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RHR: What Influences Methylation? An Interview with Dr. Ben Lynch


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Dr. Lynch and I discuss the relative roles that genetics, epigenetics, diet, and lifestyle play in influencing methylation, and the environmental influences that affect methylation beyond your diet. What do we know and what do we not know about the role of methylation-related genes beyond MTHFR?

Revolution Health Radio podcast, Chris Kresser

What I really want to do today is dive in a little bit deeper on the topic of methylation and specifically discuss the role that genetics and epigenetics and diet and lifestyle play, talk about some of the primary environmental influences that may affect methylation, go beyond MTHFR to talk about some of the other methylation-related genes, and then perhaps more than anything else, talk about what Dr. Lynch has learned in the last few years of really taking a deep dive into this material, and working with thousands of people, and hosting his conference, and what he is excited about and working on, and looking forward to.

In this episode, we cover:

The relative roles that genetics, epigenetics, and diet/lifestyle play in influencing methylation
The primary environmental influences on methylation beyond diet
Beyond MTHFR: the role of other methylation-related genes
What Dr. Lynch is interested in now

Chris Kresser: Hey, everyone, it’s Chris Kresser. Welcome to another episode of Revolution Health Radio.

Today I’m really happy and excited to welcome Dr. Ben Lynch as my guest. I became aware of Ben’s work in methylation several years ago and have been really impressed with his contribution there. I’m sure many of you are familiar with his work and maybe have done some of his trainings or attended his conference.

He’s a naturopathic physician, and he received his cell and molecular biology bachelor’s degree from the University of Washington and his ND from Bastyr University. His passion for identifying the cause of disease directed him toward nutrigenomics and methylation dysfunction. Currently he researches, writes, and presents worldwide on the topic of MTHFR and methylation defects, and you can learn more about Dr. Lynch and his work at www.MTHFR.net. Dr. Lynch is also the president and CEO of Seeking Health, which is a company oriented towards disease prevention and health promotion. He makes some really great supplements that we use in our clinic and I have used personally as well. He lives in Bothell, Washington—sorry, I’m not familiar with that town; I’m probably slaughtering the pronunciation—with his wife Nadia and three boys, Tasman, Mathew, and Theodor.

So without further ado, I’m really happy to welcome Ben Lynch, and let’s get started with the show.

Ben, thank you so much for joining me. I feel like I know you already because we’ve been kind of collaborating in this space for so long, but this is actually the first time we’ve had a chance to talk, so I’m really happy to meet you virtually, at least, and I’m looking forward to our chat today.

Dr. Ben Lynch: Likewise, Chris. Yeah, it seems like old friends, as odd as that sounds. Yeah, definitely.

Chris Kresser: No, I feel the same way, and I look forward to someday meeting you in person! I’m sure our paths will cross at some event. I almost went to the functional medicine event where you met Dr. Schweig, my colleague, but at the last minute I had to pull out for some reason I don’t even remember now.

Dr. Ben Lynch: Right. No worries. Yeah, sometime.

Chris Kresser: OK. So we are going to talk about methylation, but thankfully for both of us, I think, we’re not going to do the typical methylation 101 or even necessarily 201 review here because this is something I’ve talked about and written about a lot, and the world certainly knows that you have covered that topic exhaustively. And so what I really want to do today is dive in a little bit deeper on the topic of methylation and specifically discuss the role that genetics and epigenetics and diet and lifestyle play, talk about some of the primary environmental influences that may affect methylation, go beyond MTHFR to talk about some of the other methylation-related genes, and then perhaps more than anything else, talk about what you’ve learned in the last few years of really taking a deep dive into this material and working with thousands of people and doing your conference and what you’re excited about and working on and looking forward to.

Dr. Ben Lynch: Perfect. Let’s do it.

Chris Kresser: Great. So here’s the kind of scenario that I’ve seen play out a lot—and I’m sure you have—that troubles me. A patient comes to me and they’ve done 23andMe and they’ve run their panel through MTHFR Support or something like that. Or maybe a couple of years ago there were these outfits where you could run your 23andMe results through them, and you’d get your genes back and then they would make supplement recommendations based on the genetic results. And then the patient would come in the office with two shopping bags full of supplements, many of which kind of counteracted each other because they had one mutation that suggested a particular supplement and another mutation that suggested a different supplement that would directly kind of counteract the effects of the first supplement.

So I want to talk a little bit about this idea that genes are really driving the entire picture with methylation and that it’s safe—or even a good idea—to supplement only on the basis of genetics. What’s your take on that? How’s that for a waist-high pitch kind of coming right down the middle?!

Dr. Ben Lynch: That’s right! Yeah, well, I think I’m going to swing and hit a homerun. I might hit a couple of people in the face.

Chris Kresser: All right! OK.

Dr. Ben Lynch: I’ll stay away from the swear words, too. It’s really funny to me that these companies are out there, thinking that it works. For one, you mentioned that their own reporting themselves will contradict the statement that they said just above it. “Well, you need to wear green. Well, actually you need to wear orange.”

Chris Kresser: Right.

Dr. Ben Lynch: It’s counterproductive, it’s a total supplement mill, it’s just to generate revenue, and unfortunately I’m blamed for this too because I own a supplement company, but I don’t mix my training and education at the same time because I know it doesn’t work. But there’s an absolute apparent conflict of interest here, and it’s a shame because people get so desperate, and rightfully so, because the medical field, in general, is failing a lot of people, so they become desperate and run these reports, and hopefully they find the missing picture, right? The magic bullet.

Chris Kresser: Yeah

Dr. Ben Lynch: And the magic bullet apparently doesn’t exist, and I don’t think it’ll ever exist. The magic bullet is labeled “hard work and effort.”

Chris Kresser: Mm-hmm.

