1 2 3 4 5 6 7 8 9 10 11 Wilson JM, Fitschen PJ, Campbell B, Wilson GJ, Zanchi N, Taylor L, Wilborn C, Kalman DS, Stout JR, Hoffman JR, Ziegenfuss TN, Lopez HL, Kreider RB, Smith-Ryan AE, Antonio J (tháng 2 năm 2013). “International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB)”. Journal of the International Society of Sports Nutrition 10 (1): 6. PMC3568064. PMID23374455. doi:10.1186/1550-2783-10-6. The [International Society of Sports Nutrition] has concluded the following. 1. HMB can be used to enhance recovery by attenuating exercise induced skeletal muscle damage in trained and untrained populations. ... 4. Thirty-eight mg·kg·BM−1 daily of HMB has been demonstrated to enhance skeletal muscle hypertrophy, strength, and power in untrained and trained populations when the appropriate exercise prescription is utilized. ... 8. HMB’s mechanisms of action include an inhibition and increase of proteolysis and protein synthesis, respectively. 9. Chronic consumption of HMB is safe in both young and old populations.
“Product Information: Juven” (PDF). Abbott Nutrition. 7 tháng 5 năm 2016. Bản gốc lưu trữ (PDF) ngày 12 tháng 10 năm 2016. Truy cập ngày 22 tháng 8 năm 2016. • Administer orally or as a modular via feeding tube ... • Use under medical supervision. • Nutravigor® (CaHMB, calcium β-hydroxy-β-methylbutyrate)
↑ Zanchi NE, Gerlinger-Romero F, Guimarães-Ferreira L, de Siqueira Filho MA, Felitti V, Lira FS, Seelaender M, Lancha AH (tháng 4 năm 2011). “HMB supplementation: clinical and athletic performance-related effects and mechanisms of action”. Amino Acids 40 (4): 1015–1025. PMID20607321. doi:10.1007/s00726-010-0678-0. HMB is a metabolite of the amino acid leucine (Van Koverin and Nissen 1992), an essential amino acid. The first step in HMB metabolism is the reversible transamination of leucine to [α-KIC] that occurs mainly extrahepatically (Block and Buse 1990). Following this enzymatic reaction, [α-KIC] may follow one of two pathways. In the first, HMB is produced from [α-KIC] by the cytosolic enzyme KIC dioxygenase (Sabourin and Bieber 1983). The cytosolic dioxygenase has been characterized extensively and differs from the mitochondrial form in that the dioxygenase enzyme is a cytosolic enzyme, whereas the dehydrogenase enzyme is found exclusively in the mitochondrion (Sabourin and Bieber 1981, 1983). Importantly, this route of HMB formation is direct and completely dependent of liver KIC dioxygenase. Following this pathway, HMB in the cytosol is first converted to cytosolic β-hydroxy-β-methylglutaryl-CoA (HMG-CoA), which can then be directed for cholesterol synthesis (Rudney 1957) (Fig. 1). In fact, numerous biochemical studies have shown that HMB is a precursor of cholesterol (Zabin and Bloch 1951; Nissen et al. 2000).
↑ Coffman DD, Cramer R, Mochel WE (tháng 6 năm 1958). “Syntheses by Free-radical Reactions. V. A New Synthesis of Carboxylic Acids”. Journal of the American Chemical Society 80 (11): 2882–2887. doi:10.1021/ja01544a072.
