Furan fatty acid metabolite CMPF is associated with lower risk of type 2 diabetes, but not chronic kidney disease: a longitudinal population-based cohort study.

BACKGROUND: Furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is a strong biomarker of fish and n-3 polyunsaturated fatty acid (PUFA) intake. The relationship of CMPF with human health has been controversial, especially for type 2 diabetes and chronic kidney disease. OBJECTIVE: We performed a prospective cohort study to examine the association of serum CMPF with incident type 2 diabetes and chronic kidney disease. METHODS: In the Guangzhou Nutrition and Health Study, during a median follow-up of 8.8 y, we used a multivariable-adjusted Poisson regression model to investigate the association of baseline serum CMPF with the incidence of type 2 diabetes (1470 participants and 170 incident cases) and chronic kidney disease (1436 participants and 112 incident cases). We also examined the association of serial measures of serum CMPF with glycemic and renal function biomarkers. Mediation analysis was also performed to examine the contribution of CMPF in the association between marine n-3 PUFAs and risk of type 2 diabetes or chronic kidney disease. RESULTS: Each standard deviation increase in baseline serum CMPF was associated with an 18% lower risk of type 2 diabetes (relative risk: 0.82, 95% confidence interval [CI]: 0.68, 0.99) but was not associated with chronic kidney disease (relative risk: 0.95; 95% CI: 0.77-1.16). Correlation analyses of CMPF with glycemic and renal function biomarkers showed similar results. Mediation analysis suggested that serum CMPF contributed to the inverse association between erythrocyte marine n-3 PUFAs and incident type 2 diabetes (proportion mediated 37%, P-mediation = 0.022). CONCLUSIONS: Our findings suggest that serum CMPF was associated with a lower risk of type 2 diabetes but not chronic kidney disease. This study also suggests that CMPF may be a functional metabolite underlying the protective relationship between marine n-3 PUFA intake and type 2 diabetes.

Genetically predicted circulating vitamin C in relation to cardiovascular disease.

AIM: We conducted a two-sample Mendelian randomization (MR) study to assess the associations of genetically predicted circulating vitamin C levels with cardiovascular diseases (CVDs). METHODS AND RESULTS: Ten lead single-nucleotide polymorphisms associated with plasma vitamin C levels at the genome-wide significance level were used as instrumental variables. Summary-level data for 15 CVDs were obtained from corresponding genetic consortia, the UK Biobank study, and the FinnGen consortium. The inverse-variance-weighted method was the primary analysis method, supplemented by the weighted median and MR-Egger methods. Estimates for each CVD from different sources were combined. Genetically predicted vitamin C levels were not associated with any CVD after accounting for multiple testing. However, there were suggestive associations of higher genetically predicted vitamin C levels (per 1 standard deviation increase) with lower risk of cardioembolic stroke [odds ratio, 0.79; 95% confidence interval (CI), 0.64, 0.99; P = 0.038] and higher risk of atrial fibrillation (odds ratio, 1.09; 95% CI, 1.00, 1.18; P = 0.049) in the inverse-variance-weighted method and with lower risk of peripheral artery disease (odds ratio, 0.76, 95% CI, 0.62, 0.93; P = 0.009) in the weighted median method. CONCLUSION: We found limited evidence with MR techniques for an overall protective role of vitamin C in the primary prevention of CVD. The associations of vitamin C levels with cardioembolic stroke, atrial fibrillation, and peripheral artery disease need further study.

Circulating vitamin C concentration and risk of cancers: a Mendelian randomization study.

