Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Art & Psychiatry
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Conference Oration
Conference Summary
Continuing Medical Education
Cosmetic Dermatology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
Editor Speaks
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Miscellaneous Letter
Net Case
Net case report
Net Image
Net Letter
Net Quiz
Net Study
New Preparations
News & Views
Observation Letter
Observation Letters
Original Article
Original Contributions
Pattern of Skin Diseases
Pediatric Dermatology
Pediatric Rounds
Presedential Address
Presidential Address
Presidents Remarks
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Review Article
Review Articles
Revision Corner
Self Assessment Programme
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Special Article
Specialty Interface
Study Letter
Study Letters
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapy Letter
Therapy Letters
View Point
What’s new in Dermatology
View/Download PDF

Translate this page into:

Review Article
doi: 10.4103/0378-6323.120720
PMID: 24177606

The role of vitamin D in melanogenesis with an emphasis on vitiligo

Khalid AlGhamdi1 , Ashok Kumar2 , Noura Moussa2
1 Department of Dermatology; Vitiligo Research Chair, College of Medicine, King Saud University, Riyadh, Saudi Arabia
2 Vitiligo Research Chair, College of Medicine, King Saud University, Riyadh, Saudi Arabia

Correspondence Address:
Khalid AlGhamdi
Department of Dermatology, Vitiligo Research Chair, College of Medicine, King Saud University, P.O. Box 240997, Riyadh 11322
Saudi Arabia
How to cite this article:
AlGhamdi K, Kumar A, Moussa N. The role of vitamin D in melanogenesis with an emphasis on vitiligo. Indian J Dermatol Venereol Leprol 2013;79:750-758
Copyright: (C)2013 Indian Journal of Dermatology, Venereology, and Leprology


Vitiligo is a common pigmentary disorder caused by the destruction of functional melanocytes. Vitamin D is an essential hormone synthesized in the skin and is responsible for skin pigmentation. Low levels of vitamin D have been observed in vitiligo patients and in patients with other autoimmune diseases. Therefore, the relationship between vitamin D and vitiligo needs to be investigated more thoroughly. We reviewed the literature to date regarding the role of vitamin D in skin pigmentation. Our review revealed that vitamin D deficiency has been identified in many conditions, including premature and dysmature birth, pigmented skin, obesity, advanced age, and malabsorption. Vitamin D increases melanogenesis and the tyrosinase content of cultured human melanocytes by its antiapoptotic effect. However, a few growth-inhibitory effects on melanocytes were also reported. Vitamin D regulates calcium and bone metabolism, controls cell proliferation and differentiation, and exerts immunoregulatory activities. Vitamin D exerts its effect via a nuclear hormone receptor for vitamin D. The topical application of vitamin D increased the number of L-3,4-dihydroxyphenylalanine-positive melanocytes. The topical application of vitamin D yields significant results when used in combination with phototherapy and ultraviolet exposure to treat vitiligo in humans. Vitamin D decreases the expression of various cytokines that cause vitiligo. In conclusion, application of vitamin D might help in preventing destruction of melanocytes thus causing vitiligo and other autoimmune disorders. The association between low vitamin D levels and the occurrence of vitiligo and other forms of autoimmunity is to be further evaluated.
Keywords: Autoimmune diseases, depigmentation, melanocytes, phototherapy, vitamin D, vitamin D receptor, vitiligo


Vitiligo is a common pigmentary disorder characterized by well-demarcated depigmented patches or macules of different shapes and sizes. Vitiligo is caused by the destruction of functional melanocytes in the involved epidermis and the bulb/infundibulum of the hair follicle. [1],[2],[3] Vitiligo is an autoimmune disorder that affects 1-4% of the world′s population, [4] regardless of gender or basic skin tone. [5] The disorder results in substantial cosmetic disfigurement. In some cultures, patients with vitiligo are regarded as social outcasts and are emotionally and physically affected. [3]

A variety of therapeutic agents have been described in the literature, and many agents have been used in an attempt to treat vitiligo. However, no agent has been found to be uniformly effective. The most widely prescribed therapies are phototherapy and topical corticosteroids. [1],[6]

The active form of vitamin D, calcitriol [1,25-dihydroxyvitamin D 3 , 1,25(OH) 2 D 3 ], and analogues of this hormone (e.g., calcipotriol) are successful treatment options for patients with skin diseases, such as psoriasis and vitiligo, [7] when used topically.

Although the association between vitamin D and pigmentation and the role of vitamin D deficiency has been established in numerous autoimmune diseases, the association between vitamin D levels and vitiligo still needs to be investigated more thoroughly. In this review, we summarize the existing information on the relationship between vitamin D, autoimmune diseases and pigmentation; we also highlight the knowledge gaps concerning the relationship between vitamin D and vitiligo.

In this review, we aimed to systematically review the published scientific literature till date regarding the role of vitamin D to enhance the pigmentation in human skin. We searched databases including MEDLINE/Pubmed, Embase, and Google Scholar for vitiligo, vitamin D, autoimmune diseases, melanocytes, vitamin D receptor, phototherapy, and depigmentation.