↑ “3-OH-isovaleric acid”. ChemSpider. Royal Society of Chemistry. 2015. Bản gốc lưu trữ ngày 11 tháng 8 năm 2016. Truy cập ngày 10 tháng 8 năm 2016. Experimental Boiling Point: ... 128 °C / 7 mm ... Experimental solubility: hòa tan trong nước
↑ “beta-Hydroxyisovaleric acid”. PubChem Compound. United States National Library of Medicine – National Center for Biotechnology Information. 3 tháng 2 năm 2018. Bản gốc lưu trữ ngày 6 tháng 2 năm 2018. Truy cập ngày 6 tháng 2 năm 2018. Chemical Names: Beta-Hydroxyisovaleric acid; 3-Hydroxy-3-methylbutanoic acid; ... 3-Hydroxyisovaleric acid; 3-Hydroxy-3-methylbutyric acid
1 2 3 4 5 6 Linn J (13 tháng 5 năm 2013). “Proteins in Human Health and Performance”. Iowa State University. Bản gốc lưu trữ ngày 27 tháng 8 năm 2016. Truy cập ngày 31 tháng 7 năm 2016. Dr. Nissen and his collaborator Dr. Naji N. Abumrad, Professor and Chair, Department of Surgery, Vanderbilt University, discovered beta-hydroxy-beta-methylbutyrate (HMB) and its beneficial effects on human health and performance. HMB is currently marketed nationally by Abbott Laboratories as Revigor™, which is a component of Ensure® Muscle Health, and Juven®, which is a nutritional beverage that is clinically shown to promote healing after injury or surgery.
1 2 3 Khamsi R (tháng 5 năm 2013). “Rethinking the formula”. Nature Medicine 19 (5): 525–529. PMID23652097. doi:10.1038/nm0513-525. Bản gốc lưu trữ ngày 2 tháng 2 năm 2016. The questions about what defines a medical food will likely grow as the market does—and that market now extends far beyond PKU and other inherited metabolic disorders. ... Abbott Nutrition's Juven provides nutrients to people with HIV or AIDS experiencing excessive weight loss due to disease
1 2 3 4 5 Momaya A, Fawal M, Estes R (tháng 4 năm 2015). “Performance-enhancing substances in sports: a review of the literature”. Sports Medicine 45 (4): 517–531. PMID25663250. doi:10.1007/s40279-015-0308-9. Currently, HMB is available as an over-the-counter supplement. The drug is not tested for nor banned by any sporting organization. ... Wilson et al. [91] demonstrated that when non-resistance trained males received HMB pre-exercise, the rise of lactate dehydrogenase (LDH) levels reduced, and HMB tended to decrease soreness. Knitter et al. [92] showed a decrease in LDH and creatine phosphokinase (CPK), a byproduct of muscle breakdown, by HMB after a prolonged run. ... The utility of HMB does seem to be affected by timing of intake prior to workouts and dosage [97]. Further, chronic consumption of HMB appears safe [97]. ... No serious adverse effects from HMB consumption have been reported.
1 2 3 Fuller JC, Sharp RL, Angus HF, Khoo PY, Rathmacher JA (tháng 11 năm 2015). “Comparison of availability and plasma clearance rates of β-hydroxy-β-methylbutyrate delivery in the free acid and calcium salt forms”. primary source. The British Journal of Nutrition 114 (9): 1403–1409. PMID26373270. doi:10.1017/S0007114515003050. Recently, the free acid form of HMB (HMB-FA) has become commercially available in capsule form (gelcap). The current study was conducted to compare the bioavailability of HMB using the two commercially available capsule forms of HMB-FA and Ca-HMB. ... In conclusion, HMB-FA in capsule form improves clearance rate and availability of HMB compared with Ca-HMB in capsule form.
1 2 3 4 5 6 7 8 9 Wu H, Xia Y, Jiang J, Du H, Guo X, Liu X, Li C, Huang G, Niu K (tháng 9 năm 2015). “Effect of beta-hydroxy-beta-methylbutyrate supplementation on muscle loss in older adults: a systematic review and meta-analysis”. Archives of Gerontology and Geriatrics 61 (2): 168–175. PMID26169182. doi:10.1016/j.archger.2015.06.020. Overall, this meta-analysis indicates that HMB can prevent lean body mass loss in older adults. But the effects of HMB on muscle strength and physical function appears to vary in different populations. Additional well-designed clinical studies are necessary to confirm the effectiveness of HMB in the prevention of loss of muscle strength and physical function. ... Mechanisms underlying the role of HMB in muscle regeneration have also been explored: results indicated that HMB enhances protein synthesis via upregulation of anabolic signaling pathways and attenuate proteolysis via downregulation of catabolic signaling pathways (Wilkinson et al., 2013).
