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Comparison of Vitamin D Levels in Patients with and without Acne: A Case-Control Study Combined with a Randomized Controlled Trial

PLOS ONE

August 2016
11(8):e0161162

DOI:10.1371/journal.pone.0161162

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CC BY 4.0

Authors:

Young-Ho Lee

Osaka University

Young Lee

Chungnam National University

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Background Vitamin D plays an important role in the immune system, and its deficiency has been implicated in various skin diseases, including atopic dermatitis and psoriasis. Acne is a common inflammatory skin disease; however, the association with vitamin D remains unclear. Objectives We evaluated vitamin D levels in patients with acne to determine the effect of vitamin D supplementation. Methods This study included 80 patients with acne and 80 healthy controls. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured, and demographic data were collected. Vitamin D-deficient patients were treated with oral cholecalciferol at 1000 IU/day for 2 months. Results Deficiency in 25(OH)D was detected in 48.8% of patients with acne, but in only 22.5% of the healthy controls. The level of 25(OH)D was inversely associated with the severity of acne, and there was a significant negative correlation with inflammatory lesions. In a subsequent trial, improvement in inflammatory lesions was noted after supplementation with vitamin D in 39 acne patients with 25(OH)D deficiency. Limitations Limitations of the study include the small number of patients in the supplementation study and the natural fluctuation of acne. Conclusions Vitamin D deficiency was more frequent in patients with acne, and serum 25(OH)D levels were inversely correlated with acne severity, especially in patients with inflammatory lesions.

Baseline demographic and clinical characteristics of patients with acne and controls.

…

Flow diagram of randomized trial (CONSORT 2010 Flow Diagram).

…

Results of vitamin D deficiency according to influencing factors.

…

Percentages of patients with different vitamin D levels.

…

Vitamin D levels and disease severity (*P < 0.05, ***P < 0.001).

…

Figures - available via license: Creative Commons Attribution 4.0 International

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Available via license: CC BY 4.0

Content may be subject to copyright.

RESEARCH ARTICLE

Comparison of Vitamin D Levels in Patients

with and without Acne: A Case-Control Study

Combined with a Randomized Controlled

Trial

Seul-Ki Lim

, Jeong-Min Ha

, Young-Ho Lee

, Young Lee

, Young-Joon Seo

, Chang-

Deok Kim

, Jeung-Hoon Lee

, Myung Im

1Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea,

2Department of Anatomy, School of Medicine, Chungnam National University, Daejeon, Korea

*im1177@hanmail.net

Abstract

Background

Vitamin D plays an important role in the immune system, and its deficiency has been impli-

cated in various skin diseases, including atopic dermatitis and psoriasis. Acne is a common

inflammatory skin disease; however, the association with vitamin D remains unclear.

Objectives

We evaluated vitamin D levels in patients with acne to determine the effect of vitamin D

supplementation.

Methods

This study included 80 patients with acne and 80 healthy controls. Serum 25-hydroxyvita-

min D (25(OH)D) levels were measured, and demographic data were collected. Vitamin D-

deficient patients were treated with oral cholecalciferol at 1000 IU/day for 2 months.

Results

Deficiency in 25(OH)D was detected in 48.8% of patients with acne, but in only 22.5% of the

healthy controls. The level of 25(OH)D was inversely associated with the severity of acne,

and there was a significant negative correlation with inflammatory lesions. In a subsequent

trial, improvement in inflammatory lesions was noted after supplementation with vitamin D

in 39 acne patients with 25(OH)D deficiency.

Limitations

Limitations of the study include the small number of patients in the supplementation study

and the natural fluctuation of acne.

PLOS ONE | DOI:10.1371/journal.pone.0161162 August 25, 2016 1/11

a11111

OPEN ACCESS

Citation: Lim S-K, Ha J-M, Lee Y-H, Lee Y, Seo Y-J,

Kim C-D, et al. (2016) Comparison of Vitamin D

Levels in Patients with and without Acne: A Case-

Control Study Combined with a Randomized

Controlled Trial. PLoS ONE 11(8): e0161162.

doi:10.1371/journal.pone.0161162

Editor: Yiqun G. Shellman, University of Colorado

Denver School of Medicine, UNITED STATES

Received: November 5, 2015

Accepted: July 30, 2016

Published: August 25, 2016

article distributed under the terms of the Creative

Commons Attribution License, which permits

unrestricted use, distribution, and reproduction in any

medium, provided the original author and source are

credited.

Data Availability Statement: Data are available from

the Chungnam National University Hospital (E-mail:

cnuhirb@cnuh.co.kr, Phone: 82-42-280-6715).

Funding: The author(s) received no specific funding

for this work. This study was supported by a grantof

the Korea Healthcare technology R&D Project,

Ministry of Health & Welfare, Republic of Korea

(Grant No.: HI14C1379).

Competing Interests: The authors have declared

that no competing interests exist.

Conclusions

Vitamin D deficiency was more frequent in patients with acne, and serum 25(OH)D levels

were inversely correlated with acne severity, especially in patients with inflammatory

lesions.

