|Year : 2022 | Volume
| Issue : 1 | Page : 22-27
Serum 25-hydroxy vitamin D: A possible role in acne vulgaris
Elshahat A Sharaf1, Hamdy F Marzouk2, Walaa M Abdelmageed1, Mohammad A Gaballah1
1 Department of Dermatology, Andrology and STDs, Faculty of Medicine, Mansoura University, Mansoura, Egypt
2 Department of Clinical pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
|Date of Submission||05-Jan-2021|
|Date of Decision||20-Feb-2021|
|Date of Acceptance||25-Mar-2021|
|Date of Web Publication||25-Feb-2022|
Mohammad A Gaballah
Department of Dermatology, Andrology and STDs, Faculty of Medicine, Mansoura University, El-Gomhoria St., Mansoura
Source of Support: None, Conflict of Interest: None
Background: Acne vulgaris (AV) is a chronic inflammatory disease of the pilosebaceous apparatus. Vitamin D controls the immune system and the proliferation and differentiation of sebocytes and keratinocytes. In addition, it has antioxidant and anti-comedogenic properties. In vitro studies showed that Vitamin D had a functional part in the acne development. Serum Vitamin D levels were previously estimated in AV patients with conflicting results. Objective: To compare 25-hydroxyvitamin D (25[OH] D) serum level in AV patients with healthy controls and to assess the association between 25(OH) D and disease severity to detect any possible role of Vitamin D in AV pathogenesis and treatment. Materials and Methods: 25 (OH) D levels were estimated in 80 AV patients and 40 age- and sex-matched controls using the enzyme-linked immunosorbemt assay technique. Results: 25(OH) D serum levels were significantly lower in patients as compared to controls. Although of no statistical significances, serum 25(OH) D levels were lower in severe and very severe cases than mild and moderate cases. There was significant negative correlation between serum 25(OH) D level and age of onset of AV. However, there were nonsignificant correlations between 25(OH) D blood levels and other patients' characters such as age, sex, occupation, duration of the disease, family history of AV, body mass index, and sites of the lesions. Conclusions: Vitamin D may have a role in the pathogenesis of in AV patients. Further studies on a larger number of patients are recommended to confirm the validity of our results and to evaluate the therapeutic role of Vitamin D supplementation or topical vitamin analogs in acne treatment.
Keywords: 25-hydroxy, acne, Vitamin D, vulgaris
|How to cite this article:|
Sharaf EA, Marzouk HF, Abdelmageed WM, Gaballah MA. Serum 25-hydroxy vitamin D: A possible role in acne vulgaris. Clin Dermatol Rev 2022;6:22-7
|How to cite this URL:|
Sharaf EA, Marzouk HF, Abdelmageed WM, Gaballah MA. Serum 25-hydroxy vitamin D: A possible role in acne vulgaris. Clin Dermatol Rev [serial online] 2022 [cited 2022 Aug 19];6:22-7. Available from: https://www.cdriadvlkn.org/text.asp?2022/6/1/22/338593
| Introduction|| |
Globally, acne affects around 650 million persons or near 9.4% of the population. The pathogenesis of acne vulgaris (AV) is a complex matter and remains incompletely understood. The factors including Vitamin D, obesity, diet, and auto-inflammation are emerging nowadays.
The synthesis of Vitamin D in the dermis from cholesterol depends on sun exposure, especially ultraviolet B (UVB) radiation., The best marker of Vitamin D status is plasma 25-hydroxy Vitamin D (25 (OH) D) level. In the skin, Vitamin D acts primarily on the Vitamin D receptors (VDRs) to regulate keratinocyte and sebocyte growth, differentiation, and functions. It also influences the immune functions of dendritic cells and T-lymphocytes., It has antioxidant and anti-comedogenic properties too.,
Vitamin D insufficiency and deficiency has become universal. It was assessed that more than one billion persons worldwide are either Vitamin D deficient or insufficient. Despite significant daily availability of sunlight in Africa and the Middle East, people living in these areas are often Vitamin D insufficient or deficient due to sunlight avoidance, use of sun screens, and many dietary factors. Vitamin D deficiency was found to be associated with the progression of cancers of the breast, colon, ovary, and prostate, also with systemic inflammatory diseases as systemic lupus erythematosus (SLE), rheumatoid arthritis, and inflammatory bowel disease., It has an important role as an immune modulator in psoriasis, vitiligo, atopic dermatitis, and alopecia.
