Dietary Interventions for Non-Alcoholic Fatty Liver Disease

Overseen By Tzung Hsiai, M.D., Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: VA Greater Los Angeles Healthcare System

Disqualifiers: Diabetes, Alcohol use, Cirrhosis, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different diets might help treat non-alcoholic fatty liver disease, a condition where fat accumulates in the liver without alcohol use. Participants will follow three types of diets: a high-fat/low-carb diet, a low-fat diet, and a Mediterranean diet, each for two weeks. Researchers will monitor the effects using devices that track blood sugar and other body signals, such as a continuous glucose monitor, an integrated sweat sensor, and a vascular sensor. The trial is suitable for U.S. veterans with a waist size over 40 inches for men or 35 inches for women, who also meet specific health criteria like high blood pressure or cholesterol issues. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on dietary impacts on liver health.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have a thyroid condition, you must be on a stable dose of medication for at least 6 months to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that different diets impact liver health in various ways. The high-fat/low-carb ketogenic diet has mixed results. Some studies suggest it can lower liver fat, which might be beneficial. However, research in mice showed it could also cause liver issues over time, such as fatty liver disease.

While specific data on the low-fat diet isn't provided here, these diets are generally considered safe and are often recommended for heart and liver health.

The Mediterranean diet is recognized for being heart-healthy and is generally considered safe. It emphasizes fruits, vegetables, whole grains, and healthy fats like olive oil, and is often praised for its long-term health benefits.

Overall, these diets are usually well-tolerated. However, everyone is different, and what works for one person might not work for another. Always consult a healthcare provider before making significant dietary changes, especially when considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these dietary interventions for Non-Alcoholic Fatty Liver Disease (NAFLD) because they offer a fresh approach compared to current standard treatments, which often focus on medications and generalized lifestyle changes. These specific diets—the High-fat/Low-carb diet, Low-fat diet, and Mediterranean diet—are tailored to potentially optimize liver health by modulating metabolism in unique ways. Unlike traditional treatments, these diets incorporate the use of a continuous glucose monitor and sensors to provide real-time insights into how dietary changes affect the body, allowing for a more personalized and precise management of NAFLD. This innovative approach could lead to more effective and individualized treatment strategies, which is why researchers are eager to explore their potential.

What evidence suggests that this trial's dietary interventions could be effective for non-alcoholic fatty liver disease?

Research has shown that different diets can help manage non-alcoholic fatty liver disease (NAFLD). In this trial, participants will follow one of three diets: a high-fat/low-carb diet, a low-fat diet, or a Mediterranean diet. A high-fat/low-carb diet, such as the ketogenic diet, has effectively reduced liver fat and improved liver health. Studies suggest it can reverse fatty liver changes and enhance liver function. Similarly, a low-fat diet has lowered liver enzymes, indicating better liver health. The Mediterranean diet, which includes healthy fats like olive oil, has been linked to reducing the severity of fatty liver. Each of these diets has shown potential benefits for people with NAFLD. ^{1 6 7 8 9}

Who Is on the Research Team?

Tzung Hsiai, M.D., Ph.D.

Principal Investigator

VAGLAHS and UCLA

Are You a Good Fit for This Trial?

This trial is for individuals with liver conditions like fatty liver and non-alcoholic fatty liver disease. Participants will follow one of three diets: Mediterranean, high-fat/low-carb, or low-fat over a 12-week period while wearing monitoring devices.

Inclusion Criteria

United States Veterans

At least 2 of the following: waist circumference > 40" for men and 35" for women, FBS > 100 mg/dl, triglycerides > 150 but < 500 mg/dL, HDL < 40 mg/dL, Pre-hypertension or hypertension (BP > 120/80 mmHg but < 150/90 mmHg)

Exclusion Criteria

History of alcohol intake ≥ 20g/day

Any unstable medical conditions or terminal diagnosis

Any participant who is unwilling to sign an informed consent form will not be admitted into the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Baseline

Participants consume their habitual diet for 2 weeks to establish baseline. A continuous glucose monitor (CGM) and integrated sweat and vascular sensors are administered.

2 weeks

Diet Intervention 1

Participants are randomized to one of the three diets (Mediterranean, high-fat/low carb, or low-fat) for 2 weeks. Monitoring includes CGM and integrated sweat and vascular sensors.

2 weeks

Washout

Participants undergo a 2-week washout period between diet interventions.

2 weeks

Diet Intervention 2

Participants switch to a second diet for 2 weeks. Monitoring continues with CGM and integrated sweat and vascular sensors.

2 weeks

Washout

Participants undergo another 2-week washout period between diet interventions.

2 weeks

Diet Intervention 3

Participants switch to the final diet for 2 weeks. Monitoring continues with CGM and integrated sweat and vascular sensors.

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after the diet interventions.

