Finally, a Reasonable Dialogue on Methylation with Dr. Kara Fitzgerald

You’ve likely heard something about methylation as it’s an area of functional medicine that is ‘hot’ right now. I’ve been very cautious regarding ‘methylation testing and treatment’ recommendations for a number of reasons. In today’s episode we speak with Dr. Kara Fitzgerald and I share some of my concerns. Dr. Kara provides an excellent overview of how we can optimize methylation and do so reasonably and safely. Things you should know: testing is way overhyped, and over supplementation can actually harm you.

In This Episode

The Future of Functional Medicine Review … 00:00:42
Episode Intro … 00:01:53
What is Methylation … 00:04:45
Speculative Nature of Recommendations … 00:08:30
Too Much Methylation Can Be Dangerous … 00:12:22
Caution with Supplements … 00:15:41
Importance of Diet & Exercise … 00:22:03
Methylation Adaptogens – Polyphenols … 00:23:47
Methylation Clinical Data … 00:25:35
Upstream Methylation Support … 00:30:10
Epigenome Gene – Health and Lifestyle … 00:32:25
Specific Dietary Changes … 00:37:48
Important Testing … 00:41:27
Supplemental Treatment & Symptoms … 00:44:12
Episode Wrap Up … 00:46:49

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The Future of Functional Medicine Review

Dr. Michael Ruscio: Hey, guys. I just wanted to make one quick announcement before we start the show. If you are a healthcare practitioner, I’m very excited to announce that we just released The Future of Functional Medicine Review. This is a monthly practitioner training tool that will allow you to sharpen your clinical skills and enhance your ability to practice cost-effective functional medicine.

You’ve probably heard me say a thousand times that we need to make functional medicine more cost effective to be able to get better patient outcomes with less time and less money so that we can reach and help more people. Well, this monthly review will be a big step in that direction.

It will consist of four sections—a case study, research study reviews, the practitioner question of the month, and the practice tip. And all of this will be very helpful in making you a better clinician and steering you toward practicing a more efficacious and cost-effective functional medicine model.

If you head over to DrRuscio.com/Review. You can see a full sample issue and learn more. Again, I’m very excited about this and think you will find it, hopefully, very helpful. Okay, back to the show.

Episode Intro

Hey, everyone. Welcome to Dr. Ruscio Radio. This is Dr. Ruscio. I am here with Dr. Kara Fitzgerald. And today, we are talking about methylation.

And I have to say I’m pretty impressed with Kara because she seems to be taking a perspective, a position on methylation that’s not overzealous and seems to be pretty practical and I think will be very much in alignment with much of what we discussed on the podcast previously, which is trying to come at these issues, not getting swept up in the latest fanfare and bandwagon jumping, but rather taking a practical approach to this stuff.

So admittedly, Kara, I’m very excited to have this conversation. Welcome to the show.

Dr. Kara Fitzgerald: Yay! I’m excited about that, too. Yeah, absolutely. Really thrilled to be pushing the paradigm forward and what we’re thinking about with regards to methylation. I concur that we have gotten pretty hyped up about it.

DrMR: Right. So before we jump into all these details that I know we’re both looking to get into, tell people just briefly about your background and what kind of clinical experience you have with methylation.

DrKF: I have a pretty interesting background. I’m a naturopathic physician by training. I went to school out in Oregon at National College of Natural Medicine.

And while I was out there in the Pacific Northwest, I was able to see Jeff Bland present on numerous occasions. And really, I was sold. I just came to fall in love with functional medicine. And he’s really the father of functional medicine.

And so when it came time for me to figure out what I was going to do for my post doc training, a strictly clinical residency or—I was actually at that time pondering going on for a Ph.D. But there was a post doc position available at a laboratory, Metametrix Laboratory in Atlanta, Georgia.

And there was a clinical residency with that as well. And that just spoke to me. I would be working under Dr. Richard Lord, who is a highly, highly regarded nutritional biochemist in our field. And I would be in the middle of a lab just looking at all of these biomarkers, some of what we’re going to be talking about today, and thinking about the influence of genetics and epigenetics, all of that.

Anyway, it was home for me. I did that. And while I was there, we worked on laboratory evaluations for integrative and functional medicine. And I also wrote a collection of case studies for integrative and functional medicine as well. So lots of writing, lots of lecturing, lots of behind the scenes work plus a clinical practice. So kind of a unique training and one which I’m eternally grateful for.

