What vegans need to know about B12, homocysteine, and MTHFR

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What vegans need to know about B12, homocysteine, and MTHFR


What vegans need to know about B12, homocysteine, and MTHFR


Are you a Vegan?

You need to know about vitamin B12 deficiency, homocysteine, and MTHFR. 

Now, there’s plenty of research emphasizing the benefits of a vegan diet. 
Veganism has been shown to reduce your risk of coronary heart disease and several types of cancer, as well as many other chronic degenerative diseases.

That’s the good stuff (and there’s lots more!). Unfortunately, there’s some not-so-good stuff, too. 

Numerous studies show that vegetarians -- and especially vegans -- have both lower serum vitamin B-12 and higher homocysteine concentrations than non-vegetarians.

What does this mean?

For a start, it’s a sign that vegans are at a higher risk of nutrient deficiency when animal foods are removed from the diet. And although most vegans are aware that vitamin B12 is only present in animal foods, not everyone understands just why B12 is so important. As a result, they may not be particularly motivated to supplement, or they take the first supplements they see on the supermarket shelf without realizing these are NOT good supplements and often don’t even contain the correct forms of nutrients!

What many vegans also don’t know is the link between B12 deficiency, homocysteine, and MTHFR. 

Why do vegans need B12?

Vitamin B12 plays an important role in energy production, the formation of red blood cells, and the synthesis of fatty acids. It works closely alongside vitamin B9 (also called folate) to help make red blood cells which are required for carrying oxygen to all parts of your body.

Vitamin B12 is also required to keep homocysteine levels from becoming elevated. Elevated homocysteine has been linked to cardiovascular disease, poor cognition, and low bone mineral density. 

Vegans who don’t supplement their diet with B12 tend to have low B12 levels and elevated homocysteine. 

And, while hyperhomocysteinemia (HHcy) in vegetarians and vegans is mainly related to B12 deficiency, it’s been found that a mutation in the MTHFR gene, especially SNP (single nucleotide polymorphism) C677T, can also contribute. 

An MTHFR mutation also increases your risk of Vitamin B12 deficiency. MTR and MTRR variants are other genetic SNPs which may significantly impact the conversion and absorption of B12 in the body as well.

A 2013 study published in the International Journal for Vitamin and Nutrition Research investigated the prevalence of Hcy, B12, folate, B6, and MTHFR C677T in 109 Thai vegans and 86 omnivores

Vegans were found to have significantly higher levels of homocysteine, particularly if they had a C677T mutation. Vegans with CC, CT, and TT mutations were also found to have a significant decrease in serum folate. However, the omnivores in the study did not have high levels of either homocysteine or folate.

The researchers concluded that while elevated homocysteine in Thai vegans was mainly due to low B12 levels, the MTHFR C677T mutation also played a role.

Further research published in the Annals of Nutrition and Metabolism showed that vegetarian subjects were prone to significantly higher homocysteine levels, along with a higher prevalence of hyperhomocysteinemia, and lower serum vitamin B12 levels than controls.

What is homocysteine and why should I worry?

Homocysteine is a naturally-occurring amino acid that’s created when your body metabolizes the essential amino acid methionine. Methionine is broken down into homocysteine, and then homocysteine is ‘recycled’ back to become methionine again. Methionine is a sulfur-containing amino acid involved in building proteins and producing certain substances in the body, including the antioxidant glutathione and the molecule SAMe. 

SAMe is a universal methyl molecule that donates a methyl (CH3) group required for the proper function of the cardiovascular system, detoxification pathways, and neurological systems.  So methionine is definitely what you want more of in your body, NOT homocysteine.

A host of important nutrients are created throughout the methionine-homocysteine pathway; all of which play a part in various other biochemical reactions such as detoxification, healthy immune function, the formation of connective tissues, as well as brain and cardiovascular function.

Normally, homocysteine is broken down by your body’s stores of vitamin B12, vitamin B6, and folate and changed into substances that your body actually needs. However, a lack of any particular nutrient can lead to an undesirable elevation in homocysteine levels and a lowering of the ‘good and necessary’ compounds your body needs.

There are two pathways through which the methylation cycle can convert homocysteine to methionine. Homocysteine can either be re-methylated to form methionine and retained in the methylation cycle, or it can be converted to cysteine via the transsulfuration pathway, which also withdraws it from the methylation cycle

Remethylation of homocysteine to form methionine completes the methionine cycle. This process involves either methionine synthase (MS), which in turn requires either 5‐methyltetrahydrofolate as a methyl donor, or betaine homocysteine methyltransferase (BHMT), which requires betaine (or TMG) as a methyl donor.


When these pathways have everything they need to happen properly, there should be very little homocysteine left in your bloodstream. However, if you are deficient in B vitamins - especially B12, B6, and B9 - you are at a greater risk of developing high levels of homocysteine in your blood.

Why is high homocysteine so bad?

If homocysteine accumulates in the body due to a lack of folate, B6, and vitamin V12, serious health issues can develop. Research has linked homocysteine to vascular damage, cognitive impairment, neurological complications, congenital defects, and pregnancy complications.

