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American Journal of Clinical Dermatology

, Volume 18, Issue 5, pp 663–679 | Cite as

The Role of Micronutrients in Alopecia Areata: A Review

  • Jordan M. Thompson
  • Mehwish A. Mirza
  • Min Kyung Park
  • Abrar A. Qureshi
  • Eunyoung ChoEmail author
Review Article

Abstract

Alopecia areata (AA) is a common, non-scarring form of hair loss caused by immune-mediated attack of the hair follicle. As with other immune-mediated diseases, a complex interplay between environment and genetics is thought to lead to the development of AA. Deficiency of micronutrients such as vitamins and minerals may represent a modifiable risk factor associated with development of AA. Given the role of these micronutrients in normal hair follicle development and in immune cell function, a growing number of investigations have sought to determine whether serum levels of these nutrients might differ in AA patients, and whether supplementation of these nutrients might represent a therapeutic option for AA. While current treatment often relies on invasive steroid injections or immunomodulating agents with potentially harmful side effects, therapy by micronutrient supplementation, whether as a primary modality or as adjunctive treatment, could offer a promising low-risk alternative. However, our review highlights a need for further research in this area, given that the current body of literature largely consists of small case–control studies and case reports, which preclude any definite conclusions for a role of micronutrients in AA. In this comprehensive review of the current literature, we found that serum vitamin D, zinc, and folate levels tend to be lower in patients with AA as compared to controls. Evidence is conflicting or insufficient to suggest differences in levels of iron, vitamin B12, copper, magnesium, or selenium. A small number of studies suggest that vitamin A levels may modify the disease. Though understanding of the role for micronutrients in AA is growing, definitive clinical recommendations such as routine serum level testing or therapeutic supplementation call for additional studies in larger populations and with a prospective design.

Keywords

Hair Loss Alopecia Areata Calcipotriol Serum Zinc Level Squaric Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Compliance with Ethical Standards

Conflict of interest

Dr. Qureshi serves as a consultant for Abbvie, Amgen, the Centers for Disease Control and Prevention, Janssen, Merck, Novartis, and Pfizer, and is an investigator for Amgen, Regeneron, and Sanofi. Mr. Thompson, Ms. Mirza, Dr. Park, and Dr. Cho have no conflicts of interest.

Funding

This work was funded by the Ruth Sauber Medical Scholar Award of Alpert Medical School, Brown University.

