Effects of alternate-day fasting on body weight and dyslipidaemia in patients with non-alcoholic fatty liver disease: a randomised controlled trial

Abstract

BackgroundAlternate-day fasting (ADF) is a novel diet therapy that may achieve reduction in body weight and improvement of dyslipidaemia, but the impact of this diet on patients with non-alcoholic fatty liver disease (NAFLD) remains unknown. The aim of this study was to evaluate the effects of ADF on the body weight and lipid profile of individuals with NAFLD.MethodsNAFLD patients (n = 271) were randomised to the ADF group, time-restricted feeding (TRF) group, or the control group and subjected to the respective diet for 12 weeks. Anthropometric measurements (body weight, fat mass/fat-free mass) were performed, and plasma lipids were analysed enzymatically.ResultsWithin 4 weeks, the body weight decreased significantly (P < 0.001) in the ADF group by 4.56 ± 0.41 kg (6.1 ± 0.5%) and the TRF group by 3.62 ± 0.65 kg (4.83 ± 0.9%) compared to the control group, and it decreased even more after 12 weeks in both groups (ADF: − 4.04 ± 0.54 kg, 5.4 ± 0.7%; TRF: − 3.25 ± 0.67 kg, 4.3 ± 0.9%). Fat mass was significantly reduced by ADF (− 3.49 ± 0.37 kg; 11 ± 1.2%) and TRF (− 2.91 ± 0.41 kg; 9.6 ± 1.3%), with ADF leading to a further reduction in fat mass after 12 weeks (− 3.48 ± 0.38 kg; 11 ± 1.2%). Total cholesterol was significantly decreased at both time points in the ADF group (− 0.91 ± 0.07 mmol/L; 18.5 ± 1.5%) compared to the control and TRF groups. Both ADF (− 0.64 ± 0.06 mmol/L; 25 ± 1.9%) and TRF (0.58 ± 0.07 mmol/L; 20 ± 1.7%) achieved a significant reduction in serum triglycerides (P < 0.001) after 12 weeks. Changes in fat free mass, HDL, LDL, fasting insulin, glucose, liver stiffness, and systolic or diastolic blood pressure did not differ between the groups.ConclusionsADF appears to be an effective diet therapy for individuals with NAFLD that can achieve weight loss and improvement of dyslipidaemia within a relatively short period of time (4 to 12 weeks). Potential preventive effects of ADF on cardiovascular disease need to be confirmed by future investigations.Trial registrationChiCTR1900024411, this trial was retrospectively registered on July 10, 2019.

Beneficial Effects of Time-Restricted Eating on Metabolic Diseases: A Systemic Review and Meta-Analysis

“…Upon further review and quality assessment, we found 21 studies that met the topic of interest. Among the 21 studies [23,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45], two were excluded for meta-analysis [26,27]. Their main results have been summarized in Supplementary Materials Table S3.…”

“…In the subgroup analysis according to metabolically healthy status, the subgroup with five studies including participants with metabolic abnormality [28,[33][34][35]38] showed significant reduction of body weight (MD, −3.19; 95% CI, −4.62 to −1.77; I 2 , 0%) while the subgroup with seven studies including healthy participants [31,[38][39][40][42][43][44] did not show significant change of body weight (MD, 0.17; 95% CI, −0.81 to 1.15; I 2 , 0%). In sensitivity analysis, one study [33] showed a significant effect on result. When it was removed, statistical significance disappeared (MD, −0.01; 95% CI, −0.95 to 0.93, Supplementary Materials Figure S2A).…”

Hepatic Lipid Catabolism via PPARα-Lysosomal Crosstalk

“…Intriguingly, autophagy induction in NAFLD and NASH has been seriously considered as a key treatment regimen [86]. Already, caloric restriction, time-restricted feeding [87], and exercise which are known autophagic stimuli, at least in part, underlie some of their beneficial consequences in liver dysfunction and steatosis [88,89]. Similarly, enhancing autophagy through drugs metformin or the disaccharide trehalose, thyromimetics, green tea and caffeine to enhance lipophagy and beta-oxidation have also shown promising anti-steatogenic effects [36,88,90,91].…”

Considerations for the Optimal Timing, Duration, Frequency, and Length of an Intermittent Fasting Regimen for Health Improvement

“…Randomized trials show that both a 24-h fast and a TRF (≈16 h) fast result in important biological changes in humans that should lead to extensive health improvements such as chronic disease prevention when practiced repeatedly over a length of years [9][10][11][12][13][14][15][16]. For example, a 24-h fast reduced the microbiome-related cardiac risk factor, trimethylamine N-oxide [10] and induced various changes potentially related to autophagy and energy management [9,10].…”

“…The similarities and differences of a caloric restriction diet, the ketogenic diet, and a fasting diet are considered by Paoli, indicating many co-incident physiological influences of these three distinct dietary approaches [6]. Whether TRF produces the vast array of potential benefits in humans that animal models suggest that it might remains to be seen given that the few published randomized controlled trials of TRF are primarily small pilot studies of <50 participants [11][12][13][14][15], with one larger trial examining alternate-day fasting versus TRF and comparing these to controls [16].…”