1 2 3 Holeček M (tháng 8 năm 2017). “Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions”. Journal of Cachexia, Sarcopenia and Muscle 8 (4): 529–541. PMC5566641. PMID28493406. doi:10.1002/jcsm.12208. Bản gốc lưu trữ ngày 30 tháng 8 năm 2017. The reports summarized here indicate that HMB provides a number of benefits to subjects involved in strength-power and endurance sports. The effects on muscle mass and strength, particularly during resistance training, are likely related to the suppression of proteolysis and a positive effect on protein synthesis. Its benefits in aerobic performance are probably more associated with improved mitochondrial biogenesis and fat oxidation. Favourable effects on the recovery from exercise-induced damage may be related to the role of HMB as a precursor of cholesterol, which modulates membrane fluidity and affects ion channels, and membrane excitability. ... Studies have demonstrated that HMB can prevent the development of sarcopenia in elderly subjects and that the optimal action of HMB on muscle growth and strength occurs when it is combined with exercise.
1 2 Silva VR, Belozo FL, Micheletti TO, Conrado M, Stout JR, Pimentel GD, Gonzalez AM (tháng 9 năm 2017). “β-hydroxy-β-methylbutyrate free acid supplementation may improve recovery and muscle adaptations after resistance training: a systematic review”. Nutrition Research 45: 1–9. PMID29037326. doi:10.1016/j.nutres.2017.07.008. HMB's mechanisms of action are generally considered to relate to its effect on both muscle protein synthesis and muscle protein breakdown (Figure 1) [2, 3]. HMB appears to stimulate muscle protein synthesis through an up-regulation of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), a signaling cascade involved in coordination of translation initiation of muscle protein synthesis [2, 4]. Additionally, HMB may have antagonistic effects on the ubiquitin–proteasome pathway, a system that degrades intracellular proteins [5, 6]. Evidence also suggests that HMB promotes myogenic proliferation, differentiation, and cell fusion [7]. ... Exogenous HMB-FA administration has shown to increase intramuscular anabolic signaling, stimulate muscle protein synthesis, and attenuate muscle protein breakdown in humans [2].
↑ Luckose F, Pandey MC, Radhakrishna K (2015). “Effects of amino acid derivatives on physical, mental, and physiological activities”. Critical Reviews in Food Science and Nutrition 55 (13): 1793–1807. PMID24279396. doi:10.1080/10408398.2012.708368. HMB, a derivative of leucine, prevents muscle damage and increases muscle strength by reducing exercise-induced proteolysis in muscles and also helps in increasing lean body mass. ... HMB is converted to HMB-CoA which is then used for the synthesis of cholesterol in muscle cells (Nissen and Abumrad, 1997). Cholesterol is needed for the growth, repair, and stabilization of cellular membranes during exercise (Chen, 1984). ... The meta analysis studies and the individual studies conducted support the use of HMB as an effective aid to increase body strength, body composition, and to prevent muscle damage during resistance training.
↑ Rossi AP, D'Introno A, Rubele S, Caliari C, Gattazzo S, Zoico E, Mazzali G, Fantin F, Zamboni M (tháng 10 năm 2017). “The Potential of β-Hydroxy-β-Methylbutyrate as a New Strategy for the Management of Sarcopenia and Sarcopenic Obesity”. Drugs & Aging 34 (11): 833–840. PMID29086232. doi:10.1007/s40266-017-0496-0. Clinical trials performed in older adults confirm that HMB can attenuate the progression of sarcopenia in elderly subjects. HMB supplementation results in an increase in skeletal muscle mass and strength in the elderly and its effect is even greater when combined with physical exercise.
