Abenavoli L, Greco M, Milic N, et al. Effect of Mediterranean diet and antioxidant formulation in non-alcoholic fatty liver disease: a randomized study. Nutrients. 2017;9(870).
Randomized, prospective 6-month trial among 3 cohorts (A,B,C): dietary intervention alone (A); dietary intervention with antioxidant supplementation (B); and control without treatment (C).
Fifty Caucasian, overweight (BMI>25 kg/m2) men and women with nonalcoholic fatty liver disease (NAFLD) were recruited from an outpatient gastroenterology clinic in Italy; NAFLD diagnosis was based on Hamaguchi ultrasound scoring. Patients with hepatitis B, hepatitis C, cardiac disease, renal disease, autoimmune disease, recreational drug use, insulin treatment, excessive alcohol intake, and exposure to environmental toxins associated with hepatic steatosis were excluded from the study.
Group A (n=20) followed a low-calorie Mediterranean diet (1,400-1,600 kcal/d) while Group B (n=20) followed a low-calorie Mediterranean diet supplemented with antioxidants. Macronutrients in the Mediterranean diet intervention groups were divided as follows: 50% to 60% carbohydrates; 15% to 20% protein, with approximately 50% of the protein sources from vegetables; less than 30% monounsaturated and polyunsaturated fats, with less than 10% saturated fat; less than 300 mg per day of cholesterol; and 25 to 30 grams per day of fiber. Group B received 2 pills per day of Bilirel antioxidant supplement, which consists of artichoke, milk thistle, L-methionine, fumitory, and L-glutathione.
Group C (n=10) did not change their lifestyle or their existing pharmacologic (drug) regimen.
Study Parameters Assessed
Anthropometric parameters, blood pressure, lipid profile, homeostatic model assessment of insulin resistance (HOMA-IR), transaminases (serum levels of alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase), and liver fibrosis were evaluated at baseline and after 6 months of intervention. Liver fibrosis was assessed using transient elastography, and a fatty liver index was used to predict the likelihood of steatosis.
After 6 months of treatment, when compared to Group C (control), Group A had a significant reduction in weight (−6% vs −0.5%, P=0.0001), BMI (−7.5% vs −0.45%, P=0.0001), triglycerides (−32.16 vs +2.8%, P=0.001), total cholesterol (−14.8% vs +9.3%, P=0.0001), triglyceride-glucose index (−3.3% vs +1%, P=0.020), fatty liver index (−19% vs +4.7%, P=0.017), and transient elastography (−21% vs +8.7%, P=0.001). Similar significant reductions were seen in the Group B cohort compared with control. When compared to Group A, Group B had significant reductions in HOMA-IR (−43% vs +6.2%, P=0.0001), insulin (−38% vs +10%, P=0.0001), and fasting glucose (−11% vs −3.5%, P=0.016). These results show that a Mediterranean diet significantly reduces anthropometric parameters and lipid parameters, and improves transient elastography in patients with NAFLD. Adding antioxidants may have the added benefit of improving insulin-related biomarkers.
Many observational studies have shown that patients with NAFLD have dietary patterns that are generally high in calories, high in saturated fat, low in polyunsaturated fats, and low in antioxidants, with excessive carbohydrate intake from simple sugars1-5 and a substantial amount of calories coming from soft drinks, including sodas and juices.6
Clinicians caring for these patients should be aware of their dietary patterns and ultimately encourage a transition towards a Mediterranean-type diet or a diet that reduces simple carbohydrates and saturated fats and promotes higher intake of fruits and vegetables. Patients should also be encouraged to eliminate high-fructose corn syrup—fructose is not metabolized in the same rate-limiting manner as glucose, so it directly promotes fat deposition in the liver.7
When overweight patients are able to lose approximately 7% to 10% of their body weight, steatosis begins to resolve.8-12 In one study, steatosis resolved in 90% of NAFLD patients who lost more than 10% body weight.13 Ultimately, hepatic steatosis begins to resolve when patients are able to exercise and modify their diet.
