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Effect of Dietary Protein Content on Weight Gain, Energy Expenditure, and Body Composition During Overeating: A Randomized Controlled Trial
Open accessAbstract
CONTEXT: The role of diet composition in response to overeating and energy dissipation in humans is unclear. OBJECTIVE: To evaluate the effects of overconsumption of low, normal, and high protein diets on weight gain, energy expenditure, and body composition. DESIGN, SETTING, AND PARTICIPANTS: A single-blind, randomized controlled trial of 25 US healthy, weight-stable male and female volunteers, aged 18 to 35 years with a body mass index between 19 and 30. The first participant was admitted to the inpatient metabolic unit in June 2005 and the last in October 2007. INTERVENTION: After consuming a weight-stabilizing diet for 13 to 25 days, participants were randomized to diets containing 5% of energy from protein (low protein), 15% (normal protein), or 25% (high protein), which they were overfed during the last 8 weeks of their 10- to 12-week stay in the inpatient metabolic unit. Compared with energy intake during the weight stabilization period, the protein diets provided approximately 40% more energy intake, which corresponds to 954 kcal/d (95% CI, 884-1022 kcal/d). MAIN OUTCOME MEASURES: Body composition was measured by dual-energy x-ray absorptiometry biweekly, resting energy expenditure was measured weekly by ventilated hood, and total energy expenditure by doubly labeled water prior to the overeating and weight stabilization periods and at weeks 7 to 8. RESULTS: Overeating produced significantly less weight gain in the low protein diet group (3.16 kg; 95% CI, 1.88-4.44 kg) compared with the normal protein diet group (6.05 kg; 95% CI, 4.84-7.26 kg) or the high protein diet group (6.51 kg; 95% CI, 5.23-7.79 kg) (P = .002). Body fat increased similarly in all 3 protein diet groups and represented 50% to more than 90% of the excess stored calories. Resting energy expenditure, total energy expenditure, and body protein did not increase during overfeeding with the low protein diet. In contrast, resting energy expenditure (normal protein diet: 160 kcal/d [95% CI, 102-218 kcal/d]; high protein diet: 227 kcal/d [95% CI, 165-289 kcal/d]) and body protein (lean body mass) (normal protein diet: 2.87 kg [95% CI, 2.11-3.62 kg]; high protein diet: 3.18 kg [95% CI, 2.37-3.98 kg]) increased significantly with the normal and high protein diets. CONCLUSIONS: Among persons living in a controlled setting, calories alone account for the increase in fat; protein affected energy expenditure and storage of lean body mass, but not body fat storage. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00565149.
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“Over 12 weight-stable wk this led to 0.7 kg greater lean mass gain and fat loss compared to isoenergetic controls [33].”
From Dietary protein to maximize resistance training: a review and examination of protein spread and change theories (2012) · cites this paper as [33]
In the citing paper
“Soenen et al. had participants increase habitual protein intake 16%, from 1.13 g/kg/day to 1.31 g/kg/day via substitution of ~500 kcal with a milk protein based supplement containing 52 g protein.”
From Dietary protein to maximize resistance training: a review and examination of protein spread and change theories (2012) · cites this paper as [33]
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“Some data indicate that higher-protein diets may maintain greater REE and affect fat gain or loss differently than lower-protein diets in persons who consume deficient or excess-calorie diets (34, 35).”
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“All meals were prepared by our metabolism kitchen using a validated 5 day rotatingmenu [16] composed of 41% carbohydrate, 15% protein and 44% fat (40% saturated) [14].”
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“Studies of over nutrition of healthy volunteers showed that low protein diets result in less overall weight gain for equivalent amounts of fat gained and a loss of muscle mass [22].”
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“High-protein studies – ≥ 2.2 g/kg/d – sedentary individuals There is a dearth of investigations in which subjects consume a high amount of protein (Antonio, Ellerbroek, Peacock, & Silver, 2017; Antonio et al., 2015, 2016; Antonio, Peacock, Ellerbroek, Fromhoff, & Silver, 2014; Bray et al., 2012; Campbell et al., 2018;…”
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“Previous experimental studies have indicated that the effect of dietary protein on body weight regulation may depend on the energy balance [47].”