Studies investigated the theory that Vitamin D has a functional part in acne development but with conflicting results.,, The aim of the current study was to compare the serum level of 25(OH) D in AV patients and controls to assess the association between disease severity and serum Vitamin D level to detect any possible role of Vitamin D in acne pathogenesis.
| Materials and Methods|| |
This case–control study was conducted on two groups. The case group included 80 AV patients diagnosed clinically. The control group involved 40 healthy volunteers without acne who match the patient group with regard to age, sex, socioeconomic status, and body mass index (BMI). All participants were recruited from the outpatient clinic of dermatology and andrology department, Mansoura University Hospital from April 2017 to June 2017. Informed written consents were obtained from all participants before their participation in this study. Approval was obtained from the institutional research board of the Faulty of Medicine, Mansoura University (MS/17.04.10).
Completely healthy adults aged ≥18 years old with any degree of AV were included. The exclusion criteria included consumption of Vitamin D supplementation for the last 6 months, patients with any associated disease that alter the 25(OH) D blood level (as vitiligo, psoriasis, alopecia areata, atopic dermatitis, SLE, renal disease, liver disease, cancers, and autoimmune diseases), patients on plus ultraviolet A and/or narrowband UVB in the last 3 months, pregnant and lactating females, patients treated with topical Vitamin D3 analogue, and patients known to have a state of Vitamin D deficiency (to avoid the selection bias).
All participants were subjected to thorough history taking, complete general examination, and full dermatological examination including skin, hair, nail, and oral mucosa.
Assessment of acne severity in patients using the Global Acne Grading System (GAGS) was done. This system divides the face, chest, and back into six areas (forehead, each cheek, nose, chin and chest, and back) and assigns a factor to each area on the basis of size. The factor for nose and chin equals 1 and for forehead, right cheek and left cheek equals 2 and for chest, shoulder and back equals 3. Each type of lesion is given a value depending on severity: no lesions = 0, comedones = 1, papules = 2, pustules = 3, and nodules = 4. The score for each area (local score) is calculated using the formula: Local score = Factor × Grade (0–4). The global score is the sum of local scores, and acne severity was graded using the global score. A score of 1–18 is considered mild; 19–30, moderate; 31–38, severe; and ≥39, very severe.
Assessment of 25-hydroxyvitamin D by enzyme-linked immunosorbemt assay
Five ml venous blood samples were obtained from all participants by venipuncture under aseptic conditions. Samples were collected into serum-separator tubes. After clot formation, centrifugation of samples at 2000×g for 10 min was done, and the sera were separated and stored at − 20°C until the analysis. 25(OH) D was detected quantitatively by the enzyme-linked immunosorbent assay (ELISA) method using the ELISA kits (SunRedbio, Shanghai, China). Levels of 25(OH) D are classified as deficiency: <20 ng/ml (IU: <50 nmol/l), insufficiency: 20–29 ng/ml (IU: 51–75 nmol/l), and normal: >30 ng/ml (IU: >75 nmol/l).
The collected data were coded, processed, and analyzed using the Statistical Package for the Social Sciences (SPSS) program for Windows (Standard version 22) (SPSS Inc., Chicago, IL, USA). The normality of data was first tested with the one-sample Kolmogorov–Smirnov test. Qualitative data were described using number and percent. The association between the categorical variables was tested using the Chi-square test. Continuous variables were presented as mean ± standard deviation (SD) for parametric data and median for nonparametric data. Student's t-test was used to compare two means while ANOVA test was used to compare more than two means. Pearson correlation was used to correlate the continuous parametric data and Spearman correlation for nonparametric data. For all above-mentioned statistical tests done, the threshold of significance is fixed at 5% level (P < 0.05 is significant).
| Results|| |
[Table 1] shows no statistically significant differences between the patients and controls regarding age, sex, occupation, and BMI. Ages of the patients ranged from 18 to 39 years and of the controls ranged from 18 to 31 years.
|Table 1: Demographic data and serum 25 hydroxy Vitamin D levels of the studied groups|
Click here to view
The duration of the disease ranged from 1 to 22 years with a median of 5 years. The age of onset of disease ranged from 10 to 27 years (mean ± SD) (16.17 ± 2.54 years). Thirty-nine patients (48.8%) had a positive family history of AV. Following disease associations were seen: one patient had androgenetic alopecia, four patients had hirsutism, two patients had polycystic ovary syndrome by ultrasound, two patients had irregular menses, seven patients had warts and one patient had pityriasis versicolor. Previous AV treatments included topical treatments (retinoids, antibiotics, and unknown medications) and systemic medications (antibiotics and isotretinoin).