What is Methylation

DrMR: Beautiful. Beautiful. So now, let’s try to define for the audience methylation. And what I’d like to do, just to try to orient us a little bit—I don’t want to spend too much time going into a lot of the details of the mechanism of methylation.

I want to give people the short story on what methylation is, how it works in case they haven’t heard it before, and then really get into more of what does the clinical data say. What are some of the practical clinical take-aways for patients or doctors who are listening to this? So what’s the short primer on methylation?

DrKF: Long story short would just be that it’s quite simply a carbon with three hydrogens on it, so a little carbon. And it’s a very small molecule that we put onto structures and we take off structures literally all of the time in all of the cells all over the body.

And when we put one on, we can change what that compound does. And when we take it off, likewise, we can change it. So we use this process. We make S-Adenosyl methionine, which everybody has probably heard of which is our universal methyl donor.

And then this SAMe goes around and donates that carbon and three hydrogens to all sorts of compounds to aid in detox, to build white blood cells, to produce DNA, as well as change the behavior of DNA and other genetic material.

We use it to turn off hormones. We use it to clear histamine. We make all sorts of neurotransmitters. Really, the list goes on and on. We make energy. Mitochondrial support is reliant on methylation. Myelination of the nerve. The list is endless.

DrMR: Sure.

DrKF: Because it’s just such a fundamental, basic molecule that we can pop on and pop off all over the place. And the body really just uses it liberally as a regulating compounds.

DrMR: Right. Right. And I think that’s part of the reason why it’s so easy to get swept up in this methylation craze where there seems to be a lot of attention being given in this area.

And one of the things that I’ve said and commented on numerous times is that we have to be very cautious in trying to generate a clinical recommendation based upon a mechanism. And I think methylation is one of the areas that lends itself most so to this where we can find, as you’re saying, Kara, so many mechanisms through which methylation is involved.

And therefore, we can project from that, or speculate from that, that this could be a treatment for so-and-so or for X and Y condition, which is not a bad thing. It’s a place to start research.

But the challenge is when that speculative conjecture/hypothesis/whatever you want to call it is taken directly to a patient or a doctor’s recommendation to a patient, because if we haven’t taken the time to really vet these things through some of the clinical science, we run a very high risk at being wrong, because you don’t know if something works if you’re just looking at a mechanism.

So I just want to quickly give a few of my thoughts as a non-methylation expert. But these are a few of the things that struck me as someone trying to evaluate this quickly, looking at some of this methylation information. And then I really want to get into picking Kara’s brain on some of the specifics, as her being a methylation expert.

So Kara, bear with me for one second as I blow some hot air and give my perspective on this. And then we’ll go right into some specifics.

DrKF: Go for it.

Speculative Nature of Recommendations

DrMR: So the first thing that struck me as I’ve been watching more and more methylation information come through is what I just said, which was it seemed to be very ridden with speculation. And I’m sure the audience is probably accustomed to me fact checking.

And so I’d look at someone’s argument. It’s methylation expert So-And-So. And I’d look at their argument. And their argument would almost always be mechanism. And I very rarely saw clinical trials or even great observation data. A lot of the scientific basis supporting the recommendations was made around mechanism.

The other thing that caught me and made me a little bit suspect—and this is not an absolute rule, and I don’t want to make a pointed criticism here, but I do want to provide people with some of what goes on inside my head. So let me try to get this thought out here and then I can hopefully polish it into a little bit more diplomatic of a statement on the back end.

But I noticed that a few iconic educators in the methylation field either owned supplement companies, owned labs, and/or were not treating patients. And this does not mean that any of those things mean any of those people could not be brilliant and highly effective and highly virtuous.

However, I look at these things. And I tick these boxes in my head. So if someone who is a guru is not seeing patients and they own a lab or a supplement, it makes me quite a bit more suspicious of the quality of the information that I’m getting.

Again, I’m not saying that they’re bad people or doing any of this with mal-intent. But these are just things that go on in my head to help me try to screen the level of quality or the risk of bias for the information that I’m going to be getting.

So those are a few things that go through my head. And Kara, anything you want to add to that before we get into more of the scientific part of this?

DrKF: Well, the reason that I really became so enamored of looking at methylation was the emergence, just the epic—no pun intended—amount of knowledge on the epigenome coming out. That’s the area that I’ve been very much interested in.

I think SNPs are reasonably interesting and inferring what they might be doing by understanding the mechanisms, as you point out, and looking at the various biomarkers to marry it together. That was what we were doing back at the lab. And I’ve been doing that for a lot of my career.

