The effectiveness and acceptability of Mediterranean diet and calorie restriction in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis

Background & aims: Lifestyle interventions that focus on reduced energy intake and improved dietary pattern are the mainstay of non-alcoholic fatty liver disease (NAFLD) management. However, it remains unclear which dietary approaches are most beneficial and promote greatest adherence. We aimed to synthesise data from randomised and clinical controlled trials, describing the effects of Mediterranean Diet and Calorie Restriction interventions on NAFLD surrogate markers, in adults. Methods: We searched MEDLINE, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (October 2021). Study quality was assessed using the Cochrane Collaboration's tools: risk of bias for randomised controlled trials, and risk of bias in non-randomised studies of interventions. Meta-analyses were performed using a random effects model, and the I-2 statistic was used to assess heterogeneity. Results: Of 4041 records identified, 26 articles with 3037 participants met the inclusion criteria, including studies on calorie-restricted interventions (CRI) (n 9), Mediterranean diet (MD) interventions (n 13) and MD component interventions (n 4). Studies were heterogeneous regarding intervention components, assessment of liver status and diet outcomes. 3 studies reported zero attrition and mean attrition rate for the remaining 23 studies was 14%. Post-intervention meta-analyses revealed that dietary interventions reduced alanine aminotransferase (ALT) (P < 0.001), aspartate aminotransferase (AST) (P = 0.004), Fatty Liver Index (FLI) (P < 0.001), hepatic steatosis (HS) (P = 0.02), and liver stiffness (P = 0.01). CRI had favourable effects on ALT (P < 0.001), HS (P < 0.001) and liver stiffness (P = 0.009). MD reduced ALT (P = 0.02), FLI (P < 0.001) and liver stiffness (P = 0.05). There was a doseeresponse relationship between degree of calorie restriction and beneficial effects on liver function and weight loss, suggesting that this approach should remain the cornerstone of NAFLD management. In addition, diet composition changes have potential for improving NAFLD and the limited data suggest that MD may be an effective diet therapy. Conclusion: These results support the current guidelines in NAFLD. However, further studies, which robustly evaluate the effects of interventions on dietary intake, acceptability and sustainability of the interventions, and quality of life and other patient-related outcomes are needed to support effective care delivery. (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

This study synthesized data from randomized and clinical controlled trials to explore the effects of Mediterranean Diet and Calorie Restriction interventions on surrogate markers of non-alcoholic fatty liver disease (NAFLD) in adults. The results showed that these dietary interventions reduced liver function markers and had positive effects on liver steatosis and stiffness. There was a dose-response relationship between the degree of calorie restriction and improvements in liver function and weight loss.