A Balanced Approach to the ‘MTHFR Diet’

How to Eat for Optimal Health With MTHFR Gene Variants

A specialized “MTHFR diet” and supplement regimen has been promoted online for people who have common MTHFR gene variations. However, research has not been able to confirm that a specific diet is beneficial for people with these genetic profiles. 

That said, if you’re interested in modifying your diet and lifestyle to improve your health, and resolve symptoms like fatigue, brain fog, or digestive issues, you’re on the right track. 

In this article, we’ll dig deeper into recommendations for MTHFR diets and supplements, including dietary principles to follow for overall health, and how to know whether or not you should be taking supplements like methyl-folate or vitamin B12. 

We’ll also explain how to improve the markers that are sometimes associated with MTHFR gene mutations (including folate and homocysteine levels) through diet and lifestyle support. 

MTHFR diet: Variety of healthy food ingredients on a gray surface

What Is MTHFR? 

MTHFR, short for methylenetetrahydrofolate reductase, is a gene that instructs the body on how to make the enzyme of the same name [1 Trusted SourcePubMedGo to source]. 

The MTHFR enzyme converts folic acid from food (or supplements) into methyl-folate (the active form of folate), which is used for an important process in the body called methylation.

The methylation process helps to regulate metabolic function, detoxification, brain function, digestion, hormonal balance, and energy production.

What MTHFR Gene Variants Mean  

MTHFR diet: 3D illustration of a DNA strand

Common variants in the MTHFR gene (often referred to as genetic mutations or polymorphisms) may result in a somewhat reduced capacity to produce the MTHFR enzyme and may therefore affect methylation. 

Based on this concept, MTHFR polymorphisms have been tenuously linked to an increased risk of developing several different health issues, including Alzheimer’s disease, breast cancer, colon cancer, schizophrenia, thyroid issues, and heart disease. 

Consumer-focused genetic tests, such as those offered by 23andme, can show you whether or not you have an MTHFR gene variation.  

However, a closer look at the research shows that the health risks associated with MTHFR variants are minimal at most, and the utility of genetic testing is limited [1 Trusted SourcePubMedGo to source, 2 Trusted SourcePubMedGo to source]. 

For example, one of the biggest concerns associated with MTHFR gene variants is the potential effect on homocysteine levels. However, a 2019 analysis found that the actual impact of MTHFR gene variations on homocysteine levels was at most 1% [3]. We’ll dive deeper into this below. 

MTHFR, Folate, and Homocysteine 

Because the MTHFR gene plays a role in folate metabolism, many of the concerns that have been raised about it relate to the risk of low levels of folate (vitamin B9). 

Low levels of folate and other B vitamins may lead to higher levels of homocysteine (an amino acid found in the blood), which have been linked to various health conditions including cardiovascular disease [4 Trusted SourcePubMedGo to source, 5 Trusted SourcePubMedGo to source, 6 Trusted SourcePubMedGo to source]. 

Based on these relationships, online advice about MTHFR gene polymorphisms often involves an entire diet, supplement, and lifestyle regimen centered around increasing folate and vitamin B levels, decreasing homocysteine levels, and enhancing methylation. 

However, research shows that the actual impact of the MTHFR gene on homocysteine levels, folate metabolism, and health outcomes is quite small, so MTHFR-targeted diet and supplement measures are probably not necessary [3, 7]. 

What Is an MTHFR Diet?

MTHFR diet: Variety of green vegetables on a stone surface

Some people suggest that individuals with MTHFR gene variations should follow a specialized “MTHFR diet” and supplement regimen focused on increasing levels of folate and vitamin B12, and on improving methylation. 

While many of the foods that contain folate and B vitamins are healthy and have a place in a well-rounded diet, building your entire diet and lifestyle around the MTHFR gene is not necessary. 

