Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články, přehledy
PubMed
28493406
PubMed Central
PMC5566641
DOI
10.1002/jcsm.12208
Knihovny.cz E-zdroje
- Klíčová slova
- Cachexia, Exercise, HMB, Leucine, Sarcopenia, Supplements,
- MeSH
- kachexie dietoterapie patofyziologie MeSH
- kosterní svaly účinky léků fyziologie MeSH
- lidé MeSH
- potravní doplňky MeSH
- sarkopenie dietoterapie patofyziologie MeSH
- svalová atrofie dietoterapie patofyziologie MeSH
- svalová síla účinky léků MeSH
- syndrom chřadnutí dietoterapie patofyziologie MeSH
- valeráty aplikace a dávkování farmakologie MeSH
- zdraví MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- beta-hydroxyisovaleric acid MeSH Prohlížeč
- valeráty MeSH
Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of the essential amino acid leucine that has been reported to have anabolic effects on protein metabolism. The aims of this article were to summarize the results of studies of the effects of HMB on skeletal muscle and to examine the evidence for the rationale to use HMB as a nutritional supplement to exert beneficial effects on muscle mass and function in various conditions of health and disease. The data presented here indicate that the beneficial effects of HMB have been well characterized in strength-power and endurance exercise. HMB attenuates exercise-induced muscle damage and enhances muscle hypertrophy and strength, aerobic performance, resistance to fatigue, and regenerative capacity. HMB is particularly effective in untrained individuals who are exposed to strenuous exercise and in trained individuals who are exposed to periods of high physical stress. The low effectiveness of HMB in strength-trained athletes could be due to the suppression of the proteolysis that is induced by the adaptation to training, which may blunt the effects of HMB. Studies performed with older people have demonstrated that HMB can attenuate the development of sarcopenia in elderly subjects and that the optimal effects of HMB on muscle growth and strength occur when it is combined with exercise. Studies performed under in vitro conditions and in various animal models suggest that HMB may be effective in treatment of muscle wasting in various forms of cachexia. However, there are few clinical reports of the effects of HMB on muscle wasting in cachexia; in addition, most of these studies evaluated the therapeutic potential of combinations of various agents. Therefore, it has not been possible to determine whether HMB was effective or if there was a synergistic effect. Although most of the endogenous HMB is produced in the liver, there are no reports regarding the levels and the effects of HMB supplementation in subjects with liver disease. Several studies have suggested that anabolic effects of HMB supplementation on skeletal muscle do not occur in healthy, non-exercising subjects. It is concluded that (i) HMB may be applied to enhance increases in the mass and strength of skeletal muscles in subjects who exercise and in the elderly and (ii) studies examining the effects of HMB administered alone are needed to obtain conclusions regarding the specific effectiveness in attenuating muscle wasting in various muscle-wasting disorders.
Zobrazit více v PubMed
Kalantar‐Zadeh K, Rhee C, Sim JJ, Stenvinkel P, Anker SD, Kovesdy CP. Why cachexia kills: examining the causality of poor outcomes in wasting conditions. J Cachexia Sarcopenia Muscle 2013;4:89–94. PubMed PMC
Streat SJ, Beddoe AH, Hill GL. Aggressive nutritional support does not prevent protein loss despite fat gain in septic intensive care patients. J Trauma 1987;27:262–266. PubMed
Anker SD, Coats AJ, Morley JE. Evidence for partial pharmaceutical reversal of the cancer anorexia‐cachexia syndrome: the case of anamorelin. J Cachexia Sarcopenia Muscle 2015;6:275–277. PubMed PMC
Konishi M, Ishida J, von Haehling S, Anker SD, Springer J. Nutrition in cachexia: from bench to bedside. J Cachexia Sarcopenia Muscle 2016;7:107–109. PubMed PMC
Takala J, Ruokonen E, Webster NR, Nielsen MS, Zandstra DF, Vundelinckx G, et al. Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med 1999;341:785–792. PubMed
Van Koevering M, Nissen S. Oxidation of leucine and alpha‐ketoisocaproate to beta‐hydroxybeta‐methylbutyrate in vivo. Am J Phys 1992;262:E27–E31. PubMed
Girón MD, Vílchez JD, Salto R, Manzano M, Sevillano N, Campos N, et al. Conversion of leucine to β‐hydroxy‐β‐methylbutyrate by α‐keto isocaproate dioxygenase is required for a potent stimulation of protein synthesis in L6 rat myotubes. J Cachexia Sarcopenia Muscle 2016;7:68–78. PubMed PMC
Nissen S, Sharp R, Ray M, Rathmacher JA, Rice D, Fuller JC, et al. Effect of leucine metabolite beta‐hydroxy‐beta‐methylbutyrate on muscle metabolism during resistance‐exercise training. J Appl Physiol 1996;81:2095–2104. PubMed
Walker DK, Thaden JJ, Wierzchowska‐McNew A, Engelen MP, Deutz NE. Determination of β‐hydroxy‐β‐methylbutyrate concentration and enrichment in human plasma using chemical ionization gas chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2017;1040:233–238. PubMed PMC
Nissen SL, Abumrad NN. Nutritional role of the leucine metabolite β‐hydroxy‐β–methylbutyrate (HMB) . J Nutr Biochem 1997;8:300–311.
