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Timed Calorie Cuts Beat Standard Dieting for Fibrosis, Metabolic Measures With NAFLD
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EASL Congress 2023, June 21-24, Vienna
Mark Mascolini
Time-restricted intermittent fasting proved significantly more effective than standard-of-care (SOC) calorie cutting in improving hepatic inflammation and fibrosis in an Indian group with nonalcoholic fatty liver disease (NAFLD) [1]. And timed fasting significantly improved fasting blood sugar and some lipid measures whereas SOC dieting did not. But the two calorie-cutting strategies did not differ significantly in improving an array of other weight, liver, and metabolic variables.
With no drugs licensed to manage NAFLD or nonalcoholic steatohepatitis (NASH), diet and exercise to lower weight remain a bedrock approach to managing these conditions-and overweight or obesity in general. Time-restricted intermittent fasting, which specifies blocks of time when a person may eat or must fast [2], has sometimes proved effective in trimming weight, noted researchers from the Post Graduate Institute of Medical Education and Research in Chandigarh, India, who conducted this study. But its role in liver disease remains an open question.
To address this issue, the Chandigarh group conducted an open-label, single-center trial that randomized overweight or obese men and women with ultrasound- or FibroScan-confirmed NAFLD to time-restricted intermittent fasting or SOC calorie restriction. Participants had to be 18 to 70 years old and overweight or obese: 23 kg/m2 (the Asia-Pacific cutoff for overweight) to 35 kg/m2. The trial excluded people with type 2 diabetes, ultrasound or FibroScan evidence of cirrhosis, or a history of hepatic decompensation or hepatocellular carcinoma, as well as people taking weight-loss drugs or any medication for NASH.
Participants in both the time-restricted group and the SOC group aimed to reduce calorie intake by about 30% (500 to 750 kcal) daily. People in the time-restricted arm could eat during an 8-hour period then had to fast for 16 hours. The SOC group could cut their daily calories over 3 routine daily meals. Both groups were advised to practice moderate-intensity aerobic exercise and/or resistance exercise for 45 to 60 minutes per day or 150 to 200 minutes per week.
The trial ran for 1.5 years (July 2001 to December 2022). In 6-month follow-up periods during that time, researchers measured a dozen weight, metabolic, and liver-related variables and compared changes from starting measures in each group and between groups.
The 28 people in the time-restricted group and the 28 in the SOC group both averaged 43 years in age, and each group was fairly evenly divided between women and men. Body mass index (BMI) averaged 29 kg/m2 in the timed arm and 30 kg/m2 in the SOC arm. The groups did not differ significantly in weight, waist circumference, waist-to-hip ratio, diabetes measures, blood pressure, aspartate aminotransferase (AST), FibroScan-AST score (FAST, a NASH predictor), or liver fibrosis markers (FibroScan liver stiffness measure, APRI, FIB-4, or NAFLD fibrosis score). Average low-density lipoprotein (LDL) cholesterol was significantly higher in the time-restricted arm than the SOC arm (133.1 vs 110.9 mg/dL, P = 0.01). And there was a trend toward high alanine aminotransferase (ALT) in the time-restricted group (74.1 vs 54.4 U/mL, P = 0.09).
Most body measures and markers of hepatic steatosis, liver inflammation, liver fibrosis, and metabolic parameters improved significantly in both groups. But the researchers noted some differences favoring time-restricted intermittent fasting:
- Percentage weight reduction and proportion attaining target weight reduction were significantly greater in the time-restricted group.
- The proportion of obese participants who became nonobese was significantly higher in the time-restricted group.
- A significantly higher proportion in the time-restricted group had more than a 50% reduction in ALT (64.3% vs 60.7%, P = 0.02).
- A significantly higher proportion in the time-restricted group achieved more than a 20% reduction in liver stiffness measure by FibroScan (P = 0.043).
- A significantly higher proportion in the time-restricted group had significant fibrosis ruled out by APRI (P = 0.003) or FIB-4 (P < 0.001).
- Average reductions in fasting blood sugar, total cholesterol, and LDL cholesterol were significant in the time-restricted group in both intragroup (P < 0.001, P < 0.001, P = 0.004) and intergroup (P = 0.012, P = 0.01, P = 0.04) analyses, but average reductions in these measures were not significant in the SOC group.
- The increase in proportion of participants attaining a FAST score ruling out NASH was significantly greater in the time-restricted group (P = 0.007).
- A significantly higher proportion in the time-restricted group than the SOC group ruled out advanced fibrosis based on APRI (P = 0.003), FIB-4 (P < 0.01), and NAFLD fibrosis score (P < 0.001).
The Chandigarh team noted that their analysis is limited by reliance on self-reports of dietary compliance and exercise, and that liver disease activity depended solely on noninvasive measures. But with those limitations in mind, they concluded that timed intermittent fasting works better than standard calorie cutting "in improving the metabolic profile and hepatic fibrosis" in people with NAFLD.
References
1. Aggarwal D, Duseja AK, De A, et al. Calorie restriction by time restricted intermittent fasting is better than standard calorie restriction in improving the metabolic profile and hepatic fibrosis in patients with non-alcoholic fatty liver disease. EASL Congress 2023, June 21-24, Vienna. Abstract OS-064-YI.
2. Tinsley G. Time-restricted eating: a beginner's guide. Healthline. September 17, 2017. https://www.healthline.com/nutrition/time-restricted-eating
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