A big thing in genetics right now is MTHFR variants. Also comically known as the “motherfucker” gene, it stands for methylenetetrahydrofolate-reductase. This is the enzyme that converts folic acid into the biologically active form methylfolate.
Folate is vitamin B9, and it works very closely with B12 (cobalamin) in the so-called folate/methylation cycle. This is a fundamental biochemical process that happens in every cell in your body and is critical to a huge range of functions, from DNA repair to building neurotransmitters, lipid membranes, and cell receptors.
The problem with certain MTHFR variants, which are rather common in the general population, is they foster a reduced capacity to convert folic acid into methylfolate. Folic acid is cheap and is commonly used to enrich processed foods to prevent folate deficiency. It’s better than nothing, but it has its problems.
In fact, folic acid can act on the same receptors that methylfolate would bind to, but the folic acid is just “inert”and can actively block the function that methylfolate would serve if it were present. Folic acid can thus be an inferior, and even counterproductive, form of folate to consume, especially in those with MTHFR variants.
This is also a topic of discussion for pregnant women who have been told for years to take folic acid. Again, it’s better than nothing, but methyfolate would be better, and there are correlations between mother’s MTHFR status and various developmental and genetic problems in the offspring.
An intermediate metabolite of the methylation cycle is homocysteine, which has been implicated in a host of modern, chronic diseases, including the top causes of mortality like cardiovascular disease, cancer, and neurodegenerative diseases.
Without adequate folate and B12, homocysteine can accumulate, and not get broken down into cysteine like it should. Folate and B12 in tandem are the main driver to bring down homocysteine levels.
Active methylfolate is found largely in leafy greens, with spinach being of particularly high content, while animal foods are the main source of B12.
The standard American diet suffers largely on the folate side, being deficient in greens and veggies, only getting folate via folic acid in processed food.
On the other hand, vegans and vegetarians famously must supplement B12 because of their avoidance of many or all animal foods.
A deficiency of either is rather serious and devastating, mimicking things ranging from psychosis to multiple sclerosis. Naïve vegan teenagers have gone blind from B12 deficiency, for example.
Folate is hugely implicated in all mental health disorders, directly due to its fundamental role in neurotransmitter production, and indirectly because of its host of other actions and products.
The take-away is obviously that eating more spinach salads and/or supplementing with methylfolate is important for anyone with or without MTHFR genetic variants.
But where many come to discover the importance of this class of genes is in how issues with this pathway can be compounded by other genetic variants that one has.
For example, someone may have MTHFR variants plus a certain variant in a closely related gene leading down the pathway to make dopamine, for example. They may have always felt a tendency toward fatigue and inattention (assuming less dopamine could lead to this), but with a healthier diet that swapped junk food for greens, this pathway could literally open up and function far more optimally.
Not every modification is so simple, but it illustrates the point that innocuous-looking lifestyle changes could potentially be acting as rather potent epigenetic inputs into a particular individual’s genome, with its own unique set of resiliencies and fragilities that manifest in that person’s experience.
The fundamental role of folate is a shared springboard into that variation. Paying a little attention to it and supporting it can lead to a lot of good things.