Dr. Ben Lynch

Dr. Ben Lynch: But in short, I think that these reporting tools are very dangerous and literally so. For example, if you’re going to target a specific one gene—one gene out of 20-some-odd-thousand in your body—and let’s talk about magnesium for a second. You run this panel and it says you need magnesium, and you’re going to target this one specific gene—say, MAT or something—and this one gene requires it, and you think you can target that one gene with the magnesium, but there are about 400 other genes that work with that particular nutrient. And then you have another gene that says you actually can’t take methylcobalamin because you have COMT, but MTR demands that you have methylcobalamin, and then you become B12 deficient or… who knows what can happen. I think it’s a disaster, frankly.

Chris Kresser: Yeah. I couldn’t agree more. It’s a real mess, and I think unfortunately the advocates of that kind of approach have done people a real disservice and really set them back, I think, in a number of ways. For some reason, there’s always been an appeal to these approaches where you can get a test and it gives you some information and then it gives you, like, a perfect protocol based on that information. There was the blood type diet and many other approaches down the years, and I think you hit the nail on the head when you said that the reality is a lot messier and more difficult to work out. I can certainly understand the appeal of that kind of streamlined approach, and unfortunately, as we know as clinicians, it’s never that simple.

Dr. Ben Lynch: No, it’s not, and we want it that simple, right?

Chris Kresser: Mm-hmm.

Dr. Ben Lynch: We want the drive-thru medicine. We want it as simple as we can because as human beings we are trying to survive and you can survive by doing the least amount of effort because conserving your energy is what we want to do, because as you spend energy, you need more energy. Then you need to go out and find more food and more shelter.

Chris Kresser: Yeah.

Dr. Ben Lynch: So if you can sit there and you can read a report that says do this and that, then you conserve your energy, so I think by default we’re programmed to do the simplest thing to conserve energy, and I think it’s just inbred in us.

Chris Kresser: Right.

Dr. Ben Lynch: And I just think that people need to understand it doesn’t work that way. Genetics is a very powerful and amazing tool, but it’s just that—it’s a tool. I did landscape construction years and years ago while I was still in undergrad school at UW, and I had a lot of tools. I had saws, I had hammers, I had nails, I had dumptrucks, I had shovels—you know, it’s just another tool. Just like in medicine, you have a variety of tools. You can’t just bank on one thing.

Chris Kresser: Well, on that note, let’s help people put this into context. When we see mutations that could affect the methylation cycle, let’s say, how do you explain it to your patients? One of the things I like to say is the mutation of a gene doesn’t necessarily guarantee dysregulation of that gene. In other words, mutation doesn’t mean that you absolutely will have a dysfunctional gene. It means it’s more likely to dysfunction. I’m curious to hear how you explain it to your patients. And I know the answer to this varies depending on the mutation, but if we think about genes and epigenetics and environmental influence, what would the relative contribution be to disease burden of each of those factors, in your mind, kind of as a rough breakdown?

Dr. Ben Lynch: Well, just to keep it very simple and overreaching and broad, the statement of if you identify a certain genetic polymorphism, we’ll simplify that to say it’s a mutation. It’s not technically correct, but we’ll just say that you find that you do have a genetic mutation, like MTHFR, and you’re like, “Oh, crap,” but the reality is it may or may not be causing a problem.

Now, the flipside is you get a genetic test back and it shows that you do not have a particular genetic mutation and you’re all excited, but you could definitely be having a problem in that same gene. Just because there’s no genetic polymorphism doesn’t mean you’re in the clear, and I say that all the time, exhaustively.

Chris Kresser: Yeah.

Dr. Ben Lynch: It’s basically the degree of work that a particular enzyme has to do. Genes will make enzymes, right? That’s what they do. And as a certain thing comes into their system, that gene is triggered to make more enzymes so it can do more work. So as your body requires more work for various reasons—say, you’re more stressed or you’re not sleeping or you’re eating like crap, or you’re flying an airplane and you’re stressed out from that, or you’re giving a presentation, or you’re listening to this podcast, burning through neurotransmitters—there are certain things that your genes have to do, and so they have to do work in order to produce more dopamine so you can stay attentive. But when you’re sleeping, your genes don’t have to make more dopamine, so it’s a work-related thing. If you’re drinking a lot of alcohol, then your MTHFR enzyme and your aldehyde dehydrogenase enzymes and other enzymes will have to do more work. A lot of Asians have a very high prevalence of this enzyme, which breaks down acetaldehyde, which slows it down, and so they get this alcohol flush, right? They get red in the face. But if they don’t drink the alcohol or they drink very little, they’ll probably be OK.

Chris Kresser: Mm-hmm.

Dr. Ben Lynch: So I look at genetic polymorphisms as a degree of how much you overburden the system, and the more work that you create for that said gene, then you have to support it more. And a genetic polymorphism may affect it or it may not.

Chris Kresser: Right, so we’re talking about predispositions here, it sounds like—more a question of, you know, someone who has a polymorphism in a particular gene may be predisposed to that gene functioning less optimally, especially when you add a number of environmental challenges that we’re facing today, like poor diet, heavy metal toxicity, dysbiosis, disrupted gut microbiome, air pollution both indoor and outdoor, nutrient imbalances, a relative excess of copper and deficiency of zinc, etc., etc., etc.—in a nutshell, the modern lifestyle, right?

Dr. Ben Lynch: Yeah. Let’s pick a simple gene to go with. We’ll talk about MTHFR because it’s the golden child on the block for some reason.

Chris Kresser: Right.

Dr. Ben Lynch: Say, you identify that you have this MTHFR gene problem, and you go to the internet and you read about, and you’re like, “Oh, crap. I have this.” I have it. I went, “Oh, crap,” when I read about it. I have one copy of 677 and one copy of 1298, personally, and so do a couple of my kids, and I was really concerned about it, and then I started learning that, well, you can actually get the same nutrient that the MTHFR enzyme produces itself by eating leafy greens.