Basic Science of Vitamin D

Vitamin D

Vitamin D is an essential hormone that is synthesized in the skin via a photochemical reaction, following the exposure of the skin to ultraviolet B (UVB) wavelength present in sunlight. In this reaction, previtamin D is converted by solar UVB-radiation in the skin into vitamin D, especially during the summer months. Limitations of vitamin D synthesis are age, pigmented skin, sunscreen use, and clothing. [8] Skin pigmentation is a known risk factor in patients with hypovitaminosis D because melanin, which is responsible for skin pigmentation, filters UV-radiation. [9]

Vitamin D derivatives

The two main forms of vitamin D are cholecalciferol and ergocalciferol. Both forms of vitamin D can be obtained by nutritional intake; ergocalciferol (vitamin D 2 ) is present in fungi/yeast, whereas cholecalciferol (vitamin D 3 ) is found in foods from animal origin [10] , especially fatty fish, such as herring and mackerel. Other sources of vitamin D are milk, cheese, eggs, and cereals.

Biochemistry of vitamin D

The active form of vitamin D, 1,25-dihydroxyvitamin D 3 [ 1,25(OH) 2 D 3 ], is a secosteroid (steroid with an opened B-ring) hormone that regulates calcium and bone metabolism, controls cell proliferation and differentiation and exerts immunoregulatory activities. This range of functions has been exploited clinically to treat a variety of conditions, including secondary hyperparathyroidism, osteoporosis, psoriasis, and vitiligo. Recent advances in the understanding of 1,25(OH) 2 D 3 and its functions and novel insights into the mechanisms of its immunomodulatory properties suggest a wider applicability of this hormone in the treatment of autoimmune diseases and the prevention of allograft rejection. [11]

Physiology of vitamin D

The primary form of vitamin D, cholecalciferol [25(OH) D 3 , the form measured to determine the level of vitamin D], is synthesized in the liver. The biologically active form, 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ], is then synthesized in the kidneys via the hydroxylation of 25(OH)D 3 by 1α-hydroxylase [12] and stimulates calcium absorption from the gut. [13]

The target organs of 1,25(OH) 2 D 3 include the bone, intestine, and kidney and it stimulates calcium transport from these organs to the blood. The production of 1,25(OH) 2 D 3 is stimulated by the parathyroid hormone (PTH). There is a negative feedback through calcium that decreases PTH and a direct negative feedback from 1,25(OH) 2 D 3 to PTH. The active metabolite 1,25(OH) 2 D 3 also shows rapid activities through a membrane receptor. [8]

Vitamin D receptor

Vitamin D exerts its effect via a nuclear hormone receptor called the vitamin D receptor (VDR). VDR is a member of the superfamily of nuclear receptors for steroid hormones, thyroid hormone, and retinoic acid. The VDR is a type 1 nuclear receptor, a transcription factor that forms homodimers and heterodimers that are active in the transcription and transrepression of approximately 900 genes. [14] VDRs are present not only in cells typically involved in calcium and bone metabolism but also in other cell types, such as keratinocytes, melanocytes, fibroblasts, and immune-system cells of the skin. [15] VDR acts by binding to specific DNA sequences as a heterodimer with a retinoid X receptor and to the basal transcription machinery in a ligand-independent (TFIIB) and -dependent manner (TFIIA). Genes with vitamin D response elements directly and indirectly influence cell cycling and proliferation, differentiation, and apoptosis. [16],[17]

Birlea et al., found an association between the VDR-Apa I polymorphism and vitiligo. [18] This study revealed that aa genotype of Apa-I VDR was significantly more frequent in patients with vitiligo; allelic frequencies showed a significant difference between vitiligo with other autoimmune diseases group and controls. VDR gene polymorphisms may affect 25(OH) D levels and the risk for the development of vitiligo. The VDR variant BsmI-B allele, the ApaI-A allele, and the TaqI-t allele were associated with a decreased risk for vitiligo, and there was also a dose-response relationship between decreased risk and increased 25(OH) D level in individuals with the ApaI allele. [19] In another study, Aydingoz et al., concluded that VDR TaqI gene polymorphism and the haplotype BsmI/ApaI/TaqI/FokI/Cdx2 GCCCG may be considered as novel risk factors in vitiligo. [20]

Vitiligo, Clinical Disorders, and Vitamin D

Vitamin D deficiency and diseases

Risk factors for vitamin D deficiency are premature and dysmature birth, pigmented skin, low sunshine exposure, obesity, advanced age, and malabsorption. The prevalence of vitamin D deficiency is also higher in elderly people than in adults, and it is especially prevalent in patients with hip fractures and in the residents of homes for the elderly and nursing homes. [21] The low vitamin D levels found in Pemphigus vulgaris and Bullous pemphigoid may suggest a role for this agent in their pathogenesis. The prevalence of fracture was increased in this group. [22] Low levels of vitamin D have also been associated with cardiovascular disease, including myocardial infarction. [23]

The prevalence of vitamin D deficiency is much higher in Europe than in Asia, Australia, or the USA. The prevalence of vitamin D insufficiency is also high in African Americans, whose highly pigmented skin makes the UV-light much less efficacious. [24] A high prevalence of vitamin D deficiency has been reported in nonwestern immigrants in the Netherlands, [25] and similar data was obtained in the Middle East, [26] where life-style factors probably play a role.

