Can MTHFR Mutations Cause Thyroid Complications? | Methyl-Life®

Can MTHFR Mutations Cause Thyroid Complications? | Methyl-Life®

Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Dr. Nare Simonyan - PhD Pharmaceutical Science

Medical Reviewer:

Dr. Nare Simonyan - PhD Pharmaceutical Science
Kari Asadorian - Bachelor of Science in Nursing

Edited By:

Kari Asadorian - Bachelor of Science in Nursing

Updated On:

March 30, 2025

Table of Contents

    MTHFR and the Thyroid

    An estimated 20 million Americans have some form of thyroid disorder1, and up to 60percent don’t even know it. New research suggests that genetics—specifically the MTHFR genetic mutation—may be linked to thyroid issues.


    The causes of thyroid problems are largely unknown. However, they can increase the risk of severe health issues such as cardiovascular diseases, osteoporosis, and infertility.


    MTHFR polymorphisms can reduce the functioning of the MTHFR enzyme2 by around 30 to 70 percent, which can have severe implications for the rest of the body’s functions.


    Studies have shown that both Hashimoto’s disease (hypoactive thyroid) and Graves’ disease (hyperactive thyroid) have genetic susceptibility that involves shared genes and unique3 pathways concerning the thyroid T cells. One particular study found the 1298A>C genetic polymorphism of MTHFR may modulate the risk of thyroid disease4.


    Further research has suggested that elevated homocysteine—a common consequence of MTHFR mutations—is a risk factor for developing a thyroid disorder5.


    Results, however, are mixed. Another study6 involving thyroid patients with either Hashimoto’s or Graves’ disease claimed that MTHFR mutations occur as often in autoimmune thyroid disease (AITD) as they do in the normal population. It was also suggested that the severity of AITD wasn’t linked to having an MTHFR mutation.


    For anyone with an MTHFR polymorphism, knowing the signs and symptoms of a thyroid disorder is still very important. If you already have a condition such as hypothyroidism, it’s crucial that you know how to manage homocysteine levels, inflammation, and support your body’s nutritional needs. This article will explain the research behind the associated risk of MTHFR and thyroid disorders and how you can reduce your own risk of developing further complications.

    Will an MTHFR Gene Mutation Interfere with the Thyroid?

    MTHFR is a key enzyme in the metabolism of homocysteine and folate. It’s required to catalyze the conversion of5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the body’s main circulating form of folate. MTHFR gene polymorphisms can reduce folate levels in the body and increase homocysteine levels.


    The MTHFR enzyme is crucial for proper methylation in the body. Methylation is required for7 protein synthesis, antioxidant protection, metabolizing hormones, production of neurotransmitters, proper detoxification, and much more. All of these functions are also vital for healthy thyroid function.


    When methylation cannot happen, several bodily processes are disrupted, increasing the risk of health issues such as autoimmunity and thyroid dysfunction8.


    Changes in DNA methylation patterns have been correlated with tumorigenesis and autoimmune disease development9.


    MTHFR also contributes to the hypermethylation of genomic DNA10, which may affect genes that influence the risk of autoimmune thyroid diseases (AITD) and disrupt thyroid gland function.


    Thyroxine (T4) is required for the body to produce flavin adenine dinucleotide (FAD), the active form of vitamin B2. FAD is known to be sensitive to thyroid status11. T4 must convert Vitamin B2 into active FAD so that it can be used in the body. However, the MTHFR enzyme requires sufficient FAD to function properly. Some research has also linked hypothyroidism and riboflavin deficiency12. B2deficiency has also been found to play an etiological role in impaired methylation pathways13 in psychiatric patients.


    The two most common genetic polymorphisms of the MTHFR gene worldwide are the C677T and A1298C variants. Decreased MTHFR activity is more severe in those with the homozygous form (with two dominant alleles) of the mutation than in those with the heterozygous form (with two recessive alleles). However, compound heterozygosity of C677T and A1298C has been found to cause a significant elevation of homocysteine levels14.


    A 2020 study found that the C677T variant was significantly associated with hypothyroidism15. The study also indicated that a combination of C677T and A1298C genotypes was more prevalent in the hypothyroid patients than in those without the mutation. The authors concluded that the C677T polymorphism could increase the risk of hypothyroidism, possibly due to high levels of homocysteine.


    Previous research has already shown that theC677T variant may be a genetic risk factor for subclinical hypothyroidism16. It has also been shown that epigenetic modifications such as DNA methylation may be involved17in the development of subclinical hypothyroidism.