Chris Kresser: Right.

Dr. Ben Lynch: So if you’re eating a bunch of leafy greens, then that MTHFR enzyme isn’t really doing too much of a problem for you, and if you’re not drinking that much alcohol, then you don’t really have that much of a burden either, along with other things. So if you feel great and you find that you have a genetic polymorphism in a certain pathway, it’s just something to be aware of and be conscious about. I can look back on my lifestyle when I was in college. I would drink and I was also a collegiate athlete in rowing, so my methylation demand while exercising also goes up, so I couldn’t tolerate alcohol at all. And I looked at the gene and its function, and I was like, “Oh. Well, this kind of makes sense.”

Anyway, that’s one thing that you can do. You identify the function of that gene, and you learn how you can reduce the impact of burden on it through the environment, lifestyle, diet, mindset, and also what you can do nutritionally as well.

Chris Kresser: Mm-hmm. One of the things I’m really interested in right now is the effect of environmental influences on methylation above and beyond diet, which, of course, we talk about a lot and, of course, is important, so I don’t want to diminish the importance of that, but many of my patients and probably people that you work with are already somewhat savvy with diet and are certainly far beyond most Americans in terms of how conscious they are with food and how well they eat, and yet they’re still having issues with methylation. So what are some of the bigger non-dietary environmental influences, things like heavy metals or gut issues, that you think are contributing to methylation problems in the patient population?

Dr. Ben Lynch: Well, you hit two of them right on the head. You brought up heavy metals, and that’s a big one. That’s very pervasive in the environment. In our water we’re getting heavy metals. We’re getting arsenic in our drinking water. We’re getting arsenic in rice. We’re getting it in our green drinks that we think are healthy for us, and we’re putting massive amounts of kelp and chlorella in there, and at the same time, we’re loading up arsenic levels. RIce milk as well, and certain protein powders. Heavy metals. And then you have mercury from fish and the environment. Seattle’s in the environment where a lot of the mercury from China coal powerplants drops from the sky right onto me, right on my head.

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Chris Kresser: Right.

Dr. Ben Lynch: And you’re thinking, “Well, where is this mercury coming from?” Well, it’s coming from the environment.

Chris Kresser: Mm-hmm. Dental amalgams, which a lot of people in our generation have and still have in their mouth.

Dr. Ben Lynch: Yeah, and then they learn about the mercury dental amalgams, and then they go remove them, but they don’t remove them appropriately.

Chris Kresser: Right.

Dr. Ben Lynch: Or then they go and they learn that mercury is something to consider, and then they go and they get IV chelation of mercury, and then they realize that they’re sicker than they started.

Chris Kresser: Yeah, from the frying pan to the fire.

Dr. Ben Lynch: Yeah. So from a nutshell, I would say the key things which affect methylation from an environmental standpoint would be heavy metals, it would be the gut absolutely. I mean, the microbiome. There are one hundred of them to one of us, right?

Chris Kresser: Right.

Dr. Ben Lynch: So the acetaldehyde yeast overgrowth, and there are other compounds that they’re making: hydrogen sulfide, methane gases, and who knows what else that we have yet to discover definitely affecting it.

And then you have pathogens becoming very, very strong these days from superbugs that are becoming more and more prevalent and harder and harder to kill, especially when the standard medicine doesn’t even do culture and sensitivity anymore.

Chris Kresser: Right.

Dr. Ben Lynch: It’s like you have an ear infection and they give you an antibiotic. It has nothing to do with bacteria!

Chris Kresser: Mm-hmm.

Dr. Ben Lynch: So pathogens are a big one, and I think they’re under-evaluated.

Another one is mindset. Mindset is very important, and Bruce LIpton talks about this a lot. Your perception of the external environment really influences the internal environment. If you’re walking down a sidewalk and you have a sense of fear, then that sense of fear is going to do a lot of triggering of various pathways in your body, including stress, and stress speeds up your methylation, and at the same time while doing so, it uses up the nutrients involved in that same pathway. That’s a really important one.

Yeast overgrowth is another one.

Chris Kresser: Sure. I think sleep loss would probably be in there, too. As you know, I think, some organization, maybe the World Health Organization—I can’t remember—has classified chronic sleep loss as a carcinogen. I have to wonder if methylation isn’t one of the mechanisms that mediates that relationship.

Dr. Ben Lynch: Yeah, that’s a great point. Good for them for labeling that. That’s interesting and about time, actually. Mike Mutzel of High Intensity Health talks a lot about the clock genes and our relation to our sleep cycle and reading on our e-readers at night before bed or sleeping with TVs on or sleeping with wifi and 4G on. All these things are affecting us to a significant degree, which we try to ignore because they’re convenient.

Chris Kresser: Yeah, absolutely. There’s plenty of research, too, now, which I’m sure you’ve seen, linking use of tablets and iPads and other devices that emit blue light before bed to delayed sleep onset and poor sleep maintenance and a whole bunch of other physiological changes that you’d expect when you screw with your circadian rhythm.

Dr. Ben Lynch: Well, yeah, and then you have poor performance the next day. I actually presented at my last conference on this very subject. I presented a few studies which made it irrefutable. It’s real. So after reading about this and me working until 2 or 3 in the morning—

Chris Kresser: Yeah, right!

Dr. Ben Lynch: —it was like, “You know? I better stop this.” So now I’m way more productive because I’m going to bed at 10:30. You think that you’re wasting time by going to bed early, but you’re so much more efficient when you wake up and you’re cognitively present instead of having that daze of stupor where your wheels are turning in your brain but they’re just not quite smoothly running. Sleep is a huge one.

