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

Trial Summary

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.

What data supports the effectiveness of the ketogenic diet treatment for obesity?

Research shows that very-low-calorie ketogenic diets can lead to significant weight loss and improvements in conditions like high blood pressure and type 2 diabetes. These diets, which are high in fat and low in carbohydrates, have been found to be more effective than low-fat diets for weight loss over a period of up to two years. ^{1 2 3 4 5}

Is the ketogenic diet safe for humans?

Based on available evidence, a well-formulated ketogenic diet does not appear to have major safety concerns for the general public and can be considered a first-line approach for obesity and diabetes. ^{3 5 6 7 8}

How is the ketogenic diet treatment for obesity different from other treatments?

The ketogenic diet is unique for obesity treatment because it focuses on a high-fat, low-carbohydrate intake, which can help reduce chronic inflammation and oxidative stress associated with obesity. Unlike other diets, it induces a state called ketosis, where the body burns fat for energy instead of carbohydrates, potentially leading to more effective weight loss and improvements in heart health markers. ^{3 5 9 10 11}

What is the purpose of this trial?

The goal of this clinical trial is to investigate whether a Ketogenic Diet (KD) can increase Total Energy Expenditure (TEE), while benefiting appetite, during weight loss maintenance in reduced-obese individuals.

Eligibility Criteria

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

I am either a man or a woman.

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

Exclusion Criteria

History of eating disorder

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

My blood sugar or HbA1c levels are high.

Timeline

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

Treatment Details

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.

Participant Groups

Group I: Ketogenic Diet Experimental Treatment 3 Interventions

During the first six weeks, participants will follow a low-energy diet aiming at inducing a minimum of 5% weight loss. This will be followed by a 2-week refeeding and weight stabilization phase. Then, this group will follow an eucaloric ketogenic diet (5% CHO: 70% fat; 25% protein) for 4 weeks aiming at weight loss maintenance.

Group II: Low-Fat Diet Active Control 3 Interventions

During the first six weeks, participants will follow a low-energy diet aiming at inducing a minimum of 5% weight loss. This will be followed by a 2-week refeeding and weight stabilization phase. Then, this group will follow an eucaloric low-fat diet (50% CHO: 25% fat: 25% protein) for 4 weeks aiming at weight loss maintenance.

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+

Findings from Research

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]

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 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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Ketogenic diet as an advanced option for the management of pediatric obesity. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Dietary treatment for obesity. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

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

4. Italy pubmed.ncbi.nlm.nih.gov

Very-low-calorie ketogenic diet for the management of obesity, overweight and related disorders. [2021]

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

Could very low-calorie ketogenic diets turn off low grade inflammation in obesity? Emerging evidence. [2023]

6. England pubmed.ncbi.nlm.nih.gov

VLCKD: a real time safety study in obesity. [2022]

7. England 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. [2022]

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

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

9. United States 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. [2023]

10. Italy 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. [2023]

11. Switzerland pubmed.ncbi.nlm.nih.gov

European Guidelines for Obesity Management in Adults with a Very Low-Calorie Ketogenic Diet: A Systematic Review and Meta-Analysis. [2023]