Weight Loss and Hunger

Weight Loss and Hunger: Did we Get it Wrong All This Time?

Weight loss is difficult and weight maintenance even worse. The principles of dieting dictate that to maintain weight loss, one has to eat less calories than they did before the diet. However, there is evidence to show that it may be the diet per se and not the weight loss that makes people more hungry and vulnerable to weight regain. This study will explore whether appetite control can be restored to normal levels through an individually tailored increase in calories after weight loss. If supported, the findings from this study could alter the way we view dieting.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity & Overweight
• Intervention / Treatment: Behavioral: Exercise; Behavioral: Dietary Intervention

Detailed Description

Weight loss reduces all components of the energy budget, i.e. resting energy expenditure (EE), the thermic effect of feeding and the energy cost of physical activities. The corollary of this observation is that to achieve energy balance at a lowered body weight (if EE is not increased through purposeful physical activity), energy intake (EI) needs to be kept at this lowered level of EE. While the math of the equation is simple, the operationalization has proven to be quite different. In fact, a dominant feature of weight loss is that it produces increases in hunger that appear within the first days, persist into weight loss and for at least a year after the intervention. As such, identifying strategies that abate changes in hunger and facilitate post-weight loss appetite control should be viewed as a central tenant of obesity interventions. However, data points to the possibility that it may well be the reduction in EI needed to produce weight loss that actually increases hunger. If this were to be the case, then forcing lower EI after weight loss likely exacerbates the state of increased hunger, paving the way for weight rebound. If there is somewhat a set value of EI for each individual, then current dietary strategies aimed at tailoring a food landscape conducive of reduced hunger with reduced EI needed to sustain weight loss, are destined to fail.

Primary hypotheses- The increase of EI to pre-weight loss values will significantly attenuate weight loss induced increases in hunger.

Secondary hypothesis- The increase of EI to pre-weight loss values will significantly attenuate weight loss induced metabolic adaptations (Greater than Predicted decreased in EE).

The increase of EI to pre-weight loss will significantly improve post weight loss ghrelin, PYY and GLP-1 responses.

Research plan- Fifty individuals living with obesity (25 men and 25 women BMI ≥ 30 kg/m2) will undergo a 20-week weight-loss intervention. After weight loss they will be randomly assigned to a 1-month experimental condition comprising of either : 1) a weight maintenance diet; or to 2) an increase of EI to pre-weight loss levels combined with increased exercise to maintain energy balance. A detailed investigation of energy balance variables will be conducted at all three time points.

Relevance- Discovery drives paradigm changes, which hold the promise of catalyzing innovation in treatment. The clinical impact of a setpoint EI is that it would inform more tailored personalized dietary intervention based on one's individual pre-weight loss EI rather than post-weight loss outcomes, which is the current standard of care for maintenance of weight loss. In other words, it could inform the precise corrections in EE (from physical activity) needed to not exacerbate appetite control, and to likely favour healthier weights.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eric Doucet, PhD; Phone Number: 4271 613-562-5800‬; Email: edoucet@uottawa.ca
• Study Contact Backup: Name: Noemie Beauregard, PhD (c); Phone Number: 613-857-3960; Email: nbeau029@uottawa.ca

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1S 5S9
      • University of Ottawa
      • Contact: Eric Doucet, PhD; Phone Number: 4271 613-562-5800‬; Email: edoucet@uottawa.ca
      • Contact: Noemie Beauregard, PhD (c); Phone Number: 613-857-3960; Email: nbeau029@uottawa.ca
      • Principal Investigator: Eric Doucet, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18-55 years of age;
2. non-smoking;
3. obese class I-II (30 kg/m2 ≤ BMI < 40 kg/m2);
4. weight stable (± 2 kg during the 6 months prior to enrollment);
5. Sedentary (<2 times/week of 30 min of continuous exercise)

In addition, Females will be included if:

1) premenopausal (2 menses in the 3 months preceding testing, no increase in cycle irregularity in the 12 months preceding testing).

Exclusion Criteria:

1. have a current diagnosis of an axis 1 psychiatric disorder (i.e. mood, anxiety and eating disorders);
2. currently use antidepressants, thyroid medication, or any medication that could affect appetite;
3. have a history of cardiac problems or symptoms suggestive of any cardiac condition;
4. have a current diagnosis or history of diabetes, confirmed by a measure of HbA1c during the screening visit;
5. have alcohol intake that exceeds recommendations or alcoholism, or current addictions to opiates, cocaine or stimulants;
6. currently taking monoamine oxidase inhibitors, pressor agents, warfarin, anticonvulsants, phenylbutazone, or tricyclic antidepressants;
7. have uncontrolled thyroid disease;
8. have any osteoarticular condition, or other reasons that would prevent them from achieving the proposed walking targets.

