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

Rinott, E., A.Y. Meir, G. Tsaban, H. Zelicha, A. Kaplan, D. Knights, K. Tuohy, M.U. Scholz, O. Koren, M.J. Stampfer, D.D. Wang, I. Shai, I. Youngster, 2022. The effects of the Green-Mediterranean diet on cardiometabolic health are linked to gut microbiome modifications: a randomized controlled trial. Genome Med. 14(1):29. https://doi.org/10.1186/s13073-022-01015-z

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.

Impact of α-linolenic acid, the vegetable ω-3 fatty acid, on cardiovascular disease and cognition.

Sala-Vila, A., J. Fleming, P. Kris-Etherton, E. Ros, 2022. Impact of α-linolenic acid, the vegetable ω-3 fatty acid, on cardiovascular disease and cognition. Adv. Nutr. 13(5):1584–1602. https://doi.org/10.1093/advances/nmac016

Given the evidence of the health benefits of plant-based diets and long-chain n-3 fatty acids, there is keen interest in better understanding the role of alpha-linolenic acid (ALA), a plant-derived n-3 fatty acid, on cardiometabolic diseases and cognition. There is increasing evidence for ALA largely based on its major food sources (i.e., walnuts and flaxseed); however, this lags behind our understanding of long-chain n-3 fatty acids. Meta-analyses of observational studies have shown that increasing dietary ALA is associated with a 10% lower risk of total cardiovascular disease and a 20% reduced risk of fatal coronary heart disease. Three randomized controlled trials (Alpha Omega trial, Prevención con Dieta Mediterránea [PREDIMED] trial, and Lyon Diet Heart Study) all showed benefits of diets high in ALA on cardiovascular-related outcomes, but the Alpha Omega trial, designed to specifically evaluate ALA effects, only showed a trend for benefit. Randomized controlled trials have shown that dietary ALA reduced total cholesterol, low-density-lipoprotein cholesterol, triglycerides, and blood pressure, and epidemiological studies and some trials also have shown an anti-inflammatory effect of ALA; which collectively account for, in part, the cardiovascular benefits of ALA. A meta-analysis reported a trend toward diabetes risk reduction with both dietary and biomarker ALA. For metabolic syndrome and obesity, the evidence for ALA benefits is inconclusive. The role of ALA in cognition is in the early stages but shows promising evidence of counteracting cognitive impairment. Much has been learned about the health benefits of ALA and with additional research we will be better positioned to make strong evidence-based dietary recommendations for the reduction of many chronic diseases.

Association of nut consumption with CVD risk factors in young to middle-aged adults: The Coronary Artery Risk Development in Young Adults (CARDIA) study. 

Yi, S.Y., L.M. Steffen, X. Zhou, J.M. Shikany, D.R., Jr. Jacobs, 2022. Association of nut consumption with CVD risk factors in young to middle-aged adults: The Coronary Artery Risk Development in Young Adults (CARDIA) study. Nutr Metab Cardiovasc Dis. 32(10):2321–2329. https://doi.org/10.1016/j.numecd.2022.07.013

Background and Aims: Few studies have examined long-term associations of walnut, other nut, and no nut consumption with cardiovascular disease (CVD) risk factors. Results from prospective studies with long-term follow-up can provide further evidence for dietary guideline messaging to consume nuts. Therefore, we examined the associations of walnut, other nut, and no nut consumption with diet quality and CVD risk factors over 30 years of follow-up. Methods and Results: Data were analyzed from 3,092 young adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Dietary intake, including walnuts and other nuts, was assessed 3 times over 20 years. CVD risk factors were measured at multiple exams. General linear regression evaluated the associations of walnut, other nut, and no nut consumption with CVD risk factors over 30 years (Y30) of follow-up. The 20-year cumulative mean intake of walnuts (0.74 oz/d), other nuts (1.6 oz/d), or no nut consumption was differentially associated with HEI-2015 and CVD risk factors by Y30. Generally, walnut consumers had significantly higher HEI-2015, lower body mass index, waist circumference, blood pressure, and triglyceride concentration, and gained less weight since baseline than other nut consumers (p ≤0.05 for all). Further, walnut consumers had lower fasting blood glucose than no nut consumers (p ≤0.05). Conclusion: Study findings that walnut and other nut consumption was associated with better CVD risk factors and diet quality aligns with the 2020-2025 U.S. Dietary Guidelines for Americans recommendation to consume nuts, such as walnuts, within the context of a healthy diet.

The effect of high-polyphenol Mediterranean diet on visceral adiposity: the DIRECT PLUS randomized controlled trial.

Zelicha, H., N. Kloting, A. Kaplan, A. Yaskolka Meir, E. Rinott, G. Tsaban, Y. Chassidim,  M. Bluher, U. Ceglarek, B. Isermann, M. Stumvoll, R.N. Quayson, M. von Bergen, B. Engelmann, U.E. Rolle-Kampczyk, S.B. Haange, K.M. Tuohy, C. Diotallevi, I. Shelef, F.B. Hu, M.J. Stampfer, I. Shai, 2022. The effect of high-polyphenol Mediterranean diet on visceral adiposity: the DIRECT PLUS randomized controlled trial. BMC Medicine. 20(1):327. https://doi.org/10.1186/s12916-022-02525-8

Background: Mediterranean (MED) diet is a rich source of polyphenols, which benefit adiposity by several mechanisms. We explored the effect of the green-MED diet, twice fortified in dietary polyphenols and lower in red/processed meat, on visceral adipose tissue (VAT). Methods: In the 18-month Dietary Intervention Randomized Controlled Trial PoLyphenols UnproceSsed (DIRECT-PLUS) weight-loss trial, 294 participants were randomized to (A) healthy dietary guidelines (HDG), (B) MED, or (C) green-MED diets, all combined with physical activity. Both isocaloric MED groups consumed 28 g/day of walnuts (+ 440 mg/day polyphenols). The green-MED group further consumed green tea (3–4 cups/day) and Wolffia globosa (duckweed strain) plant green shake (100 g frozen cubes/day) (+ 800mg/day polyphenols) and reduced red meat intake. We used magnetic resonance imaging (MRI) to quantify the abdominal adipose tissues. Results: Participants (age = 51 years; 88% men; body mass index = 31.2 kg/m2; 29% VAT) had an 89.8% retention rate and 79.3% completed eligible MRIs. While both MED diets reached similar moderate weight (MED: − 2.7%, green-MED: − 3.9%) and waist circumference (MED: − 4.7%, green-MED: − 5.7%) loss, the green-MED dieters doubled the VAT loss (HDG: − 4.2%, MED: − 6.0%, green-MED: − 14.1%; p < 0.05, independent of age, sex, waist circumference, or weight loss). Higher dietary consumption of green tea, walnuts, and Wolffia globosa; lower red meat intake; higher total plasma polyphenols (mainly hippuric acid), and elevated urine urolithin A polyphenol were significantly related to greater VAT loss (p < 0.05, multivariate models). Conclusions: A green-MED diet, enriched with plant-based polyphenols and lower in red/processed meat, may be a potent intervention to promote visceral adiposity regression.