References

  1. 1.
    Bronsnick T, Murzaku EC, Rao BK. Diet in dermatology: part I. Atopic dermatitis, acne, and nonmelanoma skin cancer. J Am Acad Dermatol. 2014;71:1039.e1–12. doi: 10.1016/j.jaad.2014.06.015.CrossRefGoogle Scholar
  2. 2.
    Murzaku EC, Bronsnick T, Rao BK. Diet in dermatology: part II. Melanoma, chronic urticaria, and psoriasis. J Am Acad Dermatol. 2014;71:1053.e1–16. doi: 10.1016/j.jaad.2014.06.016.CrossRefGoogle Scholar
  3. 3.
    Villasante Fricke AC, Miteva M. Epidemiology and burden of alopecia areata: a systematic review. Clin Cosmet Investig Dermatol. 2015;8:397–403. doi: 10.2147/CCID.S53985.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Liu LY, King BA, Craiglow BG. Health-related quality of life (HRQoL) among patients with alopecia areata (AA): a systematic review. J Am Acad Dermatol. 2016. doi: 10.1016/j.jaad.2016.04.035.Google Scholar
  5. 5.
    Islam N, Leung PSC, Huntley AC, Gershwin ME. The autoimmune basis of alopecia areata: a comprehensive review. Autoimmun Rev. 2015;14:81–9. doi: 10.1016/j.autrev.2014.10.014.CrossRefPubMedGoogle Scholar
  6. 6.
    Alkhalifah A, Alsantali A, Wang E, et al. Alopecia areata update: part II. Treatment. J Am Acad Dermatol. 2010;62:191–202. doi: 10.1016/j.jaad.2009.10.031 (quiz 203–4).CrossRefPubMedGoogle Scholar
  7. 7.
    Mason JB. 218—vitamins, trace minerals, and other micronutrients, twenty fifth edition. Goldman-Cecil Med. 2016;2:1445.e1–1455.e1. doi: 10.1016/B978-1-4557-5017-7.00218-X.Google Scholar
  8. 8.
    Handjiski BK, Eichmüller S, Hofmann U, et al. Alkaline phosphatase activity and localization during the murine hair cycle. Br J Dermatol. 1994;131:303–10.CrossRefPubMedGoogle Scholar
  9. 9.
    Prie BE, Voiculescu VM, Ionescu-Bozdog OB, et al. Oxidative stress and alopecia areata. J Med Life. 2015;8(Spec Issue):43–6.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Antico A, Tampoia M, Tozzoli R, Bizzaro N. Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. Autoimmun Rev. 2012;12:127–36. doi: 10.1016/j.autrev.2012.07.007.CrossRefPubMedGoogle Scholar
  11. 11.
    Petukhova L, Duvic M, Hordinsky M, et al. Genome-wide association study in alopecia areata implicates both innate and adaptive immunity. Nature. 2010;466:113–7. doi: 10.1038/nature09114.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81. doi: 10.1056/NEJMra070553.CrossRefPubMedGoogle Scholar
  13. 13.
    Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr. 2004;80:1678S–88S.PubMedGoogle Scholar
  14. 14.
    Forrest KYZ, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. 2011;31:48–54. doi: 10.1016/j.nutres.2010.12.001.CrossRefPubMedGoogle Scholar
  15. 15.
    Ross AC, Taylor CL, Yaktine AL, Del Valle HB. Dietary Reference Intakes for Calcium and Vitamin D. Report from the Institute of Medicine of the National Academy of Sciences. Washington (DC): National Academies Press; 2011. pp. 1-4.Google Scholar
  16. 16.
    Giovannucci E. The epidemiology of vitamin D and cancer incidence and mortality: a review (United States). Cancer Causes Control. 2005;16:83–95. doi: 10.1007/s10552-004-1661-4.CrossRefPubMedGoogle Scholar
  17. 17.
    Visser M, Deeg DJH, Lips P, Longitudinal Aging Study Amsterdam. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab. 2003;88:5766–72. doi: 10.1210/jc.2003-030604.CrossRefPubMedGoogle Scholar
  18. 18.