In addition, Females will be excluded if they:

1. are pregnant or planning to become pregnant over the course of the study;
2. are peri- or post-menopausal or have had surgically induced menopause.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Energy Flux; After weight loss through a dietary intervention, the high flux group will remain in a state of energy balance through an increase in exercise and an increase in energy intake to pre-weight loss values.	Behavioral: Exercise; Daily kilometer target at normal walking pace (~5km/h). The American College of Sports Medicine (ACSM) metabolic equation for the caloric cost of walking will be used to assess the distance needed to be covered daily.; Behavioral: Dietary Intervention; Participants will be prescribed a 20-week energy-restricted diet (-25% of energy requirements). A registered dietitian will be responsible for nutrition counselling and will use the Canadian Diabetes Association's Exchange System to prescribe the diet plan. During the weight loss phase, participants will receive a revised diet plan, based on the adjusted energy requirements that will account for the achieved weight loss. After weight loss, the diet plan will be revised based on the group (high-energy flux vs low-energy flux) to be in a state of energy balance.
Placebo Comparator: Low Energy Flux; After weight loss through a dietary intervention, the low-energy flux group will remain in energy balance but at a lower energy flux, with no changes in exercise levels and energy intake remaining lower than pre-weight-loss values.	Behavioral: Dietary Intervention; Participants will be prescribed a 20-week energy-restricted diet (-25% of energy requirements). A registered dietitian will be responsible for nutrition counselling and will use the Canadian Diabetes Association's Exchange System to prescribe the diet plan. During the weight loss phase, participants will receive a revised diet plan, based on the adjusted energy requirements that will account for the achieved weight loss. After weight loss, the diet plan will be revised based on the group (high-energy flux vs low-energy flux) to be in a state of energy balance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Appetite measurements	Desire to eat, hunger, fullness, and prospective food consumption (PFC) will be rated immediately before (after a 12 h overnight fast) and every 30 min*3 h after the standardized breakfast on a 100-mm visual analog scale (VAS) adapted from Hill and Blundell. Scores range from 0 to 100 millimeters. For hunger, desire to eat, and prospective food consumption, higher scores indicate greater appetite. For fullness, higher scores indicate greater fullness (lower appetite). The satiety quotient will be calculated for each subject.	Baseline (1 week before the dietary intervention), end of week 20 (after the weight-loss intervention), onset of week 25 (after the 1-month weight-maintenance period).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentrations of appetite-regulating hormones	Blood samples will be collected during experimental sessions while fasting and every 30 minutes for 3 hours following the standardized breakfast. EDTA and Aprotinin (anti-protease) and DPP-IV inhibitors will be added to whole-blood before it is centrifuged at 3000 rpm for 5 minutes at 4˚C. Plasma will be treated within an hour of sampling and then stored at -80˚C until assayed. Total Ghrelin (EZGRT-89K), Leptin (EZHL-80SK), GLP-1 (EZGLP1T-36K) and PYY (EZHPYYT66K) will be assayed with commercially available ELISA (Millipore). All samples from one subject will be assayed in duplicates in the same plate to avoid inter-assay variability.	Blood samples will be collected at each experimental session: Baseline (1 week before the dietary intervention), end of week 20 (after the weight-loss intervention), and onset of week 25 (after the 1-month weight-maintenance period).
Resting Energy Expenditure	The ventilated hood technique and the Vmax Encore 29 N metabolic cart (SensorMedics Corporation) will be used to perform indirect calorimetry. Carts are calibrated with reference gases each day. Measures will occur between 7:00 and 9:30 am after a 12-h fasting period, while also abstaining from exercise for at least 24 h, always performed in the same room, kept dark and at an ambient temperature of 21° C. Indirect calorimetry will be performed for 30 minutes.	Resting Energy Expenditure will be measured during the screening session (2 weeks before baseline), at baseline, end of week 20 (after the weight-loss intervention), onset of week 25 (after the 1-month weight-maintenance period).
Exercise Energy Expenditure	Free-living exercise energy expenditure will be measured using accelerometry. An accelerometer (Actical-Mini Mitter Co. Inc.) will be worn on the lower back for 7 days at each sampling period. Exercise energy expenditure will also be measured with a COSMED K4b2 portable indirect calorimeter during in-laboratory exercise sessions completed on the treadmill to confirm the accuracy of exercise energy expenditure.	Accelerometer: worn for 7 days at each sampling period (screening, week 20 (end of weight loss intervention), weeks 22 and 24 (middle and end of weight maintenance). Exercise energy expenditure will be measured once per week during weight maintenance.
Total Energy Expenditure	Total EE will be determined from doubly-labelled water (DLW) over a 7-day period to estimate carbon dioxide production over time in free-living subjects. After deuterated water is administered, 2H is lost from the body water at an exponential rate. When 18O-water is administered, the 18O is also lost with body water turnover (as per the 2H isotope) and with each molecule of carbon dioxide produced because carbonic anhydrase in the body rapidly facilitates the equilibrium exchange of water and carbon dioxide/carbonic acid oxygen. The difference between the rates of disappearance of 2H and 18O corresponds to the total carbon dioxide production over that period. These rates are determined from urine samples taken at the start and at the end of the measurement period. DLW is the gold standard for assessing free-living EE.	The DLW dose will be consumed during the screening session, and participants will provide their first urine sample. A second sample will be collected on the following day, and a 3rd 7 days later.