Introduction

Acne is a common and complex skin disorder that distresses many patients because of its

chronicity. Although multiple factors contribute to acne development, chronic inflammation is

an important mechanism. Several inflammatory mediators such as cytokines, defensins, and

neuropeptides have been identified in acne lesions.[1] In addition, Propionibacterium acnes (P.

acnes) triggers cytokine activation by Toll-like receptors, which means that the innate immune

system is also important for acne development.[2]

Vitamin D has a number of functions in addition to its well-known role as a modulator of cal-

cium metabolism and homeostasis. It affects both the innate and adaptive immune system

through its effects on T and B lymphocytes, dendritic cells, and macrophages,[3,4] and it is asso-

ciated with systemic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythe-

matosus, and inflammatory bowel disease.[5,6] In dermatological diseases, it plays an important

role as an immune modulator in atopic dermatitis, psoriasis, vitiligo, and alopecia.[7–10]

A few in vitro studies have published data that support the theory that vitamin D has a func-

tional role in acne development. Identifying vitamin D receptors in human sebocytes and mod-

ulation of lipid and cytokine production by vitamin D suggest the possible association between

vitamin D and acne pathophysiology.[11–13] However, evidence is lacking regarding the clini-

cally relevant action of vitamin D in the development of acne, and its potential efficacy as a

therapeutic agent in acne also requires clarification. Accordingly, we evaluated vitamin D levels

in serum of acne patients compared to healthy controls, and the effects of vitamin D supple-

mentation. To the best of our knowledge, this is the first study to have investigated the role of

vitamin D in the pathogenesis and treatment of acne in a clinical setting.

Materials and Methods

Subjects

This case-control study included 80 patients with acne and 80 age- and sex-matched healthy

controls. All of the patients and controls were enrolled in this study from November 2014 to

February 2015 to avoid seasonal variation in vitamin D levels (recruitment end date, 28 Febru-

ary 2015; overall trial end date, 30 April 2015). Demographic data such as age, sex, body mass

index (BMI), smoking history, and sunscreen use were collected prior to enrollment. Exclusion

criteria prohibited enrollment of patients and controls who were receiving therapeutic inter-

ventions such as acne treatment, systemic corticosteroids, vitamin D supplements, or subjects

with concomitant inflammatory diseases. This study was approved by the Institutional Review

Board of Chungnam National University Hospital (CNUH 2014-07-013; date of approval, 24

July 2014). All of the subjects provided written informed consent before participating in the

study. We did not include children in this study; written consent was obtained from the sub-

jects themselves. This study was also approved by the ISRCTN registry (ISRCTN11007935;

date of approval, 15 October 2015). Because we were initially unaware of the ISRCTN registry,

the registration data were obtained after the study end date. The authors confirm that all ongo-

ing and related trials for this drug/intervention are registered.

Vitamin D and Acne

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Serum vitamin D analysis

Patients and controls had their serum 25-hydroxyvitamin D3 (25(OH)D) concentrations

measured. Blood samples were collected from veins and analyzed within 24 h of sampling

using the Roche Cobas e411 (Roche Diagnostics System, Switzerland). Levels of 25(OH)D

were categorized as adequate (>20 ng/mL), inadequate (12–20 ng/mL), or deficient (<12 ng/

mL) according to the guidelines set by the Food and Nutrition Board of the Institute of Medi-

cine.[14]

Vitamin D supplementation

A subsequent blinded controlled study was performed in acne patients with 25(OH)D defi-

ciency. Each of the 39 patients were provided with a unique patient number and randomly

assigned to one of two groups by computer: one group underwent 2-month oral administration

of cholecalciferol (one drop of 1000 IU/day), and the other group received an identical-appear-

ing placebo drop. Any other topical or systemic acne treatments, except for standard washing

and moisturizing, were not allowed. The patients were assessed at the beginning of treatment

and at 2, 4, and 8 weeks during treatment.(Fig 1)

Fig 1. Flow diagram of randomized trial (CONSORT 2010 Flow Diagram).

doi:10.1371/journal.pone.0161162.g001

Vitamin D and Acne

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Clinical assessment

Clinical assessments were performed by three blinded independent dermatologists, and their

objective assessments and inter-rater reliability were evaluated. Digital photographs at baseline

and at each follow-up visit were used for the clinical assessments. Counts of non-inflammatory

lesions (comedones) and inflammatory lesions (papules, pustules, and nodules) were also

made at each visit.

The severity of acne was assessed according to the global acne grading system (GAGS)

score.[15] GAGS divides the face, chest, and back into six areas (forehead, each cheek, nose,

chin, chest, and back) and assigns a factor to each area on the basis of the surface area and dis-

tribution/density of pilosebaceous units. 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: Factor × Grade (0–4). The global

score is the sum of the local scores, and acne severity is graded using the global score. A score

of 1–18 is considered mild; 19–30, moderate; 31–38, severe; and >39, very severe.

Statistical analysis

Statistical analyses were performed using SPSS version 15 (SSPS Inc., Chicago, IL). The chi-

square test was performed to compare the categorical data (Tables 1and 2). The correlation

between the serum vitamin D level and inflammatory acne lesions was evaluated using Pear-

son’s correlation analysis. Changes in the vitamin D levels after vitamin D supplementation

were evaluated with the Wilcoxon signed-rank test. The vitamin D levels according to disease

severity and the median percentile changes from baseline in acne lesions after vitamin D sup-

plementation were analyzed by the Kruskal–Wallis test followed by the Mann–Whitney U test

for post hoc comparison. Pvalues of <0.05 were considered statistically significant.

Results

The age, sex, BMI, smoking history, and use of sunscreen were the same when comparing the

two groups (Table 1). There were no significant differences in the mean 25(OH)D concentra-

tion between the groups, although it was lower in patients compared to the controls. However,

the prevalence of 25(OH)D deficiency was significantly higher in patients with acne compared

to healthy controls (48.8% vs. 22.5%; P= 0.019) (Table 1,Fig 2). The threshold of 25(OH)D

deficiency in this study was defined as <12 ng/mL, according to the guidelines set by the Food

and Nutrition Board of the Institute of Medicine.[14] The distribution pattern of the 25(OH)D

levels in the two groups showed the widest gap in the 12-ng/mL area (S1 Fig).

