Dr. Hedberg: Well, welcome everyone to “Functional Medicine Research.” I’m Dr. Hedberg, and I’m really looking forward today to my conversation with Dr. Kara Fitzgerald. She’s a naturopathic physician and a real thought leader in the functional medicine arena. She got her doctorate in naturopathic medicine from National College of Natural Medicine. And she did postdoctoral training with the Metametrix Laboratory, which is now in Genova. And she’s also certified through the Institute for Functional Medicine, and she’s on faculty at the Institute for Functional Medicine. So, she’s been published in a lot of papers and she’s been involved in various publications and peer review journals that she’s written. She’s contributed to functional medicine textbooks, and she recently wrote a chapter for the new “Integrative Gastroenterology” book. And that’s Dr. Gerry Mullin’s book on gastroenterology. And she’s also co-authored an e-book, it’s called the “Methylation Diet and Lifestyle.” And we’ll be talking about methylation today. So, Kara, welcome to the show.
Dr. Fitzgerald: Thanks, Nick. It’s nice to reconnect with you. I was just dialoguing with you. I’ll tell your audience that we knew each other way back when I was doing my post doc. I think you were one of our early folks to really become an expert in the specialty testing we were offering. So, anyway, it’s nice to reconnect.
Dr. Hedberg: Yes, yes, it’s great. So, some really interesting things to talk about today. And, as I mentioned, we’re going to talk about methylation. And so, why don’t we just start with some bedrock information for our laypeople and practitioners about, you know, what is methylation, and if you could just give us a basic overview of what it is and how it works.
Dr. Fitzgerald: Yeah, sure. Listen, if you’ve got any serious sort of biochemistry history geeks, it was actually…our ability to methylate compounds, to detoxify them was first discovered in 1887, if anybody needs a co*cktail party factoid. But it was long after that before the methylation cycle was actually characterized and S-Adenosyl methionine was discovered. You know, it was in the 20th century when all of that was teased out. So, methylation is really quite simply, as you know, either we’re putting a methyl group, which is a carbon and three hydrogens, either we’re adding it to a compound, or we are removing it from a compound, or we are producing S-Adenosyl methionine, which is the co-factor that carries that methyl group that can be put on compounds.
So that’s what methylation is. And it’s everywhere. You know, an internet lord [SP] says, those folks talking a lot about methylation say it’s happening in every cell all of the time. And I would argue that it’s probably pretty close to that. I mean, it’s interesting to me that we use this addition of a methyl group or the methylation cycle which interfaces, as you know, intimately with the folate-vitamer cycle and sulfuration. But, you know, it’s interesting that we use these in such important fundamental processes, you know, body-wide.
Just to give you a couple of ideas, Nick, of its importance, you know, three of the four DNA bases require a functioning folate/methylation cycle for production. Three of the four bases. And that fourth base, which is cytosine, is the base that in DNA methylation gets methylated. So, for gene expression, fundamentally for gene expression, we have to have good methylation. And for DNA repair, we need good methylation. So just think about it. To make DNA, to regulate DNA expression, to repair DNA all requires really, you know, high-functioning methylation. And so, just as I’ve been into this more, and more, and more, you know, from an evolutionary perspective, I just ponder how interesting it is that we use it everywhere. And then, additionally, a lot of the folks interested in methylation know, for instance, that we’re detoxifying hormones, toxins, histamine clearance, neurotransmitter synthesis, phospholipid synthesis. Like, you know, choline is a really methyl donor demanding process. We use it to make creatine, you know, in muscle energy. And, you know, and kind of on and on.
Stem cells. So, here’s another really interesting thing, going back to that epigenetic regulation or the regulation of DNA expression. Our stem cell fate is determined by our DNA methylation patterns. So, gametogenesis and embryogenesis, high methylation activity time, very much so. So are you going to be a brain cell, or a lung cell, or a gut cell, etc., etc. Those pluripotent stem cell rules are defined through DNA methylation patterns. And prior to that, you know, the DNA methylation patterns from mom and dad, you know, in the sperm and egg, those are mostly wiped clean and then new patterns are laid down. They’re not completely wiped clean. And so, the heritability of DNA methylation is actually established in this really early time. And I know you’re paying attention in this arena, I don’t know how much you’re focusing in it, but I know that you’re a really smart guy with a broad area of interests. So, you know, the epigenetic heritability is in this arena. The fact that we don’t completely erase all of the DNA methylation patterns from mom and dad, or grandma and grandpa, and, you know, generations prior, and they’re carried forward. So, it’s extraordinary. This whole area has become quite interesting to me. But I’m going to stop for a minute.
