What Influences Methylation? An Interview with Dr. Ben Lynch

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 LynchDr. 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.

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.

  1. Great episode, it’s interesting that, at rest, more oxygen (27%) is used in the liver than the brain!

    But I find it confusing that if methylation works by down regulating or turning off genes (and enzymes) then isn’t odd that that children would need more genes turned off (i.e. higher folate and methylation requirements) than adults.

    Also, if most methylation occurs in the liver, then why would elevated liver enzymes be a problem?

  2. I am curious to know your thoughts on high usage of essential oils since the detoxification process deals with the liver and issues with methlyation. Should people with the MTHFR gene be wary about overuse of essential oils in high concentrations?

  3. Thank you so much for this interview! One piece of information in it turned everything around for me.

    I’ve been struggling with digestive troubles for decades. Endless indigestion, being bloated, acid reflux, slow stomach emptying, constipation, pain etc.

    I went gluten and dairy free 3 years ago. That didn’t change anything. In fact I think it made me worse.

    Since then I’ve treated SIBO twice with the course of Rifaximin, once with Berberine for 2 weeks (gave me panic attacks because of lowering my blood sugar I believe, plus- awful liver pains at night. I can’t take even one pill now without immediate side-effects).
    Then I took herbal antibiotics/antifungals for 1 month. Then- chemical antifungal. Then- herbal again. All of those would give me relief for about 1 week and then I would get indigestion again.
    I tried taking Betaine HCL for awhile but it made my acid reflux worse and I developed a persistent sore throat.

    Finally I went grain free and I still am for about 5 months now. Unfortunately that didn’t fix the problem either. In fact it gave me even worse bloatiness, indigestion and constipation.
    I bought Undecenoic acid from Thorne and I had been taking it for 1 month with no noticeable change when I received a link for this interview. Ben mentioned that without choline there would be no adequate bile production and without bile SIBO was virtually guaranteed. Something clicked.

    I get dreams sometimes telling me what to eat for a problem that is bugging me. I’ve learnt to listen to the advice because it helped. But the last advice was to eat 15 eggs a day. I thought ‘You’ve got to be kidding me’ and proceeded to completely ignore it.
    But now that piece about choline made me wonder. I had some lecithin (food grade) left over from my cosmetic preparations. So I started taking it (3 tsp a day- 2 g of phosphatidylcholine/day according to directions on the can, the same amount as in 15 egg yolks btw).
    It took 2 days to kick in but what a difference it made! The speed of my digestion has tripled! No acid reflux, no indigestion. I took it for 10 days and then stopped. 2 days later indigestion returned. I resumed taking it and it resolved. I will definitely keep taking it now. I am just so amazed at how such a nutrient that nobody ever mentions in connection with SIBO can quickly resolve digestive troubles. Thank you again for this valuable interview!

  4. Hello Dr. Kessler and community of listeners. I really enjoyed the methylation podcast episode with Dr. Lynch. My only concern was that, with regard to analyzing laboratory testing options for ??polymorphisms, I got the impression that you doctors didn’t trust or didn’t like the current array of tests available. Could someone be more specific as to which companies seem to be more accurate with their testing, which companies you prefer, which companies you have more thoroughly resarched? I ask because my 8-month old son, who is healthy (God Willing), is diagnosed with Down Syndrome, and my limited research up to this point indicates that nutrigenomics might play a HUGE role in his gene expression affecting his physical/cognitive development…..if we decide to do testing on him, I wouldn’t waste the money unless we had high confidence in the lab itself. Any guidance and specific feedback is appreciated. Thank you.

    • My understanding is that there is nothing wrong with the testing eg 23&Me (which I know, as a patient, Chris’s colleagues use). It the interpreting of the SNPs that is the danger. So I would recommend getting that test but also finding a practitioner who understands what CK and Dr Lynch are discussing in this podcast.

  5. I just wanted to let you know that I am a better practitioner because of all the actionable content you put out there. I love the podcast cause my time is often tight and it allows me to keep up with practical solutions to complex issues. Keep up the tremendous work!

