Effect of an Asian-adapted Mediterranean diet and pentadecanoic acid on fatty liver disease: the TANGO randomized controlled trial

Weight loss is the most effective treatment for non-alcoholic fatty liver disease (NAFLD). There is evidence that Mediterranean diets rich in unsaturated fatty acids and fiber have beneficial effects on weight homeostasis and metabolic risk factors in individuals with NAFLD. Studies have also shown that higher circulating concentrations of pentadecanoic acid (C15:0) are associated with lower risk for NAFLD. To examine the effects of a Mediterranean-like, culturally contextualized Asian diet rich in fiber and unsaturated fatty acids, with or without C15:0 supplementation, in Chinese females with NAFLD. In a double-blinded, parallel-design, randomized controlled trial, 88 Chinese females with NAFLD were randomized to one of three groups for 12-weeks: diet with C15:0 supplementation (n=31), diet without C15:0 supplementation (n=28), or control (habitual diet and no C15:0 supplementation, n=29). At baseline and after the intervention, body fat percentage, intrahepatic lipid content, muscle and abdominal fat, liver enzymes, cardiometabolic risk factors and gut microbiome were assessed. In intention-to-treat analysis, weight reductions of 4.0±0.5 kg (5.3%), 3.4±0.5 kg (4.5%), and 1.5±0.5 kg (2.1%) were achieved in the diet-with-C15:0, diet-without-C15:0, and the control groups, respectively. The proton density fat fraction (PDFF) of the liver decreased by 33%, 30% and 10%, respectively. Both diet groups achieved significantly greater reductions in body weight, liver PDFF, total cholesterol, gamma-glutamyl transferase, and triglyceride concentrations compared to the control group. C15:0 supplementation reduced LDL-cholesterol further, and increased abundance of Bifidobacterium adolescentis. Fat mass, visceral adipose tissue, subcutaneous abdominal adipose tissue (deep and superficial), insulin, glycated hemoglobin and blood pressure decreased significantly in all groups, in parallel with weight loss. Mild weight loss induced by a Mediterranean-like diet adapted for Asians has multiple beneficial health effects in women with NAFLD. C15:0 supplementation lowers LDL-cholesterol and may cause beneficial shifts in gut microbiome. clinicaltrials.gov, NCT05259475