Vitamin D is produced in the skin and is an important factor in keratinocyte proliferation and differentiation, as well as regulation of the hair follicle cycle.1 It is implicated in the pathogenesis of various diseases, including hair loss. In our clinic, serum vitamin D levels are collected routinely during evaluation of hair loss, allowing us to address this controversial issue. We aim to evaluate the prevalence of vitamin D deficiency in patients with alopecia areata (AA), androgenic alopecia (AGA), central centrifugal scarring alopecia (CCCA), lichen planopilaris (LPP), and telogen effluvium (TE).
Patients diagnosed with AA, AGA, CCCA, LPP and TE between May 2009 and April 2010 were identified (n=358). Data on age, gender, race, hair loss type, onset, and serum 25-hydroxyvitamin D values within 3 months of a visit for new or recurrent hair loss were extracted from the electronic health record. Patients taking vitamin D supplements at the time of their visit were excluded. Vitamin D deficiency was defined as vitamin D levels < 30ng/ml, and this was further categorized into mild (21–30ng/ml), moderate (12–21ng/ml), or severe (<12ng/ml).2 Kruskall-Wallis test, χ2 test and Fisher exact were used to compare demographic variables and vitamin D levels. The association between Vitamin D and hair loss type, gender, age, and race was assessed with logistic regression.
The majority of patients had TE (n=121), followed by AA (n=77), AGA (n=73), LPP (n=58) and CCCA (n=29) (Table 1). Median age at the time of Vitamin D evaluation was 49.5 years (range 4.2–85). LPP patients tended to be older, while AA patients were the youngest (p<0.001). Males comprised 9.8% (n=35) of patients, and were most likely to have AA (p<0.001). Vitamin D deficiency was present in 64.8% of patients, with 32.96% having mild, 17.60% moderate and 14.25% severe deficiency. Patients with LPP had an 8.3 times higher odds of severe vitamin D deficiency (p<0.001), while TE patients had 3.7 times higher odds when compared to AA (p=<0.024), after adjusting for sex, age, and race (Table 2). African Americans had 6.3 fold greater odds of severe vitamin D deficiency compared to Caucasians (p<0.001), while for Asians it was 6.1 (p=0.004). Interestingly, men had a higher incidence of vitamin D deficiency, regardless of other factors.
Table 1.
Comparisons of demographic characteristics and Vitamin D levels among different types of alopecia. P values were from Chi-square test(Male) or Fisher’s exact test(Race) or Kruskal-Wallis test (Age).
| AA(n=77) | AGA(n=73) | CCCA(n=29) | LPP(n=58) | TE(n=121) | ||
|---|---|---|---|---|---|---|
|
| ||||||
| Variable | n(%) | n(%) | n(%) | n(%) | n(%) | p-values |
| Male [n(%)] | 23(30) | 8(11) | 0(0) | 3(5.2) | 1(0.83) | <0.001 |
| Race[n(%)] | <0.001 | |||||
| White/Middle Eastern | 54(70) | 65(90) | 0(0) | 47(82) | 92(77) | |
| Black, African American | 13(17) | 4(5.6) | 27(96) | 6(11) | 13(11) | |
| Hispanic | 0(0) | 1(1.4) | 0(0) | 0(0) | 3(2.5) | |
| Asian/American Indian/Alaska Native/Native Hawaiian or Other Pacific Islander | 3(3.9) | 1(1.4) | 0(0) | 1(1.8) | 9(7.5) | |
| Other/Unknown | 7(9.1) | 1(1.4) | 1(3.6) | 3(5.3) | 3(2.5) | |
| Age [Median] | 37.2 | 53.2 | 55.2 | 56.6 | 46.9 | <.001 |
| Vitamin D level [n(%)] | 0.18 | |||||
| <=12 ng/ml | 7(9.1) | 9(12) | 7(24) | 12(21) | 16(13) | |
| 12–20 ng/ml | 15(19) | 9(12) | 9(31) | 8(14) | 22(18) | |
| 20–30 ng/ml | 26(34) | 23(32) | 7(24) | 21(36) | 41(34) | |
| >30 ng/ml | 29(38) | 32(44) | 6(21) | 17(29) | 42(35) | |
| Raw Vitamin D [Median] | 27.7 | 28.5 | 18.7 | 24.6 | 25.2 | 0.018 |
Legend: AA-alopecia areata, AGA- androgenetic alopecia, CCCA- central centrifugal cicatricial alopecia, LPP- lichen planopilaris, TE- telogen effluvium. P- p value.