    Rostand SG. Ultraviolet light may contribute to geographic and racial blood pressure differences. Hypertension. 1997;30:150–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Wang L, Song Y, Manson JE, et al. Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies. Circ Cardiovasc Qual Outcomes. 2012;5:819–29. doi: 10.1161/CIRCOUTCOMES.112.967604.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Song Y, Wang L, Pittas AG, et al. Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care. 2013;36:1422–8. doi: 10.2337/dc12-0962.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Aguado P, del Campo MT, Garcés MV, et al. Low vitamin D levels in outpatient postmenopausal women from a rheumatology clinic in Madrid, Spain: their relationship with bone mineral density. Osteoporos Int. 2000;11:739–44. doi: 10.1007/s001980070052.CrossRefPubMedGoogle Scholar
  22. 22.
    Kamen DL, Cooper GS, Bouali H, et al. Vitamin D deficiency in systemic lupus erythematosus. Autoimmun Rev. 2006;5:114–7. doi: 10.1016/j.autrev.2005.05.009.CrossRefPubMedGoogle Scholar
  23. 23.
    Munger KL, Zhang SM, OReilly E, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology. 2004;62:60–5.CrossRefPubMedGoogle Scholar
  24. 24.
    Chaudhary S, Dutta D, Kumar M, et al. Vitamin D supplementation reduces thyroid peroxidase antibody levels in patients with autoimmune thyroid disease: an open-labeled randomized controlled trial. Indian J Endocrinol Metab. 2016;20:391–8. doi: 10.4103/2230-8210.179997.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Reichrath J, Schilli M, Kerber A, et al. Hair follicle expression of 1,25-dihydroxyvitamin D3 receptors during the murine hair cycle. Br J Dermatol. 1994;131:477–82.CrossRefPubMedGoogle Scholar
  26. 26.
    Xie Z, Komuves L, Yu Q-C, et al. Lack of the vitamin D receptor is associated with reduced epidermal differentiation and hair follicle growth. J Investig Dermatol. 2002;118:11–6. doi: 10.1046/j.1523-1747.2002.01644.x.CrossRefPubMedGoogle Scholar
  27. 27.
    Chen CH, Sakai Y, Demay MB. Targeting expression of the human vitamin D receptor to the keratinocytes of vitamin D receptor null mice prevents alopecia. Endocrinology. 2001;142:5386–9. doi: 10.1210/endo.142.12.8650.CrossRefPubMedGoogle Scholar
  28. 28.
    Sakai Y, Kishimoto J, Demay MB. Metabolic and cellular analysis of alopecia in vitamin D receptor knockout mice. J Clin Invest. 2001;107:961–6. doi: 10.1172/JCI11676.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Takeda E, Kuroda Y, Saijo T, et al. 1 alpha-hydroxyvitamin D3 treatment of three patients with 1,25-dihydroxyvitamin D-receptor-defect rickets and alopecia. Pediatrics. 1987;80:97–101.PubMedGoogle Scholar
  30. 30.
    Malloy PJ, Pike JW, Feldman D. The vitamin D receptor and the syndrome of hereditary 1,25-dihydroxyvitamin D-resistant rickets. Endocr Rev. 1999;20:156–88. doi: 10.1210/edrv.20.2.0359.PubMedGoogle Scholar
  31. 31.
    Forghani N, Lum C, Krishnan S, et al. Two new unrelated cases of hereditary 1,25-dihydroxyvitamin D-resistant rickets with alopecia resulting from the same novel nonsense mutation in the vitamin D receptor gene. J Pediatr Endocrinol Metab. 2010;23:843–50.CrossRefPubMedGoogle Scholar
  32. 32.
    Aksu Cerman A, Sarikaya Solak S, Kivanc Altunay I. Vitamin D deficiency in alopecia areata. Br J Dermatol. 2014;170:1299–304. doi: 10.1111/bjd.12980.CrossRefPubMedGoogle Scholar
  33. 33.
    Mahamid M, Abu-Elhija O, Samamra M, et al. Association between vitamin D levels and alopecia areata. Isr Med Assoc J. 2014;16:367–70.PubMedGoogle Scholar
  34. 34.
