Effect of vitamin D3 supplementation in winter on physical performance of university students: a one-month randomized controlled trial.

BACKGROUND: There is epidemiological evidence which suggests an association between 25-hydroxyvitamin D [25(OH)D] levels and bone and muscle function; however, it is unclear whether vitamin D supplementation has an added benefit beyond bone health. Here, we investigated the effects of vitamin D3 supplementation (1 month) on physical performance in Chinese university students in winter. METHODS: One hundred and seventeen eligible subjects with 25(OH)D (19.2 ± 7.8 ng/mL) were randomly assigned to either vitamin D3 supplement (N = 56; 1000 IU/day) or the control (N = 61) group for 1 month. Pre- and post-measurements included: 1) serum levels of 25(OH)D; 2) musculoskeletal and pulmonary function [vertical jump height (VJH) and right handgrip strength (RHS), forced vital capacity (FVC), and forced expiratory volume at 1s (FEV1)]; 3) bone turnover markers [parathyroid hormone (PTH), n-terminal osteocalcin (N-MID), and calcium]; 4) hemoglobin-related parameters [hemoglobin (Hb), hematocrit (HCT), red blood cells (RBC), and red cell distribution width (RDW)]; 5) lipid parameters [total triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)]; 6) Fatigue-related indicators [serum creatine kinase (CK), lactate dehydrogenase (LDH), and total testosterone (T)]. In addition, aerobic capacity was assessed by measuring maximal oxygen uptake (VO2max) at baseline. RESULTS: During wintertime, supplementation with 1000 IU/d of vitamin D3 significantly increased serum 25(OH)D levels (from 18.85 ± 7.04 to 26.98 ± 5.88 ng/mL, p < 0.05), accompanied by a decrease of PTH (p < 0.05). However, vitamin D3 supplementation did not significantly impact the physical performance, serum lipid parameters, and bone turnover markers of students. Furthermore, 25(OH)D was found to be positively correlated with VJH and negatively correlated with PTH and TC at the beginning and end of the study (p < 0.05). In addition, the multiple linear regression analysis showed that 25(OH)D combined with athletic, gender, height, weight, Hb, and FVC could account for 84.0% of the VO2max value. CONCLUSIONS: The study demonstrated that one-month of 1000 IU/d of vitamin D3 supplementation during the winter had beneficial effects on 25(OH)D status and PTH. However, vitamin D3 intervention was not sufficient to improve physical performance. Furthermore, 25(OH)D levels combined with athletic, Hb and FVC could be a predictor of VO2max.

Vitamin D Deficiency in Relation to the Risk of Metabolic Syndrome in Middle-Aged and Elderly Patients with Type 2 Diabetes Mellitus.

Vitamin D deficiency is highly prevalent all over the world and dietary intakes of vitamin D are very low in China. In this study we aimed to determine whether vitamin D deficiency is associated with increased risk of metabolic syndrome (MetS) among Chinese type 2 diabetes mellitus (T2DM) patients aged over 50 y. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured in a cross-sectional sample of 270 T2DM patients aged over 50 y from Zhejiang. Data on demographic characteristics, anthropometry and other variables were collected. The mean of serum 25(OH)D was 22.93 ng/mL, and percentages of vitamin D deficiency and insufficiency were 43.71% and 39.63%, respectively. Serum 25(OH)D concentrations were significantly lower in subjects with MetS than in those without MetS (21.74 vs 24.96 ng/mL, p=0.001), and the prevalence of MetS significantly increased according to tertiles of serum 25(OH)D concentrations. After adjusting for multivariate factors, the adverse effect of lower serum 25(OH)D concentrations was significant (OR: 3.26, 95% CI: 1.03-7.34; p=0.044) in the group with BMI≥24 kg/m2 while the change in OR of MetS for each 10 ng/mL decrease in the serum 25(OH)D concentrations was 2.03 (95% CI: 1.10-3.79). These results suggest that serum 25(OH)D deficiency may be a risk factor of MetS among Chinese type 2 diabetic patients, especially in the T2DM with BMI≥24 kg/m2. The challenge is determining the mechanisms of vitamin D action for recommendation of vitamin D supplementation that reduces the risks of MetS and progression to T2DM.

Vitamin D Deficiency Increases the Risk of Gestational Diabetes Mellitus: A Meta-Analysis of Observational Studies.

The results investigating the relationship between vitamin D levels and gestational diabetes mellitus (GDM) are inconsistent. Thus, we focused on evaluating the association of vitamin D deficiency with GDM by conducting a meta-analysis of observed studies. A systematic literature search was conducted via PubMed, MEDLINE, and Cochrane library to identify eligible studies before August 2015. The meta-analysis of 20 studies including 9209 participants showed that women with vitamin D deficiency experienced a significantly increased risk for developing GDM (odds ratio (OR) = 1.53; 95% confidence intervals (CI), 1.33, 1.75) with a little heterogeneity (I² = 16.20%, p = 0.252). A noteworthy decrease of 4.93 nmol/L (95% CI, -6.73, -3.14) in serum 25(OH)D was demonstrated in the participants with GDM, and moderate heterogeneity was observed (I² = 61.40%, p = 0.001). Subgroup analysis with study design showed that there were obvious heterogeneities in nested case-control studies (I² > 52.5%, p < 0.07). Sensitivity analysis showed that exclusion of any single study did not materially alter the overall combined effect. In summary, the evidence from this meta-analysis indicates a consistent association between vitamin D deficiency and an increased risk of GDM. However, well-designed randomized controlled trials are needed to elicit the clear effect of vitamin D supplementation on prevention of GDM.