Nissen S, Sharp RL, Panton L, Vukovich M, Trappe S, Fuller JC. beta‐Hydroxy‐beta‐methylbutyrate (HMB) supplementation in humans is safe and may decrease cardiovascular risk factors. J Nutr 2000;130:1937–1945. PubMed
Wilkinson DJ, Hossain T, Hill DS, Phillips BE, Crossland H, Williams J, et al. Effects of leucine and its metabolite beta‐hydroxy‐beta‐methylbutyrate on human skeletal muscle protein metabolism. J Physiol 2013;591:2911–2923. PubMed PMC
Gerlinger‐Romero F, Guimarães‐Ferreira L, Giannocco G, Nunes MT. Chronic supplementation of beta‐hydroxy‐beta methylbutyrate (HMβ) increases the activity of the GH/IGF‐I axis and induces hyperinsulinemia in rats. Growth Horm IGF Res 2011;21:57–62. PubMed
Smith HJ, Mukerji P, Tisdale MJ. Attenuation of proteasome‐induced proteolysis in skeletal muscle by {beta}‐hydroxy‐{beta}‐methylbutyrate in cancer‐induced muscle loss. Cancer Res 2005;65:277–283. PubMed
Kovarik M, Muthny T, Sispera L, Holecek M. Effects of β‐hydroxy‐β‐methylbutyrate treatment in different types of skeletal muscle of intact and septic rats. J Physiol Biochem 2010;66:311–319. PubMed
Eley HL, Russell ST, Tisdale MJ. Attenuation of depression of muscle protein synthesis induced by lipopolysaccharide, tumor necrosis factor, and angiotensin II by beta‐hydroxy‐beta‐methylbutyrate. Am J Physiol Endocrinol Metab 2008;295:E1409–E1416. PubMed
Hao Y, Jackson JR, Wang Y, Edens N, Pereira SL, Alway SE. β‐Hydroxy‐β‐methylbutyrate reduces myonuclear apoptosis during recovery from hind limb suspension‐induced muscle fiber atrophy in aged rats. Am J Physiol Regul Integr Comp Physiol 2011;301:R701–R715. PubMed PMC
Kimura K, Cheng XW, Inoue A, Hu L, Koike T, Kuzuya M. β‐Hydroxy‐β‐methylbutyrate facilitates PI3K/Akt‐dependent mammalian target of rapamycin and FoxO1/3a phosphorylations and alleviates tumor necrosis factor α/interferon γ‐induced MuRF‐1 expression in C2C12 cells. Nutr Res 2014;34:368–374. PubMed
Kornasio R, Riederer I, Butler‐Browne G, Mouly V, Uni Z, Halevy O. Beta‐hydroxy‐beta‐methylbutyrate (HMB) stimulates myogenic cell proliferation, differentiation and survival via the MAPK/ERK and PI3K/Akt pathways. Biochim Biophys Acta 1793;2009:755–763. PubMed
He X, Duan Y, Yao K, Li F, Hou Y, Wu G. Yin Y β‐Hydroxy‐β‐methylbutyrate, mitochondrial biogenesis, and skeletal muscle health. Amino Acids 2016;48:653–664. PubMed
Vallejo J, Spence M, Cheng AL, Brotto L, Edens NK, Garvey SM, Brotto M. Cellular and physiological effects of dietary supplementation with β‐hydroxy‐β‐methylbutyrate (HMB) and β‐alanine in late middle‐aged mice. PLoS One 2016;11:e0150066. PubMed PMC
Holecek M, Muthny T, Kovarik M, Sispera L. Effect of beta‐hydroxy‐beta‐methylbutyrate (HMB) on protein metabolism in whole body and in selected tissues. Food Chem Toxicol 2009;47:255–259. PubMed
Poortmans JR, Carpentier A, Pereira‐Lancha LO, Lancha A. Protein turnover, amino acid requirements and recommendations for athletes and active populations. Braz J Med Biol Res 2012;45:875–890. PubMed PMC
Bolster DR, Kubica N, Crozier SJ, Williamson DL, Farrell PA, Kimball SR, et al. Immediate response of mammalian target of rapamycin (mTOR)‐mediated signalling following acute resistance exercise in rat skeletal muscle. J Physiol 2003;553:213–220. PubMed PMC
Clarkson PM, Hubal MJ. Exercise‐induced muscle damage in humans. Am J Phys Med Rehabil 2002;81:S52–S69. PubMed
Wolfe RR, Goodenough RD, Wolfe MH, Royle GT, Nadel ER. Isotopic analysis of leucine and urea metabolism in exercising humans. J Appl Physiol Respir Environ Exerc Physiol 1982;52:458–466. PubMed