There is no diet that has been shown to be specifically beneficial for those who have MTHFR gene variations. A 2015 American Heart Association review concluded the following [1 Trusted SourcePubMedGo to source]: 

“The presence of MTHFR mutations does not require any special treatment, such as supplementation with folic acid, vitamin B6, or vitamin B12.” 

The Best Diet To Support Methylation and Overall Health 

While a diet based on your MTHFR gene is not necessary, a healthy diet is essential for your overall wellness. 

Regardless of your genetic profile, the right diet can improve methylation, detoxification, immune system health, brain function, and gut health, helping to resolve common concerns like fatigue, brain fog, and digestive issues [8 Trusted SourcePubMedGo to source, 9, 10]  

A well-rounded diet rich in whole foods can also help to naturally balance your levels of folate, vitamin B12, and homocysteine [11, 12]. 

The Paleo Diet

Key principles of a healthy diet include reducing inflammation, balancing blood sugar, and eliminating foods you may have sensitivities to. 

A diet that fits these criteria and helps many people feel better is the Paleo diet [8 Trusted SourcePubMedGo to source, 13 Trusted SourcePubMedGo to source, 14 Trusted SourcePubMedGo to source]. 

The Paleo diet eliminates processed foods, refined sugar, and artificial sweeteners, which are known to contribute to inflammation, gut health imbalances, and other health problems.

The Paleo diet also eliminates commonly inflammatory foods like grains (including gluten), dairy products, and legumes (such as beans and lentils).  

Foods to enjoy on a Paleo diet include: 

  • Fresh vegetables 
  • Fresh fruit 
  • Nuts and seeds
  • Grass-fed meats and fresh fish 
  • Eggs 
  • Healthy fats, including olive oil and avocados 
MTHFR diet: Table showing what to eat on the Paleo diet

Foods High in Folate

If you are concerned about methylation, folate, or homocysteine levels, you may want to include more foods that are high in folate in your diet. 

If you are following a Paleo or similar diet, it’s likely that you will naturally be eating many of these foods, which have several additional health benefits. 

Paleo-friendly dietary sources of folate include: 

  • Leafy green vegetables (including spinach and kale) 
  • Asparagus 
  • Broccoli 
  • Avocado 
  • Oranges and mangoes 

Supplements for MTHFR and Methylation Support 

Capsules spilling out of the bottle on top of a wooden surface

A common misconception is that everyone who has an MTHFR gene variant should take supplemental B vitamins and methyl-folate in order to enhance methylation. 

Supplements may be helpful in some cases, but they shouldn’t be taken based on genetic testing for MTHFR. 

There are a few important things to consider when it comes to supplementation for methylation:

  • Too much methylation can be harmful. While proper methylation is important, research shows that more is not always better. Too much methylation (known as hypermethylation) can be dangerous, just like too little methylation (hypomethylation) [15, 16]. Taking unnecessary supplements including high-dose B vitamins, folic acid, or methyl-folate can lead to hypermethylation [17].
  • The MTHFR gene doesn’t determine your folate or homocysteine levels. While taking folic acid and B12 supplements can help to reduce homocysteine levels, research shows that the impact of the MTHFR gene on homocysteine levels is extremely low [1 Trusted SourcePubMedGo to source, 3]. Blood tests can determine your actual levels of homocysteine, folate, and B12, in order to discern whether or not supplementation may be warranted.
  • Diet and lifestyle factors should come first. There are a number of ways to support the body’s production of B vitamins and to reduce homocysteine levels, eliminating or reducing the need for long-term vitamin supplementation. For example, one study found that increasing healthy bacteria in the gut with probiotics increased the production of B vitamins and decreased homocysteine levels [18 Trusted SourcePubMedGo to source].

With this in mind, folic acid or vitamin B supplements may be recommended in moderate doses if: 

  • Blood test results show low folate, low vitamin B12, and/or high homocysteine levels, and; 
  • Diet, lifestyle, and gut health factors are already in place. 

