Specific Diets for Obesity

Not currently recruiting at 1 trial location

Overseen By Brittney Mason

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must not be taking: Steroids, Anticoagulants, others

Disqualifiers: Diabetes, Cancer, Psychiatric illness, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests three different diets to determine which one best improves heart and metabolic health in people with obesity. Researchers aim to understand why some individuals with obesity develop health complications while others do not. Participants will follow either a low-carbohydrate ketogenic diet, a low-fat diet, or a Mediterranean diet. Individuals with obesity who struggle with issues like high blood sugar or liver fat may be well-suited for this trial. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on diet and health.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that could affect the study's results, like steroids or certain cholesterol-lowering drugs, if they can't be temporarily stopped. If you're on such medications, you might need to pause them for the study.

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

A previous study found that people on a low-carbohydrate ketogenic diet lost weight and had lower triglyceride levels, which are fats in the blood. However, concerns exist about how this diet might affect heart and kidney health over time. Ketosis, where the body uses fat for energy instead of carbs, is generally safe but can be risky for some individuals.

Research has shown that low-fat diets are usually safe and often recommended for heart health, though they might not aid weight loss as effectively as other diets.

Studies have associated the Mediterranean diet with a lower risk of obesity and found it can help reduce body weight and waist size. It is often considered one of the safest diets because it emphasizes fruits, vegetables, and healthy fats.

Each diet offers its own benefits and potential risks. Choosing the one that best fits individual health needs and goals is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these dietary approaches for obesity because they offer personalized options targeting metabolic health. Unlike conventional weight-loss plans that often focus on calorie restriction alone, these diets — low-carbohydrate ketogenic, low-fat, and Mediterranean — are tailored to the metabolic profiles of individuals. This means they consider factors like glucose control and liver fat content, potentially offering more effective and sustainable results. By addressing metabolic health directly, these diets could improve not only weight management but also overall health, setting them apart from typical one-size-fits-all diets.

What evidence suggests that this trial's dietary approaches could be effective for obesity?

This trial will compare the effects of different diets on obesity. Participants will join one of several treatment arms, each focusing on a specific diet. Studies have shown that the Mediterranean diet, which some participants will follow, effectively prevents obesity-related problems and improves heart health. It is linked to a lower risk of type 2 diabetes and heart disease. Other participants will follow a low-carbohydrate, ketogenic diet, which research shows can lead to significant weight loss and improved blood sugar levels. Additionally, some participants will be assigned to a low-fat diet, known for reducing body weight and improving cholesterol levels. Each diet offers unique benefits, and selecting the right one depends on individual health needs. ^{6 7 8 9 10}

Who Is on the Research Team?

Samuel Klein, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with obesity, either metabolically healthy or unhealthy, who have specific body mass index (BMI) and blood sugar levels. It excludes those with certain medical conditions like severe organ dysfunction, cancer within the last 5 years, major psychiatric illness, recent bariatric surgery, unstable weight or diet restrictions due to allergies.

Inclusion Criteria

If you are very overweight and have certain measures of body fat and blood sugar levels, you won't be able to participate.

I am obese but metabolically healthy with specific health markers within normal ranges.

I am lean, with healthy levels of body fat, blood sugar, and cholesterol.

Exclusion Criteria

You have a serious mental illness.

I can complete all tests; no severe mobility issues, missing limbs, or metal implants that affect imaging.

My cancer has been in remission for less than 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Comprehensive baseline assessments including insulin sensitivity, β-cell function, and various metabolic parameters

1-2 weeks

1 visit (in-person)

Dietary Intervention

Participants are randomized to follow a Mediterranean, low-carbohydrate ketogenic, or low-fat diet to assess cardiometabolic health

4-8 weeks

Weekly visits (in-person or virtual)

Longitudinal Assessment

Annual assessments of cardiometabolic health including insulin sensitivity, exosome signaling, and adipose tissue volumes

5 years

Annual visits (in-person)

Follow-up

Participants are monitored for long-term changes in cardiometabolic health post-intervention

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Low-carbohydrate, ketogenic diet
• Low-fat diet
• Mediterranean diet

Trial Overview

The study tests how different diets—Mediterranean, low-fat, and ketogenic—affect heart health and metabolism in obese individuals over five years. Participants will be monitored annually to see which diet works best for improving or maintaining metabolic health.

