Will MTHFR Cause Hair Loss? | Methyl-Life

Will MTHFR Cause Hair Loss? | Methyl-Life

Table of Contents

    Will MTHFR Cause Hair Loss?

    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.

    Why the MTHFR Gene is Important to Hair Health

    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. 

    The MTHFR Gene's Role in Folate Conversion

    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.

    How an MTHFR Gene Mutation Can Affect Hair

    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. 

    Will the Variants Have a Different Effect?

    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.

    Treating Hair Loss Associated with MTHFR Gene Mutations

    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. 

    Summary

    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. 

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    References

    1. Leila Asfour, William Cranwell, Rodney Sinclair; "Male Androgenetic Alopecia"; Endotext [Internet]; 2023 Jan

      https://www.ncbi.nlm.nih.gov/books/NBK278957/

    2. Desmond C C Gan, Rodney D Sinclair; "Prevalence of male and female pattern hair loss in Maryborough"; The journal of investigative dermatology. Symposium proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research; 2005 Dec

      https://pubmed.ncbi.nlm.nih.gov/16382660/

    3. James A Greenberg, Stacey J Bell, Yong Guan, Yan-hong Yu; "Folic Acid Supplementation and Pregnancy: More Than Just Neural Tube Defect Prevention"; Reviews in obstetrics & gynecology.; 2011

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218540/

    4. Stephan Moll, Elizabeth A. Varga; "Homocysteine and MTHFR Mutations"; Circulation; 2015 Jul

      https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.114.013311

    5. James S Graydon, Karla Claudio, Seth Baker, Mohan Kocherla, Mark Ferreira, Abiel Roche-Lima, Jovaniel Rodríguez-Maldonado, Jorge Duconge, Gualberto Ruaño; "Ethnogeographic prevalence and implications of the 677C>T and 1298A>C MTHFR polymorphisms in US primary care populations"; Biomarkers in medicine.; 2019 Jun

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630484/

    6. Daniel Leclerc, Sahar Sibani, Rima Rozen; "Molecular Biology of Methylenetetrahydrofolate Reductase (MTHFR) and Overview of Mutations/Polymorphisms"; Madame Curie Bioscience Database [Internet]; 2000-2013

      https://www.ncbi.nlm.nih.gov/books/NBK6561/

    7. SceinceDirect; "Hair Keratin"; Medicine and Dentistry | Medical Biochemistry; 2017

      https://www.sciencedirect.com/topics/medicine-and-dentistry/hair-keratin

    8. Hind M Almohanna, Azhar A Ahmed, John P Tsatalis, Antonella Tosti; "The Role of Vitamins and Minerals in Hair Loss: A Review"; Dermatology and therapy;

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380979/

    9. Olaf Stanger, Willibald Wonisch; "Enzymatic and non-enzymatic antioxidative effects of folic acid and its reduced derivates"; Sub-cellular biochemistry; 2012

      https://pubmed.ncbi.nlm.nih.gov/22116698/

    10. The American Journal of Clinical Nutrition | A journal of the American Society for Nutrition

      https://academic.oup.com/ajcn/article/82/1/188/4863359

    11. Kristine Hoffman; "When Vitamin And Nutritional Deficiencies Cause Skin And Nail Changes"; Podiatry Today; 2015 Jan

      https://www.hmpgloballearningnetwork.com/site/podiatry/when-vitamin-and-nutritional-deficiencies-cause-skin-and-nail-changes

    12. Khalid M Al-Batayneh, Mazhar Salim Al Zoubi, Murad Shehab, Bahaa Al-Trad, Khaldon Bodoor, Wesam Al Khateeb, Alaa A A Aljabali, Mohammad Al Hamad, Greg Eaton; "Association between MTHFR 677C>T Polymorphism and Vitamin B12 Deficiency: A Case-control Study"; Journal of medical biochemistry; 2018 Apr

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294092/

    13. Hanna Czeczot; "[Folic acid in physiology and pathology]"; Postȩpy higieny i medycyny doświadczalnej; 2008 Aug

      https://pubmed.ncbi.nlm.nih.gov/18772846/

    14. Elysia Tjong, Manjari Dimri, Shamim S. Mohiuddin; "Biochemistry, Tetrahydrofolate"; StatPearls [Internet]; 2023 Jun

      https://www.ncbi.nlm.nih.gov/books/NBK539712/

    15. Jin Gao, Catherine M. Cahill, Xudong Huang, Joshua L. Roffman, Stefania Lamon-Fava, Maurizio Fava, David Mischoulon, Jack T. Rogers; "S-Adenosyl Methionine and Transmethylation Pathways in Neuropsychiatric Diseases Throughout Life"; Neurotherapeutics Vol. 15 pg. 156-175; 2018

      https://link.springer.com/article/10.1007/s13311-017-0593-0

    16. Yosef Dror, Michael Hopp; "Hair for brain trade-off, a metabolic bypass for encephalization"; Open Access; 2014

      https://springerplus.springeropen.com/articles/10.1186/2193-1801-3-562

    17. C Herbert Pratt, Lloyd E King Jr, Andrew G Messenger, Angela M Christiano, John P Sundberg; "Alopecia areata"; Nature reviews. Disease primers.; 2017 Aug

