American Journal of Clinical Dermatology

, Volume 16, Issue 6, pp 463–474 | Cite as

Alternative Systemic Treatments for Vitiligo: A Review

  • Brandon E. Cohen
  • Nada Elbuluk
  • Euphemia W. Mu
  • Seth J. Orlow
Review Article


Vitiligo is a common, acquired disorder of skin pigmentation that can significantly impact quality of life. It often represents a therapeutic challenge, which has resulted in interest in alternative treatments such as herbal and vitamin supplements. In this review, we provide an overview of the most commonly studied complementary agents, describe proposed mechanisms of action, identify potential adverse effects, and discuss the primary evidence supporting their use. Our discussion focuses on l-phenylalanine, Polypodium leucotomos, khellin, Ginkgo biloba, and vitamins and minerals, including vitamins B12, C, and E, folic acid, and zinc used as monotherapy or in combination with other treatments for the management of vitiligo.


Vitiligo Psoralen Folic Acid Supplementation Ginkgo Biloba Clobetasol Propionate 
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.


Compliance with Ethical Standards


No funding was received for the preparation of this review.

Conflict of interest

Brandon E. Cohen, Nada Elbuluk, Euphemia W. Mu, and Seth J. Orlow have no conflicts of interest to disclose that are relevant to the content of this review. In the past 12 months, Dr. Elbuluk has served as a consultant to Suneva, and Dr Orlow has served as a consultant to Dermira, Galderma, GSK/Stiefel, and Provectus.


