Gut microbiota-derived metabolite Trimethylamine-N-oxide (TMAO) and multiple health outcomes:an umbrella review and updated meta-analysis

BACKGROUND: Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite produced from dietary nutrients. Many studies have discovered that circulating TMAO levels are linked to a wide range of health outcomes. OBJECTIVES: This study aimed to summarize health outcomes related to circulating TMAO levels. METHODS: We searched Embase, Medline, Web of Science and Scopus databases from inception to 15 February 2022 to identify and update meta-analyses examining the associations between TMAO and multiple health outcomes. For each health outcome, we estimated the summary effect size, 95% prediction confidence interval (CI), between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. These metrics were used to evaluate the evidence credibility of the identified associations. RESULTS: This umbrella review identified 24 meta-analyses that investigated the association between circulating TMAO levels and health outcomes including all-cause mortality, cardiovascular diseases, diabetes mellitus, cancer, and renal function. We updated these meta-analyses by including a total of 82 individual studies in 18 unique health outcomes. Among them, 14 associations were nominally significant. After evidence credibility assessment, we found six (33%) associations (i.e., all-cause mortality, cardiovascular disease mortality, major adverse cardiovascular events, hypertension, diabetes mellitus, and glomerular filtration rate) to present highly suggestive evidence. CONCLUSIONS: TMAO might be a novel biomarker related to human health conditions including all-cause mortality, hypertension, cardiovascular disease, diabetes, cancer and kidney function. Further studies are needed to investigate whether circulating TMAO levels could be an intervention target for chronic disease

Systematic meta-analyses, field synopsis and global assessment of the evidence of genetic association studies in colorectal cancer

Objective: To provide an understanding of the role of common genetic variations in colorectal cancer (CRC) risk, we report an updated field synopsis and comprehensive assessment of evidence to catalogue all genetic markers for CRC (CRCgene2). Design: We included 869 publications after parallel literature review and extracted data for 1063 polymorphisms in 303 different genes. Meta-Analyses were performed for 308 single nucleotide polymorphisms (SNPs) in 158 different genes with at least three independent studies available for analysis. Scottish, Canadian and Spanish data from genome-wide association studies (GWASs) were incorporated for the meta-Analyses of 132 SNPs. To assess and classify the credibility of the associations, we applied the Venice criteria and Bayesian False-Discovery Probability (BFDP). Genetic associations classified as â € positive' and â € less-credible positive' were further validated in three large GWAS consortia conducted in populations of European origin. Results: We initially identified 18 independent variants at 16 loci that were classified as â € positive' polymorphisms for their highly credible associations with CRC risk and 59 variants at 49 loci that were classified as â € less-credible positive' SNPs; 72.2% of the â € positive' SNPs were successfully replicated in three large GWASs and the ones that were not replicated were downgraded to â € less-credible' positive (reducing the â € positive' variants to 14 at 11 loci). For the remaining 231 variants, which were previously reported, our meta-Analyses found no evidence to support their associations with CRC risk. Conclusion: The CRCgene2 database provides an updated list of genetic variants related to CRC risk by using harmonised methods to assess their credibility.</p

The n-3 Polyunsaturated Fatty Acids Supplementation Improved the Cognitive Function in the Chinese Elderly with Mild Cognitive Impairment: A Double-Blind Randomized Controlled Trial

Objective: Intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) may protect against mild cognitive impairment (MCI). However, there is still a lack of the n-3 PUFAs intervention in the elderly with MCI in China. The aim of the present study was to investigate the effect of n-3 PUFA supplementation on cognitive function in the Chinese elderly with MCI. Methods: Eighty six MCI individuals aged 60 years or older were randomly assigned to receive either n-3 PUFAs (480 mg DHA and 720 mg EPA per day, n = 44) or placebo (olive oil, n = 42) capsules. The changes of cognitive functions were assessed using Basic Cognitive Aptitude Tests (BCAT). Results: The mean age of participants was 71 years old, and 59% of the participants were men. n-3 PUFA supplementation was associated with improved total BCAT scores, perceptual speed, space imagery efficiency, and working memory (p &lt; 0.01), but not with mental arithmetic efficiency or recognition memory (p &gt; 0.05). Subgroup analysis by sex showed that n-3 PUFAs significantly improved perceptual speed (p = 0.001), space imagery efficiency (p = 0.013), working memory (p = 0.018), and total BCAT scores (p = 0.000) in males. However, in females, the significant beneficial effects can only be observed in perceptual speed (p = 0.027), space imagery efficiency (p = 0.006), and total BCAT scores (p = 0.015)—not working memory (p = 0.113). Conclusion: n-3 PUFAs can improve cognitive function in people with MCI. Further studies with different fish oil dosages, longer intervention periods, and larger sample sizes should be investigated before definite recommendations can be made