But I think even more important is what’s happening to the epigenome. What’s going on with regard to methylation? And how are the things that we’re doing as we attempt to correct methylation augmenting the epigenome?

And that’s just an incredibly important area for us to start thinking about. There are regions on the epigenome that are actually hyper methylated. Or they’re overly methylated. And there are strong disease associations, particularly with cancer. But arguably, we could look at most chronic diseases and see this hyper methylation happening.

There are also regions on the epigenome that are hypo methylated. They’re not adequately methylated. And you can have that in the same gene. You can have these regions of imbalance. And so I think it’s very important in the light of these new data for us to back way up and ask ourselves, “How are we influencing this epigenetic behavior? And are we influencing it in the safest way possible?”

And really, I’d like to talk about that. We can unpack it a little bit and what we’re thinking about here clinically and how we might support balancing.

Too Much Methylation Can Be Dangerous

DrMR: Absolutely. And I agree with you. I don’t want you to think that I’m taking a shot at research. My problem is that when things are pre-clinical but people have access to some sort of expensive, elaborate self-help program where they’re consuming a very high number of supplements and they’re using lab testing that might not be validated for a clinical purpose—that’s what I’m driving at.

I agree completely with you that we need the research. And I’m sure you’re frustrated with the same thing where people doing these direct-to-consumer tests that aren’t validated and treatment protocols that aren’t validated. And they might even be inflicting harm unbeknownst to them.

DrKF: Right. Well, here’s the thing. We’re in agreement. If you are taking high dose B vitamins, if you’re really pushing methylation forward because you’ve determined that you don’t methylate well for whatever reason, arguably, you may cause imbalanced epigenetic methylation.

And is this unhealthy? Is this something that we really need to be concerned around? And I would say, “Yeah, perhaps.” We know that hyper methylation of the promoter regions of the genome is front and center in cancer. It’s just fact at this point that the promoter regions of tumor suppressor genes are shut down in cancers. And depending on the particular tumor suppressor gene that would be, it’s associated with different cancers.

For instance, the BRCA protein that’s a big tumor suppressor gene even without the mutation, you can actually methylate it and shut it down. P53 can be methylated and inhibited. And really the list goes on and on.

So there is active research in this arena. And already introduced clinically are demethylating agents as chemotherapeutics.

DrMR: Right.

DrKF: So hyper methylation as disease promotion is well known and has been investigated for quite some time.

And interestingly enough, in pancreatic cancer, glutathione S-transferase can be hyper methylated and turned off. And that’s part of the pathogenesis of that disease at least in certain cases. So it’s not even a genetic mutation. It’s that we have imbalanced methylation. And we shut down the gene functionality.

And I know you want to make a comment. But let me just say—

DrMR: Sure, sure.

DrKF: That in reading this literature it just prompts me to take a breath, back up a little bit, and say, “Am I doing right by my patients to be feeding them high dose methyl donors all of the time? Or do I want an endpoint? Do I want to be thinking about diet? And do I want to be thinking about upstream interventions, gentle, more tried and true interventions?”

But make your comment. And then I want to say something about folic acid because we do have some interesting research around folic acid in this arena as well.

Caution with Supplements

DrMR: Perfect. My point is essentially reaffirming what you’re saying, which is I think it’s a common habituation for some of us in this space to think supplements are the cure to everything and thinking we need to support, take more, support.

And sometimes, we don’t realize that in trying to do something helpful, we might actually do something harmful. So I love the point that you’re making.

DrKF: Yeah. Yeah. Well, think about it as a U-curve. When we’re malnourished, when we don’t have enough certain nutrients, there are all sorts of problems associated with that. So that’s one side of the U.

And then the other arm of the U is when we have too much. And when we have excess of certain nutrients, they can be toxic. So toxicity with insufficient and toxicity with excess. And many, many, many nutrients that we use in functional medicine have that U-curve distribution.

Folic acid is one of them. And I’m purposely saying folic acid, so synthetic folate—synthetic. We changed the outcome with regard to neural tube defects when we started to fortify grains with folic acid. We really significantly reduced birth defects with folic acid. So it was a big deal.

DrMR: I agree.

DrKF: I’m sure that there are people in our space who would discuss this as being a bad thing.

DrMR: Yeah.

DrKF: But the fact of the matter is the data are clear. It was a remarkable public health project that turned the course of neural tube defects around considerably in the Western countries primarily.

So we did a really good thing. But we also have a lot of research on what happens when you have long term folic acid exposure. And are there any reasons to be concerned around folic acid exposure?

