MTHFR, B12, Homocysteine and Veganism

MTHFR, B12, Homocysteine and Veganism

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Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Kari Asadorian - BSN, RN

Medical Reviewer:

Kari Asadorian - BSN, RN
Jamie Hope - Methyl-Life® Founder

Edited By:

Jamie Hope - Methyl-Life® Founder
Last updated:

Veganism is a widely adopted diet in the US. While exact numbers vary depending on research methods, estimates suggest that 1–4% of Americans identify as vegan.1 Veganism involves omitting any foods from animal sources along with their by-products. Many choose veganism to avoid contributing to animal suffering and factory farming practices. Others may become vegan for health reasons, religious beliefs, or simply dietary preferences.


Several studies have shown the beneficial effects of a vegan diet due to higher daily consumption of fresh fruits, vegetables, cereal, grains, nuts, legumes and seeds. This has been shown to reduce the risk of colon cancer, type 2 diabetes, obesity, and cardiovascular diseases.


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.2 People with MTHFR mutations are at greater risk of high homocysteine due to low folate levels. Vegans are also at risk of high homocysteine due to vitamin B12 deficiency.3 For a vegan who also has an MTHFR mutation, the risk of high homocysteine may be even greater. MTHFR mutations impair the conversion of folic acid into its active form, methylfolate. 

Why does folate intake matter for vegans?

Everyone needs folate at every stage of life. Folate is a B vitamin that helps the body make and repair DNA, cell growth and division, and many other methylation processes. Folate is required for the metabolism of homocysteine to methionine, which then leads to the production of neurotransmitters for healthy cognitive function and mood.4 Low folate levels can lead to high levels of homocysteine in the blood, which can increase the risk of heart disease, stroke, and dementia. Inadequate folate also impairs neurotransmitter production, which can lead to mood disorders.5


Fortunately, most studies suggest that vegans have adequate folate intake. A meta-analysis of 12 studies showed that vegans met the WHO recommendations for folate and had higher folate intakes compared with other diet types.6 Another study showed that people who regularly ate meat were more prone to folate inadequacies than vegetarian and vegan individuals, who typically eat high amounts of plant-based products.7

Vegan sources of folate

Good sources of plant-based folate include leafy greens such as spinach, kale, and romaine lettuce, and dark green vegetables such as broccoli and brussel sprouts. Citrus fruits including oranges and lemons are also good sources, as well as beans and other legumes.8


Folic acid is added to many fortified foods such as breads and cereals. However, folic acid is a synthetic form of folate, and people with MTHFR or DHFR mutations are unable to properly convert it to active folate.


It’s important to note that good levels of folate in vegans may mean that vitamin B12 deficiency is undetected, because folate can mask vitamin B12 deficiency until severe health issues occur.9

Vegan diet and B12

Vitamin B12 is an essential nutrient involved in healthy nerve function, red blood cell formation, and DNA synthesis. It is only available in animal products, which means that vegans and anyone else who doesn’t eat animal foods are likely to be deficient in B12 unless they supplement. Studies show high rates of vitamin B12 deficiency among vegetarians and vegans, although much higher in vegans. B12 deficiency is particularly prevalent in pregnant women or women of child-bearing age eating a plant-based diet.10


Vegans need to monitor their B12 levels closely because B12 is one of the most important nutrients for the proper functioning of the body and mind. In the US, the recommended intake of B12 for an adult is 2.4 mcg a day and 2.8 mcg for women who are pregnant or breastfeeding.11 However, it’s important to note that less than 50% of  a 1mg dose is absorbed in the intestine, and absorption decreases as dosage increases.12


Vitamin B12 is essential for two key processes in the body. First, it helps convert a molecule (methylmalonyl-CoA) into another form (succinyl-CoA), which is required for energy production in cells. Second, it works with folate to turn homocysteine into methionine, an amino acid needed for making proteins and DNA. This process also relies on vitamin B6. Proper methionine metabolism is essential for healthy cell function and DNA synthesis.13


