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, Non-statin lipid-lowering, 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 aims to explore why some people with obesity develop related conditions like type 2 diabetes and heart disease, while others do not. It also compares the effects of three popular weight loss diets: Mediterranean, low-carbohydrate, and very-low-fat plant-based diets. People with metabolically abnormal obesity (those with high blood sugar and liver fat) might be a good fit, especially if they struggle with these health issues daily. Participants will follow one of these diets to observe its impact on their health.

As an unphased trial, this study provides a unique opportunity to contribute to understanding obesity-related health issues and the effects of different diets.

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 for the study.

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

Research has shown that each diet in this trial varies in safety and effectiveness based on past studies.

The plant-based very-low-fat diet can improve body shape and insulin use, with few negative effects reported. This makes it generally easy for those trying to lose weight to follow.

The Mediterranean diet is associated with reduced belly fat and better overall health, including improved insulin use. People usually find this diet easy to adhere to, and it can lower the risk of other health issues with few side effects.

The low carbohydrate ketogenic diet effectively aids weight loss and certain health conditions. However, some studies note it might temporarily increase signs of swelling in the body, especially for beginners. Overall, it is safe for many, but starting it might be slightly uncomfortable.

In general, these diets are safe and can benefit individuals with obesity, but results may vary. Consulting a healthcare provider before making dietary changes is always wise. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for metabolically abnormal obesity because they explore how different diets can impact health in unique ways. The plant-based very-low-fat diet is distinct because it emphasizes high complex carbohydrates and low fat, which may help improve glucose levels and reduce liver fat. The Mediterranean diet offers a balanced approach, rich in fruits, vegetables, and healthy fats like olive oil, potentially supporting heart health and metabolic function. Lastly, the low carbohydrate ketogenic diet is intriguing for its potential to drastically reduce insulin levels and liver fat by limiting carbohydrates and increasing fat intake. Each of these dietary approaches offers a fresh perspective on managing obesity-related metabolic issues beyond traditional calorie-reduction strategies.

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

This trial will compare different dietary interventions for managing obesity. Participants will be assigned to one of several treatment arms. Studies have shown that a plant-based diet, one of the options in this trial, can improve insulin use and lead to weight loss. Another option, the Mediterranean diet, has been shown by research to aid in weight loss and enhance insulin management and overall health. The low-carbohydrate ketogenic diet, also tested in this trial, is known to assist with weight loss by reducing hunger and increasing fat burning. Each of these diets can effectively manage obesity and related health issues in different ways. ^{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 obese individuals with specific metabolic abnormalities, such as high intrahepatic triglyceride levels or abnormal glucose readings. Participants should have a BMI between 30.0 and 50.0 kg/m2 and not be heavy smokers, drug users, or have conditions that interfere with the study. Pregnant women, those on certain medications, or with severe diseases are excluded.

Inclusion Criteria

My liver fat, blood sugar, and cholesterol levels are within normal ranges.

My BMI is either between 18.5-24.9 or 30.0-50.0.

I am obese with high liver fat, blood sugar, or HbA1C levels.

Exclusion Criteria

I have gone through menopause naturally or due to medical reasons.

I can complete all tests without issues from severe mobility problems, missing limbs, or metal implants.

I have had weight loss surgery that changed my digestive system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Testing

Cross-sectional comparison of metabolically normal lean, metabolically normal obese, and metabolically abnormal obese subjects

4 weeks

1 visit (in-person)

Dietary Intervention

Metabolically abnormal obese participants are randomized to follow a Mediterranean, low-carbohydrate ketogenic, or plant-based very-low-fat diet

6-7 months

Monthly visits (in-person)

Weight Maintenance

Participants maintain weight loss achieved during the dietary intervention

4-8 weeks

Follow-up

Participants are monitored for changes in metabolic health and other outcomes after weight loss

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Metabolically abnormal obese

Trial Overview The study aims to understand why some obese individuals develop diabetes and heart disease while others don't. It compares three diets: Mediterranean, low-carbohydrate ketogenic, and very-low-fat plant-based in metabolically abnormal obese participants to see which diet might be most effective for weight loss and health improvement.

How Is the Trial Designed?

Group I: Metabolically abnormal obese - Plant-based very-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. Dietary intervention - A plant-based diet high in complex carbohydrates and low in fat, protein, and sodium, with approximately 70% of daily calories from carbohydrates, 15% from fat, and 15% from protein.

Group II: Metabolically abnormal 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. Dietary intervention - A nutritionally balanced diet that includes fruits, vegetables, fish, beans, whole grains, and olive oil with approximately 50% of daily calories coming from complex carbohydrates, 30% of calories from fat, and 20% of calories from protein.

