Carbohydrate-Restricted Diet for Non-alcoholic Fatty Liver Disease

Overseen By Alex Luzuriaga-McPherson

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Must not be taking: Valproate, Amiodarone, Prednisone, others

Disqualifiers: Pregnancy, Hepatic virus infections, others

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

Compensation: Varies

Number of Visits: 12

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This will be a 6-month randomized clinical trial with two arms: moderately carbohydrate-restricted diet and a fat-restricted control diet. This 6-month study will have 2 phases: a 12-week controlled feeding phase and a 12-week "free living" phase. During the controlled feeding phase, all food will be provided to the families of the participants for the entirety of the 12 weeks. Participants (n=80) will have been diagnosed with NAFLD based on the presence of current evidence of active disease, which will be determined by the ongoing presence of hepatic steatosis estimated by diffusely echogenic liver via ultrasound suggestive of fatty liver and a serum alanine aminotransferase (ALT) level of 45 U/L or greater. All participants will be children and adolescents age 10-17 yrs.; will have an HbA1c \<7.0; and will be overweight or obese (BMI \>85th percentile). It is anticipated that most participants will be sedentary. The investigators will inquire as to routine physical activity at screening. All participants will be asked to maintain their usual level of physical activity throughout the study. Physical activity will be monitored via a smart watch provided to each participant at the beginning of the study, and participants will be queried weekly by the study dietitian regarding changes in physical activity. Participants who use oral contraceptives will be asked to maintain consistent use of these preparations throughout the study. Hormone use will be examined as a potential covariate in statistical analyses.

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 participate if you have used medications known to induce steatosis, elevate liver enzymes, or affect body weight and carbohydrate metabolism in the last 6 months.

Is a carbohydrate-restricted diet safe for humans?

Research suggests that carbohydrate-restricted diets can be safe for humans, as they have been shown to decrease liver fat content and improve metabolic conditions in people with non-alcoholic fatty liver disease. However, diets high in saturated fats can increase liver fat and insulin resistance, so it's important to consider the type of fats consumed. ^{1 2 3 4 5}

How does a moderately carbohydrate-restricted diet differ from other treatments for non-alcoholic fatty liver disease?

A moderately carbohydrate-restricted diet is unique because it focuses on reducing carbohydrate intake without necessarily restricting calories or fats, which can improve liver fat content and metabolic health. This approach is different from traditional low-calorie diets that often have poor adherence due to their restrictive nature. ^{1 2 3 4 6}

What data supports the effectiveness of a carbohydrate-restricted diet as a treatment for non-alcoholic fatty liver disease?

Research suggests that low carbohydrate diets can help reduce liver fat content and improve metabolic issues related to non-alcoholic fatty liver disease (NAFLD). Studies have shown that both low carbohydrate and moderate carbohydrate diets can be effective in managing NAFLD, especially when combined with weight loss. ^{1 2 3 4 7}

Are You a Good Fit for This Trial?

This trial is for children and adolescents aged 10-17 with Non-alcoholic Fatty Liver Disease (NAFLD) who are overweight or obese. They must have evidence of fatty liver via ultrasound, elevated ALT levels, and an HbA1c below 7%. Participants should not be on certain medications affecting the liver, be pregnant, or have other specific liver diseases.

Inclusion Criteria

Overweight or obese (BMI >75th percentile)

I am between 10 and 17 years old.

I have been diagnosed with fatty liver disease and my liver tests are high.

Exclusion Criteria

I am currently undergoing a strict lifestyle change program.

I am willing and able to follow the study's requirements.

I haven't taken drugs that affect liver fat, enzymes, weight, or sugar levels in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Controlled feeding phase

Participants receive all food via home delivery for 12 weeks, with weekly monitoring and dietitian meetings

12 weeks

12 visits (in-person or virtual)

Free living phase

Participants continue their assigned diet without provided groceries, with self-monitoring and dietitian support

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fat-restricted diet
• Moderately carbohydrate-restricted diet

Trial Overview The study compares a moderately carbohydrate-restricted diet to a fat-restricted diet over six months. It includes a controlled feeding phase where food is provided for 12 weeks followed by a 'free living' phase. Physical activity will be monitored using smart watches.

How Is the Trial Designed?

Group I: Moderately carbohydrate-restricted diet Experimental Treatment 1 Intervention

For this study, the investigators will use the low glycemic, moderately carbohydrate-restricted diet that the investigators have previously shown is associated with depletion of hepatic lipid content, and improvement in insulin resistance in adolescents with NAFLD. This diet has a macronutrient composition of approximately 25% energy from carbohydrate, 20% energy from protein, and 55% energy from fat. No food group is excluded in this diet prescription; however, the diet emphasizes low-glycemic sources of carbohydrate, and includes mainly whole foods (vegetables, fruits, whole grains) with minimal highly processed grain products and added sugar. Protein foods will include meat, poultry, fish, eggs, and whey protein supplements if necessary. Fat-containing foods will include olive, coconut, and nut oils; butter; tree nuts and nut butters; cheese; cream; coconut milk; avocados; and the fat found in meat. A number of full-fat dairy products will be included.