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“Although it has been demonstrated that a plant-based protein diet, through its anabolic properties, could be an effective strategy to enhance lean mass index, when eaten in excess, these foods may result in increasing SAT, hip, and waist circumference [39].”
Mechanisms of sodium‐mediated injury in cardiovascular disease: old play, new scripts
Rossitto, G., & Delles, C. (2021) · FEBS Journal · doi:10.1111/febs.16155 · Cited by 12
Developing a new treatment paradigm for disease prevention and healthy aging
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“Studies indicate that the amount of initial weight loss often is not affected by the macronutrient content of the dietary plan, but a higher protein diet may limit weight regain [7, 8, 11, 34, 35].”
BackgroundYamamoto, S., Ohta, Y., Hasegawa, E., Hashida, S., Kaneko, Y., MIZUTANI, S., Ong, B. H. E., Naganobu, K., & Torisu, S. (2019) · Frontiers in Veterinary Science · doi:10.3389/fvets.2019.00449 · Cited by 12
Overfeeding of Polyunsaturated Versus Saturated Fatty Acids Reduces Ectopic Fat
Bray, G. A., & Krauss, R. M. (2014) · Diabetes · doi:10.2337/db14-0493 · Cited by 11
“The question of whether obesity or ectopic fat accumulation during ingestion of excess calories is influenced differentially by diet has been an intriguing question for more than 100 years (3,4).”
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“Reported benefits in ad libitum trials have included reduction in fat mass, triglycerides, and free fatty acids in healthy overweight and obese subjects [43]; increased weight loss in severely obese adolescents [44]; reduction in body weight and diastolic blood pressure in overweight and obese adults [45]; and enhance…”
BackgroundBray, G. A., Redman, L. M., de Jonge, L., Rood, J. C., Sutton, E. F., & Smith, S. R. (2017) · Obesity · doi:10.1002/oby.22087 · Cited by 10
“This strategy increases body weight, (9,10), body fat (10,11), fat cell size (FCS) (11,12)), fat-free body mass (10), and energy expenditure (8,11) and has a variety of effects on other metabolic phenotypes (6-14).”
BackgroundMethodInfluentialSelf-citationÁvila, E. T. P., Lima, T. D. R., Tibana, R. A., de Almeida, P. C., Fraga, G. A., Sena, M. D. S., Corona, L. F. P., Navalta, J. W., Rezaei, S., Ghayomzadeh, M., et al. (2018) · Nutrition · doi:10.1016/j.nut.2018.01.018 · Cited by 10
Weight Gain Recommendations for Athletes and Military Personnel: a Critical Review of the Evidence
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The Association Between Diet and Obesity in Specific European Cohorts: DiOGenes and EPIC-PANACEA
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Gender- and Age-Specific REE and REE/FFM Distributions in Healthy Chinese Adults
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Self-citationSMITH, R. W., Harty, P. S., Stratton, M. T., Rafi, Z., Rodriguez, C., Dellinger, J. R., Benavides, M. L., Johnson, B. A., White, S. J., Williams, A. D., et al. (2021) · Journal of Functional Morphology and Kinesiology · doi:10.3390/jfmk6020036 · Cited by 11
“, training status, age, sex, level of effort) [50], and the anabolic stimulus provided by an energy surplus [1,51].”
BackgroundDiet and Exercise for Weight Loss
Bray, G. A. (2012) · JAMA · doi:10.1001/jama.2012.7263 · Cited by 8
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“However, no individual or augmented increases in EE were observed, which contradicts studies in younger adults that demonstrated protein- induced increases in SMR (Bray et al., 2015; Martens et al., 2015), RMR (Bray et al., 2012), and TEE (Bray et al., 2012, 2015).”
ResultPhysical Activity: An Important Adaptative Mechanism for Body-Weight Control
Finelli, C., Gioia, S., & Sala, N. L. (2012) · ISRN Obesity · doi:10.5402/2012/675285 · Cited by 7
RetractedMalowany, J. M., van Lieshout, G. A. A., Verdijk, L. B., Moore, D. R., van Loon, L. J. C., & Trommelen, J. (2025) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2025.2541895 · Cited by 8
“There are several populations in which body protein accretion is obvious, such as infants, children, strength athletes, and other individuals who are gaining weight (Bray et al. 2012).”
