Association of daily sitting time and coffee consumption with the risk of all-cause and cardiovascular disease mortality among US adults.

BACKGROUND: Sedentary behavior has been demonstrated to be a modifiable factor for several chronic diseases, while coffee consumption is believed to be beneficial for health. However, the joint associations of daily sitting time and coffee consumption with mortality remains poorly understood. This study aimed to evaluate the independent and joint associations of daily sitting time and coffee intakes with mortality from all-cause and cardiovascular disease (CVD) among US adults. METHODS: An analysis of a prospective cohort from the 2007-2018 National Health and Nutrition Examination Survey of US adults (n = 10,639). Data on mortality were compiled from interview and physical examination data until December 31, 2019. Daily sitting time was self-reported. Coffee beverages were from the 24-hour diet recall interview. The main outcomes of the study were all-cause and cardiovascular disease mortality. The adjusted hazard ratios [HRs] and 95% confidence intervals [CI] were imputed by Cox proportional hazards regression. RESULTS: Among 10,639 participants in the study cohort, there were 945 deaths, 284 of whom died of CVD during the follow-up period of up to 13 years. Multivariable models showed that sitting more than 8 h/d was associated with higher risks of all-cause (HR, 1.46; 95% CI, 1.17-1.81) and CVD (HR, 1.79; 95% CI, 1.21-2.66) mortality, compared with those sitting for less than 4 h/d. People with the highest quartile of coffee consumption were observed for the reduced risks of both all-cause (HR, 0.67; 95% CI, 0.54-0.84) and CVD (HR, 0.46; 95% CI, 0.30-0.69) mortality compared with non-coffee consumers. Notably, joint analyses firstly showed that non-coffee drinkers who sat six hours or more per day were 1.58 (95% CI, 1.25-1.99) times more likely to die of all causes than coffee drinkers sitting for less than six hours per day, indicating that the association of sedentary with increased mortality was only observed among adults with no coffee consumption but not among those who had coffee intake. CONCLUSIONS: This study identified that sedentary behavior for more than 6 h/d accompanied with non-coffee consumption, were strongly associated with the increased risk of mortality from all-cause and CVD.

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.

1α,25-dihydroxyvitamin D3 supplementation alleviates perfluorooctanesulfonate acid-induced reproductive injury in male mice: Modulation of Nrf2 mediated oxidative stress response.

Perfluorooctanesulfonate acid (PFOS) is a typical persistent organic pollutant that widely exists in the environment. To clarify the toxic effects and mechanisms of PFOS and to find effective intervention strategies have been attracted global attention. Here, we investigated the effects of PFOS on the male reproductive system and explored the potential protective role of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2 D3 ). Our results showed that 1α,25(OH)2 D3 intervention significantly improved PFOS-induced sperm quality decline and testicular damage. Moreover, 1α,25(OH)2 D3 aggrandized the total antioxidant capacity. Furthermore, after PFOS exposure, the transcription factor nuclear factor erythroid-related factor 2 (Nrf2) was adaptively increased together with its target genes, such as HO-1, NQO1, and SOD2. Meanwhile, 1α,25(OH)2 D3 ameliorated PFOS-induced augment of Nrf2 and target genes. These findings indicated that 1α,25(OH)2 D3 might attenuate PFOS-induced reproductive injury in male mice via Nrf2-mediated oxidative stress.

Effects of long-term vitamin D supplementation on metabolic profile in middle-aged and elderly patients with type 2 diabetes.