BACKGROUND: Circulating vitamin C concentrations have been associated with several cancers in observational studies, but little is known about the causal direction of the associations. This study aims to explore the potential causal relationship between circulating vitamin C and risk of five most common cancers in Europe. METHODS: We used summary-level data for genetic variants associated with plasma vitamin C in a large vitamin C genome-wide association study (GWAS) meta-analysis on 52,018 Europeans, and the corresponding associations with lung, breast, prostate, colon, and rectal cancer from GWAS consortia including up to 870,984 participants of European ancestry. We performed two-sample, bi-directional Mendelian randomization (MR) analyses using inverse-variance-weighted method as the primary approach, while using 6 additional methods (e.g., MR-Egger, weighted median-based, and mode-based methods) as sensitivity analysis to detect and adjust for pleiotropy. We also conducted a meta-analysis of prospective cohort studies and randomized controlled trials to examine the association of vitamin C intakes with cancer outcomes. RESULTS: The MR analysis showed no evidence of a causal association of circulating vitamin C concentration with any examined cancer. Although the odds ratio (OR) per one standard deviation increase in genetically predicted circulating vitamin C concentration was 1.34 (95% confidence interval 1.14 to 1.57) for breast cancer in the UK Biobank, this association could not be replicated in the Breast Cancer Association Consortium with an OR of 1.05 (0.94 to 1.17). Smoking initiation, as a positive control for our reverse MR analysis, showed a negative association with circulating vitamin C concentration. However, there was no strong evidence of a causal association of any examined cancer with circulating vitamin C. Sensitivity analysis using 6 different analytical approaches yielded similar results. Moreover, our MR results were consistent with the null findings from the meta-analysis exploring prospective associations of dietary or supplemental vitamin C intakes with cancer risk, except that higher dietary vitamin C intake, but not vitamin C supplement, was associated with a lower risk of lung cancer (risk ratio: 0.84, 95% confidence interval 0.71 to 0.99). CONCLUSIONS: These findings provide no evidence to support that physiological-level circulating vitamin C has a large effect on risk of the five most common cancers in European populations, but we cannot rule out very small effect sizes.

Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations.

OBJECTIVE: Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants. RESULTS: We identified 11 genomic regions associated with plasma vitamin C (P < 5 × 10-8), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10). CONCLUSIONS: These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.

Dietary camellia (Camellia oleifera Abel) seed oil in traditional Chinese cooking for high-risk cardiovascular disease: A three-arm double-blind randomized controlled feeding trial protocol.

BACKGROUND AND OBJECTIVES: As the Chinese economy has developed, dietary patterns have modernized, thereby increasing the incidence of chronic diseases such as cardiovascular disease (CVD). Many observational studies have shown that the Mediterranean diet based on olive oil is associated with a decreased incidence of CVD. This article aims to study the possible effects of dietary models by using three edible oils: olive oil, camellia seed oil (CSO), and soybean oil. CSO has a fatty acid composition similar to that olive oil and is unique in China, and soybean oil is a dietary oil used in traditional Chinese cooking. METHODS AND STUDY DESIGN: This intervention is designed based on a three-arm double-blind randomized controlled feeding trial. Three dietary models are established according to traditional Chinese cooking methods, each using one of the three plant edible oils mentioned above as a leading factor. Participants will be randomly assigned to each group and provided with a designated diet for 3 months. RESULTS: The study population is planned to be women with a high risk of CVD and aged between 35 and 69 years. Weight and other CVD-related factors are treated as primary and secondary outcomes, respectively. CONCLUSIONS: This trial may inform dietary nutrition policies to a certain extent, especially concerning traditional Chinese cooking methods, for weight control and the improvement of cardiovascular-related risk factors in women with a high risk of CVD.

The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis.

BACKGROUND: Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. METHODS AND FINDINGS: We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]-InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1-standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities. CONCLUSIONS: Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D.

Plasma omega-3 polyunsaturated fatty acids and recurrence of endometrial cancer.