Folic Acid vs. Methyl-Folate 

Proponents of the MTHFR diet and lifestyle have suggested that those with MTHFR gene polymorphisms should avoid folic acid supplements (the more common and synthetic form of folate). 

Instead, they suggest opting for more expensive methyl-folate supplements (also known as 5-methyltetrahydrofolate or 5-mthf). 

However, there is no evidence to support that folic acid supplements are more harmful or less effective than methyl-folate supplements [19 Trusted SourcePubMedGo to source, 20]. Therefore, if you are going to take folate supplements, either form should be fine, regardless of your MTHFR genotype. 

Diet, Lifestyle, and Gut Health Foundations 

The best way to support methylation, detoxification, and overall health is to focus on creating a healthy environment within your body, including your gut

Eating an anti-inflammatory diet, which we covered above, is one of the most important things you can do to create this healthy environment. There are also a few other foundational pieces that work together with your diet for the best outcomes.

The foundations of a healthy internal environment include: 

A Big Picture Approach To Your Diet and Health

The best diet for your health should be based on a combination of your individual needs and fundamental health principles, not your genetic profile. 

MTHFR gene variations are common and have not been proven to have a significant impact on health outcomes. However, if you have concerns about methylation, folate levels, or homocysteine levels (which have been associated with the MTHFR gene), you can support them with your diet and lifestyle. 

The best general approach is to follow an anti-inflammatory diet (like the Paleo diet) that includes whole foods that are naturally high in folate. Supporting gut health with high-quality probiotics, regular exercise, and quality sleep is also important. 

By taking a well-rounded, big-picture approach to your diet and your health, you can likely improve or resolve many of the symptoms that have been mistakenly associated with the MTHFR gene and feel better.

To learn more about healing your gut and improving your overall health, check out my book, Healthy Gut, Healthy You.