    d’Ovidio R, Vessio M, d’Ovidio FD. Reduced level of 25-hydroxyvitamin D in chronic/relapsing Alopecia Areata. Dermatoendocrinol. 2013;5:271–3. doi: 10.4161/derm.24411.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Yilmaz N, Serarslan G, Gokce C. Vitamin D concentrations are decreased in patients with alopecia areata. VTE. 2012;01:1–4. doi: 10.4172/2167-0390.1000105.CrossRefGoogle Scholar
  36. 36.
    Akar A, Orkunoglu FE, Ozata M, et al. Lack of association between vitamin D receptor FokI polymorphism and alopecia areata. Eur J Dermatol. 2004;14:156–8.PubMedGoogle Scholar
  37. 37.
    Akar A, Orkunoglu FE, Tunca M, et al. Vitamin D receptor gene polymorphisms are not associated with alopecia areata. Int J Dermatol. 2007;46:927–9. doi: 10.1111/j.1365-4632.2007.03140.x.CrossRefPubMedGoogle Scholar
  38. 38.
    Çerman AA, Solak SS, Altunay İ, Küçükünal NA. Topical calcipotriol therapy for mild-to-moderate alopecia areata: a retrospective study. J Drugs Dermatol. 2015;14:616–20.PubMedGoogle Scholar
  39. 39.
    Kim DH, Lee JW, Kim IS, et al. Successful treatment of alopecia areata with topical calcipotriol. Ann Dermatol. 2012;24:341–4. doi: 10.5021/ad.2012.24.3.341.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Orecchia G, Rocchetti GA. Topical use of calcipotriol does not potentiate squaric acid dibutylester effectiveness in the treatment of alopecia areata. J Dermatol Treat. 2009;6:21–3. doi: 10.3109/09546639509080585.CrossRefGoogle Scholar
  41. 41.
    Berth-Jones J, Hutchinson PE. Alopecia totalis does not respond to the vitamin-D analogue calcipotriol. J Dermatol Treat. 2009;1:293–4. doi: 10.3109/09546639109086760.CrossRefGoogle Scholar
  42. 42.
    Fawzi MMT, Mahmoud SB, Ahmed SF, Shaker OG. Assessment of vitamin D receptors in alopecia areata and androgenetic alopecia. J Cosmet Dermatol. 2016;15:318–23. doi: 10.1111/jocd.12224.CrossRefPubMedGoogle Scholar
  43. 43.
    Bakry OA, El Farargy SM, El Shafiee MK, Soliman A. Serum vitamin D in patients with alopecia areata. Indian Dermatol Online J. 2016;7:371–7. doi: 10.4103/2229-5178.190504.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Narang T, Daroach M, Kumaran MS. Efficacy and safety of topical calcipotriol in management of alopecia areata: a pilot study. Dermatol Ther. 2017;88:e12464. doi: 10.1111/dth.12464.CrossRefGoogle Scholar
  45. 45.
    Ban Y, Taniyama M. Vitamin D receptor gene polymorphism is associated with Graves’ disease in the Japanese population. J Clin Endocrinol Metab. 2000;85:4639–43. doi: 10.1210/jcem.85.12.7038.PubMedGoogle Scholar
  46. 46.
    Saeki H, Asano N, Tsunemi Y, et al. Polymorphisms of vitamin D receptor gene in Japanese patients with psoriasis vulgaris. J Dermatol Sci. 2002;30:167–71.CrossRefPubMedGoogle Scholar
  47. 47.
    Thompson JM, Li T, Park MK, et al. Estimated serum vitamin D status, vitamin D intake, and risk of incident alopecia areata among US women. Arch Dermatol Res. 2016. doi: 10.1007/s00403-016-1687-y.PubMedGoogle Scholar
  48. 48.
    Vissers WHPM, Berends M, Muys L, et al. The effect of the combination of calcipotriol and betamethasone dipropionate versus both monotherapies on epidermal proliferation, keratinization and T-cell subsets in chronic plaque psoriasis. Exp Dermatol. 2004;13:106–12. doi: 10.1111/j.0906-6705.2004.00151.x.CrossRefPubMedGoogle Scholar
  49. 49.
    Rizova E, Corroller M. Topical calcitriol—studies on local tolerance and systemic safety. Br J Dermatol. 2001;144(Suppl 58):3–10.PubMedGoogle Scholar
