Multivitamins for MTHFR

Multivitamins for MTHFR

Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Dr. Conor Sheehy - PharmD, BCPS

Medical Reviewer:

Dr. Conor Sheehy - PharmD, BCPS
Kari Asadorian - Bachelor of Science in Nursing

Edited By:

Kari Asadorian - Bachelor of Science in Nursing

Updated On:

March 23, 2025

Table of Contents

    Multivitamins for MTHFR

    If you’ve heard about the MTHFR mutation—or discovered that you have the variant yourself—you may be wondering what to do next. What are the health risks of MTHFR? What can you do to protect yourself from these risks?


    The MTHFR mutation is not uncommon1: an estimated 30-40 percent of the American population may have one of the well-known forms of this mutation, including 10%-15% of the Caucasian population and more than 25% of the Latino population.  Most people don’t discover they have the mutation until they experience symptoms caused by deficiencies associated with their variant, which is usually when they get a test.

     

    One of the main questions people ask is, “Should I take multivitamins with MTHFR?” The answer is yes - but not just any old multivitamin off the shelf. There are hundreds of multivitamins out there these days, and they all vary enormously in terms of their quality, and the form of the nutrients they contain. Knowing which is right for you is crucial when it comes to managing an MTHFR polymorphism.

     

    The tricky thing about MTHFR is that symptoms can vary between carriers and variants.


    Every person with an MTHFR genetic mutation has different needs depending on their own health history, and also on the MTHFR variant they have. You need to understand what your own specific needs are, and what nutrients you might be deficient in.

     

    There’s a lot of misinformation about MTHFR mutations and how they can be managed. This article will explain what the MTHFR mutation can mean for your long-term health, and why you may need to supplement with certain vitamins. We’ll also explain how to choose a multivitamin that’s suitable for each particular variant of MTHFR.

    Are Multivitamins Good for MTHFR?

    Yes, multivitamins are the best place to start when managing MTHFR mutations.

     

    One of the first things to understand about the MTHFR enzyme is that it’s involved in an enormous range of biochemical processes in the body. The MTHFR gene provides your body with a set of instructions for making an enzyme called methylenetetrahydrofolate reductase(MTHFR), which is required for breaking down certain nutrients that you ingest.

     

    However, a mutation on the MTHFR gene will affect the breakdown of these nutrients, preventing them from being converted into active vitamins, amino acids, and enzymes that your body can use. It can even affect your body’s levels of certain hormones and neurotransmitters, along with cognitive function, digestion, cholesterol levels, and more.


    This can lead to deficiencies that seriously impair normal function2, which has significant implications for the way your body works.

     

    The MTHFR mutation can seriously compromise your ability to convert nutrients into a form that your body will be able to use. The most important of these nutrients is vitamin B9, folate.

     

    When you eat foods or take supplements that contain folic acid, the MTHFR enzyme is supposed to convert it into a form that the body can use called methyl-folate or 5-methyltetrahydrofolate. Folate is the primary form of circulating Vitamin B9 in the blood.

     

    But an MTHFR variant seriously compromises your ability to convert folic acid into a form that your body can use, often resulting in a folate deficiency3.

     

    This can have serious consequences for your health because adequate levels of folates are essential for homeostasis and reducing the risk of certain diseases. Folate deficiency is associated with several congenital malformations4, such as neural tube defects (NTDs), congenital heart defects, orofacial clefts, pregnancy-related complications, cardiovascular diseases, various psychiatric diseases, and cancer.

     

    The MTHFR gene achieves folate conversion via methylation. Methylation is a crucial step in the activation of vitamin B9. The methylation process requires a range of important nutrients, including vitaminB12 and folate. A lack of any particular nutrient can disrupt the methylation process5, which can result in an undesirable elevation in homocysteine levels and a buildup of other toxins.

     

    Another important process is there-methylation of homocysteine to methionine, a substance the body needs for proper metabolism and muscle growth. Methionine is converted to S-adenosylmethionine (SAMe) which serves as a methyl donor in many other reactions throughout the cellular system. The methionine-homocysteine pathway also creates a host of important nutrients 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.

