Dietary adjustments currently stand as the primary treatment for Non-Alcoholic Fatty Liver Disease (NAFLD). At the 58th European Association for the Study of the Liver (EASL) Annual Meeting (EASL 2023), Deepankshi Aggarwal from India presented their team’s latest findings in an oral presentation. They discussed how time-restricted intermittent fasting may be superior to standard caloric restriction in improving the metabolic status and liver fibrosis of NAFLD patients. Dr. Lungen Lu’s team from the First People’s Hospital of Shanghai Jiao Tong University School of Medicine offered insights into this research.
Due to improvements in dietary structure and living conditions, approximately 1/4 of the global adult population now suffers from Non-Alcoholic Fatty Liver Disease (NAFLD). As reliable and effective therapeutic drugs are still lacking, weight reduction and lifestyle interventions through dietary adjustments and exercise are recommended as first-line treatments for Non-Alcoholic Fatty Liver (NAFL)/Non-Alcoholic Steatohepatitis (NASH) patients who are overweight or obese. Although intermittent fasting (IF) has been effective in weight reduction, its effects on liver diseases in NAFLD patients require further investigation. Aggarwal and colleagues from India evaluated the effectiveness of calorie restriction through time-restricted intermittent fasting compared to the standard of care calorie restriction (SOC) in improving liver fat deposition, inflammation, and fibrosis in NAFLD patients.
In this open-label randomized study, 68 overweight or obese NAFLD patients with a body mass index (BMI) ≥23 kg/m2 were randomly assigned to the IF and SOC groups. After calculating the required daily calorie intake (30-35 kcal/kg/day), both groups were advised to restrict calorie intake by 30% through IF or SOC. The IF regimen involved 16:8 time-restricted eating (8 hours of eating followed by 16 hours of fasting). Body measurements, metabolic syndrome indicators, liver fat content (assessed by ultrasound and controlled attenuation parameter CAP), liver inflammation (liver enzymes and FibroScan-AST [FAST] score), and liver fibrosis changes (APRI, FIB-4, NFS, FibroScan liver stiffness measurement [LSM]) were analyzed both within and between groups at baseline and after 6 months of the study.
After excluding 6 patients from each group due to loss to follow-up, a total of 56 patients (28 in each group, with similar average age and BMI, male-to-female ratio 1:1) were included in the analysis. The study results are as follows:
1. Both groups showed significant improvements in body measurements, with both waist circumference, weight, and BMI decreasing significantly from baseline (IF group: 4.3%, 5.88%, and 6.1%; SOC group: 2.7%, 4.71%, and 4.6%; all p < 0.001), with no significant difference between the groups.
2. Both groups exhibited significant improvements in metabolic syndrome indicators, with IF performing better than SOC. Compared to baseline (p < 0.001) and SOC (p = 0.012), the IF group showed significant reductions in average blood pressure, fasting blood sugar, total cholesterol, and low-density lipoprotein levels.
3. Both groups showed significant improvements in liver fat deposition. The IF group reduced from 316 ± 43.78 to 287.7 ± 46.4 dB/m (p < 0.001), while the SOC group reduced from 323.1 ± 40.34 to 300.89 ± 45.7 dB/m (p < 0.001). The average CAP decreased in both groups, with no significant difference between them.
4. Both groups exhibited significant improvements in liver inflammation, with both ALT and FAST scores decreasing significantly. For patients with elevated ALT, the average ALT decreased significantly in both the IF group (from 74.1 ± 49 to 38.2 ± 26.4 U/ml; p < 0.001) and the SOC group (from 54.39 ± 36.7 to 37.9 ± 27.3 U/ml; p = 0.006), with no significant difference between the groups. Similarly, both the IF group (from 0.38 ± 0.23 to 0.21 ± 0.18; p < 0.001) and the SOC group (from 0.32 ± 0.18 to 0.21 ± 0.19; p = 0.001) exhibited significant reductions in the average FAST score, with no significant difference between the groups.
5. Regarding liver fibrosis, the improvement in LSM was superior in the IF group compared to the SOC group. Compared to baseline, the IF group’s average LSM significantly decreased (from 6.42 ± 2.28 to 5.89 ± 2.12 kPa; p = 0.016), while the SOC group’s LSM did not decrease significantly. Furthermore, the percentage of patients in the IF group (21.4% vs. SOC’s 3.5%) who had a reduction in LSM of more than 20% was significantly higher (p = 0.04). The average reductions in APRI, FIB-4, and NFS in both groups were not significant.
Researchers’ Remarks
Since there are currently no approved drugs for NAFLD treatment, lifestyle adjustments remain the primary choice for managing NAFL or NASH in obese/overweight patients, with traditional standard caloric restriction (SOC) being the preferred method. As research on the role of circadian rhythms in metabolic syndrome and NAFLD progresses, intermittent fasting (IF) has emerged as a hot topic in this field. Although IF has been widely reported to be effective in reducing weight, it has received less attention in NAFLD research.
In this study, Aggarwal and colleagues compared the effectiveness of IF and the traditional SOC in improving NAFLD liver disease in obese/overweight NAFLD patients. They found that both methods were similar in terms of weight reduction and improving liver fat deposition and inflammation. However, IF outperformed SOC in terms of liver fibrosis improvement and enhancing metabolic conditions. This research demonstrates the superiority of IF in preventing or halting the progression of NAFLD to NASH, with similar patient compliance between the two groups (similar dropout rates).
Given that fasting can have safety implications for patients (such as gastrointestinal symptoms, hypoglycemic episodes, fatigue, dizziness, irritability, etc.), if this study can provide additional data on the occurrence of adverse events and compare them between the two groups, it would further solidify the potential for intermittent fasting as a new preferred intervention for NAFLD.
Furthermore, research on intermittent fasting in rodent models of NASH suggests that its effects on obesity, metabolic syndrome, and the evolution of NASH may be mediated by the response of insulin and insulin-like growth factor 1 (IGF-1) to food. If this can be validated in human patient samples, it would provide further insights into the mechanisms of intermittent fasting in treating NAFLD.
In summary, this study demonstrates the advantages of intermittent fasting over standard
caloric restriction in the treatment of NAFLD. It holds practical significance for clinical practice, and if it can provide additional evidence of safety and expand on the mechanisms involved, it would strengthen the case for intermittent fasting as a new preferred intervention for NAFLD.
Reference : 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. Journal of Hepatology 2023 vol. 78(S1) | S1–S99. EASL 2023. Abstract OS-064-YI.
Director of the Department of Gastroenterology, Shanghai Jiao Tong University School of Medicine, First People’s Hospital
TAG: EASL2023;Voice of China;NAFLD