Group III: Metabolically abnormal 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. Dietary intervention - A very-low-carbohydrate, adequate protein, high-fat diet containing 20 grams of carbohydrate or less per day (about 5% of calories), derived mainly from vegetables.

Group IV: Metabolically normal obese - Baseline testing only Active Control 1 Intervention

Metabolically normal obese - Persons with obesity that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content. Dietary intervention - None.

Group V: Metabolically normal lean - Baseline testing only Active Control 1 Intervention

Metabolically normal lean - Lean individuals that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content. Dietary intervention - None.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Pershing Square Foundation

Collaborator

Trials

1

Recruited

180+

Published Research Related to This Trial

A subgroup of obese individuals, known as 'metabolically healthy obese,' appears to be protected from common obesity-related health issues like type 2 diabetes and cardiovascular diseases, despite having excess body weight.

The article explores potential mechanisms that contribute to this healthy phenotype, such as reduced liver fat accumulation and lower inflammation in fat tissue, highlighting the clinical importance of understanding this group within the broader obesity epidemic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolically healthy obese individuals -- mechanisms and clinical relevance. Hrasko, T., Bendlová, B., Hainer, V., et al.[2018]

Insulin resistance varies significantly among healthy individuals, with about one-third at high risk for serious health issues, including type 2 diabetes, when their insulin production can't keep up with their body's needs.

Dietary interventions, such as weight loss and adjusting macronutrient intake, can help improve insulin sensitivity and reduce the negative effects associated with insulin resistance syndrome (IRS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The insulin resistance syndrome: definition and dietary approaches to treatment. Reaven, GM.[2022]

Metabolically healthy obese (MHO) individuals exhibit a postprandial metabolic response similar to lean healthy (LH) individuals, showing preserved insulin sensitivity compared to metabolically unhealthy obese (MUO) individuals after consuming a high-calorie meal.

MHO individuals demonstrate a greater ability to adapt to caloric challenges, with minor differences in amino acid responses and lower changes in certain polyunsaturated fatty acids compared to MUO individuals, indicating a distinct metabolic profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolomics Reveals Metabolically Healthy and Unhealthy Obese Individuals Differ in their Response to a Caloric Challenge. Badoud, F., Lam, KP., Perreault, M., et al.[2022]

Current dietary guidelines suggest a variety of dietary patterns for weight loss, but emerging evidence indicates that specific diets may be more effective for certain groups of overweight or obese individuals based on their metabolic characteristics.

Insulin dynamics, including insulin sensitivity and secretion, may play a crucial role in how different macronutrient compositions in diets affect weight loss outcomes in individuals on a hypocaloric diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary composition and weight loss: can we individualize dietary prescriptions according to insulin sensitivity or secretion status? Pittas, AG., Roberts, SB.[2019]

Capella's gastroplasty surgery leads to significant metabolic and inflammatory changes in patients, as indicated by alterations in blood parameters such as increased C-reactive protein and glucose levels post-surgery.

The study found no technical advantage of using bilateral arciform incisions over supra-umbilical midline incisions, suggesting that both surgical approaches are equally effective in terms of patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capella's gastroplasty: metabolites and acute phase proteins changes in midline and bilateral arciform approaches. de Moura, LG., Guimarães, SB., de Castro-Filho, HF., et al.[2019]

The prevalence of metabolically healthy obesity (MHO) varies widely based on different definitions, ranging from 2.2% to 36.6% among obese individuals, highlighting the need for a standardized definition of MHO.

Higher dietary quality and compliance with food pyramid recommendations, along with moderate to high levels of physical activity, are associated with a greater likelihood of being metabolically healthy, regardless of obesity status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defining metabolically healthy obesity: role of dietary and lifestyle factors. Phillips, CM., Dillon, C., Harrington, JM., et al.[2022]

A 16-week calorie-restricted diet in 57 obese, insulin-resistant individuals showed that both moderate carbohydrate (60%) and lower carbohydrate (40%) diets resulted in similar weight loss, averaging around 6 kg.

The lower carbohydrate diet (40%) led to greater improvements in cardiovascular risk markers, including reduced insulin and triacylglycerol levels, increased HDL-cholesterol, and improved LDL particle size, suggesting it may be more beneficial for heart health compared to a higher carbohydrate diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of moderate variations in macronutrient composition on weight loss and reduction in cardiovascular disease risk in obese, insulin-resistant adults. McLaughlin, T., Carter, S., Lamendola, C., et al.[2023]

In a study of 44 patients with obesity, a Very Low Calorie Diet (VLCD) resulted in an average weight loss of 7 kg and a weight loss rate of 1.2 kg per week, indicating its effectiveness for weight management.

