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.

Highlights d VMHvl vGlut2 neurons target lPAG vGlut2 neurons that project polysynaptically to the jaw d Inactivating lPAG vGlut2 neurons results in aggressive actionspecific deficits d Single-unit lPAG activity is action specific and time locked to EMG-detected biting d VMHvl-lPAG projection relays male-biased signals to generate action selectivity

Background/Aim: To investigate the effects of vitamin D 3 supplementation on gut microbiota. Patients and Methods: Twenty adults with vitamin D insufficiency/deficiency [25(OH)D <30 ng/ml] were enrolled and given 600, 4,000 or 10,000 IUs/day of oral vitamin D 3 . Stool samples were collected at baseline and 8 weeks for identifying gut microbiota using 16S rRNA gene amplification and sequencing. Results: Baseline serum 25(OH)D was associated with increased relative abundance of Akkermansia and decreased relative abundance of Porphyromonas (p<0.05). After the intervention, we observed a dose-dependent increase in relative abundance of Bacteroides with a significant difference between the 600 IUs and the 10,000 IUs groups (p=0.027), and Parabacteroides with a significant difference between the 600 IUs and the 4,000 IUs groups (p=0.039). Conclusion: Increased serum 25(OH)D was associated with increased beneficial bacteria and decreased pathogenic bacteria. A dose-dependent increase in bacteria associated with decreased inflammatory bowel disease activity was observed after vitamin D 3 supplementation. Patients and MethodsHealthy adults who had vitamin D insufficiency/deficiency [25(OH)D<30 ng/ml] were enrolled in a randomized, doubleblinded, investigator initiated, pilot study. This study investigated broad gene expression changes in peripheral blood mononuclear cells following vitamin D 3 supplementation of 600, 4,000 or 10,000 IU/day of vitamin D 3 , as previously described (11). The study was 551