Energy Intake	EI will be measured in the laboratory and in the free-living state for 3 days with a food menu that we have developed and validated. In the laboratory, foods are served upon request, while outside the laboratory, foods are selected and packed away into coolers, somewhat like grocery shopping, and leftovers are brought back with wrappings to assess the weight of foods consumed. Food Processor SQL (ESHA Research Inc.) will be used.	In-lab energy intake: Baseline, end of week 20 (after the weight-loss intervention), and at the onset of week 25 (after one month of weight maintenance). Free-living energy intake will be measured for 3 days after the screening session.
Food Reward	The Leeds Food Preference Questionnaire, a forced-choice computer task, will be used to evaluate the implicit hedonic wanting (speed and frequency of choice) and the explicit hedonic liking (subjective visual analog scale rating) for different visual food cues, which vary in both fat and sugar content. The task assesses explicit liking and explicit wanting for food stimuli. Scores range from 0 to 100, with higher scores indicating greater liking or wanting for the presented foods. The Leeds Food Preference Questionnaire will be administered both before and after lunch.	Baseline (1 week before the dietary intervention), end of week 20 (after the weight-loss intervention), onset of week 25 (after the 1-month weight-maintenance period). The test lasts approximately 10 minutes.
Olfactory and Taste Performance	Nasal chemosensory and taste performance will be measured with Sniffin' Sticks and taste strips (Burghart Instruments, Wedel, Germany).	Olfactory and taste performance will be assessed during the in-laboratory at baseline (1 week before the dietary intervention), end of week 20 (after the weight-loss intervention), onset of week 25 (after the 1-month weight-maintenance period).
Body weight	Body weight (kg) will be measured with a digital scale (BWB-800AS Digital Scale from Tanita Corporation of America).	Baseline, weeks: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 21, 22, 23, 24, 25.
Height	Height (centimeter) will be measured using a stadiometer (HR-100 Height Rod).	Baseline (1 week before the dietary intervention), end of week 20 (after the weight-loss intervention), onset of week 25 (after the 1-month weight-maintenance period).
Fat-mass	Total body fat mass and percentage of total body fat will be assessed using dual-energy X-ray absorptiometry (DXA) (Lunar Prodigy, GE Medical Systems). Total body fat mass is reported in kilograms (kg), and percentage of total body fat is reported as a percentage (%) of total body weight. Higher values for both measures indicate greater total body fat.	Baseline (1 week before the dietary intervention), end of week 20 (after the weight-loss intervention), onset of week 25 (after the 1-month weight-maintenance period).
Fat-free mass	Total body fat-free mass will be assessed using dual-energy X-ray absorptiometry (DXA) (Lunar Prodigy, GE Medical Systems). Fat-free mass is reported in kilograms (kg) and represents the mass of all non-fat tissues, including muscle, organs, and bone. Higher values indicate greater fat-free mass.	Baseline (1 week before the dietary intervention), end of week 20 (after the weight-loss intervention), onset of week 25 (after the 1-month weight-maintenance period).
Bone mineral content	Total body bone mineral content will be assessed using dual-energy X-ray absorptiometry (DXA) (Lunar Prodigy, GE Medical Systems). Bone mineral content is reported in grams (g). Higher values indicate greater total body bone mineral content.	Baseline (1 week before the dietary intervention), end of week 20 (after the weight-loss intervention), onset of week 25 (after the 1-month weight-maintenance period).
Thermic effect of Food	A standardized breakfast consisting of 2 slices of whole wheat bread (80 g), peanut butter (20 g), strawberry jam (20 g), cheddar cheese 27% milk fat (20 g), and orange juice (250 mL). The total energy content is 575 kcal, and its food quotient will be 0.89 (57% carbohydrates, 13% protein, 30% lipids) for the 3 experimental sessions. Comparable alternatives will be offered in cases of food aversions, intolerances, or allergies. After breakfast, resting energy expenditure will be measured for 30 minutes every hour for a total of 3h. The same protocol described in the "resting energy expenditure section" will be used to assess the thermic effect of food (increase in energy expenditure above fasting values for the digestion, absorption, biosynthesis, and storage of nutrients).	Baseline (1 week before the dietary intervention), end of week 20 (after the weight-loss intervention), onset of week 25 (after the 1-month weight-maintenance period).
Eating behaviour assessed using the Three-Factor Eating Questionnaire-51	Eating behaviour will be assessed using the Three-Factor Eating Questionnaire-51 (TFEQ-51). The questionnaire assesses three domains of eating behaviour: dietary restraint, disinhibition, and perceived hunger. Scores are calculated according to published scoring procedures. Dietary restraint scores range from 0 to 21, disinhibition scores range from 0 to 16, and hunger scores range from 0 to 14. Higher scores indicate greater cognitive restraint, greater disinhibition, and greater susceptibility to hunger, respectively.	Baseline (1 week before the dietary intervention), end of week 20 (after the weight-loss intervention), onset of week 25 (after the 1-month weight-maintenance period).
Health-related quality of life assessed using the 36-Item Short Form Health Survey	Health-related quality of life will be assessed using the 36-Item Short Form Health Survey (SF-36). The SF-36 evaluates eight health domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, general health, and health change. Each domain is scored from 0 to 100, with higher scores indicating better health-related quality of life.	Baseline (1 week before the dietary intervention), end of week 20 (after the weight-loss intervention), onset of week 25 (after the 1-month weight-maintenance period).
Mood assessed using the Positive and Negative Affect Schedule	Mood will be assessed using the Positive and Negative Affect Schedule (PANAS). The questionnaire includes two subscales assessing positive affect and negative affect. Each subscale consists of 10 items scored from 1 to 5, resulting in total scores ranging from 10 to 50 for each subscale. Higher positive affect scores indicate greater positive affect, whereas higher negative affect scores indicate greater negative affect.	Baseline (1 week before the dietary intervention), end of week 20 (after the weight-loss intervention), onset of week 25 (after the 1-month weight-maintenance period).