Chris Kresser: It’s a huge one, I agree. This really interesting study just came out about caffeine and how—not surprisingly—if you drink caffeine in the evening, it will mess up your sleep. It was one of those studies that was like, did we really need to do that study? Did somebody pay for that study? C’mon! But one of the interesting things that I read in the reporting on the study is that 90 percent of people consume caffeine in the afternoon between 12 and 6 p.m., and 69 percent of people consume caffeine between 6 p.m. and 12 a.m. It’s no wonder we have a sleep epidemic!

Dr. Ben Lynch: Right, and then what do they do? They go to their doctor and say, “Doc, I can’t sleep.”

Chris Kresser: Yeah, sleeping pills. One foot on the accelerator and the other one on the break.

Dr. Ben Lynch: Yeah, and then they take the sleep med and then they wake up in the morning with the alarm and they can’t get out of bed, so then what do they do?

Chris Kresser: Yeah.

Dr. Ben Lynch: They turn to more caffeine or more stimulants. You stimulate to wake up because you’re so depressed from your sedatives in the evening, and then you can’t get off.

Chris Kresser: Yeah. It’s a mess. Sleep is something I never stop talking about, but it seems to be one of the most difficult changes for people to make. And like you said yourself, it’s not like I’m perfect and this is always easy for me, because I’m super passionate about what I do and it always does seem like there aren’t enough hours in the day, but I’ve had the same experience that you’ve had, Ben. I’ve learned the hard way so many times now that if I try to save time by sleeping less, it’s not a timesaver at all, and it actually just completely destroys my productivity and the quality of my work and the quality of my life, more importantly, and my relationships with people around me. Sleep is just non-negotiable at this point.

Dr. Ben Lynch: It is. I got in a, I would say, a tussle with my younger boys last night because it’s Veterans Day today—congratulations and thank you, veterans—but my 7-year-old and 10-year-old, it was 9:30 at night, and I was like, “Boys, you have to go to bed. What are you doing?” And they said, “Well, Dad, it’s a day off tomorrow,” and I said, “I don’t care.”

Chris Kresser: Yeah.

Dr. Ben Lynch: I said, ”You have to go to bed. You have to maintain your schedule. You have to get some sleep.” “Well, what about my older brother, Tasman?” I said, “Well, he’s going to bed, too.” And they said, “Well, what about you?” I said, “Well, I’ll be going to bed at 10:30.”

Chris Kresser: Yeah.

Dr. Ben Lynch: They’re always looking for ways to avoid it, and you just have to do it. Sometimes that Love and Logic course—you ever heard of that?

Chris Kresser: Uh-uh.

Dr. Ben Lynch: It’s a great course for us parents. Basically, in that situation, instead of fighting my kids about going to bed on time, what Love and Logic would say is, “OK, look. It’s 9:30. You should be going to bed. So either you go to bed and you wake up rested the next morning, or you wake up really tired and you might miss school because I’m not going to wake you up.”

Chris Kresser: Right.

Dr. Ben Lynch: And then they miss school and they get all frustrated, and you say, “Well, that’s the consequence.” And then the next day, they’re probably going to go to bed on time by themselves.

Chris Kresser: Yeah. We hope.

Dr. Ben Lynch: We hope!

Chris Kresser: All right. Well, not everybody, but most people listening to this show by now have heard of MTHFR and they know what it is, and they know even a little bit about the role that it plays in methylation, but let’s talk about some of the other bigger players, genes in the methylation cycle that can have a significant effect. Maybe just pick a couple that you think people should also have their radar above and beyond MTHFR.

Dr. Ben Lynch: Oh, man. There are a few of them, and before I do that, let me back up and say one thing. A lot of people are getting these SNP reports. They order their 23andMe, and they go to these reporting tool companies, and they get 40-some pages of genes that show they’re green for “good” and yellow for “be careful” and red for “oh, my God,” right?

Chris Kresser: Right.

Dr. Ben Lynch: You’re getting these reports, and there are hundreds and hundreds, maybe even thousands of genes on these reports, and you start wondering what’s going on. The bottom line is I have a research team of four people full time that I’ve hired and they continue working with me, and what we do is we evaluate the clinical significance of these genes. We’ve gone through hundreds and hundreds of them, and there are only 20 that have made the cut so far.

Chris Kresser: Mm-hmm.

Dr. Ben Lynch: Twenty.

Chris Kresser: Yep.

Dr. Ben Lynch: I will say that first. And I will say that a big one that is related to methylation—and before I do that, I want to say that the majority of methylation that occurs in our bodies is typically done at certain ages, and one is when you’re a child. You’re methylation is in high demand when you’re a kid, it’s in high demand when you’re ill and quite sick because of cell repair, and then it’s also in very high demand during pregnancy. These are the three main times your methylation is really humming along and should be supported.

Now, Chris, I don’t know your age and it doesn’t matter. I’m going on 42.

Chris Kresser: I’m 40—

Dr. Ben Lynch: You youngster.

Chris Kresser: —one.

Dr. Ben Lynch: There it is!

Chris Kresser: I’m already forgetting! Look out!

Dr. Ben Lynch: I’m 42 in January, so, yeah, you and I are both 41. Anyhow, our methylation, if we’re not over-exercising and we’re just going generally along, it shouldn’t be kicking in that high a speed.