How Is the Trial Designed?

Group I: Metabolically unhealthy obese - Mediterranean diet Experimental Treatment 2 Interventions

Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver randomized to the Mediterranean diet group.

Group II: Metabolically unhealthy obese - Low-fat diet Experimental Treatment 2 Interventions

Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver randomized to the low-fat diet group.

Group III: Metabolically unhealthy obese - Low-carbohydrate ketogenic diet Experimental Treatment 2 Interventions

Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver randomized to the low-carbohydrate, ketogenic diet group.

Group IV: Metabolically normal obese - Low-fat diet Experimental Treatment 2 Interventions

Metabolically normal obese - Persons with obesity that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content randomized to the low-fat diet group.

Group V: Metabolically healthy obese - Mediterranean diet Experimental Treatment 2 Interventions

Metabolically normal obese - Persons with obesity that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content randomized to the Mediterranean diet group.

Group VI: Metabolically healthy obese - Low-carbohydrate ketogenic diet Experimental Treatment 2 Interventions

Metabolically normal obese - Persons with obesity that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content randomized to the low-carbohydrate ketogenic diet group.

Group VII: Metabolically healthy lean Experimental Treatment 1 Intervention

Metabolically normal lean - Lean individuals that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content.

Low-carbohydrate, ketogenic diet is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ketogenic diet for:

• Epilepsy
• Type 2 diabetes management
• Weight loss

Approved in European Union as Ketogenic diet for:

• Epilepsy
• Type 2 diabetes management

Approved in Canada as Ketogenic diet for:

• Epilepsy
• Type 2 diabetes management

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Centene Corporation

Collaborator

Trials

1

Recruited

300+

Published Research Related to This Trial

A low-carbohydrate ketogenic diet was well tolerated by 15 children with stage 1-3 constitutional obesity, leading to effective weight loss and reduced appetite.

The diet also improved metabolic health by normalizing cholesterol, triglyceride, and beta-lipoprotein levels, and reducing insulin resistance, indicating its potential as a safe intervention for childhood obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of low-carbohydrate diet in the treatment of obesity in adolescents]. Sorvacheva, TN., Peterkova, VA., Titova, LN., et al.[2007]

Low-carbohydrate diets lead to greater short-term weight loss compared to low-fat diets for overweight or obese individuals, particularly within the first 6 months.

There is currently a lack of research on the long-term safety and efficacy of both low-fat and low-carbohydrate diets for sustained weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial experience with fat-restricted vs. carbohydrate-restricted weight-loss diets. Klein, S.[2007]

The very-low-calorie ketogenic diet (VLCKD) is an effective lifestyle intervention for managing overweight and obesity, leading to significant weight loss and improvements in conditions like hypertension, type 2 diabetes, and dyslipidemia.

This review synthesizes evidence from four key studies, highlighting VLCKD's potential benefits and offering practical recommendations for its implementation in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very-low-calorie ketogenic diet for the management of obesity, overweight and related disorders. Castellana, M., Biacchi, E., Procino, F., et al.[2021]

In a study of 200 obese adults over six months, the low-carbohydrate ketogenic diet (LCKD) resulted in a significant weight loss of 13.0 kg compared to 4.7 kg with the low-caloric fat low diet (LCLF), indicating that LCKD is more effective for weight reduction.

The LCKD also led to greater reductions in fat mass and visceral fat, while not increasing cholesterol or uric acid levels, suggesting it is a safe and effective option for obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of low-carbohydrate ketogenic diet in the management of obesity compared with low caloric, low-fat diet. Al Aamri, KS., Alrawahi, AH., Al Busaidi, N., et al.[2022]

A systematic review of 17 trials involving 1797 overweight and obese patients found that low carbohydrate diets led to a greater weight loss (average of -2.0 kg) compared to low fat diets, with a high probability (>99%) of achieving this result.

