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  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)

Kaplan, A., Zelicha, H., Meir, A. Y., Rinott, E., Tsaban, G., Levakov, G., et al. (2022). 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). The American Journal of Clinical Nutrition, 115(5), 1270-1281. doi:10.1093/ajcn/nqac001.

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 Creators:
Kaplan, Alon1, Author
Zelicha, Hila1, Author
Meir, Anat Yaskolka1, Author
Rinott, Ehud1, Author
Tsaban, Gal1, 2, Author
Levakov, Gidon3, 4, Author
Prager, Ofer4, Author
Salti, Moti4, Author
Yovell, Yoram5, Author
Ofer, Jonathan4, Author
Huhn, Sebastian6, Author
Beyer, Frauke7, Author              
Witte, A. Veronica7, Author              
Villringer, Arno7, Author              
Meiran, Nachshon3, Author
Emesh, Tamar B.3, Author
Kovacs, Peter8, Author
von Bergen, Martin9, Author
Ceglarek, Uta10, Author
Blüher, Matthias11, Author
Stumvoll, Michael11, AuthorHu, Frank B.12, 13, AuthorStampfer, Meir J.12, 13, AuthorFriedman, Alon4, 14, AuthorShelef, Ilan1, 2, AuthorAvidan, Galia3, 4, AuthorShai, Iris1, 12, Author more..
Affiliations:
1The Health & Nutrition Innovative International Research Center, Ben-Gurion University of the Negev, Beer Sheva, Israel, ou_persistent22              
2Soroka University Medical Center, Beer Sheva, Israel, ou_persistent22              
3School of Cognitive and Brain Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel, ou_persistent22              
4Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer Sheva, Israel, ou_persistent22              
5Department of Medical Neurobiology, The Hebrew University of Jerusalem, Israel, ou_persistent22              
6Helmholtz Centre for Environmental Research (UfZ), Leipzig, Germany, ou_persistent22              
7Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
8Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig, Germany, ou_persistent22              
9Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research (UfZ), Leipzig, Germany, ou_persistent22              
10Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics (ILM), University of Leipzig, Germany, ou_persistent22              
11Department of Medicine, University Hospital Leipzig, Germany, ou_persistent22              
12Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA, ou_persistent22              
13Department of Medicine, Women's Hospital, Boston, MA, USA, ou_persistent22              
14Department of Medical Neuroscience, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada, ou_persistent22              

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Free keywords: Green Mediterranean diet; Age-related atrophy; Aging; Dietary intervention; Hippocampal occupancy score; Neurodegeneration; Polyphenols
 Abstract: Background: The effect of diet on age-related brain atrophy is largely unproven. Objectives: We 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. Methods: This 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). Results: Among 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. 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.This trial was registered at clinicaltrials.gov as NCT03020186.

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Language(s): eng - English
 Dates: 2021-09-122022-01-082022-01-11
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1093/ajcn/nqac001
PMID: 35021194
PMC: PMC9071484
 Degree: -

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Project name : -
Grant ID : 87472511
Funding program : -
Funding organization : Israel Ministry of Health
Project name : -
Grant ID : 3-13604
Funding program : -
Funding organization : Israel Ministry of Science and Technology

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Title: The American Journal of Clinical Nutrition
Source Genre: Journal
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Publ. Info: Bethesda, MD, USA : American Society for Nutrition
Pages: - Volume / Issue: 115 (5) Sequence Number: - Start / End Page: 1270 - 1281 Identifier: ISSN: 0002-9165
CoNE: https://pure.mpg.de/cone/journals/resource/0002-9165