BACKGROUND: Omega-3 polyunsaturated fatty acids (PUFAs) were proposed to have potential effects against inflammation and cancer. However, results from epidemiology studies remain inconsistent. We aimed to explore the associations of plasma PUFAs with EC recurrence and all-cause mortality. METHOD: Women diagnosed with endometrial cancer (EC) between 2008 and 2013 and underwent surgery at Fudan University Shanghai Cancer Center of China were recruited. Survival status was followed up through September 2017. EC recurrence and total cause deaths were identified through medical record and telephone interview. In total, 202 patients with enough plasma samples at time of surgery were included. There were 195 patients who provided baseline plasma and survival information included in the current study. Plasma omega-3 PUFAs were measured by GC-FID. Cox Proportional Hazard model adjusted for potential cofounders was used to estimate HRs and 95% CIs. RESULTS: Median follow-up time for patients was 58 months after surgery. A total of 13 recurrences and 11 all-cause deaths, of which, 2 deaths from EC, were identified. Level of plasma EPA was higher in recurrent patients than total patients (0.78% vs 0.51%, P = 0.015). Higher plasma eicosapentaenoic acid (EPA) level trended to have positive association with EC recurrence (P-trend = 0.04), although comparing to the lowest tertile, the highest tertile of EPA level was not significantly associated with increased risk of EC recurrence (HRT3vsT1 = 6.02; 95%CI = 0.7-52.06). The association between total omega-3 PUFA and EC recurrence tended to be stronger among patients with deeper myometrial invasion (OR = 3.41; 95%CI = 1.06-10.95; P-interaction = 0.04). CONCLUSIONS: Higher plasma EPA level was significantly associated with EC recurrence. Further studies are warranted to confirm these findings. TRIAL REGISTRATION: ChiCTR1900025418; Retrospectively registered (26 August 2019); Chinses Clinical Trial Registry.

Changes of urine metabolites in response to n-3 fatty acid supplements and their correlation with metabolic risk factors in patients with type 2 diabetes.

The present study aimed to investigate the effects of n-3 fatty acid supplements on urine metabolite profiling and their correlation with metabolic risk factors in Chinese T2D patients. A double-blind randomized controlled trial was conducted in 59 Chinese patients with T2D, who were randomized to receive fish oil (FO), flaxseed oil (FSO) or corn oil (CO, serving as a control group) capsules for 180 days. Morning urine samples were collected before and after the intervention and were analyzed for metabolomics by UHPLC-Q-Exactive Orbitrap/MS in positive and negative ionization modes. In the FO group, levels of 2-hexenoylcarnitine (C6:1) (p < 0.001) and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) (p = 0.004) were significantly increased while hydroxyisovaleroyl carnitine (C5:OH) (p < 0.001) was significantly decreased compared with the CO group. In addition, geranylacetone (p = 0.023) and citronellyl propionate (p = 0.038) levels were significantly elevated, while dihydrojasmonic acid (p = 0.003) was significantly reduced in the FSO group compared with that in the CO group. Moreover, increased C6:1 was correlated with decreased serum triglycerides (r = -0.340, p = 0.020). The change of urine CMPF showed inverse correlation with blood urea nitrogen (BUN) (r = -0.338, p = 0.020), while C5:OH was positively correlated with apolipoprotein B (APOB) and BUN (r = 0.386, p = 0.015; r = 0.327, p = 0.025). Besides, the change of urine CMPF was positively correlated with serum CMPF (r = 0.646, p < 0.001). In conclusion, the present study confirmed that CMPF is a strong biomarker of fish oil, and indicated that marine n-3 PUFA intake might have a beneficial effect on lipid metabolism and renal function in patients with T2D.

Association of erythrocyte n-3 polyunsaturated fatty acids with incident type 2 diabetes in a Chinese population.

BACKGROUND & AIMS: The association between circulating n-3 polyunsaturated fatty acid (PUFA) biomarkers and incident type 2 diabetes in Asian populations remains unclear. We aimed to examine the association of erythrocyte n-3 PUFA with incident type 2 diabetes in a Chinese population. METHODS: A total of 2671 participants, aged 40-75 y, free of type 2 diabetes at baseline, were included in the present analysis. Incident type 2 diabetes cases (n = 213) were ascertained during median follow-up of 5.6 years. Baseline erythrocyte fatty acids were measured by gas chromatography. We used multivariable Cox regression models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of type 2 diabetes across quartiles of erythrocyte n-3 PUFA. RESULTS: After adjustment for potential confounders, HRs (95% CIs) of type 2 diabetes were 0.68 (0.47, 1.00), 0.77 (0.52, 1.15), and 0.63 (0.41, 0.95) in quartiles 2-4 of docosapentaenoic acid (C22:5n-3) (P-trend = 0.07), compared with quartile 1; and 1.08 (0.74, 1.60), 1.03 (0.70, 1.51), and 0.57 (0.38, 0.86) for eicosapentaenoic acid (C20:5n-3) (P-trend = 0.007). No association was found for docosahexaenoic acid (C22:6n-3) or alpha-linolenic acid (C18:3n-3). CONCLUSIONS: Erythrocyte n-3 PUFA from marine sources (C22:5n-3 and C20:5n-3), as biomarkers of dietary marine n-3 PUFA, were inversely associated with incident type 2 diabetes in this Chinese population. Future prospective investigations in other Asian populations are necessary to confirm our findings.