Gene-based association analysis identified novel genes associated with bone mineral density.

Genetic factors contribute to the variation of bone mineral density (BMD), which is a major risk factor of osteoporosis. The aim of this study was to identify more "novel" genes for BMD. Based on the publicly available SNP-based P values, we performed an initial gene-based analysis in a total of 32,961 individuals. Furthermore, we performed differential expression, pathway and protein-protein interaction analyses to find supplementary evidence to support the significance of the identified genes. About 21,695 genes for femoral neck (FN)-BMD and 21,683 genes for lumbar spine (LS)-BMD were analyzed using gene-based association analysis. A total of 35 FN-BMD associated genes and 53 LS-BMD associated genes were identified (P < 2.3×10(-6)) after Bonferroni correction. Among them, 64 genes have not been reported in previous SNP-based genome-wide association studies. Differential expression analysis further supported the significant associations of 14 genes with FN-BMD and 19 genes with LS-BMD. Especially, WNT3 and WNT9B in the Wnt signaling pathway for FN-BMD were further supported by pathway analysis and protein-protein interaction analysis. The present study took the advantage of gene-based association method to perform a supplementary analysis of the GWAS dataset and found some BMD-associated genes. The evidence taken together supported the importance of Wnt signaling pathway genes in determining osteoporosis. Our findings provided more insights into the genetic basis of osteoporosis.

Effect of vitamin D supplementation on the level of circulating high-sensitivity C-reactive protein: a meta-analysis of randomized controlled trials.

Vitamin D might elicit protective effects against cardiovascular disease by decreasing the level of circulating high-sensitivity C-reactive protein (hs-CRP), an inflammatory marker. Thus, we conducted a meta-analysis of randomized controlled trials to evaluate the association of vitamin D supplementation with circulating hs-CRP level. A systematic literature search was conducted in September 2013 (updated in February 2014) via PubMed, Web of Science, and Cochrane library to identify eligible studies. Either a fixed-effects or a random-effects model was used to calculate pooled effects. The results of the meta-analysis of 10 trials involving a total of 924 participants showed that vitamin D supplementation significantly decreased the circulating hs-CRP level by 1.08 mg/L (95% CI, -2.13, -0.03), with the evidence of heterogeneity. Subgroup analysis suggested a higher reduction of 2.21 mg/L (95% CI, -3.50, -0.92) among participants with baseline hs-CRP level ≥5 mg/L. Meta-regression analysis further revealed that baseline hs-CRP level, supplemental dose of vitamin D and intervention duration together may be attributed to the heterogeneity across studies. In summary, vitamin D supplementation is beneficial for the reduction of circulating hs-CRP. However, the result should be interpreted with caution because of the evidence of heterogeneity.

Vitamin D intake and risk of type 1 diabetes: a meta-analysis of observational studies.

Vitamin D is suggested to have protective effects against type 1 diabetes. However, the results from observational studies have been inconsistent. We aimed to examine their association by conducting a meta-analysis of observational studies. Multiple databases were searched in June 2013 to identify relevant studies including both case-control and cohort studies. Either a fixed- or random-effects model was used to calculate the pooled risk estimate. We identified eight studies (two cohort studies and six case-control studies) on vitamin D intake during early life and three studies (two cohort studies and one case-control study) on maternal vitamin D intake during pregnancy. The pooled odds ratio for type 1 diabetes comparing vitamin D supplementation with non-supplementation during early life was 0.71 (95% confidence interval [CI], 0.51-0.98). Similar results were observed in the case-control subgroup analysis but not in the cohort subgroup analysis. The pooled odds ratio with maternal intake of vitamin D during pregnancy was 0.95 (95% CI, 0.66-1.36). In conclusion, vitamin D intake during early life may be associated with a reduced risk of type 1 diabetes. However, there was not enough evidence for an association between maternal intake of vitamin D and risk of type 1 diabetes in the offspring.

Partial rescue of the phenotype in 1α-hydroxylase gene knockout mice by vitamin D3 injection.

OBJECTIVE: To investigate whether 25-hydroxyvitamin D [25(OH)D] can mediate effects without being converted to 1α,25-dihydroxyvitamin D [1,25(OH)2D]. METHODS: Vitamin D3 (VD3) was injected intramuscularly to 25-hydroxyvitamin D-1α-hydroxylase [1α(OH)ase] gene knockout (KO) male mice with a dose of 10,000 IU per week for 4 weeks. Skeleton Parameters and Serum biochemistry in mice were assayed. RESULTS: Serum 25(OH)D3 levels increased from 41 to 212 ng/mL in KO mice injected with VD3. Our results show that VD3 injections significantly increased the body weight of KO mice and there were no significant differences in body weight at 7 weeks of age between VD3-treated KO mice and wildtype (WT) mice. After 1 month injection, serum calcium and phosphorus levels of the KO mice were found indistinguishable from those of their WT littermates. Serum parathyroid hormone level declined significantly, but remained higher in treated KO mice. The dry weight, percentage ash weight, and calcium content of femur were returned to normal levels in VD3-treated KO mice whereas the femoral length, although increased significantly, remained significantly smaller than that of WT mice. VD3 injections also normalized the growth plate of KO mice within normal width. CONCLUSIONS: Our results demonstrate that high-dose VD3 injections can partially rescue the phenotype in 1α-hydroxylase gene KO mice. 25-Hydroxyvitamin D can mediate effects in the absence of conversion to 1α,25-dihydroxyvitamin D was confirmed in this study.