Table 1. Baseline demographic and clinical characteristics of patients with acne and controls.

Acne (n = 80) Controls (n = 80) Pvalue

Age (years) 20.9 ±4.1 21.0 ±5.7 0.768

Sex (F/M), n (%) 47/33 (58.6/41.4) 41/39 (51.3/48.7) 0.482

BMI (kg/m

)21.8 ±3.8 20.2 ±4.9 0.894

Smoking (yes), n (%) 16 (20.0) 11 (13.8) 0.645

Using sunscreen, n (%) 47 (58.8) 58 (72.5) 0.356

Serum 25(OH)D (ng/mL) 13.1 ±9.8 15.2 ±7.2 0.112

Vitamin D deﬁciency, n (%) 39 (48.8) 18 (22.5) 0.019*

All values are presented as mean ±SD unless otherwise stated. BMI, body mass index; 25(OH)D, 25-hydroxyvitamin D.

*P<0.05

doi:10.1371/journal.pone.0161162.t001

Vitamin D and Acne

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We determined whether vitamin D deficiency was influenced by any factor. No significant

correlation was seen between deficient 25(OD)D levels and age, sex, disease duration, BMI,

family history, smoking, sunscreen use, and trunk involvement. The only factor affecting 25

(OH)D deficiency was disease severity. In total, 15 of the 18 patients (83.3%) in the severe

group were 25(OH)D-deficient, whereas only 6 of the 27 (22.2%) patients in the mild group

were deficient (Table 2). In addition, the mean 25(OH)D concentration was inversely associ-

ated with the severity of acne (Fig 3). There was not a significant correlation between 25(OH)D

levels and the number of non-inflammatory lesions. However, the number of inflammatory

lesions was significantly and negatively correlated with vitamin D concentrations (r = −0.512;

P<0.001) (Fig 4), signifying a possible link between the extent of vitamin D deficiency and the

degree of acne inflammation.

We also assessed the therapeutic efficacy of vitamin D supplementation in acne patients

with 25(OD)D deficiency. The 39 patients showing vitamin D deficiency were randomly

assigned to the vitamin D (n = 20) or placebo (n = 19) group. The two groups did not

Table 2. Results of vitamin D deficiency according to influencing factors.

Total Mean 25(OH)D Vitamin D Deﬁciency Pvalue

no. (ng/mL) n (%)

Age (years)

<20 36 13.19 ±2.8 20 (55.6)

20 44 11.01 ±1.8 19 (43.2) 0.624

Sex

M 33 11.22 ±3.8 17 (53.1)

F 47 12.98 ±3.2 22 (46.9) 0.892

Duration (years)

<3 41 10.89 ±1.8 24 (58.5)

3 39 13.31 ±2.2 15 (38.5) 0.211

BMI (kg/m

)

Normal or less (<23) 50 10.89 ±1.4 28 (56.0)

Overweight or obese (23) 30 13.31 ±1.2 11 (36.7) 0.189

Family history

No 58 9.99 ±1.4 30 (51.7)

Yes 22 14.21 ±0.5 9 (40.9) 0.503

Smoking

No 64 10.44 ±0.8 29 (45.3)

Yes 16 13.76 ±1.8 10 (62.5) 0.412

Using sunscreen

No 33 13.51 ±1.2 14 (42.4)

Yes 47 10.69 ±0.6 25 (53.2) 0.398

Trunk lesions

No 54 15.56 ±1.3 22 (40.7)

Yes 26 8.69 ±0.7 17 (65.3) 0.098

Disease severity

Mild 27 17.37 ±0.6 6 (22.2)

Moderate 35 11.89 ±1.0 18 (51.4)

Severe 18 7.04 ±0.5 15 (83.3) 0.002**

25(OH)D values are presented as mean ±SD. Pvalues are for comparison of vitamin D deﬁciency. BMI, body mass index; 25(OH)D, 25-hydroxyvitamin D.

**P<0.01

doi:10.1371/journal.pone.0161162.t002

Vitamin D and Acne

PLOS ONE | DOI:10.1371/journal.pone.0161162 August 25, 2016 5/11

significantly differ by any demographic or clinical factor. Vitamin D supplementation for 2

months resulted in a statistically significant increase in 25(OH)D levels (P<0.001) (Fig 5A)

and produced a clinical improvement compared to placebo (Fig 5B). There were no differences

in the non-inflammatory and total lesion counts between the groups. However, the inflamma-

tory lesions showed a statistically significant improvement in the vitamin D group compared

with the control group (P<0.05). Inflammatory lesions in the vitamin D group decreased by

34.6% after 8 weeks of treatment, whereas those in the control group decreased by 5.8% (Fig

5C). None of the patients reported discontinuation of the intervention, and there were no

adverse events.

Discussion

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

Fig 2. Percentages of patients with different vitamin D levels.

doi:10.1371/journal.pone.0161162.g002

Fig 3. Vitamin D levels and disease severity (*P<0.05, ***P<0.001).

doi:10.1371/journal.pone.0161162.g003

Vitamin D and Acne

PLOS ONE | DOI:10.1371/journal.pone.0161162 August 25, 2016 6/11

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 lev-

els 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.

[19]

To understand the vitamin D status associated with acne patients, we investigated the fac-

tors 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 associ-

ated 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 die-

tary 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 derma-

titis, 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.