Black patients have a higher risk of insufficiency of vitamin D than White patients, and it was observed that prepubescent White girls have higher vitamin D levels than Black girls in the United States. [27] It has been reported that lower vitamin D levels in patients of color may explain the increased rates of peripheral vascular disease and invasive breast cancer. [28] VDR polymorphisms have been associated with breast cancer cases in Caucasian females, but not in African-American females, suggesting that chronic low levels of vitamin D are more at fault. [29]

Low vitamin D levels have also been associated with autoimmune diseases, including systemic lupus, diabetes mellitus, rheumatoid arthritis, and multiple sclerosis. [30],[31],[32],[33] The mechanism by which vitamin D affects autoimmunity is unknown, but there is a clear regulation of immune cells by vitamin D in vitro. [30] The association of low vitamin D levels with vitiligo and multiple forms of autoimmunity needs to be further evaluated.

In Vitro Studies

Murine B16 melanoma cells treated with vitamin D 3 exhibit an increase in tyrosinase activity and melanogenesis. [34] Tomita et al., showed that vitamin D 3 increased the tyrosinase content of cultured human melanocytes. [35] Watabe et al., provided some important clues to understand the role of vitamin D 3 in melanocyte development and melanogenesis and observed that L-3,4-dihydroxyphenylalanine-positive (DOPA-positive) cells are increased after 1,25(OH) 2 D 3 treatment in primary neural crest cell cultures. [36] These findings indicate that 1,25(OH) 2 D 3 may stimulate the differentiation of immature melanocyte precursors. Electron microscopy demonstrates the presence of melanosomes at more advanced stages in 1,25(OH) 2 D 3 -treated cells as compared with untreated cells. [36] In another study, it was observed that vitamin D and UVB irradiation promoted the proliferation of melanocytes, which indicates that this combination might be effective in the treatment of vitiligo. [37]

Growth Inhibitory Effects of Vitamin D on Melanocytes

In contrast to its stimulatory effects on melanocyte proliferation, vitamin D was also reported to have an inhibitory effect on melanocyte growth [38] as well as the melanization of cultured human melanocytes. [39] In another study, vitamin D inhibited the proliferation of melanocytes in a dose-dependent manner, though it did not show any adverse effects on the melanization process of melanocytes. [40]

In Vivo Studies

Abdel-Malek et al., showed that the topical application of 100 μg of cholecalciferol to the pinnal epidermis of DBA/2J mice for 5 or 10 days increased the number of DOPA-positive melanocytes and had a synergistic effect with a low dose of UVB-light. [41] The combination of psoralen and ultraviolet A (PUVA) with calcipotriol in vitiligo works fast, and the duration of PUVA treatment can be reduced to yield more cosmetically acceptable results. [42]

Vitamin D and Vitiligo

Topical vitamin D3 analogues are a new addition to the armamentarium of therapeutic modalities for vitiligo. The use of vitamin D analogues in combination with PUVAsol and topical calcipotriol for the treatment of vitiligo was first reported by Parsad et al.,[42] Subsequently, a number of studies have been reported the treatment of vitiligo with vitamin D analogues alone or in combination with ultraviolet light or corticosteroids to enhance repigmentation. [43] In a recent review, Birlea et al., have shown insight into the main intracellular pathways through which vitamin D3 analogues alone or in different combinations may contribute to repigmentation in vitiligo. [38] Birlea et al., reviewed 22 studies published on calcipotriol/tacalcitol used alone or in combination with other agents for evaluation and concluded that many studies have shown vitamin D3 analogues to be effective in combination with PUVA, NBUVB, or an excimer laser. [38] In another study, Oh et al., reported that high concentration of tacalcitol was applied topically with 308-nm xenon chloride excimer laser to lower the energy threshold for significant clinical purpose to treat nonsegmental vitiligo. [44]

In a recent pilot study, serum concentrations of vitamin D in vitiligo patients were estimated and divided into three groups: 31.1% were normal (>30 ng/mL), 55.6% were insufficient (<30 ng/mL), and 13.3% were very low (<15 ng/mL). [45] Insufficient vitamin D levels were associated with an increasing Fitzpatrick phototype. Very low 25-hydroxyvitamin D levels were associated with comorbid autoimmune illnesses, but not with age, gender, race/ethnicity, family history of vitiligo or autoimmune disease, new-onset disease, or body surface area affected. This study was limited, as it assessed point prevalence in a small cohort (total of 45 patients) without assessing the seasonal variations in vitamin D levels and as there was no control group. In a recently published case report, investigators found low levels of vitamin D (12 ng/mL) in a vitiligo patient. [23]

Another study investigated the association between VDR polymorphisms and vitiligo, and it revealed that the Apa-I polymorphism of the VDR gene is associated with vitiligo. [18] This suggests that vitamin D or its receptor might play a role in the etiopathogenesis of skin pigmentation.

