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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]
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“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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“Adherence is often suboptimal in advice-only trials (19, 41) and much better in supermarket studies (42), controlled-feeding studies (43, 44), or metabolic ward studies (45, 46).”
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“5% per week during energy balance (13, 21, 22) and up to 1% per day during starvation (56)], whereas adding protein to a diet that already contains the RDA of protein has no effect on lean body and muscle mass (9, 13, 115).”
BackgroundDietary Strategies to Increase Satiety
Rebello, C. J., Liu, A. G., Greenway, F. L., & Dhurandhar, N. V. (2013) · Advances in food and nutrition research · doi:10.1016/b978-0-12-410540-9.00003-x · Cited by 58
Vogtschmidt, Y. D., Raben, A., Faber, I., de Wilde, C., Lovegrove, J. A., Givens, D. I., Pfeiffer, A. F. H., & Soedamah-Muthu, S. S. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.05.011 · Cited by 54
Witard, O. C., Garthe, I., & Phillips, S. M. (2018) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.2018-0267 · Cited by 67
“A positive energy balance alone has been shown to elicit an important anabolic effect (Bray et al., 2012), but combining strength training and a positive energy balance results in the most effective gain in LBM (Kreider et al.”
BackgroundPasiakos, S. M., Margolis, L. M., & Orr, J. S. (2014) · The FASEB Journal · doi:10.1096/fj.14-266890 · Cited by 56
“…endocrine, and the behavioral mechanisms to account for body composition adaptations to energy and protein manipulations have been explored (13 – 16), the interaction between energy status and protein intake on skeletal muscle protein turn-over and associated regulatory systems remains largely…”
BackgroundRossitto, G., Maiolino, G., Lerco, S., Ceolotto, G., Blackburn, G. J., Mary, S., Antonelli, G., Berton, C., Bisogni, V., Cesari, M., et al. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa205 · Cited by 59
Gosby, A. K., Lau, N. S., Tam, C. S., Iglesias, M. A., Morrison, C. D., Caterson, I. D., Brand-Miller, J., Conigrave, A. D., Raubenheimer, D., & Simpson, S. J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0161003 · Cited by 51
Association between three non-insulin-based indexes of insulin resistance and hyperuricemia
Liu, X., Xu, X., Zhu, J. Q., & Zhao, D. B. (2019) · Clinical Rheumatology · doi:10.1007/s10067-019-04671-6 · Cited by 49
Nishimura, Y., Højfeldt, G. W., Breen, L., Tetens, I., & Holm, L. (2021) · Nutrition Research Reviews · doi:10.1017/s0954422421000329 · Cited by 54
“…oxidationand urea excretion are reduced under a positive energy balance conditionwith an increased protein intake ( > 0 · 83 g/kg/d), resulting in positive whole-body net protein and nitrogen balance (112) . expressed in terms of indispensable amino acid patterns relative to the requirement (6) .”
BackgroundTagawa, R., Watanabe, D., Ito, K., Otsuyama, T., Nakayama, K., Sanbongi, C., & Miyachi, M. (2022) · Sports Medicine - Open · doi:10.1186/s40798-022-00508-w · Cited by 55
The role of macronutrient content in the diet for weight management
Bray, G. A., & Siri-Tarino, P. W. (2016) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2016.04.009 · Cited by 47
Self-citationBonala, S., Lokireddy, S., McFarlane, C., Patnam, S., Sharma, M., & Kambadur, R. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.529925 · Cited by 48
RetractedUnderstanding Muscle Protein Dynamics: Technical Considerations for Advancing Sarcopenia Research
Kim, I., Park, S., Jang, J., & Wolfe, R. R. (2020) · Annals of Geriatric Medicine and Research · doi:10.4235/agmr.20.0041 · Cited by 49
Naturally good: Front-of-package claims as message cues
Skubisz, C. (2016) · Appetite · doi:10.1016/j.appet.2016.10.030 · Cited by 46
Anton, S. D., LeBlanc, E., Allen, H. R., Karabetian, C., Sacks, F. M., Bray, G. A., & Williamson, D. A. (2012) · Journal of Diabetes Science and Technology · doi:10.1177/193229681200600527 · Cited by 44
“23 Participants were randomly assigned and stratified by gender to one of four dietary conditions: (1) low fat (20% of energy), average protein (15% of energy); (2) moderate fat (40%), average protein (15%); (3) low fat (20%), high protein (25%); or (4) moderate fat (40%), high protein (25%).”
