Will MTHFR Cause Hair Loss? | Methyl-Life®

Hair loss is a distressing condition that affects millions of people worldwide. It can severely affect one’s confidence and self-esteem, and many people spend thousands of dollars searching for a solution.

The most common form of hair loss is male androgenetic alopecia (MAA), affecting 30-50% of men by age 50¹. In women, the prevalence of hair loss increases with age, from around 12% amongst women aged 20- 29 years to over 50% in women aged 80+².

The etiology of hair loss has been linked to a wide range of factors, from genes to psychological distress. More recently, however, the MTHFR gene has been highlighted as a possible cause.

It’s thought that around 60% of the US population³ have some form of the genetic polymorphism of the MTHFR enzyme, while up to 25% of certain populations are homozygous for variations of the MTHFR gene. A mutation in the MTHFR gene will compromise the function of the MTHFR enzyme by around 40-70%⁴, which has varying downstream effects on the body’s methylation processes.

Although there is limited research on the association between MTHFR and hair loss, there is some evidence that it may lead to the autoimmune condition alopecia. Researchers have also highlighted the role that folate plays in hair growth.

Approximately 25% of the global population⁵ are carriers of C667T mutation, while about 25% of the global population have the 1298AC variant. Identifying this genetic alteration may provide insight into many health conditions, including those related to hair loss.

This article will discuss why the MTHFR gene is important to hair health and the potential links between MTHFR and hair loss. We will also discuss how to treat hair loss linked to an MTHFR polymorphism.

The MTHFR gene provides your body with instructions⁶for making the enzyme methylenetetrahydrofolate reductase. This enzyme is required for facilitating the processing of amino acids, which are the building blocks of proteins. The MTHFR enzyme is also necessary for methylation, the signaling tool that cells use to switch genes ‘on’ and ‘off’. It repairs DNA, and supports many other key processes in the body.

The MTHFR enzyme is especially important for converting the potentially damaging amino acid homocysteine into another amino acid, methionine. Methionine is an antioxidant that can help protect the body from harmful substances, while homocysteine can cause endothelial damage and other cardiovascular injuries.

Amino acids play a major role in hair health. Around 95% of hair⁷ is made up of a tough protein called keratin, which in turn is made up of many different amino acids.

Most importantly, MTHFR is responsible for the conversion of folate into a usable form called methylfolate. Folate is crucial to maintaining hair growth and overall hair health. This water-soluble vitamin is essential for normal cell growth and metabolism and is critically required for DNA repair processes. It is one of many micronutrients involved in the growth cycle of the hair follicle and cellular turnover, which is essential for the rapidly dividing cells in the hair follicle bulb. Folate works alongside vitamin B12 in nucleic acid production⁸, which may play a role in the highly proliferative hair follicle.

Folate acts directly to produce antioxidant effects⁹ and indirectly to lower homocysteine levels and ensure optimal functioning of the methylation cycle.

However, the MTHFR gene can severely affect the conversion of folate in the body, leading to low levels of folate¹⁰. Folate deficiency can lead to changes in the hair, skin, and nails¹¹.

It’s worth noting that like folate, the MTHFR genetic mutation is significantly associated with vitamin B12 deficiency¹². Vitamin B12 is also necessary for DNA synthesis, neurological function, and red blood cell formation. Vitamin B12 is a cofactor for methionine synthase and is involved in the production of DNA, RNA, proteins, and many other substrates. 

Humans cannot synthesize folate, which means it is a dietary requirement. The primary function of folate is the transfer of methyl and formyl groups¹³. It is also essential for cell growth and reproduction, the formation of certain amino acids (methionine, serine, glycine, and histidine) and the breakdown of proteins (namely homocysteine). It plays a part in the formation of DNA and RNA, red blood cell maturation, and making neurotransmitters.

As mentioned above, the MTHFR gene produces the enzyme MTHFR, which is involved in the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the primary form of active folate circulating in the blood.

The conversion of dihydrofolate (DHF) and folic acid to L-methylfolate occurs through a four-step process¹⁴.

• First, folic acid is converted to DHF by the dihydrofolate reductase enzyme (DHFR)
• DHF is then converted to tetrahydrofolate (THF)
• THF is converted to 5, 10-methyleneTHF
• 5,10-methyleneTHF is converted to L-methylfolate by the methyltetrahydrofolate reductase enzyme (MTHFR).

5-methyltetrahydrofolate is required for the remethylation of homocysteine to methionine, which is then converted to S-adenosylmethionine. This S-adenosylmethionine is then able to serve as a methyl donor¹⁵ in various reactions throughout the body.

The amino acids methionine, arginine, cysteine, and tyrosine are structural components of all hair¹⁶. These amino acids and their derivatives are not always easily obtained from food, so they must be produced within the body.

Mutations in the MTHFR gene have been associated with a range of health conditions, including elevated homocysteine in the blood, birth defects, mood disorders, and several autoimmune disorders. The gene may also play a role in the growth and maintenance of hair.