Anyway, certain genes—I always have to have little disclaimers before I say things—a couple of genes that I want to really emphasize the importance of use the most methylation in the body. Eighty-five percent of all methylation reactions occur in the liver, and the liver is also using the most oxygen in the body at rest. The liver uses about 27 percent of the body’s oxygen at rest—that’s more than the brain—so our liver is a very, very important organ. If you see liver enzymes elevated, it’s a big problem. Now, to go back to the genes, if 85 percent of our methylation reactions occur in the liver, then my question is, which two genes use the most methylation? And the genes that use the most methylation are ones that make creatine and phosphatidylcholine. Creatine is for muscle mass—and creatine does other things, too—and then the phosphatidylcholine is for all your cell membranes and also your gallbladder for your bile flow. So if you have genetic polymorphisms in GAMT, which stands for guanidinoacetate methyltransferase—I love that!

Chris Kresser: Flows right off the tongue!

Dr. Ben Lynch: Yeah. Guanido! I think I said that probably a hundred times that day! But GAMT is very important, especially in children with speech delay. This is a known genetic polymorphism that is underrecognized for children who have speech delay or who are being born underweight and their muscle tone isn’t very good. So if you have a lifelong history of not really being toned or having difficulty gaining muscle, you had speech delay as a kid or your child does have speech delay, looking at creatine or creatinine on your lab might be useful, but also looking at the genetic polymorphism for GAMT, and if it’s present, then supplementing with creatine is very useful. Eating more meat is useful. That’s basically a really important gene to look at.

The other one is PEMT, and PEMT stands for—not so easy—phosphatidylethanolamine methyltransferase, and this is a pretty common genetic polymorphism in the population, which limits your ability to make phosphatidylcholine. If that’s the problem, then your cell membranes are more at a disadvantage and they’re going to be not very healthy. A key point to tell people how important the cell membrane is—imagine a cell and you have a cell without a nucleus and then you have another cell without a membrane. Which cell is going to survive? Do you have an idea? The cell without the membrane dies.

Chris Kresser: Yeah.

Dr. Ben Lynch: The cell without the nucleus will survive as long as the membrane is intact. That is how important the membrane is. So if you have a PEMT genetic polymorphism and you are not supporting your diet with appropriate fatty acids or you’re eating fast foods and you’re destroying your cell membranes for various reasons, then that’s a problem. So supplementing with phosphatidylcholine, eating eggs, eating more healthfully, balancing your fatty acids, looking at red blood cell fatty acids, working with a good doc, and so on is really important.

So those are two key genes for me.

Chris Kresser: The way I talk about that with my patients is “leaky cell.”

Dr. Ben Lynch: Yes.

Chris Kresser: We’ve already talked about leaky gut and leaky brain, and I’ve been talking about leaky skin more and more, and now we have leaky cell also, and that’s PEMT and the importance of phosphatidylcholine, which a lot of patients seem to respond really well to.

Dr. Ben Lynch: Amazingly, yeah. And then gallstones and bile issues. If you look at pregnancy, a lot of pregnant women have issues with their livers, right? They get a little bile stagnation, and they complain about it. It’s a big problem, so the standard medicine, what they do is they prescribe cholestyramine, which is actually a folate antagonist, which is kind of a problem during pregnancy.

Chris Kresser: Mm-hmm.

Dr. Ben Lynch: What the real problem is during pregnancy is they’re low and they’re using so much methylation for the developing baby that now their ability to have adequate bile flow goes down because bile flow is really regulated by the ratio of phosphatidylcholine to cholesterol and other fatty acids. If your ratio of phosphatidylcholine to other bile components is less than 10:1, you’re going to start getting more susceptible to gallstones and having issues. Gallstones, just in general, is a booming problem.

Chris Kresser: Oh, yeah.

Dr. Ben Lynch: And then you look at SIBO, and SIBO is a huge problem—we can use the pun of a blooming problem—and part of that, I think, is a metabolic disorder because the bile isn’t flowing. Have you seen that study, Chris, where they ligated the bile duct?

Chris Kresser: Yeah.

Dr. Ben Lynch: And then the rats got SIBO, and then they made the tube free for moving bile, and then the SIBO went away?

Chris Kresser: Yeah, I did see that.

Dr. Ben Lynch: That’s another significance for PEMT and phosphatidylcholine.

Chris Kresser: Yeah. Great point.

So tell me, Ben, what you’re really working now, what you’re exploring. You mentioned you have four research assistants. I thought that I was pretty nerdy having two, but now you’ve beaten me! You have twice the number of research assistants I have!

Dr. Ben Lynch: That’s what it’s all about, Chris, that I have more than you.

Chris Kresser: No, you have to have research! That’s what it’s all about, though.

Dr. Ben Lynch: That’s right.

Chris Kresser: It’s so great that you’re doing that because there’s so much stuff out there that’s just completely unmoored from any evidence at all. The current scientific paradigm can’t answer all the questions we have, but I just find that it’s a really helpful resource in an environment where there are so many recommendations being made by so many different people and so many different venues. It’s one way of just really separating the wheat from the chaff.

Dr. Ben Lynch: Right.

Chris Kresser: So it’s actually great to hear that you have so much support in that department, because as we both know, that’s a full-time job.

Dr. Ben Lynch: Yeah, and it’s the job which I don’t consider a job. It’s what I absolutely love doing.

Chris Kresser: Yeah.

Dr. Ben Lynch: That’s what wakes me up in the morning besides my family. It’s wonderful to be able to find key things in the research that’s been already published—

Chris Kresser: Right.

Dr. Ben Lynch: —but nobody’s connecting the dots!

Chris Kresser: Yeah. It’s a little bit like mining.

Dr. Ben Lynch: It is.

Chris Kresser: There’s all this precious stuff that’s just waiting to be found. It does feel a little bit like that to me, too. So on that note, what are you looking at right now, and what are you going to be exploring in the next year? What are you interested in and passionate about at the moment?

