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.
- fatty liver
- magnetic resonance imaging
Data availability statement
The majority of results corresponding to the current study are included in the article or uploaded as supplementary material. No further data are avialable.
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AYM and ER contributed equally.
Contributors AYM, ER, GT, HZ, AK and IShai contributed to the data collection. AYM and ER made the statistical analysis, interpreted the data, reviewed the literature and drafted the manuscript. ER, GT, HZ, AK, PR, IShelef, IY, AS, MB, KT, CD, UV, UC, MStumvoll, FH, MStampfer and IShai contributed to the analysis and interpretation of data, and reviewed the language and intellectual content of this work. AYM and IShai revised the final draft of the study and approved the final version to be published.
Funding This work was funded by grants from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project number 209933838—Collaborative Research CenterCentre SFB1052 'Obesity Mechanisms', to I Shai (SFB-1052/B11); Israel Ministry of Health grant 87472511 (to I Shai); Israel Ministry of Science and Technology grant 3-13604 (to I Shai); California Walnuts Commission (to I Shai) and the Project 'Cabala_diet&health' (http://www.cabalaproject.eu/) which received funding from the European Union’s Horizon2020 research and innovation grant agreement No 696295—ERA-Net Cofund ERA-HDHL 'Biomarkers for Nutrition and Health implementing the JPI HDHL objectives' (https://www.healthydietforhealthylife.eu/) supported polyphenol analyses at FEM (to KT). AYM is a recipient of the Kreitman Doctoral Fellowship at Ben-Gurion University of the Negev. None of the funding providers were involved in any stage of the design, conduct or analysis of the study and they had no access to the study results before publication.
Competing interests IS advises to the Hinoman, Ltd. nutritional committee. Youngster is medical advisor for Mybiotix Ltd.
Provenance and peer review Not commissioned; externally peer reviewed.
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