Effect of Exercise on Liver Function and Insulin Resistance Markers in Patients with Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background: Structured exercise as part of lifestyle modification plays an important role in the improvement of non-alcoholic fatty liver disease (NAFLD); however, its effectiveness has been shown to vary. This systematic review with meta-analysis investigated the effects of exercise on liver function and insulin resistance markers in patients with NAFLD. Methods: Six electronic databases were searched using terms related to exercise and NAFLD up to March 2022. Data were analyzed using a random-effects model to estimate the standardized mean difference (SMD) and 95% confidence interval. Results: The systematic search identified 2583 articles, of which a total of 26 studies met the inclusion criteria and were eligible. Exercise training had a moderate effect on reducing ALT (SMD: −0.59, p = 0.01) and small effects on reducing AST (SMD: −0.40, p = 0.01) and insulin (SMD: −0.43, p = 0.02). Significant reductions in ALT were found following aerobic training (SMD: −0.63, p < 0.01) and resistance training (SMD: −0.45, p < 0.001). Moreover, reductions in AST were found following resistance training (SMD: −0.54, p = 0.001), but not after aerobic training and combined training. However, reductions in insulin were found following aerobic training (SMD: −0.55, p = 0.03). Exercise interventions for <12 weeks compared to ≥12 weeks were more effective in reducing FBG and HOMA-IR, while interventions for ≥12 weeks compared to <12 weeks were more effective in reducing ALT and AST levels. Conclusions: Our findings support the effectiveness of exercise in improving liver function markers but not in blood glucose control in NAFLD patients. Additional studies are needed to determine the exercise prescription to maximize health in these patients.

Exercise in the Management of Metabolic-Associated Fatty Liver Disease (MAFLD) in Adults: A Position Statement from Exercise and Sport Science Australia

“…Coupled with poor correlation with liver histology [ 119 ], these liver enzymes should not be considered as a good surrogate for hepatic steatosis or MAFLD severity in isolation. To date, 21 meta-analyses and two network analyses have examined the efficacy of exercise for improving ALT [ 54 , 57 , 60 , 61 , 64 – 66 , 70 , 72 , 74 – 76 , 80 – 82 , 120 – 126 ]. Nineteen of these have also examined AST [ 54 , 57 , 60 , 64 – 66 , 70 , 72 , 74 – 76 , 80 – 82 , 120 – 123 , 126 ], with mixed findings for the benefits of exercise on liver enzyme reduction.…”

“…To date, 21 meta-analyses and two network analyses have examined the efficacy of exercise for improving ALT [ 54 , 57 , 60 , 61 , 64 – 66 , 70 , 72 , 74 – 76 , 80 – 82 , 120 – 126 ]. Nineteen of these have also examined AST [ 54 , 57 , 60 , 64 – 66 , 70 , 72 , 74 – 76 , 80 – 82 , 120 – 123 , 126 ], with mixed findings for the benefits of exercise on liver enzyme reduction. Based on the most current meta-analyses, low-to-medium pooled effect sizes demonstrating a benefit of exercise on ALT have been observed [ 54 , 74 – 76 , 80 , 81 , 120 , 121 , 126 ], showing absolute differences of 6.66 IU/L (95% CI 3.27, 10.04 IU/L) [ 126 ] favouring exercise versus control.…”

“…Nineteen of these have also examined AST [ 54 , 57 , 60 , 64 – 66 , 70 , 72 , 74 – 76 , 80 – 82 , 120 – 123 , 126 ], with mixed findings for the benefits of exercise on liver enzyme reduction. Based on the most current meta-analyses, low-to-medium pooled effect sizes demonstrating a benefit of exercise on ALT have been observed [ 54 , 74 – 76 , 80 , 81 , 120 , 121 , 126 ], showing absolute differences of 6.66 IU/L (95% CI 3.27, 10.04 IU/L) [ 126 ] favouring exercise versus control. Low-to-medium pooled effect sizes favouring exercise have also been observed for AST [ 74 , 75 , 81 , 120 , 121 , 126 ], showing absolute differences of 3.14 IU/L (95% CI 0.35, 5.93 IU/L) [ 116 ] favouring exercise versus control [ 126 ].…”

“…The majority of evidence supports the benefits of exercise on total cholesterol [ 64 , 71 , 74 , 75 , 121 , 124 , 125 ], potentially driven by benefits on LDL-cholesterol [ 54 , 64 , 65 , 75 , 79 , 82 , 121 , 124 , 125 ]. While one meta-analysis demonstrated within-group benefits for exercise on hepatic insulin sensitivity [ 69 ], the efficacy for improving glycaemic control [ 54 , 65 , 73 , 75 , 79 , 80 ] and the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) [ 25 , 50 , 54 , 59 , 60 , 66 , 67 , 70 , 76 , 123 ] in people with MAFLD is inconsistent. Small laboratory-based aerobic exercise trials have shown a benefit on endothelial function [ 136 ], peripheral insulin sensitivity [ 142 ] and novel risk factors such as thrombotic biomarker plasminogen activator inhibitor 1 (PAI-1) [ 139 ].…”

High fructose consumption increases liver GLUT-2 expression and the benefits of exercise on the liver metabolism: A literature review

“…Exercise provides various benefits to the liver, including increased fatty acid oxidation, prevention of triglyceride production through the reduction of lipogenic enzymes, inhibition of inflammatory responses, and enhanced insulin sensitivity (Hejazi & Hackett, 2023). As insulin sensitivity in the liver improves, the expression of GLUT-2 in hepatocytes decreases due to internalization into endosomal compartments (Narasimhan et al, 2015).…”