MTHFR and Thyroid

MTHFR and Thyroid

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Katie Stone - Naturopath

Written By:

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

Medical Reviewer:

Dr. Nare Simonyan - PhD Pharmaceutical Science
Kari Asadorian - BSN, RN

Edited By:

Kari Asadorian - BSN, RN
Last updated:

What causes thyroid issues?

Thyroid problems and disorders can be caused by a range of factors, including genetics, iodine deficiency, autoimmune diseases (such as Graves' disease or Hashimoto's disease), inflammation of the thyroid gland (thyroiditis), and some medications or therapies (such as chemotherapy).1


Lifestyle factors can also disrupt normal thyroid function. Too little or too much iodine in the diet, exposure to environmental toxins, smoking, stress, medications, and pregnancy can all change thyroid function.2

Common thyroid conditions

Hypothyroidism: Underactive thyroid. This is a common condition affecting around 11.7% of the US population.3 It results in under secretion of thyroid hormones, mainly thyroxine (T4) and triiodothyronine (T3).4


Hyperthyroidism: Overactive thyroid. This results in increased synthesis and secretion of thyroid hormones from the thyroid gland. The most common cause of hyperthyroidism is Graves’ disease, followed by toxic nodular goitre.5


Graves' disease: An autoimmune disease in which thyroid receptor autoantibodies (TRAbs) stimulate the thyroid-stimulating hormone (TSH) receptor (TSHR) on the thyroid gland, causing excessive thyroid hormone secretion (hyperthyroidism).6 It is the most common cause of hyperthyroidism.


Thyroid cancer: Cancer affecting thyroid parenchymal cells. Thyroid cancer is the fifth most common cancer in women in the US.7 Up to 80% of all thyroid cancers are papillary, which is very treatable.


Hashimoto thyroiditis: An autoimmune disease in which the body’s immune system attacks its own thyroid follicular cells. It is the most common cause of hypothyroidism and leads to production of antithyroid antibodies and activation of T-cells. If untreated, Hashimoto’s can progress to fibrosis of the thyroid gland.8 Hashimoto’s affects around 7.8% of people in the US.

How does MTHFR impact the risk of autoimmune diseases like thyroiditis?

Several clinical and epidemiological studies have linked MTHFR mutations to thyroid dysfunction, particularly hypothyroidism. This may be due to high homocysteine, which has been correlated to MTHFR and hypothyroidism.9


A 2020 study found that MTHFR C677T was significantly associated with hypothyroidism, particularly in women, and even more so in people with the T allele.10


A 2024 meta-analysis also found that the MTHFR C677T mutation may be linked to an increased risk of hypothyroidism, particularly in individuals with the TT homozygous genotype. However, the study authors suggest that further research may be necessary to confirm this finding.11

Coping with Thyroid Complications Due to an MTHFR Mutation

MTHFR is a common cause of high homocysteine levels, which is a risk factor in thyroid disorders.12 Animal studies have shown that hyperhomocysteinemia can lead to hypothyroidism and may also worsen thyroid hormone resistance.13


If you have MTHFR, talk to your health professional about monitoring your homocysteine levels. Methylfolate is highly recommended for those with MTHFR as it bypasses the mutation and participates in the remethylation of homocysteine. Clinical studies show that supplementation with methylfolate is an effective way to reduce homocysteine levels.14

Should thyroiditis patients get tested for MTHFR?

As MTHFR is a known risk factor for poor homocysteine metabolism, and elevated homocysteine may contribute to thyroid dysfunction, then yes - it is recommended that you test both for MTHFR and your homocysteine levels.

Treatment options/supplements for thyroid conditions

Methylfolate, P5P, and active B12

Supplementing with methylfolate, pyridoxal-5′-phosphate (P5P or active B6), and methylcobalamin has been shown to significantly reduce homocysteine levels. Methylfolate is a bioactive form of folate that directly facilitates the re-methylation of homocysteine to methionine.15 This process is critical for people with MTHFR as these genetic variations can impair the conversion of folate to its active form, often leading to homocysteine accumulation. Bioavailable methylfolate bypasses this metabolic block.
Vitamin B2 deficiency can significantly affect thyroid function, as it works alongside B6 as a cofactor in many biochemical reactions involved in proper metabolism. Studies have shown that vitamin B2 is significant for normal thyroid functioning, but further research is pending.16

Iodine and other minerals

Every thyroid condition is different, and it’s important to discuss your unique needs with a health professional before experimenting with supplements.


