Everything to know about MTHFR connection to hypothyroidism

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The thyroid and diseases affecting the thyroid gland are being extensively studied.

There’s always something we don’t know, and a lot of things left for us to learn. For example, when the term hypothyroidism comes to mind, you think of various symptoms it causes and how it can affect heart health, diabetes, lead to weight gain, and so much more.

Hypothyroidism, like other conditions affecting this gland, is connected with many other changes in the body.

Lately, MTHFR has become a frequently mentioned term, but what is it actually?

In this article, we will discuss MTHFR and its connection with hypothyroidism.

What is MTHFR?

Methylenetetrahydrofolate reductase (MTHFR) is a gene that contains the DNA code necessary to produce the MTHFR enzyme which plays a role in processing amino acids, the building blocks of proteins.

Additionally, MTHFR is significant for a chemical reaction that involves forms of vitamin B9, also known as folate. The enzyme converts the molecule called 5,10-methylenetetrahydrofolate to a molecule called 5-methylenetetrahydrofolate.

This conversion is crucial for the multistep process during which amino acid homocysteine is converted to yet another amino acid methionine which the body utilizes to create proteins and other compounds[i] it needs to function properly.

MTHFR is getting a lot of attention lately due to a genetic mutation that may lead to high levels of homocysteine in the blood and low levels of folate and some other vitamins.

Homocysteine is an amino acid in your blood, but we also get it from food. High levels of homocysteine can cause cardiovascular diseases such as atherosclerosis.

People can have one or two mutations of the MTHFR gene. Some people don’t have any mutation of the MTHFR gene at all.

Gene mutations are called variants i.e., parts of the DNA of a gene that is usually different from person to person.

Two variants of mutations affecting the MTHFR gene are:

  • C677T – found in 30% to 40% of the American population and affecting mainly Hispanic and Caucasian men and women[ii]
  • A1298C – found in 20% of the US population

Some people can have both C677T and A1298C variants. In most cases, gene mutations are inherited i.e., your chance of having MTHFR gene mutation is a lot higher if your parents also have it.

Do I have an MTHFR gene mutation?

After reading about MTHFR gene mutations, it’s natural to wonder whether you might also have it. Every gene mutation manifests itself through various signs, symptoms, and changes in the body. MTHFR gene mutation is not the exception.

Despite the fact that scientists are still not quite sure about all diseases and conditions that may develop due to MTHFR gene mutation, this problem is usually associated with a large variety of diseases, including hypothyroidism.[iii]

The condition and its severity in association with MTHFR gene mutation depend on the variant and how much it affects the production of MTHFR enzyme.

Is hypothyroidism linked with MTHFR gene

As shown above, the MTHFR gene mutation is associated with thyroid disorders.

Yang et al. carried out a meta-analysis which found that there is a link between MTHFR C677T polymorphism and a higher risk of thyroid cancer[iv].

But what about hypothyroidism? Is there a link between this common thyroid condition and MTHFR gene mutation?

Unlike some other topics associated with hypothyroidism are studied extensively, its potential relationship with MTHFR isn’t.

Current evidence revolves around some minor studies such as research done by Abu-Hassan et al. on 264 Jordanian women. Of these, 98 had hypothyroidism, 66 hyperthyroidism, and 100 women were in the control group.

The study found that g.1298A>C genetic polymorphism of MTHFR modulates the risk of thyroid disease. Haplotypes CC, TA, and TC contribute to the risk of hypothyroidism[v]. A haplotype is defined as a set of genetic determinants located on a single chromosome.

Bulgar et al. also carried out a smaller study which found that MTHFR gene variations are strongly associated with the risk of autoimmune thyroiditis or Hashimoto’s thyroiditis[vi]. That is an autoimmune condition which is recognized as the most common cause of hypothyroidism, and it mainly affects women.

Despite the fact the above-mentioned studies are smaller, their results shouldn’t be neglected. They confirm that people with MTHFR are more likely to have hypothyroidism and also emphasize the importance of further studies with larger sample size.

Why are hypothyroidism and MTHFR linked?

Unfortunately, it’s not easy to answer this question.

The reason is simple; more studies are needed to uncover all the underlying mechanisms that connect the two.

The thyroid status affects the expression of the MTHFR gene, regardless of whether we have the MTHFR gene mutation or not.

Earlier in the article, we mentioned that the MTHFR gene activates an enzyme that plays a role in the production of folate and other vitamins. That could be a potential pathway through which hypothyroidism and MTHFR gene variations are connected. If you have hypothyroidism, it means the body does not produce sufficient levels of hormones T3 and T4.

Low concentration of T4 doesn’t allow the body to convert Vitamin B2 to its active form called flavin adenine dinucleotide (FAD)[vii]. This means you may be deficient in this vitamin. That being said, if there is not enough FAD, a person’s MTHFR enzyme slows down and leads to low methylfolate levels which can mimic the symptoms associated with MTHFR polymorphism[viii].

MTHFR gene variations can have a negative impact on overall thyroid health. For example, MTHFR polymorphisms impair detoxification of chemicals and negatively affect the immune system health, both of which can contribute to the development of conditions such as Hashimoto’s thyroiditis.

Impaired methylation associated with MTHFR gene mutation leads to decreased concentration of methylfolate, which plays a role in biopterin (BH4) production.

Why does this matter? It’s simple; this process is necessary for the conversion of tyrosine in its active form. Your body requires tyrosine to produce thyroid hormones.

Therefore, MTHFR mutations cause a chain of reactions that can cause impaired production of much-needed thyroid hormones and thereby contribute to hypothyroidism.

Hypothyroidism and homocysteine

One of the most common manifestations of MTHFR gene mutation is high homocysteine concentration.