Dr. Hedberg: Right. I mean, so with so many connections to methylation, since it’s kind of at the core of what’s going on in the cell, it has to be difficult at times to figure out if it is truly connected to the patient’s condition.
Dr. Fitzgerald: Good question. Yeah.
Dr. Hedberg: How do you approach the need or, you know, the interest in looking deeper into methylation in particular patients? Are there any particular conditions that really stand out?
Dr. Fitzgerald: Well, that’s a really good question. Arguably, we all need to be addressing methylation, and arguably we want to be doing it really upstream. So, you know, there are certain times we’re going to be leaning on it more heavily, like preconception planning, when women who are pregnant, we want to be leaning on it more heavily. I know there are hosts of conditions that, you know, some of us in our arena have associated with methylation defects more obviously, and probably the best evidence is around depression and, you know, other neuropsychiatric conditions. Certainly in autism we commonly see methylation defects. But I guess I want to say that my…so a big practice changer for me has been thinking much more upstream and globally about methylation and really putting a lot of attention on epigenetic methylation. And I want to give you a little bit of the backstory, Nick. Interrupt me if I’m going on too long, but let me just talk about that. And that I think this will kind of elucidate where I’m coming from.
So, you know back in the lab, you know, years ago, we were looking at methylation all the time, looking at amino acids associated with the methylation cycle. Of course, we always look at hom*ocysteine, etc. We’re looking at sulfuration. And so, we’ve been thinking about it for a long time. And then we started to layer in single-nucleotide polymorphisms, and, you know, in the hopes that we would get sort of a deeper, more useful clinical picture. Arguably, we didn’t. I don’t know that MTHFR status always lends much clarity to a patient’s condition. You know, I would say it’s actually the exception that it really game changes how we approach patients. So, we had the organic acids and the various biomarkers there. We layered in the single-nucleotide polymorphisms, and, you know, maybe a little benefit, not that much.
So, you know, flash forward, epigenetic research starts really, really pouring out over maybe the last eight years or so. I mean, extraordinarily so. And for me, in about, I don’t know, 2012, 2013, enough studies on epigenetics and cancer were moving across my desk that I realized I needed to dive in. Like, I needed to start to understand this in a deeper way. Honestly, you know, it was yet another omics investigation, and I had a little bit of omics fatigue at that time. And I was like, “You know, here’s just another really complicated kind of arcane physiologic process going on that I need to understand. Damn it.” But I did dive in and the bulk of the research is in, you know, the epigenetics cancer. And, by and large, you know, the most important epigenetic mark appears to be DNA methylation. And as I unpacked it, it became a practice game changer for me.
So, the background in it is that in cancer, so the tumor micro-environment is very effective at harnessing our own epigenetic machinery and taking over DNA methylation for its own, you know, nefarious ends. So, when we hypermethylate a promoter region of a gene, that gene is effectively turned off. When we hypomethylate it, when either there’s an absence of methyl groups on the gene or those methyl groups are removed, that gene is allowed to express. So, the tumor micro-environment can very efficiently hypermethylate tumor suppressor genes.
And so, the first question for me as a functional medicine doctor, looking at methylation, prescribing B vitamins, high dose B-12, folate, all of the time was, “Geez, you know, do I need to stop doing that in my patients who I’m suspecting cancer in, or who are in, you know, an age range of an increased risk, or who have cancer, etc.?” You know, these stopped me in my tracks, these papers that were pouring out “hypermethylated.” And, you know, could supporting or pushing methylation forward have some kind of an impact? And it turns out, there isn’t a suggestion in the literature that perhaps it could. Now, has that stopped me from prescribing B vitamins when my patients need them? No, not at all. But I began to wonder about an upstream approach to methylation. There’s nothing in the literature…
So, wait. Let me actually back up and say, hypomethylation of the DNA, so global hypomethylation of all the DNA is something that happens as we age. All of us are moving towards less global methylation. But then there are these regions of hypermethylation where we don’t want them. It’s like our DNA methylation becomes disordered as a part of the aging process. And you can see that it underscores all these complex chronic diseases, including autoimmunity. You had mentioned that your audience, you know, tends to be interested in that. You see these disordered patterns happening in all these diseases of old age. So, globally, it’s low methylation with these pockets of imbalance of hypermethylation and good genes being shut down like NERF-2 or tumor suppressor genes, and on and on.
