Podcast 41 - MTHFR Gene & Methylation

MTHFR Gene and Methylation


Dr. Chad Edwards: This is Doctor Chad Edwards and you’re listening to podcast number 41 of Against the Grain.

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Host: Welcome to Against the Grain Podcast with Doctor Chad Edwards, where he challenges the status quo when it comes to medicine. We get into hot topics in the medical field with real stories from real patients, to help you on your way to a healthy lifestyle. Get ready, because we’re about to go Against the Grain.

Marshall Morris: Hello, hello. This is the super tall Marshall Morris, and today I am joined by Doctor Chad Edwards, who believes that 80% of medical recommendations are crap, technically speaking Doctor Edwards. He’s the author of Revolutionize Your Health with Customized Supplements. He served in the U.S. army. He graduated from medical school at OSU, Oklahoma State University, and he’s the founder of revolutionhealth.org and the Against the Grain podcast. Doctor Edwards, welcome.

Dr. Edwards: Thank you so much Marshall. As always I don’t know who you are talking about when you say all those things.

Marshall: Well, it is you, and it is you and most people they don’t realize that, you did all of these things. These are real things and then you went on to start Revolution Health and this podcast is just another awesome vehicle to educate a lot of listeners, and actually broaden the audience to functional medicine Tulsa prolotherapy.

Dr. Edwards: Yes, I’m excited about doing this. It’s just — I’ve had a lot of patients that have been coming in, in fact I got some patients just the other day that came in because of the podcast. Very cool, and I’ve had some of my patients that have come in and they said, “Oh, I didn’t know about this and that was great information on that.” And so, as Robb Wolf when he first started his podcast he said, “Six listeners, can’t be wrong.” [laughter] That’s kind of how it is. All three people that listen to this podcast came in to see me last week.

Marshall: [laughs] Well, let’s get into it. What is today’s hot topic?

Host: Hot topic.

Dr. Edwards: This is a common — we got this full panel lab in my clinic, and one of the things that we look at is the MTHFR gene and how someone methylates. And invariably, it provokes this gigantic discussion on what is methylation, and because I’ll say something about methylation and they’ll be like, “What in the world’s methylation?” And then, why do we get this is in a lab and why should I as a patient care about methylation? So, that’s where we’re going Tulsa prolotherapy.

Marshall: Okay, so methylation, and it’s a process in the body I’m assuming. It’s some kind of effects. Let’s start off with defining. What is methylation and what is this gene that we’re going to be talking about?

Dr. Edwards: Methylation is a chemical process, and there is a — in organic chemistry, there is this chemical group called a methyl group, and methylation simply puts a methyl group onto something. It’s just the process of that methylation. But there are a number of chemicals, there’s a number of structures, there’s a number of things in your body that need this methylation, and if you don’t methylate well, there is a whole host of problems that can occur. And we’ll talk about that in the podcast.
MTHFR and methylation has been just a big thing in the functional medicine community. I hear lots of patients about it, and they say, “Oh I can’t methylate, because I have the MTHFR gene.” We’re going to define that a little bit more, and what does that mean to us.
DNA is involved in this stuff or I should say, methylation is involved in DNA, and it definitely without question affects your overall health. It could increase risk of cardiovascular disease. It’s all kinds of stuff. It’s a very important topic. Now, what we do with it is a little bit different and again we’ll talk through that.

Marshall: Okay. Let’s get into it. What is the functional part of methylation? What is actually going on?