  50. 50.
    MacDonald Hull SP, Wood ML, Hutchinson PE, et al. Guidelines for the management of alopecia areata. Br J Dermatol. 2003;149:692–9.CrossRefPubMedGoogle Scholar
  51. 51.
    Institute of Medicine (US) Panel on Micronutrients. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Report from the Institute of Medicine of the National Academy of Sciences. Washington (DC): National Academies Press; 2001. pp. 82–83,443. doi: 10.17226/10026.
  52. 52.
    Finner AM. Nutrition and hair: deficiencies and supplements. Dermatol Clin. 2013;31:167–72. doi: 10.1016/j.det.2012.08.015.CrossRefPubMedGoogle Scholar
  53. 53.
    Abdel Fattah NSA, Atef MM, Al-Qaradaghi SMQ. Evaluation of serum zinc level in patients with newly diagnosed and resistant alopecia areata. Int J Dermatol. 2016;55:24–9. doi: 10.1111/ijd.12769.CrossRefPubMedGoogle Scholar
  54. 54.
    Kil MS, Kim CW, Kim SS. Analysis of serum zinc and copper concentrations in hair loss. Ann Dermatol. 2013;25:405. doi: 10.5021/ad.2013.25.4.405.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Bhat YJ, Manzoor S, Khan AR, Qayoom S. Trace element levels in alopecia areata. Indian J Dermatol Venereol Leprol. 2009;75:29–31.CrossRefPubMedGoogle Scholar
  56. 56.
    Amirnia M, Sinafar S, Sinafar H, Nuri M. Assessment of zinc and copper contents in the hair and serum and also superoxide dismutase, glutathion peroxidase and malondi aldehyde in serum in androgenetic alopecia and alopecia areata. Life Sci J. 2013;10:204–9.Google Scholar
  57. 57.
    Dastgheib L, Mostafavi-pour Z, Abdorazagh AA, et al. Comparison of Zn, Cu, and Fe content in hair and serum in alopecia areata patients with normal group. Dermatol Res Pract. 2014;2014:1–5. doi: 10.1155/2014/784863.CrossRefGoogle Scholar
  58. 58.
    Mussalo-Rauhamaa H, Lakomaa EL, Kianto U, Lehto J. Element concentrations in serum, erythrocytes, hair and urine of alopecia patients. Acta Derm Venereol. 1986;66:103–9.PubMedGoogle Scholar
  59. 59.
    Ead RD. Oral zinc sulphate in alopacia areata—a double blind trial. Br J Dermatol. 1981;104:483–4. doi: 10.1111/j.1365-2133.1981.tb15323.x.CrossRefPubMedGoogle Scholar
  60. 60.
    Park H, Kim CW, Kim SS, Park CW. The therapeutic effect and the changed serum zinc level after zinc supplementation in alopecia areata patients who had a low serum zinc level. Ann Dermatol. 2009;21:142–6. doi: 10.5021/ad.2009.21.2.142.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Camacho FM, García-Hernández MJ. Zinc aspartate, biotin, and clobetasol propionate in the treatment of alopecia areata in childhood. Pediatr Dermatol. 1999;16:336–8.CrossRefPubMedGoogle Scholar
  62. 62.
    Lux-Battistelli C. Combination therapy with zinc gluconate and PUVA for alopecia areata totalis: an adjunctive but crucial role of zinc supplementation. Dermatol Ther. 2015;28:235–8. doi: 10.1111/dth.12215.CrossRefPubMedGoogle Scholar
  63. 63.
    Institute of Medicine (US) Panel on Dietary Antioxidants and Related Compounds. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Report from the Institute of Medicine of the National Academy of Sciences. Washington DC: National Academies Press; 2000. pp. 285, 325–326. doi: 10.17226/9810.
  64. 64.
    Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. Report from the Institute of Medicine of the National Academy of Sciences. Washington DC: National Academies Press; 1997. pp. 190–191. doi: 10.17226/5776.
  65. 65.