Dr. Ben Lynch: I’m passionate about the fundamentals. I’m passionate about emphasizing the importance of your day-to-day, minute-to-minute decisions that are affecting your overall health and what people can do in order to maintain and optimize their health, genetics aside. That, to me, is extremely important because there’s so much fear and there’s so much other misinformation going on that if you can really teach the fundamentals of lifestyle, diet, mindset, and the environment, then you can do a lot of good that way. But doing it in a way that is accepted throughout all health professions is the trick.

So basically one thing that I’m working on right now is—well, before I say that, no matter what research I look at and no matter what dots I connect, Steve Jobs has a quote of, creativity is simply connecting the dots, simply connecting things, something along those lines, that’s what creativity is about. I love being creative, I love connecting things, just like you talked about, but I look for what we can do to make the biggest impact across all patient populations worldwide, and my true passion is to optimize the lives of unborn children. That’s my true passion. But in order to do that, you have to optimize the lives of future parents, right?

Chris Kresser: Right.

Dr. Ben Lynch: You cannot have optimal unborn children if you have suboptimal future parents. It doesn’t work. That means you need to teach parents how to be healthy. You have your pregnancy course, which is awesome.

Chris Kresser: Mm-hmm.

Dr. Ben Lynch: And what I am doing now with my research team—one of them, specifically—is looking at common conditions, such as gallstones, which is super prevalent, and looking at all the reasons why they’re there and creating algorithms and a multidimensional view—not single dimensions, but a multidimensional view—of why they’re there, how they got there, and how to reverse them and how to prevent them from coming back. And it’s like, “Why would you pick that?!” I pick that because the research gentleman that I work with, he’s a double masters and single PhD, he’s in India, he has published quite a few papers, and he’s linked quite a few pathways towards ALS. I read his paper, and I was super excited. I emailed him. I said, “Man, you’re spot on with ALS and the various mechanisms by which it’s being caused, instead of looking for multidimension, single-gene outcome.”

Chris Kresser: Right.

Dr. Ben Lynch: And so I emailed him and I said, “You have to join my team,” and he did. So what he and I sat down and determined to do was to focus on liver dysfunction because if you have liver dysfunction, then all systems are going to be affected. Neurological, immunological, digestive—it doesn’t matter. Gastrointestinal, obviously. And then as it progresses, it’s going to get more and more and more severe. You’re going to get elevated ammonia. You’re going to get methylation dysfunction. It’s just going to bloom from there. So what we want to do is we want to focus on the liver first and blossom out how to teach doctors how to really isolate and repair that area because it’s not being done. It’s not being done at all.

And then at the same time, developing clinically relevant genetic polymorphisms across the board—not just methylation, but across the board—which are affecting patients. And I emphasize the term “clinically relevant” because 100 percent of the tools that are out there now are bad, in my opinion.

Chris Kresser: Yeah. It seems like they may cause more confusion and worry, which is, of course, as we’ve been talking about through the whole show, could actually be a much bigger problem than the polymorphisms themselves.

Dr. Ben Lynch: It affects mindset, it increases stress, and then everything else goes. Mindset is so important, and you’re not going to have an appropriate mindset if all other systems are failing.

Chris Kresser: Yeah. I’m really happy to hear you say that about the liver. That’s interesting. I didn’t know you were focusing so much there, and I totally agree. The brain, the liver—it’s hard to say which organ is more important than the others because they all fulfill crucial roles that we couldn’t live without, but the liver is very high on the list, and yet it’s not one that has typically been focused on. There’s a lot of research and investigation and interest in cardiovascular health and brain health, but the liver is kind of like the poor stepchild. Of course, there are a lot of studies on liver disease and non-alcoholic fatty liver disease and full-on disease states like that, but there’s very, very little in the scientific literature about functional liver problems.

Dr. Ben Lynch: Yeah, absolutely, and they fail to see the obvious. They fail to look at what importance liver is doing. I did a presentation on cancer, and while I was preparing for this talk, one, I was nervous. I was like, “God, this is a huge topic,” and I’m sitting there trying to research, and I’m trying to solve all the world’s cancer problems—a little weight on my shoulders!—and I realize it was really stupid, but that’s what we try to do, right? And cancer is an absolute metabolic problem. I mean, yes, there’s genetics involved, but metabolically it’s definitely related, and paper after paper after paper talked about a shift from aerobic to anaerobic lactate metabolism becoming the initial trigger for carcinogenesis. I looked at that, and I said, “God, if there’s a metabolic shift here and there’s lactate metabolism increasing, then we have to look at all these cycles,” so the mitochondria are obviously important, but the liver is really key in this area as well. So I just think at this point I’m focusing on the liver because it’s easy, it’s recognizable for the doctors, and we can make a big headway.

Chris Kresser: And nearly every environmental influence that affects our health, that effect is mediated at least in part—and sometimes in very large part—by the liver.

Dr. Ben Lynch: That’s right.

Chris Kresser: We talk about heavy metal toxicity, we talk about the effects of dietary antigens that cause problems, we talk about disruptions in the gastrointestinal system, which, of course, involves the liver and the gallbladder—virtually all of these environmental influences that we discuss are mediated in part by the liver, so I look forward to seeing the results of that work.

It’s really been great to talk to you, Ben. I’ve been looking forward to it, and I look forward to more collaboration in the future.

Dr. Ben Lynch: Sounds good. I appreciate that, Chris, and I look forward to seeing what you’re coming out with as well.

Chris Kresser: All right. Take care.

Dr. Ben Lynch: You, too.

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Join the conversation

  1. Chris, I thought you cut off Ben just as he was about to expand upon his liver research. That was a great pity. Nonetheless a good interview.

  2. I have two heterozygous methylation mutations. I eat green leafy vegetables like crazy and my homocysteine level was way too high. It wasn’t until I started taking L-methylfolate in a bioavailable form that the numbers came down. Should I not be worried about my homocysteine levels? This is a real question, not a rhetorical one. Thanks.