Fig 4. Correlation between vitamin D levels and inflammatory acne.

doi:10.1371/journal.pone.0161162.g004

Vitamin D and Acne

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In the randomized controlled trial of 39 acne patients with vitamin D deficiency, oral vita-

min D supplementation produced a significant improvement in acne inflammation. In con-

trast, a previous study found no effect of vitamin D supplementation on acne lesions.[25]

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 metallo-

proteinase 9, is reduced by treatment with vitamin D in cultured sebocytes.[12] 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.[13] In addi-

tion, vitamin D has antimicrobial effects by inducing antimicrobial peptides such as LL-37 in

human sebocytes.[26] 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

Fig 5. Clinical effects of vitamin D supplementation in patients with acne. (A) Change in vitamin D levels after vitamin D supplementation

(***P<0.001). (B) Photographs showing clinical improvement in a patient with acne. Photographs showing baseline (left) and last visit (right).

doi:10.1371/journal.pone.0161162.g005

Vitamin D and Acne

PLOS ONE | DOI:10.1371/journal.pone.0161162 August 25, 2016 8/11

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 natu-

ral 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.

Supporting Information

S1 Fig. Distribution pattern of 25(OH)D levels in patients and controls. The horizontal axis

represents the 25(OH)D levels (ng/mL), and the vertical axis represents the cumulative fre-

quency of 25(OH)D levels (%).

(JPG)

S1 File. CONSORT 2010 Checklist.

(DOC)

S2 File. Study information and protocol.

(DOCX)

S3 File. Study information and protocol (Original language).

(DOCX)

Acknowledgments

This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry

of Health & Welfare, Republic of Korea (Grant No.: HI14C1379).

A preliminary version of the results was presented in the 67

annual meeting of Korean der-

matological association.

Author Contributions

Conceptualization: MI YL YJS CDK JHL.

Data curation: MI SKL.

Formal analysis: MI YHL.

Funding acquisition: MI CDK JHL.

Investigation: SKL.

Methodology: MI SKL.

Project administration: MI.

Resources: SKL.

Vitamin D and Acne

PLOS ONE | DOI:10.1371/journal.pone.0161162 August 25, 2016 9/11

Software: MI YHL.

Supervision: MI JHL.

Validation: MI YHL.

Visualization: MI.

Writing –original draft: SKL JMH.

Writing –review & editing: MI.

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Immunol.2014; 134:831–5.

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To what Extent does Vitamin D and its Serum Levels Influence the Severity of Hidradenitis Suppurativa: A Literature Review

Article

Full-text available

Sep 2024
ACTA DERM-VENEREOL

Vitamin D plays a role in inflammatory skin conditions and can improve them. Hidradenitis suppurativa (HS) is an autoinflammatory chronic skin disease in which most patients exhibit a hypovitaminosis D. However, it is uncertain whether vitamin D supplementation could relieve the severity of HS. A systematic literature search of PubMed and Web of Science was conducted on 4 September 2023. Studies that investigated vitamin D and its potential implications for the severity of HS were included. In contrast, studies that focused on the prevalence of vitamin D deficiency were excluded, as well as studies on syndromic HS. Seven studies with a total of 575 patients were included in the qualitative synthesis, of which 3 utilized a cross-sectional design, 2 were pilot studies, 1 a controlled cohort study, and 1 a prospective case-control study. In all included studies, HS patients were vitamin D deficient. There was evidence indicating that serum vitamin D levels negatively correlated with the severity of the disease, and at least suggestive evidence that vitamin D supplementation could have a positive impact on the course of HS. To better understand these correlations, conducting a randomized controlled trial study on vitamin D and its effects on HS severity is imperative.

Role of vitamin D supplement adjunct to topical benzoyl peroxide in acne: a randomized double-blinded controlled study

Article

Full-text available

Jul 2024

Background Acne is an inflammatory condition of the pilosebaceous unit. Previous studies have established a link between acne and vitamin D deficiency and the potential effectiveness of vitamin D supplementation in treatment. However, the efficacy of vitamin D as an adjuvant treatment for acne remains unknown. Objective To evaluate the efficacy of weekly vitamin D2 oral administration as an adjunctive treatment to standard topical care for acne. Methods This study was a randomized, double-blind, placebo-controlled trial including subjects with mild-to-moderate acne. Topical 2.5% benzoyl peroxide was applied twice daily for 12 weeks to all subjects. Subjects were randomly allocated to receive either oral vitamin D2 40,000 IU weekly or placebo weekly during the treatment period. No additional treatment was administered during the 4-week follow-up period. Results A total of 44 subjects were included in this study. All of them had inadequate 25(OH)D levels. Both regimens showed significant improvement in acne during the treatment period. Weekly vitamin D2 supplementation significantly prevented the relapse of inflammatory acne lesions ( P = .048) at the follow-up visit. No adverse effects or biochemical changes were observed. Limitations There were no subjects of severe acne vulgaris. Conclusion Adjunctive weekly vitamin D2 supplementation to standard topical benzoyl peroxide could reduce relapses of inflammatory lesions in mild-to-moderate acne.