➕ References
  1. Stephan Moll, Elizabeth A. Varga. Homocysteine and MTHFR Mutations. Circulation, American Heart Association Journals. July 7, 2015. Vol 132, Issue 1. https://doi.org/10.1161/CIRCULATIONAHA.114.013311 Trusted SourcePubMedGo to source
  2. Hickey SE, Curry CJ, Toriello HV. ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing. Genet Med. 2013 Feb;15(2):153-6. doi: 10.1038/gim.2012.165. Epub 2013 Jan 3. Erratum in: Genet Med. 2020 Jun 12;: PMID: 23288205. Trusted SourcePubMedGo to source
  3. Wood TR and Owens N. Using synthetic datasets to bridge the gap between the promise and reality of basing health-related decisions on common single nucleotide polymorphisms [version 1; peer review: 1 approved, 1 approved with reservations]F1000Research 2019, 8:2147 (https://doi.org/10.12688/f1000research.21797.1)
  4. Fan R, Zhang A, Zhong F. Association between Homocysteine Levels and All-cause Mortality: A Dose-Response Meta-Analysis of Prospective Studies. Sci Rep. 2017 Jul 6;7(1):4769. doi: 10.1038/s41598-017-05205-3. PMID: 28684797; PMCID: PMC5500552. Trusted SourcePubMedGo to source
  5. Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J. 2015 Jan 10;14:6. doi: 10.1186/1475-2891-14-6. PMID: 25577237; PMCID: PMC4326479. Trusted SourcePubMedGo to source
  6. Smith AD, Refsum H, Bottiglieri T, Fenech M, Hooshmand B, McCaddon A, Miller JW, Rosenberg IH, Obeid R. Homocysteine and Dementia: An International Consensus Statement. J Alzheimers Dis. 2018;62(2):561-570. doi: 10.3233/JAD-171042. PMID: 29480200; PMCID: PMC5836397. Trusted SourcePubMedGo to source
  7. Sarah Long, Jack Goldblatt. MTHFR genetic testing: Controversy and clinical implications. Australian Family Physician, Men’s health. Volume 45, No.4, April 2016 Pages 237-240.
  8. Whalen KA, McCullough ML, Flanders WD, Hartman TJ, Judd S, Bostick RM. Paleolithic and Mediterranean Diet Pattern Scores Are Inversely Associated with Biomarkers of Inflammation and Oxidative Balance in Adults. J Nutr. 2016 Jun;146(6):1217-26. doi: 10.3945/jn.115.224048. Epub 2016 Apr 20. PMID: 27099230; PMCID: PMC4877627. Trusted SourcePubMedGo to source
  9. Altobelli E, Del Negro V, Angeletti PM, Latella G. Low-FODMAP Diet Improves Irritable Bowel Syndrome Symptoms: A Meta-Analysis. Nutrients. 2017 Aug 26;9(9):940. doi: 10.3390/nu9090940. PMID: 28846594; PMCID: PMC5622700.
  10. Riccio P, Rossano R. Undigested Food and Gut Microbiota May Cooperate in the Pathogenesis of Neuroinflammatory Diseases: A Matter of Barriers and a Proposal on the Origin of Organ Specificity. Nutrients. 2019 Nov 9;11(11):2714. doi: 10.3390/nu11112714. PMID: 31717475; PMCID: PMC6893834.
  11. Lawrence J. Appel, Edgar R. MillerIII, Sun Ha Jee, Rachael Stolzenberg-Solomon, RD, Pao-Hwa Lin, Thomas Erlinger, Marie R. Nadeau, and Jacob Selhub. Effect of Dietary Patterns on Serum Homocysteine: Results of a Randomized, Controlled Feeding Study. Circulation, American Heart Association Journals. Aug 22, 2000. Vol 132, Issue 1. https://doi.org/10.1161/01.CIR.102.8.852
  12. Ingeborg A. Brouwer, Marijke van Dusseldorp, Clive E. West, Saskia Meyboom, Chris M. G. Thomas, Marinus Duran, Karin H. van het Hof, Tom K.A.B. Eskes, Joseph G.A.J. Hautvast, Régine P. M. Steegers-Theunissen, Dietary Folate from Vegetables and Citrus Fruit Decreases Plasma Homocysteine Concentrations in Humans in a Dietary Controlled Trial, The Journal of Nutrition, Volume 129, Issue 6, June 1999, Pages 1135–1139, https://doi.org/10.1093/jn/129.6.1135
  13. Jönsson T, Granfeldt Y, Ahrén B, Branell UC, Pålsson G, Hansson A, Söderström M, Lindeberg S. Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study. Cardiovasc Diabetol. 2009 Jul 16;8:35. doi: 10.1186/1475-2840-8-35. PMID: 19604407; PMCID: PMC2724493. Trusted SourcePubMedGo to source