So, my first question was, you know, “Can we effectively move upstream and prescribe a methyl donor-rich diet?” And looking in the literature, as you know, there are no studies on leafy greens causing cancer so we know these are safe. You know, beets, a beet-rich diet and cancer, really not out there. Even liver, which is a methyl donor superfood, you know, there’s no association, unless maybe you ate really, really lousy liver, with causing cancer. So, we saw that we could actually push methylation with a diet and be on safe grounds. So that was thing one, but what do we do about these regions of hypermethylation? Like, how do we support that? Well, a major “Aha” for me was reading these mostly in-vitro in animal studies. This is a new, new area, that some really beautiful polyphenols that we’re using in practice all of the time actually have the capacity to inhibit or almost adaptogenically augment DNA methylation. So those famous polyphenols include EGCG from green tea, curcumin, rosemarinic acid from rosemary lycopene, and on and on.
So, you know, in-vitro in some animal studies… Actually, diurnal methane is another one. I’m just thinking about that because I was talking about it to somebody else yesterday. These guys appear to be able to help allow for the re-expression of formerly inhibited tumor suppressor genes. And, probably, Nick, this is one of the reasons why we prescribe these polyphenols. We know that they’re very pleiotropic in their mechanisms, but I would argue that this ability to augment DNA methylation behavior is a big reason why they are such important players in our tool kit. So, I happen to have an extraordinary nutrition team here, and it’s headed by our Nutrition Director, Romilly Hodges. And I, basically, I put this on her. I said, “Romilly, let’s design this diet. You know, methyl donor heavy across the board, plus these methylation adaptogens that we were talking about.”
And then, the other piece that I started to look at was, you know, as functional medicine providers, we’re really used to sitting in there and augmenting reaction kinetics. You know, influencing the rate of reactions, pushing enzymes forward and so forth. We’re all influenced by Jeff Bland and Bruce Ames, and, you know, those guys. So that’s how we think. But if you step outside to the rest of the world, they think about regulating epigenetic expression with things that don’t, at a glance, have anything to do with methylation. And so, we started to look there as well. Turns out there’s a whole lot of research on exercise favorably augmenting DNA methylation. Turns out that sleep, if it’s disordered, can have a real detrimental effect on methylation, in particular DNA methylation. It turns out that stress can really impact DNA methylation. So, we pulled in all these lifestyle components. Not surprisingly, toxin exposure can wreak havoc on DNA methylation as well as DNA itself and DNA repair.
So, we pulled in these other pieces and created this lifestyle program. So, we have this diet, and then we added in, you know, some recommendations around exercise, paying attention to sleep, you know, bringing in meditation, you know, keeping the diet clean, and so on and so forth. And it ended up becoming this program that we enacted in practice most…you know, just based on that original research in DNA methylation and cancer.
So, once we started to do that, we enacted it fully in some patients, and then in other patients we would layer it into whatever other therapeutic dietary prescription we initiated. So, if we had somebody on a FODMAP, you can layer in some of the MDL ideas. And so, we’re addressing the methylation piece in everybody, and it’s really pretty straightforward. But once we actually started to do that in practice, and we were pretty inspired, we were pretty excited about it… I presented it at AIC. So, we had this all written down and presented it at the Institute for Functional Medicines Annual International Conference in 2016. Other places started to want to hear our content, so we presented it at Cleveland Clinic Center for Functional Medicine, and, you know, a host of other places.
But the next question became, can we actually prove that we’re changing epigenetic expression? Could we do that? And, you know, I’m a clinician in Sandy Hook, Connecticut. Like, I’m not a research scientist. And so, we thought, you know, “How would we actually do that? You know, what could we do? Do we give the diet to folks on Facebook and have them commit, and, you know, fill out a multiple symptom questionnaire? I mean, is that what we can do? Or could we have a handful of folks come in the office and track their hom*ocysteine?” I mean, how would we… Or do, you know, one of the Doctor’s Data or Genova panels looking at SAM and SAH? And we just sort of talked through these ideas, Romilly and myself, and, you know, they were all insufficiently satisfying because we weren’t really going to be able to tell from those investigations that, yes, we are affecting epigenetic methylation.
And by some, you know, just serendipity, miraculous sort of unfolding, Metagenics came into the picture, Brent Eck, their CEO. And he gave me an unrestricted grant to actually research this in earnest. And so, we’ve just completed the methylation diet and lifestyle trial. You can actually Google it and find our clinicaltrials.gov entry, and read all the details around it. We’ve just finished it. National University of Natural Medicine, they’re a health research institute. They’re basically a clinical research center. They ran our study for us, and I’m co-PI with their Director, Ryan Bradley. And so, we just finished our clinical arm of it, and we are unpacking our results now. One of the scientists helping me in this journey is Dr. Moshe Szyf who I’ve podcasted with, and he’s one of the premier epigeneticists. So, he’s helped us design it, and he’s now helping us unpack the results. And we used a research only…an array from Alumina where they’re looking at 850,000 sites. So almost a million DNA methylation sites on the genome.
