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

54 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment Continuous glucose monitor, High-fat/Low carb diet, Low-fat diet, Mediterranean diet, The integrated sweat sensor and vascular sensor for Non-Alcoholic Fatty Liver Disease?

Research shows that the Mediterranean diet can significantly reduce liver fat and improve metabolic health in people with non-alcoholic fatty liver disease. Additionally, low-carbohydrate diets have been found to reduce liver fat more effectively than low-calorie diets. ^{1 2 3 4 5}

Is the Mediterranean diet safe for humans?

The Mediterranean diet is considered safe for humans and has been shown to improve metabolic health and reduce liver fat in people with non-alcoholic fatty liver disease. It is recommended by clinical guidelines and has been tested in various studies with positive safety outcomes. ^{3 6 7 8 9}

How does the Mediterranean diet treatment for non-alcoholic fatty liver disease differ from other treatments?

The Mediterranean diet is unique for non-alcoholic fatty liver disease because it focuses on high intake of unsaturated fats and fiber, which have shown benefits in weight management and metabolic health, unlike other diets that may not emphasize these components. It is also recommended due to its potential to improve liver health beyond just calorie restriction, offering a more holistic approach to managing the condition. ^{3 4 5 10 11}

What is the purpose of this trial?

It is a 12-week study. The participants will follow three different diets, and during each diet period, and the participants will wear our device, and blood samples will be collected.

Research Team

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

Principal Investigator

VAGLAHS and UCLA

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

References

1. United States 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. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of Dietary Approaches for the Treatment of Non-Alcoholic Fatty Liver Disease: A Systematic Review. [2020]

3. England pubmed.ncbi.nlm.nih.gov

A randomised controlled trial of a Mediterranean Dietary Intervention for Adults with Non Alcoholic Fatty Liver Disease (MEDINA): study protocol. [2018]

4. Korea (South) pubmed.ncbi.nlm.nih.gov

Eating, diet, and nutrition for the treatment of non-alcoholic fatty liver disease. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of an Asian-adapted Mediterranean diet and pentadecanoic acid on fatty liver disease: The TANGO randomized controlled trial. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

The Mediterranean dietary pattern as the diet of choice for non-alcoholic fatty liver disease: Evidence and plausible mechanisms. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Ad Libitum Mediterranean and Low-Fat Diets Both Significantly Reduce Hepatic Steatosis: A Randomized Controlled Trial. [2019]

8. England pubmed.ncbi.nlm.nih.gov

The effectiveness and acceptability of Mediterranean diet and calorie restriction in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

The effect of the Spanish Ketogenic Mediterranean Diet on nonalcoholic fatty liver disease: a pilot study. [2017]

10. United States pubmed.ncbi.nlm.nih.gov

Impact of a Mediterranean diet on hepatic and metabolic outcomes in non-alcoholic fatty liver disease: The MEDINA randomised controlled trial. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Dietary strategies in non-alcoholic fatty liver disease patients: From evidence to daily clinical practice, a systematic review. [2023]