  14. Masharani U, Sherchan P, Schloetter M, Stratford S, Xiao A, Sebastian A, Nolte Kennedy M, Frassetto L. Metabolic and physiologic effects from consuming a hunter-gatherer (Paleolithic)-type diet in type 2 diabetes. Eur J Clin Nutr. 2015 Aug;69(8):944-8. doi: 10.1038/ejcn.2015.39. Epub 2015 Apr 1. PMID: 25828624. Trusted SourcePubMedGo to source
  15. Steven A. Belinsky, Kieu C. Liechty, Frederick D. Gentry, Holly J. Wolf, Justin Rogers, Kieu Vu, Jerry Haney, Tim C. Kennedy, Fred R. Hirsch, York Miller, Wilbur A. Franklin, James G. Herman, Stephen B. Baylin, Paul A. Bunn and Tim Byers. Promoter Hypermethylation of Multiple Genes in Sputum Precedes Lung Cancer Incidence in a High-Risk Cohort. Cancer Res. March 15 2006 (66) (6) 3338-3344; DOI: 10.1158/0008-5472.CAN-05-3408
  16. Cheryl M. Lewis, Leslie R. Cler, Da-Wei Bu, Sabine Zöchbauer-Müller, Sara Milchgrub, Elizabeth Z. Naftalis, A. Marilyn Leitch, John D. Minna and David M. Euhus. Promoter Hypermethylation in Benign Breast Epithelium in Relation to Predicted Breast Cancer Risk. Clin Cancer Res. January 1 2005 (11) (1) 166-172;
  17. Ortbauer, M., Ripper, D., Fuhrmann, T., Lassi, M., Auernigg‐Haselmaier, S., Stiegler, C. and König, J. (2016), Folate deficiency and over‐supplementation causes impaired folate metabolism: Regulation and adaptation mechanisms in Caenorhabditis elegans. Mol. Nutr. Food Res., 60: 949-956. https://doi.org/10.1002/mnfr.201500819
  18. Valentini L, Pinto A, Bourdel-Marchasson I, Ostan R, Brigidi P, Turroni S, Hrelia S, Hrelia P, Bereswill S, Fischer A, Leoncini E, Malaguti M, Blanc-Bisson C, Durrieu J, Spazzafumo L, Buccolini F, Pryen F, Donini LM, Franceschi C, Lochs H. Impact of personalized diet and probiotic supplementation on inflammation, nutritional parameters and intestinal microbiota – The “RISTOMED project”: Randomized controlled trial in healthy older people. Clin Nutr. 2015 Aug;34(4):593-602. doi: 10.1016/j.clnu.2014.09.023. Epub 2014 Oct 8. PMID: 25453395. Trusted SourcePubMedGo to source
  19. Viswanathan M, Treiman KA, Kish-Doto J, Middleton JC, Coker-Schwimmer EJ, Nicholson WK. Folic Acid Supplementation for the Prevention of Neural Tube Defects: An Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2017 Jan 10;317(2):190-203. doi: 10.1001/jama.2016.19193. PMID: 28097361. Trusted SourcePubMedGo to source
  20. Tod Cooperman, M.D. B Vitamin Supplements Review (B Complexes, B6, B12, Biotin, Folate, Niacin, Riboflavin & More). Be Careful Choosing B Vitamins. 18% of B Vitamins Fail Our Review. See Which Are Best. 2019. ConsumerLab.com
  21. Ghaedi E, Mohammadi M, Mohammadi H, Ramezani-Jolfaie N, Malekzadeh J, Hosseinzadeh M, Salehi-Abargouei A. Effects of a Paleolithic Diet on Cardiovascular Disease Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Adv Nutr. 2019 Jul 1;10(4):634-646. doi: 10.1093/advances/nmz007. Erratum in: Adv Nutr. 2020 Jul 1;11(4):1054. PMID: 31041449; PMCID: PMC6628854. Trusted SourcePubMedGo to source
  22. Manheimer EW, van Zuuren EJ, Fedorowicz Z, Pijl H. Paleolithic nutrition for metabolic syndrome: systematic review and meta-analysis. Am J Clin Nutr. 2015 Oct;102(4):922-32. doi: 10.3945/ajcn.115.113613. Epub 2015 Aug 12. PMID: 26269362; PMCID: PMC4588744. Trusted SourcePubMedGo to source
  23. Barbaresko J, Koch M, Schulze MB, Nöthlings U. Dietary pattern analysis and biomarkers of low-grade inflammation: a systematic literature review. Nutr Rev. 2013 Aug;71(8):511-27. doi: 10.1111/nure.12035. Epub 2013 Jun 13. PMID: 23865797. Trusted SourcePubMedGo to source