BackgroundMethodSelf-citationAyoub, J. J., Abou-Samra, M., Hlais, S., Bassil, M. S., & Obeid, O. (2015) · Nutrition and Diabetes · doi:10.1038/nutd.2015.38 · Cited by 46
Leaf, A., & António, J. (2017) · International journal of exercise science · doi:10.70252/hppf5281 · Cited by 43
“The second sedentary population study was conducted by Bray et al.(12) Using a double-blind, randomized, parallel-group design, 25 sedentary adults were overfed by 40% of energy requirements for eight weeks on diets supplying 5% protein (0.”
BackgroundMethodResultInfluentialHan, R., Zhang, Y., & Jiang, X. (2022) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s362248 · Cited by 45
Søndergaard, E., Gormsen, L. C., Christensen, M. H., Pedersen, S. B., Christiansen, P., Nielsen, S., Poulsen, P. L., & Jessen, N. (2014) · Diabetic Medicine · doi:10.1111/dme.12595 · Cited by 43
Association between hyperuricemia and nontraditional adiposity indices
Liu, X., Li, H. H., Huang, S., & Zhao, D. B. (2018) · Clinical Rheumatology · doi:10.1007/s10067-018-4374-x · Cited by 43
Rathmacher, J. A., Pitchford, L. M., Khoo, P. Y., Angus, H. F., Lang, J. A., Lowry, K. A., Ruby, C., Krajek, A. C., Fuller, J. C., & Sharp, R. L. (2020) · The Journals of Gerontology Series A · doi:10.1093/gerona/glaa218 · Cited by 43
“8 g per kg per day) is associated with reduced LBM and physical performance (9,10).”
BackgroundBosse, J. D., & Dixon, B. M. (2012) · Journal of the International Society of Sports Nutrition · doi:10.1186/1550-2783-9-42 · Cited by 42
“7 kg greater lean mass gain and fat loss compared to isoenergetic controls [33].”
BackgroundHydrolyzed Casein Reduces Diet-Induced Obesity in Male C57BL/6J Mice
Lillefosse, H. H., Tastesen, H. S., Du, Z., Ditlev, D. B., Thorsen, F., Madsen, L., Kristiansen, K., & Liaset, B. (2013) · Journal of Nutrition · doi:10.3945/jn.112.170415 · Cited by 43
Enzymatic Pea Protein Hydrolysates Are Active Trypsin and Chymotrypsin Inhibitors
Awosika, T., & Aluko, R. E. (2019) · Foods · doi:10.3390/foods8060200 · Cited by 42
Martens, E. A. P., Gonnissen, H. K. J., Gatta‐Cherifi, B., Janssens, P. L. H. R., & Westerterp‐Plantenga, M. S. (2014) · Clinical Nutrition · doi:10.1016/j.clnu.2014.10.007 · Cited by 40
“In a situation with low physical activity, fat mass as well as FFM were increased, together with an increase in resting energy expenditure [9].”
BackgroundAre metabolic adaptations to weight changes an artefact?
Müller, M. J., Heymsfield, S. B., & Bosy‐Westphal, A. (2021) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqab184 · Cited by 42
Muscle Adaptations to Heavy-Load and Blood Flow Restriction Resistance Training Methods
May, A. K., Russell, A. P., Gatta, P. A. D., & Warmington, S. A. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.837697 · Cited by 47
“Although mTOR (Ser2448) activation may increase 1–2 h post-HLRT (Dreyer et al., 2006, 2008; Camera et al., 2010), which we did not observe.”
BackgroundYasuda, J., Tomita, T., Arimitsu, T., & Fujita, S. (2020) · The Journal of Nutrition · doi:10.1093/jn/nxaa101 · Cited by 41
Rietman, A., Schwarz, J., Blokker, B., Siebelink, E., Kok, F. J., Afman, L. A., Tomé, D., & Mensink, M. (2014) · Journal of Nutrition · doi:10.3945/jn.114.191072 · Cited by 39
“Participants (males), n 27 (19) Age, y 22.”
