Table 1.

Description of the reviewed studies: study design and participants.

Author, Year (Reference)	Study’s Aim/Aims	Study Characteristics	Methods	Results
Mediterranean Diet and NAFLD
Kim et al., 2016 [21]	Compare the components and prevalence of MetS according to degree of adiposity and presence of NAFLD	n = 1695 with a history of liver cirrhosis (70.5% female) Age 49–57 Korea Cross-sectional study	Collect and compare anthropometric, clinical, and laboratory data of non-obese males/females without NAFLD; non-obese males/females with NAFLD; obese males/females without NAFLD; and obese males/females with NAFLD	− ↑ Fasting glucose in non-obese participants with NAFLD vs. obese participants without NAFLD − ↑ 3.63 times prevalence of MetS with presence of NAFLD vs. ↑ 3.84 times prevalence of MetS with obesity without NAFLD (in males) − ↑ 5.56 times prevalence of MetS with presence of NAFLD vs. ↑ 3.46 times prevalence of MetS with obesity without NAFLD (in females)
Chen et al., 2019 [23]	Investigate the relationship between NAFLD risk and nut consumption	n = 1068 (534 with NAFLD and 534 without) (31.8% female) Age 18–70 China Retrospective case–control study	Collect dietary intake to calculate nut consumption. Categorize nut consumption in quartiles on the distribution of daily nut intake of controls	− No association between nut consumption and NAFLD risk in overall sample − Significant inverse association between ↑ nut consumption and NAFLD in the highest quartile of men’s sample
Georgoulis et al., 2015 [27]	Assess the presence of MetS and its association with dietary habits in subjects with NAFLD	n = 73 with NAFLD (31.5% female) Age 34–56 Athens Cross-sectional study	NAFLD diagnosed by high liver enzyme levels and ultrasound. Subjects’ food consumption assessed by food frequency questionnaire. Adherence to Mediterranean diet assessed by MedDiet Score	− 46.5% sample with MetS, ↑ waist circumference, and ↓ HDL − Positive association between MetS and consumption of red meat and refined grains − Negative association between MetS and MedDietScore and consumption of whole grains
Aller et al., 2018 [28]	Compare dietary, genetic, and biochemical parameters among obese and overweight participants with NAFLD	n = 203 with biopsy-proven NAFLD (43.3% female) Age 44–49 Spain Cross-sectional study	Evaluate adherence to Mediterranean diet using MEDAS questionnaire, anthropometrical and biochemical parameters, and the variants rs180069 of tumor necrosis factor gene and I148M of PNPLA3 gene	− ↑ Serum adiponectin levels and ↓ resistin and leptin concentration in overweight participants vs. obese participants − ↑ Frequency of NASH in obese participants − Adherence to Mediterranean diet as an independent protective factor for liver fibrosis and NASH in overweight participants
Mediterranean Diet, Physical Activity and NAFLD
Konerman et al., 2018 [22]	Analyze the prevalence of NAFLD between subjects in the University of Michigan Metabolic Fitness (MetFit) Program and assess its impact on liver-related and metabolic parameters, and weight among subjects without and with NAFLD	n = 403 who completed the MetFit program at the University of Michigan between 2008 and 2016 (37.5% female) Age 45–63 Michigan Cohort study	Collect laboratory and clinical data at enrolment and at 12 and 24 weeks of subjects with and without NAFLD (defined based on imaging, liver biopsy, or clinical diagnosis) who have to follow a Mediterranean diet and exercise sessions	Principal group were men with severe obesity and NAFLD − 30% ↓ weight ≥ 5% − 62% resolution of hypertriglyceridemia − 33% resolution of low HDL − 27% resolution of impaired fasting glucose − 43% normalization of alanine aminotransferase
Sorrentino et al., 2015 [24]	Observe if, in participants with less advanced stages of NAFLD, a moderate regimen of diet, exercise, and a mix of vitamin E and a new formulation of silymarin could offer clinical improvements	n = 78 with MetS and ultrasound confirmation of liver steatosis (46.2% female) Age 55–57 Italy Controlled clinical study	90-days follow-up Group A: Standard Mediterranean diet, exercise, and a dietary adjunct (2 tablets/day of a nutraceutical product containing, in each tablet, 210 mg of Eurosil 85®) Group B: Standard Mediterranean diet and exercise.	Group A: ↓ BMI, abdominal circumference, ultrasound measurement of right liver lobe, HSI, and lipid accumulation product Group B: No change
Bullón-Vela et al., 2019 [25]	Examine the connection among NAFLD and lifestyle factors in participants with MetS	n = 328 with MetS who participate in PREDIMED-Plus study (45.1% female) Age 55–75 (men) and 60–75 (women) Spain Cross-sectional study	Collect dietary, clinical, and sociodemographic data. Evaluate physical activity and adherence to Mediterranean diet using validated questionnaires and NAFLD with non-invasive HSI	− ↓ HSI values with ↑ physical activity terciles − Adherence to Mediterranean diet inversely associated with HSI values − ↑ Terciles of legume consumption inversely associated with the highest tercile of HSI