Studies suggest that iodine levels are a key factor in thyroid disorders in adults, and that an underactive thyroid caused by iodine deficiency may be managed by increasing iodine intake.17 However, a sudden increase in iodine intake after deficiency can lead to transient hyperthyroidism.18


It should be noted that iodine supplementation is contraindicated in some autoimmune thyroid conditions such as Hashimoto’s, even if deficient.19

MTHFR and Thyroid

  • Icon MTHFR mutations may increase the risk of hypothyroidism, especially in individuals with the C677T variant and elevated homocysteine levels.
  • Icon Monitoring homocysteine and supplementing with methylfolate, P5P, and methylcobalamin may help manage thyroid dysfunction in those with MTHFR.
  • Icon Thyroiditis patients may benefit from MTHFR and homocysteine testing to better manage their health.

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$96.00

  • Bioactive MTHFR Folate, Methylfolate, for Max Absorption
  • Sublingual B12 to Aid B12 Sufficiency via Active Hydroxy Form
  • 3rd-Party Tested for Purity, Potency & Safety
  • 90 Day Supply to Optimize Methylation Pathways

Frequently Asked Questions about MTHFR and thyroid

Can MTHFR affect the thyroid?

The MTHFR mutation does not directly affect the thyroid, but it can impair homocysteine metabolism, which may lead to elevated homocysteine. Hyperhomocysteinemia has been linked to thyroid issues, mainly hypothyroidism. If you have MTHFR, it may be advisable to monitor your homocysteine levels.

What are signs that your thyroid is out of whack?

Signs of hypothyroidism (underactive thyroid) may include an enlarged thyroid gland, unexplained weight gain, slowed speech and movement, dry skin, dry and brittle hair, pale skin, jaundice, enlarged tongue, bradycardia, and slow reflexes. 20
Signs of hyperthyroidism (overactive thyroid) may include unexplained weight loss, anxiety or nervousness, increased sweating, tremulousness, diarrhea, palpitations, muscular weakness, and heat intolerance.

What autoimmune disease is associated with MTHFR?

A 2022 meta-analysis has linked MTHFR to the following autoimmune diseases:21
⭄ Behcet's disease: MTHFR C677T is associated with increased risk, especially the TT type.
⭄ Multiple sclerosis (MS): Both MTHFR C677T and A1298C may increase risk.
⭄ Ankylosing spondylitis: MTHFR C677T may increase risk.
⭄ Psoriasis: Some individual studies suggest a possible link.

References

  1. Juan-Sebastián Franco, Jenny Amaya-Amaya, Juan-Manuel Anaya; "Chapter 30Thyroid disease and autoimmune diseases"; Autoimmunity: From Bench to Bedside [Internet].; 2013 Jul

    https://www.ncbi.nlm.nih.gov/books/NBK459466/

  2. Juan-Sebastián Franco, Jenny Amaya-Amaya, Juan-Manuel Anaya; "Chapter 30Thyroid disease and autoimmune diseases"; Autoimmunity: From Bench to Bedside [Internet].; 2013 Jul

    https://www.ncbi.nlm.nih.gov/books/NBK459466/

  3. Kathleen L Wyne, Lekshmi Nair, Chris P Schneiderman, Brett Pinsky, Oscar Antunez Flores, Dianlin Guo, Bruce Barger, Alexander H Tessnow; "Hypothyroidism Prevalence in the United States: A Retrospective Study Combining National Health and Nutrition Examination Survey and Claims Data, 2009–2019"; Journal of the Endocrine Society; 2022 Nov

    https://pmc.ncbi.nlm.nih.gov/articles/PMC9706417

  4. Udit M Zamwar, Komal N Muneshwar; "Epidemiology, Types, Causes, Clinical Presentation, Diagnosis, and Treatment of Hypothyroidism"; Cureus; 2023 Sep

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10613832/

  5. Simone De Leo, Sun Y Lee, Lewis E Braverman; "Hyperthyroidism"; Lancet; 2016 Sep

    https://pmc.ncbi.nlm.nih.gov/articles/PMC5014602/

  6. Laura C Lane, Claire Louise Wood, Tim Cheetham; "Graves’ disease: moving forwards"; Archives of disease in childhood; 2022 Jul

