Caloric Intake Changes for Diet-Induced Thermogenesis in Obesity

Overseen By Tomas Cabeza De Baca, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Must not be taking: Energy metabolism drugs

Disqualifiers: Diabetes, Hypertension, Cardiovascular, others

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

Compensation: Varies

Number of Visits: 3

120 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medications, dietary supplements, or alternative therapies that are known to alter energy metabolism.

What data supports the effectiveness of the treatment involving changes in caloric intake and macronutrient distribution for obesity?

Research indicates that higher protein intake can help with weight loss and maintenance by increasing satiety (feeling of fullness) and energy expenditure, which are important for preventing weight regain. Additionally, diets with a higher percentage of carbohydrates compared to fats are associated with better weight management, as carbohydrates have a higher satiating effect than fats. ^{1 2 3 4 5}

Is the high-calorie diet with specific macronutrient distribution safe for humans?

Research indicates that high-protein diets can be safe and beneficial for weight management and satiety, with no kidney problems reported in healthy individuals. Very low-calorie diets, when supervised medically, have been shown to be safe for short-term use, with no diet-related fatalities reported in over 10,000 cases. ^{2 3 6 7 8}

How does the treatment for diet-induced thermogenesis in obesity differ from other treatments?

This treatment focuses on increasing diet-induced thermogenesis (the energy used to digest food) by altering macronutrient intake, particularly increasing protein, which is more thermogenic than fat or carbohydrates. Unlike other treatments that may focus on reducing calorie intake or increasing physical activity, this approach aims to enhance the body's natural energy expenditure through dietary changes. ^{1 2 6 8 9}

What is the purpose of this trial?

Background: Diet-induced thermogenesis (DIT) is the amount of energy one s body uses to eat food, absorb the nutrients from the food, and process those nutrients. Researchers would like to understand more about how changing the balances of protein, fat, carbohydrates, and total calories in the diet can affect DIT. Objective: To learn how different diets can change a person s DIT. Eligibility: Healthy people aged 18 to 60 years who have not intentionally lost weight in the past 6 months. Design: Participants will stay in a clinic for about 35 days. They will eat only the food provided. They will receive 8 different diets during the study, including 7 test diets. Participants will undergo multiple tests. They will be screened with blood and urine tests and a test of their heart function. During the first few days: Their waist, thigh, and neck circumference will be measured. They will have a DXA scan: They will lie on a padded table for about 20 minutes while an instrument measures the amount of fat in their body. They will be tested for diabetes. They will answer questionnaires about topics including eating behavior, hunger, and stress. Throughout the study: Their weight will be measured daily. Blood tests will be repeated. They will stay in a metabolic chamber a total of 9 times. They will remain in a closed room for 24 hours while researchers monitor the room temperature and levels of oxygen and carbon dioxide. Participants will collect all their urine for each 24-hour period. ...

Research Team

Tomas Cabeza De Baca, Ph.D.

Principal Investigator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Eligibility Criteria

Healthy adults aged 18-60 who haven't tried to lose weight on purpose in the last 6 months can join this study. People with heart, brain, lung diseases, diabetes, endocrine or kidney disorders, liver disease, certain cancers or infections, alcohol/drug abuse issues or pregnant/lactating women cannot participate.

Inclusion Criteria

No episodes of intentional weight loss over previous 6 months

Exclusion Criteria

Current use of tobacco products that exceed 'Very Low Dependence' on the Fagerstrom Test for Nicotine Dependence Tool (score greater than 2)

I have diabetes with high blood sugar or a history of diabetes.