Knapik J, Meredith C, Jones B, Fielding R, Young V, Evans W. Leucine metabolism during fasting and exercise. J Appl Physiol (1985) 1991;70:43–47. PubMed
Mero A. Leucine supplementation and intensive training. Sports Med 1999;27:347–358. PubMed
Gallagher PM, Carrithers JA, Godard MP, Schulze KE, Trappe SW. Beta‐hydroxy‐beta‐methylbutyrate ingestion, part I: effects on strength and fat free mass. Med Sci Sports Exerc 2000;32:2109–2115. PubMed
Jówko E, Ostaszewski P, Jank M, Sacharuk J, Zieniewicz A, Wilczak J, et al. Creatine and beta‐hydroxy‐beta‐methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight‐training program. Nutrition 2001;17:558–566. PubMed
Gonzalez AM, Stout JR, Jajtner AR, Townsend JR, Wells AJ, Beyer KS, et al. Effects of β‐hydroxy‐β‐methylbutyrate free acid and cold water immersion on post‐exercise markers of muscle damage. Amino Acids 2014;46:1501–1511. PubMed
Lowery RP, Joy JM, Rathmacher JA, Baier SM, Fuller JC, Shelley MC, et al. Interaction of beta‐hydroxy‐beta‐methylbutyrate free acid and adenosine triphosphate on muscle mass, strength, and power in resistance trained individuals. J Strength Cond Res 2016;30:1843–1854. PubMed
Portal S, Zadik Z, Rabinowitz J, Pilz‐Burstein R, Adler‐Portal D, Meckel Y, et al. The effect of HMB supplementation on body composition, fitness, hormonal and inflammatory mediators in elite adolescent volleyball players: a prospective randomized, double‐blind, placebo‐controlled study. Eur J Appl Physiol 2011;111:2261–2269. PubMed
Kraemer WJ, Hatfield DL, Volek JS, Fragala MS, Vingren JL, Anderson JM, et al. Effects of amino acids supplement on physiological adaptations to resistance training. Med Sci Sports Exerc 2009;41:1111–1121. PubMed
van Someren KA, Edwards AJ, Howatson G. Supplementation with beta‐hydroxy‐beta‐methylbutyrate (HMB) and alpha‐ketoisocaproic acid (KIC) reduces signs and symptoms of exercise‐induced muscle damage in man. Int J Sport Nutr Exerc Metab 2005;15:413–424. PubMed
Knitter AE, Panton L, Rathmacher JA, Petersen A, Sharp R. Effects of beta‐hydroxy‐beta‐methylbutyrate on muscle damage after a prolonged run. J Appl Physiol 2000;89:1340–1344. PubMed
Vukovich MD, Dreifort GD. Effect of beta‐hydroxy beta‐methylbutyrate on the onset of blood lactate accumulation and V(O)(2) peak in endurance‐trained cyclists. J Strength Cond Res 2001;15:491–497. PubMed
Robinson EH, Stout JR, Miramonti AA, Fukuda DH, Wang R, Townsend JR, et al. High‐intensity interval training and β‐hydroxy‐β‐methylbutyric free acid improves aerobic power and metabolic thresholds. J Int Soc Sports Nutr 2014;1:16. PubMed PMC
Lamboley CR, Royer D, Dionne IJ. Effects of beta‐hydroxy‐beta‐methylbutyrate on aerobic‐performance components and body composition in college students. Int J Sport Nutr Exerc Metab 2007;17:56–69. PubMed
Durkalec‐Michalski K, Jeszka J. The efficacy of a β‐hydroxy‐β‐methylbutyrate supplementation on physical capacity, body composition and biochemical markers in elite rowers: a randomised, double‐blind, placebo‐controlled crossover study. J Int Soc Sports Nutr 2015;12:31. PubMed PMC
Durkalec‐Michalski K, Jeszka J. The effect of β‐hydroxy‐β‐methylbutyrate on aerobic capacity and body composition in trained athletes. J Strength Cond Res 2016;30:2617–2626. PubMed
Panton LB, Rathmacher JA, Baier S, Nissen S. Nutritional supplementation of the leucine metabolite beta‐hydroxy‐beta‐methylbutyrate (hmb) during resistance training. Nutrition 2000;16:734–739. PubMed
