Trial reportPloS one2014
Fasting increases human skeletal muscle net phenylalanine release and this is associated with decreased mTOR signaling.
Trial report in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 85 citations in OpenAlex.
- The Influence of Intermittent Fasting on Selected Human Anthropometric Parameters.International journal of medical sciences · 2024Trial
- Greater plasma essential amino acids and lower 3-methylhistidine with higher protein intake during endurance training: a randomised control trial.Amino acids · 2023Trial
- Increasing autophagy with fasting and diet: separating fact from fiction.Biochemical Society transactions · 2026Review
- Highly-Time-Resolved Measurements of Tryptophan's Distribution and Homeostatic Regulation in Live, Intact Animals.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Systemic metabolic, hormonal, and glycomic remodeling during a 72-hour fast in healthy adults: a pilot study.Croatian medical journal · 2026Article
- Global loss of metabolic responsiveness and elevated enzyme in leptin deficient obese mice during starvation.NPJ systems biology and applications · 2026Article
- Medical nutrition therapy for the management of type 2 diabetes mellitus.Nature reviews. Endocrinology · 2025Review
- Anti-Atrophic Effects of Dichotomine B fromMolecules (Basel, Switzerland) · 2025Article
- Review
- Endurance exercise with reduced muscle glycogen content influences substrate utilization and attenuates acute mTORC1- and autophagic signaling in human type I and type II muscle fibers.Skeletal muscle · 2025Article
- Exploring the dietary strategies of phenylalanine: Improving muscle nutraceutical quality as well as muscle glycogen and protein deposition in adult grass carp (Food chemistry: X · 2024Article
- CARM1 drives mitophagy and autophagy flux during fasting-induced skeletal muscle atrophy.Autophagy · 2024Article
- Mechanisms driving fasting-induced protection from genotoxic injury in the small intestine.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Combined Aerobic Exercise with Intermittent Fasting Is Effective for Reducing mTOR and Bcl-2 Levels in Obese Females.Sports (Basel, Switzerland) · 2024Article
- Appropriate dietary phenylalanine improved growth, protein metabolism and lipid metabolism, and glycolysis in largemouth bass (Micropterus salmoides).Fish physiology and biochemistry · 2024Article
- Dietary restriction in senolysis and prevention and treatment of disease.Critical reviews in food science and nutrition · 2024Review
- Eight-day fasting modulates serum kynurenines in healthy men at rest and after exercise.Frontiers in endocrinology · 2024Article
- The Beneficial and Adverse Effects of Autophagic Response to Caloric Restriction and Fasting.Advances in nutrition (Bethesda, Md.) · 2023Review
- Eight-Day Fast and a Single Bout of Exercise: The Effect on Serum Methylarginines and Amino Acids in Men.Nutrients · 2023Article
- Chronic Vitamin E Deficiency Dysregulates Purine, Phospholipid, and Amino Acid Metabolism in Aging Zebrafish Skeletal Muscle.Antioxidants (Basel, Switzerland) · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
aimFasting is characterised by profound changes in energy metabolism including progressive loss of body proteins. The underlying mechanisms are however unknown and we therefore determined the effects of a 72-hour-fast on human skeletal muscle protein metabolism and activation of mammalian target of rapamycin (mTOR), a key regulator of cell growth.
methodsEight healthy male volunteers were studied twice: in the postabsorptive state and following 72 hours of fasting. Regional muscle amino acid kinetics was measured in the forearm using amino acid tracers. Signaling to protein synthesis and breakdown were assessed in skeletal muscle biopsies obtained during non-insulin and insulin stimulated conditions on both examination days.
resultsFasting significantly increased forearm net phenylalanine release and tended to decrease phenylalanine rate of disappearance. mTOR phosphorylation was decreased by ∼50% following fasting, together with reduced downstream phosphorylation of 4EBP1, ULK1 and rpS6. In addition, the insulin stimulated increase in mTOR and rpS6 phosphorylation was significantly reduced after fasting indicating insulin resistance in this part of the signaling pathway. Autophagy initiation is in part regulated by mTOR through ULK1 and fasting increased expression of the autophagic marker LC3B-II by ∼30%. p62 is degraded during autophagy but was increased by ∼10% during fasting making interpretation of autophagic flux problematic. MAFbx and MURF1 ubiquitin ligases remained unaltered after fasting indicating no change in protesomal protein degradation.
conclusionsOur results show that during fasting increased net phenylalanine release in skeletal muscle is associated to reduced mTOR activation and concomitant decreased downstream signaling to cell growth.
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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 OpenQuestion graph.