Higher insulin resistance is associated with decreased expression of the vitamin D receptor gene in obese type II diabetic patients with vitamin D deficiency

Article

Sep 2024

The Background: The etiology of numerous medical conditions, such as metabolic irregularities, is interconnected with the insufficiency of vitamin D. Furthermore, a theoretical association between the resistance to insulin and the insufficiency of vitamin D has been postulated. This concept is substantiated by empirical evidence obtained through various investigations. The objective of this investigation is to analyze and investigate the significance and influence of vitamin D and the expression of the vitamin D receptor (VDR) gene in the progression of insulin resistance in individuals with T2DM. Methods: The study was carried out 100 type II diabetic patients and 100 healthy controls. Both groups had anthropometry examinations to determine their weights, heights, hip and waist circumferences. Fasting glucose, insulin, insulin resistance (HOMA-IR), and vitamin D levels were all measured. Quantitative real-time PCR was used to analyze the expression of VDR genes in both groups. The folding change was computed using the conventional 2-(∆∆ct) technique. Results: T2DM patients had higher levels of all anthropological measurements, and biochemical parameters compared to controls. Patients had lower levels VDR folding change and vitamin D levels. The diagnostic accuracy of anthropological assessments and biochemical parameters in prediction disease showed significant results. VDR gene expression has a highly significant negative linear association with insulin resistance in obese with vitamin D deficiency patients. Also, negative linear correlation noted between insulin resistance and serum vitamin D levels without significant variation. Conclusion: VDR gene expression and insulin resistance were connected in obese patients T2DM with vitamin D insufficiency..

Higher insulin resistance is associated with decreased expression of the vitamin D receptor gene in obese type II diabetic patients with vitamin D deficiency

Article

Full-text available

Sep 2024

New Insights Into Systemic Drivers of Inflammation and Their Contributions to the Pathophysiology of Acne

Article

Feb 2024

Acne Vulgaris (AV) is a prominent skin disease commonly affecting teenagers. It often persists into adulthood and is associated with adverse physical and psychosocial impacts. The pathophysiology of AV is conventionally correlated with 4 factors within and around the pilosebaceous unit: increased sebum production, follicular hyperkeratinization, Cutibacterium acnes proliferation, and localized immune responses. As such, conventional therapeutic approaches for AV have primarily focused on these factors. In addition to this primarily localized pathophysiology, there is a progressively emerging body of evidence indicating that underlying systemic factors contributing to a generalized immuno-inflammatory response can contribute to or exacerbate AV. In this article, we introduce and provide the supporting data, for 6 patient-centric systems that may be implicated in the development of AV: psycho-emotional stress, diet and metabolism, dysbiosis of the gut and skin microbiome, hormonal fluctuations, oxidative stress, and immune response. Identifying these pathways and their contributions in a patient-centric approach may provide expanded therapeutic opportunities for treating patients with AV. J Drugs Dermatol. 2024;23(2):90-96. doi:10.36849/JDD.8137.

Serum Vitamin D levels in acne vulgaris patients and the impact of patient’s clinical characteristics: a case–control study

Article

Sep 2024
ARCH DERMATOL RES

Vitamin D Receptor Regulates the Expression of the Grainyhead-Like 1 Gene

Article

Full-text available

Jul 2024
INT J MOL SCI

Vitamin D plays an important pleiotropic role in maintaining global homeostasis of the human body. Its functions go far beyond skeletal health, playing a crucial role in a plethora of cellular functions, as well as in extraskeletal health, ensuring the proper functioning of multiple human organs, including the skin. Genes from the Grainyhead-like (GRHL) family code for transcription factors necessary for the development and maintenance of various epithelia. Even though they are involved in many processes regulated by vitamin D, a direct link between vitamin D-mediated cellular pathways and GRHL genes has never been described. We employed various bioinformatic methods, quantitative real-time PCR, chromatin immunoprecipitation, reporter gene assays, and calcitriol treatments to investigate this issue. We report that the vitamin D receptor (VDR) binds to a regulatory region of the Grainyhead-like 1 (GRHL1) gene and regulates its expression. Ectopic expression of VDR and treatment with calcitriol alters the expression of the GRHL1 gene. The evidence presented here indicates a role of VDR in the regulation of expression of GRHL1 and correspondingly a role of GRHL1 in mediating the actions of vitamin D.

Vitamin D and Skin

Chapter

May 2024

Skin and its associated structures together help in protection of internal body organs against, harmful effects of external environment. Epidermis, the outer layer acts as a protective barrier against harmful substances. Disturbed functions of skin result in different diseases which lead to adverse impact on physical as well as psychological state of patients. Some systemic diseases including autoimmune disease also have skin manifestations. Thus, condition of skin can reflect not only its status but also pathological changes in the internal organs [1]. Dermatologists are always in search of effective and well tolerated therapies for addressing concerns related to skin disorders or skin manifestations of other systemic disorders.

C‐reactive protein as a novel biomarker for vitamin D deficiency in alopecia areata

Article

Full-text available

Mar 2024
SKIN RES TECHNOL

Background Alopecia areata (AA) is an autoimmune condition characterized by sudden and unpredictable hair loss, with a lifetime incidence of 2%. AA can be divided into three categories: patchy alopecia, alopecia totalis, and alopecia universalis. It can affect a person's psychological health and overall quality of life. Elevated C‐reactive protein (CRP) levels in the liver may indicate an inflammatory response in autoimmune diseases. Vitamin D, essential for immune system control and skin health, may be related to AA. Hair follicles contain vitamin D receptors, which control immunological responses in the skin. However, no study has found a relationship between CRP and vitamin D in AA patients in our region. Subjects and Methods An analytical cross‐sectional study with a case‐control design research investigation of 82 AA patients and 81 healthy controls was carried out. Both groups’ medical histories were taken. Biochemical analysis was done for both groups as well as the serum vitamin D levels, and CRP. Genetic analysis for CDX2 rs11568820 variant detected by PCR (T‐ARMS‐PCR) method and vitamin D receptor (VDR) gene expression measured by real‐time PCR analysis for both patients and healthy subjects. Results CRP levels are higher in AA patients, AA patients with G/G genotypes exhibited higher concentrations of CRP when compared to those with A/A and A/G genotypes while patients with A/A genotypes have higher levels of Serum vitamin D as compared to the A/G and G/G genotypes. G allele was more abundant in AA patients. VDR gene expression was lower in AA compared to control and lower in ophiasis compared to localized and multiple patchy AA. An important inverse linear correlation was observed between vitamin D and CRP levels in ophiasis AA. Conclusion CRP concentrations were found to be elevated in AA patients. The considerable accuracy of CRP in the diagnosis of AA is substantiated by a statistically significant al. A noteworthy inverse linear association was observed between serum vitamin D and CRP concentrations in ophiasis AA.