Wilson JM, Lowery RP, Joy JM, Andersen JC, Wilson SM, Stout JR, et al. The effects of 12 weeks of beta‐hydroxy‐beta‐methylbutyrate free acid supplementation on muscle mass, strength, and power in resistance‐trained individuals: a randomized, double‐blind, placebo‐controlled study. Eur J Appl Physiol 2014;114:1217–1227. PubMed PMC
Wilson JM, Lowery RP, Joy JM, Walters JA, Baier SM, Fuller JC, et al. β‐Hydroxy‐β‐methylbutyrate free acid reduces markers of exercise‐induced muscle damage and improves recovery in resistance‐trained men. Br J Nutr 2013;110:538–544. PubMed
Miramonti AA, Stout JR, Fukuda DH, Robinson EH, Wang R, La Monica MB, et al. Effects of 4 weeks of high‐intensity interval training and β‐hydroxy‐β‐methylbutyric free acid supplementation on the onset of neuromuscular fatigue. J Strength Cond Res 2016;30:626–634. PubMed
Nissen SL, Sharp RL. Effect of dietary supplements on lean mass and strength gains with resistance exercise: a meta‐analysis. J Appl Physiol (1985) 2003;94:651–659. PubMed
Paddon‐Jones D, Keech A, Jenkins D. Short‐term beta‐hydroxy‐beta‐methylbutyrate supplementation does not reduce symptoms of eccentric muscle damage. Int J Sport Nutr Exerc Metab 2001;11:442–450. PubMed
Kreider RB, Ferreira M, Wilson M, Almada AL. Effects of calcium beta‐hydroxy‐beta‐methylbutyrate (HMB) supplementation during resistance‐training on markers of catabolism, body composition and strength. Int J Sports Med 1999;20:503–509. PubMed
O'Connor DM, Crowe MJ. Effects of beta‐hydroxy‐beta‐methylbutyrate and creatine monohydrate supplementation on the aerobic and anaerobic capacity of highly trained athletes. J Sports Med Phys Fitness 2003;43:64–68. PubMed
O'Connor DM, Crowe MJ. Effects of six weeks of beta‐hydroxy‐beta‐methylbutyrate (HMB) and HMB/creatine supplementation on strength, power, and anthropometry of highly trained athletes. J Strength Cond Res 2007;21:419–423. PubMed
Slater G, Jenkins D, Logan P, Lee H, Vukovich M, Rathmacher JA, et al. Beta‐hydroxy‐betamethylbutyrate (HMB) supplementation does not affect changes in strength or body composition during resistance training in trained men. Int J Sport Nutr Exerc Metab 2001;11:384–396. PubMed
Ransone J, Neighbors K, Lefavi R, Chromiak J. The effect of beta‐hydroxy beta‐methylbutyrate on muscular strength and body composition in collegiate football players. J Strength Cond Res 2003;17:34–39. PubMed
Thomson JS, Watson PE, Rowlands DS. Effects of nine weeks of beta‐hydroxy‐beta‐methylbutyrate supplementation on strength and body composition in resistance trained men. J Strength Cond Res 2009;23:827–835. PubMed
Hoffman JR, Cooper J, Wendell M, Im J, Kang J. Effects of beta‐hydroxy beta‐methylbutyrate on power performance and indices of muscle damage and stress during high‐intensity training. J Strength Cond Res 2004;18:747–752. PubMed
Nunan D, Howatson G, van Someren KA. Exercise‐induced muscle damage is not attenuated by beta‐hydroxy‐beta‐methylbutyrate and alpha‐ketoisocaproic acid supplementation. J Strength Cond Res 2010;24:531–537. PubMed
Albert FJ, Morente‐Sánchez J, Ortega FB, Castillo MJ, Gutiérrez Á. Usefulness of β‐hydroxy‐β‐methylbutyrate (HMB) supplementation in different sports: an update and practical implications. Nutr Hosp 2015;32:20–33. PubMed
Pasiakos SM, Carbone JW. Assessment of skeletal muscle proteolysis and the regulatory response to nutrition and exercise. IUBMB Life 2014;66:478–484. PubMed
Rowlands DS, Thomson JS. Effects of beta‐hydroxy‐beta‐methylbutyrate supplementation during resistance training on strength, body composition, and muscle damage in trained and untrained young men: a meta‐analysis. J Strength Cond Res 2009;23:836–846. PubMed