Evidence of alcohol abuse as defined by >=8-point score on the Alcohol consumption screening AUDIT questionnaire in adults

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline Assessment

Initial measurements including waist, thigh, and neck circumference, DXA scan, diabetes testing, and questionnaires on eating behavior, hunger, and stress

1 week

Multiple visits (in-person)

Dietary Intervention

Participants receive 8 different diets, including 7 test diets, and undergo multiple tests including daily weight measurements, blood tests, and metabolic chamber assessments

4 weeks

Daily monitoring (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the dietary intervention

2 weeks

2 visits (in-person)

Treatment Details

Interventions

• +150% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein
• +150% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat
• +200% of dietary requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat
• -25% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat
• -50% of energy balance requirements. 50% of calories from carbohydrates, 20% from protein, and 30% from fat
• Fasting

Trial Overview The trial is testing how different diets affect the body's energy use after eating. Participants will stay in a clinic for about 34 days and try out eight diet variations with differing amounts of calories from carbs, proteins and fats while undergoing various tests including blood work and staying in a metabolic chamber.

Participant Groups

Group I: Set 10 Active Control 7 Interventions

+200% LPF -25% Fasting +200% SOF -50% +150% LPF +150% SOF

Group II: Set 4 Active Control 7 Interventions

Fasting -25% +200% LPF -50% +200% SOF +150% SOF +150% LPF

Group III: Set 3 Active Control 7 Interventions

+150% LPF Fasting +150% SOF -25% +200% SOF +200% LPF -50%

Group IV: Set 9 Active Control 7 Interventions

+150% SOF -25% +150% LPF +200% SOF Fasting +200% LPF -50%

Group V: Set 1 Active Control 7 Interventions

+150% LPF +150% SOF -50% +200% LPF +200% SOF Fasting -25%

Group VI: Set 2 Active Control 7 Interventions

+150% LPF +200% LPF -50% +150% SOF Fasting -25% +200% SOF

Group VII: Set 5 Active Control 7 Interventions

-25% +150% SOF +200% LPF +150% LPF Fasting +200% SOF -50%

Group VIII: Set 6 Active Control 7 Interventions

Fasting +200% LPF +200% SOF -50% +150% LPF -25% +150% SOF

Group IX: Set 7 Active Control 7 Interventions

-50% +200% SOF -25% +150% SOF Fasting +200% LPF +150% LPF

Group X: Set 8 Active Control 7 Interventions

-50% +150% SOF +200% SOF +150% LPF -25% +200% LPF Fasting

Who Is Running the Clinical Trial?

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Lead Sponsor

Trials

2,513

Recruited

4,366,000+

Findings from Research

Obese women oxidized a higher percentage of fat energy (40.2%) compared to normal weight women (36.0%) despite both groups consuming a diet with the same fat energy percentage (30%), indicating a link between fat mass and fat oxidation.

Post-obese subjects showed normal insulin sensitivity but struggled to appropriately adjust their fat to carbohydrate oxidation ratios on a high-fat diet (50% fat energy), leading to a positive fat balance and negative carbohydrate balance, suggesting potential metabolic adaptations following obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary composition, substrate balances and body fat in subjects with a predisposition to obesity. Astrup, A.[2014]

In a study involving 30 women (15 lean and 15 obese), diet-induced thermogenesis (DIT) was found to be significantly higher after consuming a protein-rich meal compared to a fat-rich meal, regardless of body weight status.

However, there were no significant differences in DIT or macronutrient oxidation rates between lean and obese women after consuming either meal, suggesting that low DIT from frequent fat intake may contribute to obesity maintenance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diet-induced thermogenesis and substrate oxidation are not different between lean and obese women after two different isocaloric meals, one rich in protein and one rich in fat. Tentolouris, N., Pavlatos, S., Kokkinos, A., et al.[2011]

A high-protein diet (1.2 g/kg body weight) during weight loss and maintenance helps sustain satiety and energy expenditure while preserving fat-free mass, which is crucial for long-term weight management.

The review indicates that adequate protein intake can improve body composition and blood pressure without causing kidney issues in healthy individuals, making it a safe and effective strategy for combating obesity and metabolic syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary protein - its role in satiety, energetics, weight loss and health. Westerterp-Plantenga, MS., Lemmens, SG., Westerterp, KR.[2022]

A low-energy protein diet, used for 28 days with 49 obese patients, resulted in an average weight loss of 10.6 kg and a significant reduction in BMI, indicating its efficacy for obesity treatment.