    • Louise… Can I ask what type of Lmethylfolate you were taking? And how much?…. I was prescribed the Deplin 7.5 because my dr was worried about the quality standards of supplements. I cut It in quarters just to be safe. I just ordered a supplement (b complex called methyl guard plus) though and am gonna try it Instead or add it to the 1/4 of Deplin. I had another dr mention another script called Enlyte. And I read about another online called Mantnx…. I believe it was called.

      • Apryl,
        I was taking Deplin 7.5 but my insurance stopped paying for it. Now I’m taking a 5 mg. tablet from Methyl-Life (the folate is bound to calcium) that doesn’t require a prescription. My doc is an osteopath with a background in orthomolecular medicine. Her feeling is that even though my folate blood level is way up now, high homocysteine was more of a problem.

  3. I am a real newbie to methylation and Dr. Lynch’s amazing and overwhelming (to me) knowledge/work. As well as Chris Kresser’s. I’ve just recently ordered a 23andme kit because I’m very interested in learning about my genetic makeup. However, I have a particular question about something that’s really confusing me right now…..
    From my own online research I’ve done so far, ( which seems like a ton to my tired brain, but is really only a tiny tiny drop in an ocean 😀 ), I’ve read that some people are undermethylators and some are overmethylators (though apparently the majority are under). Where I’m confused is I’ve read that you can have the MTHFR gene mutation and also could be either an under or over methylator. Well, I’ve come across a couple articles where a Dr. Walsh (*I think his name is) and another apparently popular doctor on the subject of under and overmethylation (whose name escapes me right now), says that if you are an undermethylator- no matter what, even if you have the MTHFR gene mutation, you do not take ANY form of folate, period. And you are to avoid foods with too much folate when possible. That sort of stumps and surprises me. I don’t know if I’m an undermethylator, (haven’t gotten proper testing to see yet), but I suspect I am because I have a whole lot of listed traits of one. So this is why I’m curious. What if I have the MTHFR gene mutation, but am an undermethylator? Am I really supposed to avoid all forms of folate? Isn’t folate important, at least to some degree, for everyone with or without a MTFHR gene mutation? From the few articles I’ve read so far written by Dr. Lynch, seems to me he doesn’t really share the same views.
    Anyway, Ive rambled enough. I would love to hear from anyone and their knowledge about this please? 🙂

  4. Hi Chris, can Ben please share more insights into the 20 clinically relevant genes? Has he published this research somewhere? Thanks for a highly insightful and valuable podcast!

    • I was thinking the same thing about those 20 genes. Thank you.

      This was a great, great podcast. Love both your work. Thank you for informing us. Keep up the good work, Chris and Ben!

    • Hi Mike, love your work and follow all your posts. Have you found research to support ox bile use for bile and PEMT issues? Thanks!

  5. I read this whole interview and did not learn one thing from it. I thought I would learn how to help snps with foods and or supplements. I’m so sorry I wasted my time reading all of this and learning nothing as usual.

    • It’s free girlfriend, relax. Information is what you make of it. Perhaps, Dr. Lynch or other practitioners have books or resourceful websites on these very issues. Being sick is horrible. I am dealing with my own health torture but why get upset with those making strides that otherwise would never occur? -Best wishes

    • Rebecca, both of these compassionate men kindly provide endless amounts of free, important health information to us. We have to be respectful and appreciative of their public service.
      Google Ben Lynch and/or go to MTHFR.net to find the detailed protocols you are looking for. I have learned so much from both of these men. Just knowing not to take synthetic folic acid is the most important thing I learned from Ben Lynch.

  6. From a TCM perspective of the liver’s functions, this is really interesting. My lecturers and teachers have told me that so many of the patients they see (and that I will see) present with ‘liver qi stagnation’ (this is often the result of improper diet, emotions, overwork, stress, etc). From my understanding, a lot of liver qi stagnation symptoms correspond to methylation issues.

  7. Interesting discussion, connects to an article I read recently, you might be interested: I think it an extremely important piece of research with far-reaching effects and would be very interested to hear your thoughts on the matter.
    “Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation”
    “This is the first demonstration of an association of pre-conception parental trauma with epigenetic alterations that is evident in both exposed parent and offspring, providing potential insight into how severe psychophysiological trauma can have intergenerational effects.”

  8. Hi Chris-
    I would so love to have your help.
    How do we get better after we have been poisoned from an anti malaria prescription?
    In May of 2014 I was prescribed an anti malaria pill for a month for a mission trip to W. Africa.
    Less than 24 hours after coming home I completely crashed-
    I had many blood test done and everything came back normal.
    After researching for 9 months I got tested for MTHFR and found out I have 1 copy of a1298c and many others.
    In my research I found where Dr. Lynch advises not to take proguanil-(the one I was given ) if we have MTHFR. I feel like my body is toxic and I feel desperate for relief.
    Please help me it’s been 19 months of hell… If anyone has been through this and gotten better please reach out to me.. Thank you!?

  9. the comment about people removing their mercury amalgam fillings interests me. What do they replace them with? Its my understanding that by far and away the most commonly used material for white fillings, contains BPA. According to my dentist, mercury is relatively stable IF left alone – but BPA is not – definitely a case of “out of the frying pan and into the fire” wouldn’t you say? A good example of a knee jerk reaction to a valid health concern, but perhaps not a well thought out one. Those of us with a mouth full of mercury, but not the wealth to remove it, just have to read these scares and worry – or not. I choose not to worry about something I cannot fix.