Wilson JM, Fitschen PJ, Campbell B, Wilson GJ, Zanchi N, Taylor L, et al. International society of sports nutrition position stand: beta‐hydroxy‐beta‐methylbutyrate (HMB). J Int Soc Sports Nutr 2013;10:6. PubMed PMC
Morley JE, Anker SD, von Haehling S. Prevalence, incidence, and clinical impact of sarcopenia: facts, numbers, and epidemiology‐update 2014. J Cachexia Sarcopenia Muscle 2014;5:253–259. PubMed PMC
Russ DW, Acksel C, Boyd IM, Maynard J, McCorkle KW, Edens NK, et al. Dietary HMB and β‐alanine co‐supplementation does not improve in situ muscle function in sedentary, aged male rats. Appl Physiol Nutr Metab 2015;40:1294–1301. PubMed
Alway SE, Pereira SL, Edens NK, Hao Y, Bennett BT. beta‐Hydroxy‐beta‐methylbutyrate (HMB) enhances the proliferation of satellite cells in fast muscles of aged rats during recovery from disuse atrophy. Exp Gerontol 2013;48:973–984. PubMed
Baier S, Johannsen D, Abumrad N, Rathmacher JA, Nissen S, Flakoll P. Year‐long changes in protein metabolism in elderly men and women supplemented with a nutrition cocktail of beta‐hydroxy‐beta‐methylbutyrate (HMB), L‐arginine, and L‐lysine. JPEN J Parenter Enteral Nutr 2009;33:71–82. PubMed
Hsieh LC, Chow CJ, Chang WC, Liu TH, Chang CK. Effect of beta‐hydroxy‐beta‐methylbutyrate on protein metabolism in bed‐ridden elderly receiving tube feeding. Asia Pac J Clin Nutr 2010;19:200–208. PubMed
Vukovich MD, Stubbs NB, Bohlken RM. Body composition in 70‐year‐old adults responds to dietary beta‐hydroxy‐beta‐methylbutyrate similarly to that of young adults. J Nutr 2001;131:2049–2052. PubMed
Flakoll P, Sharp R, Baier S, Levenhagen D, Carr C, Nissen S. Effect of beta‐hydroxy‐betamethylbutyrate, arginine, and lysine supplementation on strength, functionality, body composition, and protein metabolism in elderly women. Nutrition 2004;20:445–451. PubMed
Fuller JC, Baier S, Flakoll P, Nissen SL, Abumrad NN, Rathmacher JA. Vitamin D status affects strength gains in older adults supplemented with a combination of β‐hydroxy‐β‐methylbutyrate, arginine, and lysine: a cohort study. JPEN J Parenter Enteral Nutr 2011;35:757–762. PubMed
Williams JZ, Abumrad N, Barbul A. Effect of a specialized amino acid mixture on human collagen deposition. Ann Surg 2002;236:369–374. PubMed PMC
Berton L, Bano G, Carraro S, Veronese N, Pizzato S, Bolzetta F, et al. Effect of oral beta‐hydroxy‐beta‐methylbutyrate (HMB) supplementation on physical performance in healthy old women over 65 years: an open label randomized controlled trial. PLoS One 2015;10:e0141757. PubMed PMC
Deutz NE, Pereira SL, Hays NP, Oliver JS, Edens NK, Evans CM, et al. Effect of beta‐hydroxy beta‐methylbutyrate (HMB) on lean body mass during 10 days of bed rest in older adults. Clin Nutr 2013;32:704–712. PubMed
Stout JR, Smith‐Ryan AE, Fukuda DH, Kendall KL, Moon JR, Hoffman JR, et al. Effect of calcium beta‐hydroxy‐beta‐methylbutyrate (CaHMB) with and without resistance training in men and women 65+yrs: a randomized, double‐blind pilot trial. Exp Gerontol 2013;48:1303–1310. PubMed
Wu H, Xia Y, Jiang J, Du H, Guo X, Liu X, et al. Effect of beta‐hydroxy‐beta‐methylbutyrate supplementation on muscle loss in older adults: a systematic review and meta‐analysis. Arch Gerontol Geriatr 2015;61:168–175. PubMed
Shreeram S, Ramesh S, Puthan JK, Balakrishnan G, Subramanian R, Reddy MT, et al. Age associated decline in the conversion of leucine to β‐hydroxy‐β‐methylbutyrate in rats. Exp Gerontol 2016;80:6–11. PubMed
