Effects of Two Personalized Dietary Strategies During a 2-year Intervention in Subjects With Nonalcoholic Fatty Liver Disease

A Randomized Trial

Bertha A. Marin-Alejandre; Irene Cantero; Nuria Perez-Diaz-del-Campo; Jose I. Monreal; Mariana Elorz; Jose I. Herrero; Alberto Benito-Boillos; Jorge Quiroga; Ana Martinez-Echeverria; Juan I. Uriz-Otano; Maria P. Huarte-Muniesa; Josep A. Tur; Jose A. Martinez; Itziar Abete; Maria A. Zulet


Liver International. 2021;41(7):1532-1544. 

In This Article

Abstract and Introduction


Background and Objectives: Nonalcoholic fatty liver disease (NAFLD) management is focused on lifestyle modifications, but long-term maintenance is a challenge for many individuals. This study aimed to evaluate the long-term effects of two personalized energy-restricted dietary strategies on weight loss, metabolic and hepatic outcomes in overweight/obese subjects with NAFLD.

Methods: Ninety-eight subjects from the Fatty Liver in Obesity (FLiO) study (NCT03183193) were randomly assigned to the American Heart Association (AHA) or the FLiO dietary group in a 2-year controlled trial. Anthropometry, body composition (DXA), biochemical parameters and hepatic status (ultrasonography, Magnetic Resonance Imaging, and elastography) were assessed at baseline, 6, 12 and 24 months.

Results: Both the AHA and FLiO diets significantly reduced body weight at 6 (−9.7% vs −10.1%), 12 (−6.7% vs −9.6%), and 24 months (−4.8% vs −7.6%) with significant improvements in body composition, biochemical and liver determinations throughout the intervention. At the end of the follow-up, the FLiO group showed a greater decrease in ALT, liver stiffness and Fatty Liver Index, among others, compared to AHA group, although these differences were attenuated when the analyses were adjusted by weight loss percentage. The FLiO group also showed a greater increase in adiponectin compared to AHA group.

Conclusions: The AHA and FLiO diets were able to improve body weight and body composition, as well as metabolic and hepatic status of participants with overweight/obesity and NAFLD within a 2-year follow-up. These findings show that both strategies are suitable alternatives for NAFLD management. However, the FLiO strategy may provide more persistent benefits in metabolic and hepatic parameters.


Nonalcoholic fatty liver disease (NAFLD) is currently considered as the most common form of chronic liver disease in the majority of the world regions with a prevalence that parallels the worldwide increase of obesity.[1,2] NAFLD encompasses a spectrum of chronic liver diseases characterized by the excessive accumulation of intrahepatic triglycerides that occurs in the absence of significant consumption of alcohol.[3] This condition ranges from simple steatosis to nonalcoholic steatohepatitis (NASH) when inflammation and hepatocyte injury accompanies triglyceride retention, to a variable degree of hepatic fibrosis, to cirrhosis and/or to hepatocellular carcinoma in latter stages of the disease.[4] NAFLD is strongly associated with obesity, insulin resistance, type 2 diabetes mellitus and cardiovascular disease.[3] The natural history of NAFLD is highly variable and reflects diverse mechanisms that converge in the onset and development of this disease,[5] including environmental factors (diet and exercise), microbiome and genetic risk factors.[2]

Lifestyle modifications aiming at weight loss through dietary and physical activity interventions remain the cornerstone therapy for the treatment of subjects with NAFLD.[6] Caloric restriction plays a fundamental role in the reduction of body weight, visceral, subcutaneous and hepatic fat, being the most important element in the dietary treatment of this condition.[7] Current knowledge suggests that there is no single optimal diet for the treatment of NAFLD, and therefore, customized dietary recommendations and personalized nutritional counselling would be appropriate to treat individuals with NAFLD.[8] The consumption of omega-3 fatty acids, foods high in monounsaturated fatty acids (MUFA), fruit, vegetables and fibre, as well as the reduction of the intake of saturated fats, simple carbohydrates and sweetened drinks may be advisable for all patients with NAFLD.[9]

Moreover, the interventions based on the Mediterranean Diet (MedDiet) seem to be the most supported nutritional approach for NAFLD management.[6,10] However, more research is needed to clarify the effects of different dietary approaches and specific components of the diet on the health of patients with NAFLD. Furthermore, the maintenance of weight loss is a considerable challenge for many individuals,[7] and there is a lack of studies evaluating the long-term effects of dietary interventions on liver status features of subjects with NAFLD.[11]

In this context, the aim of this study was to evaluate the long-term effects of two personalized energy-restricted dietary strategies on weight loss, anthropometric measurements, biochemical determinations and hepatic status within a 2-year follow-up in overweight or obese subjects with NAFLD.