Dr. Edwards: Again this methyl group will take it from one chemical usually called a methyl donor, and will — through this enzyme, released in part, will add that methyl group to something else, so for example like your DNA. And the methylation process turns on some of the genes, some of the genetics, and it allows — because already we’ve got tons of genes, not all of them are turned on. We have cancer genes and they’re turned off. They should be turned off and I often think about genetics or our genes as like little dip switches on electronics, on a little electronics boards, and if you want certain effects then you’ll turn this dip switch on, this one off, this one on, these two off, that kind of thing.
Methylation is the process by which we go through and turn little ones on and off. That’s the DNA portion. Another one that I see frequently is in hormone metabolism. We’re going to talk about this a little bit more detail in the next podcast, on estrogens and estrogen metabolism. But how we metabolize these hormones, and so women will come in and they’ll say, “Oh, you know, someone I saw had breast cancer, I don’t ever want to be on estrogen,” thinking that estrogen causes breast cancer. Estrogen, specifically estradiol, does not cause breast cancer. To my knowledge, there’s no study that shows estradiol increases risk of breast cancer. There are studies showing estrone, a different estrogen, can increase risk of breast cancer. What changes estrone into estradiol, is all in the way your hormones metabolize. Part of the way your hormones metabolize is through methylation. It’s incredibly important for that and then detoxifying other chemicals, other junk and things like that. The methylation process is incredibly important, detoxifying, all those kinds of things.

Marshall: Okay. What happens if maybe I don’t methylate? What’s the big deal there?

Dr. Edwards: There are a list of things, and this will be kind of a brief list, but some things that are associated with poor methylation. The first one and this is one of the most common cardiovascular disease, one of the most common causes of death in the United States, heart attacks. It can definitely — heart attacks are at increased risk if you don’t methylate well. Strokes. Similar mechanism. Dementia, like Alzheimer’s, not necessarily Alzheimer’s itself but dementia, the decline in brain function over time, that can certainly do it. Depression, migraine headaches, autism, fertility or infertility, different kinds of cancers, birth defects and there’s a whole lot of other things that can go along with inability to methylate and methylate well.

Marshall: Okay. We’ve talked about this first part, methylation and the potential effects of not being able to methylate well or disruptions in the methylation process. And then, you also mentioned MTHFR. What is that?

Dr. Edwards: MTHFR stands for methylenetetrahydrofolate reductase. Big word. Folate reductase is the end of the word, and so we’re taking folate and we’re basically converting five 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. It’s part of this biochemical process, we’re converting one chemical to another, but it’s the enzyme that converts this whole process. And it’s that 5-methyltetrahydrafolate that for example converts homocysteine to methionine. And there’s a — it just has a bunch of different impacts. One gene that’s central to this process is the MTHFR. And it lets us know, if we have a speed bump in our methylation process. In my clinic, we measure two different SNPs. And so SNPs are single nucleotide polymorphisms Tulsa prolotherapy.

Marshall: Oh gosh.

Dr. Edwards: I know, right?

Marshall: SNP is better.

Dr. Edwards: Basically this is your genetics, your gene, you have one little nucleotide, one little chunk of DNA that is going to eventually convert into an amino acid, is a little bit different in one person than in another. And so you have — basically they are numbered by the amino acid that they attach into the protein. There’s two different ones that we look at. So, there’s big long gene and we look at these different codons. Codons are three nucleotides in length. And we number these codons. And on the MTHFR, what we look for is at the 677 spot. At 677 it can either encode for a T or a C. I don’t remember exactly which ones is which, but they are the amino acids. And they are switch, so one — you can be a CC or a TT or a TC, and have one of each. And so you get one copy of genes from mom, one copy of genes from dad, and so you’ll have two of these MTHFR genes. And we’re looking to see how does that work. Now, the genes if anyone understands genetics, basically what the DNA does is it encodes for a protein. And in this case, it encodes for an enzyme, the MTHFR enzyme. At the 677 spot, we swap an amino acids, so instead of being the T it’s the C, or instead of being the C it’s the T, and it changes the conformational shape of that enzyme. So, the enzyme doesn’t have the same shape. If it doesn’t have the same shape, it usually doesn’t have the same affinity for its like it, what it’s trying to work on. And so if it doesn’t work on it as well, it doesn’t attach as strongly, doesn’t convert it as easily, then it slows the process down. Basically, that’s what the gene is. It’s the difference in one person to the next, on how that MTHFR protein is made. And we’re looking for these conformational changes that would suggest that that enzyme doesn’t work as well or as efficient.

Marshall: Essentially you’re testing for how efficiently the MTHFR gene is working within the body.

