Time-Restricted Eating and Its Influence on Nonalcoholic Fatty Liver Disease (NAFLD)

A recent study published in JAMA Network Open compared time-restricted eating (TRE) to daily calorie restriction (DCR) for treating nonalcoholic fatty liver disease (NAFLD). Both methods proved effective in reducing liver fat, improving liver function, and aiding weight loss. While there were no significant differences between the two, TRE might offer additional benefits for insulin sensitivity. The study suggests that consistent calorie reduction is crucial for NAFLD improvement, and individuals can choose either TRE or DCR based on their preferences. Overall, the findings emphasize the effectiveness of lifestyle interventions for managing NAFLD, providing hope for those affected by this condition.

Ket points

• Both TRE and DCR are effective for NAFLD: both time-restricted eating and daily calorie restriction effectively reduce liver fat, improve liver function, and aid weight loss in individuals with NAFLD.

• Calorie reduction is crucial: The primary driver of health improvements is overall calorie reduction, regardless of whether you use TRE or DCR.

• TRE might offer additional benefits: TRE may provide a slight advantage in improving insulin sensitivity compared to DCR.

• Choose the approach that suits you: Individuals can select either TRE or DCR based on their personal preferences and lifestyle.

• Lifestyle interventions are effective: The study reinforces the effectiveness of lifestyle modifications for managing NAFLD, emphasizing the power of dietary changes.

• Consistent calorie reduction is key: Achieving a moderate calorie deficit is essential for long-term success in treating NAFLD.

Time-Restricted Eating vs Daily Calorie Restriction for Treating Nonalcoholic Fatty Liver

DiseaseNonalcoholic fatty liver disease (NAFLD) has emerged as a major global health challenge, affecting approximately 20–30% of adults worldwide. The prevalence is even higher among individuals with obesity or diabetes, reaching up to 70%. In China specifically, nearly 30% of adults are estimated to have NAFLD. This condition is closely linked to obesity, type 2 diabetes, high cholesterol, and hypertension, and it increases the risk of cardiovascular disease.

Given the growing prevalence of NAFLD, there is significant interest in identifying effective lifestyle interventions to treat and manage this condition. Weight loss through dietary changes has been shown to improve liver fat levels and metabolic health in NAFLD patients. However, long-term adherence to lifestyle modifications can be challenging for many individuals.

In recent years, time-restricted eating (TRE) has gained popularity as a potential alternative to traditional calorie restriction for weight loss and metabolic health improvement. TRE involves limiting food intake to a specific window of time each day, typically 8–12 hours. Some research on animals has suggested that the timing of food intake, rather than just calorie reduction, may underlie the benefits of TRE.

However, the efficacy of TRE specifically for treating NAFLD in humans has remained uncertain. To address this knowledge gap, researchers in China conducted a 12-month randomized clinical trial comparing the effects of TRE versus daily calorie restriction (DCR) in patients with obesity and NAFLD. The results of this important study were recently published in JAMA Network Open.

Study Design and Methods

1. Study Overview: The TREATY-FLD trial, conducted at Nanfang Hospital in Guangzhou, China, between April 2019 and August 2021, involved 88 adults aged 18-75 with obesity (BMI 28-45) and confirmed nonalcoholic fatty liver disease (NAFLD).

2. Participant Groups: Participants were randomly assigned to either a Time-Restricted Eating (TRE) group, which consumed all calories between 8:00 am and 4:00 pm, or a Daily Calorie Restriction (DCR) group, which reduced overall calorie intake without a specific eating window.

3. Dietary Plan: Both groups followed the same calorie-restricted diet: 1500-1800 calories/day for men and 1200-1500 calories/day for women, with a macronutrient distribution of 40-55% carbohydrates, 15-20% protein, and 20-30% fat.

4. Support and Monitoring: Intensive support was provided for the first 6 months, including dietary counselling, protein shakes, food diaries, bi-weekly nutritionist meetings, and frequent follow-ups. Support was reduced but continued during months 7-12 with monthly meetings and weekly follow-ups.

5. Outcomes Measured: The primary outcome was the change in intrahepatic triglyceride (IHTG) content measured by MRI at baseline, 6 months, and 12 months. Secondary outcomes included changes in body weight, waist circumference, body composition, liver stiffness, liver enzymes, and metabolic risk factors.

Key Findings

1. Liver Fat Reduction: Both groups experienced similar reductions in intrahepatic triglyceride (IHTG) content at 6 and 12 months, with no significant differences between the Time-Restricted Eating (TRE) and Daily Calorie Restriction (DCR) groups.

2. Liver Stiffness Improvement: Significant reductions in liver stiffness were observed in both groups (TRE: -2.1 kPa, DCR: -1.7 kPa), with no significant differences between them.

3. NAFLD Resolution: The resolution of nonalcoholic fatty liver disease (IHTG <5%) at 12 months was similar between the groups (TRE: 33%, DCR: 49%), with no statistically significant difference.

4. Weight Loss: Both TRE and DCR groups achieved significant weight loss (TRE: -8.4 kg, DCR: -7.8 kg) with no significant difference between the groups.

5. Body Composition: Significant reductions in waist circumference, body fat percentage, fat mass, lean mass, abdominal fat, subcutaneous fat, and visceral fat were observed in both groups, with no differences between TRE and DCR.

