Nutritional metabolomics is rapidly evolving to integrate nutrition with complex metabolomics data to discover new biomarkers of nutritional exposure and status.
The purpose of this review is to ...provide a broad overview of the measurement techniques, study designs, and statistical approaches used in nutrition metabolomics, as well as to describe the current knowledge from epidemiologic studies identifying metabolite profiles associated with the intake of individual nutrients, foods, and dietary patterns.
A wide range of technologies, databases, and computational tools are available to integrate nutritional metabolomics with dietary and phenotypic information. Biomarkers identified with the use of high-throughput metabolomics techniques include amino acids, acylcarnitines, carbohydrates, bile acids, purine and pyrimidine metabolites, and lipid classes. The most extensively studied food groups include fruits, vegetables, meat, fish, bread, whole grain cereals, nuts, wine, coffee, tea, cocoa, and chocolate. We identified 16 studies that evaluated metabolite signatures associated with dietary patterns. Dietary patterns examined included vegetarian and lactovegetarian diets, omnivorous diet, Western dietary patterns, prudent dietary patterns, Nordic diet, and Mediterranean diet. Although many metabolite biomarkers of individual foods and dietary patterns have been identified, those biomarkers may not be sensitive or specific to dietary intakes. Some biomarkers represent short-term intakes rather than long-term dietary habits. Nonetheless, nutritional metabolomics holds promise for the development of a robust and unbiased strategy for measuring diet. Still, this technology is intended to be complementary, rather than a replacement, to traditional well-validated dietary assessment methods such as food frequency questionnaires that can measure usual diet, the most relevant exposure in nutritional epidemiologic studies.
Due to the rapidly increasing availability of metabolomics data in prospective studies, an update of the meta evidence on metabolomics and type 2 diabetes risk is warranted.
To conduct an updated ...systematic review and meta-analysis of plasma, serum, and urine metabolite markers and incident type 2 diabetes.
We searched PubMed and Embase until 6 March 2021.
We selected prospective observational studies where investigators used high-throughput techniques to investigate the relationship between plasma, serum, or urine metabolites and incident type 2 diabetes.
Baseline metabolites per-SD risk estimates and 95% CIs for incident type 2 diabetes were extracted from all eligible studies.
A total of 61 reports with 71,196 participants and 11,771 type 2 diabetes cases/events were included in the updated review. Meta-analysis was performed for 412 metabolites, of which 123 were statistically significantly associated (false discovery rate-corrected P < 0.05) with type 2 diabetes risk. Higher plasma and serum levels of certain amino acids (branched-chain, aromatic, alanine, glutamate, lysine, and methionine), carbohydrates and energy-related metabolites (mannose, trehalose, and pyruvate), acylcarnitines (C4-DC, C4-OH, C5, C5-OH, and C8:1), the majority of glycerolipids (di- and triacylglycerols), (lyso)phosphatidylethanolamines, and ceramides included in meta-analysis were associated with higher risk of type 2 diabetes (hazard ratio 1.07-2.58). Higher levels of glycine, glutamine, betaine, indolepropionate, and (lyso)phosphatidylcholines were associated with lower type 2 diabetes risk (hazard ratio 0.69-0.90).
Substantial heterogeneity (I2 > 50%, τ2 > 0.1) was observed for some of the metabolites.
Several plasma and serum metabolites, including amino acids, lipids, and carbohydrates, are associated with type 2 diabetes risk.
Objective
The objective of this study was to evaluate the effect of skipping breakfast on body composition and cardiometabolic risk factors.
Methods
This study conducted a systematic review and ...meta‐analysis of randomized controlled trials (RCTs) evaluating breakfast skipping compared with breakfast consumption. Inclusion criteria included age ≥ 18, intervention duration ≥ 4 weeks, ≥ 7 participants per group, and ≥ 1 body composition measure. Random‐effects meta‐analyses of the effect of breakfast skipping on body composition and cardiometabolic risk factors were performed.