Plus, we also looked at S-Adenosyl methionine and S-Adenosyl-l-hom*ocysteine, and we got a bunch of validated subjective questionnaires. And we had another big thing we did and then I’m going to hush and let you take over for a minute, is we used our nutrition team as nutrition coaches. And so, our participants had careful attention and support in enacting the plan. And, in fact, NUNM thought our program was onerous, and they didn’t anticipate the kind of success that we had in adherence. So, they were studying us enacting this diet. They were really curious how the nutrition team would bear out in executing it, and I think it went really well. And we’ll be able to sort of track adherence data as well. So, it was middle-aged men. It’s a pilot study. We had 20 controls and we had 18 participants at the end that completed everything. So, there it is, Nick. My download.
Dr. Hedberg: That’s excellent, very exciting.
Dr. Fitzgerald: Isn’t it exciting?
Dr. Hedberg: Yeah. I want to get clear on a few things regarding genetic snips and testing. So, you can have an individual who has a lot of genetic snips for “poor methylation.” But they might actually be doing okay because they’re doing all the right things in their life.
Dr. Fitzgerald: That’s right.
Dr. Hedberg: And then you can have another individual who has very good genetics for methylation, but it’s not doing well because they’re not sleeping well. They’re enflamed…
Dr. Fitzgerald: Maybe they’re hypermethylated? Yeah, that’s right.
Dr. Hedberg: Those kinds of things.
Dr. Fitzgerald: That’s right. That’s right.
Dr. Hedberg: So, regarding…
Dr. Fitzgerald: Let me tell you. Let me actually say this like…
Dr. Hedberg: Sure, sure.
Dr. Fitzgerald: You can see I’m pretty impassioned about it. So, what we know, you know, when we look at the genetics of breast cancer, for instance, it’s a minority of women who have the BRCA mutation, a minority. So, we always look at genetics as far as a risk factor. Of course, if you have the BRCA mutation, your likelihood is incredibly high. But only a small minority of us actually have it. Well, it turns out that BRCA gene can be hypermethylated and inhibited. And it is indeed associated with hormone-sensitive cancers. So just, you know, that’s a clear example of what you’ve just stated.
Dr. Hedberg: Right, right. So, let’s just cover a couple of these. So, most people are going to be aware of things like MTHFR, COMT. And then things like in the blood, hom*ocysteine, B-12, folate, things like that. Can you just talk a little bit about your approach to identifying the snips and then the other testing that you’re doing to see if methylation is compromised?
Dr. Fitzgerald: Yeah. So, we will eventually be using the epigenetic tests in our clinical practice. These will come to be ready for prime time, and we’ll be looking at them routinely soon enough. But they’re not yet, so, you know, hopefully we’ll have them at our fingertips. So, barring epigenetic investigations… And there is actually, and we can talk about this later, we can talk about the limited testing that is available if we have time, Nick, but there is a DNA age…there’s a whole DNA methylation clock, and there’s all sorts of interesting stuff that we have some limited access to right now.
So, barring access to the bulk of those investigations, yeah, we have to just look at, you know, there are some decent methylation panels available. As I mentioned earlier, Doctor’s Data panel is available to clinicians. Genova just launched a panel, and those are fabulous starting points. And they include, you know, a SAM SAH ratio, which is very useful, well-documented in the literature. Of course, hom*ocysteine. Even with hom*ocysteine’s limitations, it’s still a workhorse assessment. It’s still useful. I will say this, though, this is what we saw in our study, and, you know, what I’m reading in the literature. We as functional medicine providers put a lot of emphasis in having, you know, a hom*ocysteine somewhere in the neighborhood of seven or, you know, whatever. I can tell you that in our study, we didn’t move hom*ocysteine significantly. We did change other markers significantly. S-adenosyl-l-hom*ocysteine, we did even though I told you before I’m not supposed to talk about that, but I’m going to give you those two limited pieces.
And, as a functional medicine clinician, we might look at that and say, “Geez, that’s not much,” except that when you jump over and look at the DNA methylation changes where, without going into specifics yet until we publish, we did make some really big changes. So, the take home for me here is, you know, we’re in there pushing the methylation cycle all of the time as functional medicine providers. You know, probably we’re not able to yet realize what kind of an impact or see what kind of impact that’s having on what they call the methylone or DNA methylation. And the take home for me is that it didn’t take, you know, some heavy lifting in the methylation cycle to affect pretty big change in DNA methylation.