6. Metabolic Health Improvements: Both diets led to improvements in blood pressure, cholesterol levels (total, HDL, LDL), triglycerides, fasting plasma glucose, HbA1c, liver enzymes (ALT, AST, GGT), and insulin resistance.

7. Insulin Resistance: The only significant difference between groups was in insulin resistance at 12 months, where TRE showed a greater improvement than DCR.

Implications and Discussion

This well-designed randomized clinical trial provides important insights into the comparative effectiveness of time-restricted eating versus daily calorie restriction for treating nonalcoholic fatty liver disease. The key takeaway is that both approaches appear to be equally effective when calorie intake is matched.

Here are some of the main implications of these findings:

1. Calorie Restriction is Crucial: The study shows that overall calorie reduction, rather than meal timing, is the primary factor in improving liver fat content and metabolic health in NAFLD patients. Both time-restricted eating (TRE) and daily calorie restriction (DCR) were equally effective.

2. TRE is Sustainable Long-Term: The high adherence rates (85% of days) over 12 months suggest that TRE is a feasible long-term dietary approach for many individuals, offering flexibility in meal planning.

3. Moderate Interventions Yield Significant Results: Even with moderate calorie reduction and an 8-hour eating window, participants experienced significant improvements, including a 7-8% reduction in liver fat content and an 8 kg weight loss. This shows that drastic changes aren't necessary to achieve meaningful health benefits.

4. Broad Health Benefits: The study found that participants not only improved liver health but also saw widespread benefits in cardiovascular risk factors, glycemic control, and body composition, demonstrating the interconnected nature of metabolic health.

5. TRE may enhance insulin sensitivity: TRE showed a potential advantage over DCR in improving insulin resistance at 12 months, suggesting that TRE might have specific benefits for glucose metabolism, though further research is needed.

6. Population-Specific Results: The findings are based on a relatively young, obese, Chinese population with NAFLD. Results may differ in other groups, such as older adults or those with different ethnic backgrounds, emphasizing the need for further research in diverse populations.

7. Lifestyle Changes as First-Line Treatment: The study highlights the effectiveness of lifestyle modifications in treating NAFLD, with a significant portion of participants resolving their condition through diet alone, underscoring the importance of non-invasive interventions.

Practical Implications for Patients and Healthcare Providers

For individuals with NAFLD and their healthcare providers, this study offers several practical insights:

1. Focus on calorie reduction: Whether using TRE or traditional calorie restriction, the key is to achieve a moderate calorie deficit. Work with a healthcare provider or registered dietitian to determine an appropriate calorie target.

2. Choose the approach that fits your lifestyle: Both TRE and DCR can be effective. Patients should choose the method that aligns best with their schedule, preferences, and ability to adhere long-term.

3. Aim for gradual, sustainable weight loss: The study achieved significant benefits with moderate weight loss of about 8 kg over a year. Crash diets or extreme restrictions are not necessary and may be counterproductive.

4. Monitor multiple health markers: While liver fat is the primary concern in NAFLD, it's valuable to track other metrics like weight, waist circumference, blood pressure, and blood sugar. Improvements often occur across multiple domains.

5. Provide adequate support: The high adherence rates in this study were likely influenced by the regular check-ins, counseling, and education provided to participants. Healthcare systems should strive to offer similar support to patients attempting lifestyle changes.

6. Consider TRE for insulin resistance: For patients struggling with insulin sensitivity, TRE may offer a slight advantage and could be worth trying.

Limitations and Future Research Directions

While this study provides valuable insights, there are some limitations and areas where further research would be beneficial:

1. Lack of liver biopsies: The primary outcome was measured by MRI rather than liver biopsy. While MRI is a reliable non-invasive method, biopsies could provide more detailed information about changes in liver histology.

2. Relatively young population: The mean age of participants was 32. Studies in older adults with NAFLD would be valuable, as the condition becomes more common with age.

3. No control for physical activity: While physical activity was measured, it wasn't controlled or prescribed as part of the intervention. Future studies could examine the combined effects of TRE or DCR with exercise programs.

Conclusion

The TREATY-FLD randomized clinical trial provides robust evidence that both time-restricted eating and daily calorie restriction can be effective strategies for treating nonalcoholic fatty liver disease. When calorie intake is matched, these approaches appear to be equally beneficial for reducing liver fat, promoting weight loss, and improving various metabolic risk factors.

This study reinforces the importance of calorie reduction as the primary driver of health improvements in NAFLD. It also demonstrates that patients have flexibility in how they approach calorie restriction, whether through a defined eating window or more traditional portion control throughout the day. The high adherence rates and significant health improvements observed in this trial are encouraging. They suggest that even moderate dietary changes, when sustained over time, can lead to meaningful benefits for liver health and overall metabolic function.

Reference Article

Wei, X., Lin, B., Huang, Y., Yang, S., Huang, C., Shi, L., Liu, D., Zhang, P., Lin, J., Xu, B., Guo, D., Li, C., He, H., Liu, S., Xue, Y., Xu, Y., & Zhang, H. (2023). Effects of Time-Restricted Eating on Nonalcoholic Fatty Liver Disease: The TREATY-FLD Randomized Clinical Trial. JAMA network open, 6(3), e233513. https://doi.org/10.1001/jamanetworkopen.2023.3513

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