DIRECT PLUS Interventional (Clinical Trial)

  • Iris Shai (Creator)
  • Ilan Shelef (Creator)
  • Dov Brikner (Creator)
  • Ilan Youngster (Creator)



Harvard School of Public Health (HSPH)
University of Leipzig
Soroka University Medical Center
Harvard Medical School (HMS and HSDM)
The Nuclear Research Center, Dimona
Ben-Gurion University of the Negev

IV. PI: Effects of Green-MED Diet Via the Gut-fat-brain Axis (DIRECT-PLUS) (NCT03020186). We hypothesize that long-term intake of selected high polyphenol-containing foods will significantly potentiate the effects of a healthy lifestyle (physical activity and Mediterranean diet), constituting a powerful strategy to halt or even reverse the progression of several age-related processes related to adiposity, cardiometabolic health and cognition. The specific aims include assessing adiposity, cognitive function and brain anatomy, and cardiometabolic biomarkers across the intervention groups. Dietary polyphenols may have a pronounced beneficial effect on age-related declines that begin in middle age, reflected by changes in adiposity, cognitive function, and cardiometabolic risk. In an 18-months randomized controlled trial (RCT), 294 eligible participants, >age 30 with abdominal adiposity or dyslipidemia, were randomized to one of the three groups: A. Physical activity+ Basic health-promoting guidelines; B. PA + Mediterranean (MED) diet + walnuts; C. PA + MED + walnuts + polyphenol intensification (green-MED). All groups received a free gym membership, and both assigned MED groups will aim for moderate weight-loss of 5-10% of baseline weight. Groups B and C were provided 1oz/day of walnuts. The polyphenols enriched group (group C) was instructed to consume polyphenols-rich food items, with supplement of 3-4 cups/day green tea and 5000ml fresh Mankai green shake. Mankai is a cultivated strain of Wolffia globosa, which is an aquatic plant known commonly as duckweed. We have completed the intervention phase. 6-month analysis of the data showed that the green MED diet, supplemented with walnuts, green tea and Mankai and lower in meat/ poultry, may amplify the beneficial cardiometabolic effects of Mediterranean diet (Heart 2020). Analyzing the 18-month MRI data of intrahepatic fat revealed that non-alcoholic fatty liver disease (NAFLD) can be reduced in half by the strategy of green-Mediterranean diet, amplified with green plant-based proteins/polyphenols, and restricted in red/processed meat (Gut 2021).
Date made available13 Jan 2017
Date of data production1 Jan 2017 - 31 Dec 2018

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