PT - JOURNAL ARTICLE AU - Yaskolka Meir, Anat AU - Rinott, Ehud AU - Tsaban, Gal AU - Zelicha, Hila AU - Kaplan, Alon AU - Rosen, Philip AU - Shelef, Ilan AU - Youngster, Ilan AU - Shalev, Aryeh AU - Blüher, Matthias AU - Ceglarek, Uta AU - Stumvoll, Michael AU - Tuohy, Kieran AU - Diotallevi, Camilla AU - Vrhovsek, Urska AU - Hu, Frank AU - Stampfer, Meir AU - Shai, Iris TI - Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial AID - 10.1136/gutjnl-2020-323106 DP - 2021 Nov 01 TA - Gut PG - 2085--2095 VI - 70 IP - 11 4099 - http://gut.bmj.com/content/70/11/2085.short 4100 - http://gut.bmj.com/content/70/11/2085.full SO - Gut2021 Nov 01; 70 AB - Objective To examine the effectiveness of green-Mediterranean (MED) diet, further restricted in red/processed meat, and enriched with green plants and polyphenols on non-alcoholic fatty liver disease (NAFLD), reflected by intrahepatic fat (IHF) loss.Design For the DIRECT-PLUS 18-month randomized clinical trial, we assigned 294 participants with abdominal obesity/dyslipidaemia into healthy dietary guidelines (HDG), MED and green-MED weight-loss diet groups, all accompanied by physical activity. Both isocaloric MED groups consumed 28 g/day walnuts (+440 mg/day polyphenols provided). The green-MED group further consumed green tea (3–4 cups/day) and Mankai (a Wolffia globosa aquatic plant strain; 100 g/day frozen cubes) green shake (+1240 mg/day total polyphenols provided). IHF% 18-month changes were quantified continuously by proton magnetic resonance spectroscopy (MRS).Results Participants (age=51 years; 88% men; body mass index=31.3 kg/m2; median IHF%=6.6%; mean=10.2%; 62% with NAFLD) had 89.8% 18-month retention-rate, and 78% had eligible follow-up MRS. Overall, NAFLD prevalence declined to: 54.8% (HDG), 47.9% (MED) and 31.5% (green-MED), p=0.012 between groups. Despite similar moderate weight-loss in both MED groups, green-MED group achieved almost double IHF% loss (−38.9% proportionally), as compared with MED (−19.6% proportionally; p=0.035 weight loss adjusted) and HDG (−12.2% proportionally; p<0.001). After 18 months, both MED groups had significantly higher total plasma polyphenol levels versus HDG, with higher detection of Naringenin and 2-5-dihydroxybenzoic-acid in green-MED. Greater IHF% loss was independently associated with increased Mankai and walnuts intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, changes in microbiome composition (beta-diversity) and specific bacteria (p<0.05 for all).Conclusion The new suggested strategy of green-Mediterranean diet, amplified with green plant-based proteins/polyphenols as Mankai, green tea, and walnuts, and restricted in red/processed meat can double IHF loss than other healthy nutritional strategies and reduce NAFLD in half.Trial registration number NCT03020186.The majority of results corresponding to the current study are included in the article or uploaded as supplementary material. No further data are avialable.