Protein Leverage: Theoretical Foundations and Ten Points of Clarification
Abstract
Much attention has been focused on fats and carbohydrates as the nutritional causes of energy overconsumption and obesity. In 2003, a model of intake regulation was proposed in which the third macronutrient, protein, is not only involved but is a primary driver of calorie intake via its interactions with carbohydrates and fats. This model, called protein leverage, posits that the strong regulation of protein intake causes the overconsumption of fats and carbohydrates (hence total energy) on diets with a low proportion of energy from protein and their underconsumption on diets with a high proportion of protein. Protein leverage has since been demonstrated in a range of animal studies and in several studies of human macronutrient regulation, and its potential role in contributing to the obesity epidemic is increasingly attracting discussion. Over recent years, however, several misconceptions about protein leverage have arisen. Our aim in this paper is to briefly outline some key aspects of the underlying theory and clarify 10 points of misunderstanding that have the potential to divert attention from the substantive issues.
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During amino acid restriction, mammals increase their consumption of diets low in protein to acquire sufficient protein to satisfy organismal requirements, despite increasing their overall caloric intake.
“During amino acid restriction, mammals increase their consumption of diets low in protein to acquire sufficient protein to satisfy organismal requirements, despite increasing their overall caloric intake125–129.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [127]
A large and growing literature clearly demonstrates that animals selectively detect and adaptively respond to the restriction of dietary protein.
“there is a large and growing literature that rather clearly demonstrates that animals selectively detect and adaptively respond to the restriction of dietary protein”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [32]
Protein is prioritized and regulated to a specific target, so small changes in the proportion of dietary protein can induce large changes in total food and energy intake (protein leveraging).
“The observation that protein is prioritized and regulated to a specific target suggests that small changes in the proportion of dietary protein can induce large changes in total food and energy intake, a concept termed protein leveraging”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [32]
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Hill, C. M., Qualls-Creekmore, E., Berthoud, H.-R., Soto, P., Yu, S., McDougal, D. H., Münzberg, H., & Morrison, C. D. (2020) · Endocrinology · doi:10.1210/endocr/bqaa019 · Cited by 99 · see citing works
Flippo, K. H., Jensen-Cody, S. O., Claflin, K. E., & Potthoff, M. J. (2020) · Scientific Reports · doi:10.1038/s41598-020-76593-2 · Cited by 49 · see citing works
A Systematic Review and Meta-Analyses of Food Preference Modifications After Bariatric Surgery
Guyot, E., Dougkas, A., Nazare, J., Bagot, S., Disse, E., & Iceta, S. (2021) · Obesity Reviews · doi:10.1111/obr.13315 · Cited by 27 · see citing works
Dietary and Behavioral Strategies for Weight Loss and Weight Loss Maintenance: A Narrative Review
Żurawski, T., & Bartosiewicz, A. (2025) · Nutrients · doi:10.3390/nu18010012 · Cited by 18 · see citing works
Food Reward After Bariatric Surgery and Weight Loss Outcomes: An Exploratory Study
Guyot, E., Nazare, J.-A., Oustric, P., Robert, M., Disse, E., Dougkas, A., & Iceta, S. (2022) · Nutrients · doi:10.3390/nu14030449 · Cited by 12 · see citing works
- Authors
- Raubenheimer, D., & Simpson, S. J.
- Affiliations
- The University of Sydney (AU)
- Corresponding author
- Raubenheimer, David
- Venue
- Obesity
- Publisher
- Wiley
- Published
- 2019-07-24
- Volume
- 27
- Issue
- 8
- Pages
- 1225-1238
- ISSN
- 1930-7381 (ISSN-L)
- 1930-739X
- OpenAlex
- W2963930807
- Cited by
- 157
- References
- 93
- Citations by year
- 2026: 11 · 2025: 31 · 2024: 17 · 2023: 25 · 2022: 28 · 2021: 21 · 2020: 20 · 2019: 3 · 2014: 1
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Obesity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NHMRC Program (GNT1149976)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Nursing › Nutrition and Dietetics › Nutrition, Health and Food Behavior
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Keywords
- energy intake regulation, protein intake, energy overconsumption, dietary protein
- MeSH terms
- Nutrients, Animals, Energy Intake, Diet, Dietary Carbohydrates, Dietary Fats, Dietary Proteins, Humans, Obesity
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