Kougias DG, Nolan SO, Koss WA, Kim T, Hankosky ER, Gulley JM, et al. Beta‐hydroxy‐beta‐methylbutyrate ameliorates aging effects in the dendritic tree of pyramidal neurons in the medial prefrontal cortex of both male and female rats. Neurobiol Aging 2016;40:78–85. PubMed
Hankosky ER, Sherrill LK, Ruvola LA, Haake RM, Kim T, Hammerslag LR, et al. Effects of β‐hydroxy‐β‐methyl butyrate on working memory and cognitive flexibility in an animal model of aging. Nutr Neurosci 2016; https://doi.org/10.1080/1028415X.2016.1145376. PubMed DOI
Sandri M. Protein breakdown in muscle wasting: role of autophagy‐lysosome and ubiquitin‐proteasome. Int J Biochem Cell Biol 2013;45:2121–2129. PubMed PMC
Kadlcikova J, Holecek M, Safranek R, Tilser I, Kessler BM. Effects of proteasome inhibitors MG132, ZL3VS and AdaAhx3L3VS on protein metabolism in septic rats. Int J Exp Pathol 2004;85:365–371. PubMed PMC
Muthny T, Kovarik M, Sispera L, Tilser I, Holecek M. Protein metabolism in slow‐ and fast‐twitch skeletal muscle during turpentine‐induced inflammation. Int J Exp Pathol 2008;89:64–71. PubMed PMC
Evans WJ. Skeletal muscle loss: cachexia, sarcopenia, and inactivity. Am J Clin Nutr 2010;91:1123S–1127S. PubMed
Holecek M. Leucine metabolism in fasted and tumor necrosis factor‐treated rats. Clin Nutr 1996;15:91–93. PubMed
Holecek M, Sprongl L, Skopec F, Andrýs C, Pecka M. Leucine metabolism in TNF‐alpha‐ and endotoxin‐treated rats: contribution of hepatic tissue. Am J Phys 1997;273:E1052–E1058. PubMed
Holecek M, Sprongl L, Tichý M, Pecka M. Leucine metabolism in rat liver after a bolus injection of endotoxin. Metabolism 1998;47:681–685. PubMed
Eley HL, Russell ST, Baxter JH, Mukerji P, Tisdale MJ. Signaling pathways initiated by beta‐hydroxy‐beta‐methylbutyrate to attenuate the depression of protein synthesis in skeletal muscle in response to cachectic stimuli. Am J Physiol Endocrinol Metab 2007;293:E923–E931. PubMed
Smith HJ, Wyke SM, Tisdale MJ. Mechanism of the attenuation of proteolysis‐inducing factor stimulated protein degradation in muscle by beta‐hydroxy‐beta‐methylbutyrate. Cancer Res 2004;64:8731–8735. PubMed
Mirza KA, Pereira SL, Voss AC, Tisdale MJ. Comparison of the anticatabolic effects of leucine and Ca‐β‐hydroxy‐β‐methylbutyrate in experimental models of cancer cachexia. Nutrition 2014;30:807–813. PubMed
Russell ST, Tisdale MJ. Mechanism of attenuation by beta‐hydroxy‐beta‐methylbutyrate of muscleprotein degradation induced by lipopolysaccharide. Mol Cell Biochem 2009;330:171–179. PubMed
Aversa Z, Alamdari N, Castillero E, Muscaritoli M, Rossi Fanelli F, Hasselgren PO. β‐Hydroxy‐β‐methylbutyrate (HMB) prevents dexamethasone‐induced myotube atrophy. Biochem Biophys Res Commun 2012;423:739–743. PubMed PMC
Mobley CB, Fox CD, Ferguson BS, Amin RH, Dalbo VJ, Baier S, et al. L‐leucine, beta‐hydroxy‐beta‐methylbutyric acid (HMB) and creatine monohydrate prevent myostatin‐induced Akirin‐1/Mighty mRNA down‐regulation and myotube atrophy. J Int Soc Sports Nutr 2014;11:38. PubMed PMC
Girón MD, Vílchez JD, Shreeram S, Salto R, Manzano M, Cabrera E, et al. β‐Hydroxy‐β‐methylbutyrate (HMB) normalizes dexamethasone‐induced autophagy‐lysosomal pathway in skeletal muscle. PLoS One 2015;10:e0117520. PubMed PMC
Aversa Z, Bonetto A, Costelli P, Minero VG, Penna F, Baccino FM, et al. beta‐hydroxy‐betamethylbutyrate (HMB) attenuates muscle and body weight loss in experimental cancer cachexia. Int J Oncol 2011;38:713–720. PubMed