MethodLiu, M., Liu, Q.-J., Wen, J., Wang, M., Wu, L., Qu, M., Li, M., Shen, M., & Wu, J. (2018) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2018.04.006 · Cited by 38
Hollstein, T., Ando, T., Basolo, A., Krakoff, J. A., Votruba, S. B., & Piaggi, P. (2019) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqz062 · Cited by 38
“Another study showed that protein intake is a determinant of adaptive thermogenesis during 8 wk of daily overfeeding (11).”
BackgroundMenni, C., Migaud, M. E., Kastenmüller, G., Pallister, T., Zierer, J., Peters, A., Mohney, R. P., Spector, T. D., Bagnardi, V., Gieger, C., et al. (2017) · Obesity · doi:10.1002/oby.21922 · Cited by 38
“Two models were fitted: (1) demographics and lifestyle, including age, baseline BMI, and smoking and (2) all variables in (1) plus the inverse normal concentrations of the four successfully replicated metabolites.”
BackgroundMethodLi, Y., Li, F., Wu, L., Wei, H., Liu, Y., Li, T., Tan, B., Kong, X., Kang, Y., Chen, S., et al. (2016) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-016-0106-8 · Cited by 40
“However, over the past few years, some studies pointed out that a high protein diet failed to translate into muscle mass [19, 20], suggesting that a high protein intake may not necessarily lead to accumulation of muscle protein.”
BackgroundPredictors of body composition and body energy changes in response to chronic overfeeding
Bouchard, C., Tchernof, A., & Tremblay, A. (2013) · International Journal of Obesity · doi:10.1038/ijo.2013.77 · Cited by 34
The role of dietary protein in obesity
Magkos, F. (2020) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-020-09576-3 · Cited by 37
“the latter two studies [48, 49] makes interpretation of these results difficult with regard to the effects of high-protein diets on weight gain during overfeeding.”
BackgroundResultMizgier, M., Jarząbek‐Bielecka, G., Opydo-Szymaczek, J., Wendland, N., Więckowska, B., & Kędzia, W. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9093041 · Cited by 36
“The beneficial effects of a higher-protein diet on body composition and weight loss are likely related to the greater effect of protein (compared to carbohydrate and fat) on inducing postprandial thermogenesis [68,69].”
BackgroundMillward, D. J. (2021) · Nutrients · doi:10.3390/nu13030729 · Cited by 44
Inadequacy of BMI as an Indicator for Bariatric Surgery
Livingston, E. H. (2012) · JAMA · doi:10.1001/jama.2011.1950 · Cited by 34
Synergistic effects of resistance training and protein intake: Practical aspects
Guimarães-Ferreira, L., Cholewa, J. M., Naimo, M. A., Zhi, X. I. A., Magagnin, D., Dal Ponte de Sá, R. B., Streck, E. L., da Silva Teixeira, T., & Zanchi, N. E. (2014) · Nutrition · doi:10.1016/j.nut.2013.12.017 · Cited by 34
Tappy, L., Egli, L., Lecoultre, V., & Schneider, P. (2013) · Nutrition & Metabolism · doi:10.1186/1743-7075-10-54 · Cited by 38
“It also differs from several overfeeding studies, in which subjects overfed with 700 kcal fat /day [63], or with about 1000 kcal/day of a mixed diet [64-66] showed either no change or an increase in BMR.”
MethodVu, J. P., Luong, L., Parsons, W. F., Oh, S., Sanford, D., Gabalski, A. H., Lighton, J. R. B., Pisegna, J. R., & Germano, P. M. (2017) · Journal of Nutrition · doi:10.3945/jn.117.257873 · Cited by 35
“However, these TEE increases were found only during the first 2 wk, whereas in a longer-term study of 6 wk, no significant differences were observed (52, 53).”
BackgroundOvereating, caloric restriction and breast cancer risk by pathologic subtype: the EPIGEICAM study
Lope, V., Martín, M., Castelló, A., Ruı́z, A., Casas, A. M., Baena-Cañada, J. M., Antolín, S., Ramos-Vázquez, M., García-Sáenz, J. Á., Muñoz-Mateu, M., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-39346-4 · Cited by 36
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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