Group II: Fat-restricted diet Active Control 1 Intervention

The fat-restricted, control diet will consist of approximately 60% carbohydrate, 20% protein, 20% fat. Participants will be given low-fat foods, whole-grain foods, fruits, and vegetables. The meal plans will minimize cholesterol, high-fat foods, high-cholesterol foods, processed starches, and added sugar, and will provide \<2300 mg/day sodium. Saturated fat will be limited to 10% of total fat intake, and all dairy products will be fat-free (or low fat).

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study of 240 adults (120 with NAFLD and 120 without), low carbohydrate diets (LCDs) did not show a significant association with the risk of developing non-alcoholic fatty liver disease, suggesting that higher protein and fat intake alone may not contribute to NAFLD risk.

Patients with NAFLD had significantly higher intakes of protein, carbohydrates, and cholesterol compared to controls, indicating that while these dietary factors are prevalent in NAFLD, they do not correlate with the consumption of low carbohydrate diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to low carbohydrate diets and non-alcoholic fatty liver disease: a case control study. Yaghoubi, F., Darand, M., Vasmehjani, AA., et al.[2023]

A moderate-carbohydrate diet (150-200 g/day) for patients with nonalcoholic fatty liver disease (NAFLD) showed high compliance and adherence rates, with 80% of participants maintaining the diet after 6 months.

After 12 months, 65% of participants achieved complete response (normalization of ALT levels), indicating that this diet effectively improves liver health without the need for strict caloric or lipid restrictions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderate-carbohydrate diet without caloric or lipid restriction for Japanese adult patients with nonalcoholic fatty liver disease: A prospective cohort study. Tamai, H., Okamura, J., Nanjo, K.[2023]

Hypocaloric diets, especially low carbohydrate ketogenic diets, are effective in rapidly reducing liver fat and improving metabolic issues associated with non-alcoholic fatty liver disease (NAFLD).

Diets high in saturated fats are particularly harmful, as they increase liver fat and insulin resistance, while vitamin E supplementation can reduce liver fat and fibrosis but does not improve insulin resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional Modulation of Non-Alcoholic Fatty Liver Disease and Insulin Resistance. Yki-Järvinen, H.[2018]

This randomized clinical trial will assess the effects of a moderately carbohydrate-restricted diet on liver health in 52 normal-weight patients with non-alcoholic fatty liver disease (NAFLD) over 12 weeks, focusing on liver enzymes, steatosis, and fibrosis.

The study aims to determine if carbohydrate restriction can improve liver function and reduce fat accumulation in the liver, even without weight loss, which has not been previously explored in normal-weight individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a moderately carbohydrate-restricted diet on liver enzymes, steatosis and fibrosis in normal-weight individuals with non-alcoholic fatty liver disease: study protocol for a parallel randomised controlled clinical trial. Dashti, F., Alavian, SM., Sohrabpour, AA., et al.[2023]

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]

In a study of 106 Korean patients with non-alcoholic fatty liver disease (NAFLD), a low-carbohydrate diet was more effective than a low-fat diet in reducing intrahepatic fat accumulation and normalizing liver enzyme levels after 8 weeks.

The low-carbohydrate group not only showed a significant decrease in liver fat and improved liver enzyme activity (38.5% normalization of ALT) but also experienced reductions in LDL cholesterol and blood pressure, indicating a broader health benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of efficacy of low-carbohydrate and low-fat diet education programs in non-alcoholic fatty liver disease: A randomized controlled study. Jang, EC., Jun, DW., Lee, SM., et al.[2020]

In a pilot study of 5 patients with obesity-related fatty liver disease, a low-carbohydrate ketogenic diet for 6 months resulted in an average weight loss of 12.8 kg, indicating its potential effectiveness for weight management.

Post-treatment liver biopsies showed significant histological improvements in liver fat content, inflammation, and fibrosis, suggesting that this dietary approach may help reverse fatty liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study. Tendler, D., Lin, S., Yancy, WS., et al.[2018]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Adherence to low carbohydrate diets and non-alcoholic fatty liver disease: a case control study. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Moderate-carbohydrate diet without caloric or lipid restriction for Japanese adult patients with nonalcoholic fatty liver disease: A prospective cohort study. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Nutritional Modulation of Non-Alcoholic Fatty Liver Disease and Insulin Resistance. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Effect of a moderately carbohydrate-restricted diet on liver enzymes, steatosis and fibrosis in normal-weight individuals with non-alcoholic fatty liver disease: study protocol for a parallel randomised controlled clinical trial. [2023]

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

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

6. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of efficacy of low-carbohydrate and low-fat diet education programs in non-alcoholic fatty liver disease: A randomized controlled study. [2020]

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

The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study. [2018]