Caperuto EC, Tomatieli RV, Colquhoun A, Seelaender MC, Costa Rosa LF. Beta‐hydoxy‐beta‐methylbutyrate supplementation affects Walker 256 tumor‐bearing rats in a time‐dependent manner. Clin Nutr 2007;26:117–122. PubMed
Nunes EA, Kuczera D, Brito GA, Bonatto SJ, Yamazaki RK, Tanhoffer RA, et al. Beta‐hydroxy‐beta‐methylbutyrate supplementation reduces tumor growth and tumor cell proliferation ex vivo and prevents cachexia in Walker 256 tumor‐bearing rats by modifying nuclear factor‐kappaB expression. Nutr Res 2008;28:487–493. PubMed
Baptista IL, Silva WJ, Artioli GG, Guilherme JP, Leal ML, Aoki MS, et al. Leucine and HMB differentially modulate proteasome system in skeletal muscle under different sarcopenic conditions. PLoS One 2013;8:e76752. PubMed PMC
Payne ET, Yasuda N, Bourgeois JM, Devries MC, Rodriguez MC, Yousuf J, Tarnopolsky MA. Nutritional therapy improves function and complements corticosteroid intervention in mdx mice. Muscle Nerve 2006;33:66–77. PubMed
Noh KK, Chung KW, Choi YJ, Park MH, Jang EJ, Park CH, et al. β‐Hydroxy β‐methylbutyrate improves dexamethasone‐induced muscle atrophy by modulating the muscle degradation pathway in SD rat. PLoS One 2014;9:e102947. PubMed PMC
Park BS, Henning PC, Grant SC, Lee WJ, Lee SR, Arjmandi BH, et al. HMB attenuates muscle loss during sustained energy deficit induced by calorie restriction and endurance exercise. Metabolism 2013;62:1718–1729. PubMed
Clark RH, Feleke G, Din M, Yasmin T, Singh G, Khan FA, et al. Nutritional treatment for acquired immunodeficiency virus‐associated wasting using beta‐hydroxy beta‐methylbutyrate, glutamine, and arginine: a randomized, double‐blind, placebo‐controlled study. JPEN J Parenter Enteral Nutr 2000;24:133–139. PubMed
May PE, Barber A, D'Olimpio JT, Hourihane A, Abumrad NN. Reversal of cancer‐related wasting using oral supplementation with a combination of beta‐hydroxybetamethylbutyrate, arginine, and glutamine. Am J Surg 2002;183:471–479. PubMed
Berk L, James J, Schwartz A, Hug E, Mahadevan A, Samuels M, et al. A randomized, double‐blind, placebo‐controlled trial of a beta‐hydroxyl beta‐methyl butyrate, glutamine, and arginine mixture for the treatment of cancer cachexia (RTOG 0122). Support Care Cancer 2008;16:1179–1188. PubMed
Rathmacher JA, Nissen S, Panton L, Clark RH, Eubanks May P, Barber AE, et al. Supplementation with a combination of beta‐hydroxy‐beta‐methylbutyrate (HMB), arginine, and glutamine is safe and could improve hematological parameters. JPEN J Parenter Enteral Nutr 2004;28:65–75. PubMed
Hsieh LC, Chien SL, Huang MS, Tseng HF, Chang CK. Anti‐inflammatory and anticatabolic effects of short‐term beta‐hydroxy‐beta‐methylbutyrate supplementation on chronic obstructive pulmonary disease patients in intensive care unit. Asia Pac J Clin Nutr 2006;15:544–550. PubMed
Deutz NE, Matheson EM, Matarese LE, Luo M, Baggs GE, Nelson JL, et al. Readmission and mortality in malnourished, older, hospitalized adults treated with a specialized oral nutritional supplement: a randomized clinical trial. Clin Nutr 2016;35:18–26. PubMed
Olveira G, Olveira C, Doña E, Palenque FJ, Porras N, Dorado A, et al. Oral supplement enriched in HMB combined with pulmonary rehabilitation improves body composition and health related quality of life in patients with bronchiectasis (prospective, randomised study). Clin Nutr 2016;35:1015–2102. PubMed
Kuhls DA, Rathmacher JA, Musngi MD, Frisch DA, Nielson J, Barber A, et al. Beta‐hydroxy‐beta‐methylbutyrate supplementation in critically ill trauma patients. J Trauma 2007;62:125–131. PubMed
