Ketogenic Diet for Obesity

(KETOWEI Trial)

Overseen By Catia Martins, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Must not be taking: Glucocorticoids, GLP-1 analogues, others

Disqualifiers: Pregnancy, Cognitive impairment, Diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a Ketogenic Diet can boost energy use and help control appetite during weight loss maintenance for those who have lost weight. Participants will follow either a high-fat, low-carb diet or a low-fat diet for six weeks. Researchers aim to determine which diet better supports weight loss maintenance. Suitable candidates for this trial are individuals with a BMI between 30 and 45 who lead a mostly sedentary lifestyle, engaging in less than two hours of exercise per week. As an unphased trial, this study offers a unique opportunity to contribute to understanding the impact of diet on weight maintenance.

Will I have to stop taking my current medications?

The trial requires that you do not use any medications that could interfere with the study outcomes, such as glucocorticoids, GLP-1 analogues, or hormone replacement therapy. If you are on these medications, you may need to stop taking them to participate.

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

Research has shown that the ketogenic diet, high in fat and low in carbohydrates, can aid in weight loss and body fat reduction. However, it may also lead to muscle loss, which might not suit everyone. Some participants in studies have thrived on the diet, while others have faced side effects such as tiredness and stomach issues. The long-term effects remain unclear, and some animal studies suggest potential risks with prolonged use. Prospective trial participants considering a ketogenic diet should weigh these factors and consult a healthcare professional. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the ketogenic diet for obesity because it offers a unique way of managing weight by significantly reducing carbohydrate intake to just 5% of daily energy, while increasing fat consumption to 70%. This is different from typical low-fat diets, which usually involve higher carbohydrate intake. The ketogenic approach aims to shift the body's metabolism to burn fat for energy, a process known as ketosis, which could potentially lead to more effective and faster weight loss. Additionally, this diet might help improve certain metabolic markers, offering benefits beyond just weight reduction.

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

This trial will compare the ketogenic diet with a low-fat diet for obesity. Research has shown that the ketogenic diet, high in fat and low in carbs, can aid in weight loss. Studies have found it reduces body weight and body fat. However, it might also cause some muscle loss, which is important to consider. Notably, the diet may improve body mass index (BMI), a measure of body fat based on height and weight, and reduce fat mass. This makes it a potential option for maintaining weight loss. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for individuals with obesity who have recently lost weight and are looking to maintain their weight loss. Participants should be interested in following a ketogenic diet, which is low in carbohydrates and high in fats.

Inclusion Criteria

BMI 30-45 kg/m2

Sedentary to moderately active (<2 h/wk of moderate, structured, intentional, exercise)

I am either a man or a woman.

Exclusion Criteria

History of eating disorder

My blood sugar or HbA1c levels are high.

I am a pre-menopausal woman with a regular menstrual cycle or on hormonal contraceptives.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Weight Loss Phase

Participants undergo a low-energy diet aiming to induce a minimum of 5% weight loss

4 weeks

Weekly visits for monitoring

Refeeding and Weight Stabilization

Participants undergo a refeeding and weight stabilization phase

2 weeks

Bi-weekly visits for monitoring

Weight Loss Maintenance

Participants are randomized to either a ketogenic diet or a low-fat diet for weight loss maintenance

4 weeks

Weekly visits for monitoring and dietary adherence checks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketogenic Diet

Trial Overview The study tests if a Ketogenic Diet can help people who've lost weight burn more calories at rest (Total Energy Expenditure) and feel less hungry. It includes dietary therapy, calorie restriction, and behavioral support.

How Is the Trial Designed?

Group I: Ketogenic Diet Experimental Treatment 3 Interventions

Participants randomized to the ketogenic diet will follow a diet with 5% energy from carbohydrates, 70% from fat, and 25% from protein for 6 weeks. The first 2 of the 6 weeks weeks will be a gradual refeeding, with participants slowly withdrawing from the meal replacements used during the 4-week weight loss phase, while introducing more food.