    Feizy V, Mortazavi H, Barikbin B, et al. Serum selenium level in Iranian patients with alopecia areata. J Eur Acad Dermatol Venereol. 2008;22:1259–60. doi: 10.1111/j.1468-3083.2008.02612.x.CrossRefPubMedGoogle Scholar
  66. 66.
    World Health Organization, Centers for Disease Control and Prevention, Prevention. Assessing the iron status of populations. 2nd ed. Geneva: World Health Organization; 2004.Google Scholar
  67. 67.
    Trost LB, Bergfeld WF, Calogeras E. The diagnosis and treatment of iron deficiency and its potential relationship to hair loss. J Am Acad Dermatol. 2006;54:824–44. doi: 10.1016/j.jaad.2005.11.1104.CrossRefPubMedGoogle Scholar
  68. 68.
    Kantor J, Kessler LJ, Brooks DG, Cotsarelis G. Decreased serum ferritin is associated with alopecia in women. J Investig Dermatol. 2003;121:985–8. doi: 10.1046/j.1523-1747.2003.12540.x.CrossRefPubMedGoogle Scholar
  69. 69.
    Walters GO, Miller FM, Worwood M. Serum ferritin concentration and iron stores in normal subjects. J Clin Pathol. 1973;26:770–2. doi: 10.1136/jcp.26.10.770.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Boffa MJ, Wood P, Griffiths CE. Iron status of patients with alopecia areata. Br J Dermatol. 1995;132:662–4.CrossRefPubMedGoogle Scholar
  71. 71.
    White MI, Currie J, Williams MP. A study of the tissue iron status of patients with alopecia areata. Br J Dermatol. 1994;130:261–3.CrossRefPubMedGoogle Scholar
  72. 72.
    Gonul M, Cakmak S, Soylu S, et al. Serum vitamin B12, folate, ferritin, and iron levels in Turkish patients with alopecia areata. Indian J Dermatol Venereol Leprol. 2009;75:552. doi: 10.4103/0378-6323.55430.CrossRefPubMedGoogle Scholar
  73. 73.
    Tzellos TG, Tahmatzidis DK, Lallas A, et al. Pernicious anemia in a patient with type 1 diabetes mellitus and alopecia areata universalis. J Diabetes Complic. 2009;23:434–7. doi: 10.1016/j.jdiacomp.2008.05.003.CrossRefGoogle Scholar
  74. 74.
    Esfandiarpour I, Farajzadeh S, Abbaszadeh M. Evaluation of serum iron and ferritin levels in alopecia areata. Dermatol Online J. 2008;14:21.Google Scholar
  75. 75.
    Hugh Rushton D, Ramsay ID. The importance of adequate serum ferritin levels during oral cyproterone acetate and ethinyl oestradiol treatment of diffuse androgen-dependent alopecia in women. Clin Endocrinol (Oxf). 1992;36:421–7. doi: 10.1111/j.1365-2265.1992.tb01470.x.CrossRefGoogle Scholar
  76. 76.
    Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Report from the Institute of Medicine of the National Academy of Sciences. Washington DC: National Academies Press; 1998. pp. 306-307, 313. doi: 10.17226/6015.
  77. 77.
    Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency. BMJ. 2014;349:g5226.CrossRefPubMedGoogle Scholar
  78. 78.
    Yousefi M, Shakoei S, Namazi M, et al. Evaluation of serum homocysteine, high-sensitivity CRP, and RBC folate in patients with alopecia areata. Indian J Dermatol. 2014;59:630. doi: 10.4103/0019-5154.143567.PubMedPubMedCentralGoogle Scholar
  79. 79.
    Ertugrul DT, Karadag AS, Takci Z, et al. Serum holotranscobalamine, vitamin B12, folic acid and homocysteine levels in alopecia areata patients. Cutan Ocul Toxicol. 2013;32:1–3. doi: 10.3109/15569527.2012.683499.CrossRefPubMedGoogle Scholar
  80. 80.
    Kalkan G, Yigit S, Karakuş N, et al. Methylenetetrahydrofolate reductase C677T mutation in patients with alopecia areata in Turkish population. Gene. 2013;530:109–12. doi: 10.1016/j.gene.2013.08.016.CrossRefPubMedGoogle Scholar
  81. 81.