    • Hi Dale,

      My own fabulous naturopath told me that amalgam fillings that are at least 15 years old should be left alone unless the tooth is injured in some fashion and the filling is broken. She quoted Walter Crinnion, ND and said she got this information from him. Hope this helps. Never get an amalgam removed by anyone but a biological dentist who uses the correct removal protocol. Conventional dentist do not know how to remove them and place you and them at risk. I also just learned that conventional dental offices can be toxic if the fumes are not removed properly. Best in health! A great book is Whole-Body Dentistry by Dr. Marc Breiner, DDS.

      • I heard recently that what they replace BPA with (BPS I think it may have been) is as bad or possibly worse……..sigh.

    • My natureopath replaced hers with ceramic fillings. I had 13 amalgams removed as they were NOT stable. I was at deaths door. Grey in colour and had metallic taste in my mouth after eating or drinking. My migraines were killers lasting 3 days on each side of my head. Vomiting for at least 2 days of that. Could not eat or even drink water during those 2 days. I had the amalgams removed by proper method of using a rubber dam in mouth to prevent fumes from going down into the lungs. Google Dr Eric Davis dental for excellent info. Had some immediate improvement on my health but other symptoms are taking longer and of course there is some permanent damage. Good luck with your health.

  10. So insightful. I am PEMT ++ and have bile issues, and very high ammonia levels making it difficult to treat Lyme disease. Where would I find information to help support this gene issue more? Is taking the phosphatiydal choline/ diet recommendation all that is needed to address this or does this mean I’m going to have a difficulty getting out of the metabolic disorder I’m dealing with? And how do you feel about coffee enemas to keep liver clean/gall bladder clean?

  11. Dr Lynch made a mistake, which should be corrected Chris, it’s 10 bacterial cells for every human cell, and not 100 bacterial organisms per human cell.

    • I’ve linked a podcast on my name that I’ve done with Dr. Albert Mensah.. An expert on methylation.

      The whole thing is overblown he says. I’ve personally seen that many of my clients have genetic defects, but it does not change much in terms of their adrenal protocols and getting them better, things that like. It’s a valid issue, but overhyped for sure.

      Check out that episode for Dr. Mensah’s takeaways.

      • Eat leafy greens, unless u have sulfur metabolism issues. (CBS/SUOX) mutations. Which is a significant percentage of people.
        There isn’t an easy answer for everybody.

      • I have been wondering the same thing… Like there are just so many factors involved. Even though since I started eating more greens and taking Lmethylfolate I have felt a significant increase in mood and energy. But I do find it ironic that he said statement in such such a “matter of fact” way, and then devotes a whole webpage and supplement line to dealing with MTHFR mutations.

  12. Can you be more specific on the GAMT and PEMT snps that can be a problem, the rs would be useful since the MTHFRSupport Variant Report I have from several years ago lists 2 GAMT and 3 PEMT. For PEMT support do you have any other recommendations besides eggs and phosphatidylcholine? Thanks.

  13. Really good information. Based on the SIBO comments, it seems there might be too a little much emphasis being placed on reducing bacterial overgrowth itself in the current model if bile flow is possibly the critical factor?

    • Hi there Scott,

      I think Ben’s main point here, which is substantiated by ample research, is that bile salts are are key component to keeping gut ecology in check. Bile acids not only fat emulsifiers, they’re antimicrobial as well.


  14. Great conversation, and such valuable insights: not only about the two areas of snp’s that Lynch discussed, but your collective insights about all the environmental influences that interweave to determine our health.

    I’m glad you’re focusing on the health of new parents, and note that it’s your age group! I am focusing more on the health of people passing the age of 40 or 50 — who have had enough conventional medicine to be disillusioned, but whose doctors don’t have a clue about how to manage routine complaints of aging with lifestyle interventions.

    would love to talk with you about that sometime!

    Thanks for your great work,

    Deborah Gordon

  15. HELLO! I have a very important question that I can not find any clear clarification on anywhere. Do individuals that have a mutated MTHFR gene ALSO have a limited ability to convert naturally occurring folate from food???
    I’m asking because I’m wondering if the ultimately the MTHFR mutation is only relevant because of the mass addition of synthetic folic acid to the food supply. As I understand it, the different types of “folates” competes for access the channel and the and the synthetic stuff builds up due to poor conversion and blocks it not allowing the natural folate to get it. So the synthetic stuff should be avoided. BUT what I’m not understand is whether or not the MTHFR is also hindering the ability to use naturally occurimg folate as well…. hence the need to supplement. I understand that dietary folate is good and should not be avoided. But will I actually be able to eat enough?? Hope I’m making sense. I have the compound version. Otherwise if this isn’t the case then is would appear that the MTHFR mutation is irrelevant and this is ultimately a government made problem.

    • I would like to ask the same question. I have the MTHFR mutation and my Red Cell Folate is 4 times the max listed on the blood test. I already eat a lot of greens. Does eating greens contribute to the problem or the solution..?

      • Marie…. My understanding is that the synthetic version of folic acid builds up into your system and checking your folic acid levels would show it is abnormally high. How long does it stay like that once you’ve obstained from the synthetic stuff??? I don’t know. That’s another question I have.

        • Marie… And the real folate you eat from foods (even thought poorly converted also, according to other commenter not this thread) won’t build up to ridiculous levels and be recycled out of your body. Again… This is my understanding so far.

        • I have the very same question about how long the synthetic Folic Acid stays in the blood and how to get rid of it. On another site a poster named Michael wrote quite a bit about folic acid being pteroyl-l-glutamate and sugar from fruit breaks this down. There was a pretty good discussion about this on the site MTHFR Living.

    • In answer to your question, YES, you have a limited ability to convert naturally occurring folate from food into methlyfolate if your have MTHFR issues. Consequently, obtaining your folate from pre methylated sources becomes critical (MTHFR converts folate into the methylated i.e active form). Eating the already active form effectively bypasses the issue of not being able to manufacture the active form yourself.