Trial reportCell reports2016
Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health.
3 registry-linked trialsOpen access · goldAbstract readRandomized Controlled Trial
In one paragraph
Trial report in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 307 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
307citing papers in PubMed, 3 pooled it
22.6field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Does Protein Restriction Inhibit Prostrate Cancer Growth
The Metabolic Response to Reduced Branched-chain Amino Acids in Humans
ISOLeucine Addition Treatment Effects (ISOLATE) in a Controlled Diet Study
Who cites it
307 citing papers in PubMed, 3 syntheses or guidelines pooled it, 469 citations in OpenAlex.
- Meta-analysis links dietary branched-chain amino acids to metabolic health in rodents.BMC biology · 2022Pooled it
- Close association between lifestyle and circulating FGF21 levels: A systematic review and meta-analysis.Frontiers in endocrinology · 2022Pooled it
- Association between magnesium concentrations and prediabetes: a systematic review and meta-analysis.Scientific reports · 2021Pooled it
- Trial
- Dietary Protein Reduction During Isocaloric Conditions Reduces Body Weight in Men With Overweight or Obesity.Obesity (Silver Spring, Md.) · 2026Trial
- Rapid benefits in older age from transition to whole food diet regardless of protein source or fat to carbohydrate ratio: Arandomised control trial.Aging cell · 2024Trial
- Intermediate leucine catabolism is associated with longevity and sustained reproduction in grasshoppers.GeroScience · 2026Article
- The emerging role of branched-chain amino acid metabolism in obesity.International journal of obesity (2005) · 2026Review
- The hallmarks of protein and amino acid restriction in aging and longevity.Cell press blue · 2026Article
- Diet-responsive proteogenomic effects following short-term restriction of animal products in humans.Nature communications · 2026Article
- Association of BCAAs/BCKAs with pancreatic steatosis in patients with type 2 diabetes mellitus: A cross-sectional study.Journal of diabetes investigation · 2026Article
- Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice.Nature aging · 2026Article
- Strategies to optimize the nutritional profile of mammalian meat for infants and geriatric population.Food science of animal resources · 2026Review
- Effect of Branched-Chain Amino Acid Supplementation Alone or Combined With Tryptophan or Methionine on Appetite Control and Related Health Outcomes in Older Adults: Protocol for a Randomized Controlled Trial.JMIR research protocols · 2026Article
- Review
- Restriction of Individual Branched-Chain Amino Acids has Distinct Effects on the Development and Progression of Alzheimer's Disease in 3xTg Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Liver-Targeted AAV-DJ-hCBS Therapy Achieves Long-Term Correction of Metabolic Imbalance in CBS-Deficient Mice.International journal of molecular sciences · 2026Article
- Female resistance to the metabolic benefits of protein restriction is reversed by ovariectomy in mice.bioRxiv : the preprint server for biology · 2026Article
- Maternal BCAA overnutrition programs persistent dysglycemia in lean adult offspring.Molecular metabolism · 2026Article
- Association between the Planetary Health Diet Index and growth differentiation factor-15: the Seniors ENRICA-2 cohort.GeroScience · 2026Article
247 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 5 institutions in 2 countries.
Luigi FontanaDivision of Geriatrics and Nutritional Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA; Department of Clinical and Experimental Sciences, University of Brescia Medical School, 25121 Brescia, Italy; CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy. Electronic address: lfontana@dom.wustl.edu.
Nicole E CummingsDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Endocrinology and Reproductive Physiology Graduate Training Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Sebastian I Arriola ApeloDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
Joshua C NeumanDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
Ildiko KaszaMcArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53705, USA.
Brian A SchmidtDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
Edda CavaDivision of Geriatrics and Nutritional Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA; Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy.
Francesco SpeltaDivision of Geriatrics and Nutritional Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA; Department of Medicine, University of Verona, 37129 Verona, Italy.
Valeria TostiDivision of Geriatrics and Nutritional Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA; Department of Medicine, University of Verona, 37129 Verona, Italy.
Faizan A SyedDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
Emma L BaarDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
Nicola VeroneseDivision of Geriatrics and Nutritional Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA; Division of Geriatrics, Department of Medicine, University of Padova, 35122 Padova, Italy.
Sara E CottrellDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Rural and Urban Scholars in Community Health Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Rachel J FenskeDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
Beatrice BertozziDivision of Geriatrics and Nutritional Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA.
Harpreet K BrarDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
Terri PietkaDivision of Geriatrics and Nutritional Sciences, Washington University in St. Louis, St. Louis, MO 63130, USA.
Arnold D BullockDivision of Urology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
Robert S FigenshauDivision of Urology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
Gerald L AndrioleDivision of Urology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
Matthew J MerrinsDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Caroline M AlexanderMcArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53705, USA.
Michelle E KimpleDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Endocrinology and Reproductive Physiology Graduate Training Program, University of Wisconsin-Madison, Madison, WI 53706, USA; Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53705, USA.
Dudley W LammingDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA; Endocrinology and Reproductive Physiology Graduate Training Program, University of Wisconsin-Madison, Madison, WI 53706, USA; Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA; Rural and Urban Scholars in Community Health Program, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: dlamming@medicine.wisc.edu.
University of Wisconsin–Madison · USWashington University in St. Louis · USWilliam S. Middleton Memorial Veterans Hospital · USSapienza University of Rome · ITUniversity of Brescia · IT
Funding
Washington University Institute of Clinical and Translational Sciences (UL1)UL1RR024992 · NCRR · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2007 to 2011
$45.4MWashington University Institute of Clinical and Translational SciencesUL1TR000448 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$41.4MWisconsin Alzheimer's Disease Research CenterP50AG033514 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI KIND, AMY J. · 2009 to 2018
$16.2MBiology of Aging and Age-Related Diseases Training GrantT32AG000213 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Rozalyn M. Anderson, Sanjay Asthana · 1991 to 2026
$9.9MMolecular Mechanisms of Dysfunctional Prostaglandin Signaling in the Beta-CellR01DK102598 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI KIMPLE, MICHELLE E · 2014 to 2018
$1.7MThe in vivo regulation of glucose homeostasis and lifespan by mTORC2R00AG041765 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI LAMMING, DUDLEY WILLIAM · 2014 to 2016
$738kCyclin-Dependant Kinase 2 (CDK2) Function in Pancreatic Beta-CellsK01DK101683 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI MERRINS, MATTHEW J. · 2014 to 2016
$426kThe in vivo regulation of glucose homeostasis and lifespan by mTORC2K99AG041765 · NIA · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI LAMMING, DUDLEY WILLIAM · 2012 to 2013
$141kNCATS NIH HHS UL1 TR000448NCRR NIH HHS UL1 RR024992NIA NIH HHS K99 AG041765NIA NIH HHS P50 AG033514NIA NIH HHS R00 AG041765NIA NIH HHS T32 AG000213NIDDK NIH HHS K01 DK101683NIDDK NIH HHS R01 DK102598
Abstract
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.
Indexed as
Adipose Tissue, WhiteAmino Acids, Branched-ChainAnimalsBlood GlucoseDietary ProteinsFibroblast Growth FactorsGluconeogenesisGlucose IntoleranceHumansInsulin-Secreting CellsMaleMice, Inbred C57BLMiddle AgedObesityOrgan SizeStress, PhysiologicalAmino Acids, Branched-ChainBlood GlucoseDietary Proteinsfibroblast growth factor 21Fibroblast Growth Factors
Identifiers
What Socratic holds
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Read underepoch 390
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.