Aidan:
Hello and welcome to the Ideal Nutrition podcast. My name is Aidan Muir and I’m here with my co-host, Leah Higl and we are going to be talking about whether you should worry about the MTHFR gene, which is a common one that comes up in the health optimisation space.
I personally listen to a lot of podcasts. I hear it on a lot of podcasts and I did want to talk about it a bit. Technically, gene variations are quite prevalent. A large percentage of the population has MTHFR gene variation, so it is a bit of a relevant one. And it’s something that is pretty relevant in relation to pregnancy, which is the main concern, which we’ll cover pretty in depth on this. Noticeably, it’s not really a huge topic in mainstream health and medicine. It’s more in that kind of health optimisation type space, which kind of indicates that mainstream health and medicine doesn’t really care about it.
I’m not necessarily somebody who has my tinfoil hat on. Like I don’t think it’s something that’s like, these people don’t want you to know about this or anything like that. I think if it’s not something they care about, there’s typically a reason for it, but we’ll go through both sides of it. But it’s kind of implying that it’s not a big deal on a large scale, unless you personally have like huge distress of like mainstream medicine. But yeah, we’re gonna go through everything and cover both sides of it.
Leah:
MTHFR is an abbreviation that is used interchangeably for both a gene and an enzyme. And it does stand for… Now I take a big breath when I say this. If we think MTHFR doesn’t roll off the tongue, this next thing definitely doesn’t. So it stands for Methylene Tetrahydrofolate Reductase. So this is, again, enzyme gene. So the enzyme is involved in folate metabolism and the gene provides instructions for the enzyme. And there are actually over 40 known mutations, but there are two main ones that we see more commonly, and we’re going to actually spend most of this podcast talking about one of those.
Aidan:
I was talking to Leah off air and I don’t know if I should be sharing this on a podcast, but when I’m like going deep on topics, I make a promise to myself that like when I open certain studies, I’ll be like, I’m going to read every word of this study. And there was one paper I was reading on this, as part of the prep for all the content I was making on it, that I’d opened, and I’d made myself that promise. And it was like the driest read I have ever read. It was so deep on genetics and I had to do a little bit of brushing up on like, obviously I’ve done like biology and stuff like that to become a dietitian, but like I do a bit of brushing up on genetics just in general, just to like really understand this topic well.
But this specific paper, it was trying to cover all of the 40 plus known different variations and leading into the prevalence for a second, the 40 to 60 % of the population has some form of two of the variations. So two of these variants are super prevalent. And I knew that going into reading this article, I was like, damn, like now I’m just reading about these variations that are really not that prevalent. It’s one of the few times I’ve broken that promise to myself. I’ve got like a third of the way through that. I’m like, nah, I’m cutting this list. This is not a good use of my time.
But anyway, let’s go back to the fact that 40 to 60 % of the population has some form of these variants. At face value, that therefore means that if this mattered a fair bit, it would matter for like half of the population, which is 100 % why we’re talking about this, because it is so common. Going deeper, there are obviously differences here. So everyone has two copies of the MTHFR gene, one from each parent. If you got two copies of a mutation, it would matter more than if you just had one copy of that mutation. Statistically, 30 to 50 % of people have one copy of the most studied one, which is the C677T variant. And 10 to 15 % of the population have two copies.
Even that’s still a really big percentage of people. 10 to 15 % of the people have two copies of that variant, which is more impactful. So therefore it’s another one being like, this is why we’re talking about this. How much does this matter? What should we know about it?
Leah:
So why is this relevant? Why are we talking about it on a nutrition podcast? So, these gene mutations and the MTHFR gene plays a role in processing folate and regulating homocysteine levels. And that’s where a lot of the relevance is here. So for example, elevated homocysteine has been linked with cardiovascular disease. And then also in pregnancy, as Aidan mentioned, that’s a topic that’s very linked to this, is often recommended to supplement folic acid. So this would potentially reduce the metabolism of the folic acid. And we’re gonna talk more about the pregnancy stuff, but overall, this is the relevance, this is how it relates.
Aidan:
Talking about cardiovascular disease, because this will be quicker than the pregnancy stuff, so we’ll start here. It’s pretty debated. My own interpretation of looking at the research seems to point in the direction of there being a link between these variations of this gene and cardiovascular disease risk outcomes. I say my own because it’s not, I haven’t seen many people talking about this, but I did go through research and there does seem to be a link. Anyway, the main mechanism is that it’s related to homocysteine being elevated. Having a good intake of folate, B6 and B12, either through food or supplements could help reduce that. We’re also gonna talk a little bit more specifically about supplements later as well.
If you’re concerned, you can test your levels for all four of those things. So the three nutrients I just listed, but also homocysteine levels as well. Technically, there isn’t evidence looking at whether having a good intake of folate, B6 and B12 reduces the risk of cardiovascular disease with those gene variants, but I think it’s still a good idea for people to do that anyway. So I think everyone should be doing that. It doesn’t really change what I’m recommending. And another thing is like, let’s say my interpretation of the research is right and there is a little bit of a link there.
