidative stress is high and you know their oxidative stress is high through their lipid peroxidation, their lactate, and their glutathione levels are low and glutathione peroxidase enzyme is high or superoxide dismutase levels are high or their manganese levels are low and their zinc levels are low and so on.
If you put all these together you can immediately understand and say, ‘Hey, your oxidative stress is high and it is disturbing all of these enzymes downstream. It is messing up your glutathione, it is messing up your biopterin, your B12, your folates, your cells. We have got to get that oxidative stress down. But we need to understand your oxidative stress is elevated in the first place. So you can bypass the need for these new tests that I want to come up with if you order all these different things at once. But it is expensive, it is a pain in the ass, and it is time-consuming.
[Damien Blenkinsopp]: So it would be better if you could go straight to – it is kind of like you have to take these proxies and these indicators rather than getting directly at the issue.
[Dr. Ben Lynch]: Yeah, inflammatory cytokines can be really useful to look at, So [inaudible 01:02:00] 1, 6, 10, and then if you look at TNF alpha, these are coming back elevated and that can be a problem but again, why are they elevated? These mess up things too. I would like to see different forms of B12 and I would like to see adenosylcobalamin, I would like to see cobalamin itself, I would like to see oxidized cobalamin, and I think that would be very , very useful.
[Damien Blenkinsopp]: Especially with so many people supplementing these kinds of things.
[Dr. Ben Lynch]: Yeah, and if they are taking B12 and most of that B12 is going to oxidize cobalamin, which is causing more damage to their body, then they need to stop taking that B12, support the glutathione, but if they can’t support the glutathione because they are reacting to the sulphur or they are not hydrated enough, then that’s a problem. If they have urinary – they are not peeing well for various reasons because of dehydration or what have you, taking glutathione could be a big problem.
Or if they are sensitive to sulphites, glutathione if you take it then it can build up your cysteine levels and your cysteine levels go down and they make sulphites. That could be a problem too, so if people feel like crap taking glutathione, it could be they are not hydrated or their cell membranes are not appropriate, they are not healthy, or their sulphites are messes up and too elevated.
So it gets tricky fast, as you saw in Chicago, because I try to teach all this in an hour-and-a-half, just like we are talking now for an hour-and-a-half. But the point is just take this stuff and listen to it and relisten and if you glean one or two things from this, that is great. And if you listen to it again you might glean something something else or you might have an a-ha moment for this particular pathway in one patient and an a-ha moment for a different part of this combination in another patient. So it is bit by bit.
[Damien Blenkinsopp]: So you are obviously doing a lot of work on this research. What are the most important things coming out for you in that area? What are you working on right now, maybe for next year? What is the most interesting for you?
[Dr. Ben Lynch]: What is most interesting for me right now is why people react unfavorably to certain nutrients, like methyl folate, B12, glutathione, and so one and then understanding how to identify these patients before they even take these nutrients to say hey, you have this and this and this. You need to optimize this and this before you take this and this.
That is what I am working on right now. I am trying to prevent patients from flaring by identifying where they are currently and if they can respond to a particular nutrient or not and getting the reason why. That is what I am working on because I know that the majority of patients who are under 30 or even under 40 and they are not too bad, a lot of them can be taking these methyl donors and feel great.
But you start getting in the conundrum cases with the Lyme patients, the autistic patients and so on – the cancer patients. And if you start with them out of order you can flare them. If you flare them you lose patient compliance and you lose trust and it can take longer for them to get better. So what I am doing now is trying to do that work flow.
Part of that work flow seems simple when I say it like that, but the issue is I am tying it to the mitochondria and I am tying it to the hormones and inflammation. So I have always had a big hole in hormones and so I am looking at hormone-related connections. But if you look at hormones, how are hormones affected? Well, they are affected by methylation, inflammation, and mitochondrial function. And Sarah Myhill so eloquently stated in her recent book that every single pathway in the body is affected by mitochondria.
So my biggest focus right now is mitochondrial health, which is I am reading her book, because she is very well-versed in it. I agree with a lot of things in her book and she has provided me quite a bit of insight. I also disagree with a few things in her book but that is how medicine is. None of us are perfect and I say things that are wrong and we will collaborate and I will give Sarah a call or an email here at some point after I finish her book. But what I am working on now is that and when I was at that part two conference at [inaudible 01:05:57] and there were 300 docs there and I asked them what do you want me focusing on next? A few things were brought up and then I said, ‘What about mitochondria?’ And then the whole room was just in an uproar. Right now it is mitochondria in a nutshell.
