Very Low Calorie Diet for Non-alcoholic Fatty Liver Disease

Overseen By Constance R Shelsky, RN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Iowa

Must not be taking: Insulin, Warfarin, Lithium, Prednisone

Disqualifiers: Type 1 diabetes, Heart failure, Chronic kidney disease, Severe mental health disease, others

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

Compensation: Varies

Number of Visits: 5

Duration: 8 weeks

20 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, but you cannot participate if you use insulin for type 2 diabetes or take warfarin, lithium, or chronic prednisone (20mg or more daily).

What data supports the effectiveness of the treatment Very low calorie diet (VLCD) for Non-alcoholic Fatty Liver Disease?

Research shows that a very low calorie diet (VLCD) can help people with non-alcoholic fatty liver disease (NAFLD) lose weight and improve liver health. Studies found that VLCDs can lead to significant weight loss and improvements in liver function, making it a promising option for managing NAFLD. ^{1 2 3 4 5}

Is a very low calorie diet safe for humans?

Very low calorie diets (VLCDs) are generally safe for humans, but they can cause mild side effects. In studies, most people tolerated the diet well, though a few stopped due to adverse effects. It's important to monitor for potential issues like gallstones when following a VLCD. ^{1 2 3 6 7}

How does a very low calorie diet (VLCD) differ from other treatments for non-alcoholic fatty liver disease (NAFLD)?

A very low calorie diet (VLCD) is unique because it focuses on achieving significant weight loss, which is crucial for improving non-alcoholic fatty liver disease (NAFLD). Unlike standard dietary approaches, VLCDs can help patients reach the recommended weight loss goal of 10% or more, leading to improvements in liver health and function. ^{1 2 3 4 8}

What is the purpose of this trial?

Non-alcoholic fatty liver disease (NAFLD) is a common complication of obesity which can progress to deadly complications like end-stage liver disease and hepatocellular carcinoma. In the wake of the obesity epidemic, NAFLD is becoming the main etiology of liver transplantation in the US. Currently, there are no FDA approved pharmacological treatments for NAFLD. Weight loss through lifestyle modifications, pharmacotherapy and bariatric surgery can be effective strategies for the management of NAFLD. Even though substantial weight loss and improvement in NAFLD can be achieved with bariatric surgery, only a small proportion of patients with obesity undergo surgery. Very-low calorie diets (VLCD) are replacement meals manufactured to substitute natural foods and limited total intake of 800-960 kcal in divided meals. Very low-calorie diets can produce substantial weight loss of 10% over 2 to 3 months. We hypothesize that VLCD reduce liver steatosis and, fibrosis measured non-invasively with transient elastography. Our main aim is #1 to assess the effect of VLCD on liver fatty infiltration and fibrosis. We also have three exploratory aims exploring novel pathogenic factors that mediate the improvement of NAFLD by VLCD: #2 assess the effect of VLCD on micro RNAs (miRs) associated with pathophysiology of NAFLD: #3 assess the effect of VLCD on changes of salivary and fecal microbiome in the setting of NAFLD: #4 to determine the effect of VLCD on platelet function. This pilot project will produce preliminary data for the development of a larger grant application to study the efficacy of VLCD in the management of NAFLD. Furthermore, it will potentially identify factors that mediate improvement of NAFLD after VLCD. We will treat 10 subjects with obesity and NAFLD for 8 weeks with VLCD or lower calorie diet (control group) and obtain transient elastography before and after the interventions along with other measurements of interest. Our project may have significant impact by establishing VLCD as a clinically effective option for the improvement of liver steatosis and fibrosis in patients with obesity and NAFLD ineligible or without access to bariatric surgery.

Research Team

Marcelo Correia

Principal Investigator

University of Iowa

Eligibility Criteria

This trial is for adults aged 18-70 with obesity (BMI between 30 and 50) and non-alcoholic fatty liver disease, confirmed by imaging or specific elastography scores. Participants must not have viral hepatitis, autoimmune hepatitis, uncontrolled thyroid issues, severe alcohol use, certain heart conditions, type 1 diabetes or insulin-using type 2 diabetes, significant kidney disease or other serious health problems.

Inclusion Criteria

My BMI is between 30 and 50.

I have signs of fatty liver on an ultrasound, CT scan, MRI, or my elastography score is F1 or higher/S1 or higher.

Negative tests for viral hepatitis C (hepatitis C antibody) and autoimmune hepatitis (anti-smooth muscle antibody)

Exclusion Criteria

I have porphyria.

Subjects with no elastography in the previous 12 months will be excluded from the study

I have had a heart attack in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive a Very Low-Calorie Diet (VLCD) intervention for 8 weeks to assess its effect on liver steatosis and fibrosis

8 weeks

4 visits (in-person) at weeks 0, 2, 4, and 8; weekly telephone or video-call contacts

Follow-up

Participants are monitored for adherence to a low calorie, low fat diet and weight trajectory after the VLCD intervention

4 weeks

Weekly telephone or video-call contacts

Treatment Details

Interventions

• Very low calorie diet (VLCD)

Trial Overview The study tests if a very low calorie diet (VLCD), which limits intake to about 800-960 calories per day through meal replacements, can reduce fat and fibrosis in the liver compared to a lower calorie diet. The effects on micro RNAs related to NAFLD pathophysiology will also be explored.

Participant Groups

Group I: Very Low Calorie Diet Arm Experimental Treatment 1 Intervention

We plan to perform a controlled, non-randomized, open-label, pilot clinical trial to evaluate the effect of an 8-week VLCD intervention on NAFLD.

Group II: Control Arm Experimental Treatment 1 Intervention

The control group will consume a lower calorie diet and will be instructed to reduce their usual intake of normally consumed foods by up to 500 kcal per day but no less than 1200 kcal per day.