Replication of a Gene-Diet Interaction at CD36, NOS3 and PPARG in Response to Omega-3 Fatty Acid Supplements on Blood Lipids: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Modulation of genetic variants on the effect of omega-3 fatty acid supplements on blood lipids is still unclear. METHODS: In a double-blind randomized controlled trial, 150 patients with type 2 diabetes (T2D) were randomized into omega-3 fatty acid group (n = 56 for fish oil and 44 for flaxseed oil) and control group (n = 50) for 180 days. All patients were genotyped for genetic variants at CD36 (rs1527483), NOS3 (rs1799983) and PPARG (rs1801282). Linear regression was used to examine the interaction between omega-3 fatty acid intervention and CD36, NOS3 or PPARG variants for blood lipids. FINDINGS: Significant interaction with omega-3 fatty acid supplements was observed for CD36 on triglycerides (p-interaction = 0.042) and PPAGR on low-density lipoprotein-cholesterol (p-interaction = 0.02). We also found a significant interaction between change in erythrocyte phospholipid omega-3 fatty acid composition and NOS3 genotype on triglycerides (p-interaction = 0.042), total cholesterol (p-interaction = 0.013) and ratio of total cholesterol to high-density lipoprotein cholesterol (p-interaction = 0.015). The T2D patients of CD36-G allele, PPARG-G allele and NOS3-A allele tended to respond better to omega-3 fatty acids in improving lipid profiles. The interaction results of the omega-3 fatty acid group were mainly attributed to the fish oil supplements. INTERPRETATION: This study suggests that T2D patients with different genotypes at CD36, NOS3 and PPARG respond differentially to intervention of omega-3 supplements in blood lipid profiles.

Prolonged Exclusive Breastfeeding Duration Is Positively Associated with Risk of Anemia in Infants Aged 12 Months.

BACKGROUND: The association between exclusive breastfeeding duration and infant anemia is not clear. OBJECTIVE: This study aimed to assess the association of exclusive breastfeeding duration with risk of anemia in infants at 12 mo of age and in children aged 48-71 mo in mainland China. METHODS: Detailed breastfeeding information and anthropometric data were obtained for 65,256 children enrolled in the Jiaxing Birth Cohort at 1, 3, and 6 mo of age. Hemoglobin was measured in 25,549 children at 12 mo and in 32,770 children between the ages of 48 and 71 mo. Anemia was defined as hemoglobin concentrations <110 g/L in children aged <60 mo and <115 g/L in children aged ≥60 mo. The associations between exclusive breastfeeding duration and risk of anemia were assessed as adjusted ORs by using multiple logistic regression. RESULTS: Overall anemia prevalences at 12 and 48-71 mo were 24.9% and 9.9%, respectively. Exclusive breastfeeding for ≥6 mo, but not for 3-5 mo, was significantly associated with a higher risk of anemia in infants at age 12 mo (OR: 1.15; 95% CI: 1.02, 1.29; P = 0.02) compared with exclusive breastfeeding for <3 mo. For young children aged 48-71 mo, this finding was only marginally significant (OR: 1.13; 95% CI: 0.99, 1.29; P = 0.08). Prolonged duration of exclusive breastfeeding was also significantly associated with decreased hemoglobin concentrations of -0.56 g/L (95% CI: -1.10, -0.03; P = 0.04) in infants and -0.99 g/L (95% CI: -1.44, -0.55; P < 0.001) in young children. CONCLUSIONS: Exclusive breastfeeding for ≥6 mo was associated with an increased risk of anemia in infants aged 12 mo and with lower hemoglobin concentrations in both infants aged 12 mo and young children aged 48-71 mo. Parents should provide infants with an adequate source of iron after 6 mo of exclusive breastfeeding.

