ArticleJournal of the International Society of Sports Nutrition2014
L-leucine, beta-hydroxy-beta-methylbutyric acid (HMB) and creatine monohydrate prevent myostatin-induced Akirin-1/Mighty mRNA down-regulation and myotube atrophy.
Article in Journal of the International Society of Sports Nutrition, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02773771 (Strategies to Reduce Organic Muscle Atrophy in the Intensive Care Unit), which is not on this map. Cited by 18 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.
Strategies to Reduce Organic Muscle Atrophy in the Intensive Care Unit (STROMA-ICU)
Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Efficacy of leucine-rich high protein supplementation on body composition and muscle function among older adults with sarcopenia: a randomized controlled trial.European journal of nutrition · 2026Trial
- Supplementing With Which Form of Creatine (Hydrochloride or Monohydrate) Alongside Resistance Training Can Have More Impacts on Anabolic/Catabolic Hormones, Strength and Body Composition?Physiological research · 2024Trial
- Nutritional intervention targeting muscle-brain axis in dementia continuum: from mechanisms to practice.Frontiers in nutrition · 2026Review
- Glucose, glutamine, lactic acid and α‑ketoglutarate restore metabolic disturbances and atrophic changes in energy‑deprived muscle cells.Molecular medicine reports · 2025Article
- Acute and Chronic Resistance Training, Acute Endurance Exercise, nor Physiologically Plausible Lactate In Vitro Affect Skeletal Muscle Lactylation.International journal of molecular sciences · 2024Article
- Role of nuclear protein Akirin in the modulation of female reproduction inFrontiers in physiology · 2024Article
- Does β-Hydroxy-β-Methylbutyrate Have Any Potential to Support the Treatment of Duchenne Muscular Dystrophy in Humans and Animals?Biomedicines · 2023Review
- Article
- Effects of dietary leucine on growth, antioxidant capacity, immune response, and inflammation in juvenile yellow catfishFrontiers in physiology · 2023Article
- Linoleic Acid Attenuates Denervation-Induced Skeletal Muscle Atrophy in Mice through Regulation of Reactive Oxygen Species-Dependent Signaling.International journal of molecular sciences · 2022Article
- Creatine for Exercise and Sports Performance, with Recovery Considerations for Healthy Populations.Nutrients · 2021Review
- Akirin proteins in development and disease: critical roles and mechanisms of action.Cellular and molecular life sciences : CMLS · 2020Review
- Mycobacterium tuberculosis curli pili (MTP) is associated with significant host metabolic pathways in an A549 epithelial cell infection model and contributes to the pathogenicity of Mycobacterium tuberculosis.Metabolomics : Official journal of the Metabolomic Society · 2020Article
- Article
- Functional Evolution of Subolesin/Akirin.Frontiers in physiology · 2018Review
- Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions.Journal of cachexia, sarcopenia and muscle · 2017Review
- The Combination of Physical Exercise with Muscle-Directed Antioxidants to Counteract Sarcopenia: A Biomedical Rationale for Pleiotropic Treatment with Creatine and Coenzyme Q10.Oxidative medicine and cellular longevity · 2017Review
- Effects of protein type and composition on postprandial markers of skeletal muscle anabolism, adipose tissue lipolysis, and hypothalamic gene expression.Journal of the International Society of Sports Nutrition · 2015Article
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 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe purpose of this study was to examine if L-leucine (Leu), β-hydroxy-β-methylbutyrate (HMB), or creatine monohydrate (Crea) prevented potential atrophic effects of myostatin (MSTN) on differentiated C2C12 myotubes.
methodsAfter four days of differentiation, myotubes were treated with MSTN (10 ng/ml) for two additional days and four treatment groups were studied: 1) 3x per day 10 mM Leu, 2) 3x per day 10 mM HMB, 3) 3x per day 10 mM Crea, 4) DM only. Myotubes treated with DM without MSTN were analyzed as the control condition (DM/CTL). Following treatment, cells were analyzed for total protein, DNA content, RNA content, muscle protein synthesis (MPS, SUnSET method), and fiber diameter. Separate batch treatments were analyzed for mRNA expression patterns of myostatin-related genes (Akirin-1/Mighty, Notch-1, Ski, MyoD) as well as atrogenes (MuRF-1, and MAFbx/Atrogin-1).
resultsMSTN decreased fiber diameter approximately 30% compared to DM/CTL myotubes (p < 0.001). Leu, HMB and Crea prevented MSTN-induced atrophy. MSTN did not decrease MPS levels compared to DM/CTL myotubes, but MSTN treatment decreased the mRNA expression of Akirin-1/Mighty by 27% (p < 0.001) and MyoD by 26% (p < 0.01) compared to DM/CTL myotubes. shRNA experiments confirmed that Mighty mRNA knockdown reduced myotube size, linking MSTN treatment to atrophy independent of MPS. Remarkably, MSTN + Leu and MSTN + HMB myotubes had similar Akirin-1/Mighty and MyoD mRNA levels compared to DM/CTL myotubes. Furthermore, MSTN + Crea myotubes exhibited a 36% (p < 0.05) and 86% (p < 0.001) increase in Akirin-1/Mighty mRNA compared to DM/CTL and MSTN-only treated myotubes, respectively.
conclusionsLeu, HMB and Crea may reduce MSTN-induced muscle fiber atrophy by influencing Akirin-1/Mighty mRNA expression patterns. Future studies are needed to examine if Leu, HMB and Crea independently or synergistically affect Akirin-1/Mighty expression, and how Akirin-1/Mighty expression mechanistically relates to skeletal muscle hypertrophy in vivo.
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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.