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573125/

    18. Göknur Kalkan, Serbulent Yigit, Nevin Karakuş, Omer Ateş, Nihan Bozkurt, Atiye Ozdemir, Günseli Şefika Pancar; "Methylenetetrahydrofolate reductase C677T mutation in patients with alopecia areata in Turkish population"; Gene; 2013 Nov

      https://pubmed.ncbi.nlm.nih.gov/23954881/

    19. Göknur Kalkan, Serbulent Yigit, Nevin Karakuş, Omer Ateş, Nihan Bozkurt, Atiye Ozdemir, Günseli Şefika Pancar; "Methylenetetrahydrofolate reductase C677T mutation in patients with alopecia areata in Turkish population"; Gene; 2013 Nov

      https://pubmed.ncbi.nlm.nih.gov/23954881/

    20. Maryam Yousefi, Mohammad Reza Namazi, Hoda Rahimi, Shima Younespour, Amir Houshang Ehsani, Safoura Shakoei; "Evaluation of Serum Homocysteine, High-Sensitivity CRP, and RBC Folate in Patients with Alopecia Areata"; Indian Journal of Dermatology; 2014 Nov-Dec

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248520/

    21. Hind M Almohanna, Azhar A Ahmed, John P Tsatalis, Antonella Tosti; "The Role of Vitamins and Minerals in Hair Loss: A Review"; Dermatology and therapy; 2018

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380979/

    22. Dinesh Gowda, V Premalatha, DB Imtiyaz; "Prevalence of Nutritional Deficiencies in Hair Loss among Indian Participants: Results of a Cross-sectional Study"; International journal of trichology; 2017 Jul-Sep

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596642/

    23. Laura Dean; "Methylenetetrahydrofolate Reductase Deficiency"; Medical Genetics Summaries [Internet]; 2012 Mar

      https://www.ncbi.nlm.nih.gov/books/NBK66131/

    24. Deepashree Daulatabad, Archana Singal, Chander Grover, Neelam Chhillar; "Prospective Analytical Controlled Study Evaluating Serum Biotin, Vitamin B12, and Folic Acid in Patients with Premature Canities"; International Journal of Trichology; 2017 Jan-Mar

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514791/

    25. Dinesh Gowda, V Premalatha, DB Imtiyaz; "Prevalence of Nutritional Deficiencies in Hair Loss among Indian Participants: Results of a Cross-sectional Study"; Internation Journal of Trichology; 2017 Jul-Sep

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596642/

    26. Stephan Moll, Elizabeth A. Varga; "Homocysteine and MTHFR Mutations"; Circulation; 2015 Jul

      https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.114.013311

    27. Stephan Moll, Elizabeth A. Varga; "Homocysteine and MTHFR Mutations"; Circulation; 2015 Jul

      https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.114.013311

    28. Göknur Kalkan, Serbulent Yigit, Nevin Karakuş, Omer Ateş, Nihan Bozkurt, Atiye Ozdemir, Günseli Şefika Pancar; "Methylenetetrahydrofolate reductase C677T mutation in patients with alopecia areata in Turkish population"; Gene; 2013 Nov

      https://pubmed.ncbi.nlm.nih.gov/23954881/

    29. Maša Vidmar Golja, Alenka Šmid, Nataša Karas Kuželički, Jurij Trontelj, Ksenija Geršak, Irena Mlinarič-Raščan; "Folate Insufficiency Due to MTHFR Deficiency Is Bypassed by 5-Methyltetrahydrofolate"; Journal of Clinical Medicine; 2020 Sep

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564482/

    30. National Institutes of Health | Office of Dietary Supplements

      https://ods.od.nih.gov/factsheets/folate-Health%20Professional/

    31. Maša Vidmar Golja, Alenka Šmid, Nataša Karas Kuželički, Jurij Trontelj, Ksenija Geršak, Irena Mlinarič-Raščan; "Folate Insufficiency Due to MTHFR Deficiency Is Bypassed by 5-Methyltetrahydrofolate"; Journal of Clinical Medicine; 2020 Sep

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564482/

    32. Maryam Yousefi, Mohammad Reza Namazi, Hoda Rahimi, Shima Younespour, Amir Houshang Ehsani, Safoura Shakoei; "Evaluation of Serum Homocysteine, High-Sensitivity CRP, and RBC Folate in Patients with Alopecia Areata"; Indian Journal of Dermatology; 2014 Nov-Dec

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248520/

    33. Zenglin Lian, Hong Chen, Kang Liu, Qianghua Jia, Feng Qiu, Yongzhi Cheng; "Improved Stability of a Stable Crystal Form C of 6S-5-Methyltetrahydrofolate Calcium Salt, Method Development and Validation of an LC–MS/MS Method for Rat Pharmacokinetic Comparison"; Molecules; 2021

      https://www.mdpi.com/1420-3049/26/19/6011/htm

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      https://www.freepik.com/

    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!