Overfeeding Effects on Obesity

(EAT 2 Trial)

Overseen By Ursula White, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Pennington Biomedical Research Center

Must not be taking: Steroids, Antipsychotics, Antidepressants, others

Disqualifiers: Diabetes, Hypertension, Organ disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

58 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how fat tissues expand during weight gain and how this affects heart and overall metabolic health. Participants will either maintain their weight (Control) or consume 30% more calories than their usual diet (Overfeeding) to observe bodily adjustments. The study could offer new insights into how weight gain impacts health, particularly conditions like type 2 diabetes. Men and pre-menopausal women with stable weight who are willing to follow study procedures might be suitable candidates. As an unphased study, this trial provides a unique opportunity to contribute to groundbreaking research on weight gain and metabolic health.

Will I have to stop taking my current medications?

The trial requires that you do not use certain medications that can affect weight, such as steroids, beta-blockers, and antipsychotics. If you are on these medications, you may need to stop them to participate.

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

Research shows that consuming more calories than needed can lead to weight gain and increase the risk of health problems like type 2 diabetes and heart disease. Studies indicate that excessive calorie intake is a key factor in weight gain and can cause issues related to obesity. One study found that consuming too many calories, especially from highly processed foods, can lead to weight gain.

While overeating isn't usually a safety concern by itself, the long-term effects, such as potential heart problems, are important to consider. This study aims to understand how short-term weight gain affects fat tissue and overall health. Although participants in this trial temporarily consume more calories, the process is carefully monitored to ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the effects of overfeeding on obesity, a novel approach compared to typical treatments like dietary changes, exercise, and medication. Unlike standard methods that focus on weight loss, this trial investigates how controlled overfeeding impacts the body's energy balance and weight regulation. By understanding the body's response to increased caloric intake, researchers hope to uncover new insights into obesity management and potentially develop innovative strategies to address weight gain and its associated health risks.

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

This trial will compare the effects of overfeeding with a control group. Research has shown that consuming more calories than the body needs, known as overfeeding, can lead to weight gain. One study found that overfeeding caused an average weight gain of 2.2 kg, with about half of that being fat. Another study demonstrated that eating excessively for two weeks resulted in noticeable weight gain and reduced hunger afterward. However, some individuals gain weight more easily than others when they overeat. While the amount of weight and fat gained can vary, the general trend is an increase in body size. Understanding how fat tissue grows during overeating can help predict future health issues like metabolic syndrome or type 2 diabetes. ^{3 6 7 8 9}

Who Is on the Research Team?

Ursula White, Ph.D.

Principal Investigator

Pennington Biomedical Research Center

Are You a Good Fit for This Trial?

This trial is for men and pre-menopausal women aged 18-42 with a BMI of 25-30, willing to follow study procedures, maintain physical activity levels, drink labeled water for research, and use contraception if necessary. Excluded are those pregnant or planning pregnancy soon, with diabetes or high fasting blood glucose, high blood pressure, eating disorders, certain medication usage including weight loss drugs or antidepressants less than 3 months old.

Inclusion Criteria

I agree to use effective birth control or practice abstinence during the study.

Agree to maintain the same level of physical activity throughout the duration of the study

I am a man or a pre-menopausal woman aged 18-42.

Exclusion Criteria

I regularly use weight loss medications that could affect the study.

You have been diagnosed with a mental condition that causes you to lose touch with reality.

I am not on long-term medications that significantly affect my weight.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo overfeeding with a 30% increase in caloric intake to study adipose tissue expansion and remodeling

8 weeks

Follow-up

Participants are monitored for changes in adipose tissue and cardiometabolic health outcomes after the treatment phase

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Control
• Overfeeding

Trial Overview The study tests how short-term weight gain affects the ability of subcutaneous fat tissue to expand and remodel. Participants will be randomly assigned to either continue their normal diet (control group) or increase their calorie intake by 30% (overfeeding group), examining impacts on metabolic health outcomes.

How Is the Trial Designed?

Group I: Overfeeding Experimental Treatment 1 Intervention

The overfeeding group will be subjected to a similar relative change in energy intake, in which their dietary intake will be 30% more kcal/d than needed for weight maintenance.

Group II: Control Experimental Treatment 1 Intervention

The control group will be expected to maintain their weight within 1 kg of baseline weight throughout the duration of the study.

Who Is Running the Clinical Trial?

Pennington Biomedical Research Center

Lead Sponsor

Trials

314

Recruited

183,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Revisiting classic overfeeding studies from the 1960s, researchers found that low-protein overfeeding significantly stimulates thermogenesis, which is the body's heat production process.

This low-protein overfeeding approach can help identify genetic and metabolic factors that influence individual differences in body weight regulation, potentially aiding in obesity management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-protein overfeeding: a tool to unmask susceptibility to obesity in humans. Dulloo, AG., Jacquet, J.[2019]

Overfeeding female rat pups through continuous intragastric infusion led to significant weight gain, with overfed pups weighing more than normally reared pups by day 18 and maintaining this difference even after switching to a standard diet.