Severity of AV according to GAGS ranged from mild to very severe degrees (Min-Max 8–51) (mean ± SD) (25.73 ± 10.61) divided as; 24 patients (30%) had mild acne, 30 patients (37.5%) had moderate acne, 13 patients (16.2%) had severe acne, and 13 patients (16.2%) had very severe acne. Serum 25(OH) D levels were significantly lower in the patient group (mean ± SD) (75.51 ± 22.74) than the control group (mean ± SD) (114.67 ± 42.36) [Table 1].
Correlations between serum 25(OH) D level and patients' parameters showed significant negative correlation between serum 25(OH) D level and age of onset of AV (r = −0.291 and P = 0.009). However, there were nonsignificant associations between serum 25(OH) D level and other patients' parameters such as age, sex, occupation, special habits, marital status, occupation, duration of the disease, family history of AV, body weight, BMI, and sites of the lesions. No significant correlation between serum Vitamin D and AV severity (P = 0.927) was noted.
| Discussion|| |
Our results of lower serum 25OH) D in AV were in agreement with other authors. El-Hamd et al. reported significantly low serum levels of 25(OH) D in AV Egyptian patients compared with controls. Yildizgören and Togral reported that patients with nodulocystic acne had lower Vitamin D levels. In addition, Stewart and Bazergy observed significantly decreased 25(OH) D serum levels in patients' group than normal controls.
In agreement with this, Swelam et al. also noted that VDR polymorphisms may be a risk factor in AV development. They also reported that serum level 25(OH) D is very low in AV patients compared to controls; however, it seems to be affected by the several factors other than just being affected by the ApaI and TaqI gene polymorphism. Finally, they concluded that Vitamin D deficiency could be a risk factor in AV development regardless of VDR gene polymorphisms; therefore, Vitamin D supplements could help in the treatment of acne patients, especially those who have insufficient levels.
The reason for lower serum 25(OH) D in our acne patients is not fully understood. It may be related to polymorphism of VDRs in AV patients. Patients with severe acne may be subjected 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. However, other factors, for example, dieting habits, life style, occupation, and use of sun screens may be involved, and this may be supported by the beneficial effect of Vitamin D supplementation in AV patients regardless of VDR gene polymorphisms.,
On contrary, in a study from Kuwait, Al-Taiar et al. reported no significant differences between serum Vitamin D level in participants with or without AV. All participants in the last study were students with a mean age of 12 years. The same study included only those with mild-to-moderate AV with the exclusion of those with severe AV. Two-thirds of the participants were Kuwaiti and one-third was non-Kuwaiti from different nationalities. Some of the participants were on Vitamin D supplementations. In contrast, our study included all grades of acne severity in adults (>18 years) with different jobs and same Egyptian nationality. All of these factors may explain the difference between our study and the last study. Social, genetic, occupational, and environmental factors may contribute also to this difference.
Toossi et al. detected nonsignificant differences in serum 25(OH) D levels between AV patients and health controls in Iran. This would be partially explained by recall bias which reminds the fact that people usually forget previous involvement in such a disease as a common complaint. Furthermore, small sample size (39 patients with AV and 40 healthy controls) affected the statistical analysis. Furthermore, low serum Vitamin D contents among Iranians would be a general problem which rationally bothers the above correlation because cases and controls in the mentioned population face hypovitaminose D.
In addition, Lim et al. noted that there were no significant differences in the mean 25(OH) D concentration between the AV patients and controls. However, the prevalence of 25(OH) D deficiencies was significantly higher in patients with acne compared to healthy controls. This may be the result of the characteristics of Vitamin D status in the Korean population as most healthy controls had inadequate levels of Vitamin D, as reported previously in the general Korean population. They also found no significant correlation between deficient 25(OH) D levels and age, sex, disease duration, BMI, family history, smoking, sunscreen use, trunk involvement, and the number of noninflammatory lesions. In addition, they reported that Vitamin D supplementation significantly improved only the inflammatory lesions.
In a contrasting study, 25(OH) D level was significantly higher in AV patient group than the control group. Vitamin D level in the mild group was 18.5 (12.8–23.1) ng/mL, whereas the Vitamin D level in the moderate-severe group was 18.0 (11.2–23.1) ng/ml. They concluded that no significant relationship between AV disease and Vitamin D levels was observed. The reason for the high level of Vitamin D found in the patient group may be because the patient group was included more in the spring months and not all parameters affecting the Vitamin D level could be matched in the patient and control groups. In the patient group, 22 (27.5%) participants were included in the study in the winter months and 58 (72.5%) in the spring months. In the control group, 46 (57.5%) participants were included in the study in the winter months and 34 (42.5%) in the spring months. The distribution of the patient and control groups by the season of sampling was significantly different. The median vitamin 25(OH) D level measured in the spring months was significantly higher than the vitamin 25(OH) D level measured in the winter months in both groups.
