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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how bodies manage weight by testing responses to a cycle of fasting and refeeding, which involves periods of not eating followed by periods of eating. The main goal is to study changes in energy use and food intake when participants fast for two days and then eat freely for two days. The trial seeks to better understand weight regulation and how bodies attempt to prevent weight loss. Suitable candidates for this trial are adults who are either underweight or have obesity, maintain a stable weight, and are willing to consume specific flavored meal replacements. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research on 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 prior data suggests that this fasting-refeeding cycle is safe for humans?

Research has shown that fasting cycles can be safe and manageable. In one study with 1,422 participants, fasting for 4 to 21 days was generally safe, with no major safety issues reported. Another study found that fasting could aid weight loss and improve energy metabolism. Although fasting might cause temporary inflammation, it usually did not lead to serious problems. Overall, these findings suggest that fasting and refeeding cycles are typically well-tolerated. However, individual experiences can vary, so personal health should be considered before participating. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the fasting-refeeding cycle for obesity because it offers a unique approach compared to traditional treatments like diet modification, exercise, and medication. Unlike these standard options, which often focus on sustained calorie reduction or increased physical activity, this method involves cycles of fasting and unrestricted eating. The idea is to potentially reset the body's metabolism in a way that could make it easier to lose weight and keep it off. By alternating between fasting and refeeding, this approach might also improve metabolic health markers more effectively than constant calorie restriction.

What evidence suggests that the fasting-refeeding cycle is effective for obesity?

Research has shown that cycles of fasting and eating can help people with obesity lose weight and improve their health. In this trial, participants will undergo a fasting-refeeding cycle, which includes 1 day of energy balance, 2 days of fasting, and 2 days of ad-libitum refeeding. Studies have found that intermittent fasting aids in weight loss and speeds up metabolism. For instance, one study reported an average weight loss of 5.6 kg over 10 weeks with a modified fasting plan. Fasting is also linked to better insulin sensitivity and healthier blood fat levels, which are important for heart health. Additionally, fasting can improve body composition, making it a promising method for managing obesity. ^{2 6 7 8 9}

Who Is on the 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

Are You a Good Fit for This Trial?

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

I am between 20 and 40 years old.

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

My BMI is either below 18.5 or above 30.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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]

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Fasting-Refedding Cycle for Obesity (DIP Trial)

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