Intermittent Fasting for Non-alcoholic Fatty Liver Disease

Overseen By Hayley Schultz, BA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must not be taking: Insulin, Sulfonylureas

Disqualifiers: Heavy alcohol use, Type II diabetes, Chronic liver disease, Chronic kidney disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests intermittent fasting as a potential treatment for non-alcoholic fatty liver disease (NAFLD) in individuals who are not obese. The goal is to identify a lifestyle-based method to assist those with NAFLD. Participants will adhere to a specific fasting schedule for six weeks. The trial seeks adults with a BMI between 23 and 30 who have been diagnosed with NAFLD through a recent scan or biopsy. As an unphased trial, it offers a unique opportunity to explore a non-drug approach to managing NAFLD.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used any pharmacological treatments for NAFLD/NASH in the past 6 months, except for vitamin E. If you're on a stable dose of vitamin E, you can still join the study.

What prior data suggests that intermittent fasting is safe for non-obese adults with NAFLD?

Research shows that intermittent fasting (IF) might be safe for treating non-alcoholic fatty liver disease (NAFLD). Studies have found that IF can aid in weight loss and improve liver health in people with NAFLD, suggesting it is generally well-tolerated.

Different methods of IF, such as time-restricted eating and the 5:2 diet, have been studied for their effects on liver health. Research indicates that these methods can help reduce liver fat, which signals safety and effectiveness.

Overall, evidence suggests that intermittent fasting can be a safe option for managing NAFLD, particularly for individuals who are not obese. Consulting a healthcare provider is important to determine if this approach is suitable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about intermittent fasting for non-alcoholic fatty liver disease (NAFLD) because it offers a unique approach compared to traditional treatments like lifestyle changes and medications targeting metabolic factors. Unlike many treatments that focus on reducing liver fat through drugs, intermittent fasting leverages the body's natural rhythms by limiting eating to specific times of the day, potentially improving metabolism and liver health without medication. This method could provide an accessible, low-cost alternative that empowers patients to manage their condition through dietary habits, offering a fresh perspective on tackling NAFLD.

What evidence suggests that intermittent fasting might be an effective treatment for NAFLD?

Research has shown that intermittent fasting can benefit individuals with non-alcoholic fatty liver disease (NAFLD). Studies have found that this eating plan can reduce body weight and liver fat, both crucial for treating NAFLD. In this trial, participants will follow a method called time-restricted eating, which has improved liver health by reducing liver fat. Another method, the 5:2 diet, also aids by decreasing fat and enhancing liver function. Overall, these findings suggest that intermittent fasting could serve as a useful non-drug option for managing NAFLD, particularly for those who are not obese. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults with non-obese NAFLD (BMI between 23-30), confirmed by a recent liver assessment, who are not heavy drinkers, without other chronic liver diseases or severe illnesses. Participants must not be on weight loss treatments or have unstable body weight and should not be pregnant or trying to conceive.

Inclusion Criteria

Evidence of NAFLD confirmed by historical procedure obtained no more than 6 months prior to the screening visit, defined as:

Hepatitis C antibody and Hepatitis B surface antigen negative at screening

Willing and able to provide informed consent

Exclusion Criteria

Known positivity for human immunodeficiency virus infection

My kidney function is reduced with an eGFR below 60.

I have had a liver transplant or am on the liver transplant list.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants follow a time-restricted, intermittent fasting diet for 6 weeks

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Intermittent Fasting

Trial Overview The trial is exploring the effects of Intermittent Fasting as a lifestyle treatment for adults with Non-alcoholic Fatty Liver Disease (NAFLD) who aren't obese. It aims to find non-drug methods to manage this condition.

How Is the Trial Designed?

Group I: Time-Restricted, Intermittent Fasting Group Experimental Treatment 1 Intervention

Special type of diet for 6 weeks, called time-restricted, intermittent fasting.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

Long-term alternate day fasting (ADF) significantly reduces hepatic inflammation and lipid accumulation in mice with high-fat diet-induced nonalcoholic fatty liver disease (NAFLD), suggesting its efficacy as a dietary intervention.

The protective effects of ADF against NAFLD are linked to the activation of PPARα and increased expression of fibroblast growth factor 21 (Fgf21), indicating a specific mechanism of action that could be targeted for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternate-day fasting alleviates high fat diet induced non-alcoholic fatty liver disease through controlling PPARα/Fgf21 signaling. Liu, X., Zhang, Y., Ma, C., et al.[2022]

In a study of 32 participants with non-alcoholic fatty liver disease (NAFLD), time-restricted fasting (TRF) for 16 hours daily led to significant reductions in liver fat (steatosis), weight, waist circumference, and BMI compared to standard care over 12 weeks.

