Association of folate, vitamin B-12 and vitamin B-6 intake with diabetes and prediabetes in adults aged 20 years and older.

BACKGROUND AND OBJECTIVES: This study aimed to assess the association of folate, vitamin B-12 and vitamin B-6 from diet and supplements with diabetes and prediabetes in U.S. adults. METHODS AND STUDY DESIGN: We used data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016 to conduct this crosssectional study. Diabetes and prediabetes status were based on self-report, medication use, fasting plasma glucose levels (FPG), haemoglobin A1c (HbA1c) levels and the two hours plasma glucose (PG) value during a 75-g oral glucose tolerance test (OGTT). Logistic regression models and restricted cubic spline models were used to evaluate the associations between dietary folate, vitamin B-12, vitamin B-6 and diabetes. RESULTS: After adjustment for the potential confounders, compared with the lowest quartile, the ORs (odds ratios) with 95%CIs (confidence intervals) of diabetes for the highest quartile intakes of folate and vitamin B-6 were 0.65 (0.47-0.90) and 0.61 (0.42-0.89), the OR with 95% CI of diabetes for the third quartile of dietary vitamin B-12 was 0.76 (0.60-0.97). Further excluded participants with diabetes history, the ORs with 95% CI of newly diagnosed diabetes were 0.60 (0.39-0.94), 0.84 (0.58-1.23), and 0.65 (0.43-0.98) for the third quartile of dietary folate, vitamin B-12 and vitamin B-6, respectively. A linear inverse relationship was found between vitamin B12 and diabetes, and a nonlinear inverse relationship was found between dietary folate, dietary vitamin B6 and diabetes. CONCLUSIONS: Our study suggested that folate, vitamin B-12 and vitamin B-6 intake were inversely associated with the risk of diabetes in US adults.

Limonin ameliorates acetaminophen-induced hepatotoxicity by activating Nrf2 antioxidative pathway and inhibiting NF-κB inflammatory response via upregulating Sirt1.

BACKGROUND: Limonin, a bioactive compound from citrus plants, exerts antioxidant activities, however its therapeutic potential in acetaminophen (APAP)-induced hepatotoxicity remains unclear. PURPOSE: Our study aims to investigate the protective effect of limonin on APAP-induced hepatotoxicity and illuminate the underlying mechanisms. STUDY: design In vitro, we chose L-02 cells to establish in vitro APAP-induced liver injury model. L-02 cells were treated with APAP (7.5 mM) for 24 h after pre-incubation with limonin (10, 25, 50 µM) or NAC (250 µM) for 2 h. In vivo, we used C57BL/6 mice as an in vivo APAP-induced liver injury model. C57BL/6 mice with pre-treatment of limonin (40, 80 mg/kg) or NAC (150 mg/kg) for 1 h, were given with a single dose of APAP (300 mg/kg). METHODS: After pre-incubation with limonin (10, 25, 50 µM) for 2 h, L-02 cells were treated with APAP (7.5 mM) for 24 h.The experiments in vitro included MTT assay, Annexin V/PI staining, measurement of reactive oxygen species (ROS), quantitative real-time PCR analysis, Western blot analysis, immunofluorescence microscopy and analysis of LDH activity. Transfection of Nrf2 or Sirt1 siRNA was also conducted in vitro. In vivo, C57BL/6 mice with pre-treatment of limonin (40, 80 mg/kg) or NAC (150 mg/kg) for 1 h, were given with a single dose of APAP (300 mg/kg). Mice were sacrificed at 4, 12 h after APAP poisoning, and analysis of ALT and AST in serum, GSH level in liver tissues, liver histological observation and immunohistochemistry were performed. RESULTS: Limonin increased the cell viability and alleviated APAP-induced apoptosis in hepatocytes. Limonin also inhibited APAP-induced mitochondrial-mediated apoptosis by decreasing the ratio of Bax/Bcl-2, recovery of mitochondrial membrane potential (MMP), inhibiting ROS production and cleavage of caspase-3 in L-02 cells. Moreover, limonin induced activation of Nrf2 and increased protein expression and mRNA levels of its downstream targets, including HO-1, NQO1 and GCLC/GCLM. The inhibition of limonin on apoptosis and promotion on Nrf2 antioxidative pathway were lessened after the application of Nrf2 siRNA. In addition, limonin inhibited NF-κB transcriptional activation, NF-κB-regulated genes and protein expression of inflammatory related proteins iNOS and COX2. Furthermore, limonin increased the protein expression of Sirt1. Sirt1 siRNA transfection confirmed that limonin activated Nrf2 antioxidative pathway and inhibited NF-κB inflammatory response by upregulating Sirt1. Finally, we established APAP-induced liver injury in vivo and demonstrated that limonin alleviated APAP-induced hepatotoxicity by activating Nrf2 antioxidative signals and inhibiting NF-κB inflammatory response via upregulating Sirt1. CONCLUSION: In summary, this study documented that limonin mitigated APAP-induced hepatotoxicity by activating Nrf2 antioxidative pathway and inhibiting NF-κB inflammatory response via upregulating Sirt1, and demonstrated that limonin had therapeutic promise in APAP-induced liver injury.

