A randomized controlled double-blind investigation of the effects of vitamin D dietary supplementation in subjects with atopic dermatitis

Abstract

Background: Subjects with atopic dermatitis (AD) have defects in antimicrobial peptide (AMP) production possibly contributing to an increased risk of infections. In laboratory models, vitamin D can alter innate immunity by increasing AMP production.

Objective: To determine if AD severity correlates with baseline vitamin D levels, and to test whether supplementation with oral vitamin D alters AMP production in AD skin.

Methods: This was a multi-centre, placebo-controlled, double-blind study in 30 subjects with AD, 30 non-atopic subjects, and 16 subjects with psoriasis. Subjects were randomized to receive either 4000 IU of cholecalciferol or placebo for 21 days. At baseline and day 21, levels of 25-hydroxyvitamin D (25OHD), cathelicidin, HBD-3, IL-13, and Eczema Area and Severity Index (EASI) and Rajka-Langeland scores were obtained.

Results: At baseline, 20% of AD subjects had serum 25OHD below 20 ng/mL. Low serum 25OHD correlated with increased Fitzpatrick Skin Type and elevated BMI, but not AD severity. After 21 days of oral cholecalciferol, mean serum 25OHD increased, but there was no significant change in skin cathelicidin, HBD-3, IL-13 or EASI scores.

Conclusions: This study illustrated that darker skin types and elevated BMI are important risk factors for vitamin D deficiency in subjects with AD, and highlighted the possibility that seasonality and locale may be potent contributors to cathelicidin induction through their effect on steady state 25OHD levels. Given the molecular links between vitamin D and immune function, further study of vitamin D supplementation in subjects with AD is warranted.

Conflict of interest statement

The authors have no conflict of interest to declare

© 2013 European Academy of Dermatology and Venereology.

Figures

Figure 1. Association of baseline serum 25OH vitamin D levels with skin pigmentation, body mass index and atopic disease severity

Atopic Dermatitis subjects with darkest skin pigmentation as measured at Fitzpatrick Skin Type V/VI had significantly lower serum 25OH vitamin D levels (mean= 18.8 ng/ml) compared to Type III/IV (mean= 28.7 ng/ml; p=0.04).

Figure 2. Association of baseline serum 25OH vitamin D levels with body mass index and atopic disease severity

A: Scatterplot of serum 25OH vitamin D levels versus body mass index (BMI) showed a significant negative correlation (r=−0.38, p=0.04) with lower vitamin D levels associated with higher BMI. B: Scatterplot of baseline 25OH vitamin D levels versus atopic disease severity as measured by Rajka-Langeland scores showed no correlation (r=0.04, p=0.85).

Figure 3. Baseline relative abundance of cathelicidin, HBD-3 and IL-13 mRNA in lesional and non-lesional skin in subjects with atopic dermatitis and psoriasis

A: Cathelicidin gene (CAMP) mRNA expression from skin biopsies as measured by qRT-PCR in lesional (L) and non-lesional (NL) skin of atopics (AD), psoriatics (Psor) and skin of non-atopic (NA) control subjects. B: Human beta-defensin-3 (HBD-3) mRNA expression from skin biopsies as determined in figure 2A. C: Interleukin-13 (IL-13) mRNA expression from skin biopsies as determined in figure 2A. All data are normalized to expression of GAPDH mRNA and mean value determined for NA skin. Both cathelicidin and HBD-3 levels were significantly higher in lesional psoriatic skin compared to controls (p<0.01 and p< 0.01, respectively), and HBD-3 in AD lesional skin was significantly lower than lesional skin in psoriatics (p<0.01). IL-13 levels were higher in AD lesional and non-lesional skin compared to controls (p=0.01 and p=0.02, respectively).

Figure 4. Cathelicidin and HBD-3 mRNA abundance in lesional skin by diagnostic group at screening and after 21days of oral vitamin D3

A: Cathelicidin (CAMP) mRNA measured as in Figure 2 at initial study screening (Scr) visit and after 21 days of supplementation with oral vitamin D3 at 4000IU/day (21) in subjects with atopic dermatitis (AD) and Psoriasis receiving active oral vitamin D. B: Human beta-defensin-3 (HBD-3) mRNA measured as in A. All data are normalized to expression of GAPDH mRNA and mean value determined for non-atopic control skin. Box plot data are shown with median, mean (+), upper and lower quartiles, minimum value and maximum value. Data showed no significant change in the means following supplementation. AD subjects (n=15), Psoriasis subjects (n=8)

Figure 5. Vitamin D serum 25OHD levels by diagnostic group at screening and after 21days of oral vitamin D3

Serum 25OH vitamin D measured at initial study screening (Scr) visit and after 21 days of supplementation with oral vitamin D3 at 4000IU/day (21) for subjects receiving actual oral vitamin D. Box plot data are shown with median, mean (+), upper and lower quartiles, minimum value and maximum value. Data showed a significant increase in serum vitamin D levels in AD and non-atopic (NA) control subjects after 21 days of vitamin D supplementation (p

Figure 6. Relationship between the change in lesional IL-13 mRNA and change in 25OHD after 21days of oral vitamin D3

A: Scatterplot of screening serum 25OHD levels (ng/ml) versus change in 25OHD from screening after the end of supplementation showed that AD subjects with the lowest vitamin D levels had the greatest increase in vitamin D (r= −0.77, p<0.01). The non-atopic controls and psoriatic subjects did not exhibit the same association. B) Scatterplot of change in serum 25OHD versus change in log relative abundance of IL-13 mRNA in AD lesional skin measured by qPCR as described in Figure 2. A weak trend was observed for decreasing change in IL-13 with increasing change in serum 25OHD (r=−0.36, p=0.06).

Figure 7. Baseline cathelicidin mRNA and serum 25OHD distinguished by site

A: Cathelicidin mRNA measured at initial study screening (Scr) visit and after 21 days of supplementation in subjects with AD (n=15) and Psoriasis (n=8) receiving active oral vitamin D stratified by site. Data is normalized to GAPDH mRNA and mean value determined from non-atopic control skin. Portland had a statistically significant decrease in cathelicidin when compared to San Diego and Denver both at day 0 and day 21 (*p=0.006,** p=0.001) B: We then compared baseline 25OHD in Portland as compared to the San Diego and Denver sites. Portland subjects (mean = 23.7 ng/mL) showed a significantly lower 25OHD level as compared to the other sites (mean=32.8 ng/mL) at baseline, controlling for Fitzpatrick skin type (p=0.0287).