Nishizaki K, Ikegami H, Tanaka Y, Imai R, Matsumura H. Effects of supplementation with a combination of β‐hydroxy‐β‐methyl butyrate, L‐arginine, and L‐glutamine on postoperative recovery of quadriceps muscle strength after total knee arthroplasty. Asia Pac J Clin Nutr 2015;24:412–420. PubMed
Ekinci O, Yanık S, Terzioğlu Bebitoğlu B, Yılmaz Akyüz E, Dokuyucu A, Erdem Ş. Effect of calcium β‐hydroxy‐β‐methylbutyrate (CaHMB), vitamin D, and protein supplementation on postoperative immobilization in malnourished older adult patients with hip fracture: a randomized controlled study. Nutr Clin Pract 2016;31:829–835. PubMed
Clements RH, Saraf N, Kakade M, Yellumahanthi K, White M, Hackett JA. Nutritional effect of oral supplement enriched in beta‐hydroxy‐beta‐methylbutyrate, glutamine and arginine on resting metabolic rate after laparoscopic gastric bypass. Surg Endosc 2011;25:1376–1382. PubMed PMC
Fitschen PJ, Biruete A, Jeong J, Wilund KR. Efficacy of beta‐hydroxy‐beta‐methylbutyrate supplementation in maintenance hemodialysis patients. Hemodial Int 2016; [Epub ahead of print]. PubMed
Marcora S, Lemmey A, Maddison P. Dietary treatment of rheumatoid cachexia with beta‐hydroxy‐betamethylbutyrate, glutamine and arginine: a randomized controlled trial. Clin Nutr 2005;24:442–454. PubMed
Dasarathy S. Consilience in sarcopenia of cirrhosis. J Cachexia Sarcopenia Muscle 2012;3:225–237. PubMed PMC
Holecek M, Tilser I, Skopec F, Sprongl L. Leucine metabolism in rats with cirrhosis. J Hepatol 1996;24:209–216. PubMed
Holecek M, Kandar R, Sispera L, Kovarik M. Acute hyperammonemia activates branched‐chain amino acid catabolism and decreases their extracellular concentrations: different sensitivity of red and white muscle. Amino Acids 2011;40:575–584. PubMed
Yonamine CY, Teixeira SS, Campello RS, Gerlinger‐Romero F, Rodrigues CF Jr, Guimarães‐Ferreira L, et al. Beta hydroxy beta methylbutyrate supplementation impairs peripheral insulin sensitivity in healthy sedentary Wistar rats. Acta Physiol (Oxf) 2014;212:62–74. PubMed
Holecek M, Siman P, Vodenicarovova M, Kandar R. Alterations in protein and amino acid metabolism in rats fed a branched‐chain amino acid‐ or leucine‐enriched diet during postprandial and postabsorptive states. Nutr Metab (Lond) 2016;13:12. PubMed PMC
Fuller JC, Sharp RL, Angus HF, Baier SM, Rathmacher JA. Free acid gel form of β‐hydroxy‐β‐methylbutyrate (HMB) improves HMB clearance from plasma in human subjects compared with the calcium HMB salt. Br J Nutr 2011;105:367–372. PubMed
Shreeram S, Johns PW, Subramaniam S, Ramesh S, Vaidyanathan V, Puthan JK, et al. The relative bioavailability of the calcium salt of β‐hydroxy‐β‐methylbutyrate is greater than that of the free fatty acid form in rats. J Nutr 2014;144:1549–1555. PubMed
Baxter JH, Carlos JL, Thurmond J, Rehani RN, Bultman J, Frost F. Dietary toxicity of calcium–hydroxy–methylbutyrate (CaHMB). Food Chem Toxicol 2005;43:1731–1741. PubMed
Buchman AL. Glutamine for the gut: mystical properties or an ordinary amino acid? Curr Gastroenterol Rep 1999;1:417–423. PubMed
Holecek M, Sispera L. Glutamine deficiency in extracellular fluid exerts adverse effects on protein and amino acid metabolism in skeletal muscle of healthy, laparotomized, and septic rats. Amino Acids 2014;46:1377–1384. PubMed
von Haehling S, Morley JE, Coats AJS, Anker SD. Ethical guidelines for publishing in the Journal of Cachexia, Sarcopenia and Muscle: update 2015. J Cachexia Sarcopenia Muscle 2015;6:315–316. PubMed PMC
Role of Impaired Glycolysis in Perturbations of Amino Acid Metabolism in Diabetes Mellitus
Side effects of amino acid supplements