In this episode of Functional Medicine Research I interview Dr. Kara Fitzgerald about her book, "The Methylation Diet" and a preview of her upcoming study on The Methylation Diet. We had a great discussion about topics like methylation and diet, MTHFR, COMT, SAMe, methylated folate and B12, homocysteine, epigenetics and much more.
The Methylation Diet with Dr. Kara Fitzgerald Interview Transcript
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 cocktail 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 homocysteine, 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,