    Other research has indicated that those with hypothyroid tend to have higher levels of homocysteine than those with normal thyroid. Some experimental studies have also shown decreased MTHFR activity in hypothyroid patients18.


    The 1298A/C variant is found to result in a glutamic acid-to-alanine substitution, which in turn leads to a significant decrease of MTHFR enzyme activity19 in those with the CC genotype. This genetic variation has been linked to increased susceptibility to thyroid cancer20.

    MTHFR and Hyperthyroidism

    A South Korean study21 found an association between MTHFR and susceptibility to Graves’ ophthalmopathy (GO) in patients with Graves' disease (GD). Graves’ disease is an immune system disorder that causes excess production of thyroid hormones (hyperthyroidism). This study showed that having a C677T genotype significantly increased the risk of GO compared with that in healthy controls. In fact, the C677T genotype caused a 292% increase in the risk of GO. Homocysteine levels in patients with Graves’ disease who didn’t have GO were also found to be significantly higher than in patients with GO.


    Thyroid status was shown to affect theC677T polymorphism by modifying the synthesis of FAD (vitamin B2)22,which may affect the metabolism of folates and homocysteine. Hyperthyroid patients are found to have lower homocysteine concentrations, but these are shown to increase during antithyroid treatment23 -especially in patients with the MTHFR genotype. It has been suggested that this is due to a decrease in tissue FAD concentrations which may reduce MTHFR activity24, particularly in the case of MTHFR polymorphisms, because the enzyme has a low affinity for FAD.

    Coping with Thyroid Complications Due to an MTHFR Mutation

    Scientists have recommended that patients focus on lowering homocysteine levels25 by supplementing with Vitamin B6, B12, and folate. This is also effective for the long-term outcome in the treatment of hypothyroidism. Glutathione and folate are strongly associated with methylation, MTHFR function, and thyroid-related conditions.


    Glutathione is the body’s most abundant antioxidant and is crucial for reducing inflammation.


    Glutathione peroxidase (GPx) is one of the major selenoproteins which protects the thyroid cells from oxidative damage26. Low glutathione levels are linked to Hashimoto’s disease.


    Some research has also found a link between blood clotting disorders and high homocysteine levels to autoimmune thyroiditis. Of 50 patients with autoimmune thyroiditis, 15 were found to have an MTHFR mutation27. Those with thyroid disorders and high homocysteine (and/or an MTHFR mutation) should be aware of these cardiovascular risks.

    Preventing Thyroid Issues Associated with MTHFR Through Supplementation

    Several studies have suggested that the nutritional deficiencies caused by an MTHFR genetic mutation may increase the risk of developing thyroid disorders. This appears to be a consequence of B vitamin metabolism in the body, which is impaired by the MTHFR mutation, and subsequently affects the proper functioning of thyroid hormones28.


    The resulting increase in homocysteine level scan also disrupt thyroid function. Elevated homocysteine level may be linked to a higher prevalence of cardiovascular diseases29 in those with hypothyroidism.


    Supporting nutritional intake may help to reduce the risk of thyroid issues associated with MTHFR. The right nutrients can optimize methylation pathways and reduce overall homocysteine levels30.


    The body depends on two main nutrient pathways for breaking down homocysteine. Deficiencies in either of the pathways may result in elevated homocysteine levels. One of the pathways requires B vitamins, while the other one uses TMG (trimethylglycine) which is discovered as the first betaine.


    Increased intake of folate, vitamin B6,vitamin B12, and betaine may control or alleviate the risk of elevated homocysteine31.  Levothyroxine (a manufactured form of the thyroid hormone thyroxine) is often used to reduce homocysteine levels, and it has been shown to work more effectively when combined with folate32.


    DMG (dimethylglycine) is also an integral part of the one-carbon cycle via the methylfolate pathway33. Both TMG and DMG send methyl groups into the methyl pool to produce SAM-e (S-Adenosyl methionine) from homocysteine. If your body can use two pathways, methylation is much more efficient.

    L-methylfolate

    Mutations of the MTHFR gene(methylenetetrahydrofolate reductase) are a significant risk factor in elevated homocysteine. A mutation on the MTHFR gene can seriously affect the ability of the MTHFR enzyme to function normally34, which has severe implications for the homocysteine cycle. When compared to folic acid, L-MTHF is found to be more effective35 in lowering homocysteine levels.


    One of the best supplements for those with an MTHFR mutation and/or a thyroid disorder includes Methyl-Life’s® Methylated Multivitamin. The Methyl-Life® product range has been created by a team of natural health experts and contains the purest, most stable, and most potent of four of the world’s industry-leading patented L-methylfolate. It is also suitable for vegans and those with cardiovascular risks.