    Zafad S, Madani A, Harif M, et al. Pernicious anemia associated with autoimmune hemolytic anemia and alopecia areata. Pediatr Blood Cancer. 2007;49:1017–8. doi: 10.1002/pbc.20896.CrossRefPubMedGoogle Scholar
  82. 82.
    Mao R, Fan Y, Zuo L, et al. Association study between methylenetetrahydrofolate reductase gene polymorphisms and Graves’ disease. Cell Biochem Funct. 2010;28:585–90. doi: 10.1002/cbf.1694.CrossRefPubMedGoogle Scholar
  83. 83.
    Klotz L, Farkas M, Bain N, et al. The variant methylenetetrahydrofolate reductase c.1298A>C (p. E429A) is associated with multiple sclerosis in a German case–control study. Neurosci Lett. 2010;468:183–5. doi: 10.1016/j.neulet.2009.10.057.CrossRefPubMedGoogle Scholar
  84. 84.
    Osborne D, Sobczyńska-Malefora A. Autoimmune mechanisms in pernicious anaemia and thyroid disease. Autoimmun Rev. 2015;14:763–8. doi: 10.1016/j.autrev.2015.04.011.CrossRefPubMedGoogle Scholar
  85. 85.
    McMahon RJ. Biotin in metabolism and molecular biology. Annu Rev Nutr. 2002;22:221–39. doi: 10.1146/annurev.nutr.22.121101.112819.CrossRefPubMedGoogle Scholar
  86. 86.
    Goldberg LJ, Lenzy Y. Nutrition and hair. Clin Dermatol. 2010;28:412–9. doi: 10.1016/j.clindermatol.2010.03.038.CrossRefPubMedGoogle Scholar
  87. 87.
    Colombo VE, Gerber F, Bronhofer M, Floersheim GL. Treatment of brittle fingernails and onychoschizia with biotin: scanning electron microscopy. J Am Dermatol. 1990;23:1127–32. doi: 10.1016/0190-9622(90)70345-I.CrossRefGoogle Scholar
  88. 88.
    Knight JA. Review: free radicals, antioxidants, and the immune system. Ann Clin Lab Sci. 2000;30:145–58.PubMedGoogle Scholar
  89. 89.
    Naziroglu M, Kokcam I. Antioxidants and lipid peroxidation status in the blood of patients with alopecia. Cell Biochem Funct. 2000;18:169–73. doi: 10.1002/1099-0844(200009)18:3<169:AID-CBF870>3.0.CO;2-T.CrossRefPubMedGoogle Scholar
  90. 90.
    Ramadan R, Tawdy A, Abdel Hay R, et al. The antioxidant role of paraoxonase 1 and vitamin E in three autoimmune diseases. Skin Pharmacol Physiol. 2013;26:2–7. doi: 10.1159/000342124.CrossRefPubMedGoogle Scholar
  91. 91.
    Holler PD, Cotsarelis G. Retinoids putting the “A” in alopecia. J Investig Dermatol. 2013;133:285–6. doi: 10.1038/jid.2012.441.CrossRefPubMedGoogle Scholar
  92. 92.
    Mora JR, Iwata M, von Andrian UH. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol. 2008;8:685–98. doi: 10.1038/nri2378.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Duncan FJ, Silva KA, Johnson CJ, et al. Endogenous retinoids in the pathogenesis of alopecia areata. J Investig Dermatol. 2013;133:334–43. doi: 10.1038/jid.2012.344.CrossRefPubMedGoogle Scholar
  94. 94.
    Suo L, Sundberg JP, Everts HB. Dietary vitamin A regulates wingless-related MMTV integration site signaling to alter the hair cycle. Exp Biol Med (Maywood). 2015;240:618–23. doi: 10.1177/1535370214557220.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Jordan M. Thompson
    • 1
  • Mehwish A. Mirza
    • 2
  • Min Kyung Park
    • 3
  • Abrar A. Qureshi
    • 3
    • 4
  • Eunyoung Cho
    • 3
    • 4
    Email author
  1. 1.Warren Alpert Medical SchoolBrown UniversityProvidenceUSA
  2. 2.Frank H. Netter MD School of MedicineQuinnipiac UniversityNorth HavenUSA
  3. 3.Department of Dermatology, Warren Alpert Medical SchoolBrown UniversityProvidenceUSA
  4. 4.Department of EpidemiologySchool of Public Health, Brown UniversityProvidenceUSA

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