Serum metabolomics profiles in response to n-3 fatty acids in Chinese patients with type 2 diabetes: a double-blind randomised controlled trial.

We aimed to investigate the change of serum metabolomics in response to n-3 fatty acid supplements in Chinese patients with type 2 diabetes (T2D). In a double-blind parallel randomised controlled trial, 59 Chinese T2D patients were randomised to receive either fish oil (FO), flaxseed oil (FSO) or corn oil capsules (CO, served as a control group) and followed up for 180 days. An additional 17 healthy non-T2D participants were recruited at baseline for cross-sectional comparison between cases and non-cases. A total of 296 serum metabolites were measured among healthy controls and T2D patients before and after the intervention. Serum 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) (P-interaction = 1.8 × 10(-7)) was the most significant metabolite identified by repeated-measures ANOVA, followed by eicosapentaenoate (P-interaction = 4.6 × 10(-6)), 1-eicosapentaenoylglycerophosphocholine (P-interaction = 3.4 × 10(-4)), docosahexaenoate (P-interaction = 0.001), linolenate (n-3 or n-6, P-interaction = 0.005) and docosapentaenoate (n-3, P-interaction = 0.021). CMPF level was lower in T2D patients than in the healthy controls (P = 0.014) and it was significantly increased in the FO compared with CO group (P = 1.17 × 10(-7)). Furthermore, change of CMPF during the intervention was negatively correlated with change of serum triglycerides (P = 0.016). In conclusion, furan fatty acid metabolite CMPF was the strongest biomarker of fish oil intake. The association of CMPF with metabolic markers warrants further investigation.

Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.

BACKGROUND: Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations. METHODS AND FINDINGS: Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries. Country-specific hazard ratios (HRs) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs, α-linolenic acid (ALA) was inversely associated with T2D (HR per standard deviation [SD] 0.93; 95% CI 0.88-0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77-0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85-0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with γ-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs. CONCLUSIONS: These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class.

Effects of n-3 fatty acid supplements on glycemic traits in Chinese type 2 diabetic patients: A double-blind randomized controlled trial.

SCOPE: To investigate the effects of n-3 fatty acid supplements, both marine and plant-based, on glycemic traits in Chinese type 2 diabetes patients. METHOD AND RESULTS: In a double-blind randomized controlled trial, 185 recruited Chinese type 2 diabetes patients were randomized to either fish oil (FO, n = 63), flaxseed oil (FSO, n = 61), or corn oil group (served as control group, n = 61) for 180 days. The patients were asked to take corresponding oil capsules (four capsules/day), which totally provided 2 g/day of eicosapentaenoic acid + docosahexaenoic acid in FO group and 2.5 g/day of alpha-linolenic acid in FSO group. No group × time interaction was observed for homeostatic model assessment of insulin resistance, fasting insulin, or glucose. Significant group × time interaction (P = 0.035) was observed for glycated hemoglobin A1c (HbA1c), with HbA1c decreased in FO group compared with corn oil group (P = 0.037). We also found significant group × time interactions for lipid traits, including LDL cholesterol (P = 0.043), total cholesterol (P = 0.021), total cholesterol/HDL cholesterol (P = 0.009), and triacylglycerol (P = 0.003), with the lipid profiles improved in FO group. No significant effects of FSO on glycemic traits or blood lipids were observed. CONCLUSIONS: Marine n-3 PUFA supplements may improve glycemic control and lipid profiles among Chinese type 2 diabetic patients.

Effect of Marine-Derived n-3 Polyunsaturated Fatty Acids on Major Eicosanoids: A Systematic Review and Meta-Analysis from 18 Randomized Controlled Trials.