B12 deficiency can occur within the first two years of eating a plant-based diet.14


Early symptoms of vitamin B12 deficiency may include unusual fatigue, digestion problems, and frequent upper respiratory infections, which are difficult to link to B12.15


Signs of vitamin B12 deficiency in vegans may include:

  • Pernicious anemia
  • Poor bone health and greater bone fractures due to high homocysteine levels.16 
  • Mood disorders such as depression, as B12 works alongside folate in producing neurotransmitters.17
  • Cognitive changes such as poor memory, confusion, brain fog.18
  • Fatigue and tiredness.19
  • Shortness of breath (dyspnoea).20, 21
  • Nervous system issues including loss of feeling in the limbs, low blood pressure, muscle weakness, or low mental and physical drive.

Sources of B12 for vegans

Although the best sources of B12 are animal foods (such as organ meats, dairy products and eggs), vegans choose not to eat these foods. Research suggests that small amounts of B12 are present in non-animal sources such as seaweeds, mushrooms, and fermented foods.22


A type of seaweed called nori (dried purple laver) appears to have the highest content of B12 source for vegans and also contains high levels of other nutrients often lacking in vegetarian diets, such as iron and Omega-3 fatty acids.23


However, another study found that vegans trying to supplement with alternative products such as algae, kombucha, and other fermented foods had the lowest levels of holotranscobalamin, a form of vitamin B12 bound to the transport protein transcobalamin, which is a marker of vitamin B12 status and used to diagnose vitamin B12 deficiency.24


While some plant foods contain compounds that resemble B12, they are often not bioavailable (absorbed by the body). The only “reliable” plant-based sources of B12 are fortified foods, such as plant milks, cereals, soy products, and nutritional yeasts.25 However, these fortified foods are usually made with cyanocobalamin, the synthetic form of B12, which is less bioavailable than active B12.26

Homocysteine and vegan diet

Low B12 intake can lead to higher homocysteine concentrations in vegans. High levels of homocysteine are often more common in vegans than in people who eat animal products. One study found that 66% of vegans had high homocysteine compared to 45-50% of the omnivores and vegetarians.27


Other research has also shown that vegetarians have significantly higher homocysteine levels and lower vitamin B12 levels than meat-eaters.28 This demonstrates how important it is for vegans to supplement with B12 if they are unable to obtain it from their diet.

Supplements suitable for vegans

Nutritionists recommend vegans supplement with vitamin B12, iron, vitamin D, and EPA/DHA.29 The most commonly available vitamin B12 supplements are cyanocobalamin and methylcobalamin. Methylcobalamin is an active, natural bioidentical form of B12 and is ready-to-use when consumed. Cyanocobalamin is the synthetic form, and must go through a complicated multi-step process to be activated before it can be used by the body.30


Supplementing with the natural, bioidentical forms of B12 (methylcobalamin, hydroxocobalamin and adenosylcobalamin) is recommended over cyanocobalamin as they are better absorbed by the body. Research shows that people with particular genetic mutations affecting B12 absorption may improve their B12 levels more efficiently with one or more of these bioactive forms.31 A 2019 study found that sublingual B12 was absorbed more effectively than intramuscular B12 and was superior in increasing B12 levels. Sublingual absorption overcomes barriers to intramuscular injections, and researchers have recommended it as a first-line option for patients with B12 deficiency.32

MTHFR, B12, Homocysteine and Veganism

Key takeaways:

  • Icon Vegans with an MTHFR mutation are at higher risk of elevated homocysteine if they do not get enough B12.
  • Icon The vegan diet contains plenty of natural folate, but those with MTHFR should avoid foods fortified with folic acid.
  • Icon Vegans should supplement with bioactive B12 to support their mental and physical health and reduce the risk of deficiency.

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Frequently Asked Questions about MTHFR, B12 and vegan diet

Can vegans get B12 naturally?