Results
Seven RCTs (n = 425 participants) with an average duration of 8.6 weeks were included. Compared with breakfast consumption, breakfast skipping significantly reduced body weight (weighted mean difference WMD = −0.54 kg 95% CI: −1.05 to −0.03, P = 0.04, I2 = 21.4%). Percent body fat was reported in 5 studies and was not significantly different between breakfast skippers and consumers. Three studies reported on low‐density lipoprotein cholesterol (LDL), which was increased in breakfast skippers as compared with breakfast consumers (WMD = 9.24 mg/dL 95% CI: 2.18 to 16.30, P = 0.01). Breakfast skipping did not lead to significant differences in blood pressure, total cholesterol, high‐density lipoprotein (HDL) cholesterol, triglycerides, C‐reactive protein, insulin, fasting glucose, leptin, homeostatic model assessment of insulin resistance, or ghrelin.
Conclusions
Breakfast skipping may have a modest impact on weight loss and may increase LDL in the short term. Further studies are needed to provide additional insight into the effects of breakfast skipping.
To conduct a systematic review of cross-sectional and prospective human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on prediabetes and type 2 ...diabetes.
We searched MEDLINE and EMBASE databases through August 2015. We conducted a qualitative review of cross-sectional and prospective studies. Additionally, meta-analyses of metabolite markers, with data estimates from at least three prospective studies, and type 2 diabetes risk were conducted, and multivariable-adjusted relative risks of type 2 diabetes were calculated per study-specific SD difference in a given metabolite.
We identified 27 cross-sectional and 19 prospective publications reporting associations of metabolites and prediabetes and/or type 2 diabetes. Carbohydrate (glucose and fructose), lipid (phospholipids, sphingomyelins, and triglycerides), and amino acid (branched-chain amino acids, aromatic amino acids, glycine, and glutamine) metabolites were higher in individuals with type 2 diabetes compared with control subjects. Prospective studies provided evidence that blood concentrations of several metabolites, including hexoses, branched-chain amino acids, aromatic amino acids, phospholipids, and triglycerides, were associated with the incidence of prediabetes and type 2 diabetes. We meta-analyzed results from eight prospective studies that reported risk estimates for metabolites and type 2 diabetes, including 8,000 individuals of whom 1,940 had type 2 diabetes. We found 36% higher risk of type 2 diabetes per study-specific SD difference for isoleucine (pooled relative risk 1.36 1.24-1.48; I(2) = 9.5%), 36% for leucine (1.36 1.17-1.58; I(2) = 37.4%), 35% for valine (1.35 1.19-1.53; I(2) = 45.8%), 36% for tyrosine (1.36 1.19-1.55; I(2) = 51.6%), and 26% for phenylalanine (1.26 1.10-1.44; I(2) = 56%). Glycine and glutamine were inversely associated with type 2 diabetes risk (0.89 0.81-0.96 and 0.85 0.82-0.89, respectively; both I(2) = 0.0%).
In studies using high-throughput metabolomics, several blood amino acids appear to be consistently associated with the risk of developing type 2 diabetes.
More than 50 years after the Seven Countries Study, a large number of epidemiological studies have explored the relationship between the Mediterranean diet (MD) and health, through observational, ...case-control, some longitudinal and a few experimental studies. The overall results show strong evidence suggesting a protective effect of the MD mainly on the risk of cardiovascular disease (CVD) and certain types of cancer. The beneficial effects have been attributed to the types of food consumed, total dietary pattern, components in the food, cooking techniques, eating behaviors and lifestyle behaviors, among others. The aim of this article is to review and summarize the knowledge derived from the literature focusing on the benefits of the MD on health, including those that have been extensively investigated (CVD, cancer) along with more recent issues such as mental health, immunity, quality of life, etc. The review begins with a brief description of the MD and its components. Then we present a review of studies evaluating metabolic biomarkers and genotypes in relation to the MD. Other sections are dedicated to observation and intervention studies for various pathologies. Finally, some insights into the relationship between the MD and sustainability are explored. In conclusion, the research undertaken on metabolomics approaches has identified potential markers for certain MD components and patterns, but more investigation is needed to obtain valid measures. Further evaluation of gene-MD interactions are also required to better understand the mechanisms by which the MD diet exerts its beneficial effects on health. Observation and intervention studies, particularly PREDIMED, have provided invaluable data on the benefits of the MD for a wide range of chronic diseases. However further research is needed to explore the effects of other lifestyle components associated with Mediterranean populations, its environmental impact, as well as the MD extrapolation to non-Mediterranean contexts.
