Mediterranean diet and nonalcoholic fatty liver disease

Table 3 Longitudinal studies on the effects of Mediterranean diet on non-alcoholic fatty liver disease in adult patients

Authors, year, country[ref.]	Study design	Patient population	Intervention (duration, type, number of patients)	Liver outcome	Other outcomes
Fraser, 2008, Israel[41]	An open label, parallel design, quasi-randomized (allocation by alternation) controlled trial	Overweight /obese patients with T2DM	3 groups at 6/12 mo: 1. ADA diet, n = 64/54; 2. Low GI diet, n = 73/64; 3. Modified MD, n = 64/61. Energy contents similar in all three diets	ALT levels significantly decreased at 6 and 12 mo in modified MD vs low GI or ADA diets, independently of waist to hip ratio, BMI, HOMA and triacylglycerol values
Bozzetto, 2012, Italy[43]	Randomized, controlled, parallel-group design	36 overweight /obese patients with T2DM	8 wk, 4 groups: 1. High-CHO/ high-fiber/ low GI diet, n = 9; 2. MUFA diet, n = 8; 3. High-CHO/ high-fiber/ low GI diet + exercise, n = 10; 4. MUFA diet + exercise, n = 9.	Liver fat (as measured by 1H MRS) decreased more in groups 2 (-25%) and 4 (-29%) than in groups 1 (-4%) or 3 (-6%). Two-way repeated-measures ANOVA showed a significant effect on liver fat content for MUFA diet, independently of exercise. There were no significant ALT and AST changes in all groups.	At the end of intervention, there were no significant changes in body weight,WC, as well as in glucose, total cholesterol, LDL-C, HDL-C, TG, and HOMA-IR values from baseline in all groups
Ryan, 2013, Australia[42]	A randomized, controlled, cross-over study	12 non-diabetic patients with a biopsy-proven NAFLD at baseline	A cross-over 6-wk dietary intervention study comparing traditional MD vs low fat/high-CHO	MD group demonstrated a significant decrease in liver fat (as measured by 1H MRS) compared to the low fat/ high-CHO group (39% vs 7%). ALT and GGT did not significantly decrease with either diet	At the end of intervention, no significant changes in body weight, WC, as well as in TG, and HDL-C in both groups. Peripheral insulin sensitivity improved only in the MD group. Systolic BP declined significantly in both groups, though to a lesser degree in the low fat/ high-CHO group
Trovato, 2015, Italy[44]	Single arm	Non-diabetic overweight/obese patients with ultrasound evaluation of liver fat changes from baseline	90 patients following intervention with MD alone for 1, 3, and 6 mo	Liver fat significantly decreased only after 6 mo of intervention. By a multiple linear regression model, changes in adherence to the MD and BMI were found to independently explain the variance of decrease of liver fat (R2 = 0.519; P < 0.0001). No significant ALT changes were observed throughout the follow-up	Significant decrease of BMI followed by parallel increases of the MD adherence as well as of physical activity were observed from the first month of intervention. Significant decrease of HOMA-IR was observed only after 3 and 6 mo
Abenavoli, 2015, Italy[45]	Controlled randomized study	Overweight/obese patients with ultrasound evaluation of liver fat changes from baseline	6 mo, 3 groups: 1. Hypocaloric MD, n = 10; 2. Hypocaloric MD plus Realsil complex, n = 10; 3. No treatment, n = 10.	Compared to the group that did not undergo any treatment, MD either alone or associated with the Realsil complex led to significant improvement in liver steatosis	Compared to the group that did not undergo any treatment, those following the MD either alone or associated with the Realsil complex had improvement in BMI, WC, hip circumference, as well as in total cholesterol, and TG. Improvement in insulin sensitivity occurred only in patients receiving MD plus the Reasil complex
Misciagna, 2016, Italy[46]	Randomized, controlled, parallel-group design	A population almost composed of non-diabetic overweight/ obese patients (18 to 79 years old, without overt CVD) with ultrasound evaluation of liver fat at baseline and follow-up	3 and 6 mo, 2 groups: 1. MD with low GI, n = 44; 2. Control diet(based on INRAN guidelines), n = 46	MD with low GI was associated until 55 yr of age, in both men and women, with a more intense reduction in liver fat than a control diet, at both the 3rd and 6th month	Six months after intervention, in both groups, the number of obese patients decreased while the number of overweight subjects increased. Lower TG and glucosemia were found at 6 mo in both groups
Gelli, 2017, Italy[33]	Single arm	46 (11 normal weight; 35 overweight/obese) subjects (42 with ≥ 1 MetS component; 4 with T2DM) with ultrasound evaluation of liver fat at baseline and follow-up	All patients followed intervention with MD alone for 6 mo	At end-intervention, the percentage of patients with hepatic steatosis grade ≥ 2 was reduced from 93% to 48%; mean AST, ALT, GGT decreased significantly	At end of intervention, of the 35 overweight/obese patients, 12 showed ≥ 7% weight reduction while 7 achieved normal weight; mean serum total cholesterol, HDL-C, AST, TG, glucose concentrations, and HOMA-IR values significantly improved

ADA: American Diabetes association; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BMI: Body mass index; BP: Blood pressure; CHO: Carbohydrates; GGT: Gamma-glutamyl transferase; GI: Glycemic index;

¹H MRS: Proton magnetic resonance spectroscopy; HDL-C: High density lipoprotein-cholesterol; HOMA-IR: Homeostasis model assessment of insulin resistance; INRAN: Italian National Research Institute for Foods and Nutrition; LDL-C: Low density lipoprotein-cholesterol; MD: Mediterranean diet; MetS: Metabolic syndrome; MUFA: Monounsaturated fatty acid; T2DM: Type 2 diabetes mellitus; TG: Triglycerides; WC: Waist circumference.