[Damien Blenkinsopp]: Yeah, have you connected with Dr. [Terry Wyle 01:06:14]?
[Dr. Ben Lynch]: No, I haven’t. I know of her book and I know what she went through. I have read her book. I haven’t connected with her yet but she is another one I need to look into. And her book was pretty basic for me but she definitely recovered, which was beautiful.
[Damien Blenkinsopp]: I spoke to her a couple of weeks back so maybe I can connect you with her if that is interesting for you.
[Dr. Ben Lynch]: Yeah, that would be great, it definitely would be. And my thing too is this is all about collaboration. The stuff I am working on is the stuff that I want to give out and give people and not holding and hoarding. If I am able to help a doctor or two or 1,000, then that is my ultimate goal here. So the more doctors I can work with and collaborate with, the better.
[Damien Blenkinsopp]: And the more feedback you get as well so that is useful to you as well.
[Dr. Ben Lynch]: Yeah, exactly. Every doctor out there has got something that I don’t know. So Terry is going to have something I don’t know for sure and she might answer the puzzles faster than me sitting here in my office, digging through PubMed and she is like I wish I knew that ten years ago.
[Damien Blenkinsopp]: Yeah, collaboration is definitely the way to go. So what would be your number one recommendation to someone trying to use data to help them with the area of methylation? Is there once piece of advice you would give them?
[Dr. Ben Lynch]: Don’t be biased – look for bias. I don’t know if that is what you are going for, but bias is a big problem in research. So if you are reading papers and you are trying to gather data or you, yourself are working on a particular project make sure that you are eliminating bias. And I say that because when I got called in to present to the Cancer Treatment Centers of America and they wanted me to talk about MTHFR I quickly told them that cancer is about more than just MTHFR.
And I could have presented an hour-and-a-half on how MTHFR is related to cancer but I would have done them a major disservice because there are a lot of articles out there and papers that talk about MTHFR and how it is not related. So I could have presented an hour-and-a-half of totally biased research and when I say bias I mean personal bias. And some of these papers on MTHFR and cancer, a lot of them are totally legitimate saying that MTHFR isn’t related and some of them saying it is.
I think it is a bigger picture than this. And that is another thing, to keep the bigger picture. So if you dial down into MTHFR is not related to gastric cancer then you need to understand the bigger picture. You have got to zoom out, so keep the bigger picture when you are collecting data and you can’t forget the basics of diet and lifestyle. And I think that is so hugely important and compliance is super important and however you get your patients compliant, whether it is with 23andMe and MTHFR tests and you plop down in front of them and say, ‘You are a mutant,’ or you tell them, ‘Mitochondria are being destroyed because of your alcohol.’
You have got to find that pain point for that particular individual to get them compliant. So anyway, I would say keeping the bigger picture, don’t zoom in too close and make sure that you are not being biased and you are not reading papers that are biased.
[Damien Blenkinsopp]: Great, thanks for that. Okay, last question – looking at yourself, are there any data metrics or biometrics that you track for your own body on a routine basis yearly or whatever it is?
[Dr. Ben Lynch]: I look at fatigue for my own. I don’t look at data points and I look at my fatigue and my mental capacity and my moods. I look at a few data points with me personally. So if I am more tired than I should be then I ask myself why and then I review what I have been eating, if I have been more stressed, or if I am not exercising or exercising too hard. I am 40 years old now and you hit 40 and your mitochondria slow down more and more.
So I would say I look at my ability to think and my ability to maintain endurance, not only mentally but also physically. Muscle mass I think is super important because the more muscle you have the more mitochondria you have, so I am going to be starting lifting here soon so I can restore my glycogen and make more ATP. Muscle mass is a very important marker to look at. I am not going to be the Incredible Hulk by any means but if I am 213 pounds now I don’t know what my body fat is, probably 10 to 15.
But when I was rowing at UW I was 213 pounds and I was 4% body fat. I am not going to be 4% body fat again probably but I look at leanness and weight and the ratio of muscle to fat, so being fit is a marker that I am focusing on right now.
[Damien Blenkinsopp]: Great, thanks for that. Those are very interesting ones. Also the mood is something I think a lot of people don’t think too much about. They think they are in a bad mood today but do you always kind of relate that to something that might have gone on? Do you think there might be some kind of biological basis or could it just be stressful events?