Effects of Anthocyanin on Serum Lipids in Dyslipidemia Patients: A Systematic Review and Meta-Analysis

<div><p>Background</p><p>Dyslipidemia was present in most of the patients with coronary heart disease. Epidemiological evidence suggests that anthocyanin has some effects on the serum lipid. However, these results are controversial. This study aimed at collecting current clinical evidence and evaluating the effects of anthocyanin supplementation on total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in dialysis patients.</p><p>Methods</p><p>The search included PubMed, Web of Science, MEDLINE, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database (up to July 2015) to identify randomized controlled trials (RCTs) on the association between anthocyanin and serum lipids. RevMan (version 5.2) was used for Meta-analysis. Meta-regression analysis, sensitivity analysis and Egger’s weighted regression tests were performed by using STATA software (version 12.0; StatCorp, College Station, TX, USA).</p><p>Results</p><p>Six studies (seven arms) involving 586 subjects were included in this meta-analysis. The results showed that anthocyanin supplementation has significant effects on TC [MD = -24.06, 95% <i>CI</i>(-45.58 to -2.64) mg/dL, <i>I</i>² = 93%], TG [MD = -26.14, 95%<i>CI</i>(-40.20 to -3.08) mg/dL, <i>I</i>² = 66%1], LDL-C [MD = -22.10, 95% <i>CI</i> (-34.36 to -9.85) mg/dL, <i>I</i>² = 61%], and HDL-C(MD = 5.58, 95% <i>CI</i> (1.02 to 10.14) mg/dL;<i>I</i>² = 90%).</p><p>Conclusion</p><p>Anthocyanin supplementation significantly reduces serum TC, TG, and LDL-C levels in patients with dyslipidemia, and increases HDL-C. Further rigorously designed RCTs with larger sample sizes are needed to confirm the effectiveness of anthocyanin supplementation for dyslipidemia, especially hypo high density lipoprotein cholesterolemia.</p></div

Flow diagram of the study selection process.

<p>Flow chart of number of studies identified and included into the review.</p

Demographic characteristics and baseline parameters of included studies in this study.

<p>Demographic characteristics and baseline parameters of included studies in this study.</p

Forest plot between anthocyanin supplementation and serum lipids (A: total cholesterol, B: triglycerides, C: low-density lipoprotein cholesterol, D: high-density lipoprotein cholesterol).

<p>Forest plot between anthocyanin supplementation and serum lipids (A: total cholesterol, B: triglycerides, C: low-density lipoprotein cholesterol, D: high-density lipoprotein cholesterol).</p

The association between dietary isoflavones intake and gastric cancer risk: a meta-analysis of epidemiological studies

Abstract Background Isoflavones, a class of phytoestrogenic compounds, are abundant in soybeans. A number of epidemiological studies have investigated the association between dietary isoflavones intake and the risk of gastric cancer. However, the results are inconclusive. Therefore, the meta-analysis was conducted to evaluate the effect of dietary isoflavones intake on the risk of gastric cancer. Methods Relevant studies from May 1992 to May 2017 were identified through searching PubMed and Web of Science. Additional articles were identified from the reference lists of relevant review articles. Pooled risk ratios (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a fixed-effects model. Funnel plot and Egger’s test were used to evaluate publication bias. Results Seven articles reporting 12 studies were included in the current meta-analysis. We found no significant association between dietary isoflavones intake and gastric cancer risk with the highest versus the lowest categories of dietary isoflavones intake (OR = 0.97, 95% CI = 0.87–1.09, I 2 = 27.5%). Subgroup analyses generally yield similar results. Conclusions Higher dietary isoflavones intake is not associated with a decline in the risk of gastric cancer

