Episode 207 – Should We Worry About the MTHFR Gene?

Key Topic

This is a common one that comes up in the health optimisation space
Technically gene variations are quite prevalent. So if it is relevant, the majority of women should be aware of it prior to pregnancy.
Given it isn’t a huge topic in mainstream health and medicine, it kind of indicates that mainstream health and medicine doesn’t care about it lol.
That implies it likely can’t be a big deal on a large scale (unless you just have general distrust of mainstream stuff). But we will go through the ins and outs of it.

MTHFR is an abbreviation that is used interchangeably for both a gene and an enzyme.
It stands for Methylenetetrahydrofolate reductase (pronounced methylene-tetra-hydro-folate reductase)
The enzyme is involved in folate metabolism.
The gene provides instructions for the enzyme
There are actually over 40 known mutations. But there are two main ones that we see more commonly ( C677T and A1298C – but we don’t need to say them).
We will spend most of this podcast talking about those ones.

Roughly 40-60% of the population has some form of these two variants.
At face value, that means that if these mattered, it would matter for like half the population.
Going deeper though, obviously there are differences.
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 got one.
Statistically 30-50% of people have one copy of the most studied one which is the C677T variant and 10-15% have two copies
So even still 10-15% is a big percentage of people.

Since the MTHFR plays a role in processing folate and regulating homocysteine levels, a lot of the relevance is related to those.
For example. Elevated homocysteine has a link with cardiovascular disease
AND In pregnancy it is often recommended to supplement folic acid, so this would reduce the metabolism of that
And there are a bunch of other proposed links also

We will briefly touch on the CVD stuff since it will likely be quicker than pregnancy
It’s debated but the research does seem to point in the direction of there being a link between MTHFR variations and CVD outcomes.
The main mechanism is related to homocysteine being elevated
Having a good intake of folate, B6, and B12 (through either food or supplements) can help reduce this.
If concerned you can test your levels for all 4 of those things.
Technically there isn’t evidence looking at whether having a good intake of folate, B6 and B12 reduces the risk of CVD in those with MTHFR variants, but it’s still a good idea to do that anyway for other reasons.

This is the most common context where MTHFR gets talked about.
The concern is that reduced folate metabolism in people with MTHFR variants means folic acid (especially the synthetic form) could cause issues.
But when you look at how common these variants are, it raises the question — if this were truly a problem, why is folic acid still the gold-standard recommendation during pregnancy?
In fact, most medical guidelines now advise against testing for MTHFR variants.

Even with a variant, most people can still convert folic acid into its active form — the process might be slower, but it still works.
Folic acid consistently reduces the risk of neural tube defects in large studies — and those studies naturally include people with MTHFR variants.
There’s no evidence-based treatment that changes based on knowing whether the gene variants are present

Folic acid is the man-made, synthetic form of folate.
For those concerned about it being an issue, the proposed alternative is methylfolate.
If somebody wanted to go down that route, it’s likely fine. The recommended dosage is the same at 400-500mcg per day.
The only downsides of it are: 1) It costs a lot more 2) It has less research. Specifically, it doesn’t have research finding that it reduces neural tube defects. We don’t know for sure whether it does or doesn’t. Whereas folic acid has clear evidence that it does, which is why it’s still the gold standard.

If you were interested in this area, technically you could get the relevant info without testing for the variants.
For example, measuring your levels of homocysteine, B12, B6 and folate will give you the info you want.
And if there were any abnormalities you would focus on addressing those.
Outside of whether or not you would choose the active forms of the supplements such as methylfolate, which is debated anyway, the treatment would be exactly the same.

One last caveat I want to add is that we’ve focused on the two main variants, since they are relevant for around half the population.
Rarer variations do exist and are arguably more relevant.
It’s possible that the enzyme is very suppressed or completely inactive.
In those cases, ideally it is picked up in infancy or early childhood.
In those cases, the approach is very different. There is often far more aggressive nutrient support of things like betaine (to help clear homocysteine), methylfolate, methylcobalamin and a few other things, in addition to more frequent monitoring.
I’m largely mentioning it on the off chance we have somebody listening who falls into that category and feels like we have downplayed this.

These gene varietns are high very prevalent, but the practical relevance is arguably limited in most cases
Which is a large part of why there aren’t that many mainstream recommendations.
So overall, whilst it might be something interesting to know about, it doesn’t really change things from a health perspective

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