    Best Multivitamin for MTHFR

    An MTHFR variant can mean that your body is missing out on many vital nutrients, which is why taking a comprehensive multivitamin is so important.


    Not just any multivitamin will do. Those with an MTHFR polymorphism(s) are advised to supplement with nutrients that are already in their bioactive form, especially l-methylfolate. This means the nutrient will be instantly available to the body without the need for further breakdown. Your most effective source of nutrients for optimal health is a multi that contains a methylated B complex.


    A good option is Methyl-Life’s® Methylated Multivitamin, which provides many of the needed ingredients for methylation to occur optimally in the body. It’s been specially formulated with L-Methylfolate and Active B12 to assist with the biochemical processes required for overall wellbeing.


    The formula is designed to support the myelin sheath for nerve health, promote glutathione (your body’s most valuable antioxidant), and boost serotonin, an important neurotransmitter required for a healthy mood.


    The Methylated Multivitamin also helps to reduce harmful homocysteine levels in the body, which is a major risk factor with the MTHFR polymorphism. It can also be used during preconception and pregnancy to support fertility and prenatal health. Ask your doctor about this.

    Vitamins You Need with MTHFR

    Methylfolate

    It’s important to know that folic acid and folate are NOT the same molecule6. Folic acid is a synthetic form of folate, while folate is the form that your body can use in circulation. For this reason, it’s also important for those who have MTHFR and/or are pregnant to avoid supplements or foods that contain folic acid.


    Only the active form 5-methyltetrahydrofolate7 can participate in the gene activation and DNA repair, as well as supporting rapid cell growth, regulation, and division.


    Some of the best methylfolate supplements for those with MTHFR mutations 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. They contain the purest, stable, and most potent of the four world’s industry-leading, patented L-Methylfolates, Magnafolate® PRO.

    Pyridoxal5’-Phosphate (active vitamin B6)

    Pyridoxal 5'-phosphate (P5P) is also necessary for the recycling of homocysteine8. It facilitates the breakdown of homocysteine to cysteine and then to taurine.


    P5P is involved in the body's production of hemoglobin. It is also involved in supporting the healthy formation of the myelin sheath9 that surrounds and protects nerve cells10.

    Active Vitamin B12

    B12 plays a major role as a cofactor in the methylation process of L-methylfolate, as well as the conversion of homocysteine to methionine.


    Vitamin B12 is crucial for proper brain development and is associated with the one-carbon metabolism required for transmethylation reactions. It’s also involved in the formation of S-adenosylmethionine (SAMe). Supplementation with a highly bioavailable form of vitamin B12 is the most efficient way to optimize levels quickly.

    Magnesium

    Magnesium is an essential mineral and also a cofactor for the COMT enzyme, which is required for the manufacturing of dopamine, norepinephrine, and epinephrine. Alongside the B vitamins, magnesium is vital in supporting a healthy mood, cardiovascular function, and nerve function.

    NAC(N-acetylcysteine)

    NAC is a precursor for glutathione, which has potent antioxidant and anti-inflammatory properties. Researchers have described NAC as a neuroprotective nutrient, and recommend combining it with L-5-Methylenetetrahydrofolate, methyl B12, and betaine11(or TMG) for helping to reduce homocysteine.

    Glutathione

    Methylfolate promotes glutathione in the body, so those with MTHFR mutations who are low in methylfolate are also likely to be low on glutathione12.


    Glutathione is a powerful antioxidant that serves as a precursor for a reaction in the methylation/folate cycle. It neutralizes free radicals, helps make DNA, supports immune function, and enhances the effect of other antioxidants including vitamin C, E, and lipoic acid.


    Glutathione’s sulfur groups aid heavy metal detoxification13 by adhering to these toxic compounds and moving them out of the body. It also protects vitamin B-1214 from reacting with toxins and being unable to perform its metabolic tasks.

    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 methylation15 and is also involved as a mechanism of modulation of gene expression.

    Prenatal Vitamins

    Folate is required for proper DNA replication16 and the prevention of neural tube defects. It’s especially important during the first few weeks of a fetus' development, which is often before a woman discovers she’s pregnant. Folate deficiency during this time can lead to serious, lifelong birth defects17 in the baby's brain or spine.