So just like anything, there were some benefits around using folic acid in birth defect reduction. But there was also a whole bunch of data around too much folic acid or people who might not tolerate folic acid and some potential problems.

And so what they found was that unmetabolized folic acid, or the synthetic folic acid, can actually have genotoxicity potentially. They found that folic acid exposure can increase risk for allergic disease, for diabetes, for, paradoxically, possibly embryonic loss or growth delay, insulin resistance, natural killer cell activity impairment, and on and on. So excess folic acid appears to be problematic in and of itself.

And another big piece—perhaps where the bulk of the research on folic acid is with regard to promoting cancer. So hyper methylation. Folic acid can stimulate DNA and methyl transferase, and in so doing can lead to hyper methylation of certain regions of the genome. And it’s likely through this mechanism that folic acid can actually promote cancer. So—

DrMR: And that’s going to—Sorry, Kara. That’s going to apply then for methylated folate also, I would assume. Right?

DrKF: Mm-hm. Yep, yep, yep.

DrMR: Okay, yeah.

DrKF: Because it can also stimulate DNMT or DNA and methyl transferase. That’s right.

DrMR: I asked that question more for the audience of people who may have been brainwashed into thinking that methyl folate is the cure to everything. So thank you.

DrKF: Yeah. Yeah, so even these natural folates if you have too much can promote imbalance hyper methylation. And we need to be mindful around that for sure.

And it doesn’t mean that we don’t, for a short period of time, choose to use some supplemental Bs or some natural folates or B12 and so forth.

But first of all, know what your objective is. What are you attempting to address? And why? And have a specific timeframe in mind with a clear endpoint or do a taper. And concurrently—we’ll talk about in a little while here—we’ve cast a much wider net. And there are many other interventions we can do. There are many ways we can support balanced methylation that don’t require us to take high dose B vitamins.

DrMR: Right. So one simple question, and I definitely want to continue to develop this, but for someone who walks into your office and says, “I have MTHFR. And so I need to be taking a methylated folate supplement for the rest of my life.” I’m assuming for many people, you would think that would be a bad idea. Or maybe not. Correct me if I’m wrong on that assumption.

DrKF: Well, you know what? It depends on what’s going on with them. I think the MTHFR has been well researched. And there’s sufficient evidence to show that it does slow down—be you hetero or homozygous—it slows down the enzymatic activity. There is reason to suggest that things could be sluggish.

So I wouldn’t say conclusively you need to be on methyl folate or conclusively you don’t need to be on it. I wouldn’t say either. Everybody is an individual.

Gut health—so a nice robust microbiome, healthy mitochondrial behavior. All the myriad cofactors that are produced in the mitochondria help methylation, the gut microbiome does.

DrMR: Right.

DrKF: Our stress response will dictate and influence methylation behavior. So there are so many reasons outside of just that B, the folate that are going to influence whether one needs to be supplementing with additional. Yeah, go ahead.

DrMR: Okay. Well, no. I think that’s well said.

Importance of Diet & Exercise

I asked this question for people that are—it’s easy to get pulled into thinking that there’s a supplement for everything that potentially could ail you and forget about the fact that if you do a good job with the items—and I’m so glad you mentioned these—diet, exercise, stress, lifestyle, gut health—then you’re going to greatly decrease the need for any type of supplement.

And that’s important to keep in mind in the long term, because what I see anyway is sometimes a patient who has gone through the steps and is admittedly feeling pretty great overall, yet they still think they need to be taking a fairly high dose methyl folate supplement because this one gene test came back positive.

DrKF: Yeah, I would caution you at this point. Now that we know that hyper methylation is a disease-promoting proposition—

DrMR: Right.

DrKF: I would back up and be mindful. And really that’s why we wrote this book. Actually, long before we wrote the book, this was just a transition I was making in my practice because I wanted to do right by my patients and treat them as effectively and as safely as possible. And I couldn’t ignore the research on the epigenome. I just simply couldn’t.

And what’s interesting though is that it’s really all about balance. There’s excess hyper methylation that’s associated with disease. But likewise, hypo methylation is as well. We need to look at both pieces. It’s fascinating!

So there’s this sweet spot balance. And we need to be mindful, and clinicians and just savvy consumers, if you’re out there treating yourself, to remember that we need this balance.

Methylation Adaptogens – Polyphenols

Another area that we’ve really fallen in love with is this idea of—in furthering this conversation around balance—there’s a whole group of compounds that we’re calling methylation adaptogens. So these are primarily polyphenols.