Dietary polyphenols come mainly from plant-based foods including fruits, vegetables, whole grains, coffee, tea, and nuts. Polyphenols may influence glycemia and type 2 diabetes (T2D) through ...different mechanisms, such as promoting the uptake of glucose in tissues, and therefore improving insulin sensitivity. This review aims to summarize the evidence from clinical trials and observational prospective studies linking dietary polyphenols to prediabetes and T2D, with a focus on polyphenol-rich foods characteristic of the Mediterranean diet. We aimed to describe the metabolic biomarkers related to polyphenol intake and genotype-polyphenol interactions modulating the effects on T2D. Intakes of polyphenols, especially flavan-3-ols, and their food sources have demonstrated beneficial effects on insulin resistance and other cardiometabolic risk factors. Several prospective studies have shown inverse associations between polyphenol intake and T2D. The Mediterranean diet and its key components, olive oil, nuts, and red wine, have been inversely associated with insulin resistance and T2D. To some extent, these associations may be attributed to the high amount of polyphenols and bioactive compounds in typical foods conforming this traditional dietary pattern. Few studies have suggested that genetic predisposition can modulate the relationship between polyphenols and T2D risk. In conclusion, the intake of polyphenols may be beneficial for both insulin resistance and T2D risk.
Magnesium (Mg) is an essential dietary element for humans involved in key biological processes. A growing body of evidence from epidemiological studies, randomized controlled trials (RCTs) and ...meta-analyses have indicated inverse associations between Mg intake and cardiovascular diseases (CVD). The present review aims to summarize recent scientific evidence on the topic, with a focus on data from epidemiological studies assessing the associations between Mg intake and major cardiovascular (CV) risk factors and CVD. We also aimed to review current literature on circulating Mg and CVD, as well as potential biological processes underlying these observations. We concluded that high Mg intake is associated with lower risk of major CV risk factors (mainly metabolic syndrome, diabetes and hypertension), stroke and total CVD. Higher levels of circulating Mg are associated with lower risk of CVD, mainly ischemic heart disease and coronary heart disease. Further, RCTs and prospective studies would help to clarify whether Mg intake and Mg circulating levels may also protect against other CVDs and CVD death.
Background: Although several studies have assessed the effects of nut consumption (tree nuts, peanuts, and soy nuts) on blood pressure (BP), the results are conflicting. Objective: The aim was to ...conduct a systematic review and meta-analysis of published randomized controlled trials (RCTs) to estimate the effect of nut consumption on BP. Design: The databases MEDLINE, SCOPUS, ISI Web of Science, and Google Scholar were searched for RCTs carried out between 1958 and October 2013 that reported the effect of consuming single or mixed nuts (including walnuts, almonds, pistachios, cashews, hazelnuts, macadamia nuts, pecans, peanuts, and soy nuts) on systolic BP (SBP) or diastolic BP (DBP) as primary or secondary outcomes in adult populations aged ≥18 y. Relevant articles were identified by screening the abstracts and titles and the full text. Studies that evaluated the effects for <2 wk or in which the control group ingested different healthy oils were excluded. Mean ± SD changes in SBP and DBP in each treatment group were recorded for meta-analysis. Results: Twenty-one RCTs met the inclusion criteria. Our findings suggest that nut consumption leads to a significant reduction in SBP in participants without type 2 diabetes mean difference (MD): −1.29; 95% CI: −2.35, −0.22; P = 0.02 but not in the total population. Subgroup analyses of different nut types suggest that pistachios, but not other nuts, significantly reduce SBP (MD: −1.82; 95% CI: −2.97, −0.67; P = 0.002). Our study suggests that pistachios (MD: −0.80; 95% CI: −1.43, −0.17; P = 0.01) and mixed nuts (MD: −1.19; 95% CI: −2.35, −0.03; P = 0.04) have a significant reducing effect on DBP. We found no significant changes in DBP after the consumption of other nuts. Conclusions: Total nut consumption lowered SBP in participants without type 2 diabetes. Pistachios seemed to have the strongest effect on reducing SBP and DBP. Mixed nuts also reduced DBP.