The possible role of Vitamin D in AV pathogenesis was suggested depending on several evidences. Vitamin D normally suppresses of Th1 and Th17. Studies showed the active role of Th1 and Th17 lymphocytes in the inflammation stage of AV pathogenesis.,, In addition, VDRs in human sebocytes and modulation of lipid and cytokine assembly were reported. Furthermore, Vitamin D suppresses Cutibacterium acnes-induced Th17 differentiation with decreased expression of interleukin (IL)-17, which is an inflammatory cytokine that is up-regulated in acne patients. In addition, Vitamin D has antimicrobial properties by inducing antimicrobial peptides as Leucine-37 (LL-37) in human sebocytes. Furthermore, the expression of inflammatory biomarkers, such as IL-6, IL-8, and matrix metalloproteinase 9, was reduced by treatment with Vitamin D in cultured sebocytes.
In addition, the inhibition of cell proliferation is mediated through an arrest of sebocytes in the G1-phase which is induced by VDR-mediated genomic effects. It is reported that cultivation of human sebaceous gland cell line with 1,25 dihydroxyvitamin D (1,25(OH) 2D) lead to dose-dependent inhibition of cell proliferation. It has been determined that local production or metabolism of Vitamin D metabolites may have an important role for growth regulation and other cellular functions in sebaceous glands and that sebaceous glands denote promising targets for therapy with Vitamin D equivalents or for pharmacological modulation of calcitriol synthesis/metabolism.
As shown also by Zouboulis et al., the deficient 1,25(OH) 2D levels seen in the serum of patients with AV may contribute to the increased volume of sebaceous gland and the seborrhea, which are characteristic signs for AV. Agak et al. demonstrate the inhibitory effect of 1,25(OH)2D in Cutibacterium acnes-induced IL-17, which provides a therapeutic application of 1,25(OH) 2D for the treatment of acne and other Th17-mediated skin disease.
In the current study, serum 25(OH) D levels were lower in severe and very severe cases than mild and moderate cases. However, the difference was not statistically significant. This is in agreement with Topan et al. and Toossi et al. who found no significant correlation between severity of the disease and Vitamin D levels.
On the other hand, other authors reported a significant strong inverse correlation between mean serum 25(OH) D level and AV severity.,, In addition, Lim et al. found that the number of inflammatory lesions was significantly and negatively correlated with Vitamin D concentrations, signifying a possible link between the extent of Vitamin D deficiency and the degree of acne inflammation.
In another study, Yahya et al. reported that lower levels of serum 25(OH) D were significantly associated with more severe AV and higher numbers of inflammatory, noninflammatory, and total lesions. The proportions of Vitamin D insufficiency were 90% both in mild and moderate groups, whereas the proportions of Vitamin D deficiency were 70% in the severe group (P = 0.005). Significant negative correlations were found between serum 25(OH) D levels and inflammatory lesions, noninflammatory lesions, and total AV lesions.
The difference between our study and the other authors may be related to differences in study design or due to the presence of other circumstances which may affect the severity of acne or Vitamin D status, including genetic factors, seasonal variations, dietary intake, Vitamin D supplementation, the length of exposure to sunlight that varies in each individual or other socioeconomic or environmental factors. For example, Lim et al. did their study in winter, El-Hamd et al. study was done along a whole year, while our study was done in spring months.
In addition, the number of participants in studies investigating the relationship between Vitamin D and AV is usually small and these studies so far do not cover the entire factors affecting the Vitamin D level such as seasonal differences, diet, latitude, altitude, clothing, use of sunscreens, and skin type.
| Conclusions|| |
The present study indicates a possible role for Vitamin D in acne pathogenesis and treatment. The main limitation of this study is the small number of patients which may affect the statistical significance of the results. Hence, we recommend further studies on larger number of patients to confirm the validity and reliability of our results and to search for any therapeutic benefit of Vitamin D supplementation or topical vitamin analogues in acne treatment.
There was inequality in patients and controls with respect to a number of factors affecting the Vitamin D level (direct sun exposure, diet, clothing, and use of sunscreens). For more accurate results, Vitamin D levels before and after treatment can be studied in AV patients. The measurements can be performed in a patient group of a narrower age interval and of the same gender.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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