    Vitamin B6

    Low B6 status can also cause homocysteine to accumulate36 while also reducing the availability of SAMe for methylation processes.


    The active form of vitamin B6 is known aspyridoxal-5-phosphate (P5P), which is involved in reducing homocysteine levels and also in overall detoxification, as up to 50% of the cysteine produced through this pathway is used to create glutathione.

    Vitamin B12

    B12 works alongside folate and vitamin B6 in the methionine-homocysteine pathway to maintain normal concentrations of homocysteine. A deficiency of vitamin B12 may lead to increased homocysteine levels. Folate and vitamin B1237 are both necessary for the remethylation of homocysteine.

    Betaine

    Supplementation of the active form of betaine, TMG, can indirectly improve methylation by donating a methyl group to break down homocysteine38 into L-methionine. Betaine also boosts levels of S-Adenosyl Methionine (SAMe).

    Glutathione

    Glutathione (GSH) is one of the most important products of the methylation cycle. Low levels of GSH can lead to oxidative stress39 and the development of immunological intolerance in Hashimoto’s disease. Supplementing with the precursors to glutathione40- N-acetylcysteine (NAC) and selenium - is recommended as a means of supporting thyroid function.

    Product Recommendations

    L Methylfolate 7.5 mg + Vitamin B12 Tablets - Methyl-Life® Supplements

    L Methylfolate 7.5 mg + Vitamin B12 Tablets
    (8)

    $56.00

    • Therapeutic, Professional Strength L Methylfolate
    • Bioactive, Sublingual Vitamin B12 Tablets
    • 3rd-Party Tested for Purity, Potency & Safety
    • 90 Vegan, Non-GMO, Chewable Mint Tablets

    References

    1. American Thyroid Association; "General Information/Press Room"; 2025

      https://www.thyroid.org/media-main/press-room/

    2. Damali N Martin, Brenda J Boersma, Tiffany M Howe, Julie E Goodman, Leah E Mechanic, Stephen J Chanock, Stefan Ambs; "Association of MTHFR gene polymorphisms with breast cancer survival"; BMC Cancer; 2006 Oct

      https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-6-257

    3. ​Abu-Hassan DW, Alhouri AN, Altork NA, Shkoukani ZW, Altamimi TS, Alqaisi OM, Mustafa B; "MTHFR gene polymorphisms in hypothyroidism and hyperthyroidism among Jordanian females"; Archives of Endocrinology and Metabolism; May-June 2019.

      https://www.scielo.br/j/aem/a/GTxtjPYZ9gJFnmcScwXrHfh/?lang=en

    4. Abu-Hassan DW, Alhouri AN, Altork NA, Shkoukani ZW, Altamimi TS, Alqaisi OM, Mustafa B; "MTHFR gene polymorphisms in hypothyroidism and hyperthyroidism among Jordanian females"; Archives of Endocrinology and Metabolism; May-June 2019. ​

      https://pubmed.ncbi.nlm.nih.gov/31066758/

    5. ​Catargi B, Parrot-Roulaud F, Cochet C, Ducassou D, Roger P, Tabarin A; "Homocysteine, hypothyroidism, and effect of thyroid hormone replacement"; Thyroid; December 1999

      https://pubmed.ncbi.nlm.nih.gov/10646653/

    6. ​Arakawa Y, Watanabe M, Inoue N, Sarumaru M, Hidaka Y, Iwatani Y; "Association of polymorphisms in DNMT1, DNMT3A, DNMT3B, MTHFR and MTRR genes with global DNA methylation levels and prognosis of autoimmune thyroid disease"; Clinical and Experimental Immunology; November 2012.

      https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2249.2012.04646.x

    7. ​Jessica M. Pizano, Christy B. Williamson; "Nutritional Influences on Methylation"; Integrative and Functional Medical Nutrition Therapy; March 28, 2020

      https://link.springer.com/chapter/10.1007/978-3-030-30730-1_18

    8. ​Coppedè F; "Epigenetics and Autoimmune Thyroid Diseases"; Frontiers in Endocrinology; June 29, 2017.

