The effects of the Green-Mediterranean diet on cardiometabolic health are linked to gut microbiome modifications: a randomized controlled trial.

BACKGROUND: Previous studies have linked the Mediterranean diet (MED) with improved cardiometabolic health, showing preliminary evidence for a mediating role of the gut microbiome. We recently suggested the Green-Mediterranean (Green-MED) diet as an improved version of the healthy MED diet, with increased consumption of plant-based foods and reduced meat intake. Here, we investigated the effects of MED interventions on the gut microbiota and cardiometabolic markers, and the interplay between the two, during the initial weight loss phase of the DIRECT-PLUS trial. METHODS: In the DIRECT-PLUS study, 294 participants with abdominal obesity/dyslipidemia were prospectively randomized to one of three intervention groups: healthy dietary guidelines (standard science-based nutritional counseling), MED, and Green-MED. Both isocaloric MED and Green-MED groups were supplemented with 28g/day walnuts. The Green-MED group was further provided with daily polyphenol-rich green tea and Mankai aquatic plant (new plant introduced to a western population). Gut microbiota was profiled by 16S rRNA for all stool samples and shotgun sequencing for a select subset of samples. RESULTS: Both MED diets induced substantial changes in the community structure of the gut microbiome, with the Green-MED diet leading to more prominent compositional changes, largely driven by the low abundant, "non-core," microorganisms. The Green-MED diet was associated with specific microbial changes, including enrichments in the genus Prevotella and enzymatic functions involved in branched-chain amino acid degradation, and reductions in the genus Bifidobacterium and enzymatic functions responsible for branched-chain amino acid biosynthesis. The MED and Green-MED diets were also associated with stepwise beneficial changes in body weight and cardiometabolic biomarkers, concomitantly with the increased plant intake and reduced meat intake. Furthermore, while the level of adherence to the Green-MED diet and its specific green dietary components was associated with the magnitude of changes in microbiome composition, changes in gut microbial features appeared to mediate the association between adherence to the Green-MED and body weight and cardiometabolic risk reduction. CONCLUSIONS: Our findings support a mediating role of the gut microbiome in the beneficial effects of the Green-MED diet enriched with Mankai and green tea on cardiometabolic risk factors. TRIAL REGISTRATION: The study was registered on ClinicalTrial.gov ( NCT03020186 ) on January 13, 2017.

Dietary n-6 polyunsaturated fatty acids and cardiovascular disease: Epidemiologic evidence.

Epidemiologists have been studying the effect of n-6 polyunsaturated fatty acids (PUFAs) intake on the risk of cardiovascular disease (CVD) for many decades. Abundant evidence from prospective studies on the clinical endpoints of CVD, including cohort studies measuring n-6 PUFA intake by food frequency questionnaires and nested case-control studies using biomarkers of intake level, strongly support that higher intakes of n-6 PUFAs are associated with a lower risk of CVD. Furthermore, a significant reduction in CVD risk can be achieved when saturated fatty acids (SFAs) is replaced by n-6 PUFAs. Evidence from appropriately designed and vigorously executed randomized controlled trials support that high-PUFA (predominantly linoleic acid) and low-SFA diets, compared to high-SFA diets, reduced the risk of coronary heart disease. Overall, epidemiologic studies provide a solid evidence base of the current dietary guidelines that recommend replacing SFA by PUFA, both n-6 and n-3 PUFA, for CVD prevention.

Precision nutrition for prevention and management of type 2 diabetes.

Precision nutrition aims to prevent and manage chronic diseases by tailoring dietary interventions or recommendations to one or a combination of an individual's genetic background, metabolic profile, and environmental exposures. Recent advances in genomics, metabolomics, and gut microbiome technologies have offered opportunities as well as challenges in the use of precision nutrition to prevent and manage type 2 diabetes. Nutrigenomics studies have identified genetic variants that influence intake and metabolism of specific nutrients and predict individuals' variability in response to dietary interventions. Metabolomics has revealed metabolomic fingerprints of food and nutrient consumption and uncovered new metabolic pathways that are potentially modified by diet. Dietary interventions have been successful in altering abundance, composition, and activity of gut microbiota that are relevant for food metabolism and glycaemic control. In addition, mobile apps and wearable devices facilitate real-time assessment of dietary intake and provide feedback which can improve glycaemic control and diabetes management. By integrating these technologies with big data analytics, precision nutrition has the potential to provide personalised nutrition guidance for more effective prevention and management of type 2 diabetes. Despite these technological advances, much research is needed before precision nutrition can be widely used in clinical and public health settings. Currently, the field of precision nutrition faces challenges including a lack of robust and reproducible results, the high cost of omics technologies, and methodological issues in study design as well as high-dimensional data analyses and interpretation. Evidence is needed to support the efficacy, cost-effectiveness, and additional benefits of precision nutrition beyond traditional nutrition intervention approaches. Therefore, we should manage unrealistically high expectations and balance the emerging field of precision nutrition with public health nutrition strategies to improve diet quality and prevent type 2 diabetes and its complications.