  6. Methylation the more we study the more confused we become as a common man.It refers to attatcment of methyl group to the DNA molecule in such a way as to prevent the gene from being read.such genes are considered silenced.I am a patient of mCRC and with metastses of to peritoneum.The metastses is loco regional and not spread to any other body part.My KRAS was mutant in codone 12. All others are wild or negative.Please throw some more light to understand.

  7. The gentic reports that are bad rapped in this podcast actually have a lot of value when you can place the information provided into the proper context.

    When you don’t look at single snps like mthfr, but instead look at entire pathways which contain those snps, you can potentially gain insights into health conditions you are trying to figure out.

    You can see where you may have vulnerabilities that could possibly be preventing your body from healing itself.

    I was able to figure out the biochemistry behind my reactions to certain foods and supplements and learned a lot in doing so.

    Dr Lynch and Chris are right on regarding supplements.
    Supplements are mostly a disaster. You can override your bodies biochemistry and push pathways too hard and wind up with more problems.

    Stay away from supplements unless you have a specific reason to take them, like a high homocysteine test result indicating your mthfr snp may actually be a problem.

    Just eat whole foods.

    • The tools available today can be very useful, if, as you mentioned, one looks at entire pathways and then how various pathways work together, especially when looked at in the context of environmental factors.

      I know understand how my serious health problems have developed, which is a lot better than having as doctor say, “Well, we just don’t know…”

      I disagree, however, with your warning to only eat whole food and to stay away from supplements. Due to these same gene, pathway, and environmental problems, some if us need enormous quantities of certain nutrients to function. My pocketbook wishes it weren’t so, but that’s the way it is.

      Working with someone literate in all if this is essential to avoid unforeseen consequences, but miracles can and do happen using this approach.

  8. Hi Chris,

    Thanks – as always – for taking time to share your growing body of knowledge!

    If you and/or Ben Lynch could clarify two questions, I would be very appreciative – whenever practitioners use the terms “undermethylation” or “overmethylation”, I wish I understood the definition of these terms more precisely.

    — Is it correct to say that the term “methylation” refers to two things? That is, 1. the methyl “bookmarks” on a DNA strand, as well as 2. the degree to which methyl is biochemically available to DNA/histone tails, thus influencing gene expression.

    — In an organism, if methyl production/other conditions cause one gene to be overly- or under-expressed, does that mean that conditions are right for ALL other genes to be similarly over- or under-“methylated”? Or does the methylation of each gene happen independently of all/some others?

    Thanks for your time!!
    Regards,
    Sarabeth

  9. Everything I have been saying agrees with this interview. Cancer is definitely a metabolic problem as proven by Otto Warburg in the 50’s! Why have we gone down this useless genetic pathway? Because there’s so much money in it, it’s a run away freight train, anyone that tries to say “stop, you’re going the wrong way: is just run over.

    I see these tests being done, hundreds of genes being looked at, all meaning nothing, confusing patients to no end. The human genome took billions of years to get it right, it really is pretty perfect. We need to find out how we are screwing it up, not how it is screwing us up.

    • That is my sense as well, though my lack of techical background mean it’s just a general sense. Not sure i understand the point of 23andme and similar tests. Seems like it’s mainly just a bunch of suppositions.

  10. This was a very interesting discussion. I didn’t realize that homocystinuria is related to 40 different mutations in the MTHFR gene. Homocystinuria is a disorder in which the body is unable to process certain amino acids properly. Research also shows that variations (polymorphisms) in the MTHFR gene have been associated with neural tube defects in developing fetuses including anencephaly and spina bifida. Variations in the MTHFR gene may also increase the risk of heart disease, stroke, high blood pressure (hypertension), high blood pressure during pregnancy (preeclampsia), an eye disorder called glaucoma, psychiatric disorders, and certain types of cancer.

  11. Hi there,

    Dr. Lynch quickly mentioned some important studies about ALS…and the PhD doc who has written some great papers on it. My father is suffering from ALS. Does anyone have information about this doc or his papers that I could research?

    Thank you!