Diet and Acne: Should Teenagers Avoid Pizza and Chocolate?

Chapter

Dec 2023

Michael S. Kramer

Acne is a skin disease originating in the sebaceous (oil) glands around the time of puberty that usually improves in the late teens or twenties. Its development and peak severity in adolescence may have led to suspicion about the causal role of teen dietary preferences for pizza, other oily foods, dairy products, and chocolate. Beliefs about the causal role of these dietary preferences are highly prevalent among adolescents and young adults around the world. Most studies of diet and acne have been cross-sectional in design and do not permit cause-and-effect inferences. Randomized trials of adding or eliminating specific foods have been published only for chocolate, which has been shown not to affect acne severity. Oral zinc supplements, however, do appear effective in reducing its severity.

Factors Affecting 25-Hydroxyvitamin D Concentration in Response to Vitamin D Supplementation

Article

Full-text available

Jun 2015

Sun exposure is the main source of vitamin D. Due to many lifestyle risk factors vitamin D deficiency/insufficiency is becoming a worldwide health problem. Low 25(OH)D concentration is associated with adverse musculoskeletal and non-musculoskeletal health outcomes. Vitamin D supplementation is currently the best approach to treat deficiency and to maintain adequacy. In response to a given dose of vitamin D, the effect on 25(OH)D concentration differs between individuals, and it is imperative that factors affecting this response be identified. For this review, a comprehensive literature search was conducted to identify those factors and to explore their significance in relation to circulating 25(OH)D response to vitamin D supplementation. The effect of several demographic/biological factors such as baseline 25(OH)D, aging, body mass index(BMI)/body fat percentage, ethnicity, calcium intake, genetics, oestrogen use, dietary fat content and composition, and some diseases and medications has been addressed. Furthermore, strategies employed by researchers or health care providers (type, dose and duration of vitamin D supplementation) and environment (season) are other contributing factors. With the exception of baseline 25(OH)D, BMI/body fat percentage, dose and type of vitamin D, the relative importance of other factors and the mechanisms by which these factors may affect the response remains to be determined.

Preliminary evidence for vitamin D deficiency in nodulocystic acne

Article

Full-text available

Jan 2015

Abstract Objective: Acne vulgaris is a chronic inflammatory disease, and hormonal influences, follicular plugging and follicular hyperkeratinization, increased sebum secretion, Propionibacterium acnes colonization, and inflammation are involved in its pathogenesis. Recently, a significant body of evidence has accumulated that describes the comedolytic properties of vitamin D and its roles as a modulator of the immune system, a regulator of the proliferation and differentiation of sebocytes and keratinocytes, and as an antioxidant. In this study, we aimed to compare serum vitamin D levels in a group of patients with nodulocystic acne with vitamin D levels in a group of control subjects to determine whether there was any relationship between the vitamin D and acne. Methods: Levels of 25-hydroxyvitamin D (25[OH]D) were measured in 43 patients with newly diagnosed nodulocystic acne and in 46 healthy control subjects, and participants were grouped according to their 25[OH]D levels as follows: normal/sufficient (>20 ng/mL) or insufficient/deficient (<20 ng/mL). Serum concentrations of calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and parathyroid hormone (PTH) were measured. Results: Forty-three patients and 46 control individuals, with mean ages of 23.13 (± 5.78) years and 25.23 (± 4.73) years, respectively, were included in this study. There were no significant differences between the groups in relation to their body mass indices and Ca, P, ALP, and PTH levels. However, the patients with nodulocystic acne had significantly lower 25[OH]D levels than the subjects in the control group (P< 0.05). Conclusion: The patients with nodulocystic acne had relatively low serum vitamin D levels compared with the subjects in the control group. The findings from this study suggest that there is a connection between low vitamin D levels and acne. Larger epidemiologic studies are needed to confirm the status of vitamin D levels in patients with acne.

The effect of calcium and vitamin D supplementation on menstrual cycle, body mass index and hyperandrogenism state of women with poly cystic ovarian syndrome

Article

Full-text available

Sep 2014
J Res Med Sci

Poly cystic ovary syndrome (PCOS) is considered one of the most common endocrine disorders of women in reproductive age. The aim of this study was evaluating the efficacy of calcium and Vitamin D supplementation on the regularity of menstrual cycles, body mass index (BMI) and hyper androgenism state of women with PCOS. In this clinical trial, 80 women with PCOS were evaluated. They randomly located in four groups receiving metformin (group 1), metformin plus calcium and Vitamin D (group 2), calcium and Vitamin D (group 3) and placebo (group 4) for 4 months. BMI, regularity of menstrual cycles, hyperandrogenism (hirsutism and acne) and serum calcium and Vitamin D levels were compared in four studying groups at baseline and 4 months after the trial. All studied subjects were similar at baseline (P > 0.05). After trial, the frequency of hirsutism and acne were not different among groups. Frequency regular menstrual cycle and dominant follicle were significantly higher in group 1 and 2 than others (P < 0.05). After trial, there was no significant difference with respect to BMI among groups. Vitamin D and calcium supplementation in addition to metformin therapy in women with PCOS could result in a better outcome in a variety of PCOS symptoms including menstrual regularity, and ovulation.

