The effect of a high-polyphenol Mediterranean diet (Green-MED) combined with physical activity on age-related brain atrophy: the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT PLUS).

Content Provider	Europe PMC
Author	Kaplan, Alon Zelicha, Hila Yaskolka Meir, Anat Rinott, Ehud Tsaban, Gal Levakov, Gidon Prager, Ofer Salti, Moti Yovell, Yoram Ofer, Jonathan Huhn, Sebastian Beyer, Frauke Witte, Veronica Villringer, Arno Meiran, Nachshon B Emesh, Tamar Kovacs, Peter von Bergen, Martin Ceglarek, Uta Blüher, Matthias Stumvoll, Michael Hu, Frank B Stampfer, Meir J Friedman, Alon Shelef, Ilan Avidan, Galia Shai, Iris
Copyright Year	2022
Abstract	ABSTRACTBackgroundThe effect of diet on age-related brain atrophy is largely unproven.ObjectivesWe aimed to explore the effect of a Mediterranean diet (MED) higher in polyphenols and lower in red/processed meat (Green-MED diet) on age-related brain atrophy.MethodsThis 18-mo clinical trial longitudinally measured brain structure volumes by MRI using hippocampal occupancy score (HOC) and lateral ventricle volume (LVV) expansion score as neurodegeneration markers. Abdominally obese/dyslipidemic participants were randomly assigned to follow 1) healthy dietary guidelines (HDG), 2) MED, or 3) Green-MED diet. All subjects received free gym memberships and physical activity guidance. Both MED groups consumed 28 g walnuts/d (+440 mg/d polyphenols). The Green-MED group consumed green tea (3–4 cups/d) and Mankai (Wolffia-globosa strain, 100 g frozen cubes/d) green shake (+800 mg/d polyphenols).ResultsAmong 284 participants (88% men; mean age: 51 y; BMI: 31.2 kg/m2; APOE‐ε4 genotype = 15.7%), 224 (79%) completed the trial with eligible whole-brain MRIs. The pallidum (−4.2%), third ventricle (+3.9%), and LVV (+2.2%) disclosed the largest volume changes. Compared with younger participants, atrophy was accelerated among those ≥50 y old (HOC change: −1.0% ± 1.4% compared with −0.06% ± 1.1%; 95% CI: 0.6%, 1.3%; P < 0.001; LVV change: 3.2% ± 4.5% compared with 1.3% ± 4.1%; 95% CI: −3.1%, −0.8%; P = 0.001).In subjects ≥ 50 y old, HOC decline and LVV expansion were attenuated in both MED groups, with the best outcomes among Green-MED diet participants, as compared with HDG (HOC: −0.8% ± 1.6% compared with −1.3% ± 1.4%; 95% CI: −1.5%, −0.02%; P = 0.042; LVV: 2.3% ± 4.7% compared with 4.3% ± 4.5%; 95% CI: 0.3%, 5.2%; P = 0.021). Similar patterns were observed among younger subjects. Improved insulin sensitivity over the trial was the parameter most strongly associated with brain atrophy attenuation (P < 0.05). Greater Mankai, green tea, and walnut intake and less red and processed meat were significantly and independently associated with reduced HOC decline (P < 0.05). Elevated urinary concentrations of the polyphenols urolithin-A (r = 0.24; P = 0.013) and tyrosol (r = 0.26; P = 0.007) were significantly associated with lower HOC decline.ConclusionsA Green-MED (high-polyphenol) diet, rich in Mankai, green tea, and walnuts and low in red/processed meat, is potentially neuroprotective for age-related brain atrophy.This trial was registered at clinicaltrials.gov as NCT03020186.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC9071484&blobtype=pdf
Page Count	12
ISSN	00029165
Journal	The American Journal of Clinical Nutrition [Am J Clin Nutr]
Volume Number	115
DOI	10.1093/ajcn/nqac001
PubMed Central reference number	PMC9071484
Issue Number	5
PubMed reference number	35021194
e-ISSN	19383207
Language	English
Publisher	Oxford University Press
Publisher Date	2022-05-01
Access Restriction	Open
Rights License	This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. © The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.
Subject Keyword	polyphenols dietary intervention Green Mediterranean diet aging age-related atrophy neurodegeneration hippocampal occupancy score
Content Type	Text
Resource Type	Article
Subject	Nutrition and Dietetics Medicine