A Randomised Controlled Trial on the Effectiveness and Adherence of Modified Alternate-day Calorie Restriction in Improving Activity of Non-Alcoholic Fatty Liver Disease

Abstract

Currently, there is no effective therapy for non-alcoholic fatty liver disease (NAFLD), although intensive calorie restriction is typically recommended but dietary adherence is an issue. The current study aimed to determine the effectiveness and adherence of eight weeks of modified alternate-day calorie restriction (MACR) in the control of NAFLD activity. This was a randomized controlled trial with MACR as the intervention and normal habitual diet as control. The outcome measures were body mass index (BMI), blood lipids, fasting blood sugar (FBS), liver enzymes (ALT and AST), and ultrasonographic measurements of liver steatosis and shear wave elastography (SWE). Per-protocol (PP) and intention-to-treat (ITT) analysis were performed within and between-groups with P < 0.05 as significant. 43 individuals with NAFLD satisfied study entry criteria, 33 were randomized to MACR and 10 to control group, and, 30 from MACR and 9 from control group completed PP. In between-group analysis of MACR vs. control, BMI were reduced in PP (P = 0.02) and ITT (P = 0.04). Only ALT was reduced in between-group analysis of MACR vs. control, both PP and ITT (P = 0.02 and 0.04 respectively). No reductions in all lipid parameters and FBS were found in between-group analyses (PP and ITT, all P > 0.22). Both liver steatosis grades and fibrosis (SWE) scores were reduced in between-group analyses of MACR vs. controls (PP and ITT, all P < 0.01). Adherence level remained between 75–83% throughout the study. As conclusion, 8 weeks of MACR protocol appears more effective than usual habitual diet in the control of NAFLD activity and with good adherence rate.

Health Effects of Alternate-Day Fasting in Adults: A Systematic Review and Meta-Analysis

“…The traditional methods of losing weight (such as the daily calorie restriction), although the effect is affirmative, the control and compliance are poor (41). Based on this foundation, intermittent fasting regimens, especially ADF protocols, are being proposed in many pieces of literature (9,19,(33)(34)(35)(36)(37). The important unsolved issue is whether the effects of ADF can play a role for people who want to lose weight.…”

Evidence-based clinical advice for nutrition and dietary weight loss strategies for the management of NAFLD and NASH

“…An 8 weeks modified alternate-day calorie restriction was found to lead to reductions in BMI, liver enzymes, liver steatosis and liver stiffness (based on shear wave elastography) compared to no intervention with adherence rates of 75-83%. 28 A larger trial comparing alternate-day and time-restricted feeding with a control group for 12 weeks revealed that both diets led to significant short-term reductions in weight and improvements in dyslipidaemia, although no changes were seen for fasting levels of insulin or liver stiffness. 29…”

Evaluation of Dietary Approaches for the Treatment of Non-Alcoholic Fatty Liver Disease: A Systematic Review

“…All six studies evaluated the impact of the dietary intervention on alanine aminotransferase (ALT) levels, but only half of these studies demonstrated a significant improvement (LGMD and INRAN, MD and LF and MACR). Patients achieved weight loss in all of these studies, with significant weight loss in 5/6 studies [22,25,26].…”

“…On the basis of abstract review, 26 were selected for full-text review. Two study authors classified six articles as meeting the predefined criteria for analysis [17,[22][23][24][25][26]. A total of 317 patients from six unique populations were represented.…”

“…Two study arms employed a low-fat diet, but only one of these arms had a statistically significant reduction in amount of hepatic steatosis [17,25]. The intermittent-fasting arm study also showed statistically significant improvement in amount of hepatic steatosis [26]. Four studies evaluated change in liver stiffness via elastography, with 2/3 MD-based interventions associated with statistically significantly improved liver stiffness measurements, which was also seen in the MACR diet intervention.…”