But there are more than just polyphenols—vitamin D, vitamin A, soy isoflavone, which actually is a polyphenol. Those are. So your fruits and your vegetables—rosemary, curcumin. What else? Luteolin, lutein, etc.

All of these fabulous isoflavones or polyphenols that we get in a good, rich, vegetable-and-fruit-heavy diet help to actually balance methylation expression. That is, they have an ability to inhibit hyper methylation and, in some cases, promote increasing areas of hypo methylation to improve—let me restate that.

So they’ll increase methylation activity at regions of hypo methylation in some cases and decrease regions of hyper. So they have this adaptogenic or balancing effect. Pretty important stuff.

And again, we’re not looking at taking B vitamins. We’re not directly taking any kind of a methyl donor. We’re going way upstream and treating through diet and lifestyle.

DrMR: I really, really like that actually. I had not heard of methylation adaptogens. But that makes perfect sense that if you use food, you decrease your risk of causing some type of harm, whereas if you take a hyper, isolated, and concentrated supplement, then if you’re not very discerning in your approach, you may inadvertently do harm. I think that’s an excellent point.

Methylation Clinical Data

I want to transition us now to get your take on what kind of clinical data do we have? Have there been randomized control trials that have looked at treatment of some of these methylation-based issues? Or if not a lot there, what do we have at in terms of pretty solid observational or associational-type studies?

DrKF: Can you be a little bit more specific?

DrMR: Sure.

DrKF: So are you talking specifically about depression and using folate?

DrMR: So are there any conditions that are highly associated with MTHFR or some of the associated polymorphisms. So I know there is some association data there.

And then to go even a step further, have we taken the next step and performed a clinical trial where, let’s say we have a group of patients who have PCOS (polycystic ovarian syndrome)? And half of them are given a methyl folate or a methylated B complex vitamin. And the other half are given a placebo. And do we show a significant impact from a treatment outcome perspective?

Or is it not that simple? Or what do you see in this area?

DrKF: Oh. Yeah, okay. I get where you’re coming from. I have to be honest and say that it’s not an area that I’ve spent a ton of time on. It’s a little bit outside what my wheelhouse is in focusing on upstream methylation support and looking specifically at the epigenome.

But I think the data have been mixed in my read on it. I absolutely think there is a place for us to do a good, broad sweep of what’s happening nutritionally and metabolically. And there’s a place for looking at SNPs (single nucleotide polymorphisms) in clinic practice, looking at folate status, B12 status be it using MMA or methylmalonic acid or FIGLU as well as getting serum B12.

I am in favor, when patients come to see me, of doing a decent broad sweep of what’s happening, looking at the methylation index, homocysteine, amino acids, and so on and so forth as it’s indicated and then from that, using our clinical and treating.

So in PCOS, I do think, especially if you’ve got evidence in biomarkers that folate is indicated, that we should absolutely try it. But I don’t know that it’s always the cause or even often the cause. And therefore, I think the clinical studies looking at it are mixed. They’re always mixed.

And there are so many other variables that are going to impact whether a particular single nucleotide polymorphism is functional or not.

DrMR: Right.

DrKF: The genome-wide association studies have been, for this reason, a little bit disappointing in that they haven’t shown sweeping significance. Only a handful of GWA studies have.

And I think a piece of it is the more that we start evaluating SNPs in groups and looking at increased risks associated with SNP patterns in particular disease, I think we might see better outcome with that kind of analysis.

But just looking at one single SNP and expecting to see a strong disease association, I think by and large we’ve been pretty disappointed.

There was recently a study that just came out of JAMA, I believe, another evaluation on the utility of MTHFR. And the conclusion was despite the various data out there, it’s still not—

DrMR: Super fruitful, clinical endeavor.

DrKF: Yeah. Yeah, the evidence against it outweighs the evidence for it was their conclusion. I think that they erred a little bit too strongly. But it was interesting because the study was just published. I’m going to try to look it up so I can give you the citation on it while we’re talking.

DrMR: Yeah, if you would. Or you can give it to me after. And I’ll make sure to include it in the links section of this with the transcript. But I’d be curious to have a look. And I’m sure there are plenty of people listening who would like to have a look also.

DrKF: Yeah.

DrMR: And while you’re looking for that, this reminds me of an analogy in an area that is within my wheelhouse, which is the microbiota. And I’m assuming this translates over, but I want to throw this out there and you let me know if you think it translates over.