BACKGROUND: Marine-derived n-3 polyunsaturated fatty acids (PUFA) may have a beneficial effect on inflammation via lowering pro-inflammatory eicosanoid concentrations. We aimed to assess the effect of marine-derived n-3 PUFA on prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and leukotriene B4 (LTB4) through systematic review and meta-analysis of randomized controlled trials. METHOD AND FINDINGS: A structured search strategy on PubMed, Web of Science and Cochrane up to November 2015 was undertaken in this meta-analysis. Standard mean difference was used to calculate the effect size of marine-derived n-3 PUFA on PGE2, TXB2 and LTB4 in a random-effect model. A total of 18 RCTs with 826 subjects were included in this systematic review and meta-analysis. Supplementation of marine-derived n-3 PUFA significantly decreased concentrations of TXB2 in serum/plasma in subjects with high risk of cardiovascular diseases (SMD:-1.26; 95% CI: -1.65, -0.86) and LTB4 in neutrophils in unhealthy subjects (subjects with non-autoimmune chronic diseases or auto-immune diseases) (SMD:-0.59: 95% CI: -1.02, -0.16). Subgroup analyses showed a significant reduction of LTB4 in subjects with rheumatoid arthritis (SMD: -0.83; 95% CI: -1.37, -0.29), but not in non-autoimmune chronic disease patients (SMD: -0.33; 95% CI: -0.97, 0.31). No significant publication bias was shown in the meta-analysis. CONCLUSIONS: Marine-derived n-3 PUFA had a beneficial effect on reducing the concentration of TXB2 in blood of subjects with high risk of CVD as well as LTB4 in neutrophils in unhealthy subjects, and that subjects with RA showed lower LTB4 content with supplementation of marine-derived n-3 PUFA.

Pre-conceptional intake of folic acid supplements is inversely associated with risk of preterm birth and small-for-gestational-age birth: a prospective cohort study.

Associations of folic acid supplementation with risk of preterm birth (PTB) and small-for-gestational-age (SGA) birth were unclear for the Chinese populations. The aim of the present study was to investigate the associations in a large Chinese prospective cohort study: the Jiaxing Birth Cohort. In the Jiaxing Birth Cohort, 240 954 pregnant women visited local clinics or hospitals within their first trimester in Southeast China during 1999-2012. Information on anthropometric parameters, folic acid supplementation and other maternal characteristics were collected by in-person interviews during their first visit. Pregnancy outcomes were recorded during the follow-up of these participants. Multinomial logistic regression was used to examine the association of folic acid supplementation with pregnancy outcomes. The prevalence of folic acid supplementation was 24·9% in the cohort. The prevalence of PTB and SGA birth was 3·48 and 9·2%, respectively. Pre-conceptional folic acid supplementation was associated with 8% lower risk of PTB (relative risk (RR) 0·92; 95% CI 0·85, 1·00; P=0·04) and 19% lower risk of SGA birth (RR 0·81; 95% CI 0·70, 0·95; P=0·008), compared with non-users. Higher frequency of pre-conceptional folic acid use was associated with lower risk of PTB (P trend=0·032) and SGA birth (P trend=0·046). No significant association between post-conceptional initiation of folic acid supplementation and either outcome was observed. In conclusion, the present study suggests an association between pre-conceptional, but not post-conceptional, folic acid supplementation and lower risk of PTB and SGA birth in the Jiaxing Birth Cohort. Further research in other cohorts of large sample size is needed to replicate these findings.

Tea consumption and mortality of all cancers, CVD and all causes: a meta-analysis of eighteen prospective cohort studies.

Epidemiological studies have demonstrated inconsistent associations between tea consumption and mortality of all cancers, CVD and all causes. To obtain quantitative overall estimates, we conducted a dose-response meta-analysis of prospective cohort studies. A literature search in PubMed and Embase up to April 2015 was conducted for all relevant papers published. Random-effects models were used to calculate pooled relative risks (RR) with 95 % CI. In eighteen prospective studies, there were 12 221, 11 306 and 55 528 deaths from all cancers, CVD and all causes, respectively. For all cancer mortality, the summary RR for the highest v. lowest category of green tea and black tea consumption were 1·06 (95 % CI 0·98, 1·15) and 0·79 (95 % CI 0·65, 0·97), respectively. For CVD mortality, the summary RR for the highest v. lowest category of green tea and black tea consumption were 0·67 (95 % CI 0·46, 0·96) and 0·88 (95 % CI 0·77, 1·01), respectively. For all-cause mortality, the summary RR for the highest v. lowest category of green tea and black tea consumption were 0·80 (95 % CI 0·68, 0·93) and 0·90 (95 % CI 0·83, 0·98), respectively. The dose-response analysis indicated that one cup per d increment of green tea consumption was associated with 5 % lower risk of CVD mortality and with 4 % lower risk of all-cause mortality. Green tea consumption was significantly inversely associated with CVD and all-cause mortality, whereas black tea consumption was significantly inversely associated with all cancer and all-cause mortality.