Group II: Low-Fat Diet Active Control 3 Interventions

Participants randomized to the low-fat diet will follow a diet with 50% energy from carbohydrates, 25% energy from fat, and 25% energy from protein for 6 weeks. The first 2 of the 6 weeks weeks will be a gradual refeeding, with participants slowly withdrawing from the meal replacements used during the 4-week weight loss phase, while introducing more food.

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

Low-fat diets in obese patients result in modest weight loss of 3-4 kg over 3 years, while calorie-controlled diets show better outcomes with 6-7 kg weight loss at 4 years, although long-term data is limited.

Bariatric surgery, such as gastric bypass, can lead to significant weight loss (up to 25% over 10 years) and reduce mortality and comorbidities, but it carries risks of nutritional deficiencies and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary treatment for obesity. Clifton, PM.[2022]

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]

Ketogenic diets, which consist of over 70% fat and very low carbohydrates, may be more effective than low-fat diets for treating obesity and diabetes, showing potential benefits in reducing blood glucose and insulin levels.

A well-formulated ketogenic diet appears to be safe for the general public and could be considered a first-line treatment for obesity and diabetes, although more high-quality clinical trials are needed to explore its long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ketogenic Diet: Evidence for Optimism but High-Quality Research Needed. Ludwig, DS.[2023]

In a study involving 11 healthy, normal-weight participants, a high-fat ketogenic diet (KD) did not improve cognitive function, mood, or sleep quality compared to a high-carbohydrate, low-fat diet over a 3-week period.

Despite achieving nutritional ketosis, the KD showed no significant effects on tasks measuring vigilance, memory, or executive function, indicating that this diet may not enhance cognitive performance in healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three consecutive weeks of nutritional ketosis has no effect on cognitive function, sleep, and mood compared with a high-carbohydrate, low-fat diet in healthy individuals: a randomized, crossover, controlled trial. Iacovides, S., Goble, D., Paterson, B., et al.[2023]

Individuals on a very-low-carbohydrate ketogenic diet (VLCKD) experienced greater long-term weight loss compared to those on a conventional low-fat diet (LFD), with a mean difference of -0.91 kg across 13 studies involving 1415 patients.

The VLCKD also led to improvements in cardiovascular risk factors, including lower triglycerides and diastolic blood pressure, as well as increased HDL cholesterol, suggesting it may be a beneficial approach for managing obesity and related health risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. Bueno, NB., de Melo, IS., de Oliveira, SL., et al.[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]

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]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK499830/

Ketogenic Diet - StatPearls - NCBI Bookshelf One diet regimen that has shown efficacy in rapid weight loss is the very low-carbohydrate and high-fat ketogenic diet. This activity aims ...

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

Effects of ketogenic and low-carbohydrate diets on the ... We investigated the effects of ketogenic diet (KD) and low-carbohydrate diet (LCD) in improving body weight (BW), body mass index (BMI), fat mass (FM), and body ...

3. bmcmedicine.biomedcentral.com bmcmedicine.biomedcentral.com/articles/10.1186/s12916-023-02874-y

Effects of ketogenic diet on health outcomes: an umbrella ... K-LCHF was associated with reduced body weight and body fat percentage, but also reduced muscle mass in healthy participants. Conclusions. This ...

4. nutritionsource.hsph.harvard.edu nutritionsource.hsph.harvard.edu/healthy-weight/diet-reviews/ketogenic-diet/

Diet Review: Ketogenic Diet for Weight Loss Strong emphasis on fats at each meal and snack to meet the high-fat requirement. · Some dairy foods may be allowed. · Protein stays moderate.

5. healthcare.utah.edu healthcare.utah.edu/newsroom/news/2025/10/new-study-mice-reveals-long-term-metabolic-risks-of-ketogenic-diet

New Study in Mice Reveals Long-Term Metabolic Risks ... Research in mice shows dangerous consequences of a very high-fat, low-carb ketogenic diet. ... In keto diets, almost all calories come from fats, ...

6. nature.com nature.com/articles/s41392-021-00831-w

Ketogenic diet for human diseases: the underlying ... Besides fat and weight loss, the KD can exert a series of other beneficial effects on obesity. Insulin resistance is common in obese patients.