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Continuous glucose monitor
• High-fat/Low carb diet
• Low-fat diet
• Mediterranean diet
• The integrated sweat sensor and vascular sensor

Trial Overview

The study tests the effects of different diets on cardiometabolic disorders in patients with liver disease. It integrates wearable sensors to monitor changes alongside continuous glucose monitoring and regular blood sample collection.

How Is the Trial Designed?

Group I: Habitual diet as a baseline Experimental Treatment 2 Interventions

All participants will consume their habitual diet for 2 weeks to establish baseline. A continuous glucose monitor (CGM) will be placed and the integrated sweat sensor and vascular sensor will be administered.

Group II: Diet 3 (the final remaining diet) Active Control 3 Interventions

participants will be randomized to diet 3 for 2 weeks. A continuous glucose monitor (CGM) will be placed and the integrated sweat sensor and vascular sensor will be administered.

Group III: Diet 1 (one of the three kinds of diets) Active Control 3 Interventions

participants will be randomized to diet 1 for 2 weeks. A continuous glucose monitor (CGM) will be placed and the integrated sweat sensor and vascular sensor will be administered.

Group IV: Diet 2 (one of the two remaining kinds of diets, excluding Diet 1) Active Control 3 Interventions

participants will be randomized to diet 2 for 2 weeks. A continuous glucose monitor (CGM) will be placed and the integrated sweat sensor and vascular sensor will be administered.

Who Is Running the Clinical Trial?

VA Greater Los Angeles Healthcare System

Lead Sponsor

Trials

53

Recruited

8,700+

Published Research Related to This Trial

Caloric restriction, regardless of macronutrient composition, is crucial for managing non-alcoholic fatty liver disease (NAFLD), and adherence to a Mediterranean diet low in added sugars and processed meats can provide additional benefits.

Intermittent fasting shows promise in reducing liver fat and promoting ketogenesis, but more research is needed; personalized dietary recommendations based on genetics and microbiome may enhance treatment effectiveness for NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eating, diet, and nutrition for the treatment of non-alcoholic fatty liver disease. Semmler, G., Datz, C., Trauner, M.[2023]

A 12-week study involving 88 Chinese females with nonalcoholic fatty liver disease (NAFLD) showed that a Mediterranean-like diet led to significant weight loss and reductions in liver fat content, with the diet group losing an average of 4.0 kg compared to only 1.5 kg in the control group.

Supplementation with pentadecanoic acid (C15:0) further improved health outcomes by lowering LDL-cholesterol and positively affecting gut microbiome composition, indicating that this dietary approach can enhance metabolic health in individuals with NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of an Asian-adapted Mediterranean diet and pentadecanoic acid on fatty liver disease: The TANGO randomized controlled trial. Chooi, YC., Zhang, QA., Magkos, F., et al.[2023]

The Spanish Ketogenic Mediterranean Diet (SKMD) significantly improved various health markers in 14 obese men over 12 weeks, including body weight, liver enzymes, and cholesterol levels, indicating its efficacy in treating metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD).

After following the SKMD, all participants were free of metabolic syndrome according to the International Diabetes Federation criteria, demonstrating the diet's potential as a safe and effective intervention for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of the Spanish Ketogenic Mediterranean Diet on nonalcoholic fatty liver disease: a pilot study. Pérez-Guisado, J., Muñoz-Serrano, A.[2017]

Lifestyle changes, particularly optimizing nutrition and increasing physical activity, are crucial for improving or resolving non-alcoholic fatty liver disease (NAFLD).

Among various dietary interventions studied in 317 adults with NAFLD, the Mediterranean Diet showed the most significant reductions in liver fat and weight loss, indicating its potential effectiveness, although more research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Dietary Approaches for the Treatment of Non-Alcoholic Fatty Liver Disease: A Systematic Review. Saeed, N., Nadeau, B., Shannon, C., et al.[2020]

The Mediterranean diet (MD) is recommended for treating non-alcoholic fatty liver disease (NAFLD) as it can improve liver health and metabolic conditions even without weight loss, making it a beneficial dietary approach for patients.

Components of the MD, such as olive oil, fish, and whole grains, have been shown to positively impact NAFLD, while Western dietary elements like soft drinks and saturated fats are linked to worsening the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Mediterranean dietary pattern as the diet of choice for non-alcoholic fatty liver disease: Evidence and plausible mechanisms. Zelber-Sagi, S., Salomone, F., Mlynarsky, L.[2019]

A systematic review of three trials involving 128 adults with non-alcoholic fatty liver disease (NAFLD) found that specific dietary patterns, particularly the Mediterranean diet, can significantly reduce hepatic fat content and triglyceride levels.

The Mediterranean diet showed strong evidence of reducing hepatic fat by 4.1% and triglycerides by 16.9 mg/dL compared to low-fat diets, highlighting its potential as an effective lifestyle modification for managing NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of dietary patterns on non-alcoholic fatty liver disease diagnosed by biopsy or magnetic resonance in adults: a systematic review of randomised controlled trials. Angelidi, AM., Papadaki, A., Nolen-Doerr, E., et al.[2022]

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