Alopecia areata (AA) is a common type of hair loss affecting 1-2% of the general population¹⁷ and can lead to a complete loss of hair from the scalp. It is considered to be a tissue-specific autoimmune disease as the hair follicle has been targeted and antibodies to their own hair follicle structures have been developed.

The MTHFR enzyme is key to regulating folate metabolism, which in turn is thought to influence DNA methylation and nucleic acid synthesis. For this reason, researchers have hypothesized that there may be an association between the MTHFR gene mutations¹⁸ and susceptibility to AA.

This Turkish study¹⁹ demonstrated an association between MTHFR and increased risk of AA. The researchers found that the C677T mutation was higher in people who suffered from AA, suggesting that the MTHFR mutation may have contributed to an increased risk of developing the condition. As a result, the researchers suggested that screening AA patients for folate deficiencies could provide some hope for the management of their condition.

A 2014 study also found a link between folate deficiency and the development of alopecia²⁰. The study measured levels of folate in the red blood cells (RBC) along with homocysteine and the inflammatory marker C-Reactive Protein (CRP). The patients with hair loss all had markedly lower levels of RBC folate. The patients who had the most severe hair loss also had the lowest levels of folate. The researchers noted that although other studies had reported no significant findings in folate levels of those with alopecia, in these studies, the folate level has been measured in serum. RBC is a more accurate indicator as serum folate can be impaired by diet and other external factors.

Nutritional deficiencies are associated with both MTHFR mutation and with hair loss. Folate plays a crucial role in healthy cell growth, particularly in the cells of skin, hair, and nails²¹. It is also required for the proper formation of red blood cells. 

Participants with different types of hair loss have been shown to have various deficiencies in amino acids and micronutrients²². The MTHFR enzyme plays an important role in processing amino acids²³, including the conversion of homocysteine to methionine. Genetic variations in the MTHFR gene can lead to impaired function or inactivation of this enzyme, which may result in similar deficiencies.

There is also evidence that folate deficiency may be linked to premature greying. One study found that adults with premature greying were deficient in folic acid²⁴ and vitamins B-7 and B-12.

An Indian study showed a high prevalence of folate deficiency²⁵ in patients with androgenetic alopecia and telogen effluvium, a condition in which stress causes temporary hair loss. 

The impact of an MTHFR mutation on the body generally depends on how the variant affects enzymatic function. In a heterozygous MTHFR C677T mutation, MTHFR enzyme function is reduced to around 65%²⁶; in the homozygous mutation, enzyme function is only around 30%.

Homozygous MTHFR A1298C is thought to be less severe, resulting in around 60% of normal enzyme function²⁷.

These differences suggest that C677T generally may have a more pronounced effect on hair loss. This was shown by the Turkish study mentioned above, which found that the C677T mutation²⁸ was higher in people who suffered from AA, suggesting that this variant is linked to a higher risk of hair loss.

An MTHFR mutation impairs the conversion of folic acid to bioavailable folate, which means that many people with MTHFR mutations are also low in folate²⁹. This has a downstream effect on many other methylation processes in the body, including the possible link to hair loss, as discussed above.

Fortunately, folate deficiency caused by the MTHFR mutation can be treated by taking a specific methylated form of folate.

L-methylfolate is an active form of folate³⁰, which means it doesn’t require enzymatic conversion to enter the folate cycle. This form of folate can bypass folate insufficiency due to a reduction in MTHFR. Supplementation with L-methylfolate is shown to be more efficient than supplementation³¹ with folic acid for this very reason and may also be used to overcome metabolic defects caused by the MTHFR mutation. 

Hair loss is a distressing but common condition with a wide range of causes. In the case of genetic factors, research suggests that the MTHFR genetic mutations may have an influence on hair health and maintenance.

However, it is important to note that while MTHFR mutations have been linked to many health conditions, they will not necessarily cause hair loss. Currently, a causal link has not been established.

While studies are still limited, it has been established that a link exists between the autoimmune hair loss condition androgenetic alopecia and MTHFR³². The impaired MTHFR enzyme in C677T polymorphism appears to be higher in people who suffer from AA, suggesting that this particular variant may increase susceptibility.

Links have also been made between folate deficiency and hair loss. These links highlight the need for supplementing with a bioactive form of folate such as L-methylfolate.

Some of the most highly recommended methylfolate supplements are in the Methyl-Life® product range, which includes a range of dosage levels: Methylfolate 7.5+, Methylfolate 10, and Methylfolate 15.

Each of the methylfolate products in the Methyl-Life’s® range contains the internationally-patented Magnafolate® PRO  [(6S)-5-methyltetrahydrofolic acid, Calcium salt, Type C Crystalline molecule (L-Methylfolate)]. These best-selling products are formulated especially for people with a heightened need for bioavailable folate due to MTHFR defects.

This unique and internationally-patented L-5-Methylfolate ingredient is crystalline calcium salt-based for superior stability and absorption. Most importantly, research has revealed that it is approximately three times purer making it more stable than other L-methylfolates³³available on the health supplement market today - which makes it ideal for those concerned about their risk of hair loss or other MTHFR-related health conditions.