Fasting-Refedding Cycle for Obesity

(DIP Trial)

Overseen By Rodrigo Fernandez-Verdejo, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Pennington Biomedical Research Center

Must not be taking: GLP-1 agonists, Metformin, Amphetamines, others

Disqualifiers: Eating disorders, Diabetes, Cancer, others

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

Compensation: Varies

Number of Visits: Unknown

12 Participants Needed

Trial Summary

What is the purpose of this trial?

The regulation of human body weight and fatness is not fully understood. Although some models of regulation have been proposed (set point, dual-intervention point, others), no studies have been designed to test their predictions. In this pilot and feasibility study, the investigators will implement an experimental approach to test the predictions of models of body weight regulation in humans. Men and women with either low body weight or obesity will be exposed to a 2-day fasting followed by a 2-day ad-libitum refeeding. During the entire fasting-refeeding period, energy intake and expenditure will be accurately measured within metabolic chambers. The investigators will therefore determine the compensatory responses to fasting elicited to prevent weight loss. The results will serve to design and power future studies to better understand body weight regulation.

Will I have to stop taking my current medications?

You may need to stop taking certain medications that affect energy intake or expenditure, like semaglutide or metformin, to participate in this trial. The protocol doesn't specify a washout period, but it's best to discuss with the trial team.

What data supports the effectiveness of the fasting-refeeding cycle treatment for obesity?

Research shows that alternate day modified fasting can effectively help with weight loss in obese adults. Additionally, a study found that a longer refeeding period after a very-low-energy diet helps maintain weight loss better over a year. ^{1 2 3 4 5}

Is the fasting-refeeding cycle generally safe for humans?

The studies reviewed do not directly address the safety of fasting-refeeding cycles in humans, but they suggest that refeeding after fasting can help maintain weight loss and improve eating behavior. However, the long-term effects and safety in humans are not clearly established, and more research is needed to understand potential risks. ^{5 6 7 8 9}

How does the fasting-refeeding cycle treatment for obesity differ from other treatments?

The fasting-refeeding cycle treatment for obesity is unique because it involves alternating periods of fasting and eating freely, which can lead to increased food efficiency and rapid weight regain due to the body's energy conservation mechanisms. This approach contrasts with continuous caloric restriction, which often leads to long-term weight regain due to hormonal and metabolic changes. ^{1 6 8 9 10}

Research Team

Rodrigo Fernandez-Verdejo, PhD

Principal Investigator

Pennington Biomedical Research Center

Eric Ravussin, PhD

Principal Investigator

Pennington Biomedical Research Center

Dragana Lovre, MD

Principal Investigator

Tulane University

Eligibility Criteria

This trial is for men and women aged 20-40 with stable body weight who are either underweight (BMI < 18.5) or obese (BMI ≥ 30). Participants must have normal thyroid, blood count, and chemistry levels, enjoy Ensure Plus drinks to some extent, and women should not have given birth and must have regular menstrual cycles.

Inclusion Criteria

My BMI is either below 18.5 or above 30.

I am between 20 and 40 years old.

My blood tests for thyroid, blood count, and chemistry are normal.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Inpatient Energy Balance

Participants are maintained in metabolic chambers for 1 day of energy balance

1 day

Inpatient stay

Fasting

Participants undergo 2 days of fasting to measure compensatory responses

2 days

Inpatient stay

Ad-libitum Refeeding

Participants undergo 2 days of ad-libitum refeeding to measure compensatory responses

2 days

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after the fasting-refeeding cycle

1-2 weeks

Treatment Details

Interventions

• Fasting-refeeding cycle

Trial Overview The study tests how the human body regulates weight by having participants go through a fasting-refeeding cycle: two days of fasting followed by two days where they can eat as much as they want. Their energy intake and expenditure will be measured in metabolic chambers.

Participant Groups

Group I: Fasting-refeeding cycle Experimental Treatment 1 Intervention

Participants will be maintained in metabolic chambers and exposed to 1 day of energy balance, 2 days of fasting, and 2 days of ad-libitum refeeding.

Who Is Running the Clinical Trial?

Pennington Biomedical Research Center

Lead Sponsor

Trials

314

Recruited

183,000+

Tulane University

Collaborator

Trials

129

Recruited

259,000+

Findings from Research

In a 10-week study with 16 obese participants, alternate day modified fasting (ADMF) led to an average weight loss of 5.6 kg, demonstrating its effectiveness as a weight loss strategy.

Participants adapted well to ADMF, with significant reductions in energy intake on fasting days and no increase in hunger, while maintaining physical activity levels, suggesting that dietary and activity adaptations contribute to the weight loss observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary and physical activity adaptations to alternate day modified fasting: implications for optimal weight loss. Klempel, MC., Bhutani, S., Fitzgibbon, M., et al.[2021]

In a study of 38 adults with severe obesity, one cycle of intentional weight loss and regain did not lead to significant negative effects on physical health measures, including weight, body composition, or cardiovascular risk factors.