Cardiovascular diseases (CVD) pose a significant public health challenge, contributing to 422 million disability-adjusted life years in 2021. The role of high-density lipoproteins (HDL) and alcohol ...consumption, one of their major modifiable determinants, remains controversial. The objective of this review is to provide a comprehensive narrative overview of HDL functionality and its predictive value for CVD in relation to patterns of alcohol consumption.
HDL phenotypes beyond HDL-cholesterol (HDL-c) such as distribution of HDL subspecies, HDL particle abundance, and reverse cholesterol transport capacity are promising indicators of atherosclerotic CVD risk. Low-to-moderate alcohol consumption seems to improve HDL functionality and reduce the incidence of CVD among primarily middle-aged men and postmenopausal women. Advancements in our understanding of HDL biogenesis, structure, and function hold promise for improving HDL-related measures and their predictive value for cardiovascular health.
Low-to-moderate alcohol consumption appears to not only increase HDL-c concentration found in the HDL fraction of plasma but also enhance HDL functionality, providing insights into the underlying mechanisms linking alcohol exposure and cardiovascular health benefits. However, rigorous, well designed intervention trials of alcohol consumption on hard cardiovascular outcomes are needed to identify robust causal associations of HDL phenotypes and alcohol consumption with cardiovascular risk.
BACKGROUND:Findings among randomized controlled trials evaluating the effect of red meat on cardiovascular disease risk factors are inconsistent. We provide an updated meta-analysis of randomized ...controlled trials on red meat and cardiovascular risk factors and determine whether the relationship depends on the composition of the comparison diet, hypothesizing that plant sources would be relatively beneficial.
METHODS:We conducted a systematic PubMed search of randomized controlled trials published up until July 2017 comparing diets with red meat with diets that replaced red meat with a variety of foods. We stratified comparison diets into high-quality plant protein sources (legumes, soy, nuts); chicken/poultry/fish; fish only; poultry only; mixed animal protein sources (including dairy); carbohydrates (low-quality refined grains and simple sugars, such as white bread, pasta, rice, cookies/biscuits); or usual diet. We performed random-effects meta-analyses comparing differences in changes of blood lipids, apolipoproteins, and blood pressure for all studies combined and stratified by specific comparison diets.
RESULTS:Thirty-six studies totaling 1803 participants were included. There were no significant differences between red meat and all comparison diets combined for changes in blood concentrations of total, low-density lipoprotein, or high-density lipoprotein cholesterol, apolipoproteins A1 and B, or blood pressure. Relative to the comparison diets combined, red meat resulted in lesser decreases in triglycerides (weighted mean difference WMD, 0.065 mmol/L; 95% CI, 0.000–0.129; P for heterogeneity <0.01). When analyzed by specific comparison diets, relative to high-quality plant protein sources, red meat yielded lesser decreases in total cholesterol (WMD, 0.264 mmol/L; 95% CI, 0.144–0.383; P<0.001) and low-density lipoprotein (WMD, 0.198 mmol/L; 95% CI, 0.065–0.330; P=0.003). In comparison with fish, red meat yielded greater decreases in low-density lipoprotein (WMD, –0.173 mmol/L; 95% CI, –0.260 to –0.086; P<0.001) and high-density lipoprotein (WMD, –0.065 mmol/L; 95% CI, –0.109 to –0.020; P=0.004). In comparison with carbohydrates, red meat yielded greater decreases in triglycerides (WMD, –0.181 mmol/L; 95% CI, –0.349 to –0.013).
CONCLUSIONS:Inconsistencies regarding the effects of red meat on cardiovascular disease risk factors are attributable, in part, to the composition of the comparison diet. Substituting red meat with high-quality plant protein sources, but not with fish or low-quality carbohydrates, leads to more favorable changes in blood lipids and lipoproteins.
PDF