Coffee and caffeine intake and incidence of type 2 diabetes mellitus: a meta-analysis of prospective studies.

PURPOSE: Coffee and caffeine have been linked to type 2 diabetes mellitus (T2DM). A dose-response meta-analysis of prospective studies was conducted to assess the association between coffee and caffeine intake and T2DM incidence. METHODS: Pertinent studies were identified by a search of PubMed and EMBASE. The fixed- or random-effect pooled measure was selected based on between-study heterogeneity. Dose-response relationship was assessed by restricted cubic spline. RESULTS: Compared with the lowest level, the pooled relative risk (95 % CI) of T2DM was 0.71 (0.67-0.76) for the highest level of coffee intake (26 articles involving 50,595 T2DM cases and 1,096,647 participants), 0.79 (0.69-0.91) for the highest level of decaffeinated coffee intake (10 articles involving 29,165 T2DM cases and 491,485 participants) and 0.70 (0.65-0.75) for the highest level of caffeine intake (6 articles involving 9,302 T2DM cases and 321,960 participants). The association of coffee, decaffeinated coffee and caffeine intake with T2DM incidence was stronger for women than that for men. A stronger association of coffee intake with T2DM incidence was found for non-smokers and subjects with body mass index <25 kg/m(2). Dose-response analysis suggested that incidence of T2DM decreased by 12 % [0.88 (0.86-0.90)] for every 2 cups/day increment in coffee intake, 11 % [0.89 (0.82-0.98)] for every 2 cups/day increment in decaffeinated coffee intake and 14 % [0.86 (0.82-0.91)] for every 200 mg/day increment in caffeine intake. CONCLUSIONS: Coffee and caffeine intake might significantly reduce the incidence of T2DM.

Coffee and caffeine intake and breast cancer risk: an updated dose-response meta-analysis of 37 published studies.

OBJECTIVE: We conducted an updated meta-analysis to summarize the evidence from published studies regarding the association of coffee and caffeine intake with breast cancer risk. METHODS: Pertinent studies were identified by a search of PubMed and by reviewing the reference lists of retrieved articles. The fixed or random effect model was used based on heterogeneity test. The dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression. RESULTS: 37 published articles, involving 59,018 breast cancer cases and 966,263 participants, were included in the meta-analysis. No significant association was found between breast cancer risk and coffee (RR=0.97, P=0.09), decaffeinated coffee (RR=0.98, P=0.55) and caffeine (RR=0.99, P=0.73), respectively. And the association was still not significant when combining coffee and caffeine (coffee/caffeine) (RR=0.97, P=0.09). However, an inverse association of coffee/caffeine with breast cancer risk was found for postmenopausal women (RR=0.94, P=0.02), and a strong and significant association of coffee with breast cancer risk was found for BRCA1 mutation carriers (RR=0.69, P<0.01). A linear dose-response relationship was found for breast cancer risk with coffee and caffeine, and the risk of breast cancer decreased by 2% (P=0.05) for every 2 cups/day increment in coffee intake, and 1% (P=0.52) for every 200mg/day increment in caffeine intake, respectively. CONCLUSIONS: Findings from this meta-analysis suggested that coffee/caffeine might be weakly associated with breast cancer risk for postmenopausal women, and the association for BRCA1 mutation carriers deserves further investigation.