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.

Abstract

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 wk blinded pilot study in 32 NAFLD patients (hepatic steatosis by ultrasound), randomised 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 hrs (8pm to 12pm the following day). Co-primary endpoints were changes in visceral fat (single abdominal slice CT) and liver stiffness and steatosis (controlled attenuation parameter (CAP) using transient elastography - Fibroscan); measured at baseline and 12 wks. Secondary endpoints included fat mass (whole body DEXA scan), anthropometric and biochemical measurements. Food consumption, hunger scores, activity and quality of life were measured every 4 wks. Result(s): 32 patients were enrolled; 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 wks, 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, the IF group showed decreased liver stiffness (IF 7.33 to 5.84 kPa, p = 0.0088; SC 6.32 to 6.09 kPa p = 0.7305), liver steatosis (IF 287 to 263 dB/m, p = 0.012; SC 268 to 268 dB/m, p = 0.981), waist circumference (3.0 cm, p = 0.028) and visceral fat volume (13%, p = 0.0186). HOMA-IR decreased by 10% in the IF group compared to a 2.5% increase in SC group (p = 0.039). There was no difference in dietary energy consumption, activity levels, hunger or quality of life scores between the groups. Conclusion(s): IF is a well tolerated strategy to treat NAFLD and central adiposity with significantly greater improvement in transient elastography (liver stiffness and CAP), waist circumference, visceral fat and insulin resistance compared to standard diet and exercise advice in this pilot study.