To evaluate the effects of long-term vitamin D supplementation on metabolic profiles in middle-aged to elderly patients with type 2 diabetes (T2D), a randomized controlled trial was conducted among patients with T2D aged 50-70 years. A total of 270 patients underwent randomization with 135 being allocated to the vitamin D group and 135 to the control group, and participants in the vitamin D group received oral vitamin D3 (800 IU/day) for 30 months. Serum 25(OH)D and metabolic variables were measured at baseline, and after 6, 12, 18, and 30 months of intervention. After 30 months, the vitamin D group showed a greater increase in serum 25(OH)D than the control group (12.39 ± 6.99 vs 5.35 ± 5.29 ng/ml, P < 0.001). Meanwhile, changes in the levels of fasting insulin, HOMA-IR, non-high-density-lipoprotein cholesterol (non-HDL-C), high-sensitivity C-reactive protein (hs-CRP), and uric acid differed significantly between the two groups (all P < 0.05). Stratified analysis indicated that change in uric acid differed significantly between the two groups in subgroup with baseline 25(OH)D ≥ 20 ng/ml (P = 0.042) or subgroup with female patients (P = 0.034). And the change in fasting blood glucose (FBG) differed significantly between the vitamin D group (-0.30 ± 2.52 mmol/L) and the control group (0.49 ± 1.78 mmol/L, P = 0.049) among patients achieving 25(OH)D concentrations of 30 ng/ml at the end of this trial. A significant difference in the change of triglyceride was observed between the two groups among patients with obesity at baseline [0.05(-0.59, 0.23) vs 0.41(-0.01, 0.80) mmol/L, P = 0.023]. These findings suggested that long-term vitamin D supplementation significantly reduced fasting insulin, HOMA-IR, and serum concentrations of non-HDL-C, hs-CRP, and uric acid among middle-aged to elderly patients with T2D. And vitamin D status, gender, and baseline obesity may modify the effects of vitamin D supplementation.

Mechanical Insights into Thiol-Mediated Synergetic Biotransformation of Cadmium and Selenium in Nematodes.

Cadmium ion (Cd2+) is a common environmental pollutant with high biotoxicity. Interestingly, the Cd2+ biotoxicity can be alleviated by the coexisting selenite (SeO32-), which induces the formation of cadmium selenide-rich nanoparticles (CdSe NPs) under the function of thiol-capping peptides. However, the detailed biochemical mechanisms by which Cd and Se are synergistically transformed into CdSe NPs in living organisms remain unclear so far. Here, we shed light on the molecular basis of such biotransformation processes in Caenorhabditis elegans by focusing on the roles of several key thiol-capping peptides. By monitoring the compositional and structural changes of the Cd and Se species and the genetic-level responses of nematodes, we revealed the specific roles of glutathione (GSH) and phytochelatins (PCs) in mediating the CdSe NP formation. With the aid of in vitro bioassembly assay and density functional theory calculations, the detailed Cd-Se interaction pathways were further deciphered: the ingested Cd binds predominantly to GSH and PCs in sequence, then further interacts with selenocysteine to form tetrahedral-structured PC2-Cd2-Sec2 complex, and ultimately grows into CdSe NPs. This work provides molecular-level insights into the Cd-Se interaction in C. elegans and lays a basis for controlling the ecological and health risks of heavy metals in polluted environment.

The Association between Polymorphisms of Vitamin D Metabolic-Related Genes and Vitamin D3 Supplementation in Type 2 Diabetic Patients.

OBJECTIVE: To investigate the effect of single nucleotide polymorphisms (SNPs) of the key genes in vitamin D metabolic pathway on the serum 25(OH)D level after long-term vitamin D3 supplementation and provide a theoretical basis for rational vitamin D3 supplementation in diabetic patients with different genetic backgrounds. METHODS: Patients with type 2 diabetes (T2DM) who met the inclusive criteria were given 800 IU of vitamin D3 daily for 30 consecutive months. Serum 25(OH)D levels was measured at enrollment and every 6 months after enrollment. The average value of four-time measurements represented individual serum 25(OH)D level during vitamin D3 supplementation. Multiplex TaqMan genotyping was used to determine the distribution of eight candidate SNPs in genes of DHCR7, CYP2R1, CYP27B1, CYP24A1, and VDR, which are key genes in the vitamin D metabolic pathway, in diabetic patients. RESULTS: At baseline, the average serum 25(OH)D level was 22.71 ± 6.87 ng/mL, and 17.9% of patients had a ≥30 ng/mL level. During supplementation, the level of 25(OH)D increased significantly at each time point, and the average 25(OH)D level increased to 30.61 ± 5.04 ng/mL; however, there were 44.6% of patients whose serum 25(OH)D levels were still below 30 ng/mL. In the patients with CYP27B1 (rs10877012) G/T genotype, 71.79% achieved sufficient level of 25(OH)D, which was significantly higher than the other two genotypes (P < 0.05). Compared with those with T/T genotype, the RR of the patients with rs10877012 for <30 ng/mL level was 0.544 (95% CI: 0.291-0.917), and the RR after adjusting age and outdoor activity was 0.560 (95% CI: 0.292-0.970). CONCLUSION: The serum 25(OH)D level in patients with diabetes mellitus after long-term vitamin D3 supplementation is associated with CYP27B1 polymorphism. Patients with rs10877012 G/T allele have a better response to vitamin D3 supplementation. TRIAL REGISTRATION: This trial is registered with ChiCTR-IPC-17012657.

