Non-alcoholic fatty liver disease intermittent fasting time intervention (NIFTI): Fasting without calorie restriction improves hepatic transient elastography, visceral adiposity and insulin resistance compared to standard care.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is closely associated with central adiposity and the metabolic syndrome. Standard care (SC) includes lifestyle modification through diet and exercise, however, this approach is often ineffective. Alternative approaches are clearly needed. We explored manipulation of oral intake through intermittent fasting (IF) without prescribed calorie restriction. Method(s): We undertook a proof-of-concept 12 week pilot study in 32 NAFLD patients (hepatic steatosis by ultrasound), randomized to either standard diet and exercise recommended by the Gastroenterological Society of Australia [standard care, (SC)] or IF defined as withholding caloric intake for 16 hours (8 pm to 12 pm the following day). Co-primary endpoints were changes in visceral fat [single abdominal slice computerized tomography (CT)] and liver stiffness and steatosis (controlled attenuation parameter (CAP) using transient elastography - Fibroscan); measured at baseline and 12 weeks. Secondary endpoints included fat mass (whole body DEXAscan), anthropometric and biochemical measurements. Food consumption, hunger scores, activity and quality of life were measured every 4 weeks. Result(s): 32 patients were enrolled; 2 left for personal reasons, 1 for reflux and 1 after gallstone pancreatitis. 28 completed the study (IF n = 17; SC n = 15). Baseline demographics were similar; metabolic syndrome was present in 8 in the IF and 7 in the SC groups. At the end of 12 weeks, compared to baseline, SC and IF both resulted in a decrease in weight (IF 81.9 to 79.8 kg, p = 0.0024; SC 82.3 to 81 kg, p = 0.0066), BMI (IF 29 to 28 kg/m2, p = 0.002; SC 30 to 29 kg/m2, p = 0.006) and total body fat mass (IF 29 to 28 kg, p = 0.0001; SC 31 to 29 kg, p = 0.0031). In both groups, leptin decreased (IF 8.3 to 7.4 ng/mL, p = 0.033; SC 7.0 to 5.5 ng/mL p = 0.0004) and adiponectin increased (IF 15.2 to 17.9 mug/mL, p = 0.003; SC 16.7 to 19.6 mug/mL, p = 0.0003). However, compared to SC, t