An adaptive metabolic demand model for protein and amino acid requirements
Open accessAbstract
The shortcomings of the metabolic implications of the current protein requirements model are reviewed, and an alternative model, validated with [1-13 C]leucine balance results in human adults, is presented and evaluated in the context of defining protein requirements. The model identifies metabolic demands for amino acids as comprising a small fixed component and a variable adaptive component that is relatively insensitive to acute food or protein intake, but which changes slowly with a sustained change in intake, enabling N equilibrium to be achieved. The model accounts for the apparent low efficiency of utilisation of animal proteins in N balance studies and enables more realistic efficiency values to be measured within an experimental framework that takes account of the adaptive metabolic demand. However, the complex relationship between the adaptive metabolic demand and habitual level and quality of protein intake prevents prediction of protein quality by amino acid scoring, which can markedly underestimate actual values. In contrast to the current model, for fully adapted individuals risk of deficiency (i.e. negative N balance after complete adaptation) will only start to increase when intakes fall below the range of the true minimum requirements, i.e. a value that is currently unknown, but likely to be between 0·40 and 0·50 g/kg per d at the lower end of the reported distribution of requirements. At intakes greater than this with additional metabolic demands varying directly with intake, deficiency is only likely as a short-term response to a change to a lower intake within the adaptive range. Thus, for adults satisfying energy needs on most mixed human diets, intakes will be within the adaptive range, and N equilibrium ceases to be a useful indicator of nutritional adequacy of protein. In the context of prescriptive dietary guidelines it may be expedient to retain current values until the benefits (and any risks) of protein intakes within the adaptive range can be quantified. However, from a diagnostic perspective, indicators other than N balance need to be identified, since maintenance of N balance can no longer be used as a surrogate of adequate protein-related health.
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The body's response to protein is not static, but adjusts to the diet it is afforded.
“The body’s response to protein is not static, but adjusts to the diet it is afforded [42-44].”
From Dietary protein to maximize resistance training: a review and examination of protein spread and change theories (2012) · cites this paper as [44]
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Self-citationBorges, J. H. D. S., Júnior, P. L., de Brito, F. F., Rezende, H. P., Silva, M. V. D. S., de Oliveira, M. R., & Barin, F. R. (2024) · European Journal of Orthopaedic Surgery & Traumatology · doi:10.1007/s00590-023-03824-3 · Cited by 2 · see citing works
Limitations of the indicator amino acid oxidation method for determining amino acid requirements
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Self-citationLamont, L. S. (2012) · Nutrition Research Reviews · doi:10.1017/s0954422412000030 · Cited by 2 · see citing works
Layman, D. K., Evans, M., Erickson, D. J., Seyler, J., Weber, J., Bagshaw, D., Griel, A. E., Psota, T., & Kris‐Etherton, P. M. (2009) · Cited by 2 · see citing works
Paoletti, A. (2019) · TSpace (University of Toronto) · Cited by 2 · see citing works
Starck, C. S., Wolfe, R. R., & Moughan, P. J. (2026) · Journal of Nutrition · doi:10.1016/j.tjnut.2026.101417 · Cited by 1 · see citing works
Arencibia‐Albite, F. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2026.1777554 · Cited by 1 · see citing works
Human Protein Requirements and Infection Stress among Young Children at the Origins of Agriculture
Ulijaszek, S. J. (2008) · Society for the Study of Human Biology/Society for the Study of Human Biology series · doi:10.1201/9781420051377.ch3 · Cited by 1 · see citing works
SPORCU İÇECEKLERİ FAYDALI MI ?
Anlı, R. E., & Müniroğlu, S. (2022) · Journal of Global Sport and Education Research · doi:10.55142/jogser.1181809 · Cited by 1 · see citing works
Millward, D. J. (2025) · Proceedings of The Nutrition Society · doi:10.1017/s0029665125100591 · Cited by 1 · see citing works
Self-citationSyauki, A. Y., Ogawa, A., Simanjuntak, U. R. P., Mangiwa, I. G., Doi, M., Kageyama, S., Inoue, R., Taslim, N. A., & Irie, Y. (2022) · F1000Research · doi:10.12688/f1000research.76099.1 · Cited by 1 · see citing works
Protein: Requirements and role in diet
Millward, D. J. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821848-8.00003-2 · Cited by 1 · see citing works
Self-citationMillward, D. J. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-384947-2.00573-0 · Cited by 1 · see citing works
Self-citationProtein: Requirements and Role in Diet
Millward, D. J. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-375083-9.00242-7 · Cited by 1 · see citing works
Self-citationMillward, D. J. (2004) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/80.5.1093
Self-citationDrommer, J., Schneider, H., Alteheld, B., Stehle, P., & Meier, R. F. (2013) · Clinical Nutrition · doi:10.1016/s0261-5614(13)60195-8
Protein Intake in Critically Ill Adults
Ferrie, S., & Rand, S. (2015) · Springer eBooks · doi:10.1007/978-1-4614-7836-2_4
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Diet, Nutrition, and Disease across the Lifespan
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John Conrad Waterlow. 13 June 1916—19 October 2010
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Interaction of dietary protein with energy balance
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Protein Intake in Critically Ill Adults
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EFFECT OF LEUCINE ON THE MORPHO-GUNCTIONAL STATE OF RAT LIVER
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Self-citationTherapeutic intervention for type 5 diabetes mellitus: an overview
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Self-citationPhysiological Adaptation to Plant-Based Diets: A Homeostatic Framework for Sustained Dietary Change
López‐Moreno, M., Nagra, M., Jiménez, M. D. C. F.-F., Gomez-Herrera, G. P., & Kahleová, H. (2026) · Biology · doi:10.3390/biology15171520
Caracterização de compostos nutricionais e antinutricionais em taiobas (Xanthosoma Schott)
Lima, T. D. A. (2009) · Americanae (AECID Library)
- Authors
- Millward, D. J.
- Affiliations
- University of Surrey (GB)
- Corresponding author
- Millward, D. J.
- ORCID
- Millward, D. J.
- Venue
- British Journal of Nutrition
- Publisher
- Cambridge University Press (CUP)
- Published
- 2003-08
- Volume
- 90
- Issue
- 2
- Pages
- 249-260
- ISSN
- 0007-1145 (ISSN-L)
- 1475-2662
- OpenAlex
- W2115256296
- Cited by
- 100
- References
- 47
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 2 · 2016: 6 · 2015: 5 · 2014: 5 · 2013: 6 · 2012: 12
- FWCI
- 0.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal Of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Life Sciences › Agricultural and Biological Sciences › Food Science › Nutrition, Health, and Society Studies
- Keywords
- protein requirements, amino acid requirements, nitrogen balance, protein quality, protein deficiency, dietary guidelines
- MeSH terms
- Adult, Aged, Amino Acids, Dietary Proteins, Energy Metabolism, Female, Humans, Leucine, Male, Middle Aged, Models, Biological, Nitrogen, Reference Values, Time Factors
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