Homocysteine is also shown to stimulate the growth of smooth muscle cells, causing the deposition of extracellular matrix and collagen. Artery walls can become tough and thickened, increasing the risk of cardiovascular disease.

This is because raised homocysteine affects the way cells use oxygen, causing a buildup of oxidized fats and proteins within developing arterial plaques. This oxidation injury - along with methylation defects and impaired DNA repair due to poor folate metabolism - has also been linked to the development of cancer.

As if that weren’t enough, homocysteine has also been linked to neurodegenerative disorders, particularly in the case of vitamin B12 deficiency. 

Why vegans are at risk of elevated homocysteine

A significant proportion of the population has a genetic variant in folate metabolism, the MTHFR polymorphism. And in vegans, elevated homocysteine levels are normally due to low B12 intake.

One good thing about the vegetarian or vegan diet is that many plant-based foods are rich in folate. In fact, non-vegetarians with elevated homocysteine tend to have more of a problem with low folate than with low B12. However, the lack of B12 can have serious consequences. 

Several studies have measured the vitamin B12 and homocysteine levels in vegetarians. The results have been fairly consistent: that vegetarians who don’t supplement their diets with B12 tend to have high levels of homocysteine levels. This result is even more significant in vegans, but also present in lacto-ovo vegetarians.

These studies also showed that the average homocysteine levels of vegans were 14 to 20 µmol/l compared to about 8 to 12 µmol/l for omnivores.  The ideal range for homocysteine in a healthy adult is 5-9 µmol/l.


What if you’re vegan and you also have MTHFR?

Along with the risk of B12 deficiency, the MTHFR genetic mutation can pose even more problems for vegans. 

The MTHFR gene provides your body with a set of instructions for making an enzyme called methylenetetrahydrofolate reductase (MTHFR). This enzyme has the job of converting folic acid you eat (or take in supplements) into methyl-folate - the active form of folate. 

Mutations of the MTHFR gene can change the way your body converts nutrients into active vitamins, minerals, and proteins that you can use. It can even affect your body’s levels of certain hormones and neurotransmitters, along with cognitive function, digestion, cholesterol levels, and more.

The active form of folate that the MTHFR gene is required to produce - L-Methylfolate - also plays a vital role in the synthesis of neurotransmitters: particularly serotonin, dopamine, and norepinephrine. Another important product of methylation is S-adenosylmethionine, or SAMe. 

Without methyl-folate, your body can’t carry out proper methylation. Methylation is crucial to the proper functioning of many different processes in your body - from the production of DNA and metabolism of hormones to healthy detoxification and cognitive function. If your body is lacking in methylfolate, this entire process grinds to a halt. 

This can lead to a range of symptoms that can end up severely affecting normal bodily functions. Some chronic health issues linked to MTHFR include behavioral disorders, autoimmune diseases, thyroid problems, cardiovascular disease, chronic fatigue, fibromyalgia, digestive issues, hormonal issues, migraines, depression, schizophrenia, and more. 

Unfortunately, solving the problem of B12 deficiency is not as simple as taking any old supplement! 

How to treat MTHFR mutation symptoms as a vegan

If you’ve been tested and found that you do have the MTHFR mutation, don’t panic! Symptoms can vary depending on the type of mutation you have and whether the variations affect one or more of your MTHFR gene SNPs, as well as whether or not you have other genetic variants along the methylation pathway in the body.

Making changes to your diet and lifestyle should be your first step in optimizing your body’s methylation processes and reducing the risk of symptoms. 

Dietary recommendations for vegans to optimize methylation

Increase your dietary intake of folate

Remember, folate is NOT the same as folic acid. Folate is the natural form of the vitamin as it occurs in food, while folic acid is a synthetic form. The bioavailability of L-Methylfolate is much higher than folic acid alone.

Eating folate-rich foods is a good way to improve methylation. Some of the best plant-based sources of folate include vegetables (especially dark leafy greens), fruits and fruit juices, nuts, beans, peas, and grains.

Additional foods that support healthy methylation include asparagus, avocado, broccoli, and legumes.

Improve gut microbiome and integrity

A healthy gut microbiome will optimize your body’s ability to obtain nutrients from food, which in turn will support your overall health and wellbeing.

Promote the health of your gut bacteria by eating fermented foods such as kimchi, kefir, miso, and kombucha. These contain natural probiotics that help with proper digestion.

Reduce intake of inflammatory foods such as sugar, refined grains, trans fats, and processed snacks. 

Gluten is a major cause of inflammation in the gut lining, so avoid where possible. Those with gluten sensitivity and MTHFR can suffer a double blow as each condition can amplify the other.

Eat more healthy fats, especially N-butyrate: a short-chain fatty acid that nourishes the cells lining the gut. N-butyrate occurs naturally in ghee and coconut oil.

Other gut-healing foods include bone broth, flaxseeds, chia seeds, and turmeric. 

And if you choose a probiotic, consider a spore-based option as the bacillus strains are very hardy and can get to your gut easily bypassing the acidic stomach that typically kills many other strain types.

Support detoxification pathways

Impaired methylation can hinder your body’s ability to detoxify properly, especially in the liver. This means it’s more important than ever to support your body’s natural elimination processes.

