Intermittent fasting improves hepatic end points in nonalcoholic fatty liver disease: A systematic review and meta-analysis

Abstract

Background and aims: Despite NAFLD being the most prevalent liver disease globally, currently there are no FDA-approved treatments, and weight loss through caloric restriction and enhanced physical activity is the recommended treatment strategy. Intermittent fasting (IF) has been proposed as an alternative strategy with additional cardiometabolic benefits. In this systematic review and meta-analysis, we evaluated the anthropometric, biochemical, and hepatic impacts of IF in patients with NAFLD.

Methods: MEDLINE, EMBASE, Cochrane Central, and conference abstracts were searched for IF interventions in adults with NAFLD until April 2, 2023. Meta-analysis with a random effects model was used to compare pre-intervention and post-intervention changes in anthropometric, biochemical, and hepatic end points in the IF intervention group with the control group. Publication bias was assessed using Egger's test.

Results: Fourteen studies were included in the systematic review and ten in the meta-analysis (n = 840 participants, 44.64% male). Studies varied in modalities for NAFLD diagnosis, duration of IF (4-52 weeks), and type of IF (5:2 diet, modern alternate-day fasting, time-restricted eating, or religious fasting). Body weight, body mass index, and waist to hip ratio all significantly improved following fasting intervention (p< 0.05). Adults with NAFLD showed an improvement in serum alanine transaminase, aspartate aminotransferase, hepatic steatosis (controlled attenuation parameter measured by vibration-controlled transient elastography), and hepatic stiffness (measured by vibration-controlled transient elastography) after fasting intervention (p < 0.05).

Conclusions: There is limited, but moderate- to high-quality evidence to suggest that IF can improve hepatic end points and promote weight loss in adults with NAFLD. Larger randomized controlled studies with extended duration are needed to further validate our findings.

FIGURE 1

PRISMA flowchart of search for study inclusion in the systematic review and meta-analysis. Abbreviations: PRISMA, preferred reporting items for systematic reviews and meta-analyses.

FIGURE 2

Risk of bias assessment for studies included in meta-analysis. (A) Risk of bias assessment for nonrandomized double-arm studies using ROBINS-I; (B) Risk of bias assessment for randomized controlled studies using RoB2.

FIGURE 3

Pooled analysis of the impact of intermittent fasting on anthropometric end points. Forest plots correspond to pooled analysis of body weight (A), BMI (B), WHR (C), and WC (D). Abbreviations: BMI, body mass index; WC, waist circumference; WHR, waist to hip ratio.

FIGURE 4

Pooled analysis of the impact of intermittent fasting on biochemical end points. Forest plots correspond to pooled analysis of total cholesterol (A), triglycerides (B), HDL (C), and LDL (D).

FIGURE 5

Pooled analysis of the impact of intermittent fasting on HOMA-IR and fasting glucose. Forest plots correspond to pooled analysis of HOMA-IR (A) and fasting blood glucose level (B). Abbreviations: HOMA-IR, homeostatic model assessment for insulin resistance.

FIGURE 6

Pooled analysis of the impact of intermittent fasting on liver-specific end points. Forest plots for pooled analysis of ALT (A), AST (B), liver steatosis (C), and liver stiffness (D). Abbreviations: ALT, alanine transaminase; AST, aspartate aminotransferase.