Some non-animal foods contain small amounts of B12, such as seaweeds, mushrooms, and fermented foods. However, this may not be enough to maintain healthy B12 levels, which is why many vegans and vegetarians are deficient. Nutritionists recommend supplementing with a bioactive form of B12 if you are not obtaining enough from your diet.33

Why is B12 a concern for vegans?

B12 deficiency is common in vegans, especially in pregnant women or women of childbearing age. This is because Vitamin B12 is only available in animal products, apart from trace amounts in some seaweeds and fermented foods. Low B12 can lead to a range of health problems including megaloblastic anemia, a condition in which red blood cells become abnormally large due to impaired DNA synthesis. It can also cause elevated homocysteine, which is linked to cardiovascular and neurological issues.34 Low B12 is also associated with nervous system issues such as mood disorders, cognitive changes such as poor memory, confusion, brain fog, fatigue, loss of feeling in the limbs, low blood pressure, muscle weakness and low mental and physical function.

Does a vegan diet lower homocysteine?

Yes, a vegan diet can lower homocysteine, but only if vitamin B12 levels are sufficient. B12 and folate work together to lower homocysteine by converting it to methionine. If B12 is low, this conversion process won’t happen properly. Studies show that vegans often have higher homocysteine levels than non-vegans due to being low in B12.35

What deficiency is more common in vegans?

Vitamin B12 is the most common deficiency in vegans due to a lack of animal foods in the diet. Vegans must supplement with a bioavailable form of B12 as plant food generally does not contain enough to support healthy levels.

References

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  2. Elmadfa Ibrahim, Singer Ingrid; "Vitamin B-12 and homocysteine status among vegetarians: a global perspective"; The American Journal of Clinical Nutrition Vol 89, Iss 5, Pgs 1693S-1698S; 2009 May

    https://www.sciencedirect.com/science/article/pii/S0002916523238460

  3. Aditi Mohan, Ravi Kumar, Vivek Kumar, Mahendra Yadav; "Homocysteine, Vitamin B12 and Folate Level: Possible Risk Factors in the Progression of Chronic Heart and Kidney Disorders"; Current cardiology reviews.; 2023 Jul

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10494275

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    https://www.sciencedirect.com/science/article/pii/S0022316623020126?via%3Dihub

  5. Qiangqiang He, Jianping Li; "The evolution of folate supplementation – from one size for all to personalized, precision, poly-paths"; Journal of translational internal medicine; 2023 Jul

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10318921/

  6. Dimitra Rafailia Bakaloudi, Afton Halloran, Holly L Rippin, Artemis Christina Oikonomidou, Theodoros I Dardavesis, Julianne Williams, Kremlin Wickramasinghe, Joao Breda, Michail Chourdakis; "Intake and adequacy of the vegan diet. A systematic review of the evidence"; Clinical nutrition : official journal of the European Society of Parenteral and Enteral Nutrition; 2021 May

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  10. Ali Niklewicz, A David Smith, Alison Smith, Andre Holzer, Andrew Klein, Andrew McCaddon, Anne M Molloy, Bruce H R Wolffenbuttel, Ebba Nexo, Helene McNulty, Helga Refsum, Jean-Louis Gueant, Marie-Joe Dib, Mary Ward, Michelle Murphy, Ralph Green, Kourosh R Ahmadi, Luciana Hannibal, Martin J Warren, P Julian Owen, on behalf of CluB-12; "The importance of vitamin B12 for individuals choosing plant-based diets"; European journal of nutrition; 2022 Dec