Propionibacterium acnes Induces an IL-17 Response in Acne Vulgaris that Is Regulated by Vitamin A and Vitamin D

Article

Full-text available

Aug 2013
J INVEST DERMATOL

Acne vulgaris is the most common skin disorder affecting millions of people worldwide and inflammation resulting from the immune response targeting Propionibacterium acnes plays a significant role in its pathogenesis. In this study, we have demonstrated that P. acnes is a potent inducer of Th17 and Th1, but not Th2 responses in human PBMCs. P. acnes stimulated expression of key Th17-related genes, including IL-17A, RORα, RORc, IL-17RA and IL-17RC, and triggered IL-17 secretion from CD4(+), but not CD8(+) T cells. Supernatants from P. acnes-stimulated PBMCs were sufficient to promote the differentiation of naïve CD4(+)CD45RA T cells into Th17 cells. Furthermore, we found that the combination of IL-1β, IL-6 and TGF-β neutralizing antibodies completely inhibited P. acnes-induced IL-17 production. Importantly, we showed that IL-17-expressing cells were present in skin biopsies from acne patients but not from normal donors. Finally, vitamin A (all-trans retinoic acid) and vitamin D (1,25-dihydroxyvitamin D3) inhibited P. acnes-induced Th17 differentiation. Together, our data demonstrate that IL-17 is induced by P. acnes and expressed in acne lesions and that both vitamin A and vitamin D could be effective tools to modulate Th17-mediated diseases such as acne.Journal of Investigative Dermatology accepted article preview online, 7 August 2013. doi:10.1038/jid.2013.334.

Vitamin D Supplementation Modulates the Immune System and Improves Atopic Dermatitis in Children

Article

Mar 2015
INT ARCH ALLERGY IMM

Vitamin D seems to influence the evolution of atopic dermatitis (AD) in children. We tested the vitamin D serum levels of 39 children with AD (AD group t0) and of 20 nonallergic healthy controls (C group). AD severity was evaluated using the AD scoring system (SCORAD index). Cytokine serum levels (IL-2, IL-4, IL-6, IFN-γ, TNF-α) and atopy biomarkers were also measured. The patients were then treated with vitamin D oral supplementation of 1,000 IU/day (25 mg/day) for 3 months. We then reevaluated the vitamin D serum levels, AD severity and cytokine serum levels in all of the treated children (AD group t1). The cross-sectional analysis on patients affected by AD (AD group t0) showed that the initial levels of all the tested cytokines except for TNF-α were higher than those of the healthy control group (C group), falling outside the normal range. After 3 months of supplementation the patients had significantly increased vitamin D levels (from 22.97 ± 8.03 to 29.41 ± 10.73 ng/ml; p = 0.01). A concomitant significant reduction of both the SCORAD index (46.13 ± 15.68 at the first visit vs. 22.57 ± 15.28 at the second visit; p < 0.001) and of all the altered cytokines (IL-2, IL-4, IL-6, IFN-γ) was also found. This study showed vitamin D supplementation to be an effective treatment in reducing AD severity in children through normalization of the Th1 and Th2 interleukin serum pattern. © 2015 S. Karger AG, Basel.

Randomized trial of vitamin D supplementation for winter-related atopic dermatitis in children

Article

Oct 2014
J ALLERGY CLIN IMMUN

Background Epidemiologic and preclinical data, and a small randomized trial in Boston, suggest that vitamin D supplementation may improve winter-related atopic dermatitis (AD). Objective To determine the effect of vitamin D supplementation on winter-related AD. Methods We performed a randomized, double-blind, placebo-controlled trial of Mongolian children with winter-related AD (clinicaltrials.gov identifier: NCT00879424). Baseline eligibility included age 2 to 17 years, AD score 10 to 72 using the Eczema Area and Severity Index (EASI), and winter-related AD (eg, history of AD worsening during the fall-to-winter transition). Subjects were enrolled in Ulaanbaatar during winter and randomly assigned to oral cholecalciferol (1000 IU/day) versus placebo for 1 month. All children and parents received emollient and patient education about AD and basic skin care. The main outcomes were changes in EASI score and in Investigator's Global Assessment. Results The 107 enrolled children had a mean age of 9 years (SD 5), and 59% were male. Their median age of AD onset was 3 months (interquartile range 2 months to 1 year) and mean EASI score at baseline 21 (SD 9). One-month follow-up data were available for 104 (97%) children. Compared with placebo, vitamin D supplementation for 1 month produced a clinically and statistically significant improvement in EASI score (adjusted mean change: −6.5 vs −3.3, respectively; P = .04). Moreover, change in Investigator's Global Assessment favored vitamin D over placebo (P = .03). There were no adverse effects in either group. Conclusion Vitamin D supplementation improved winter-related AD among Mongolian children, a population likely to have vitamin D deficiency in winter.