Vitiligo Treatment and Vitamin D

Application of vitamin D with phototherapy and UV exposure to treat vitiligo

The occurrence of hyper-pigmentation in psoriatic lesions treated with calcipotriol led to the discovery of a new therapeutic modality in vitiligo. [46] Calcipotriol is effective on immunomodulatory systems, inflammatory mediators, and melanocytes [47] and it may stimulate melanin production by activating melanocytes and keratinocytes. [48] It has been found in vivo that melanocytes in the epidermis become swollen with elongated dendrites after UV-irradiation of the skin. The tyrosinase activity in these melanocytes is increased by microphthalmia transcription factor (MITF), [49] resulting in the deposition of the enzyme product, melanin, in the epidermis, several days after irradiation. Tomita et al., found that vitamin D 3 -induced features similar to those noted in UV-irradiated skin; specifically, it increased the cell size, the number of dendrites, and the amount of immunoreactive tyrosinase. [35] Ermis et al., also reported that combination treatment with calcipotriol and PUVA seems to be safe and much more effective in initiating and achieving complete repigmentation than a placebo with PUVA. [50]

A marginal type of repigmentation pattern occurred more frequently with these topical agents, and it was observed that the onset of repigmentation induced by calcipotriol was slow. [51] However, in a few cases, treatment failure or no added response to combination therapy with these analogues was also observed at the end of 3 months. [43]

Influence of Narrowband UVB Phototherapy on Vitamin D

A recent study investigated the influence of low-dose narrowband UVB phototherapy on serum levels of vitamin D. [52] The results of the study revealed that UVB phototherapy increased vitamin D levels in patients with low initial levels of 25-hydroxyvitamin D (25(OH) D) (the serum marker for vitamin D status), which indicates that the beneficial effect of UVB depends, at least partially, on the induction of vitamin D.

Vitamin D Regulates CA 2+ for Pigmentation

Defective calcium (Ca 2+ ) transport has been shown in keratinocytes and melanocytes obtained from vitiliginous skin samples. [53] Ca 2+ controls the activity of both plasma membrane-associated and cytosolic thioredoxin reductase. Decreased intracellular Ca 2+ leads to high levels of reduced thioredoxin, the product of thioredoxin, which inhibits tyrosinase activity and results in the inhibition of melanin synthesis. Moreover, it has been shown that melanocytes express 1,25-dihydroxyvitamin D 3 receptors, which take part in the regulation of melanin synthesis. [41],[54] It is likely that calcipotriol may play a role in Ca 2+ regulation by 1,25-dihydroxyvitamin D 3 receptors on melanocytes and/or by the regulation of defective Ca 2+ homeostasis. [50]

Effects of Vitamin D on Vitiligo by Decreasing the Expression of Cytokines

It has been reported that the increased expression of proinflammatory and proapoptotic cytokines, such as IL-6, IL-8, IL-10, IL-12, INF-α, and TNF-α, cause vitiligo and play a role in the pathogenesis of vitiligo. [2],[55] Vitamin D might exert immunomodulatory effects by inhibiting the expression of IL-6, IL-8, TNF-α, and TNF-γ. [56] Vitamin D compounds were shown to have modulatory effects on dendritic cell maturation, differentiation, and activation in both human and murine culture systems, [57] probably via a VDR-dependent pathway. [58] Furthermore, vitamin D compounds are shown to induce the inhibition of antigen presentation. [57],[58]

Effects of Oral Vitamin D Supplements on Autoimmune Diseases

In many studies, it was observed that vitamin D supplementation was therapeutically effective in different experimental animal models, such as allergic encephalomyelitis, collagen-induced arthritis, type 1 diabetes mellitus, inflammatory bowel disease, autoimmune thyroiditis, and systemic lupus erythematosus. [59],[60],[61],[62],[63] Therefore, the supplementation of vitamin D can possibly be used as a treatment in autoimmune diseases such as vitiligo.

Molecular Mechanism of Repigmentation by Vitamin D

Vitamin D protects the epidermal melanin unit and restores melanocyte integrity by two main mechanisms: By controlling the activation, proliferation, migration of melanocytes and pigmentation pathways by modulating T cell activation, which is apparently correlated with melanocyte disappearance in vitiligo. The multiple effects of VDR on immune cells lead to the recognition that vitamin D could be a potent immunomodulator. The coordination of T cell activation is exerted mainly by the inhibition of T cell transition from the early to the late G1 phase and by the inhibition of several cytokine genes, such as those encoding TNF-α and IFN-γ. [64]

The mechanism through which vitamin D exerts its effects on melanocytes is not yet fully understood. Vitamin D is believed to be involved in melanocyte physiology by coordinating melanogenic cytokines [most likely endothelin-3 (ET-3)] and the activity of the SCF/c-Kit system, which is one of the most important regulators of melanocyte viability and maturation. [64] Furthermore, a proposed mechanism involving vitamin D in the protection of vitiliginous skin is based on its antioxidant properties and regulatory function towards the reactive oxygen species that are produced in excess in vitiligo epidermis.

