Genetics and epigenetics are the scientific explanations for “nature vs. nurture”. While your genetic code (nature) has some control over your potential physiology, the way you are raised, take care of your body, and the experiences you have (nurture) will all affect when and whether you reach your genetic potential. These are epigenetic factors. 

Below is a deeper explanation, focused around the genetic and epigenetic factors affecting the MTHFR gene, L-methylfolate production, and methylation.


When a baby is conceived, they inherit 2 copies of every gene; one from each parent. MTHFR is the name of one particular gene, out of thousands, that each person has 2 copies of. The gene codes for an enzyme called “methylenetetrahydrofolate reductase (MTHFR)”, which is responsible for the conversion of dietary folate (vitamin B-9 or folic acid) into its biologically active form, L-methylfolate, to be used by your cells in the process of methylation. Methylation is happening in almost every cell of your body at a rate of billions of times per second and contributes to a multitude of different biological processes. 
Unfortunately, many people have a slight change to the code in either one or both copies of their MTHFR gene. A difference in a code for a certain gene is known as a “mutation”, “variant”, or “polymorphism” depending on the context. If the MTHFR gene is coded incorrectly, the MTHFR enzyme cannot be produced efficiently or correctly, so folate will not be activated at a normal rate and the downstream effect can be detrimental to methylation, and therefore, your health.

When a person has inherited one copy of a dysfunctional gene, and one normal copy, they have a 50% chance of passing on the mutation to each of their children. If a person has 2 dysfunctional genes, each of their children is guaranteed to inherit at least one dysfunctional gene. That is how the MTHFR variants are passed on genetically, and is the genetic reason that you may be under-producing MTHFR and experiencing a deficiency in L-methylfolate and reduced methylation.

If you are experiencing symptoms that indicate a possible L-methylfolate deficiency (link to L-methylfolate info), it may be advisable to have your blood tested for L-methylfolate, and your genotype tested for MTHFR polymorphisms. Genetic tests can be administered through recommendation by your healthcare professional, or through an at-home testing kit such as 23andMe. 


It is possible that you have two perfect copies of the MTHFR gene, but are still under-producing MTHFR enzyme and experiencing a deficiency in L-methylfolate and inefficient methylation. It could be the result of a phenomenon called “epigenetics” which directly translates to “above the genome”. Epigenetics is the study of environmental factors that do not alter the genetic code directly, but modify the way the genes are expressed, changing the abundance of resulting proteins, and thereby affecting the health and/or structure of the organism to whom the genetic code belongs. 

Epigenetic factors that negatively affect methylation can include a poor diet or a lack of cofactors such as vitamin B-12, environmental toxins like pollutants or pesticides, the amount of activity or rest your body gets, or a disease state, among others. Epigenetic factors act like on/off switches for certain genes, controlling when and how much of the associated protein gets built. Epigenetics is the reason identical twins living different lifestyles can look different or have different levels of health, even though they have the same genetic code. 

In terms of specific factors that can alter the effectiveness of MTHFR, there are some drugs, such as methotrexate, that are known to block intermediaries in the folate cycle [1]. Methotrexate is the most prescribed medication for rheumatoid arthritis and has significant anti-arthritic data to back up its use. However, it is an antifolate, and prescribing physicians may not always consider the holistic, cellular effects it may be having throughout the body, such as slowing methylation through antagonization of the folate process [1]. 

How much dairy are you consuming? It has been demonstrated that high levels of dietary milk intake are associated with high levels of folate-blocking antibodies [2]. These antibodies, which can prevent the absorption of folate, have been shown to cause similar downstream effects as those seen in patients with severe folate deficiency or an MTHFR mutation [3]. 

But just to make things more complicated, how much dairy are you consuming? It turns out, there’s a balance, because methionine, an essential amino acid that has a critical role in methylation and the folate cycle, has to come from your diet and is found in foods such as dairy products, meat, and fish. Low methionine in the diet (higher risk for those on plant-based, vegan/dairy-free diets) can alter the efficiency of methylation, even when MTHFR is plentiful. 

What Can I Control?

You can’t change your genes, but you are (most likely) in total control of your folate status. If you have genetic testing done and find out you carry one or two polymorphisms of the MTHFR gene, you can begin supplementing with L-methylfolate. This is the easiest way to make sure your body is getting all of the activated form of vitamin B-9 that it needs for the folate pathway and methylation, without depending on the MTHFR enzyme as the middleman. 

Even if you do not have an MTHFR mutation, you can supplement with L-methylfolate instead of folate or folic acid to ensure epigenetic factors that may be altering MTHFR efficiency are not in control of your L-methylfolate availability.

Whether or not you have an MTHFR mutation, you can take a look at your lifestyle, your healthy (and maybe-not-so-healthy) habits, and your diet, to make sure your body is getting all the precursors and cofactors necessary for the essential cellular processes to work at maximum efficiency. If you are on medications that may be affecting your folate status, talk to your doctor about combating this issue nutritionally, or discuss possible alternatives that will benefit your health across the board, rather than sacrificing one element of your health to improve another.


  1. Kremer, Joel M. “Toward a better understanding of methotrexate.” Arthritis & Rheumatism 50.5 (2004): 1370-1382.
  2. Berrocal-Zaragoza, Maria Isabel, et al. “High milk consumers have an increased risk of folate receptor blocking autoantibody production but this does not affect folate status in Spanish men and women.” The Journal of nutrition 139.5 (2009): 1037-1041.
  3. Cabrera, Robert M., et al. “Autoantibodies to folate receptor during pregnancy and neural tube defect risk.” Journal of reproductive immunology 79.1 (2008): 85-92.