Abbate et al., 2021 [26]	Examine the efficacy of lifestyle intervention on the reduction of MetS and NAFLD, and if these reductions could influence renal outcomes	n = 155 with MetS and NAFLD (39.1% female) Age 40–60 Spain Randomized controlled trial	6-months follow-up Group A (CD): Conventional diet based on American Association for the Study of Liver Disease recommendations with 10,000 steps a day Group B (MD-HMF): Mediterranean diet: high meal frequency (7 meals a day) with 10,000 steps a day Conventional Group C (MD-PA): Mediterranean diet: physical activity with instructed sessions 3 times a week	− No significant differences between 3 groups − ↓ Urinary albumin-to-creatine ratio in participants with ↑ levels at baseline, but without changes in liver fat − ↓ Estimated glomerular filtration in participants with hyperfiltration at baseline, associated with ↓ liver fat and insulin resistance and ↑ energy expenditure − Energy expenditure, ↓ hepatic fat accumulation, and insulin resistance = ↓ glomerular hyperfiltration − ↓ Increased albuminuria, without association with reduced liver fat
Gelli et al., 2017 [29]	Define the clinical effectiveness of nutritional recommendation on weight loss and the reduction of liver enzymes, anthropometric and metabolic indexes, and NAFLD	n = 46 with NAFLD (37% female) Age 26–71 Italy Observational study	Examine a Mediterranean diet and clinical intervention with physical activity over 6 months, monitoring and collecting metabolic parameters, liver enzymes, severity NAFLD (by ultrasound), cardiovascular risk indexes, and biochemistry at the middle of interventions and at the end	− ↓ 93% to 48% of percentage of participants with steatosis grade ≥ 2 − Regression of steatosis in 9 participants − 25 of 46 participants achieved a reduction of 7% of their weight or maintained a normal weight − ↓ Liver enzymes (especially alanine aminotransferase enzyme) − Improvement of waist circumference, BMI, waist-to-hip ratio, LDL/HDL, total cholesterol/HDL, triglycerides/HDL, serum glucose, HDL, fatty liver index, HOMA, Kotronen index, NAFLD liver fat score, visceral adipose index, and lipid accumulation product
Copaci et al., 2015 [30]	Examine if lifestyle intervention and exercise during a 12-month period could reduce weight and improve steatosis	n = 86 overweight with steatosis (40.7% female) Age 35–59 Romania Prospective observational study	12-months follow-up Caloric goal based on starting weight, daily fat goal, and physical activity (moderate intensity)	− ↓ Weight, BMI, waist circumference − ↓ Gamma glutamyl transferase, alanine aminotransferase, cholesterol, LDL, HOMA-R − Steatotest improved − Modification of leptin and adiponectin as factors related to improved steatosis (BMI and alanine aminotransferase also)
Takahashi et al., 2015 [31]	Examine the effects of resistance exercise on metabolic parameters of NAFLD	n = 53 with NAFLD (64.2% female) Age 37–68 Japan Randomized controlled study	12-months follow-up Group A: 12 weeks of resistance exercise and regimen Group B: Lifestyle counseling (dietary restrictions and regular physical activities)	Group A: ↑ Muscle mass and fat-free mass ↓ Mean insulin and ferritin levels, hepatic steatosis grade, HOMA-IR index Group B: ↓ LDL
Lee et al., 2018 [32]	Examine the association between NAFLD index and HGS in older adults	n = 538 with NAFLD (80.3% female) Age > 60 Korea Cross-sectional study	High HGS / Mid HGS / Low HGS groups (based on relative HGS) High risk / Low risk groups (based on FIB-4, SNS, HSI, and NFS) Assess body-composition parameters, HGS, and NAFLD	− ↓ Linear in NAFLD index (SNS, HSI, NFS, FIB-4) across ↑ HGS levels − Low HGS group: ↑ ORs of SNS, HSI, and NFS (compared to High HGS group)
Cho et al., 2021 [33]	Investigate the effect of HGS and SES on the risk of NAFLD in middle-aged adults	n = 5272 who participated in KNHANES (68.2% female) Age 53–61 Korea Cross-sectional study	NAFLD defined by HSI and comprehensive NAFLD score. SES based on self-reported questionnaire. Assessment of anthropometric data, blood markers, health-related factors, and HGS	↑ Risk of NAFLD in subjects with ↓ SES and HGS vs. subjects with ↑ SES and HGS

BMI = body mass index, FIB-4 = fibrosis 4 calculator, HDL = high-density lipoprotein, HGS = hand-grip strength, HOMA = homeostasis model assessment, HSI = Hepatic Steatosis Index, KNHANES = Korea National Health and Nutrition Examination Surveys, LDL = low-density lipoprotein, MEDAS = Mediterranean diet adherence screener, MedDietScore = Mediterranean diet score, MetS = metabolic syndrome, NAFLD = non-alcoholic fatty liver disease, NASH = non-alcoholic steatohepatitis, NFS = NAFLD fibrosis score, ORs = odds ratio, PNPLA3 = patatin-like phospholipase domain containing 3, SES = socioeconomic status, SNS = simple NAFLD score. ↑: Increase; ↓: Decrease.