This study highlights the impact of early nutrition on obesity development, providing a new method to investigate how early dietary interventions can influence long-term weight outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infant gastrostomy and chronic formula infusion as a technique to overfeed and accelerate weight gain of neonatal rats. West, DB., Diaz, J., Woods, SC.[2018]

The study involved 8 overweight/obese participants and assessed the reproducibility of their energy intake after consuming a liquid preload, showing that ad libitum energy intake was highly reproducible with an intraclass correlation of 0.97 for control preloads.

Participants consumed more energy after a control preload compared to a whey protein preload, indicating that the type of preload can influence subsequent food intake, but overall energy intake remained consistent across repeated trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is ad libitum energy intake in overweight subjects reproducible in laboratory studies using the preload paradigm? Lara, J., Taylor, MA., Macdonald, IA.[2015]

After weight loss, individuals who were previously obese required significantly fewer calories (about 28% less) to maintain their new weight compared to their previous obese state, indicating a metabolic adaptation.

Despite still weighing significantly more than individuals who have never been obese, the reduced-obese patients needed to consume fewer calories than expected based on their body size, suggesting that long-term weight maintenance may require stricter dietary restrictions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diminished energy requirements in reduced-obese patients. Leibel, RL., Hirsch, J.[2019]

A study involving 12 pairs of identical twins showed that genetic factors significantly influence how individuals respond to overfeeding, affecting body weight, fat mass, and metabolic markers like insulin and cholesterol.

Specific genetic polymorphisms, such as those in the adipsin and beta2 adrenergic receptor genes, were linked to increased body weight and fat accumulation in response to excess calories, highlighting the role of genetics in energy balance and obesity risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of candidate genes in the responses to long-term overfeeding: review of findings. Ukkola, O., Bouchard, C.[2019]

Overfeeding consistently leads to weight gain across various demographics, including adolescents and older adults, with a strong correlation between energy intake and fat storage observed in longer studies lasting up to 6 months.

The effects of overfeeding on weight gain and metabolic responses are influenced by individual factors such as insulin sensitivity, genetic predisposition, and dietary composition, highlighting the complexity of how different bodies respond to excess energy intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The biology of human overfeeding: A systematic review. Bray, GA., Bouchard, C.[2021]

In two studies involving a total of 60 participants over 8 weeks of controlled overfeeding, hunger and food cravings decreased, while depressive symptoms and fear of fatness increased, indicating psychological impacts of overfeeding.

Body dissatisfaction rose during the overfeeding period and persisted for up to three months after, suggesting that even temporary weight gain can have lasting effects on body image, highlighting the importance of addressing these issues in individuals who experience weight fluctuations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of 8 weeks of supervised overfeeding on eating attitudes and behaviors, eating disorder symptoms, and body image: Results from the PROOF and EAT studies. Höchsmann, C., Fearnbach, N., Dorling, JL., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5786199/

The Effects of Overfeeding on Body Composition The average body weight gain was 2.2 kg, of which 50% was FM. However, there was considerable variability in the response to overfeeding. It is ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3782097/

The Effects of Overfeeding on Spontaneous Physical Activity ... ... overfeeding may contribute to future weight gain in individuals prone to obesity. ... Whether or not weight gain occurs continuously or episodically, it results ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0002916522009686

The pain of weight gain: self-experimentation with ... Following overfeeding, the participants in Sims' studies rapidly lost weight over the ensuing weeks when they stopped overeating. This clearly contrasts with ...

4. nature.com nature.com/articles/s41467-024-45223-0

Protection against overfeeding-induced weight gain is ... We found that two weeks of overfeeding resulted in a rapid and pronounced weight gain associated with a profound and sustained suppression of ...

5. royalsocietypublishing.org royalsocietypublishing.org/doi/10.1098/rstb.2022.0229

Physiological protection against weight gain: evidence from ... One study reported that food intake was significantly suppressed following 21 days of overfeeding in young men, however changes of dietary ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7299757/

Health and Economic Impacts of the National Menu Calorie ... Excess caloric intake is linked to weight gain, obesity, and related diseases including type 2 diabetes and cardiovascular disease (CVD).

7. sciencedirect.com sciencedirect.com/science/article/pii/S2589936825000313

Obesity: Prevalence, causes, consequences, management ... Most notably, obesity greatly elevates the risk of cardiovascular diseases such as coronary heart disease and stroke [[61], [62], [63]], which are the leading ...

8. pnas.org pnas.org/doi/10.1073/pnas.2420902122

Energy expenditure and obesity across the economic ... Our results suggest that dietary intake plays a far greater role than reduced expenditure in the elevated prevalence of obesity associated with economic ...

9. cell.com cell.com/cell-metabolism/fulltext/S1550-4131(19)30248-7

Ultra-Processed Diets Cause Excess Calorie Intake and ... In conclusion, our data suggest that eliminating ultra-processed foods from the diet decreases energy intake and results in weight loss, whereas ...