  24. van den Brink AC, Brouwer-Brolsma EM, Berendsen AAM, van de Rest O. The Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) Diets Are Associated with Less Cognitive Decline and a Lower Risk of Alzheimer’s Disease-A Review. Adv Nutr. 2019 Nov 1;10(6):1040-1065. doi: 10.1093/advances/nmz054. PMID: 31209456; PMCID: PMC6855954. Trusted SourcePubMedGo to source
  25. Covassin N, Singh P. Sleep Duration and Cardiovascular Disease Risk: Epidemiologic and Experimental Evidence. Sleep Med Clin. 2016 Mar;11(1):81-9. doi: 10.1016/j.jsmc.2015.10.007. Epub 2016 Jan 9. PMID: 26972035; PMCID: PMC4791534.
  26. Worley SL. The Extraordinary Importance of Sleep: The Detrimental Effects of Inadequate Sleep on Health and Public Safety Drive an Explosion of Sleep Research. P T. 2018 Dec;43(12):758-763. PMID: 30559589; PMCID: PMC6281147.
  27. Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol (1985). 2005 Apr;98(4):1154-62. doi: 10.1152/japplphysiol.00164.2004. PMID: 15772055. Trusted SourcePubMedGo to source
  28. Ticinesi A, Lauretani F, Tana C, Nouvenne A, Ridolo E, Meschi T. Exercise and immune system as modulators of intestinal microbiome: implications for the gut-muscle axis hypothesis. Exerc Immunol Rev. 2019;25:84-95. PMID: 30753131. Trusted SourcePubMedGo to source
  29. Sears ME, Kerr KJ, Bray RI. Arsenic, cadmium, lead, and mercury in sweat: a systematic review. J Environ Public Health. 2012;2012:184745. doi: 10.1155/2012/184745. Epub 2012 Feb 22. PMID: 22505948; PMCID: PMC3312275.
  30. Leblhuber F, Steiner K, Schuetz B, Fuchs D, Gostner JM. Probiotic Supplementation in Patients with Alzheimer’s Dementia – An Explorative Intervention Study. Curr Alzheimer Res. 2018;15(12):1106-1113. doi: 10.2174/1389200219666180813144834. PMID: 30101706; PMCID: PMC6340155. Trusted SourcePubMedGo to source
  31. Toribio-Mateas M. Harnessing the Power of Microbiome Assessment Tools as Part of Neuroprotective Nutrition and Lifestyle Medicine Interventions. Microorganisms. 2018 Apr 25;6(2):35. doi: 10.3390/microorganisms6020035. PMID: 29693607; PMCID: PMC6027349. Trusted SourcePubMedGo to source
  32. Mujagic Z, de Vos P, Boekschoten MV, Govers C, Pieters HH, de Wit NJ, Bron PA, Masclee AA, Troost FJ. The effects of Lactobacillus plantarum on small intestinal barrier function and mucosal gene transcription; a randomized double-blind placebo controlled trial. Sci Rep. 2017 Jan 3;7:40128. doi: 10.1038/srep40128. PMID: 28045137; PMCID: PMC5206730. Trusted SourcePubMedGo to source
  33. Sindhu KN, Sowmyanarayanan TV, Paul A, Babji S, Ajjampur SS, Priyadarshini S, Sarkar R, Balasubramanian KA, Wanke CA, Ward HD, Kang G. Immune response and intestinal permeability in children with acute gastroenteritis treated with Lactobacillus rhamnosus GG: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2014 Apr;58(8):1107-15. doi: 10.1093/cid/ciu065. Epub 2014 Feb 5. PMID: 24501384; PMCID: PMC3967829. Trusted SourcePubMedGo to source
  34. Lamprecht M, Bogner S, Schippinger G, Steinbauer K, Fankhauser F, Hallstroem S, Schuetz B, Greilberger JF. Probiotic supplementation affects markers of intestinal barrier, oxidation, and inflammation in trained men; a randomized, double-blinded, placebo-controlled trial. J Int Soc Sports Nutr. 2012 Sep 20;9(1):45. doi: 10.1186/1550-2783-9-45. PMID: 22992437; PMCID: PMC3465223. Trusted SourcePubMedGo to source

Need help or would like to learn more?
View Dr. Ruscio’s additional resources

Get Help


I care about answering your questions and sharing my knowledge with you. Leave a comment or connect with me on social media asking any health question you may have and I just might incorporate it into our next listener questions podcast episode just for you!