Vitamin D Deficiency in Alopecia Areata

Article

Mar 2014
BRIT J DERMATOL

Background Alopecia areata is a T-cell mediated autoimmune disease that causes inflammation around anagen-stage hair follicles. Deficient vitamin D levels have been implicated in patients with a variety of autoimmune diseases in recent years. Previous reports have described the effects of vitamin D on hair follicles.Objectives The aim of the study was to evaluate the status of vitamin D in patients with alopecia areata and the relationship between vitamin D levels and disease severity.MethodsA cross-sectional study was conducted of 86 patients with alopecia areata, 44 patients with vitiligo, and 58 healthy controls. Serum vitamin D levels of the study group were determined by liquid chromatography/tandem mass spectrometry.ResultsSerum 25(OH)D levels in patients with alopecia areata were significantly lower than those of the patients with vitiligo and the healthy controls (P= 0.001 and P<0.001, respectively). The prevalence of 25(OH)D deficiency was significantly higher in the patients with alopecia areata (90.7%) compared with the patients with vitiligo (70.5%) and the healthy controls (32.8%) (P= 0.003 and P<0.001, respectively). Furthermore, a significant inverse correlation was found between disease severity and serum 25(OH)D level in the patients with alopecia areata (r= - 0.409; P<0.001).Conclusion Deficient serum 25(OH)D levels are present in alopecia areata patients and inversely correlate with disease severity. Accordingly, screening alopecia areata patients for vitamin D deficiency seems to be of value for the possibility of vitamin D supplementation.This article is protected by copyright. All rights reserved.

Low Vitamin D levels are associated with atopic dermatitis, but not allergic rhinitis, asthma, or IgE sensitization, in the adult Korean population

Article

Dec 2013

The effect of vitamin D on allergic conditions is unclear. In particular, large-scale, population-based studies examining this relationship in adult Asian populations are lacking. To evaluate the association between serum vitamin D levels and allergic conditions in the general adult Korean population. A cross-sectional study was performed by using data collected from 15,212 individuals 19 years or older who participated in the Korean National Health and Nutrition Examination Survey from 2008 to 2010. The confounder-adjusted mean serum 25-hydroxyvitamin D (25[OH]D) levels of participants with and without allergic conditions (including atopic dermatitis, asthma, allergic rhinitis, and increased total and allergen-specific serum IgE) were compared by using multiple linear regression analyses. Multiple logistic regression analyses with confounder adjustment estimated the odds ratios (ORs) for developing each condition according to adequate, inadequate, or deficient serum 25(OH)D levels. After adjusting for potential confounders, mean serum 25(OH)D levels were significantly lower in participants diagnosed with atopic dermatitis than in those without this diagnosis (mean ± SE, 18.58 ± 0.29 ng/mL vs 19.20 ± 0.15 ng/mL; P = .02). Compared with participants with adequate vitamin D levels (≥20 ng/mL), confounder-adjusted ORs of atopic dermatitis were significantly higher in those with inadequate (12-19.99 ng/mL) or deficient (<12 ng/mL) levels (OR [95% CI], 1.50 [1.10-2.06] and 1.48 [1.04-2.12], respectively; P = .02). This relationship was not observed in participants with the other allergic conditions. Vitamin D-insufficient adult individuals within the general Korean population have an increased likelihood of atopic dermatitis, but not asthma, allergic rhinitis, or IgE sensitization.

The Role of Inflammation in the Pathology of Acne

Article

Sep 2013

Emil Tanghetti

The conventional perspective of acne pathogenesis holds that Propionibacterium acnes colonizes the duct of the sebaceous follicle, causing an innate immune response and the progression from a so-called noninflammatory comedo to an inflammatory papule, pustule, or nodule. However, this viewpoint has come under increasing scrutiny over the last decade, as evidence has emerged supporting a role for inflammation at all stages of acne lesion development, perhaps subclinically even before comedo formation. The immunochemical pathways underlying the initiation and propagation of the inflammation in acne are complex and still being elucidated, but may involve Propionibacterium acnes as well as several inflammatory mediators and their target receptors, including cytokines, defensins, peptidases, sebum lipids, and neuropeptides. This review presents evidence to support the notion that acne is primarily an inflammatory disease, challenging the current nomenclature of noninflammatory versus inflammatory acne lesions and suggesting that the nomenclature is outdated and incorrect. The evidence in support of acne as an inflammatory disease also has clinical implications, in that anti-inflammatory drugs used to treat the disease can be expected to exert effects against all lesion stages, albeit via distinct mechanisms of anti-inflammation.

Expression of Inflammatory Biomarkers from Cultured Sebocytes was Influenced by Treatment with Vitamin D

Article

Jul 2013

Inflammatory cytokines are the key factor in the pathophysiology of acne. It is well known that keratinocytes synthesize many kinds of inflammatory cytokines. In addition, it is reported that inflammatory cytokines are also expressed from sebocytes, which originate from the same stem cells with keratinocytes. To clarify changes in the expression of inflammatory biomarkers from cultured sebocytes after treatment with vitamin D. Reverse transcription-polymerase chain reaction (RT-PCR) was done to measure changes in the expression of inflammatory biomarkers, including interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor-α (TNF-α), and several subtypes of matrix metalloproteinases (MMPs) after treatment of a group of cultured sebocytes with vitamin D. Vitamin D receptor (VDR) small interfering RNA (siRNA) was added in the other group of cultured sebocytes to assure the role of vitamin D on the expression of inflammatory biomarkers. Enzyme-linked immunosorbent assay (ELISA) was also performed in the vitamin D-treated sebocytes. Cultured sebocytes showed non-significant changes in the gene expression of inflammatory biomarkers after treatment with vitamin D. In cultured sebocytes treated with a VDR siRNA, the expression of inflammatory biomarkers was not blocked after treatment with vitamin D. ELISA showed a significant decrease in the expression of IL-6, IL-8, and MMP-9, but a significant increase in the expression of MMP-1 and MMP-3, after treatment with vitamin D (10(-6) M). Expression of inflammatory biomarkers is influenced by treatment with vitamin D in cultured sebocytes, but not through VDR.