  1. 1.
    Taieb A, Picardo M. Clinical practice. Vitiligo. N Engl J Med. 2009;360(2):160–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Lotti T, Gori A, Zanieri F, Colucci R, Moretti S. Vitiligo: new and emerging treatments. Dermatol Ther. 2008;21(2):110–7.CrossRefPubMedGoogle Scholar
  3. 3.
    Szczurko O, Boon HS. A systematic review of natural health product treatment for vitiligo. BMC Dermatol. 2008;8:2.PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Kostopoulou P, Jouary T, Quintard B, Ezzedine K, Marques S, Boutchnei S, et al. Objective vs. subjective factors in the psychological impact of vitiligo: the experience from a French referral centre. Br J Dermatol. 2009;161(1):128–33.CrossRefPubMedGoogle Scholar
  5. 5.
    Parsad D, Dogra S, Kanwar AJ. Quality of life in patients with vitiligo. Health Qual Life Outcomes. 2003;1:58.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Yaghoobi R, Omidian M, Bagherani N. Vitiligo: a review of the published work. J Dermatol. 2011;38(5):419–31.CrossRefPubMedGoogle Scholar
  7. 7.
    Hann SK, Park YK, Chun WH. Clinical features of vitiligo. Clin Dermatol. 1997;15(6):891–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Harris JE, Harris TH, Weninger W, Wherry EJ, Hunter CA, Turka LA. A mouse model of vitiligo with focused epidermal depigmentation requires IFN-gamma for autoreactive CD8(+) T-cell accumulation in the skin. J Invest Dermatol. 2012;132(7):1869–76.PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Spritz RA. Recent progress in the genetics of generalized vitiligo. J Genet Genomics. 2011;38(7):271–8.PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Spritz RA. Shared genetic relationships underlying generalized vitiligo and autoimmune thyroid disease. Thyroid. 2010;20(7):745–54.PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Egli F, Walter R. Images in clinical medicine. Vitiligo and pernicious anemia. N Engl J Med. 2004;350(26):2698.CrossRefPubMedGoogle Scholar
  12. 12.
    Schallreuter KU, Chavan B, Rokos H, Hibberts N, Panske A, Wood JM. Decreased phenylalanine uptake and turnover in patients with vitiligo. Mol Genet Metab. 2005;86(Suppl 1):S27–33.CrossRefPubMedGoogle Scholar
  13. 13.
    Xiao BH, Wu Y, Sun Y, Chen HD, Gao XH. Treatment of vitiligo with NB-UVB: a systematic review. J Dermatolog Treat. 2015;26(4):340–6.CrossRefPubMedGoogle Scholar
  14. 14.
    Siddiqui AH, Stolk LM, Bhaggoe R, Hu R, Schutgens RB, Westerhof W. L-phenylalanine and UVA irradiation in the treatment of vitiligo. Dermatology. 1994;188(3):215–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Antoniou C, Schulpis H, Michas T, Katsambas A, Frajis N, Tsagaraki S, et al. Vitiligo therapy with oral and topical phenylalanine with UVA exposure. Int J Dermatol. 1989;28(8):545–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Cormane RH, Siddiqui AH, Westerhof W, Schutgens RB. Phenylalanine and UVA light for the treatment of vitiligo. Arch Dermatol Res. 1985;277(2):126–30.CrossRefPubMedGoogle Scholar
  17. 17.
    Thiele B, Steigleder GK. Repigmentation treatment of vitiligo with l-phenylalanine and UVA irradiation [in German]. Z Hautkr. 1987;62(7):519–23.PubMedGoogle Scholar
  18. 18.
    Camacho F, Mazuecos J. Treatment of vitiligo with oral and topical phenylalanine: 6 years of experience. Arch Dermatol. 1999;135(2):216–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Kuiters GR, Hup JM, Siddiqui AH, Cormane RH. Oral phenylalanine loading and sunlight as source of UVA irradiation in vitiligo on the Caribbean island of Curacao NA. J Trop Med Hyg. 1986;89(3):149–55.PubMedGoogle Scholar
  20. 20.
    Camacho F, Mazuecos J. Oral and topical l-phenylalanine, clobetasol propionate, and UVA/sunlight–a new study for the treatment of vitiligo. J Drugs Dermatol. 2002;1(2):127–31.PubMedGoogle Scholar
  21. 21.
    Schulpis CH, Antoniou C, Michas T, Strarigos J. Phenylalanine plus ultraviolet light: preliminary report of a promising treatment for childhood vitiligo. Pediatr Dermatol. 1989;6(4):332–5.CrossRefPubMedGoogle Scholar
  22. 22.