Modulation of the Association between the PEPD Variant and the Risk of Type 2 Diabetes by n-3 Fatty Acids in Chinese Hans.

BACKGROUND/AIMS: Type 2 diabetes (T2D) is modulated by the interactions between genetic and dietary factors. This study sought to examine whether the associations of genome-wide association study (GWAS)-identified genetic variants with T2D risk were modulated by n-3 fatty acids in Chinese Hans. METHODS: Six hundred and twenty-two T2D patients and 293 healthy controls were recruited. Erythrocyte phospholipid fatty acids were measured by standard methods. Nine GWAS-identified T2D-related single-nucleotide polymorphisms (SNPs) were genotyped. These SNPs were all identified in GWAS of Asian populations with a high minor allele frequency (>0.2). RESULTS: Among the 9 SNPs, only rs3786897 at PEPD (peptidase D) showed a significant interaction with n-3 fatty acids (p(interaction) after Bonferroni correction = 0.027). The rs3786897 A allele was associated with a higher risk of T2D [GA+AA vs. GG: odds ratio (OR) = 2.16, 95% confidence interval (CI) 1.32-3.55] when n-3 fatty acids were lower than the population median, but no significant association (GA+AA vs. GG: OR = 0.63, 95% CI 0.35-1.12) was observed when n-3 fatty acids were higher than the median. CONCLUSIONS: The association between the PEPD genetic variant and the risk of T2D was modulated by n-3 fatty acids. Higher n-3 fatty acids may abolish the adverse effect of the risk allele at PEPD for T2D.

Effect of individual omega-3 fatty acids on the risk of prostate cancer: a systematic review and dose-response meta-analysis of prospective cohort studies.

Epidemiological studies have suggested inconsistent associations between omega-3 polyunsaturated fatty acids (n-3 PUFAs) and prostate cancer (PCa) risk. We performed a dose-response meta-analysis of prospective observational studies investigating both dietary intake and circulating n-3 PUFAs and PCa risk. PubMed and EMBASE prior to February 2014 were searched, and 16 publications were eligible. Blood concentration of docosahexaenoic acid, but not alpha-linolenic acid or eicosapentaenoic acid, showed marginal positive association with PCa risk (relative risk for 1% increase in blood docosahexaenoic acid concentration: 1.02; 95% confidence interval, 1.00-1.05; I(2) = 26%; P = 0.05 for linear trend), while dietary docosahexaenoic acid intake showed a non-linear positive association with PCa risk (P < 0.01). Dietary alpha-linolenic acid was inversely associated with PCa risk (relative risk for 0.5 g/day increase in alpha-linolenic acid intake: 0.99; 95% confidence interval, 0.98-1.00; I(2) = 0%; P = 0.04 for linear trend), which was dominated by a single study. Subgroup analyses indicated that blood eicosapentaenoic acid concentration and blood docosahexaenoic acid concentration were positively associated with aggressive PCa risk and nonaggressive PCa risk, respectively. Among studies with nested case-control study designs, a 0.2% increase in blood docosapentaenoic acid concentration was associated with a 3% reduced risk of PCa (relative risk 0.97; 95% confidence interval, 0.94-1.00; I(2) = 44%; P = 0.05 for linear trend). In conclusion, different individual n-3 PUFA exposures may exhibit different or even opposite associations with PCa risk, and more prospective studies, especially those examining dietary n-3 PUFAs and PCa risk stratified by severity of cancer, are needed to confirm the results.