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489553/

    9. ​Rountree MR, Bachman KE, Herman JG, Baylin SB; "DNA methylation, chromatin inheritance, and cancer"; Oncogene; May 31, 2001

      https://www.nature.com/articles/1204339

    10. ​Stern LL, Bagley PJ, Rosenberg IH, Selhub J; "Conversion of 5-formyltetrahydrofolic acid to 5-methyltetrahydrofolic acid is unimpaired in folate-adequate persons homozygous for the C677T mutation in the methylenetetrahydrofolate reductase gene"; Journal of Nutrition; September 2000

      https://pubmed.ncbi.nlm.nih.gov/10958818/

    11. I. R. Bell, F.D. Morrow, M. Read, S. Berkes, G. Perrone; "Low thyroxine levels in female psychiatric inpatients with riboflavin deficiency: implications for folate-dependent methylation"; Acta Psychiatrica Scandinavica; May 1992

      https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0447.1992.tb10319.x

    12. Richard S. Rivlin; "Regulation of flavoprotein enzymes in hypothyroidism and in riboflavin deficiency"; Advances in Enzyme Regulation Vol. 8, Pg. 239-250; 1970

      https://www.sciencedirect.com/science/article/abs/pii/0065257170900208

    13. I R Bell, F D Morrow, M Read, S Berkes, G Perrone; "Low thyroxine levels in female psychiatric inpatients with riboflavin deficiency: implications for folate-dependent methylation"; Acta psychiatrica Scandinavica; May 1992

      https://pubmed.ncbi.nlm.nih.gov/1605056/

    14. Shuji Ogino, Robert B Wilson; "Genotype and haplotype distributions of MTHFR677C>T and 1298A>C single nucleotide polymorphisms: a meta-analysis"; Journal of human genetics; 2003

      https://pubmed.ncbi.nlm.nih.gov/12560871/

    15. Tamar Kvaratskhelia, Elene Abzianidze, Ketevan Asatiani, Merab Kvintradze, Sandro Surmava, Eka Kvaratskhelia; "Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Polymorphisms in Georgian Females with Hypothyroidism"; Global medical genetics; 2020 Jul

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490122/

    16. Joseph G Hollowell, Norman W Staehling, W Dana Flanders, W Harry Hannon, Elaine W Gunter, Carole A Spencer, Lewis E Braverman; "Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III)"; The Journal of clinical endocrinology and metabolism; 2002 Feb

      https://pubmed.ncbi.nlm.nih.gov/11836274/

    17. T Kvaratskhelia, E Kvaratskhelia, K Kankava, E Abzianidze; "MTHFR GENE C677T POLYMORPHISM AND LEVELS OF DNA METHYLTRASFERASES IN SUBCLINICAL HYPOTHYROIDISM"; Georgian medical news; 2017 Apr

      https://pubmed.ncbi.nlm.nih.gov/28574380/

    18. Yande Zhou, Yufang Chen, Xueqin Cao, Chunfeng Liu, Ying Xie; "Association between plasma homocysteine status and hypothyroidism: a meta-analysis"; International journal of clinical and experimental medicine; 2014 Nov

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276243/

    19. K J Lievers, G H Boers, P Verhoef, M den Heijer, L A Kluijtmans, N M van der Put, F J Trijbels, H J Blom; "A second common variant in the methylenetetrahydrofolate reductase (MTHFR) gene and its relationship to MTHFR enzyme activity, homocysteine, and cardiovascular disease risk"; Journal of molecular medicine: official organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"; 2001 Sep

      https://pubmed.ncbi.nlm.nih.gov/11692165/

    20. Ying Chen, Bin Wang, Shengli Yan, Yan-Gang Wang; "Significant association between MTHFR C677T polymorphism and thyroid cancer risk: evidence from a meta-analysis"; Genetic testing and molecular biomarkers; 2014 Oct

      https://pubmed.ncbi.nlm.nih.gov/25007377/

    21. Jae Yeun Lee, Nam Keun Kim, Yong Wook Cho, Helen Lew; "Association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and susceptibility to Graves' ophthalmopathy"; Molecular Medicine Reports; 2016 Jun

      https://www.spandidos-publications.com/10.3892/mmr.2016.5458

    22. The American Journal of Clinical Nutrition

      https://academic.oup.com/ajcn/article/80/4/1050/4690360

    23. M J Diekman, N M van der Put, H J Blom, J G Tijssen, W M Wiersinga; "Determinants of changes in plasma homocysteine in hyperthyroidism and hypothyroidism"; Clinical endocrinology; 2001 Feb

      https://pubmed.ncbi.nlm.nih.gov/11207634/

    24. K Narisawa, T Tamura, K Tanno, K Ohara, T Arakawa; "Tetrahydrofolate-dependent enzyme activities of the rat liver in riboflavin deficiency"; The Tohoku journal of experimental medicine; 1968 Apr

      https://pubmed.ncbi.nlm.nih.gov/4970398/

    25. Tamar Kvaratskhelia, Elene Abzianidze, Ketevan Asatiani, Merab Kvintradze, Sandro Surmava, Eka Kvaratskhelia; "Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Polymorphisms in Georgian Females with Hypothyroidism"; Global medical genetics; 2020 Jul