Intakes of Folate, Vitamin B6, and Vitamin B12 in Relation to All-Cause and Cause-Specific Mortality: A National Population-Based Cohort

The evidence regarding the intake of dietary folate, vitamin B6, and vitamin B12 in relation to mortality in the general population is limited. This study aimed to examine the relationship between dietary intakes of folate, vitamin B6, and vitamin B12 in relation to all-cause and cause-specific mortality in a large U.S. cohort. This study included a total of 55,569 adults from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 1999–2014. Vital data were determined by linking with the National Death Index records through 31 December 2015. Cox proportional hazards models were used to investigate the relationships of all-cause and cause-specific mortality with dietary folate, vitamin B6, and vitamin B12 intake. Dietary intakes of folate and vitamin B6 were inversely associated with mortality from all-cause, cardiovascular disease, and cancer for men and with mortality from all-cause and cardiovascular disease for women. In men, the multivariable hazard ratios (95% confidence intervals) for the highest versus lowest quintiles of folate and vitamin B6 were 0.77 (0.71–0.85) and 0.79 (0.71–0.86) for all-cause mortality, 0.59 (0.48–0.72) and 0.69 (0.56–0.85) for CVD mortality, and 0.68 (0.56–0.84) and 0.73 (0.60–0.90) for cancer mortality, respectively. Among women, the multivariable hazard ratios (95% confidence intervals) for the highest versus lowest quintiles of folate and vitamin B6 were 0.86 (0.78–0.95) and 0.88 (0.80–0.97) for all-cause mortality and 0.53 (0.41–0.69) and 0.56 (0.44–0.73) for CVD mortality, respectively. No significant associations between dietary vitamin B12 and all-cause and cause-specific mortality were observed. In conclusion, higher dietary intakes of folate and vitamin B6 were significantly associated with lower all-cause and cardiovascular mortality. Our findings suggest that increasing the intake of folate and vitamin B6 may lower the mortality risk among U.S. adults

Effects of Coenzyme Q10 on Markers of Inflammation: A Systematic Review and Meta-Analysis

<div><p>Background/Objective</p><p>Chronic inflammation contributes to the onset and development of metabolic diseases. Clinical evidence has suggested that coenzyme Q10 (CoQ10) has some effects on inflammatory markers. However, these results are equivocal. The aim of this systematic review was to assess the effects of CoQ10 on serum levels of inflammatory markers in people with metabolic diseases.</p><p>Methods</p><p>Electronic databases were searched up to February 2016 for randomized controlled trials (RCTs). The outcome parameters were related to inflammatory factors, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and C reactive protein (CRP). RevMan software was used for meta-analysis. Meta-regression analysis, Egger line regression test and Begg rank correlation test were performed by STATA software.</p><p>Results</p><p>Nine trials involving 428 subjects were included in this meta-analysis. The results showed that compared with control group, CoQ10 supplementation has significantly improved the serum level of CoQ10 by 1.17μg/ml [MD = 1.17, <i>95% CI</i> (0.47 to 1.87) μg/ml, <i>I</i>² = 94%]. Meanwhile, it has significantly decreased TNF-α by 0.45 pg/ml [MD = -0.45, <i>95% CI</i> (-0.67 to -0.24) pg/ml, <i>I</i>² = 0%]. No significant difference was observed between CoQ10 and placebo with regard to CRP [MD = -0.21, <i>95% CI</i> (-0.60 to 0.17) mg/L, <i>I</i>² = 21%] and IL-6 [MD = -0.89, <i>95% CI</i> (-1.95 to 0.16) pg/ml, <i>I</i>² = 84%].</p><p>Conclusions</p><p>CoQ10 supplementation may partly improve the process of inflammatory state. The effects of CoQ10 on inflammation should be further investigated by conducting larger sample size and well-defined trials of long enough duration.</p></div