You can boost detoxification by eating a clean, wholesome diet and taking up lifestyle habits.

Increase your fiber intake to 30-50 grams per day

Drink at least 2 liters of pure, filtered water per day (consider water with a high alkaline content and a negative ORP measurement for optimal health)

Eat plenty of anti-inflammatory foods: brightly colored fruits and vegetables, high-quality protein, healthy fats.

Avoid or limit all refined sugars 

Get active by exercising at least five days a week for 30 minutes a day

Attend regular sauna treatments (if you’re looking for a revolutional infrared home sauna, check out this company’s line up) and Epsom salt baths.

Avoid or limit exposure to toxins such as artificial additives in food and chemical house cleaners. These can impair methylation further


Reduce or limit alcohol intake

Minimize stress levels 

Studies have shown that long-term stress results in decreased DNA methylation. In particular, there is decreased methylation of a gene called fkbp5, a glucocorticoid-responsive gene that plays an important role in the stress response.

It’s impossible to avoid stress completely, but there are lots of ways you can reduce its impact on your body. 

Learn to meditate and engage in regular meditation practice every day

Start journaling

Try forest bathing

Avoid situations, people, and environments that you know stress you out


What supplements to take if I am vegan with MTHFR?

Vegan-friendly supplements

Impaired methylation can mean that a huge range of important molecules cannot be efficiently produced. This is why those with MTHFR are often low in B12 as well as folate and a number of other key nutrients. These must be replaced with the right supplements. 

Vegan-friendly B12

Vitamin B12 is crucial for reducing homocysteine. It also plays a major role as a cofactor in the methylation process of L-methylfolate, and is then required for the conversion of homocysteine to methionine. The conversion of homocysteine to cysteine also requires B-6 (specifically pyridoxal-5-phosphate).

One study showed that when vegans took 500 µg/day of vitamin B12 for 2 months, their homocysteine levels were reduced to less than 5 µmol/.

Similarly, another study showed vegans who averaged 5.6 µg/day of B12 to have homocysteine levels of 7.9 µmol/l, which was slightly lower than the omnivores in the study. This means that taking B12 can help vegans maintain healthy homocysteine levels.

In addition, Vitamin B12 is vital for proper brain development and is associated with one-carbon metabolism required for transmethylation reactions. It’s also involved in the formation of S-adenosylmethionine (SAMe) which we know to be the neurotransmitter generator - so this is a key nutrient to take along with L-Methylfolate for maximum effect against depression.

Supplementation with a highly bioavailable form of vitamin B12 5,000 mcg is the most efficient way to ensure optimal levels quickly. This is particularly important for vegans/vegetarians, the elderly, and anyone who is unable to absorb B12 efficiently.

Methy-Life’s™ B12 Complete is ideal for people who have  MTR, MTRR, COMT, or other gene mutations that may be affecting B12 absorption. B12 Complete contains a combination of the 3 most bioactive forms of B12 (hydroxocobalamin, methylcobalamin and adenosylcobalamin) for maximum delivery and absorption.

The B12s within this supplement have already been converted into forms that can be absorbed and used by the body’s cells immediately. This is a full-spectrum B12 product.


Vegan-friendly methylfolate

The MTHFR mutation can seriously compromise your ability to convert folic acid into a form that your body can use, so it’s important to avoid any supplements or foods that contain folic acid. 

L-methylfolate supplements are known to reduce homocysteine levels, so if you know your levels are high, be sure to consider this important nutrient.

Supplementation with L-methylfolate at higher levels has also been found to be beneficial for those with depression: especially those who have not responded adequately to treatment with antidepressant medications.

Folate 5-MTHF has been classified as a ‘medical food’ at these higher dosage levels and is also available as an over-the-counter dietary supplement. However, some of the best methylfolate supplements for those with MTHFR mutations or suffering from depression include Methyl-Life products (Methylfolate 7.5+, Methylfolate 10, and Methylfolate 15+).

These have been created by a team of natural health experts and used successfully by hundreds of people all over the world. It’s worth noting that Methyl-Liferecently received data from a study that showed theirs to be the purest, stable, and most potent of four of the world’s industry-leading, patented L-Methylfolates. Check out the study comparison details to learn more.

Vitamin D


Vitamin D is known for its role in the regulation of gene expression via the vitamin D receptor, a nuclear transcription factor. Recent research has shown vitamin D is crucial in regulating DNA methylation, and is also involved as a mechanism of modulation of gene expression.

Studies show that low levels of vitamin D correlates with low activity of methylation. However, when young black people with low vitamin D and methylation levels were treated with varying doses of vitamin D supplements for 16 weeks, researchers found a significant dose response: the more vitamin D a person received, the higher their methylation activity.

While it’s possible to obtain Vitamin D by spending 20-30 minutes in the sunshine each day, this may pose a risk for UV-related skin damage. Instead, seek out a comprehensive multivitamin such as Methyl-Life’s™ Chewable Multivitamin, which contains Vitamin D along with L-Methylfolate AND Active B12 as well as B6 (pyridoxal-5-phosphate) for a complete methylation-enhancing experience.


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