It’s also not really much we can do about that since my advice to people is still the same. It’s like, I should have a good intake of folate B6, B12, so on and so forth. And maybe certain genes are linked with more of certain outcomes, but we can also only play with the cards where dealt is my own two cents. But I’d still take the same actions there in terms of having a relatively good intake of those nutrients.
Leah:
Moving into pregnancy. So this is the most common context in where we end up talking about these gene variants. And the concern here is that the reduced folate metabolism in people with the MTHFR variants means that folic acid, especially the synthetic form, so through supplementation, could cause issues. But when you look at how common these variants are, it does raise the question, if this were truly a problem, why is folic acid still the gold standard recommendation during pregnancy? And why are we not looking at other options there? So in fact, most medical guidelines now advise against testing for these variants and we could boil this down to a few different reasons.
Even with a variant, most people can still convert folic acid into its active form. The process might be slower, but it does still work. Folic acid also consistently reduces the risk of neural tube defects in large studies and those studies naturally include plenty of people with these variants because of how prominent it is. And then there’s also no evidence-based treatment that changes based on knowing whether or not you have these gene variants or not, like whether they’re present. Nothing really changes in regards to overall recommendations thus far.
Aidan:
Yeah, and the main concern I would assume based on that is that it stresses a lot of people out if they find out that they have these gene variants, particularly during a time like pregnancy. So like not testing for it, particularly if it doesn’t change any outcome or anything like that, I can see why that’s the perspective.
I’m going to talk about methylfolate here and folic acid is the man-made synthetic form of folate, and if anyone is concerned about that, the proposed alternative is methylfolate. If somebody wanted to go down that route, it’s likely fine. The recommended dosage is the same during pregnancy of 400 to 500 micrograms per day. There are only two downsides that I could see of using this proposed alternative because like the way I’m looking at it is like, let’s say somebody had got a test, they had concluded that they wanted to do something about it. They wanted an alternative, even with the knowledge that everything we’ve spoken about being like, the research is still quite positive and everything about using folic acid. But say they did want to go to an alternative.
The only two downsides I see are one, it costs more money, noticeably more money. Two, it has less research. Specifically, it doesn’t have research finding that reduces neural tube defects. That doesn’t mean that it doesn’t, we just don’t have research at large scales showing that. We don’t know for sure whether it does or doesn’t. If I was going to speculate, I would make the assumption that it does. It’s just, I think in the case of pregnancy, a lot of people are cautious about a lot of things. It kind of, in my own opinion, makes sense to go with the thing that we know works consistently. So we have that clear evidence with folic acid, which is why it’s still the gold standard.
Leah:
Now, if you were interested in this area, I think a big thing to mention is technically you could just get all of the relevant information you need without actually testing for the variants and knowing whether or not you do have the gene variants. For example, measuring your levels of homocysteine, B12, B6 and folate will give you the information you want and the information that is required to like act upon, regardless of whether there is a gene variant there. And if there were any abnormalities in the bloods with those things, you would focus on addressing those individually.
So regardless, the treatment is going to be exactly the same, whether or not you know the gene variant is there or it’s not there. But the thing that could potentially change is you potentially considering what folic acid you’re going to use or folate supplement. Are you going to use methylfolate? Do you want to use the regular form of folic acid? Like that’s the thing that would change potentially, or you could start questioning if you did have the gene variant. But outside of that, nothing else changes.
Aidan:
I’ve left it a little bit late in this podcast, but I’m going to talk about some rare exceptions here. I don’t think anyone listening will fall into this category, but just in case they might’ve been annoyed so far, but there we’ve just really focused on the two main variants because it’s relevant for so many people. But I talked about, or we both talked about how there’s like 40 plus different variations. So rare variations do exist and could arguably be more relevant in certain cases. It is possible that the enzyme is very suppressed or completely inactive. And in those cases, it’s ideally picked up in infancy or in early childhood because issues would be very likely to be presenting themselves. And in those cases, the approach is different.
Everything we’ve spoken about so far has been, doesn’t really change what we’re doing. But in those cases, the approach could be different. There’s often far more aggressive nutrition support from things like B-Tain, which can help clear homocysteine, which would be elevated in that. And they might also be doing things with methylfolate and methylcobalamin, is basically vitamin B12 and a few other things in addition to more frequent monitoring. I’m largely mentioning that on the off chance it’s relevant for somebody listening to that, but I also think it’s worth knowing that as well.
Leah:
So overall, these gene variants are highly prevalent, but the practical relevance is arguably limited in most cases, except for maybe more of those rare versions of the variations. So overall, nothing really changes in regards to mainstream recommendations around supplementation, dietary intake, etc. Whilst it might be something that’s interesting to know about, particularly if you have plans on becoming pregnant or if you are pregnant, it doesn’t really change things from a health perspective.
This has been episode 207 of the Ideal Nutrition Podcast. If you haven’t yet left a rating or review, it’s always greatly appreciated for you to do so. Otherwise, thanks for tuning in.