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10030528/

  11. National Institutes of Health, Office of Dietary Supplements; "Vitamin B12, Fact Sheet for Consumers"; https://ods.od.nih.gov/; 2023 Dec

    https://ods.od.nih.gov/factsheets/VitaminB12-Consumer/

  12. Heather M Guetterman, Samantha L Huey, Rob Knight, Allison M Fox, Saurabh Mehta, Julia L Finkelstein; "Vitamin B-12 and the Gastrointestinal Microbiome: A Systematic Review"; Advances in nutrition; 2021 Dec

    https://pmc.ncbi.nlm.nih.gov/articles/PMC8970816

  13. Elmadfa Ibrahim, Singer Ingrid; "Vitamin B-12 and homocysteine status among vegetarians: a global perspective"; The American Journal of Clinical Nutrition Vol. 89, Iss. 5, Pgs. 1693S-1698S; 2009 May

    https://www.sciencedirect.com/science/article/pii/S0002916523238460#bib30

  14. Lindsay H Allen; "How common is vitamin B-12 deficiency?"; The American Journal of Clinical Nutrition Vol. 89, Iss. 2, Pages 693S-696S; 2009 Feb

    https://www.sciencedirect.com/science/article/pii/S0002916523239982?via%3Dihub

  15. Elmadfa Ibrahim, Singer Ingrid; "Vitamin B-12 and homocysteine status among vegetarians: a global perspective"; The American Journal of Clinical Nutrition Vol. 89, Iss. 5, Pgs. 1693S-1698S; 2009 May

    https://www.sciencedirect.com/science/article/pii/S0002916523238460

  16. Isabel Iguacel, María L Miguel-Berges, Alejandro Gómez-Bruton, Luis A Moreno, Cristina Julián; "Veganism, vegetarianism, bone mineral density, and fracture risk: a systematic review and meta-analysis"; Nutrition Reviews, Vol. 77, Iss. 1, Pgs. 1–18; 2019 Jan

    https://doi.org/10.1093/nutrit/nuy045

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    https://academic.oup.com/nutritionreviews/article-abstract/79/4/361/5850123?redirectedFrom=fulltext

  18. Andrew McCaddon; "Vitamin B12 in neurology and ageing; clinical and genetic aspects"; Biochimie; 2013 May

    https://pubmed.ncbi.nlm.nih.gov/23228515/

  19. Alex Ankar, Anil Kumar; "Vitamin B12 Deficiency"; StatPearls [Internet].; 2024 Sep

    https://www.ncbi.nlm.nih.gov/books/NBK441923

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    https://pubmed.ncbi.nlm.nih.gov/23228515/

  21. Atasi Bhattacharjee, Arpith Easo Samuel; "Vitamin B12 Deficiency in a Patient Presenting with Dyspnea: A Case Report"; Advanced journal of emergency medicine; 2018 Nov

    https://pubmed.ncbi.nlm.nih.gov/31172130/

  22. Marques de Brito, B., Campos, V. de M., Neves, F. J., Ramos, L. R., Tomita, L. Y.; "Vitamin B12 sources in non-animal foods: a systematic review."; Critical Reviews in Food Science and Nutrition, 63(26), 7853–7867; (2022)

    https://www.tandfonline.com/doi/full/10.1080/10408398.2022.2053057

  23. Fumio Watanabe, Yukinori Yabuta, Tomohiro Bito, Fei Teng; "Vitamin B12-Containing Plant Food Sources for Vegetarians"; Nutrients.; 2014 May

    https://pmc.ncbi.nlm.nih.gov/articles/PMC4042564/

  24. Corina-Aurelia Zugravu, Adriana Macri, Nastasia Belc, Roxana Bohiltea; "Efficacy of supplementation with methylcobalamin and cyanocobalamin in maintaining the level of serum holotranscobalamin in a group of plant-based diet (vegan) adults"; Experimental and therapeutic medicine.; 2021 Jul

    https://pmc.ncbi.nlm.nih.gov/articles/PMC8311243/

  25. Gregory A Plotnikoff, Linda Dobberstein, Susan Raatz; "Nutritional Assessment of the Symptomatic Patient on a Plant-Based Diet: Seven Key Questions"; Nutrients.; 2023 Mar

