MTHFR Gene Mutations and Veganism

Veganism has increased by an estimated 300% over the past 15 years. Around 6% of US consumers—or 9.7 million people—now claim to be vegan.

Reasons for choosing a vegan diet may relate to health, religious beliefs, and ethical stance on animal rights. While there are benefits to following a plant-based diet, research suggests that vegans with an MTHFR gene mutation may be at risk of several deficiencies and health concerns. 

Vegans are frequently found to have lower serum vitamin B-12 and higher homocysteine concentrations than non-vegetarians, suggesting that avoiding animal products results in a shortfall of essential nutrients. 

Low levels of B12 and high levels of homocysteine can contribute to a range of cardiovascular and nervous system problems, among others. 

This article will examine the issues vegans with an MTHFR gene mutation face and why they may be at risk of elevated homocysteine levels. We will also explain how these issues can be managed and what supplements may be of benefit. 

Excluding animal products from the diet may affect the status of certain B-vitamins, leading to a rise in homocysteine concentration. This stems mainly from B12 deficiency, which is common in vegans.

Homocysteine is a sulfur-containing amino acid produced when the amino acid methionine is broken down in the body. Accumulation of homocysteine can cause inflammation and hardening of the blood vessels, increasing the risk of atherosclerosis, heart attack and/or stroke, and blood clots.

Homocysteine levels are governed by several factors, including B12, B6, folate, and enzymes involved in methionine metabolism. Their levels are inversely correlated, which means homocysteine levels increase as vitamin B concentrations decrease. 

Hence, hyperhomocysteinemia among vegetarians and vegans appears to be caused mostly by vitamin B12 deficiency. 

Vitamin B12 is the only vitamin that is synthesized exclusively by microorganisms. Dietary sources are primarily of animal origin, including meats, dairy products, and eggs.

One study found that in a group of vegetarians, the average homocysteine level was 13.18 vs. 10.19 micromol/l in omnivores, while the frequency of hyperhomocysteinemia was 29% in vegetarians vs. 5% in omnivores. In the group of vegans, the average homocysteine levels were 15.79 micromol/l (53% of the individual values exceeded 15 micromol/l). Optimal homocysteine levels (as recommended by leading naturopaths) should be between 5-7 micromol/l.

Two major enzymatic reactions are dependent on vitamin B12. The first involves the conversion of methylmalonic acid, a compound that reacts with vitamin B-12 to produce coenzyme A. Increased levels of methylmalonic acid are a sign that B12 levels are suboptimal. 

In the second reaction, homocysteine is converted to methionine by using vitamin B12 and folic acid as cofactors. Again, vitamin B12 or folic acid deficiency may lead to increased homocysteine levels.

Elevated homocysteine may also result from a mutation on the MTHFR gene, which affects 30-40 percent of the American population. The MTHFR enzyme is crucial to both homocysteine metabolism and the conversion of 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate, the predominant circulating form of folate. The C-to-T mutation in the MTHFR 677 gene results in a defective MTHFR enzyme, which may affect homocysteine levels.

The link between veganism, B12 deficiency, and hyperhomocysteinemia is even greater for those with an MTHFR gene mutation due to their inability to carry out specific biochemical processes. 

The MTHFR mutation—particularly C677T— is associated with reduced enzymatic activity, decreased concentrations of folate in serum, plasma, and red blood cells, and higher total homocysteine concentrations.

B12 and folate are both crucial for proper methylation and maintaining healthy homocysteine levels, along with many other functions. Vegans—especially those with MTHFR C677T—would be well-advised to supplement B vitamins, namely bioactive B12 and folate. 

The natural forms of vitamin B12 include methylcobalamin (MeCbl), adenosylcobalamin (AdoCbl), and hydroxocobalamin (OHCbl), all of which have been shown in clinical studies to improve vitamin B12 status. 

They are bioidentical to the B12 forms occurring in human physiology and animal foods. 

Cyanocobalamin, by contrast, is a synthetic B12 compound used in some supplements and to fortify certain foods. It occurs only in trace amounts in the body.

One study showed that vegans who took 500 µg/day of vitamin B12 for two months reduced their homocysteine levels to less than 5 µmol/L.

Other research has suggested that those with genetic mutations affecting B12 absorption might raise their B12 status more efficiently by using a supplement with a combination of all three naturally occurring forms of B12, such as Methy-Life’s® B12 Complete.

Vegans with an MTHFR mutation are advised to focus on optimizing their body’s methylation processes to reduce the risk of elevated homocysteine and B12 deficiency. This should involve supplementing with methylated folate. 

Low folate levels are typical of MTHFR mutations, and folate plays a crucial role alongside B12 in homocysteine metabolism. For those with a defective MTHFR enzyme, folic acid cannot be efficiently metabolized: only 5-methyl-THF (methylfolate) can participate in the conversion of homocysteine to methionine. 

For this reason, it is essential to avoid foods and supplements containing folic acid. Folic acid is a synthetic form of the vitamin, which undergoes a multi-step conversion process in the body catalyzed by the MTHFR enzyme.

As explained above, both B12 and methylated folate are crucial for supporting methylation and homocysteine metabolism. For vegans with an MTHFR gene mutation, these nutrients are best obtained through quality supplementation of naturally-occurring B12 and methylfolate. These forms of nutrients are readily absorbed by the body even when metabolic defects are present.

Methy-Life’s® B12 Complete is ideal for vegans and/those with gene mutations that may compromise B12 absorption. B12 Complete is a full-spectrum B12 product containing a combination of the three most bioactive forms of B12: hydroxocobalamin, methylcobalamin, and adenosylcobalamin. These forms can be absorbed and used immediately by the body’s cells, offering maximum delivery and absorption. 

Folate supplements are also readily available over the counter and online. The most biologically active forms of folate include ((6S)-5-methyltetrahydrofolate or (6S)-5-MTHF), ((6S)-5-methyl-tetrahydrofolic acid, calcium salt or L-methylfolate) and ((6S)-5-methyltetrahydrofolic acid, monosodium salt or L-methylfolate). These are pure, stable crystalline forms of the naturally-occurring predominant form of folate. 

Methyl-Life® Methylfolate 7.5+, Methylfolate 10, and Methylfolate 15+ contain the most bioactive nutrient form of folate available, Magnafolate® PRO. This form of folate can cross the blood-brain barrier and be immediately used by the body’s cells. 

Alternatively, vegans may choose Methyl-Life® L-Methylfolate B-Methylated-II, which contains both L-Methylfolate (3 mg) and Methylcobalamin (3.75 mg).