Vitamin D Reduces Apoptotic Activity in Melanocytes

Vitiligo is characterized by the loss of melanocytes from the epidermis, which causes depigmentation in the skin. [65] Apoptosis has been reported to be a mechanism that removes melanocytes from the skin. [66] The active form of vitamin D reduces the apoptotic activity induced by UVB in keratinocytes [67] and melanocytes [68] by the production of interleukin-6. [67] In another study, it was observed that vitamin D protected melanocytes from apoptosis through the formation of sphingosine-1-phosphate [Table - 1], which opposes apoptotic action in diverse melanoma cell lines. [69] A recent study reported that vitamin D protects DNA against oxidative damage, with net tumoristatic and anticarcinogenic effects. [70] The mentioned studies provide evidence that vitamin D can prevent the death of melanocytes, thus preventing the loss of pigment in the skin, which could be a very useful finding in the treatment of vitiligo, if approached correctly.

Table 1: Response of Vitamin D on melanocytes and skin repigmentation

Patient Selection Criteria for Treatment of Vitiligo with Vitamin D Analogues

There are a few important steps that should be followed during the treatment of vitiligo with vitamin D in the clinic. The first step is the selection of patients, as variation in patient features, such as age or duration, extent and type of vitiligo, and affected areas, are important considerations in determining the applicability of treatment and may result in variable responses. As the mechanism of vitamin D action is slow, vitamin D analogues will be effective in patients with stable disease or slow-spreading disease. The second step is to measure the vitiligo affected area by a standard method before and after treatment, as it is an important limiting factor and there is no uniformly accepted scoring system for disease activity. Recently, our group reviewed different vitiligo assessment methods to assess the depigmented and pigmented areas in vitiligo patients before and after treatment. [71]

Conclusions and Future Directions

Vitiligo is caused by the destruction of functional melanocytes in the epidermis. Vitiligo is generally considered to be an autoimmune disorder. There is preliminary evidence that vitiligo patients, as well as patients with other autoimmune disorders have low levels of vitamin D. Vitamin D is synthesized in the skin in the presence of UVB wavelengths that come from sunlight. Vitamin D and its analogues have been used to successfully treat vitiligo and psoriasis. Vitamin D efficiency is increased when used in combination with UV or corticosteroids. However, in a few in vitro studies, vitamin D showed inhibitory effects on the growth of melanocytes, while in some cases, it was not effective for repigmentation. Other effects of vitamin D on melanocytes are summarized in [Table - 1].

It is still unknown if vitamin D deficiency plays a role in causing vitiligo, as it does in other autoimmune diseases. If vitamin D deficiency does cause vitiligo, then its supplementation could help control the disease. Therefore, the relationship between the level of serum vitamin D and vitiligo should be tested in a large controlled study. Moreover, oral vitamin D intake should be observed to prevent disease onset in susceptible family members of vitiligo patients. More studies are to be performed on this topic to reveal the effect of phototherapy and the application of vitamin D on repigmentation. Additionally, more studies are necessary to determine the association of VDR polymorphisms and disease activity in vitiligo patients.


The authors would like to thank Professor Zalfa A. Abdel-Malek, Department of Dermatology, University of Cincinnati, College of Medicine, Cincinnati, OH, USA for kindly and critically reviewing the paper and providing valuable comments.[74]