Dr. Edwards: Sort of. We’re actually testing what’s the structure of that enzyme.

Marshall: Okay. What is the shape of it and how does it look?

Dr. Edwards: Basically, basically, that’s right. And the way we actually test the function, I think this is where the disconnect occurs for a lot of people when they start thinking, “Oh, I’ve got the MTHFR.” The reality is our genetics hasn’t changed in tens of thousands of years. We have the same genes we had 10,000 years ago. Why is it that all of a sudden MTHFR is a problem? And some people will run around like their hair is on fire thinking, “I’ve got the MTHFR. I’m going to die.” I mean it’s just — that’s crap. Even in the functional — where we’re looking leaning forward and we’re trying to think, “Okay, what could be an issue?” Just because you have the MTHFR does not mean you’re going to die. Well, it means everybody’s going to die, but it doesn’t mean you’re going to die because of that. This thing’s been around forever.
This tells us about the structure of the enzyme and its ability to methylate. Now, the difference I think is how fast do you need to methylate. And I think that depends on a whole host of factors, and this is why I think it’s important to test and important to understand. But it really depends– If you got the abnormal, like at the 677, if you have TT on your MTHFR, then that enzyme is going to be less efficient. It may only work at 60% to 70% of the full enzyme. It does not mean it doesn’t work at all, and I think some people think that that’s the case. It just means it’s less efficient they’re doing so. The real question then is how are you actually methylating? Understanding the MTHFR gene helps us understand your risk for how you are methylating, but it’s also important to understand how you are actually methylating. There’s a few tests that we can use Tulsa prolotherapy.
The one that I use just kind of every day because it doesn’t cost patients a lot of money is the homocysteine. Homocysteine’s an amino acid and this 5-methyltetrahydrofolate that we talked about which comes from the MTHFR, is what converts homocysteine into L-methionine. If you can’t convert homocysteine, you can’t methylate homocysteine, it can’t become methionine. If it can’t become methionine, then you’re going to have low levels of methionine, and high levels of homocysteine. Using homocysteine we can get an idea of how efficiently they’re methylating. It’s not the end all, be all, but it is kind of a poor man’s test for methylation.

Marshall: Okay. We’re going to take a quick break and when we come back we’re going to wrap this all up all together, put it all together and talk about what we can do about it.

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Marshall: We are back and we’re talking about the MTHFR gene, okay, and methylation here. And we were just talking about what do you do if you’re not methylating well. And the first step is to get your MTHFR tested, okay, to understand the shape of the gene there, right?

Dr. Edwards: Right.

Marshall: And then the second thing is that is just an indicator of how well you might be methylating. The next thing is to actually test how well are you methylating and we talked about that’s with homocysteine, correct?

Dr. Edwards: Yes.

Marshall: What’s the next step here in this process? Talk me through this.

Dr. Edwards: Yes. Obviously the first piece is getting tested and knowing what your MTHFR status is, which again, I say that it kind of lets you know what kind of car you’re driving. It doesn’t tell me how fast your car goes, or how fast your car is going. It just lets me know how fast your car’s capable of going. If you’re driving a scooter, and it only goes 25 miles an hour, if you’re driving around a school zone, you’re good to go. If you’re going to get on the Turnpike, and go across the country on I-10 or I-70 or something, then you’re not going to be able to keep up. You’re going to be dumb and dumber driving up the mountain with every car behind him.
It just gives us an idea of what you’re capable of doing. Then we want to understand how are you actually methylating and that’s with measurement of homocysteine. And you do not want high levels of homocysteine. And just kind of tie this in a little bit with that increased risk of heart attack, homocysteine steals or robs away nitric oxide and we’ve talked before about endothelial function and nitric oxide on previous podcasts, and homocysteine steals that away, robs it. And so when you have high levels of homocysteine, it’s actually an independent risk factor for cardiovascular disease or having a heart attack. So, we want to make sure that you are methylating well and make sure that that homocysteine level decreases. Get tested for the MTHFR. Should we go ahead and talk about the 1298? You want to mention that?

