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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a very low-calorie diet (VLCD) can improve liver health in individuals with non-alcoholic fatty liver disease (NAFLD) and obesity. Participants will follow either an 8-week VLCD or a lower-calorie diet to assess changes in liver fat and stiffness. Researchers will also explore how these diets affect specific biological markers, such as micro RNAs (tiny molecules in cells) and gut bacteria. Individuals with a BMI of 30–50 who have NAFLD and no insulin-dependent diabetes may be suitable for this trial. As an unphased trial, this study provides a unique opportunity to contribute to understanding 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, but you cannot participate if you use insulin for type 2 diabetes or take warfarin, lithium, or chronic prednisone (20mg or more daily).

What prior data suggests that this very low calorie diet is safe for individuals with non-alcoholic fatty liver disease?

Research shows that very low-calorie diets (VLCDs) are generally safe under a doctor's supervision. Often used for short-term weight loss, these diets have been studied for their effects on liver health. Studies indicate that VLCDs can help reduce liver fat and improve liver function in people with obesity.

Some research includes individuals with type 2 diabetes, who tolerated the diet well without serious side effects. However, healthcare professionals must monitor VLCDs to ensure safety. Common side effects might include fatigue or feeling cold, but these are usually mild and temporary. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the very low calorie diet (VLCD) for non-alcoholic fatty liver disease (NAFLD) because it offers a unique approach to managing this condition. Unlike standard treatments that often focus on medications to control liver inflammation or insulin resistance, the VLCD directly targets weight loss and fat reduction in the liver through significant dietary changes. This method could lead to faster and more sustainable improvements in liver health by reducing liver fat more effectively than traditional calorie-restricted diets. Furthermore, the potential for substantial weight loss over just eight weeks makes it an attractive option for patients seeking quicker results.

What evidence suggests that a very low calorie diet might be an effective treatment for non-alcoholic fatty liver disease?

Research has shown that very low-calorie diets (VLCDs), which participants in the Very Low Calorie Diet Arm of this trial will follow, can lead to significant weight loss, often around 10% in just 2 to 3 months. This weight loss is important because it can help reduce fat buildup and scarring in the liver for people with non-alcoholic fatty liver disease (NAFLD). Studies have found that VLCDs effectively help patients lose weight and improve liver health. Specifically, one study found that about 45% of people who followed a VLCD for 12 weeks maintained at least 10% of their weight loss after a year. Overall, VLCDs seem promising for managing NAFLD by aiding in weight loss and improving liver health. ^{1 2 3 4 6}

Who Is on the Research Team?

Marcelo Correia

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7494144/

Feasibility of a Very Low Calorie Diet to Achieve ... Another study showed that 45% of obese patients undertaking a 12-week VLCD maintained ≥10% weight loss at 1-year follow-up (18). Research ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04861571

Effect of VLCD on the Reduction of Liver Steatosis and ... 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 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S026156142200231X

The effectiveness and acceptability of Mediterranean diet ... MD reduced ALT (P = 0.02), FLI (P < 0.001) and liver stiffness (P = 0.05). There was a dose–response relationship between degree of calorie restriction and ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/osp4.589

The use of very low‐calorie diets in subjects with obesity ... While studies reported variable weight loss and liver outcomes, they all reflect that VLCD is effective in assisting patients lose weight and ...

5. frontiersin.org frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.987921/full

Low fat diet versus low carbohydrate diet for management ... Low fat diets seem to be markedly successful in reducing transaminase levels. Further research is needed to explore diet intensity, duration and ...

6. mdpi.com mdpi.com/2072-6643/16/7/1030

Effect of a Low-Calorie Dietary Intervention on Liver Health ... Conclusions: In people with MASLD and obesity, an LCD intervention reduces IHL and body weight. Trials should focus on the recruitment of Black ...