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10086272/

  7. Kenny Lee, Catherine Anastasopoulou, Chandriya Chandran, Sebastiano Cassaro; "Thyroid Cancer"; StatPearls [Internet]; 2023 May

    https://www.ncbi.nlm.nih.gov/books/NBK459299/

  8. Jasleen Kaur, Ishwarlal Jialal; "Hashimoto Thyroiditis"; StatPearls [Internet]; 2025 Feb

    https://www.ncbi.nlm.nih.gov/books/NBK459262/

  9. Rui Yang, Danhua Pu, Rongrong Tan, Jie Wu; "Association of methylenetetrahydrofolate reductase ( MTHFR ) gene polymorphisms (C677T and A1298C) with thyroid dysfunction: A meta-analysis and trial sequential analysis"; Archives of endocrinology and metabolism; 2022 Jun

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10697641/

  10. 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://pmc.ncbi.nlm.nih.gov/articles/PMC7490122/

  11. Rui Yang, Danhua Pu, Rongrong Tan, Jie Wu; "Association of methylenetetrahydrofolate reductase ( MTHFR ) gene polymorphisms (C677T and A1298C) with thyroid dysfunction: A meta-analysis and trial sequential analysis"; Archives of endocrinology and metabolism; 2022 Jun

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10697641/

  12. Angelika De Bree, W M Monique Verschuren, Daan Kromhout, Leo A J Kluijtmans, Henk J Blom; "Homocysteine determinants and the evidence to what extent homocysteine determines the risk of coronary heart disease"; Pharmacological reviews; 2002 Dec

    https://pubmed.ncbi.nlm.nih.gov/12429870/

  13. Xiaoyu Ding, Ying Wang, Jia Liu, Guang Wang; "Impaired Sensitivity to Thyroid Hormones Is Associated With Elevated Homocysteine Levels in the Euthyroid Population"; The Journal of Clinical Endocrinology & Metabolism; 2022 Sep

    https://academic.oup.com/jcem/article/107/9/e3731/6609259

  14. Doreen Schmidl, Kinga Howorka, Stephan Szegedi, Kristina Stjepanek, Stefan Puchner, Ahmed Bata, Ulrike Scheschy, Gerold Aschinger, René M Werkmeister, Leopold Schmetterer, Gerhard Garhofer; "A pilot study to assess the effect of a three-month vitamin supplementation containing L-methylfolate on systemic homocysteine plasma concentrations and retinal blood flow in patients with diabetes"; Molecular vision; 2020 Apr

    https://pmc.ncbi.nlm.nih.gov/articles/PMC7190578/

  15. Evgeny Pokushalov; Andrey Ponomarenko, Sevda Bayramova, Claire Garcia, Inessa Pak, Evgenya Shrainer, Marina Ermolaeva, Dmitry Kudlay, Michael Johnson, Richard Miller; "Effect of Methylfolate, Pyridoxal-5′-Phosphate, and Methylcobalamin (SolowaysTM) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized Controlled Trial"; Nutrients; 2024

    https://www.mdpi.com/2072-6643/16/11/1550

  16. Hari Krishnan Krishnamurthy, Swarnkumar Reddy, Vasanth Jayaraman, Karthik Krishna, Qi Song, Karenah E Rajasekaran, Tianhao Wang, Kang Bei, John J Rajasekaran; "Effect of Micronutrients on Thyroid Parameters"; Journal of thyroid research; 2021 Sep

    https://pubmed.ncbi.nlm.nih.gov/35140907/

  17. Institute for Quality and Efficiency in Health Care; "Overview: Underactive thyroid (hypothyroidism)"; InformedHealth.org [Internet]; 2024 May

    https://www.ncbi.nlm.nih.gov/books/NBK279601

  18. Hye Rim Chung; "Iodine and thyroid function"; Annals of pediatric endocrinology & metabolism; 2014 Mar

    https://pmc.ncbi.nlm.nih.gov/articles/PMC4049553

  19. National Institute of Diabetes and Digestive and Kidney Diseases; "Hashimoto's Disease"; 2021 Jun

    https://www.niddk.nih.gov/health-information/endocrine-diseases/hashimotos-disease

  20. Nikita Patil, Anis Rehman, Catherine Anastasopoulou, Ishwarlal Jialal; "Hypothyroidism"; StatPearls [Internet]; 2024 Feb

    https://www.ncbi.nlm.nih.gov/books/NBK519536/

  21. Mao Lu, Ke Peng, Li Song, Li Luo, Peng Liang, Yundan Liang; "Association between Genetic Polymorphisms in Methylenetetrahydrofolate Reductase and Risk of Autoimmune Diseases: A Systematic Review and Meta-Analysis"; Disease markers; 2022 May

    https://pmc.ncbi.nlm.nih.gov/articles/PMC9173919/

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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