Upstream Methylation Support

We have all these microbiota studies that look in meticulous detail at changes in the microbiota, trying to correlate them with certain diseases. And when you really look at this literature honestly, you see that it is not about a certain microbiota signature or about manipulating these ratios as you want them to be in terms of you want less Prevotella or more Bifidobacter or what have you.

But rather the most important and the most clinically beneficial exercise one can go through for their microbiota is trying to create the healthiest internal environment.

And that consists of a number of things that might seem obvious, like getting enough sleep, exercising the appropriate amount for you, and then things that are less obvious—potentially eating a higher fiber and prebiotic diet if that works better for you or potentially eating a lower fiber and prebiotic diet like a low FODMAP diet if that works for you.

And it’s about creating an internal environment that works best for your body. And that is what leads us to the best outcome. It’s not about doing these tests, most of which have not even been validated to have any clinical significance yet, and trying to custom treat those tests with specific probiotics or vitamins or what have you to force a certain result but rather just focusing broadly on creating the healthiest internal environment.

And it sounds like your upstream methylation support is probably pretty akin to that. Is that right?

DrKF: Yep, absolutely.

DrMR: Okay.

DrKF: Yep, it totally is. Yep, absolutely. Okay, so let me just give you this citation. I just found it. It’s actually from—let me see—Levin and Varga.

DrMR: Okay.

DrKF: And it came out The Journal of Genetic Counseling. And it’s “MTHFR Addressing Genetic Counseling Dilemmas Using Evidence-Based Literature.”

DrMR: Gotcha.

DrKF: Okay.

DrMR: We’ll put that one in the show notes for people to have a look at. Thank you for looking that up.

DrKF: Yep.

DrMR: Okay, so as we’re transitioning now into more of your treatment recommendations, I think we’ve laid a nice perspective about—we don’t necessarily want to get into these highly specific trying to treat based upon these SNPs that we have or these self-diagnosis home gene testing type tests but rather trying to treat more so upstream which I think is brilliant.

Epigenome Gene – Health and Lifestyle

So let’s jump into your clinical experience with methylation support. And I’m looking at this, in my head anyway, like a pyramid. There are these bottom rungs that are going to be diet and lifestyle. And as we come up, there are things that are maybe less broadly important but can also be used on select cases.

DrKF: That’s reasonable, yep.

DrMR: Can we wade into it like that?

DrKF: Sure. Sure.

So I just have to underscore that the diet and lifestyle piece is huge. One of the many reasons the epigenome is just so wildly interesting is because it’s heritable. We pass on what epigenome looks like. Is it inflammatory biased? Is it balanced? What’s your stress response?

We pass so much information around how our genes are expressing with regard to what’s imprinted on the epigenome to our offspring. So it influences us directly. But we can pass it on. And you can pass it on generationally. And the research on this is profound. It’s absolutely profound.

And so to that end, interesting research has been done around lifestyle in utero. So a stressful—when Mom is pregnant, if her life is extremely stressful, she’s going to be impacting the fetal development for sure. And that’s going to almost lower the stress threshold in her offspring.

Even prior to conception, her stress experience and Dad’s actually—Dad is not out of the picture. Epigenetic imprinting on Dad absolutely has an influence on offspring. Actually, specifically, there was some interesting research in a mouse model on father’s stress experience and then ADHD observed in offspring.

So this kind of imprinting can happen, but it really hits home why lifestyle is so important. Sleep! Sleep can have a profound impact on epigenetic expression. Disordered sleep can augment the expression of myriad genes through changing epigenetic marks biasing towards neural inflammation, etc., etc.

Eating a whole lot of sugar can change methylation patterns of the epigenome. It really goes on and on. So your exercise—God! Good, healthy exercise profoundly supports healthy methylation expression in the epigenome, actually beyond just the epigenome. Healthy exercise can lower homocysteine and all sorts of really wonderful things.

There’s interesting research on the epigenetic “clock genes,” so reversing aging. And exercise has been shown to actually support reversing aging through modifying epigenetic expression.

The microbiome, as you were talking about, without question, plays a massive role in epigenetic expression. Even beyond the epigenetic expression, a good, robust microbiome, as you know, makes a lot of B vitamins and helps in absorption of the nutrients that we consume and just really on and on. This is interesting.

And likewise, toxin exposures are, not surprisingly, incredibly damaging to healthy epigenetic expression or healthy methylation.

DrMR: So coming to diet for a second, Kara—

DrKF: Yeah.

DrMR: Because I’d be curious to see, as someone who looks at this through a methylation-type lens as you do, if you’ve come to the same conclusion that I have, looking at this through more of a microbiota and gut lens, which is you can have two different people that do better on two completely different diets.