    Schallreuter KU, Zschiesche M, Moore J, Panske A, Hibberts NA, Herrmann FH, et al. In vivo evidence for compromised phenylalanine metabolism in vitiligo. Biochem Biophys Res Commun. 1998;243(2):395–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Ryan WL, Carver MJ. Inhibition of antibody synthesis by l-phenylalanine. Science. 1964;143(3605):479–80.CrossRefPubMedGoogle Scholar
  24. 24.
    Emanuel P, Scheinfeld N. A review of DNA repair and possible DNA-repair adjuvants and selected natural anti-oxidants. Dermatol Online J. 2007;13(3):10.PubMedGoogle Scholar
  25. 25.
    Nestor M, Bucay V, Callender V, Cohen JL, Sadick N, Waldorf H. Polypodium leucotomos as an adjunct treatment of pigmentary disorders. J Clin Aesthet Dermatol. 2014;7(3):13–7.PubMedCentralPubMedGoogle Scholar
  26. 26.
    Mohammad A. Vitiligo repigmentation with anapsos (Polypodium leucotomos). Int J Dermatol. 1989;28(7):479.PubMedGoogle Scholar
  27. 27.
    Middelkamp-Hup MA, Bos JD, Rius-Diaz F, Gonzalez S, Westerhof W. Treatment of vitiligo vulgaris with narrow-band UVB and oral Polypodium leucotomos extract: a randomized double-blind placebo-controlled study. J Eur Acad Dermatol Venereol. 2007;21(7):942–50.CrossRefPubMedGoogle Scholar
  28. 28.
    Pacifico A, Vidolin AP, Leone G, Iacovelli P. Combined treatment of narrowband ultraviolet B light (NBUVB) phototherapy and oral Polypodium leucotomos extract versus NB UVB phototherapy alone in the treatment of patients with vitiligo. J Am Acad Dermatol. 2009;3(Suppl 1):AB154.Google Scholar
  29. 29.
    Reyes E, Jaen P, de las Heras E, Carrion F, Alvarez-Mon M, de Eusebio E, et al. Systemic immunomodulatory effects of Polypodium leucotomos as an adjuvant to PUVA therapy in generalized vitiligo: a pilot study. J Dermatol Sci. 2006;41(3):213–6.Google Scholar
  30. 30.
    Brieva A, Guerrero A, Pivel JP. Immunomodulatory properties of a hydrophilic extract of Polypodium leucotomos. Inflammopharmacology. 2002;9(4):361–71.CrossRefGoogle Scholar
  31. 31.
    Middelkamp-Hup MA, Pathak MA, Parrado C, Goukassian D, Rius-Diaz F, Mihm MC, et al. Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin. J Am Acad Dermatol. 2004;51(6):910–8.CrossRefPubMedGoogle Scholar
  32. 32.
    El-Haj N, Goldstein N. Sun protection in a pill: the photoprotective properties of Polypodium leucotomos extract. Int J Dermatol. 2015;54(3):362–6.CrossRefPubMedGoogle Scholar
  33. 33.
    Gonzalez S, Gilaberte Y, Philips N, Juarranz A. Current trends in photoprotection: a new generation of oral photoprotectors. Open Dermatol J. 2011;5:6–14.CrossRefGoogle Scholar
  34. 34.
    Hofer A, Kerl H, Wolf P. Long-term results in the treatment of vitiligo with oral khellin plus UVA. Eur J Dermatol. 2001;11(3):225–9.PubMedGoogle Scholar
  35. 35.
    Ortel B, Tanew A, Honigsmann H. Treatment of vitiligo with khellin and ultraviolet A. J Am Acad Dermatol. 1988;18(4 Pt 1):693–701.CrossRefPubMedGoogle Scholar
  36. 36.
    Morliere P, Honigsmann H, Averbeck D, Dardalhon M, Huppe G, Ortel B, et al. Phototherapeutic, photobiologic, and photosensitizing properties of khellin. J Invest Dermatol. 1988;90(5):720–4.CrossRefPubMedGoogle Scholar
  37. 37.
    Abdel-Fattah A, Aboul-Enein MN, Wassel GM, El-Menshawi BS. An approach to the treatment of vitiligo by khellin. Dermatologica. 1982;165(2):136–40.CrossRefPubMedGoogle Scholar
  38. 38.
    de Leeuw J, Assen YJ, van der Beek N, Bjerring P, Martino Neumann HA. Treatment of vitiligo with khellin liposomes, ultraviolet light and blister roof transplantation. J Eur Acad Dermatol Venereol. 2011;25(1):74–81.CrossRefPubMedGoogle Scholar
  39. 39.
    Valkova S, Trashlieva M, Christova P. Treatment of vitiligo with local khellin and UVA: comparison with systemic PUVA. Clin Exp Dermatol. 2004;29(2):180–4.CrossRefPubMedGoogle Scholar
  40. 40.
    Szczurko O, Shear N, Taddio A, Boon H. Ginkgo biloba for the treatment of vitilgo vulgaris: an open label pilot clinical trial. BMC Complement Altern Med. 2011;11:21.PubMedCentralCrossRefPubMedGoogle Scholar
  41. 41.
    Trompezinski S, Bonneville M, Pernet I, Denis A, Schmitt D, Viac J. Gingko biloba extract reduces VEGF and CXCL-8/IL-8 levels in keratinocytes with cumulative effect with epigallocatechin-3-gallate. Arch Dermatol Res. 2010;302(3):183–9.CrossRefPubMedGoogle Scholar
  42. 42.