Who Is Running the Clinical Trial?

University of Iowa

Lead Sponsor

Trials

486

Recruited

934,000+

Findings from Research

A very low calorie diet (VLCD) of approximately 800 kcal/day was found to be an acceptable and feasible treatment for patients with clinically significant nonalcoholic fatty liver disease (NAFLD), with 34% achieving and maintaining a weight loss of 10% or more at 9-month follow-up.

Patients who completed the VLCD showed significant improvements in liver health, cardiovascular risk, and metabolic health, indicating that this dietary approach can lead to better overall health outcomes for individuals with NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of a Very Low Calorie Diet to Achieve a Sustainable 10% Weight Loss in Patients With Nonalcoholic Fatty Liver Disease. Scragg, J., Avery, L., Cassidy, S., et al.[2021]

A scoping review of 19 studies involving 968 subjects indicates that very low-calorie diets (VLCDs) are effective for inducing weight loss and improving liver health in patients with nonalcoholic fatty liver disease (NAFLD) and end-stage liver disease (ESLD).

Most studies showed acute improvements in liver biomarkers and had high adherence rates (69% to 93%), with only mild adverse effects reported, suggesting that VLCDs are safe and tolerable for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of very low-calorie diets in subjects with obesity complicated with nonalcoholic fatty liver disease: A scoping review. Herrington, GJ., Peterson, JJ., Cheng, L., et al.[2023]

Very-low-calorie diets (VLCDs) lead to significantly greater short-term weight loss compared to conventional low-calorie diets (LCDs), with participants losing an average of 16.1% of their initial weight versus 9.7% for LCDs.

However, after one year, the long-term weight loss results were similar for both VLCDs and LCDs, with VLCDs resulting in a 6.3% loss compared to 5.0% for LCDs, indicating that VLCDs do not provide a sustained weight loss advantage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolution of very-low-calorie diets: an update and meta-analysis. Tsai, AG., Wadden, TA.[2009]

In a study of 139 obese patients undergoing bariatric surgery, 76.3% were found to have non-alcoholic fatty liver disease (NAFLD) post-very low calorie diet (VLCD), with 61.9% having simple steatosis and 14.4% having non-alcoholic steatohepatitis (NASH).

The VLCD led to significant improvements in metabolic markers such as BMI, fasting glucose, and cholesterol levels, indicating that pre-surgery dietary interventions can positively impact liver health, although the prevalence of NAFLD post-VLCD was lower than previously reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-alcoholic Fatty Liver Disease in Morbidly Obese Individuals Undergoing Bariatric Surgery: Prevalence and Effect of the Pre-Bariatric Very Low Calorie Diet. Schwenger, KJP., Fischer, SE., Jackson, TD., et al.[2018]

In a study involving 35 Wistar rats with diet-induced non-alcoholic fatty liver disease (NAFLD), sleeve gastrectomy (SG) was found to be more effective than a very-low calorie diet (VLCD) in improving liver histology and reducing insulin resistance.

SG led to significant weight loss and decreased cardiovascular risk by lowering insulin resistance, leptin, total cholesterol, and triglyceride levels, while both SG and VLCD improved liver histology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morphofunctional Changes After Sleeve Gastrectomy and Very Low Calorie Diet in an Animal Model of Non-Alcoholic Fatty Liver Disease. Talavera-Urquijo, E., Rodríguez-Navarro, S., Beisani, M., et al.[2018]

Very low-calorie diets (VLCDs), providing 800 kcal/day or less, can lead to significant weight loss of 1.5 to 2.5 kg per week, with an average total loss of 20 kg over 12 to 16 weeks, which is more effective than standard low-calorie diets.

VLCDs are generally safe for moderately and severely obese patients when supervised by medical professionals, although long-term weight maintenance remains a challenge; incorporating behavioral therapy and physical activity can help improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very low-calorie diets. National Task Force on the Prevention and Treatment of Obesity, National Institutes of Health. [2022]

In a study of 6640 adults over one year, those on very-low-calorie diets (VLCD) experienced a significantly greater weight loss (-11.1 kg) compared to those on low-calorie diets (LCD) (-8.1 kg), but this came with increased risks.

The risk of developing symptomatic gallstones requiring hospital care was three times higher in the VLCD group compared to the LCD group, with 48 cases in VLCD versus 14 in LCD, indicating a notable safety concern for VLCDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of symptomatic gallstones and cholecystectomy after a very-low-calorie diet or low-calorie diet in a commercial weight loss program: 1-year matched cohort study. Johansson, K., Sundström, J., Marcus, C., et al.[2021]

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]

References

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

Feasibility of a Very Low Calorie Diet to Achieve a Sustainable 10% Weight Loss in Patients With Nonalcoholic Fatty Liver Disease. [2021]

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

The use of very low-calorie diets in subjects with obesity complicated with nonalcoholic fatty liver disease: A scoping review. [2023]

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

The evolution of very-low-calorie diets: an update and meta-analysis. [2009]

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

Non-alcoholic Fatty Liver Disease in Morbidly Obese Individuals Undergoing Bariatric Surgery: Prevalence and Effect of the Pre-Bariatric Very Low Calorie Diet. [2018]

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

Morphofunctional Changes After Sleeve Gastrectomy and Very Low Calorie Diet in an Animal Model of Non-Alcoholic Fatty Liver Disease. [2018]

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

Very low-calorie diets. National Task Force on the Prevention and Treatment of Obesity, National Institutes of Health. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Risk of symptomatic gallstones and cholecystectomy after a very-low-calorie diet or low-calorie diet in a commercial weight loss program: 1-year matched cohort study. [2021]

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

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