AlGhamdi KM. A survey of vitiligo management among dermatologists in Saudi Arabia. J Eur Acad Dermatol Venereol 2009;23:1282-8.
[Google Scholar]
AlGhamdi K, Kumar A. Depigmentation therapies for normal skin in vitiligo universalis. J Eur Acad Dermatol Venereol 2011;25:749-57.
[Google Scholar]
Hartmann A, Brocker EB, Becker JC. Hypopigmentary skin disorders: Current treatment options and future directions. Drugs 2004;64:89-107.
[Google Scholar]
Mosher DB. Hypomelanoses and Hypermelanoses. In: Freedberg IM, Eisen AZ, Wol VK, Austen KF, Goldsmith LA, Katz SI, editors. Fitzpatrick's Dermatology in General Medicine. New York: McGraw-Hill; 1999. p. 945-1018.
[Google Scholar]
Nordlund JJ. The epidemiology and genetics of vitiligo. Clin Dermatol 1997;15:875-78.
[Google Scholar]
Kovacs SO. Vitiligo. J Am Acad Dermatol 1998;38:647-66.
[Google Scholar]
Sigmon JR, Yentzer BA, Feldman SR. Calcitriol ointment: A review of a topical vitamin D analog for psoriasis. J Dermatol Treat 2009;20:208-12.
[Google Scholar]
Lips P. Vitamin D physiology. Prog Biophys Mol Biol 2006;92:4-8.
[Google Scholar]
Loomis WF. Skin-pigment regulation of vitamin-D biosynthesis in man. Science 1967;157:501-6.
[Google Scholar]
Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin D: Modulator of the immune system. Curr Opin Pharmacol 2010;10:482-96.
[Google Scholar]
Van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: Basic concepts. J Steroid Biochem Mol Biol 2005;97:93-101.
[Google Scholar]
Mora JR, Iwata M, von Adrian UH. Vitamin effects on the immune system: Vitamins A and D take center stage. Nat Rev Immunol 2008;8:685-98.
[Google Scholar]
Yasuda H, Higashio K, Suda T. Vitamin D and Osteoclastogenesis. In: Feldman D, Pike JW, Glorieux FH, editors. Vitamin D. vol 1. San Diego, CA: Elsevier Academic Press; 2005. p. 665-85.
[Google Scholar]
Wang TT, Tavera-Mendonza LE, Laperriere, D, Libby E, MacLeod NB, Nagai Y, et al. Large-scale in silico and microarray-based identification of direct 1,25-dihydroxivitamin D3 target genes. Mol Endocrinol 2005;19:2685-95.
[Google Scholar]
Arnson Y, Amital H, Shoenfeld Y. Vitamin D and autoimmunity: New aetiological and therapeutic considerations. Ann Rheum Dis 2007;66:1137-42.
[Google Scholar]
Prentice A, Goldberg GR, Schoenmakers I. Vitamin D across the lifecycle: Physiology and biomarkers. Am J Clin Nutr 2008;88:500S-6S.
[Google Scholar]
Samuel S, Sitrin MD. Vitamin D's role in cell proliferation and differentiation. Nutr Rev 2008;66:S116-24.
[Google Scholar]
Birlea S, Birlea M, Cimponeriu D, Apostol P, Cosqarea R, Gavrila L, et al. Autoimmune diseases and vitamin D receptor Apa-I polymorphism are associated with vitiligo in a small inbred Romanian community. Acta Derm Venereol 2006;86:209-14.
[Google Scholar]
Li K, Shi Q, Yang L, Li X, Liu L, Wang L, et al. The association of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D levels with generalized vitiligo. Br J Dermatol 2012;167:815-21.
[Google Scholar]
Aydýngöz IE, Bingül I, Doðru-Abbasoðlu S, Vural P, Uysal M. Analysis of vitamin D receptor gene polymorphisms in vitiligo. Dermatology 2012;224:361-8.
[Google Scholar]
Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: Consequences for bone loss and fractures and therapeutic implications. Endocrine Rev 2001;22:477-501.
[Google Scholar]
Marzano AV, Trevisan V, Eller-Vainicher C, Cairoli E, Marchese L, Morelli V, et al. Evidence for vitamin D deficiency and increased prevalence of fractures in autoimmune bullous skin diseases. Br J Dermatol 2012;167:688-91.
[Google Scholar]
Nunes JP, Martins CS. Myocardial infarction, hypovitaminosis D and vitiligo. Rev Port Cardiol 2010;29:839-40.
[Google Scholar]
Holick MF. McCollum award lecture 1994: Vitamin D: New horizons for the 21 st century. Am J Clin Nutr 1994;60:619-30.
[Google Scholar]
Grootjans-Geerts I. Hypovitaminosis D: A veiled diagnosis. Ned Tijdschr Geneeskd 2001;145:2057-60.
[Google Scholar]
Gannage-Yared MH, Chemali R, Yaacoub N, Halaby G. Hypovitaminosis D in a sunny country: Relation to lifestyle and bone markers. J Bone Miner Res 2000;15:1856-62.
[Google Scholar]
Willis CM, Laing EM, Hall DB, Hausman DB, Lewis RD. A prospective analysis of plasma 25-hydroxyvitamin D concentrations in white and black prepubertal females in the southeastern United States. Am J Clin Nutr 2007;85:124-30.
[Google Scholar]
Neuhouser ML, Sorensen B, Hollis BW, Ambs A, Ulrich CM, McTiernan A, et al. Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors. Am J Clin Nutr 2008;88:133-9.