[Dr. Ben Lynch]: Yeah, great question and I think you are absolutely right. If there is a stressful event you need to be able to understand that. But you should be able to adapt to a stressful event. And it is interesting – I was just at this conference last week and you know how loud noises can sometimes make people jump?
I was sitting there and the room was absolutely dark and people were holding up candles. It was the end of the conference and it was this little ceremony that we do every time which is really cool. So they turn off the lights and hold up candles and it was quiet for a long time. I was thinking this was going to be really interesting, how are they going to end this period of silence? Is somebody going to scream and whoop and go crazy or is there going to be a gong or a bell? What is it?
So I kept waiting for it and all of a sudden the band behind us just really laid into it. It was really loud and the woman next to me jumped and I was just as calm as can be – so your ability to adapt to stress is so important. So we started this whole conversation today about adapting to stress and adrenals and so I think adapting is really important. But your original question of moods, so if I am stressed I immediately know that I need to be focusing on my adaptogens, licorice and [inaudible 01:11:56] and what have you, and eating smaller amounts but more frequently with some type of protein, and healthy carbohydrates and veggies are super important.
And not only eating it but chewing it well and absorbing it is even more important but if I am moody when I wake up, something is wrong. And I have to say that I don’t wake up in moods. I don’t wake up on the wrong side of the bed anymore. I might wake up tired or foggy-headed because I am working too hard or I stayed up too late. But I don’t wake up pissed off or irritable or sad. I don’t have those moods. And if I do get mad – I have got three boys and they can definitely put you over the edge sometimes, but I always look inward in that situation and say, ‘Okay, why am I doing this? Do I need more support in something?’
I am MTHFR compound heterozygous and I have got histamine snips, I have got GAD snips. And when I say GAD, GAD is a big one. So I am more prone to have lot of glutamate in my head compared to GAVA, because the GAD enzyme works with converting glutamate to GAVA. I am very conscious of this and so I will take some more magnesium and B6 if I notice I am a little bit on edge and protein for me is very, very important.
But your mood is super important. If people are moody, depressed, sad, glad – sad and glad are great, but if they are overly glad then something might be off too.
[Damien Blenkinsopp]: Right, just what you were saying about yourself and how you understand your own biology thanks to some of the work that you have done with methylation and you understand that protein is important and so some certain vitamins might help you if you are in a mood and stuff. You can see how important this is to inform our lifestyles and they could just be like I need to eat a bit more liver or whatever it is at the moment because my mood is a bit off, or whatever. And so this is an incredible area, this methylation.
I would really like to thank you for all the information you have shared today. It has been really amazing.
[Dr. Ben Lynch]: Yeah, and one thing too Damien is when I presented at the [inaudible 01:13:56] I talked about how important food was from a research standpoint because there are a lot of MDs that come to my conferences and they don’t have any nutrition training to speak of. So I talk about nutrition and how important it is and I talked about how carbohydrates increase serotonin and proteins increase your dopamine.
So you think wait a minute, proteins also increase your serotonin. But tryptophan is very tough to absorb. So that is why carbs can increase the serotonin and so if people are down and out then they get addicted to carbs and you need to understand and sit back – why are they doing this? Maybe because they are trying to selectively increase their tryptophan levels because if they eat protein they are not really getting the tryptophan because the tyrosine competes with it.
So my point here is that the last paper I presented on this is that if the person eats a fair amount of protein consistently, 75 grams was what they used and I think they used 75 grams because the average weight of a person is about 150 pounds – so 75 grams and 75 kilos of weight as a really rudimentary measure of how much protein to get. But my point here is people who ate adequate protein in a day had consistent neurotransmitter balance.
So if you eat adequate amounts of protein your neurotransmitters get balanced. So it is not only eating it but you have to absorb it. You have to make sure your absorption is also good. So people who have difficulty absorbing it is an issue but again my point here is if you are eating a carb-based diet because you are sad and you need to increase your serotonin levels but you don’t know why you are eating carbs, that could be one reason. But just eat more protein and that might be the answer.
[Damien Blenkinsopp]: Well thanks. As I say again this has been really amazing and information-filled. I know the audience is really going to learn a lot from this.
[Dr. Ben Lynch]: Good. Thank you Damien for asking fantastic questions. You ask some fantastic questions that no other interviewer has asked me before. So thanks for that. I think people will get some good information from this.