The findings suggest that weight cycling may not have detrimental physical or psychological consequences, indicating that concerns about weight regain should not deter patients from pursuing weight loss efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight cycling in adults with severe obesity: A longitudinal study. El Ghoch, M., Calugi, S., Dalle Grave, R.[2019]

A study of 66 severely obese outpatients on a very low calorie diet (VLCD) for a median of 55 days showed significant improvements in body weight, blood pressure, triglycerides, and cholesterol levels.

Participants with a history of weight cycling experienced less benefit from the VLCD, suggesting that more intensive maintenance strategies may be needed for those individuals to achieve optimal health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss and biomedical health improvement on a very low calorie diet: the moderating role of history of weight cycling. Hart, KE., Warriner, EM.[2016]

In a study comparing overweight and obese patients who underwent modified Buchinger fasting with a control group on a weight reduction diet, fasting patients initially lost more weight during treatment but regained it over time, with only 10.7% maintaining a 5% weight loss compared to 31.9% in the control group.

The control group showed greater success in adopting lasting dietary changes and increasing physical activity, suggesting that standard dietary therapy may be more effective for long-term weight management and lifestyle modification than fasting therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective long-term comparison of naturopathic fasting therapy and weight reduction diet in overweight patients. Beer, AM., Ismar, LE., Wessely, DK., et al.[2021]

In a study of 269 patients who underwent a very-low-energy diet (VLED) for weight loss, those who had a longer refeeding period of 6 weeks regained significantly less weight (3.9%) compared to those who re-fed for only 1 week (8.2%) over the following 40 weeks.

Patients with the longer refeeding duration also maintained better dietary restraint after the refeeding phase, suggesting that a gradual transition back to a regular diet can help with long-term weight maintenance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged refeeding improves weight maintenance after weight loss with very-low-energy diets. Gripeteg, L., Torgerson, J., Karlsson, J., et al.[2021]

After a 65-hour fasting period, male Sprague-Dawley rats showed a compensatory increase in food intake during an 8-day refeeding phase, leading to body weight and composition returning to normal levels.

The study suggests that the rats experienced increased 'food efficiency' during refeeding, meaning they gained more weight per gram of food consumed, which may explain weight gain after dieting in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Refeeding after fasting in the rat: effects on body composition and food efficiency. Björntorp, P., Yang, MU.[2018]

Intermittent energy restriction (IER), such as intermittent fasting, does not lead to greater weight loss compared to continuous energy restriction (CER), where daily energy intake is consistently limited.

Achieving energy balance during refeeding phases of IER may enhance weight loss outcomes, as some studies suggest that this approach could mitigate adaptive responses that hinder ongoing weight loss, although results from existing trials are mixed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale for novel intermittent dieting strategies to attenuate adaptive responses to energy restriction. Sainsbury, A., Wood, RE., Seimon, RV., et al.[2019]

Caloric restriction is effective for reducing body mass and improving insulin resistance, but maintaining this weight loss long-term is challenging due to hormonal and metabolic changes that promote weight regain.

The review highlights that while significant weight loss can improve insulin resistance, the cycle of losing and regaining weight (body mass cycling) can negate these benefits and may lead to worse metabolic health over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Body mass cycling and predictors of body mass regain and its impact on cardiometabolic health. Cornejo, MA., Ortiz, RM.[2021]

Fasting for 24 to 72 hours in mice primarily reduces mesenteric fat mass and decreases the size of fat cells in that area, indicating a targeted effect on visceral fat during periods of food deprivation.

Refeeding after fasting leads to a recovery of fat mass and cell size in subcutaneous adipose tissues, suggesting that the body preferentially restores these fat stores over visceral fat, highlighting the dynamic nature of fat distribution in response to fasting and refeeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasticity of adipose tissue in response to fasting and refeeding in male mice. Tang, HN., Tang, CY., Man, XF., et al.[2020]

Refed rats, after a period of food restriction, gained body fat and weight at rates approximately three times higher than control rats, indicating a significant impact of refeeding on fat accumulation.

The study found that the rapid fat gain in refed rats was primarily due to a depressed rate of fatty acid oxidation, which was influenced by increased carbohydrate and protein intake during refeeding, allowing for fat storage despite a lower metabolic rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatty acid oxidation and fatty acid synthesis in energy restricted rats(1). Brooks, SP., Lampi, BJ.[2019]

References

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

Dietary and physical activity adaptations to alternate day modified fasting: implications for optimal weight loss. [2021]

2. Australia pubmed.ncbi.nlm.nih.gov

Weight cycling in adults with severe obesity: A longitudinal study. [2019]

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

Weight loss and biomedical health improvement on a very low calorie diet: the moderating role of history of weight cycling. [2016]

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

Retrospective long-term comparison of naturopathic fasting therapy and weight reduction diet in overweight patients. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Prolonged refeeding improves weight maintenance after weight loss with very-low-energy diets. [2021]

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

Refeeding after fasting in the rat: effects on body composition and food efficiency. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Rationale for novel intermittent dieting strategies to attenuate adaptive responses to energy restriction. [2019]

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

Body mass cycling and predictors of body mass regain and its impact on cardiometabolic health. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Plasticity of adipose tissue in response to fasting and refeeding in male mice. [2020]

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

Fatty acid oxidation and fatty acid synthesis in energy restricted rats(1). [2019]