Dr. Hedberg: Excellent. And, epigenetics, just so everyone can understand what that is…a lot of people might not understand the connection there, you know, the real definition of epigenetics and how it connects to methylation.
Dr. Fitzgerald: Yes, okay. Then, yeah, let’s back up and get a little bit, you know, more fundamental. And if you need some information, I could do a little writeup Q&A or something if your folks want the background. So, you’re familiar with methylation, like, Catechol-O-methyltransferase. You talked about COMT. And so, that’s a methyltransferase reaction that takes that SAM-e molecule and transfer some methyl group from compound A to compound B. In the case of COMT, we use it to metabolize out adrenaline, noradrenaline, you know, dopamine and actually to produce and metabolize out methyltransferase reactions. There’s actually a few hundred or a couple hundred methyltransferase enzymes in the body. So, we’re doing it all over the place. We’re transferring a methyl group on to a different compound. We use COMT to metabolize out estrogens, as you know as well.
Same thing in the DNA. So, DNA methyltransferase, another methyltransferase enzyme, is quite simply putting a methyl group on cytosine which is one of the DNA bases. When cytosine is actually next to a guanine, so it’s a CG site, it’s a CG relationship, the fifth position, the fifth carbon on a cytosine, can be methylated. And mostly in mammals, the CG sites are methylated, and, you know, a sufficient amount of methyl groups on CG sites of a given gene will inhibit it. And we can talk about these… The gene has different regions. The promoter region of a gene is where transcription factors are going to land and turn that, you know, and allow that gene to be expressed. So, whatever that gene codes for, it’ll be turned on and making it. So, whatever protein it happens to participate in, let’s say, insulin, for example, transcription factor’s is going to land on that insulin gene and turn it on and allow insulin to be produced. If the promoter region is methylated, if you think about it, you know, it’s a carbon and three hydrogens, but if that whole promoter region, all of those CG sites, you know, or the thousands of CG sites there are just riddled with methyl groups, that transcription factor isn’t really going to be able to land on it and turn it on for expression. And so, hypermethylation inhibits gene expression.
And, you know, famously, again, circling back to what I was talking about previously, we see the microenvironment in tumors able to really hypermethylate and turn off tumor suppressor genes. So, we want our tumor suppressor genes up and running. We want them, you know, dealing with any cancerous changes in the body. We want a good BRCA protein functionality. We want, you know, p53 on and humming, and all, you know the myriad tumor suppressor genes. There’s many, many, many of them. But in cancer, they’re able to hypermethylate and turn expression off. So, you know, we want to be able to deal with that, and, you know, just to complete the thought, that’s where I learned in the literature that, you know, some of our known and beloved polyphenols that exert such potent anti-cancer activity actually augment that. They inhibit the tumor micro-environment from shutting down tumor suppressor genes, or at least they help us do that.
Dr. Hedberg: One other quick question about testing. Have you used the sulfate marker on your organic acids as any clinical utility with impaired methylation?
Dr. Fitzgerald: No. No, I haven’t.
Dr. Hedberg: Okay.
Dr. Fitzgerald: It would be a real distant cousin. Maybe not even a cousin. Maybe a cousin, like, two times removed.
Dr. Hedberg: Got it.
Dr. Fitzgerald: Yeah. Yeah, it’s not quite there.
Dr. Hedberg: And let’s just talk a little bit more of some of the specifics regarding the diet and the methylation diet. You’d mentioned, you know, sleep, exercise, you know, stress and things like that, and polyphenols. Can you talk a little bit more about some specifics as far as the foods that are emphasized in this diet?
Dr. Fitzgerald: Yeah, for sure I can. Yep. Well, you know, if your folks would like to, they can head over to our website, and it’s just my name. It’s just drkarafitzgerald.com. And there’s a whole recipe tab. And if they go to that recipe tab and they type in methylation, they’ll get loads of recipes that are designed for, you know, with the MDL principles in mind, with the methylation diet and lifestyle principles in mind. In fact, I think we’ve got documents they can download. So, the list of the methylation adaptogens, I think if you sign up for our newsletter, you can get that download if you want to. But just a little bit of background. So, the diet is, it’s got eggs. We want folks to have eggs as long as they can tolerate it because, of course, eggs are high in choline. And, you know, choline is a really methylation demanding nutrient for our bodies to make, and it’s considered conditionally essential because there are three steps of SAM-e needed. There’s a lot of SAM-e needed for us to be able to make choline/phosphatidylcholine. So, if we supply the body with a little bit of choline, and eggs is, you know, arguably the best source, we can preserve it. We can save methyl donor drain.