Collaborators and Investigators

• Sponsor: University of Ottawa
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Eric Doucet, PhD, University of Ottawa

Publications and helpful links

General Publications

• Anderson JW, Konz EC, Frederich RC, Wood CL. Long-term weight-loss maintenance: a meta-analysis of US studies. Am J Clin Nutr. 2001 Nov;74(5):579-84. doi: 10.1093/ajcn/74.5.579.
• Dulloo AG, Jacquet J, Girardier L. Poststarvation hyperphagia and body fat overshooting in humans: a role for feedback signals from lean and fat tissues. Am J Clin Nutr. 1997 Mar;65(3):717-23. doi: 10.1093/ajcn/65.3.717.
• Machado AM, Guimaraes NS, Bocardi VB, da Silva TPR, Carmo ASD, Menezes MC, Duarte CK. Understanding weight regain after a nutritional weight loss intervention: Systematic review and meta-analysis. Clin Nutr ESPEN. 2022 Jun;49:138-153. doi: 10.1016/j.clnesp.2022.03.020. Epub 2022 Mar 31.
• Doucet E, McInis K, Mahmoodianfard S. Compensation in response to energy deficits induced by exercise or diet. Obes Rev. 2018 Dec;19 Suppl 1:36-46. doi: 10.1111/obr.12783.
• Cameron JD, Goldfield GS, Riou ME, Finlayson GS, Blundell JE, Doucet E. Energy depletion by diet or aerobic exercise alone: impact of energy deficit modality on appetite parameters. Am J Clin Nutr. 2016 Apr;103(4):1008-16. doi: 10.3945/ajcn.115.115584. Epub 2016 Feb 17.
• Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995 Mar 9;332(10):621-8. doi: 10.1056/NEJM199503093321001.
• Schwartz A, Doucet E. Relative changes in resting energy expenditure during weight loss: a systematic review. Obes Rev. 2010 Jul;11(7):531-47. doi: 10.1111/j.1467-789X.2009.00654.x. Epub 2009 Sep 17.
• Ryan DH. Risks and benefits of weight loss: challenges to obesity research. European Heart Journal 2005; (7): L27-L31.
• Anderson JW, Luan J, Hoie LH. Structured weight-loss programs: meta-analysis of weight loss at 24 weeks and assessment of effects of intervention intensity. Adv Ther. 2004 Mar-Apr;21(2):61-75. doi: 10.1007/BF02850334.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: July 14, 2026
• First Submitted That Met QC Criteria: July 27, 2026
• First Posted (Actual): July 31, 2026

Study Record Updates

• Last Update Posted (Actual): July 31, 2026
• Last Update Submitted That Met QC Criteria: July 27, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: exercise; weight loss; Appetite; dietary intervention
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Body Weight Changes; Pathological Conditions, Signs and Symptoms; Behavior; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Weight Loss; Motor Activity; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Therapeutics; Nutrition Therapy; Exercise; Diet Therapy
• Other Study ID Numbers: H-10-25-12071; 541343 (Other Grant/Funding Number: Canadian Institutes of Health Research)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No