    Other recommendations include a high-quality, purified DHA and EPA supplement. These two fatty acids are crucial for a baby’s brain18 and nervous system development.  DHA also helps reduce the risk of developing postpartum mood disorders.


    Probiotics help to reduce levels of harmful bacterial strains and yeast in the gut, which can increase systemic inflammation and upset hormonal balance; two factors that can reduce fertility.


    Vitamin D3 is essential for proper skeletal development of the fetus19. D3also helps reduce inflammation, support immune system function, and manage healthy sleep and mood.

    Best Supplements for MTHFR

    While the two most-studied variants of the MTHFR mutation both have certain health risks, these risks differ slightly. This can mean that management may vary depending on which type you have.


    Being homozygous for MTHFR 1298CC (or carrying two of the same variant for MTHFR deficiency)) results in around 60% of normal enzyme function20, as does being double heterozygous (carrying one abnormal gene of two different genes for MTHFR deficiency [MTHFR C677T and MTHFR A1298C]).


    Some data suggests that people with two copies of the 677TT mutation, as well as people who have one copy of both mutations have increased health risks21.


    The MTHFR variants C677T and MTR A2756G have been shown to independently increase the risk of elevated homocysteine levels22.

    Supplements for A1298C Variant

    However, another study found the A1298Cpolymorphism may be a predictor of colon cancer risk23. They also found that the risk of colon cancer reduced with higher intakes of folate, vitamin B2, B6, B12, and methionine among women with the MTHFR677CC/1298AA genotypes24.

    Supplements for C677T Variant

    The C677T has been shown to clearly affect enzyme function and has also been associated with increased homocysteine levels and poor folate status.


    One study showed that people who are homozygous (TT) for the C677T (double mutation) had significantly greater homocysteine levels25 than people without the mutation (CC). This indicates that those with the C677T variant may need to pay special attention to addressing their homocysteine levels.


    Further research has found that plasma homocysteine decreases as vitamin B-12 concentration increases26 in people who were heterozygous for both the C677T and A1298C variants. This indicates that increasing B12 status may help to significantly decrease homocysteine in people with C677T and/or A1298C MTHFR polymorphisms.

    Summary

    An MTHFR polymorphism may have implications for health risks, but these risks can be managed by taking a specialized multivitamin.


    Even with a healthy diet, your body’s inability to properly convert folic acid means that your need for supplementation is much greater. It also means that supplemented nutrients must be provided in a methylated form to allow for optimal uptake and utilization.


    Methyl-Life® products contain the most bioactive nutrient form of B-vitamins and other nutrients available. They contain the form of folate that has already been converted, so it can be immediately used by the body’s cells. The Chewable Methylated Multivitamin also contains a range of nutrients specifically designed for optimizing methylation and supporting overall wellbeing in those with C677T and/or A1298C MTHFR polymorphisms.

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    References

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    2. Dean L; "Methylenetetrahydrofolate Reductase Deficiency"; Medical Genetics Summaries; 2012 Mar

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    4. ​De-Regil LM, Fernández-Gaxiola AC, Dowswell T, Peña-Rosas JP; "Effects and safety of periconceptional folate supplementation for preventing birth defects"; Cochrane Database of Systematic Reviews; 2010 Oct

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    8. Zhou X, Han D, Andl T; "Cancer-Associated Fibroblasts in Tumor Microenvironment – Recent Progress and Future Outlook"; Journal of Cancer; 2015

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    9. ​Calderón-Ospina CA, Nava-Mesa MO; "B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin"; CNS Neurosci Ther; 2020 Jan

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    10. ​Hwang IK, Yoo KY, Kim DH, Lee BH, Kwon YG, Won MH; "Time course of changes in pyridoxal 5'-phosphate (vitamin B6 active form) and its neuroprotection in experimental ischemic damage"; Experimental Neurology; 2007 Jul