Some people, fiber will absolutely decimate them. Other people do much better on higher fiber. And so the recommendation oftentimes is steered back through a very empiric barometer which is just using the person’s response to gauge what’s going to work best.

Of course, we’re going to work within a generally healthy framework. We’re never going to recommend a low fiber, McDonald’s diet. It’s always going to be within the framework of fresh, whole, unprocessed, try to get a good assortment of different fruits and vegetables, healthy meats, healthy cuts of fat, what have you.

Specific Dietary Changes

But are you finding that there is some nuance in terms of everyone does better with this type of diet? Or certain people do better with the following modifications? Can you give people any more specifics in terms of how they might be able to optimize their diet in the regard of methylation?

DrKF: Well, I think that’s pretty interesting. And you’re getting into pinpoint prescription in your work on the microbiome.

DrMR: Which is probably hard for you to do without a patient right in front of you.

DrKF: Yeah, so certainly in the context of my practice, I get into very, very individualized diets based on what’s going on with them. As far as the methylation recommendations, everyone needs support in healthy methylation.

So I’ve talked about hyper methylation and hypo methylation and how we need a good, balanced sweet spot. Well, there are plenty of data out there on hypo methylation being associated with accelerated aging and all sorts of disease processes—hypo methylation.

And then you can look specifically at certain regions on the genes and see this hyper methylation happening, and we don’t want that either.

So arguably, we need to have a diet that’s rich in methyl donors that we consume. So we’re providing the body with the ingredients to then make the decisions on how it’s going to use them.

So when you do high-dose supplements, not dissimilar from a drug, you override the body’s decision making points. And you’re just pushing the reaction forward with very high dose.

So we’re saying consume it in the diet. Consume a nice breadth of nutrients. Put it into a healthy gut. Put it into a well-exercised, as peaceful as possible being. And the body is really going to be able to make these decision points in allowing the highest expression.

So our diet is absolutely rich in methyl donors. But it also is, as I mentioned earlier, very rich in the methyl adaptogens—so those compounds that can actually inhibit, in some cases, methylation which promoting it in others.

So as you can imagine, it’s lots of fruits and vegetables. It’s not high sugar. It’s low glycemic. We don’t have in this iteration—it’s gluten free. And we’re keeping it dairy free. And it’s lower carb. It’s a paleo-leaning, higher fat diet. There’s research on ketone production as being really helpful for balanced epigenetic expression. So there are some generalizations in this protocol.

DrMR: And Kara, sorry. Just one quick thing here. And protein is also going to be a source of methyl donors, correct?

DrKF: Yep.

DrMR: Okay.

DrKF: Yep, absolutely.

DrMR: Okay.

DrKF: That’s right.

DrMR: I just don’t want people thinking that’s it’s exclusively fruits and vegetables.

DrKF: Yeah, it’s not vegan. No, in fact, we love liver in the methylation diet. Liver is a methylation superfood. So is roe if you’re up for eating some fish eggs. That’s really helpful for methylation.

DrMR: Alright. So I think we’ve got some good basics listed there. And there are a couple other things I want to ask you about like testing and supplements.

Important Testing

But before we go there, I’m assuming if someone has done a good job with these dietary and lifestyle foundational pieces and they’re still not feeling well, they might go see a clinician and try to order some testing to start to steer where they should go next clinically.

Are there any tests that you think are highly useful in the clinical setting in the regard of methylation? I know, of course, gut testing is probably one you would recommend because we’ve talked about gut. So a basic gut evaluation and maybe things like anemias and screening for hypothyroidism.

Is there anything that’s highly important—one, in general and then, two, that’s specific to methylation or some kind of gene testing?

DrKF: So having a background in laboratory science, I do think there is a place for good quality labs. I do all of the standard chemistries that any physician does. I want to look at CBC and chem etc. I think it’s worth it, looking for toxic metals for most of our patients, even as a screen looking at in whole blood.

I do find the organic acids to be a helpful snapshot into what’s happening under the metabolic hood, what’s going on in the mitochondria and little bit of a snapshot in gut and some nutrient markers that can be useful.

I think homocysteine is a great methylation marker. Of course, it’s not the only methylation marker. And it’s not going to be positive or elevated in everybody. So it’s a piece of the puzzle. I think looking at S-Adenosyl homocysteine and S-Adenosyl methionine (the so-called methylation index), there’s a lot of good data around looking at that.

