ABSTRACT
BACKGROUND/AIM: To assess the impact of vitamin D supplementation on genomic and metabolomic profiles and relate them to the individual's responsiveness to varying doses of vitamin D3 Patients and Methods: Healthy adults were given either 600, 4000 or 10,000 IUs vitamin D3/day for 6 months. Circulating parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], calcium, peripheral white blood cells broad gene expression and urine and serum metabolomic profiles were evaluated. RESULTS: There was a dose-dependent effect of vitamin D supplementation on serum 25(OH)D, PTH and broad gene expression. Serum calcium levels remained normal for all study subjects and no untoward toxicity was observed. The metabolomic profiles were related to the genomic expression analysis. There were significant inter-individual effects on gene expression and metabolomic profile in response to the same dose of vitamin D3 supplementation, despite similar changes in 25(OH)D and PTH concentrations. CONCLUSION: These results may help explain the variability observed in clinical trials regarding vitamin D's non-calcemic health benefits.
Subject(s)
Dietary Supplements , Genomics , Metabolomics , Vitamin D/pharmacology , Adult , Dose-Response Relationship, Drug , Female , Gene Expression Regulation/drug effects , Humans , Male , Parathyroid Hormone/blood , Principal Component Analysis , Protein Interaction Maps/drug effects , Vitamin D/analogs & derivatives , Vitamin D/bloodABSTRACT
The aims of this randomized controlled double-blind clinical trial were to assess the impact of vitamin D supplementation on calcium metabolism and non-calcemic broad gene expression by relating them to the individual's responsiveness to varying doses of vitamin D3. Thirty healthy adults were randomized to receive 600, 4,000 or 10,000 IU/d of vitamin D3 for 6 months. Circulating parathyroid hormone (PTH), 25(OH)D, calcium and peripheral white blood cells broad gene expression were evaluated. We observed a dose-dependent increase in 25(OH)D concentrations, decreased PTH and no change in serum calcium. A plateau in PTH levels was achieved at 16 weeks in the 4000 and 10,000 IU/d groups. There was a dose-dependent 25(OH)D alteration in broad gene expression with 162, 320 and 1289 genes up- or down-regulated in their white blood cells, respectively. Our results clearly indicated that there is an individual's responsiveness on broad gene expression to varying doses of vitamin D3. Vitamin D3 supplementation at 10,000 IU/d produced genomic alterations several fold higher than 4,000 IU/d even without further changes in PTH levels. Our findings may help explain why there are some inconsistency in the results of different vitamin D's clinical trials.