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490122/

    26. Mitra Nourbakhsh, Fatemeh Ahmadpour, Behnam Chahardoli, Zahra Malekpour-Dehkordi, Mona Nourbakhsh, Seyed Reza Hosseini-Fard, Amirhossein Doustimotlagh, Abolfazl Golestani, Maryam Razzaghy-Azar; "Selenium and its relationship with selenoprotein P and glutathione peroxidase in children and adolescents with Hashimoto's thyroiditis and hypothyroidism"; Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS); 2016 Mar

      https://pubmed.ncbi.nlm.nih.gov/26854239/

    27. Alexandra Bulgar, Andreea Brehar, Diana Paun, Constantin Dumitrache; "MTHFR mutations in female patients with autoimmune thyroiditis"; Endocrine Abstracts; 2011

      https://www.endocrine-abstracts.org/ea/0026/ea0026p110

    28. Tamar Kvaratskhelia, Elene Abzianidze, Ketevan Asatiani, Merab Kvintradze, Sandro Surmava, Eka Kvaratskhelia; "Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Polymorphisms in Georgian Females with Hypothyroidism"; Global medical genetics; 2020 Jul

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490122/

    29. Amir Ziaee, Nader Hajibagher Tehrani, Zahra Hosseinkhani, Amir Kazemifar, Amir Javadi, Toktam Karimzadeh; "Effects of folic acid plus levothyroxine on serum homocysteine level in hypothyroidism"; Caspian journal of internal medicine; 2012

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861905/

    30. Avinash Kumar, Henry A Palfrey, Rashmi Pathak, Philip J Kadowitz, Thomas W Gettys, Subramanyam N Murthy; "The metabolism and significance of homocysteine in nutrition and health"; Nutrition & metabolism; 2017 Dec

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741875/

    31. Caterina Tinelli, Antonella Di Pino, Elena Ficulle, Serena Marcelli, Marco Feligioni; "Hyperhomocysteinemia as a Risk Factor and Potential Nutraceutical Target for Certain Pathologies"; Frontiers in nutrition; 2019 Apr

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491750/

    32. Amir Ziaee, Nader Hajibagher Tehrani, Zahra Hosseinkhani, Amir Kazemifar, Amir Javadi, Toktam Karimzadeh; "Effects of folic acid plus levothyroxine on serum homocysteine level in hypothyroidism"; Caspian journal of internal medicine; 2012

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861905/

    33. Rima Obeid; "The Metabolic Burden of Methyl Donor Deficiency with Focus on the Betaine Homocysteine Methyltransferase Pathway"; Nutrients; 2013 Sep

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798916/

    34. Testing.com | MTHFR Mutation

      https://labtestsonline.org/tests/mthfr-mutation

    35. The American Journal of Clinical Nutrition

      https://academic.oup.com/ajcn/article/77/3/658/4689715

    36. Marcelina Parra, Seth Stahl, Hanjo Hellmann; "Vitamin B6 and Its Role in Cell Metabolism and Physiology"; Cells; 2018

      https://www.mdpi.com/2073-4409/7/7/84

    37. Seema Bhargava, Arif Ali, Eishaan Kamta Bhargava, Anjali Manocha, Mamta Kankra, Sabari Das, Lalit Mohan Srivastava; "Lowering homocysteine and modifying nutritional status with folic acid and vitamin B12 in Indian patients of vascular disease"; Journal of clinical biochemistry and nutrition; 2012 Feb

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334376/

    38. Rima Obeid; "The Metabolic Burden of Methyl Donor Deficiency with Focus on the Betaine Homocysteine Methyltransferase Pathway"; Nutrients; 2013 Sep

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798916/

    39. R Rostami, M R Aghasi, A Mohammadi, J Nourooz-Zadeh; "Enhanced oxidative stress in Hashimoto's thyroiditis: inter-relationships to biomarkers of thyroid function"; Clinical biochemistry; 2013 Mar

      https://pubmed.ncbi.nlm.nih.gov/23219737/

    40. Rebecca L Gould, Robert Pazdro; "Impact of Supplementary Amino Acids, Micronutrients, and Overall Diet on Glutathione Homeostasis"; Nutrients; 2019 May

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566166/

    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!

    Browse Categories

    Product Recommendations

    L Methylfolate 7.5 mg + Vitamin B12 Tablets - Methyl-Life® Supplements

    L Methylfolate 7.5 mg + Vitamin B12 Tablets
    (8)

    $56.00

    BOOST YOUR MOOD[2]