A randomized clinical trial in vitamin D-deficient adults comparing replenishment with oral vitamin D3 with narrow-band UV type B light: effects on cholesterol and the transcriptional profiles of skin and blood

Abstract

Background: Vitamin D deficiency, defined as a serum 25-hydroxyvitamin D [25(OH)D] concentration <20 ng/mL, is correlated with a more atherogenic lipid profile. However, oral vitamin D supplementation does not lower LDL-cholesterol concentrations or raise HDL-cholesterol concentrations. This uncoupling between association and causation may result from a failure of oral vitamin D to mimic the effect of dermally synthesized vitamin D in response to ultraviolet type B (UVB) light.Objective: We tested the hypothesis that, in vitamin D-deficient adults, the replenishment of vitamin D with UVB exposure would lower LDL-cholesterol concentrations compared with the effect of oral vitamin D3 supplementation.Design: We performed a randomized clinical trial in vitamin D-deficient adults and compared vitamin D replenishment between subjects who received oral vitamin D3 (n = 60) and those who received narrow-band UVB exposure (n = 58) ≤6 mo.Results: There was no difference in the change from baseline LDL-cholesterol concentrations between oral vitamin D3 and UVB groups (difference in median of oral vitamin D3 minus that of UVB: 1.5 mg/dL; 95% CI: -5.0, 7.0 mg/dL). There were also no differences within groups or between groups for changes in total or HDL cholesterol or triglycerides. Transcriptional profiling of skin and blood, however, revealed significant upregulation of immune pathway signaling with oral vitamin D3 but significant downregulation with UVB.Conclusions: Correcting vitamin D deficiency with either oral vitamin D3 or UVB does not improve the lipid profile. Beyond cholesterol, these 2 modalities of raising 25(OH)D have disparate effects on gene transcription. This trial was registered at clinicaltrials.gov as NCT01688102.

Keywords: 25-hydroxycholesterol; UV light; cholesterol; gene transcription; oxysterol; vitamin D.

© 2017 American Society for Nutrition.

Figures

FIGURE 1

Study participant flow. Potential subjects were screened for eligibility, and a 25(OH)D concentration >20 ng/mL was the most common reason for exclusion. Eligible subjects were randomly assigned to receive either 50,000 IU oral vitamin D3/wk for 8 wk, which was followed by supplemental doses of 50,000 IU/mo if 25(OH)D concentrations were <35 ng/mL, or a narrow-band UVB treatment delivered 2 times/wk for 8 wk with the dose adjusted on the basis of skin pigmentation with supplemental doses of 4 treatments/mo if 25(OH)D concentrations were <35 ng/mL. Participants were followed for ≤6 mo, and subjects with ≥2 mo of follow-up data were included in the primary analysis. UVB, UV type B; 25(OH)D, 25-hydroxyvitamin D.

FIGURE 2

Mean ± SD longitudinal 25(OH)D concentrations by month after treatment with either oral D3 or UV. Dashed lines indicate common clinical thresholds of vitamin D status with 30 ng/mL indicating replete. The number of subjects in each group over time is also shown. 25(OH)D concentrations rose significantly with both modalities. After 2 mo of active repletion, the oral D3 group had higher 25(OH)D concentrations than the UV group did, although after the maintenance phase, there was no difference between groups in terms of the change from baseline 25(OH)D concentrations (per-protocol analysis). In the oral D3 group, n = 60 at months 0–2, n = 57 at month 3, n = 53 at month 4, n = 51 at month 5, and n = 44 at month 6. In the UV group, n = 58 at months 0–2, n = 53 at month 3, n = 46 at month 4, n = 42 at month 5, and n = 40 at month 6. D3, vitamin D3; UV, narrow-band UV type B; 25(OH)D, 25-hydroxyvitamin D.

FIGURE 3

Mean ± SD longitudinal changes by month after treatment with either oral D3 or UV for serum calcium concentrations (A), serum phosphorus concentrations (B), and serum PTH concentration (C). Neither calcium nor phosphorus concentrations changed from baseline values either during the active repletion phase or the maintenance phase. However, PTH concentrations showed a significant, early, and sustained decline from baseline with either modality of vitamin D repletion (per-protocol analysis). In the oral D3 group, n = 60 at months 0–2, n = 57 at month 3, n = 53 at month 4, n = 51 at month 5, and n = 44 at month 6. In the UV group, n = 58 at months 0–2, n = 53 at month 3, n = 46 at month 4, n = 42 at month 5, and n = 40 at month 6. D3, vitamin D3; PTH, parathyroid hormone; UV, narrow-band UV type B.

FIGURE 4

Mean ± SD longitudinal changes by month after treatment with either oral D3 or UV for serum LDL concentrations (A) and serum HDL concentrations (B). Neither LDL nor HDL cholesterol concentrations changed from baseline values for either group throughout the duration of treatment (per-protocol analysis). In the oral D3 group, n = 60 at months 0–2, n = 57 at month 3, n = 53 at month 4, n = 51 at month 5, and n = 44 at month 6. In the UV group, n = 58 at months 0–2, n = 53 at month 3, n = 46 at month 4, n = 42 at month 5, and n = 40 at month 6. D3, vitamin D3; UV, narrow-band UV type B.