↑ Wilkinson DJ, Hossain T, Hill DS, Phillips BE, Crossland H, Williams J, Loughna P, Churchward-Venne TA, Breen L, Phillips SM, Etheridge T, Rathmacher JA, Smith K, Szewczyk NJ, Atherton PJ (tháng 6 năm 2013). “Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism”. The Journal of Physiology 591 (11): 2911–2923. PMC3690694. PMID23551944. doi:10.1113/jphysiol.2013.253203. The stimulation of MPS through mTORc1-signalling following HMB exposure is in agreement with pre-clinical studies (Eley et al. 2008). ... Furthermore, there was clear divergence in the amplitude of phosphorylation for 4EBP1 (at Thr37/46 and Ser65/Thr70) and p70S6K (Thr389) in response to both Leu and HMB, with the latter showing more pronounced and sustained phosphorylation. ... Nonetheless, as the overall MPS response was similar, this cellular signalling distinction did not translate into statistically distinguishable anabolic effects in our primary outcome measure of MPS. ... Interestingly, although orally supplied HMB produced no increase in plasma insulin, it caused a depression in MPB (−57%). Normally, postprandial decreases in MPB (of ~50%) are attributed to the nitrogen-sparing effects of insulin since clamping insulin at post-absorptive concentrations (5 μU ml−1) while continuously infusing AAs (18 g h−1) did not suppress MPB (Greenhaff et al. 2008), which is why we chose not to measure MPB in the Leu group, due to an anticipated hyperinsulinaemia (Fig. 3C). Thus, HMB reduces MPB in a fashion similar to, but independent of, insulin. These findings are in-line with reports of the anti-catabolic effects of HMB suppressing MPB in pre-clinical models, via attenuating proteasomal-mediated proteolysis in response to LPS (Eley et al. 2008).
1 2 3 4 5 6 7 8 Brioche T, Pagano AF, Py G, Chopard A (tháng 8 năm 2016). “Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention”. Molecular Aspects of Medicine 50: 56–87. PMID27106402. doi:10.1016/j.mam.2016.04.006. In conclusion, HMB treatment clearly appears to be a safe potent strategy against sarcopenia, and more generally against muscle wasting, because HMB improves muscle mass, muscle strength, and physical performance. It seems that HMB is able to act on three of the four major mechanisms involved in muscle deconditioning (protein turnover, apoptosis, and the regenerative process), whereas it is hypothesized to strongly affect the fourth (mitochondrial dynamics and functions). Moreover, HMB is inexpensive (~30– 50 US dollars per month at 3 g per day) and may prevent osteopenia (Bruckbauer and Zemel, 2013; Tatara, 2009; Tatara et al., 2007, 2008, 2012) and decrease cardiovascular risks (Nissen et al., 2000). For all these reasons, HMB should be routinely used in muscle-wasting conditions especially in aged people. ... 3 g of CaHMB taken three times a day (1 g each time) is the optimal posology, which allows for continual bioavailability of HMB in the body (Wilson et al., 2013)
1 2 3 4 Molfino A, Gioia G, Rossi Fanelli F, Muscaritoli M (tháng 12 năm 2013). “Beta-hydroxy-beta-methylbutyrate supplementation in health and disease: a systematic review of randomized trials”. Amino Acids 45 (6): 1273–1292. PMID24057808. doi:10.1007/s00726-013-1592-z. Normally, an individual metabolizes 60 g of L-LEU to obtain 3 g of HMB but a 70 kg person produces 0.2–0.4 g of HMB per day, depending on the dose of LEU in the diet (Van Koevering and Nissen 1992). ... The usual dose of 3 g/day may be routinely recommended to maintain or improve muscle mass and function in health and disease. The safety profile of HMB is unequivocal. ... These results show that HMB/ARG/GLN can be safely used to treat AIDS- and cancer-related muscle wasting
↑ Borack MS, Volpi E (tháng 12 năm 2016). “Efficacy and Safety of Leucine Supplementation in the Elderly”. The Journal of Nutrition 146 (12): 2625S–2629S. PMC5118760. PMID27934654. doi:10.3945/jn.116.230771. One study tested the safety of HMB for long-term use in rats. Fuller et al. (50) conducted a 91-d study with the use of Sprague-Dawley rats that tested the safety of β-hydroxy-β-methylbutyric free acid (HMBFA). This new form of HMB results in higher HMB serum concentrations than CaHMB. In this study, rats were administered an HMBFA intervention of 0%, 0.8%, 1.6%, or 4% of the diet by body weight. The highest dose is the equivalent of ~400 mg ⋅ kg−1 ⋅ d−1 for humans. No adverse advents were observed for any treatment group. Similarly, blood and urine analyses were within the normal range in all groups, with no group differences. The authors concluded that HMBFA was safe for consumption in a rat model. ... No serious side effects have been reported with leucine, EAA, or HMB supplementation; and the health risks associated with these supplements are few and predictable.
