Overall , intervention groups obtained higher 25(OH)D concentration than controls and there was obvious dose – response effect between intake dose and 25(OH)D concentration .
Baseline 25(OH)D concentration and age were significant indicators for 25(OH)D concentration .
Conclusions Regional- and age-specific recommended dosages of VitD supplements for population to achieve optimal 25(OH)D concentrations have been suggested
Background / Objectives Optimal doses of vitamin D ( VitD ) supplement in different population s are unclear .
We aim to evaluate the relationship between VitD supplementation and post-intervention serum 25-hydroxyvitamin D [ 25(OH)D ] concentration , to provide a recommended dosage of VitD for achieving an optimal 25(OH)D concentration for different population s .
Genomic Response to Vitamin D Supplementation in the Setting of a Randomized, Placebo-Controlled Trial
Background Vitamin D deficiency has been associated with multiple diseases , but the causal relevance and underlying processes are not fully understood . Elucidating the mechanisms of action of drug treatments in humans is challenging , but application of functional genomic approaches in r and omized trials may afford an opportunity to systematic ally assess molecular responses . Methods In the Biochemical Efficacy and Safety Trial of Vitamin D ( BEST-D ) , a double-blind , placebo-controlled , dose-finding , r and omized clinical trial , 305 community-dwelling individuals aged over 65 years were r and omly allocated to treatment with vitamin D3 4000 IU , 2000 IU or placebo daily for 12 months . Genome-wide genotypes at baseline , and transcriptome and plasma levels of cytokines ( IFN-γ , IL-10 , IL-8 , IL-6 and TNF-α ) at baseline and after 12 months , were measured . The trial had > 90 % power to detect 1.2-fold changes in gene expression . Findings Allocation to vitamin D for 12-months was associated with 2-fold higher plasma levels of 25-hydroxy-vitamin D ( 25[OH]D , 4000 IU regimen ) , but had no significant effect on whole-blood gene expression ( FDR < 5 % ) or on plasma levels of cytokines compared with placebo . In pre-specified analysis , rs7041 ( intron variant , GC ) had a significant effect on circulating levels of 25(OH)D in the low dose , but not in the placebo or high dose vitamin D regimen . A gene expression quantitative trait locus analysis ( eQTL ) demonstrated evidence of 31,568 cis-eQTLs ( unique SNP-probe pairs ) among individuals at baseline and 34,254 after supplementation for 12 months ( any dose ) . No significant associations involving vitamin D supplementation response eQTLs were found . Interpretation We performed a comprehensive functional genomics and molecular analysis of vitamin D supplementation in a r and omized , placebo-controlled trial . Although this study was limited to mostly Caucasian individuals aged over 65 years , the results differ from many previous studies and do not support a strong effect of vitamin D on long-term transcriptomic changes in blood or on plasma cytokine levels . The trial demonstrates the feasibility of applying functional genomic and genetic approaches in r and omized trials to assess molecular and individual level responses . Key Result Supplementation with high-dose vitamin D in older people for 12 months in a r and omized , placebo-controlled trial had no significant effect on gene expression or on plasma concentrations of selected cytokines . Trial Registration S RCT N registry ( Number 07034656 ) and the European Clinical Trials Data base ( EudraCT Number 2011 - 005763 - 24 )
Overall , intervention groups obtained higher 25(OH)D concentration than controls and there was obvious dose – response effect between intake dose and 25(OH)D concentration .
Baseline 25(OH)D concentration and age were significant indicators for 25(OH)D concentration .
Conclusions Regional- and age-specific recommended dosages of VitD supplements for population to achieve optimal 25(OH)D concentrations have been suggested
Background / Objectives Optimal doses of vitamin D ( VitD ) supplement in different population s are unclear .
We aim to evaluate the relationship between VitD supplementation and post-intervention serum 25-hydroxyvitamin D [ 25(OH)D ] concentration , to provide a recommended dosage of VitD for achieving an optimal 25(OH)D concentration for different population s .