Creatine, you know, for muscle energetics. Sometimes we’ll give people creatine to help with good methylation because, again, it’s such a methylation demanding process for the body to make it. So, give a little bit in a smoothie. Or, you know, just give somebody some extra creatine as a nutrient, we can preserve methyl donor drain. What else do we have in there as superfoods? All the greens. You know, kale, and spinach, and sprouts, sea vegetables. You know, what else? Beets, of course, you know, as long as somebody doesn’t have kidney stones. I mean, if somebody did come to you with kidney stones, then you would want to look at this diet and be a little bit mindful around the oxalates. But that’s an easy tweak. Seeds. Pumpkin seeds, sesame seeds, sunflower seeds. Again, all rich in those methyl donor nutrients. Just dance around the methylation cycle and, you know, you’ll see it’s a mineral intensive cycle. We need, you know, B-12 foods, folate foods, etc. And so, we’ve just tried to pack those methylation cycle nutrients into the diet. We give a little extra…
It’s not an animal-protein-heavy diet, but we do recommend animal protein and liver because methionine, of course, is an amino acid essential to the methylation cycle. And then we layer in all of the so-called methylation superfoods, and those…methylation adaptogens, excuse me. And those are, of course, the, you know, quercetin. Resveratrol is another one, rosemarinic acid, EGCG, diindolylmethane, curcumin, and so forth. Genistein, interestingly, is a potent methylation adaptogen and has some great research and animal studies, you know, on effecting pretty profound change. In fact, anybody who is familiar with the agouti mice research, there’s some good publications regarding genistein. And the lead scientist in the agouti mouse studies is Randy Jirtle. And I podcasted with him, so if anybody decides they want to do a dive in this area, you can check out my conversation with Dr. Jirtle. It was really extraordinary.
I’ll also add that, you know, I mentioned earlier when I was talking about gametogenesis and embryogenesis, that this demethylation, active demethylation happens as well. So, we put the methyl groups down on our DNA to inhibit expression and we can actually go in and remove them. We can clean them off using a group of enzymes called ten-eleven translocation enzymes. And the nutrients involved in optimal demethylation activity of the genome include vitamin C, α-ketoglutarate. Vitamin A can actually potentiate the Tet enzyme activity as they’re called. Vitamin D, E, selenium, zinc. All of these guys seem to have sort of an ability to make a difference on regulating DNA methylation activity.
Dr. Hedberg: So, a skeptic might come in and say, “Well, you know…” look at this diet and say, “Well, there’s no sugar. There’s no processed foods. There’s no junk food.”
Dr. Fitzgerald: Yep. Intermittent fasting is in there. Yep, it’s a lower carb. Yep. Yep. So, give me your best skeptic pitch.
Dr. Hedberg: It’s just a really, really healthy diet.
Dr. Fitzgerald: Yeah, that’s right.
Dr. Hedberg: It’s nutrient-dense, healthy fats, good protein, lots of vegetables, nuts and seeds. What would be, you know, kind of the best explanation to say, “Well, this is really the methylation that is really the factor that’s causing some really good results?”
Dr. Fitzgerald: In making the difference? Well, okay. So, I’ll talk to you about that. I have a few comments. One would be that if you look in the literature, you’ll see that sugar messes up the methylone. So, of course, we want to because it actually can have a pretty profoundly negative influence on epigenetic expression. You know, and, again, a lot of this is animal studies, but more human trials are coming forward. What else? Intermittent fasting. You know, transitioning into ketosis a little bit here and there. All of these are beneficial in epigenetic expression. So, we do want to think about them and we did want to build them into the diet.
So, some of the markers that we’ll get into later on very clearly suggest that we influence methylation favorably using the diet. So, our methyl donor heavy diet did have an impact, and we’ll tease that out. We did not have any supplements, but we did use a probiotic. We used lactobacillus plantarum. And there are some suggestions that certain strains will increase folate production, you know, endogenous, you know, bacterial production of folate so we included that. And we did include what we call a methylation adaptogen powder. So, it’s basically a greens food concentrate full of all those polyphenols. We included that with our participants.