However, you need to bear in mind that elevated homocysteine doesn’t always indicate the presence of MTHFR gene variations. It can also increase due to other causes such as family history, psoriasis, kidney disease, some medications, just to name a few.

Conversely, having both hypothyroidism and high homocysteine levels doesn’t automatically mean you have MTHFR gene mutation. Why? The reason is simple – underactive thyroid gland i.e., hypothyroidism causes high homocysteine levels[ix] independently of whether you have MTHFR or not.

That’s why it’s always useful to consult your doctor who will order tests to monitor thyroid levels, cholesterol, homocysteine, and explain what you can do to keep them in a healthy range while undergoing treatment for hypothyroidism.

How to know if I have MTHFR gene mutation?

The term “gene mutation” seems scary and daunting. We believe all the worst things can happen if the mutation is present and want to learn whether we have it. At this point, you’re probably thinking about the possibility of finding out if you have some MTHFR gene variant.

However, according to multiple health organizations such as the American College of Medical Genetics, American Heart Association, College of American Pathologists, and the American College of Obstetricians and Gynecologists do not recommend testing for MTHFR gene variants unless you have high homocysteine levels or other health indications that are associated with this gene mutation[x]. In other words, if you don’t have heart problems and other conditions that are known for their relationship with MTHFR gene mutation, you don’t really need to get tested.

But, if you really want to know if you have MTHFR gene mutation, you may want to consult your healthcare provider who will inform you about all the pros and cons of getting tested by giving blood.

It’s useful to bear in mind that genetic testing may or may not be covered by your insurance. There are also some at-home genetic testing kits that screen for MTHFR gene mutation as well.

What to do if I have MTHFR gene mutation?

Having a gene mutation can come as a shock as we immediately picture all the worst-case scenarios in our mind. But you shouldn’t think that way. Let’s say your doctor recommended MTHFR testing for some reason and results show you do have one or two variations of the gene.

What now? For starters – don’t panic!

In many cases, people with MTHFR gene mutation don’t need any medical treatment. Considering the fact that these mutations affect the conversion of vitamins from their inactive to active forms and thereby pave the way to deficiencies it may be practical to take B-complex vitamin supplements. This will prevent deficiencies and complications that come with them.

You may also want to make some healthier diet-related choices. For instance, try to enrich the diet with foods abundant in folate in order to support levels of this vitamin in a natural manner. In some cases, supplementation could still be necessary, but your doctor will inform you about this.

Some foods you may want to include into your diet include sunflower seeds, peanut butter, cooked beans, peas, and lentils, vegetables such as beets, fruits like cantaloupe, grapefruit, and strawberries, juices such as pineapple, grapefruit, tomato, orange.

Bear in mind juices should be freshly made at home without added sugar. Store-bought juices are laden with sugar and are bad for your health.


MTHFR is a widely used term nowadays, but many people aren’t quite sure what it is. In essence, it’s a gene that activates an enzyme needed for the production of vitamins.

Mutations of this gene cause various health problems, including high homocysteine levels and thyroid diseases.

Studies have shown that MTHFR gene mutation is strongly associated with higher hypothyroidism risk.

However, testing for this gene mutation isn’t recommended unless a person displays clinical signs associated with MTHFR gene variation.


[i] MTHFR gene, National Institutes of Health, U.S. National Library of Medicine. Retrieved from: https://ghr.nlm.nih.gov/gene/MTHFR

[ii] MTHFR gene variant, National Institutes of Health. Retrieved from: https://rarediseases.info.nih.gov/diseases/10953/mthfr-gene-mutation

[iii] Methylenetetrahydrofolate reductase and psychiatric diseases. Nature. Retrieved from: https://www.nature.com/articles/s41398-018-0276-6

[iv] Yang YM, Zhang TT, Yuan L, Ren Y. (2014). The association between the C677T polymorphism in the MTHFR gene and the risk of thyroid cancer: a meta-analysis. European Review for Medical and Pharmacological Sciences, 18(15):2097-2101. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/25070812

[v] Abu-Hassan DW, Alhouri AN, Altork NA. (2019). MTHFR gene polymorphisms in hypothyroidism and hyperthyroidism among Jordanian females. Archives of Endocrinology and Metabolism, ahead of print. Doi: 10.20945/2359-3997000000133. Retrieved from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972019005003102

[vi] Bulgar A, Brehar A, Paun D, Dumitrache C. MTHFR mutations in female patients with autoimmune thyroiditis. (2011). 13th European Congress of Endocrinology. Retrieved from: https://www.endocrine-abstracts.org/ea/0026/ea0026p110

[vii] Cimino JA, Jhangiani S, Schwartz E, Cooperman JM. Riboflavin metabolism in the hypothyroid human adult. (1987) Proceedings of the Society for Experimental Biology and Medicine, 184(2):151-153. Doi: 10.3181/00379727-184-42459. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/3809170

[viii] Hustad S, Nedrebo BG, Ueland PM, et al. (2004). Phenotypic expression of the methylenetetrahydrofolate reductase 677C→T polymorphism and flavin cofactor availability in thyroid dysfunction. American Journal of Clinical Nutrition, 80(4):1050-1057. Doi: 10.1093/ajcn/80.4.1050. Retrieved from: https://academic.oup.com/ajcn/article/80/4/1050/4690360

[ix] Nedrebo BG, Nygard O, Ueland PM, Lien EA. (2001). Plasma total homocysteine in hyper- and hypothyroid patients before and during 12 months of treatment. Clinical Chemistry, 47(9):1738-1741. Retrieved from: http://clinchem.aaccjnls.org/content/47/9/1738

[x] What you need to know about the MTHFR gene? Healthline. Retrieved from: https://www.healthline.com/health/mthfr-gene#testing

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