Plasma lipidomic profiles and cardiovascular events in a randomized intervention trial with the Mediterranean diet.

Background: Lipid metabolites may partially explain the inverse association between the Mediterranean diet (MedDiet) and cardiovascular disease (CVD).Objective: We evaluated the associations between 1) lipid species and the risk of CVD (myocardial infarction, stroke, or cardiovascular death); 2) a MedDiet intervention [supplemented with extra virgin olive oil (EVOO) or nuts] and 1-y changes in these molecules; and 3) 1-y changes in lipid species and subsequent CVD.Design: With the use of a case-cohort design, we profiled 202 lipid species at baseline and after 1 y of intervention in the PREDIMED (PREvención con DIeta MEDiterránea) trial in 983 participants [230 cases and a random subcohort of 790 participants (37 overlapping cases)].Results: Baseline concentrations of cholesterol esters (CEs) were inversely associated with CVD. A shorter chain length and higher saturation of some lipids were directly associated with CVD. After adjusting for multiple testing, direct associations remained significant for 20 lipids, and inverse associations remained significant for 6 lipids. When lipid species were weighted by the number of carbon atoms and double bonds, the strongest inverse association was found for CEs [HR: 0.39 (95% CI: 0.22, 0.68)] between extreme quintiles (P-trend = 0.002). Participants in the MedDiet + EVOO and MedDiet + nut groups experienced significant (P < 0.05) 1-y changes in 20 and 17 lipids, respectively, compared with the control group. Of these changes, only those in CE(20:3) in the MedDiet + nuts group remained significant after correcting for multiple testing. None of the 1-y changes was significantly associated with CVD risk after correcting for multiple comparisons.Conclusions: Although the MedDiet interventions induced some significant 1-y changes in the lipidome, they were not significantly associated with subsequent CVD risk. Lipid metabolites with a longer acyl chain and higher number of double bonds at baseline were significantly and inversely associated with the risk of CVD.

Potential Impact of Time Trend of Life-Style Factors on Cardiovascular Disease Burden in China.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of death in China. Evaluation of risk factors and their impacts on disease burden is important for future public health initiatives and policy making. OBJECTIVES: The study used data from a cohort of the China Health and Nutrition Survey to estimate time trends in cardiovascular risk factors from 1991 to 2011. METHODS: We applied the comparative risk assessment method to estimate the number of CVD events attributable to all nonoptimal levels (e.g., theoretical-minimum-risk exposure distribution [TMRED]) of each risk factor. RESULTS: In 2011, high blood pressure, high low-density lipoprotein cholesterol, and high blood glucose were associated with 3.1, 1.4, and 0.9 million CVD events in China, respectively. Increase in body mass index was associated with an increase in attributable CVD events, from 0.5 to 1.1 million between 1991 and 2011, whereas decreased physical activity was associated with a 0.7-million increase in attributable CVD events. In 2011, 53.4% of men used tobacco, estimated to be responsible for 30.1% of CVD burden in men. Dietary quality improved, but remained suboptimal; mean intakes were 5.4 (TMRED: 2.0) g/day for sodium, 67.7 (TMRED: 300.0) g/day for fruits, 6.2 (TMRED: 114.0) g/day for nuts, and 25.0 (TMRED: 250.0) mg/day for marine omega-3 fatty acids in 2011. CONCLUSIONS: High blood pressure remains the most important individual risk factor related to CVD burden in China. Increased body mass index and decreased physical activity were also associated with the increase in CVD burden from 1991 to 2011. High rates of tobacco use in men and unhealthy dietary factors continue to contribute to the burden of CVD in China.