The diet improved cardiovascular risk factors, leading to lower blood pressure, cholesterol, and insulin levels, while being well tolerated with fewer side effects compared to intermittent fasting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A Czechoslovak low-energy protein diet in the treatment of obesity]. Hainer, V., Kunesová, M., Stich, V., et al.[2006]

A study involving 30 overweight individuals showed that consuming a higher protein diet (35% of energy) in six meals per day led to greater reductions in body fat and abdominal fat compared to traditional protein intake over three meals.

The higher frequency of meals not only decreased body fat but also increased lean body mass and postprandial thermogenesis, suggesting that eating more often with higher protein can improve metabolic health during both energy balance and deficit phases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased protein intake and meal frequency reduces abdominal fat during energy balance and energy deficit. Arciero, PJ., Ormsbee, MJ., Gentile, CL., et al.[2013]

High-protein diets are the most effective at increasing thermogenesis compared to high-carbohydrate and high-lipid diets, which can help in energy expenditure and potentially aid in obesity prevention.

Protein is the most satiating macronutrient, while fat is the least, indicating that diet composition can significantly influence energy intake and feelings of fullness, which is important for managing obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Macronutrient profile affects diet-induced thermogenesis and energy intake]. Hermsdorff, HH., Volp, AC., Bressan, J.[2016]

Very low calorie diets can lead to significant weight loss, averaging 20 kg in just 12 weeks, making them effective for treating moderate to severe obesity.

When conducted under careful medical supervision for up to 3 months, these diets are considered safe, with no diet-related fatalities reported in over 10,000 cases, contrasting sharply with earlier liquid protein diets that had serious safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very low calorie diets: their efficacy, safety, and future. Wadden, TA., Stunkard, AJ., Brownell, KD.[2022]

Diet-induced thermogenesis, which is the increase in energy expenditure after eating, can account for 5 to 15% of daily energy expenditure, depending on the diet's macronutrient composition.

Protein and alcohol significantly enhance diet-induced thermogenesis, while high fat consumption reduces it; this suggests that protein not only helps with energy expenditure but also plays a crucial role in regulating body weight by promoting feelings of fullness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diet induced thermogenesis. Westerterp, KR.[2022]

Obesity can result from both excessive food intake (hyperphagia) and a reduced ability to burn energy (thermogenic capacity), with factors like sympathetic nervous system sensitivity and insulin resistance playing a role in this energy imbalance.

A protein-sparing modified fast, which emphasizes high protein intake while reducing carbohydrates and fats, can help in weight loss, but after losing weight, individuals need to adjust their diet to maintain lower fat intake and allow for some carbohydrates, as their energy needs decrease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Physiopathology and treatment of obesity]. Jéquier, E.[2008]

References

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

Dietary composition, substrate balances and body fat in subjects with a predisposition to obesity. [2014]

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

Diet-induced thermogenesis and substrate oxidation are not different between lean and obese women after two different isocaloric meals, one rich in protein and one rich in fat. [2011]

3. England pubmed.ncbi.nlm.nih.gov

Dietary protein - its role in satiety, energetics, weight loss and health. [2022]

4. Czech Republic pubmed.ncbi.nlm.nih.gov

[A Czechoslovak low-energy protein diet in the treatment of obesity]. [2006]

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

Increased protein intake and meal frequency reduces abdominal fat during energy balance and energy deficit. [2013]

6. Venezuela pubmed.ncbi.nlm.nih.gov

[Macronutrient profile affects diet-induced thermogenesis and energy intake]. [2016]

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

Very low calorie diets: their efficacy, safety, and future. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Diet induced thermogenesis. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

[Physiopathology and treatment of obesity]. [2008]