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10056340

  26. Haiyan Wang, Linyi Li, Ling Ling Qin, Yanan Song, Josep Vidal‐Alaball, Tong Hua Liu; "Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency"; The Cochrane database of systematic reviews.; 2018 Mar

    https://pmc.ncbi.nlm.nih.gov/articles/PMC6494183/

  27. D Majchrzak, I Singer, M Männer, P Rust, D Genser, K-H Wagner, I Elmadfa; "B-vitamin status and concentrations of homocysteine in Austrian omnivores, vegetarians and vegans"; Annals of nutrition & metabolism.; 2006

    https://pubmed.ncbi.nlm.nih.gov/16988496

  28. L Bissoli, V Di Francesco, A Ballarin, R Mandragona, R Trespidi, G Brocco, B Caruso, O Bosello, M Zamboni; "Effect of vegetarian diet on homocysteine levels"; Annals of nutrition & metabolism.; 2002

    https://pubmed.ncbi.nlm.nih.gov/12011576/

  29. Edyta Łuszczki, Faustina Boakye, Magdalena Zielińska, Katarzyna Dereń, Anna Bartosiewicz, Łukasz Oleksy, Artur Stolarczyk; "Vegan diet: nutritional components, implementation, and effects on adults’ health"; Frontiers in nutrition.; 2023 Nov

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10665534/

  30. Aimee Rachel Mathew, Giacomo Di Matteo, Piergiorgio La Rosa, Saviana Antonella Barbati, Luisa Mannina, Sandra Moreno, Ada Maria Tata, Virve Cavallucci, Marco Fidaleo; "Vitamin B12 Deficiency and the Nervous System: Beyond Metabolic Decompensation—Comparing Biological Models and Gaining New Insights into Molecular and Cellular Mechanisms"; International journal of molecular sciences.; 2024 Jan

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10778862/

  31. Cristiana Paul, David M Brady; "Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms"; Integrative medicine.; 2017 Feb

    https://pmc.ncbi.nlm.nih.gov/articles/PMC5312744/

  32. Merav Jacobson Bensky, Irit Ayalon-Dangur, Roi Ayalon-Dangur, Eviatar Naamany, Anat Gafter-Gvili, Gideon Koren, Shachaf Shiber; "Comparison of sublingual vs. intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency"; Drug delivery and translational research; 2019 Jun

    https://pubmed.ncbi.nlm.nih.gov/30632091/

  33. Sávio Fernandes, Leandro Oliveira, Alda Pereira, Maria do Céu Costa, António Raposo, Ariana Saraiva, Bruno Magalhães; "Exploring Vitamin B12 Supplementation in the Vegan Population: A Scoping Review of the Evidence"; Nutrients.; 2024 May

    https://pmc.ncbi.nlm.nih.gov/articles/PMC11124153

  34. Ali Niklewicz, A David Smith, Alison Smith, Andre Holzer, Andrew Klein, Andrew McCaddon, Anne M Molloy, Bruce H R Wolffenbuttel, Ebba Nexo, Helene McNulty, Helga Refsum, Jean-Louis Gueant, Marie-Joe Dib, Mary Ward, Michelle Murphy, Ralph Green, Kourosh R Ahmadi, Luciana Hannibal, Martin J Warren, P Julian Owen, on behalf of CluB-12; "The importance of vitamin B12 for individuals choosing plant-based diets"; European journal of nutrition; 2022 Dec

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10030528

  35. L Bissoli, V Di Francesco, A Ballarin, R Mandragona, R Trespidi, G Brocco, B Caruso, O Bosello, M Zamboni; "Effect of vegetarian diet on homocysteine levels"; Annals of nutrition & metabolism.; 2002

    https://pubmed.ncbi.nlm.nih.gov/12011576/

Katie Stone - Naturopath

About the Author

Katie is a qualified Naturopath (BNatMed) and freelance writer from New Zealand. She specializes in all things health and wellness, particularly dietary supplements and nutrition. Katie is also a dedicated runner and has completed more half-marathons than she can count!

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