So, there are a number of epigenetic clocks out there. So, we can look at patterns of DNA methylation and predict somebody’s biological age. This research has come out of UCLA, out of Steve Horvath’s laboratory. Steve Horvath, incidentally, lectured at this year’s PLMI in October. Jeff Bland’s Personalized Lifestyle Medicine Institute. And Jeff makes those recordings available on his site, so if somebody is interested in listening to Steve, they can probably access his recording on Jeff’s site, or they just can Google him on YouTube and there’s plenty of lectures there. So, they can hear him talk about developing the epigenetic clocks. These clocks are looking at DNA methylation patterns. And so, an obvious question is, what reverses epigenetic age, you know, or biological age? And, what, you know, adds to biological age? And they looked at some diet and lifestyle influences and found that, you know, the so-called healthy diet filled with healthy fats and, you know, adequate nutrients and veggie intake moved the clock slightly. And, you know, there are some other data out there that show that they improve it. I think that’s sort of the generic healthy diet that you are articulating. Maybe we did a little bit better, you’ll just have to stay tuned and see that.
Dr. Hedberg: Right, right. Well…
Dr. Fitzgerald: So that would kind of be a comparison right there.
Dr. Hedberg: Yeah. I mean, and that would be enough to make it convincing because, obviously, it’s a very, very healthy diet. But, you know, two people can be feeling pretty good, but one person, everything might just be working at a better level and they could have a reduced risk of certain diseases if they were potentially following something like this. Is that kind of the way you’re looking at it?
Dr. Fitzgerald: Yeah, yup.
Dr. Hedberg: Okay.
Dr. Fitzgerald: Oh, yes. Can we improve health span? Can we improve lifespan? Yes, yes. And because DNA methylation is an important piece and, you know, an important process at, I think, all points in life, you know, and probably most intensely, you know, early on in development from embryogenesis to, you know, early childhood, very intense. And then as we’re aging, again, DNA methylation comes in, you know, and arguably is either, you know, improving our health span or not. And so, I think it’s important for us to be thinking about it, you know, as we’re on the aging journey. And so, here’s the other thing. Because of this heritability component…
So, one thing that I didn’t mention is that DNA methylation marks are pretty stable over time. It’s actually a continuum. Some marks are so stable that they’re heritable. Other marks are pretty changeable. It’s a continuum. And I know it’s a lot to wrap our head around, but it means that, you know, unlike, say, having a piece of sugar or a piece of cake and watching your blood sugar rise and fall over a discrete period of time, epigenetic changes can be lasting. You know, they can be lasting on to future generations if you’re preconception, for instance.
And so, there’s a good argument that we want to be tending to optimal expression all of the time. Especially as we begin to tease out which marks are, you know, very labile and changeable, you know, and which marks, you know, when we inhibit a certain gene expression are going to be around for a long time. You know, so as we really kind of tease out and understand that, I would say it’s best to incorporate some of these concepts most of the time. An example of DNA methylation that’s not changing would be in chromosomal expression in female mammals. So, you know, me for instance or, you know, any other female mammal, two X chromosomes, one X chromosome, and every cell of the body is always shut down via methylation. And so that’s always going to be preserved. That’s a long-term mark that is changed. That’s not going anywhere. But, really interesting, one of the things that they tested… Were you paying attention with the Kelly twins, Scott Kelly went to outer space for a year? They’re astronauts, and he spent a year in space. And his astronaut twin, identical twin brother, Mark, stayed home?
Dr. Hedberg: I didn’t read about that.
Dr. Fitzgerald: Okay. Well, they were tested at baseline. So, before Scott went to space, they tested him every which way including their epigenome and, you know, all sorts of telomere lengths. And they just looked at them every which way till Tuesday. So, it turns out that after that year in space when he came back, you know, I think the Guardian proclaimed, “Identical twins no longer identical after a year of space travel.” The genetic expression changed so profoundly in Scott, you know, that they proclaimed them no longer identical twins. It was really kind of a funny, but, you know, sort of appropriate proclamation. And as they tracked them over time when Scott landed back on Earth, some of those epigenetic changes reverted back to baseline within days. Like, they were very labile, and they changed right back. Some of those are lasting. So, we’re still teasing that information out.
Dr. Hedberg: Okay. Yeah, that’s an interesting observation with him. I’m going to have to read about that. So why don’t we close with a case study so people can kind of get an overview of what this might look like. Are there any particular cases that come to mind in your practice and how you use this MDL plan?
Dr. Fitzgerald: Yeah. Okay, that’s a good question. And I’m thinking about it now because I can see her in my email box here, Emily Rydbom, her and her mom, Leslie stone… Leslie Stone teaches over at the Institute for Functional Medicine. She’s a gynecologist. Emily is a nutritionist. And, Michael Stone, people might know because he’s a long, long, long time IFM faculty and that’s Emily’s dad. Leslie and Emily have a company called GrowBaby Health. And they have, for preconception, for during pregnancy, been using the MDL in their patients since we launched it. And they have the most extraordinary birth outcomes. So just thinking about her now as a part of their whole care package, they use the MDL, particularly early on when methylation is happening in embryogenesis. So, so, so profoundly. Like, in the first trimester, arguably, our principles are so important and impactful.