Vitamin D Resists Cyclophosphamide-Induced Genomic and DNA Damage in CHL Cells In Vitro and in Mice In Vivo.

Vitamin D as an adjuvant therapy for cancer patients is hoped to have a beneficial outcome based on its physiological activity, but clinical trials so far by addition of vitamin D show unremarkable curative improvement, mechanism for explain this phenomena is not well-understood. The aim of this study was to determine whether vitamin D resists cyclophosphamide (CP)-induced genomic and DNA damage. In CHL cells in vitro, 1α,25-(OH)2D3 at 10, 50, and 100 nM was found to alleviate the frequency of chromosomal aberration with an alleviation range of 40.7-44.0%. There was a dose-dependent decrease for a proportion of γ-H2AX foci positive cells in response to an increase in 1α,25-(OH)2D3 concentration. Two vitamin D3 injections of 1,000, 5,000, or 10,000 IU suppressed CP-induced micronucleus formation in mice BMCs with an alleviation range of 36.7-44.5%, mitigated lymphocytes DNA damage reflected by lower tail DNA, tail length and olive tail moment parameter in comet assay. Vitamin D showed an antagonistic effect on CP-induced genomic and DNA damage. Our data suggest that vitamin D as an adjuvant combine antineoplastic drug with genotoxicity administer to tumor patients is contraindicant.

Effects of Quercetin Intervention on Cognition Function in APP/PS1 Mice was Affected by Vitamin D Status.

SCOPE: To explore how quercetin will affect memory impairments in APP/PS1 mice under different vitamin D status. METHODS AND RESULTS: APP/PS1 mice are divided into four groups, i.e., control (CON), low (LVD), medium, and high vitamin D supplemented with quercetin. During Morris Water Maze test, mice of the LVD group function best for improving cognitive function demonstrated by reduced latency to platform, and increased number of crossing and swimming distance in the target quadrant. Compared to the CON group, in both hippocampus and cortex, the LVD group has significant reduction in Aß plaques, p-Tau at Ser396&Ser404, and neuroinflammation. In the hippocampus, BDNF is elevated, miR-26a and miR-125b is decreased, while miR-132 is increased in the LVD group. The LVD group demonstrates increased gut microbial diversity and elevated relative abundance of Glutamicibacter, Facklamia and Aerocorrus. In the hippocampus, p-Tau at ser396&404, GFAP, Ibα1, miR-26a, and miR-132 are negatively correlated with Aerococcus; and p-Tau at ser404 and Ibα1 are negatively correlated with Facklamia. CONCLUSION: Quercetin is more efficacious for improving cognitive function under low vitamin D status. This might be owing to that interventions reduce Aß plaques, tau phosphorylation, and neuroinflammation, upregulate BDNF, reduce miR-26a and miR-125b, increase miR-132, and elevate gut microbial diversity including Facklamia and Aerococcus.

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.

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.

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.

[Scientometrics and bibliometrics of chronotherapy].

In order to retrieve Chinese and foreign articles of chronotherapy, we searched Chinese databases of CBM, CMCC and foreign series databases in OVID and hence revealed and assessed the current status, research trend and level of chronotherapy in China and in foreign countries by means of scientometric and bibliometric parameters. ProCite5 software and handsearching were used to manage, check and statistically analyze the searched papers so as to find the parameters which included distributions of databases, years, authors, periodicals, subject headings, organizations and nations. 91 Chinese papers were identified which were distributed in 73 kinds of journals and in subject headings, e.g., Traditional Chinese medicine, cardiovascular diseases, neoplasms, asthma, peptic ulcer, diabetes mellitus, general review of chronotherapy, etc. 480 foreign articles were identified which mainly came from EMBASE and MEDLINE and were distributed in 285 types of journals and 35 nations and regions. There were 14 journals which recorded five or more articles. 12 researchers published more than five articles. Paul Brousse Hospital, University of Texas, University of Connecticut School of Medicine, Jichi Medical School and University of Minnesota were the core research institutes. There was no core author or core journal or core institute in China up till now. However, core authors, core journals and core research institutes had come into being in foreign countries; they were mainly from the Euro-American developed countries and had done well in chronotherapy.