[Google Scholar]
Trabert B, Malone KE, Daling JR, Doody DR, Bernstein L, Ursin G, et al. Vitamin D receptor polymorphisms and breast cancer risk in a large population-based case-control study of Caucasian and African-American women. Breast Cancer Res 2007;9:R84.
[Google Scholar]
Adorini L, Penna G. Control of autoimmune diseases by the vitamin D endocrine system. Nat Clin Pract Rheumatol 2008;4:404-12.
[Google Scholar]
Kamen DL, Aranow C. The link between vitamin D deficiency and systemic lupus erythematosus. Curr Rheumatol Rep 2008;10:273-80.
[Google Scholar]
Liu E, Meigs JB, Pittas AG, McKeown NM, Economos CD, Booth SL, et al. Plasma 25-hydroxyvitamin d is associated with markers of the insulin resistant phenotype in nondiabetic adults. J Nutr 2009;139:329-34.
[Google Scholar]
Tremlett H, van der Mei IA, Pittas F, Blizzard L, Paley G, Mesaros D, et al. Monthly ambient sunlight, infections and relapse rates in multiple sclerosis. Neuroepidemiology 2008;31:271-9.
[Google Scholar]
Oikawa A, Nakayasu M. Stimulation of melanogenesis in cultured melanoma cells by calciferols. FEBS Lett 1974;42:32-5.
[Google Scholar]
Tomita Y, Torinuki W, Tagami H. Stimulation of human melanocytes by vitamin D3 possibly mediates skin pigmentation after sun exposure. J Invest Dermatol 1988;90:882-4.
[Google Scholar]
Watabe H, Soma Y, Kawa Y, Ito M, Ooka S, Ohsumi K, et al. Differentiation of murine melanocyte precursors induced by 1,25-dihydroxyvitamin D3 is associated with the stimulation of endothelin B receptor expression. J Invest Dermatol 2002;119:583-9.
[Google Scholar]
Xu QX, Du J, He PY, Zhang JZ, Zhu TJ. Effects of 1alpha, 25-dihydroxyvitamin D(3) and UVB on cell proliferation and melanin synthesis of cultured human melanocyte. Beijing Da Xue Xue Bao 2004;36:483-6.
[Google Scholar]
Birlea SA, Costin GE, Norri DA. New insights on therapy with Vitamin D analogs targeting the intracellular pathways that control repigmentation in human vitiligo. Med Res Rev 2009;29:514-46.
[Google Scholar]
Mansur CP, Gordon PR, Ray S, Holick MF, Gilchrest BA. Vitamin D, its precursors, and metabolites do not affect melanization of cultured human melanocytes. J Invest Dermatol 1988;91:16-21,
[Google Scholar]
Hong DK, Kim TJY, Park JK, Haw CR. Effect of calcipotriol (MC 903), a novel synthetic derivative of vitamin D on the growth of cultured human keratinocytes and melanocytes. Korean J Dermatol 1992;30:811-23.
[Google Scholar]
Abdel-Malek ZA, Ross R, Trinkle L, Swope V, Pike JW, Nordlund JJ. Hormonal effects of vitamin D3 on epidermal melanocytes. J Cell Physiol 1988;136:273-80.
[Google Scholar]
Parsad D, Saini R, Verma N. Combination of PUVAsol and topical calcipotriol in vitiligo. Dermatology 1998;197:167-70.
[Google Scholar]
Parsad D, Kanwar AJ. Topical vitamin D3 analogues in the treatment of vitiligo. Pigment Cell Melanoma Res 2009;22:487-8.
[Google Scholar]
Oh SH, Kim T, Jee H, Do JE, Lee JH. Combination treatment of nonsegmental vitiligo with a 308-nm xenon chloride excimer laser and topical high-concentration tacalcitol: A prospective, single-blinded, paired, comparative study. J Am Acad Dermatol 2011;65:428-30.
[Google Scholar]
Silverberg JI, Silverberg AI, Malka E, Silverberg NB. A pilot study assessing the role of 25 hydroxy vitamin D levels in patients with vitiligo vulgaris. J Am Acad Dermatol 2010;62:937-41.
[Google Scholar]
Hartmann A, Lurz C, Hamm H, Brocker EB, Hofmann UB. Narrow-band UVB 311-nm vs. broad-band UVB therapy in combination with topical calcipotriol vs. placebo in vitiligo. Int J Dermatol 2005;44:736-42.
[Google Scholar]
Baysal V, Yildirim M, Erel A, Kesici D. Is the combination of calcipotriol and PUVA effective in vitiligo? J Eur Acad Dermatol Venereol 2003;17:299-302.
[Google Scholar]
Yalçýn B, Sahin S, Bükülmez G, Karaduman A, Atakan N, Akan T, et al . Experience with calcipotriol as adjunctive treatment for vitiligo in patients who do not respond to PUVA alone: A preliminary study. J Am Acad Dermatol 2001;44:634-7.
[Google Scholar]
Tadokoro T, Yamaguchi Y, Batzer J, Coelho SG, Zmudzka BZ, Miller SA, et al. Mechanisms of skin tanning in different racial/ethnic groups in response to ultraviolet radiation. J Invest Dermatol 2005;124:1326-32.
[Google Scholar]
Ermis O, Alpsoy E, Cetin L, Yilmaz E. Is the efficacy of psoralen plus ultraviolet A therapy for vitiligo enhanced by concurrent topical calcipotriol? A placebo-controlled double-blind study. Br J Dermatol 2001;145:472-5.
[Google Scholar]