The low carbohydrate diet also significantly reduced the predicted risk of atherosclerotic cardiovascular disease events compared to the low fat diet, suggesting it may be a safer and more effective option for weight management and cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary Intervention for Overweight and Obese Adults: Comparison of Low-Carbohydrate and Low-Fat Diets. A Meta-Analysis. Sackner-Bernstein, J., Kanter, D., Kaul, S.[2022]

Ketogenic diets, which are low in carbohydrates and high in fats, have been shown to be effective for weight loss and can improve triglyceride and HDL cholesterol levels compared to low-fat diets.

Despite concerns about their high fat content, the degree of carbohydrate restriction needed to achieve ketosis is still unclear, indicating a need for more standardized research on these diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diets for weight loss: A review of their principles, safety and efficacy. Sumithran, P., Proietto, J.[2022]

The Mediterranean diet, characterized by its balanced intake of macronutrients and micronutrients, is recommended for long-term weight maintenance and health benefits, unlike short-term restrictive diets that are difficult to sustain.

Low-carbohydrate ketogenic diets may pose medical risks, particularly for individuals with obesity, as they can lead to metabolic acidosis and renal issues, potentially reducing life expectancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-carbohydrate ketogenic diets in body weight control: A recurrent plaguing issue of fad diets? Schutz, Y., Montani, JP., Dulloo, AG.[2021]

A 21-day very low-calorie ketogenic diet (VLCKD) resulted in significant weight loss and improvements in insulin resistance without negatively impacting overall nutritional status or causing adverse changes in liver and kidney function.

Both VLCKD1 and VLCKD2 led to similar reductions in body mass index and fat mass, but also resulted in increased levels of uric acid and creatinine, indicating the need for monitoring these parameters during such diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of very-low-calorie ketogenic diet: a double blind randomized crossover study. Colica, C., Merra, G., Gasbarrini, A., et al.[2022]

Pre-ketogenic diet counseling is essential for patients with obesity and diabetes, focusing on understanding the risks and benefits of the diet, as well as the patient's self-care responsibilities.

This communication highlights the need for patient-centered counseling strategies, which have been largely overlooked in existing literature on ketogenic diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre ketogenic diet counselling. Kalra, S., Singla, R., Rosha, R., et al.[2019]

A study involving 80 patients with overweight/obesity and type 2 diabetes showed that both a very-low-calorie Mediterranean diet and a very-low-calorie ketogenic Mediterranean diet significantly reduced body weight and BMI over 30 days.

The very-low-calorie ketogenic Mediterranean diet was particularly effective, leading to greater reductions in waist and hip circumferences, as well as significant improvements in fasting blood glucose, HbA1c, insulin, and cholesterol levels, indicating its potential as a rapid intervention for metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Italian Ketogenic Mediterranean Diet in Overweight and Obese Patients with Prediabetes or Type 2 Diabetes. Ivan, CR., Messina, A., Cibelli, G., et al.[2022]

Low-carbohydrate diets can lead to greater initial weight loss (3-6 kg) compared to conventional low-fat diets, particularly noticeable at 6 months, but this difference diminishes after 12 months.

While low-carb diets do not increase LDL cholesterol and can improve HDL cholesterol and lower triglycerides, they may pose long-term health risks due to low intake of essential nutrients and fiber, making them unsuitable for general recommendation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Low-carbohydrate diets for obesity]. Keller, U., Rastalsky, N.[2008]

Current guidelines recommend a comprehensive treatment for obesity that includes diet, exercise, and behavior therapy, emphasizing the importance of cognitive change for better long-term results.

Cognitive behavioral therapy combined with the Mediterranean diet has shown effectiveness in promoting weight loss and improving health markers, making it a practical approach for managing obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional and behavioral modification therapies of obesity: facts and fiction. Vranešić Bender, D., Krznarić, Z.[2018]

Both very-low-calorie ketogenic diets (VLCKD) and low-calorie ketogenic diets (LCKD) have been shown to effectively promote weight loss and improve metabolic and cardiovascular risk factors in both short-term (less than 12 months) and long-term (more than 12 months) studies.

These diets, characterized by low carbohydrate intake and controlled calorie consumption, have demonstrated benefits in reducing glucose and cholesterol levels, suggesting their potential as effective nutritional strategies for obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short- and long-term effects of very low- and low-calorie ketogenic diets on metabolism and cardiometabolic risk factors: a narrative review. Gaspa, G., Naciu, AM., DI Rosa, C., et al.[2023]

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