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The effect of a high-polyphenol Mediterranean diet (GREEN-MED) combined with physical activity on age-related brain atrophy: the DIRECT PLUS randomized controlled trial.
Authors: Kaplan, A., Zelicha, H., Meir, A. Y., Rinott, E., Tsaban, G., Levakov, G., Prager, O., Salti, M., Yovell, Y., Ofer, J., Huhn, S., Beyer, F., Witte, V., Villringer, A., Meiran, N., Emesh, T. B., Kovacs, P., von Bergen, M., Ceglarek, U., Blüher, M., … Shai,
- Journals: The American Journal of Clinical Nutrition
- Pages: nqac001
- Year: 2022
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Background: The effect of diet on age-related brain atrophy is largely unproven. Objective: To explore the effect of a Mediterranean diet higher in polyphenols and lower in red/processed meat (Green-MED diet) on age-related brain atrophy. Methods: This 18-month clinical trial longitudinally measured brain structure volumes by magnetic-resonance-imaging using hippocampal-occupancy (HOC) and lateral-ventricle-volume (LVV) expansion scores as neurodegeneration markers. Abdominally obese/dyslipidemic participants were randomly assigned to (1)-healthy dietary guidelines (HDG), (2)-Mediterranean (MED) diet, or (3)-Green-MED diet (MED diet higher in polyphenols and lower in red/processed meat). All subjects received free gym memberships and physical activity guidance. Both MED groups consumed 28g/day walnuts (+440 mg/d polyphenols). The Green-MED group consumed green-tea (3-4 cups/day) and Mankai (Wolffia-globosa strain, 100g frozen-cubes/day) green shake (+800mg/day polyphenols). Results: Among 284 participants (age = 51years; 88% men; BMI = 31.2kg/m2; apolipoprotein E-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 to younger participants, atrophy was accelerated among those ≥ 50 years [HOC change = -1.0±1.4% vs. -0.06±1.1%; 95% confidence-interval (CI):0.6, 1.3; p<0.001; LVV change = 3.2±4.5% vs. 1.3±4.1%; 95%CI:-3.1, -0.8;p = 0.001]. In subjects ≥50years, HOC decline and LVV expansion were attenuated in both MED groups, with the best outcomes among Green-MED diet participants, as compared to HDG (HOC: -0.8±1.6% vs. -1.3±1.4%;95%CI: -1.5, -0.02;p = 0.042, LVV: 2.3±4.7% vs. 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 strongest parameter associated with brain atrophy attenuation (p<0.05). Greater Mankai, green-tea and walnuts intake and less red and processed meat were significantly and independently associated with reduced HOC decline (p<0.05). Elevated urinary levels of the Mankai-derived polyphenols: urolithin-A (r = 0.24;p = 0.013) and tyrosol (r = 0.26;p = 0.007) were significantly associated with lower HOC decline. Conclusions: A 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. https://doi.org/10.1093/ajcn/nqac001