Table 2.
Logistic regression for dichotomized Vitamin D (Inadequate: <=12 ng/ml VS. sufficient: > 12 ng/ml). Inadequacy was modeled.
| Effect | OR(95%CI) | P-value |
|---|---|---|
| Diagnosis | ||
| AA | Reference | |
| AGA | 3.31(0.99–11.04) | 0.051 |
| CCCA | 2.63(0.64–10.77) | 0.18 |
| LPP | 8.34(2.41–28.84) | <0.001 |
| TE | 3.66(1.19–11.32) | 0.024 |
| Age | 0.98(0.96–1.01) | 0.15 |
| Sex | ||
| Female | Reference | |
| Male | 4.4(1.48–13.03) | 0.008 |
| Ethnicity* | ||
| White/Middle Eastern | Reference | |
| Black, African American | 6.38(2.61–15.58) | <.001 |
| Asian/American Indian/Alaska Native/Native Hawaiian or Other Pacific Islander | 6.11 (1.76–21.2) | 0.004 |
| Other/Unknown | 2.37(0.58–9.77) | 0.23 |
All Hispanic(n=4) had Vitamin D>12, which caused quasi-complete separation for the logistic regression model. Therefore, Hispanic was excluded for the logistic regression model.
Legend: AA-alopecia areata, AGA- androgenetic alopecia, CCCA- central centrifugal cicatricial alopecia, LPP- lichen planopilaris, TE- telogen effluvium.
Vitamin D alters immune response by inhibiting the adaptive immune system and improving the innate immune response.3, 4 Furthermore, prior studies suggest that the autoimmune effects of vitamin D are due to an increase in autoreactive T-cells as a result of altered maturation and function of dendritic cells which maintain self-tolerance.3, 4 Efficacy of vitamin D supplementation is controversial, and some studies demonstrate harmful effects of supplementation.3 Limitations include retrospective collection at a tertiary care center, and lack of controls. Testing for vitamin D deficiency should be considered in patients with alopecia due to its high prevalence. While supplementation is controversial, we recommend giving cholecalciferol 50,000 IU once weekly for 12 weeks followed by 2,000 IU daily. Future studies should evaluate if vitamin D supplementation affects the immunologic inflammatory milieu found in scarring alopecia.5
Acknowledgments
Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number 5 T32 AR 7569-23. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
ABBREVIATIONS
- AA
alopecia areata
- AGA
androgenetic alopecia
- CCCA
central centrifugal cicatricial alopecia
- LPP
lichen planopilaris
- TE
telogen effluvium
Footnotes
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References
- 1.Mady LJ, Ajibade DV, Hsaio C, Teichert A, Fong C, Wang Y, et al. The Transient Role for Calcium and Vitamin D during the Developmental Hair Follicle Cycle. J Invest Dermatol. 2016;136:1337–45. doi: 10.1016/j.jid.2016.02.813. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Ross AC. The 2011 report on dietary reference intakes for calcium and vitamin D. Public Health Nutr. 14:938–9. doi: 10.1017/S1368980011000565. [DOI] [PubMed] [Google Scholar]
- 3.Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients. 5:2502–21. doi: 10.3390/nu5072502. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.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. 12:127–36. doi: 10.1016/j.autrev.2012.07.007. [DOI] [PubMed] [Google Scholar]
- 5.Vegesna V, O'Kelly J, Uskokovic M, Said J, Lemp N, Saitoh T, et al. Vitamin D3 analogs stimulate hair growth in nude mice. Endocrinology. 2002;143:4389–96. doi: 10.1210/en.2002-220118. [DOI] [PubMed] [Google Scholar]