TRF proved to be more effective than standard dietary advice, suggesting it could be a primary intervention for weight loss and management of NAFLD without requiring calorie restrictions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-Restricted Fasting Improves Liver Steatosis in Non-Alcoholic Fatty Liver Disease-A Single Blinded Crossover Trial. Feehan, J., Mack, A., Tuck, C., et al.[2023]

Intermittent fasting has been shown to significantly reduce body weight, body mass index (BMI), and improve liver enzymes (ALT and AST) in adults with non-alcoholic fatty liver disease (NAFLD), based on a meta-analysis of six studies involving 417 patients.

While intermittent fasting appears effective for weight management and liver health, further research is needed to assess its long-term safety and feasibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Intermittent Fasting on Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis. Yin, C., Li, Z., Xiang, Y., et al.[2021]

Fasting regimens may serve as a promising adjunctive treatment strategy for nonalcoholic fatty liver disease (NAFLD), which currently has no confirmed treatments.

The potential mechanisms by which fasting diets could benefit NAFLD include modulation of hepatic steatosis, signaling of fibroblast growth factors 19 and 21, and improvements in lipophagy and metabolic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of fasting diets on nonalcoholic fatty liver disease. Mokhtari, Z., Hosseini, E., Hekmatdoost, A., et al.[2023]

In a study of 80 adults with obesity and non-alcoholic fatty liver disease (NAFLD), combining alternate day fasting (ADF) with exercise significantly reduced intrahepatic triglyceride (IHTG) content by 5.48% over 3 months, compared to minimal changes in the exercise and control groups.

While the combination of ADF and exercise improved liver health markers and body composition, it did not show significantly greater benefits compared to ADF alone, suggesting that fasting alone may be sufficient for reducing liver fat in NAFLD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of alternate day fasting combined with aerobic exercise on non-alcoholic fatty liver disease: A randomized controlled trial. Ezpeleta, M., Gabel, K., Cienfuegos, S., et al.[2023]

A study involving 98 NAFLD patients showed that 16 hours of daily fasting during Ramadan significantly improved liver enzymes (ALT and AST) and lipid profiles, with some patients achieving normalization of ALT levels after one month of fasting.

Intermittent fasting also led to reductions in body mass index (BMI) and improvements in glycemic indices, indicating its potential as an effective lifestyle modification for managing NAFLD, especially in early phases and among prediabetic individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of intermittent fasting on laboratory, radiological, and anthropometric parameters in NAFLD patients. Badran, H., Elsabaawy, M., Sakr, A., et al.[2022]

In a study of 271 patients with non-alcoholic fatty liver disease (NAFLD), alternate-day fasting (ADF) led to significant weight loss and fat mass reduction within just 4 weeks, with continued improvements over 12 weeks.

ADF also resulted in a notable decrease in total cholesterol and triglycerides, indicating its potential effectiveness in improving lipid profiles in NAFLD patients, although further research is needed to confirm its long-term cardiovascular benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of alternate-day fasting on body weight and dyslipidaemia in patients with non-alcoholic fatty liver disease: a randomised controlled trial. Cai, H., Qin, YL., Shi, ZY., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8310935/

Effect of Intermittent Fasting on Non-Alcoholic Fatty Liver ... ... non-alcoholic fatty liver disease (NAFLD). Intermittent fasting has shown favorable effects on body weight (BW) and relevant indicators of NAFLD in several ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2802553

Effects of Time-Restricted Eating on Nonalcoholic Fatty ... Key Points. Question Is time-restricted eating more effective in improving nonalcoholic fatty liver disease than daily calorie restriction?

3. frontiersin.org frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.948655/full

Effects of the 5:2 intermittent fasting diet on non-alcoholic ... The 5:2 diet can reduce weight loss and related parameters (fat mass and anthropometric indicators of obesity), as well as hepatic steatosis, ...

4. nutritionandmetabolism.biomedcentral.com nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-024-00885-x

Efficacy of intermittent fasting on improving liver function in ... Effects of time-restricted eating on intrahepatic fat ... Effects of the 5: 2 intermittent fasting diet on non-alcoholic fatty liver disease: a ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2405457723022088

Effects of intermittent fasting regimens on glycemic, hepatic ... Non-alcoholic fatty liver disease (NAFLD) represents a hepatic disorder characterized by the accumulation of fat in the liver with no identifiable causes (e.g., ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04004403

NCT04004403 | Alternate Day Fasting, Exercise, and NAFLD Nonalcoholic fatty liver disease (NAFLD) is characterized by an accumulation of fat in the liver (not resulting from excessive alcohol consumption).

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10564080/

The Impact of Intermittent Fasting on Non-Alcoholic Fatty ... It encompasses a continuum of hepatic disorders spanning from uncomplicated fatty liver (steatosis) to non-alcoholic steatohepatitis (NASH), the ...