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    11. Dell'Edera D, Tinelli A, Milazzo GN, et al.; "Effect of multivitamins on plasma homocysteine in patients with the 5,10 methylenetetrahydrofolate reductase C677T homozygous state"; Molecular Medicine Reports; 2013 Aug

      https://www.spandidos-publications.com/10.3892/mmr.2013.1563

    12. Xuezhi Cui, Soumya Navneet, Jing Wang, Penny Roon, Wei Chen, Ming Xian, Sylvia B Smith; "Analysis of MTHFR, CBS, Glutathione, Taurine, and Hydrogen Sulfide Levels in Retinas of Hyperhomocysteinemic Mice"; Investigative ophthalmology & visual science.; 2017 Apr

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381329/

    13. Marijke Jozefczak, Tony Remans, Jaco Vangronsveld, Ann Cuypers; "Glutathione Is a Key Player in Metal-Induced Oxidative Stress Defenses"; International Journal of Molecular Sciences; 2012 Mar

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317707/

    14. William P. Watson, Tony Munter, Bernard T. Golding; "A New Role for Glutathione:  Protection of Vitamin B12 from Depletion by Xenobiotics"; Chemical Research in Toxicology, Vol 17, Iss 12; 2004 Nov

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    15. Emma Louise Beckett, Konsta Duesing, Charlotte Martin, Patrice Jones, John Furst, Katrina King, Suzanne Niblett, Zoe Yates, Martin Veysey, Mark Lucock; "Relationship between methylation status of vitamin D-related genes, vitamin D levels, and methyl-donor biochemistry"; Journal of Nutrition & Intermediary Metabolism; 2016 Dec

      https://www.sciencedirect.com/science/article/pii/S2352385915300372?via%3Dihub

    16. Nassim Naderi, James D. House; "Chapter Five - Recent Developments in Folate Nutrition"; Advances in Food and Nutrition Research; 2018

      https://www.sciencedirect.com/science/article/pii/S1043452617300505?via%3Dihub

    17. Apolline Imbard, Jean-François Benoist, Henk J Blom; "Neural Tube Defects, Folic Acid and Methylation"; International Journal of Environmental Research and Public Health; 2013 Sep

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799525/

    18. Jaclyn M Coletta, Stacey J Bell, Ashley S Roman; "Omega-3 Fatty Acids and Pregnancy"; Reviews in obstetrics & gynecology.; 2010

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    22. Wen-Xing Li, Fei Cheng, A-Jie Zhang, Shao-Xing Dai, Gong-Hua Li, Wen-Wen Lv, Tao Zhou, Qiang Zhang, Hong Zhang, Tao Zhang, Fang Liu, Dahai Liu, Jing-Fei Huang; "Folate Deficiency and Gene Polymorphisms of MTHFR, MTR and MTRR Elevate the Hyperhomocysteinemia Risk"; Clinical Laboratory; 2005

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    23. Karen Curtin; Jeannette Bigler; Martha L. Slattery; Bette Caan; John D. Potter; Cornelia M. Ulrich; "MTHFR C677T and A1298C Polymorphisms: Diet, Estrogen, and Risk of Colon Cancer"; Cancer Epidemiology, Biomarkers & Prevention; 2004 Feb

      https://cebp.aacrjournals.org/content/13/2/285#ref-9

    24. Karen Curtin; Jeannette Bigler; Martha L. Slattery; Bette Caan; John D. Potter; Cornelia M. Ulrich; "MTHFR C677T and A1298C Polymorphisms: Diet, Estrogen, and Risk of Colon Cancer "; Cancer Epidemiology, Biomarkers & Prevention; 2004 Feb

      https://cebp.aacrjournals.org/content/13/2/285

    25. The Journal of Nutrition | A journal of the American Society for Nutrition

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    26. Lynn B Bailey, Robert L Duhaney, David R Maneval, Gail P A Kauwell, Eoin P Quinlivan, Steven R Davis, Aisha Cuadras, Alan D Hutson, Jesse F Gregory 3rd; "Vitamin B-12 status is inversely associated with plasma homocysteine in young women with C677T and/or A1298C methylenetetrahydrofolate reductase polymorphisms"; The Journal of nutrition; 2002 Jul

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    27. Banner Image Designed by Freepik

      https://www.freepik.com/

    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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