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In the Footsteps of Wilbur Olin Atwater: The Atwater Lecture for 2019
Bray, G. A. (2020) · Advances in Nutrition · doi:10.1093/advances/nmz128 · Cited by 6
“Thus, specifying the amount of protein is important in any metabolic study (17).”
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“WP’s popularity is mainly due to the many science-backed benefits elicited from its ingestion, including increased satiety [3], as well as increased rates of muscle protein synthesis, which often produce positive body composition changes, especially when paired with resistance training [4,5].”
BackgroundConnolly-Schoonen, J., Danowski, L., Bistricer, M., Catalan, L. C., Ailawadi, S., Sicinski, E. M., Schoonen, M., Ingram, B. O., & Montrose, D. C. (2023) · Nutrition and Cancer · doi:10.1080/01635581.2023.2217542 · Cited by 6
Modifying dietary amino acids in cancer patients
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Obésité. Pourquoi les régimes échouent-ils ?
Lecerf, J. (2013) · Nutrition Clinique et Métabolisme · doi:10.1016/j.nupar.2012.10.014 · Cited by 5
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Modeling energy balance while correcting for measurement error via free knot splines
Ries, D., Carriquiry, A., & Shook, R. P. (2018) · PLoS ONE · doi:10.1371/journal.pone.0201892 · Cited by 5
Bray, G. A. (2015) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-121214-104412 · Cited by 5
Self-citationAdeoye, I. A., Fakorede, J. I., Salawu, M. M., & Adediran, K. (2025) · BMC Pediatrics · doi:10.1186/s12887-025-05397-y · Cited by 4
Stentz, F. B., Lawson, D., Tucker, S., Christman, J. V., & Sands, C. (2022) · Obesity Pillars · doi:10.1016/j.obpill.2022.100047 · Cited by 6
“…have been recommended for T2DM [18 – 22] and non-diabetics, while some studies suggested advantages of low-carbohydrate diet [23,24] and other studies suggested advantages of a high-protein diet [25,26], there is no consensus on a speci fi c weight loss diet to manage blood glucose in T2DM [27].”
BackgroundChagas, C. L., Pinho, C. P. S., da Silva, N. F., Rodrigues, I. G., Arcoverde, G. M. P. F., Cabral, P. C., & de Arruda, I. K. G. (2025) · Nutrition · doi:10.1016/j.nut.2025.112874 · Cited by 4
Metadata
- Authors
- Bray, G. A., Smith, S. R., de Jonge, L., Xie, H., Rood, J., Martin, C. K., Most, M., Brock, C., Mancuso, S., & Redman, L. M.
- Affiliations
- Pennington Biomedical Research Center (US)
- Corresponding author
- Bray, George A.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2012-01-04
- Volume
- 307
- Issue
- 1
- Pages
- 47
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC3777747
- OpenAlex
- W2151035323
- Semantic Scholar
- 35084a4991db22c42be3fd1b5b7641943f3ce15e
- Cited by
- 285
- References
- 32
- Citations by year
- 2026: 17 · 2025: 13 · 2024: 5 · 2023: 6 · 2022: 19 · 2021: 19 · 2020: 27 · 2019: 24 · 2018: 19 · 2017: 20 · 2016: 23 · 2015: 18 · 2014: 26 · 2013: 25 · 2012: 24
- FWCI
- 13.17
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Louisiana State University
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK072476)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R00HD060762)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- dietary protein level, overeating, overfeeding, weight gain, energy expenditure, resting energy expenditure, total energy expenditure, body composition, fat mass, protein intake, energy balance, fat-free mass, lean body mass, fat-free mass index, fat mass index, body mass index, body age
- MeSH terms
- Adipose Tissue, Adolescent, Adult, Body Composition, Dietary Proteins, Energy Metabolism, Female, Humans, Hyperphagia, Male, Weight Gain, Single-Blind Method, Young Adult
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