Parsad D, Pandhi R, Dogra S, Kumar B. Clinical study of repigmentation patterns with different treatment modalities and their correlation with speed and stability of repigmentation in 352 vitiliginous patches. J Am Acad Dermatol 2004;50:63-7.
[Google Scholar]
Cicarma E, Mørk C, Porojnicu AC, Juzeniene A, Tam TT, Dahlback A, et al. Influence of narrowband UVB phototherapy on vitamin D and folate status. Exp Dermatol 2010;19:e67-72.
[Google Scholar]
Schallreuter-Wood KU, Pittelkow MR, Swanson NN. Defective calcium transport in vitiliginous melanocytes. Arch Dermatol Res 1996;288:11-3.
[Google Scholar]
Nordlund JJ, Abdel-Malek ZA, Boissy RE, Rheins LA. Pigment cell biology: An historical review. J Invest Dermatol 1989; 92:53-9.
[Google Scholar]
Dahl MV. Imiquimod: A cytokine inducer. J Am Acad Dermatol 2002;47:S205-8.
[Google Scholar]
Koizumi H, Kaplan A, Shimizu T, Ohkawara A. 1,25-Dihydroxyvitamin D3 and a new analogue, 22-oxacalcitriol, modulate proliferation and interleukin-8 secretion of normal human keratinocytes. J Dermatol Sci 1997;15:207-13.
[Google Scholar]
Penna G, Adorini L. 1 Alpha, 25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 2000;164:2405-11.
[Google Scholar]
Griffin MD, Lutz W, Phan VA, Bachman LA, McKean DJ, Kumar R. Dendritic cell modulation by 1alpha, 25 dihydroxyvitamin D3 and its analogs: A vitamin D receptor-dependent pathway that promotes a persistent state of immaturity in vitro and in vivo. Proc Natl Acad Sci USA 2001;98:6800-5.
[Google Scholar]
Lemire JM, Archer DC. 1,25-dihydroxyvitamin D3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis. J Clin Invest 1991;87:1103-7.
[Google Scholar]
Mathieu C, Waer M, Laureys J, Rutgeerts O, Bouillon R. Prevention of autoimmune diabetes in NOD mice by 1,25 dihydroxyvitamin D3. Diabetologia 1994;37:552-8.
[Google Scholar]
Cantorna MT, Hayes CE, DeLuca HF. 1,25-Dihydroxycholecalciferol inhibits the progression of arthritis in murine models of human arthritis. J Nutr 1998;128:68-72.
[Google Scholar]
Cantorna M, Munsick TC, Bemiss C, Mahon BD. 1,25-Dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease. J Nutr 2000;130:2648-52.
[Google Scholar]
Van Etten E, Branisteanu DD, Overbergh L, Bouillon R, Verstuyf A, Mathieu C. Combination of a 1,25-dihydroxyvitamin D3 analog and a bisphosphonate prevents experimental autoimmune encephalomyelitis and preserves bone. Bone 2003;32:397-404.
[Google Scholar]
Birlea SA, Costin GE, Norris DA. Cellular and molecular mechanisms involved in the action of vitamin D analogs targeting vitiligo depigmentation. Curr Drug Targets 2008;9:345-59.
[Google Scholar]
Njoo MD, Westerhof W. Vitiligo. Pathogenesis and treatment. Am J Clin Dermatol 2001;2:167-81.
[Google Scholar]
Huang CL, Nordlund JJ, Boissy R. Vitiligo: A manifestation of apoptosis? Am J Clin Dermatol 2002;3:301-8.
[Google Scholar]
De Haes P, Garmyn M, Degreef H, Vantieghem K, Bouillon R, Seqaert S. 1,25-Dihydroxyvitamin D3 inhibits ultraviolet B-induced apoptosis, Jun kinase activation, and interleukin-6 production in primary human keratinocytes. J Cell Biochem 2003;89:663-73.
[Google Scholar]
Mason RS, Holliday CJ. 1,25-Dihydroxyvitamin D Contributes to Photoprotection in Skin Cells. In: Norman A, Bouillon R, Thomasset M, editors. Vitamin D Endocrine System: Structural, Biological, Genetic and Clinical Aspects. Riverside: University of California; 2000. p. 605-8.
[Google Scholar]
Sauer B, Ruwisch L, Kleuser B. Antiapoptotic action of 1alpha, 25-dihydroxyvitamin D3 in primary human melanocytes. Melanoma Res 2003;13:339-4770.
[Google Scholar]
Bro¿yna AA, Jozwicki W, Janjetovic Z, Slominski AT. Expression of vitamin D receptor decreases during progression of pigmented skin lesions. Hum Pathol 2011;42:618-31.
[Google Scholar]
AlGhamdi KM, Kumar A, Taieb A, Ezzedine K. Assessment Methods for the Evaluation of Vitiligo. J Eur Acad Dermatol Venereol 2012;26:1463-71.
[Google Scholar]
Wong G, Gupta R, Dixon KM, Deo SS, Choong SM, Halliday GM, et al. 1,25-Dihydroxyvitamin D and three low-calcemic analogs decrease UV-induced DNA damage via the rapid response pathway. J Steroid Biochem Mol Biol 2004; 89-90:567-70.
[Google Scholar]
Lu-yan T, Wen-wen F, Lei-hong X, Yi J, Zhi-zhong Z. Topical tacalcitol and 308-nm monochromatic excimer light: A synergistic combination for the treatment of vitiligo. Photodermatol Photoimmunol Photomed 2006;22:310-4.
[Google Scholar]
Han J, Colditz GA, Hunter DJ. Polymorphisms in the MTHFR and VDR genes and skin cancer risk. Carcinogenesis 2007;28:390-7.
[Google Scholar]

Fulltext Views

PDF downloads
Show Sections