Vitamin D and Immunity: Photosynthesis Versus Supplementation

Guy's and St Thomas' NHS Foundation Trust36 enrolled

Overview

The optimal way to restore serum 25-hydroxyvitamin D sufficiency is currently debatable. UV irradiation through sunshine exposure promotes endogenous vitamin D synthesis, although this can also be associated with a risk of UVR-induced skin cancer. Dietary supplements represent an alternative, which are increasingly being used in clinical trials to correct deficiency. However, it is unclear whether sunshine exposure and vitamin D supplementation induce comparable changes in immune function, or whether additional UVR-induced molecules may be responsible for proposed health benefits. Several studies report an inverse correlation between exposure to UVR and immune-mediated diseases, further supporting the theory that UVR may also be protective through non vitamin-D mediated pathways. So far it has been difficult to distinguish between immune-regulation by vitamin D and other mediators induced by UVR as the downstream effects are similar. A direct comparison of the biological effects of vitamin D obtained by UVR versus supplementation has never been made. This study aims to elucidate the differences in vitamin D generated by UVR exposure versus supplementation by comparing immunological endpoints

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Vitamin D Deficiency

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Age: 18-40 * Fitzpatrick skin type I/II * Healthy * Serum 25(OH)D3 \<50nmol/L Exclusion Criteria: Serum 25(OH)D3 \>50nmol/L * Pregnant or nursing women * Women of child bearing age not using adequate contraception * Are taking photosensitizing medication (i.e. causes you to be more sensitive to sunlight) * Have had a history of skin disorders, sensitive skin, sensitivity to sunlight or skin cancer * Have previously had an organ transplant * Have partaken in a clinical study within the last 14 days * Have had recent exposure to sunbeds (last 4 months) or holiday sun (including skiing) * Are currently or have taken vitamin D supplements in the last 4 months Are asthmatic or suffer from any allergies

Outcomes

Primary Outcomes

Vitamin D status of healthy participants treated with oral vitamin D (cholecalciferol) or UVR (SSR) exposures and control (untreated)

Measure 25(OH)D3nmol/L via LC-MS/MS

Time frame: 3 years

Secondary Outcomes

Changes to peripheral blood cell frequency

Frequency of major peripheral immune cells (e.g. CD3+ T cells, CD3+ CD4+ T cells, CD3+ CD8+ T cells, CD19+ B cells, Natural Killer Cells, Classical, Non-classical and Intermediate Monocytes) in participants when vitamin D insufficient and sufficient. Via flow cytometry.

Time frame: 3 years

Impact upon the frequency and phenotype of peripheral blood dendritic cells

Frequency of peripheral blood dendritic cells (myeloid and plasmacytoid) in individuals with insufficient vitamin D levels and following vitamin D repletion via supplementation or UVR (SSR) exposures. Assessment of markers of maturation/tolerogenicity (MFI and frequency expressing) on myeloid and plasmacytoid dendritic cells direct ex vivo and after stimulation in vitro in participants when vitamin D insufficient and sufficient.

Time frame: 3 years

Gene expression in peripheral blood myeloid and plasmacytoid dendritic cells

Differentially regulated genes in myeloid and plasmacytoid dendritic cells in participants after vitamin D repletion via supplementation and UVR (SSR) exposure via Microarray.

Time frame: 3 years