    Bent S, Goldberg H, Padula A, Avins AL. Spontaneous bleeding associated with Ginkgo biloba: a case report and systematic review of the literature: a case report and systematic review of the literature. J Gen Intern Med. 2005;20(7):657–61.PubMedCentralCrossRefPubMedGoogle Scholar
  43. 43.
    Karadag AS, Tutal E, Ertugrul DT, Akin KO, Bilgili SG. Serum holotranscobalamine, vitamin B12, folic acid and homocysteine levels in patients with vitiligo. Clin Exp Dermatol. 2012;37(1):62–4.CrossRefPubMedGoogle Scholar
  44. 44.
    Shaker OG, El-Tahlawi SM. Is there a relationship between homocysteine and vitiligo? A pilot study. Br J Dermatol. 2008;159(3):720–4.PubMedGoogle Scholar
  45. 45.
    Howitz J, Schwartz M. Vitiligo, achlorhydria, and pernicious anaemia. Lancet. 1971;1(7713):1331–4.CrossRefPubMedGoogle Scholar
  46. 46.
    Sabry HHSJ, Hashim HM. Serum levels of homocysteine, vitamin B12, and folic acid in vitiligo. Egypt J Dermatol Venereol. 2014;34:65–9.CrossRefGoogle Scholar
  47. 47.
    Montes LF, Diaz ML, Lajous J, Garcia NJ. Folic acid and vitamin B12 in vitiligo: a nutritional approach. Cutis. 1992;50(1):39–42.PubMedGoogle Scholar
  48. 48.
    Juhlin L, Olsson MJ. Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure. Acta Derm Venereol. 1997;77(6):460–2.PubMedGoogle Scholar
  49. 49.
    Don P, Iuga A, Dacko A, Hardick K. Treatment of vitiligo with broadband ultraviolet B and vitamins. Int J Dermatol. 2006;45(1):63–5.CrossRefPubMedGoogle Scholar
  50. 50.
    Tjioe M, Gerritsen MJ, Juhlin L, van de Kerkhof PC. Treatment of vitiligo vulgaris with narrow band UVB (311 nm) for one year and the effect of addition of folic acid and vitamin B12. Acta Derm Venereol. 2002;82(5):369–72.CrossRefPubMedGoogle Scholar
  51. 51.
    Singh S, Singh U, Pandey SS. Increased level of serum homocysteine in vitiligo. J Clin Lab Anal. 2011;25(2):110–2.CrossRefPubMedGoogle Scholar
  52. 52.
    Silverberg JI, Silverberg NB. Serum homocysteine as a biomarker of vitiligo vulgaris severity: a pilot study. J Am Acad Dermatol. 2011;64(2):445–7.CrossRefPubMedGoogle Scholar
  53. 53.
    Elgoweini M, Nour El Din N. Response of vitiligo to narrowband ultraviolet B and oral antioxidants. J Clin Pharmacol. 2009;49(7):852–5.CrossRefPubMedGoogle Scholar
  54. 54.
    Passi S, Grandinetti M, Maggio F, Stancato A, De Luca C. Epidermal oxidative stress in vitiligo. Pigment Cell Res. 1998;11(2):81–5.CrossRefPubMedGoogle Scholar
  55. 55.
    Khan R, Satyam A, Gupta S, Sharma VK, Sharma A. Circulatory levels of antioxidants and lipid peroxidation in Indian patients with generalized and localized vitiligo. Arch Dermatol Res. 2009;301(10):731–7.CrossRefPubMedGoogle Scholar
  56. 56.
    Dell’Anna ML, Mastrofrancesco A, Sala R, Venturini M, Ottaviani M, Vidolin AP, et al. Antioxidants and narrow band-UVB in the treatment of vitiligo: a double-blind placebo controlled trial. Clin Exp Dermatol. 2007;32(6):631–6.CrossRefPubMedGoogle Scholar
  57. 57.
    Akyol M, Celik VK, Ozcelik S, Polat M, Marufihah M, Atalay A. The effects of vitamin E on the skin lipid peroxidation and the clinical improvement in vitiligo patients treated with PUVA. Eur J Dermatol. 2002;12(1):24–6.PubMedGoogle Scholar
  58. 58.
    Shameer P, Prasad PV, Kaviarasan PK. Serum zinc level in vitiligo: a case control study. Indian J Dermatol Venereol Leprol. 2005;71(3):206–7.CrossRefPubMedGoogle Scholar
  59. 59.
    Bagherani N, Yaghoobi R, Omidian M. Hypothesis: zinc can be effective in treatment of vitiligo. Indian J Dermatol. 2011;56(5):480–4.PubMedCentralCrossRefPubMedGoogle Scholar
  60. 60.
    Yaghoobi R, Omidian M, Bagherani N. Original article title: “Comparison of therapeutic efficacy of topical corticosteroid and oral zinc sulfate-topical corticosteroid combination in the treatment of vitiligo patients: a clinical trial”. BMC Dermatol. 2011;11:7.PubMedCentralCrossRefPubMedGoogle Scholar
  61. 61.
    Greiner D, Ochsendorf FR, Milbradt R. Vitiligo therapy with phenylalanine/UVA. Catamnestic studies after five years [in German]. Hautarzt. 1994;45(7):460–3.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Brandon E. Cohen
    • 1
  • Nada Elbuluk
    • 1
  • Euphemia W. Mu
    • 1
  • Seth J. Orlow
    • 1
  1. 1.The Ronald O. Perelman Department of DermatologyNew York University School of MedicineNew YorkUSA

Personalised recommendations