Vitamin D and Immunity: Photosynthesis Versus Supplementation

Study Overview
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Brief Summary
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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

Official Title
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Vitamin D and Immunity: Photosynthesis Versus Supplementation

Conditions
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Vitamin D Deficiency

Intervention / Treatment
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* Dietary Supplement: Vitamin D
* Radiation: UVR (Solar simulated radiation)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>No intervention | |
| Experimental: UVR (Solar simulated radiation)<br>Twice weekly 1.25 SED (sub-erythemal) (4 weeks) | Radiation: UVR (Solar simulated radiation)<br>* 1.25 SED Solar simulated radiation twice weekly<br>|
| Experimental: Vitamin D3 supplementation<br>4X 1000IU cholecalciferol tablets daily (28 days) | Dietary Supplement: Vitamin D<br>* Daily 4X 1000IU cholecalciferol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D, UVR, Immune system