Nonalcoholic fatty liver disease is insidious because most patients are asymptomatic and serum transaminases can be misleading.
Many specialists are predicting that in the next 15 to 20 years the leading reason for orthotropic liver transplant will be fatty liver–related, displacing hepatitis C and alcoholism.14 It is currently estimated that 20% to 30% of simple steatosis will progress to NASH, the inflammatory stage of NAFLD, and 7% to 25% of NASH will progress towards cirrhosis.15 No one has identified a single mechanism that triggers the progression from simple steatosis to NAFLD; however, multiple studies reveal that NAFLD is more prevalent in patients with metabolic syndrome and its subsets.16-19
Nonalcoholic fatty liver disease is insidious because most patients are asymptomatic and serum transaminases can be misleading. Our approach to patients with NAFLD should include early identification along with appropriate dietary and lifestyle recommendations, such as the Mediterranean diet paired with exercise.
- Capristo E, Miele L, Forgione A, et al Nutritional aspects in patients with non‐alcoholic steatohepatitis (NASH). Eur Rev Med Pharmacol Sci. 2005;9(5):265-268.
- Cortez-Pino H, Jesus L, Barros H, et al. How différent is the dietary pattern in non-alcoholic steatohepatitis patents? Clin Nutr. 2006;25(5):816-823.
- Musso G, Gambino R, De Michieli F, et al. Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology. 2003; 37(4):909-916.
- Toshimitsu K, Matsuura B, Ohkubo I, et al. Dietary habits and nutrient intake in non-alcoholic steatohepatitis. Nutrition. 2007;23(1):46-52.
- Abdelmalek MF, Suzuki A, Guy C, et al. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. Hepatology. 2010;51(6):1961-1971.
- Abid A. Soft drink consumption is associated with fatty liver disease independent ofmetabolic syndrome. J Hepatol. 2009;51(5):918-924.
- Teff KL, Grudziak J, Townsend RR, et al. Endocrine and metabolic effects of consuming fructose- and glucose-sweetened beverages with meals in obese men and women: influence of insulin resistance on plasma triglyceride responses. J Clin Endocrinol Metab. 2009;94(5):1562-1569.
- Promrat K, Kleiner DE, Niemeier HM, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010;51(1):121-129.
- Suzuki A, Lindor K, St Saver J, et al. Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease. J Hepatol. 2005;43(6):1060-1066.
- St George A, Bauman A, Johnston A, et al. Effect of a lifestyle intervention in patients with abnormal liver enzymes and metabolic risk factors. J Gastroenterol Hepatol. 2009;24(3):399-407.
- Oza N, Eguchi Y, Mizuta T, et al. A pilot trial of body weight reduction for nonalcoholic fatty liver disease with a home-based lifestyle modification intervention delivered in collaboration with interdisciplinary medical staff. J Gastroenterol. 2009;44(12):1203-1208.
- Dixon JB, Bhathal PS, Hughes NR, et al. Nonalcoholic fatty liver disease: improvement in liver histological analysis with weight loss. Hepatology. 2004;39(6):1647-1654.
- Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149(2):367-378.
- Zezos P, Renner EL. Liver transplantation and non-alcoholic fatty liver disease. World J Gastroenterol. 2014;20(42):15532-15538.
- Tirosh O. Liver Metabolism and Fatty Liver Disease. Boca Raton, FL: CRC Press. 2014:4-45.
- Younossi ZM, Koenig AB, Abdelatif D. Global epidemiology of NAFLD-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84.
- Bhatt HB, Smith RJ. Fatty liver disease in diabetes mellitus. HepatoBiliary Surg Nutr 2015;4(2):101-108.
- Fabbrini E, Sullivan S, Klein S. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic and clinical implications. Hepatology. 2010;51(2):679-689.
- Firneisz G. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age? World J Gastroenterol. 2014;20(27):9072-9089.