To the best of our knowledge, this is the first study to assess vitamin D status in acne patients. There were no significant differences in the mean vitamin D concentration between acne patients and healthy controls. This may be the result of the characteristics of vitamin D status in the Korean population. As shown in Fig 1, most healthy control subjects had inadequate levels of vitamin D, as reported previously in the general Korean population.[16-18] However, the prevalence of 25(OH)D deficiency was significantly higher in patients with acne (48.8%) compared to healthy controls (22.5%). A similar finding was reported in a previous clinical trial in which patients with nodulocystic acne showed relatively low serum vitamin D levels.
To understand the vitamin D status associated with acne patients, we investigated the factors that influence vitamin D deficiency. Although obesity and decreased sun exposure using sunscreen are known to be associated with low 25(OH)D levels,[20-24] they were not associated with vitamin D deficiency in this study. The serum vitamin D level is also influenced by food such as fish oil or pork[16,17]; unfortunately, however, we were unable to evaluate the dietary habits of the patients. Our analysis revealed that the only factor associated with 25(OH)D deficiency was acne severity, similar to previous findings that disease severity of atopic dermatitis, psoriasis, and vitiligo is associated with lower levels of vitamin D.[7-9] Patients with severe acne may be subject to more psychological stress, and may tend to avoid spending extended periods outdoors, suggesting a possible explanation for low vitamin D levels in patients with severe acne.
In the randomized controlled trial of 39 acne patients with vitamin D deficiency, oral vitamin D supplementation produced a significant improvement in acne inflammation. In contrast, a previous study found no effect of vitamin D supplementation on acne lesions. However, this result was due to the fact that patients with acne had polycystic ovary syndrome, and there was no consideration of the specific acne type, such as inflammatory lesions. The observed anti-inflammatory effects of vitamin D have several biological mechanisms. The expression of inflammatory biomarkers, such as interleukin (IL)-6, IL-8, and matrix metalloproteinase 9, is reduced by treatment with vitamin D in cultured sebocytes. There is also published evidence that vitamin D inhibits P. acnes-induced Th17 differentiation with reduced expression of IL-17, an inflammatory cytokine that is increased in acne patients. In addition, vitamin D has antimicrobial effects by inducing antimicrobial peptides such as LL-37 in human sebocytes. These previous reports support the theory that vitamin D has an immune regulatory function in sebocytes, which supports the possible anti-inflammatory effects of vitamin D in acne patients.
Our vitamin D supplementation trial had a few potential limitations, such as the use of a low dose and short duration of treatment. The daily dose of vitamin D in this study was 1000 IU/day, lower than in previous studies.[27,28] However, some studies have shown that a daily dose of 1000 IU vitamin D is an effective treatment for atopic dermatitis.[29,30] In addition, as shown in Fig 4, the vitamin D level was significantly improved by 1000 IU/day for 2 months, although it was an inadequate level. Future trials need to examine the impact of regimens that are more likely to achieve adequate levels of vitamin D, which is often associated with optimal health. Moreover, given the frequent disease fluctuations that characterize acne, future trials of more patients with a longer treatment duration are needed to determine if acne lesions recur after the initial improvement or if the benefits are sustained by longer duration of treatment.
In conclusion, we found that vitamin D deficiency was more frequent in patients with acne, which was inversely correlated with disease severity, indicating a potential role of vitamin D deficiency in acne pathogenesis. A further study with a larger sample size is needed to confirm our results because of the small number of patients in the supplementation study and the natural fluctuation of acne. Evaluation of the tissue level of vitamin D in patients with acne will also require a further study to reveal direct evidence of the effect of vitamin D on acne.