Decreased consumption of branched-chain amino acids improves metabolic health
Open accessAbstract
Protein-restricted (PR), high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet.
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In another randomized clinical trial, feeding customized, isocaloric, moderately protein-restricted diets for 4-6 weeks to middle-aged overweight and mildly obese men resulted in a significant decrease in body weight, fat mass, and fasting blood glucose levels, and a major increase in circulating FGF21 concentration.
“In contrast, in another randomized clinical trial, feeding customized, isocaloric, moderately protein-restricted diets for 4–6 weeks to middle-aged overweight and mildly obese men resulted in a significant decrease in body weight, fat mass, and fasting blood glucose levels, and a major increase in circulating FGF21 concentration (79).”
From Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms (2018) · cites this paper as [79]
Selectively reducing dietary intake of branched-chain amino acids significantly improves glucose tolerance, β cell metabolic stress, and body composition in a recent rodent study.
“In contrast, data from a recent rodent study show that selectively reducing the dietary intake of branched-chain amino acids significantly improves glucose tolerance, β cell metabolic stress, and body composition (79).”
From Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms (2018) · cites this paper as [79]
FGF21 is also increased by the restriction of individual amino acids.
“with FGF21 also being increased by the restriction of individual amino acids”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [157]
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- Authors
- Fontana, L., Cummings, N. E., Arriola Apelo, S. I., Neuman, J. C., Kasza, I., Schmidt, B. A., Cava, E., Spelta, F., Tosti, V., Syed, F. A., Baar, E. L., Veronese, N., Cottrell, S. E., Fenske, R. J., Bertozzi, B., Brar, H. K., Pietka, T., Bullock, A. D., Figenshau, R. S., Andriole, G. L., Merrins, M. J., Alexander, C. M., Kimple, M. E., & Lamming, D. W.
- Affiliations
- Washington University in St. Louis (US)
- University of Wisconsin–Madison (US)
- University of Verona (IT)
- University of Padua (IT)
- Corresponding author
- Fontana, Luigi
- Lamming, Dudley W.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 16
- Issue
- 2
- Pages
- 520-530
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC4947548
- OpenAlex
- W2466033342
- Cited by
- 466
- References
- 48
- Citations by year
- 2026: 31 · 2025: 45 · 2024: 57 · 2023: 53 · 2022: 57 · 2021: 59 · 2020: 48 · 2019: 44 · 2018: 51 · 2017: 16 · 2016: 5
- FWCI
- 38.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by-nc-nd)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- National Institute on Aging (T32 AG000213, AG041765)
- Glenn Foundation for Medical Research
- Longer Life Foundation
- National Institute of Diabetes and Digestive and Kidney Diseases (1-16-PMF-001, K01 DK101683, R01 DK102598, 1-16-IBS-212)
- National Center for Research Resources (UL1 RR024992)
- School of Medicine and Public Health, University of Wisconsin-Madison
- American Diabetes Association (1-14-BS-115)
- National Institutes of Health
- American Foundation for Aging Research
- American Federation for Aging Research
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Health Sciences › Medicine › Physiology › Diet and metabolism studies
- Keywords
- branched-chain amino acids, low-protein diet, metabolic health, glucose tolerance, body composition, dietary amino acids, high-carbohydrate diet
- MeSH terms
- Amino Acids, Branched-Chain, Animals, Blood Glucose, Dietary Proteins, Fibroblast Growth Factors, Gluconeogenesis, Humans, Male, Mice, Inbred C57BL, Middle Aged, Obesity, Organ Size, Stress, Physiological, Glucose Intolerance, Insulin-Secreting Cells, Adipose Tissue, White
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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