While 33% of participants reported mild side effects, such as constipation and dizziness, the majority (84%) adhered to the VLCD, suggesting that with proper support, adherence can be maintained.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness and safety of Very Low Calory Diets in obese patients]. Sáez Belló, M., Segarra Villalba, C., Gras Colomer, E., et al.[2018]

A 9-month lifestyle intervention for 262 non-diabetic obese individuals led to significant reductions in visceral fat and improved insulin sensitivity (IS) in those with obese insulin-resistant (OIR) profiles, but their IS remained much lower than that of metabolically healthy obese (MHO) individuals.

Despite improvements in the OIR group, their insulin sensitivity did not reach levels that would adequately protect against type 2 diabetes and cardiovascular disease, highlighting the need for early pharmacological treatment alongside lifestyle changes for certain obese individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a lifestyle intervention in metabolically benign and malign obesity. Kantartzis, K., Machann, J., Schick, F., et al.[2021]

In a study of 12 obese subjects, a hypo-energetic diet significantly improved insulin sensitivity by 353% and 147% during two separate 6-week periods, indicating that weight loss through negative energy balance is crucial for improving metabolic health.

The study found that maintaining weight on an iso-energetic diet led to a 43.5% decrease in insulin sensitivity, suggesting that simply keeping weight stable is less effective than actively losing weight for managing insulin resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin resistance in obesity: body-weight or energy balance? Assali, AR., Ganor, A., Beigel, Y., et al.[2019]

In a study of 46 very obese individuals (11 inpatients and 35 outpatients), it was found that their caloric intake was directly related to their level of obesity, with both groups consuming high-calorie density foods and engaging in occasional binge eating.

By replacing high-calorie density foods with lower-calorie options, participants could potentially reduce their caloric intake by 20%, which could significantly aid in weight loss efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Food intake of very obese persons: quantitative and qualitative aspects. Strain, GW., Hershcopf, RJ., Zumoff, B.[2007]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10962461/

Effect of Ketogenic Diet on Obesity and Other Metabolic ... A ketogenic diet, low-carb, high-fat, helps weight loss by reducing appetite, increasing lipolysis, and improving metabolic efficiency, and is ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0261561425000184

Effects of ketogenic and low-carbohydrate diets on the ... Overall meta-analysis results indicated that KD/LCD significantly reduced BW, BMI, and BFP, but not FM, in individuals with a carbohydrate intake of ≤100 g/d.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10385501/

The Effects of Ketogenic Diet on Insulin Sensitivity and Weight ... Some studies have observed, intriguingly, a significant improvement in insulin sensitivity in response to low carbohydrate diets even in the absence of weight ...

4. drc.bmj.com drc.bmj.com/content/12/5/e004199

Effect of weight-maintaining ketogenic diet on glycemic ... A low carbohydrate ketogenic diet has no beneficial effect on glucose tolerance, insulin sensitivity, or other metabolic parameters.

5. nature.com nature.com/articles/s41387-020-00142-z

Effect of the ketogenic diet on glycemic control, insulin ... Obesity is closely related to insulin resistance; KD consumption is confirmed to be effective in reducing body weight, and it is expected that ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0924224421000893

Recent advances in the application of a ketogenic diet for ... Markers of adipose tissue inflammation are transiently elevated during intermittent fasting in women who are overweight or obese. Obesity Research & Clinical ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666154325003527

Nutritional ketosis as therapeutic regimen for metabolic ... Lack of physical activity and increased BMI lead to elevated ... Cincione, et al. Effects of mixed of a ketogenic diet in overweight and obese women with ...

8. liebertpub.com liebertpub.com/doi/full/10.1089/met.2021.0042

Examining the Efficacy of a Very-Low-Carbohydrate ... ... ketogenic diet on eutrophic and overweight populations with mildly elevated LDL-C. ... Weight loss with a low-carbohydrate, mediterranean, or low-fat diet.

9. mdpi.com mdpi.com/2072-6643/13/8/2805

Metabolic Derangement in Pediatric Patient with Obesity BMI is the accepted clinical standard measure to diagnose overweight and obesity. Nevertheless, it is not a direct measure of body fat, it does not predict the ...

10. frontiersin.org frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.753039/pdf

Ketogenic Diets and Cardio-Metabolic Diseases Diabetes mellitus is often associated with obesity (80), and recent estimates showed that 87.5% of T2DM patients are overweight or obese (24).