MTHFR and the Thyroid
An estimated 20 million Americans have some form of thyroid disorder, 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 enzyme 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 unique pathways concerning the thyroid T cells. One particular study found the 1298A>C genetic polymorphism of MTHFR may modulate the risk of thyroid disease.
Further research has suggested that elevated homocysteine—a common consequence of MTHFR mutations—is a risk factor for developing a thyroid disorder.
Results, however, are mixed. Another study 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 for 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 dysfunction.
Changes in DNA methylation patterns have been correlated with tumorigenesis and autoimmune disease development.
MTHFR also contributes to the hypermethylation of genomic DNA, 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 status. 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 deficiency. B2deficiency has also been found to play an etiological role in impaired methylation pathways 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 levels.
A 2020 study found that the C677T variant was significantly associated with hypothyroidism. 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 hypothyroidism. It has also been shown that epigenetic modifications such as DNA methylation may be involved in 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 patients.
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 activity in those with the CC genotype. This genetic variation has been linked to increased susceptibility to thyroid cancer.
MTHFR and Hyperthyroidism
A South Korean study 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),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 treatment -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 activity, 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 levels 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 damage. 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 mutation. 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 hormones.
The resulting increase in homocysteine level scan also disrupt thyroid function. Elevated homocysteine level may be linked to a higher prevalence of cardiovascular diseases 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 levels.
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 homocysteine. 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 folate.
DMG (dimethylglycine) is also an integral part of the one-carbon cycle via the methylfolate pathway. 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.
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 normally, which has severe implications for the homocysteine cycle. When compared to folic acid, L-MTHF is found to be more effective 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.
Low B6 status can also cause homocysteine to accumulate 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.
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 B12 are both necessary for the remethylation of homocysteine.
Supplementation of the active form of betaine, TMG, can indirectly improve methylation by donating a methyl group to break down homocysteine into L-methionine. Betaine also boosts levels of S-Adenosyl Methionine (SAMe).
Glutathione (GSH) is one of the most important products of the methylation cycle. Low levels of GSH can lead to oxidative stress and the development of immunological intolerance in Hashimoto’s disease. Supplementing with the precursors to glutathione- N-acetylcysteine (NAC) and selenium - is recommended as a means of supporting thyroid function.