I think that looking for food reactions, food sensitivities via IgG or food allergies, via IgE, looking at gut health. I do stool testing on pretty much all of my patients.

There are a number of decent tools. There are a number of decent tests that we can use. But it really is on an individual basis.

And we walk through some of our recommendations in the book. So if people are interested in seeing our diet protocol, seeing our rationale for the methylation diet and lifestyle and looking at what labs, you can do a pretty good drill down in the book. And we’re going to make that available to people as well.

DrMR: Okay. Yeah, and I want to get the site where people can check out the book because I think it’s a good read for people definitely.

As we transition things to a close, two questions that I know people are going to be asking. I at least want to ask the question even if it’s not necessarily a simple answer.

Supplemental Treatment & Symptoms

What are some supplements that you find helpful? And then how do people know if the supplements are working? Are there key things that they should be looking for that tell them they’re on the right track?

DrKF: Well, definitely how they feel. We use various symptom trackers in my practice. And definitely anybody who is in my practice, we’re paying very close attention to.

And then if you’ve gotten a panel of baseline labs, you want to look at follow-up labs and correlate that to how somebody is doing clinically.

What was I going to say? I’m sorry. I’m just on the cusp of getting this cold. And I find my train is leaving the station a little more quickly today than it should be.

DrMR: Yeah.

DrKF: But I would say working with a good clinician and just paying careful attention. If you’re going to do this on your own, again, just really pay careful attention.

There’s a place for supplementation. I am not at all anti-supplementation. I am not anti-B complex by a long shot. I absolutely think that they’re essential and incredibly important for some of my patients. In fact, probably the majority of my patients for a shorter period may be on a B complex at the beginning of our work together when I see that it’s indicated.

But the difference today is that it’s a shorter period of time that I transition people off. And I’m really looking at diet lifestyle to pick up the slack and move them into the most holistic approach possible. So I do use supplements. But I keep it short term.

DrMR: Gotcha. Fair enough. And I think it’s helpful for people to hear this. And I’m sure you probably see quite a bit of this. People come in. They’ve maybe done a 23andMe test. And they’ve gotten scared at some of the results. And they think they need to be on 15 supplements for the rest of their life.

DrKF: Yes.

DrMR: And that is one of the main disservices I think functional medicine is doing for people. And so I ask these questions in part knowing what you’re going to answer. But I say it more for other people to hear than for my own edification. So I appreciate you making that recommendation, yeah.

DrKF: Okay, great. Well, thank you.

Episode Wrap Up

DrMR: Yeah, absolutely. Tell people where they can connect with you and where they can view your e-book if they wanted to have a look at that, please.

DrKF: Yep, so just go over to our website. It’s DrKaraFitzgerald (D-R-K-A-R-A-Fitzgerald, F-I-T-Z-G-E-R-A-L-D).com. And right on the homepage, you’ll find a link to the “Methylation Diet and Lifestyle” page.

There’s actually a free download that you can grab. You can get the preface and the table of contents for free. And you can take a look at those two things and see whether or not they interest you.

I think we have a couple of recipes that were given away on the site as well. You can swim around the site, look at what we’re talking about with regard to methylation and diet and lifestyle. And if it interests you, grab it. We do give you a 10% discount.

DrMR: And when you say “e-book,” I think sometimes people think 20, 30 pages. Your book is pretty thorough.

DrKF: Yeah, it is. It’s actually written for the clinician. I think savvy regular folks can understand it absolutely. Plenty of regular folks have gotten it. But it was written towards the clinician. And it’s very well referenced.

DrMR: Yeah, 140 pages here. And I think there are 167 references. So yeah, this definitely is not just a quick, “Here are the three basic concepts,” 15, 20 page e-book. This is something that you’ll pull a lot out of. So I just want to mention that because I think—

DrKF: Thank you.

DrMR: We’re sometimes accustomed to think that an e-book is 20 pages, a quick little excerpt. But this is a legit book.

DrKF: Yeah. Yep, that’s right.

DrMR: Well, Kara, thank you so much for taking the time. I really appreciate what you’re doing which is looking at this stuff practically which I think we so desperately need more of in functional medicine.

So thank you both for taking the time but more so for just looking at this practically and trying to give people some evidence-based and reasonable recommendations for trying to improve their health.

DrKF: Why, thank you! My pleasure. Thanks for having me.

DrMR: Absolutely. Well, thanks, guys. And thanks again, Kara. We’ll talk to you guys next time. Bye-bye.

DrKF: Bye-bye.