So, that’s one area where, you know, you could go to GrowBaby Health and actually read about their birth outcomes, they’ve published on them. But just, you know, the incidence of gestational diabetes, pre-eclampsia, of, you know, early delivery. I don’t know why the term is completely leaving my brain, but… And then outcomes such as autism or, you know, issues in early infancy, you know, eczema, allergies, etc., etc., their whole, you know, mortality, morbidity, all of their outcomes are much, much, much lower than general birth outcomes in this country. And we’re actually not doing great considering we’re such a wealthy, developed Western country with, you know, access to perfect medical care. Our birth outcomes are pretty poor. So, using it in that context has been really helpful.
In our practice, we layer MDL principles into every single patient, and that means that regardless of our therapeutic intervention, we’re starting them on something, even if it’s just adding like blueberries and rosemarinic acid, and the brassica veggies, and a little bit of liver, or something like that. We’re using these principles. So probably the two cases that are the most standout that we’ve written about are, you know, a case of chronic Lyme with mycotoxicity. He lives on the shoreline here in the East Coast and is…
Dr. Hedberg: Sounds like an easy case.
Dr. Fitzgerald: Yeah, really. That’s right, that’s right. He responded best to IVIG. He actually did IVIG for years, and that took him out of the woods. And then IVIG stopped working for him. I mean, nobody can go on for years getting IVIG. But he lived in a flooded house. You know, it was flooded by the Long Island Sound here, you know, over and over again. But his elderly parents were there and he didn’t want to leave and so basically he refused to get out of this environment that was toxic to him. He couldn’t tolerate, so, you know, his condition rendered it impossible for him to take any B-12 or vitamin D. Neither he could tolerate. He had this pretty profound polyneuropathy presentation. So, a burning sensation on his thighs, in his arms. Just really, really profound fallout from his condition. And he was able to tolerate the MDL. So, you can imagine methylation, his hom*ocysteine was always very high and his B-12 was really low. Certainly, the B-12 deficiency was compounding the polyneuropathy and so forth. And we used the MDL on him. And when he was dialed into what we call our MDL intensive, he did fabulously. He was able to tolerate the nutrients, his hom*ocysteine dropped, his symptoms abated. And so, it was, by far, the best intervention that we gave him.
Similarly, another patient with a very complex neuropathic condition, you know, with intolerance to methyl donor supplementation of any kind, you know, also adopted our program. And, you know, likewise, we were able to turn her around. And then, we’ll have the study, the study to report. So, the interesting thing about our study is that these are all healthy middle-aged guys, and we’ll have that outcome to report soon enough. In our practice, the people that we put on the intensive program tend to be these people with really complex conditions who’ve failed elsewhere. And we’ve seen nice outcome with them. Otherwise, we layer it into whatever other therapeutic prescription we’re doing.
Dr. Hedberg: Excellent. So, Kara, your website is drkarafitzgerald.com, is that correct?
Dr. Fitzgerald: Yeah, that’s right.
Dr. Hedberg: And is there anywhere else you’d like people to find you online, or is your website the main hub?
Dr. Fitzgerald: Well, yeah, my website is the main hub. Actually, we’ve got a really big and active Instagram, and we’ve got an active Facebook. And you’ll find stuff on this content there.
Dr. Hedberg: Excellent. And any idea when the study might be published?
Dr. Fitzgerald: We’re writing it up for publication now. I am scheduled to present at the Annual International Conference at the Institute for Functional Medicine in May. And then again at PLMI in October of 2020. So, you know, hopefully, before May. But we are, we’re actively writing now and we’ll get it in as soon as we can.
Dr. Hedberg: Well, this has been great. I appreciate you coming on the show.
Dr. Fitzgerald: Yeah, Nick. Thanks for reaching out to me and asking me. I know, it’s surprising, isn’t it? I bet you didn’t quite expect to get an earful in this way.
Dr. Hedberg: Oh, this was great. And I’m really looking forward to the study because I’ll cover that and break it down as well. So, to all the listeners, if you go to drhedberg.com and just search for Dr. Fitzgerald, I’ve made a full transcript of this show so you’ll get all the details of what we talked about. And then when the study is published, I’ll link to that as well. So, thanks for listening, everyone. Take care, and I will talk to you next time.