Marshall: Yes. I know that we have in our notes here the 1298 is another type of MTHFR mutation, and so it was – how frequently does that happen?

Dr. Edwards: As far as frequency — it’s not uncommon, I’ll say that. Now, it really only — the mutation in this gene really only accounts for about a 25 — 0 to 20% decrease in the actual function of the gene. Compared to the 677, it can have up to a 45% — I’m sorry that one’s a different– that was a different number there. On the 677, 45% of the population will have the 677, but on the 1298 I believe it’s 20% declined in the actual function of that enzyme. I don’t know how many actually have it. But it’s a — I would call it a mild player in altering the gene. 677 is more important, 1298 seems to be more important. I wouldn’t say that’s a hard and fast rule, but it’s a good indicator Tulsa prolotherapy.
Then if you’ve got abnormal, abnormal, on both of them, you may have a real problem with the function of your MTHFR. Then what do you do about all of this? The first thing that we want to do is give you some methyl support. Give you some things that are good methylaters, and the very first place I start is with the B vitamins, and your B vitamins are very, very, important so make sure you get good quality B vitamins. [coughs] Sorry. Struggling here. The B vitamins that I always look for, so B12, we’ll start there. B12 is called cobalamin, and what most doctor’s offices use, what I was trained to use, was called cyanocobalamin. That means the cobalamin or the B12 has a cyanide group attached to it. This is not normally found in nature, but it’s produced and we give it as injections, and it’s in most of your cheap vitamins and the daily multivitamins things, and it’s cyanocobalamin, that’s the form of B12.
That is not that helpful in this MTFHR methylation deficient environment. You want to use methylcobalamin. Methylcobalamin is natural in the environment. It is what your body actually uses, and it has a methyl group attached to it, and it’s part of this methylation cycle. It’s very important. Use methylcobalamin. And I will often use higher doses. I’ll use anywhere between one and five milligrams depending on the patient and what’s going on. So, fairly high doses, that’s 1,000 to 5,000 micrograms which if you look at the back of your multivitamin and it says cyanocobalamin, a hundred micrograms, that’s a drop in the bucket. I use a little bit of a higher dose. The second thing that I want to do is add folate or 5-MTHF, that’s that 5-methyltetrahydrofolate that we talked about earlier. So, on your multivitamins you don’t want one that says folic acid, you want folate generally in the 5-MTHF form. That is what converts homocysteine to methionine. So, you want high levels of that 5-MTHF. Again I’ll often use about 5 milligrams on that. Usually with those two things and when we get them — into them consistently, we’ll see homocysteine levels decline quite a bit.
I’ve seen them come — in fact, I had one guy that came to me, I think his homocysteine level was in the 60s. I had never seen anything that has. It’s not uncommon to see 11s and 12s. I usually like it between six and eight or so. This guy was way high and his first follow-up lab, he had already come down to 20 which was still way too high but we were making good headway in lowering those homocysteine levels.
So, get tested on the MTHFR gene, know where you are. Get tested on your homocysteine. If there’s still a question you can check your estrogen metabolites because we can look at methylated estrogens and that will give us further understanding. Then make sure your B vitamins are of good high quality B vitamins. There are certainly other things like trimethylglycine or betaine that are very good for methylation support as well Tulsa prolotherapy.

Marshall: Okay. So we’ve gone through methylation and the MTHFR gene here and talked about specifically what they are, where these disruptions could occur, how they occur and what to do about it. What am I missing here? What are we missing?

Dr. Edwards: You pretty much got it. Get tested, know where you are and make sure you got good B vitamins and follow through with that because we can make a big difference on a lot of this.

Marshall: Knowledge without application is pretty much meaningless.

Dr. Edwards: Exactly right.

Marshall: Boom. Dr. Edwards. Thank you so much.

Dr. Edwards: Thanks Marshall. Have a great day.

Host: Thanks for listening to this week’s podcast with Dr. Chad Edwards. Tune in next week where will be going Against The Grain.

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