↑ Ehling S, Reddy TM (tháng 9 năm 2015). “Direct Analysis of Leucine and Its Metabolites β-Hydroxy-β-methylbutyric Acid, α-Ketoisocaproic Acid, and α-Hydroxyisocaproic Acid in Human Breast Milk by Liquid Chromatography-Mass Spectrometry”. primary source. Journal of Agricultural and Food Chemistry 63 (34): 7567–7573. PMID26271627. doi:10.1021/acs.jafc.5b02563.
1 2 3 4 5 6 Argilés JM, Campos N, Lopez-Pedrosa JM, Rueda R, Rodriguez-Mañas L (tháng 9 năm 2016). “Skeletal Muscle Regulates Metabolism via Interorgan Crosstalk: Roles in Health and Disease”. Journal of the American Medical Directors Association 17 (9): 789–796. PMID27324808. doi:10.1016/j.jamda.2016.04.019. Studies suggest dietary protein and leucine or its metabolite β-hydroxy β-methylbutyrate (HMB) can improve muscle function, in turn improving functional performance. ... These have identified the leucine metabolite β-hydroxy β-methylbutyrate (HMB) as a potent stimulator of protein synthesis as well as an inhibitor of protein breakdown in the extreme case of cachexia. ... A growing body of evidence suggests HMB may help slow, or even reverse, the muscle loss experienced in sarcopenia and improve measures of muscle strength. ... However, dietary leucine does not provide a large amount of HMB: only a small portion, as little as 5%, of catabolized leucine is metabolized into HMB. ... Thus, although dietary leucine itself can lead to a modest stimulation of protein synthesis by producing a small amount of HMB, direct ingestion of HMB more potently affects such signaling, resulting in demonstrable muscle mass accretion. ... Indeed, a vast number of studies have found that supplementation of HMB to the diet may reverse some of the muscle loss seen in sarcopenia and in hypercatabolic disease. ... The overall treatment of muscle atrophy should include dietary supplementation with HMB, although the optimal dosage for each condition is still under investigation. ... Figure 4: Treatments for sarcopenia. It is currently recommended that patients at risk of or suffering from sarcopenia consume a diet high in protein, engage in resistance exercise, and take supplements of the leucine metabolite HMB.
1 2 Landi F, Calvani R, Tosato M, Martone AM, Ortolani E, Savera G, D'Angelo E, Sisto A, Marzetti E (tháng 5 năm 2016). “Protein Intake and Muscle Health in Old Age: From Biological Plausibility to Clinical Evidence”. Nutrients 8 (5): 295. PMC4882708. PMID27187465. doi:10.3390/nu8050295. HMB is an active leucine metabolite which activates the mTOR signaling pathway in muscle. Following its absorption, dietary leucine is converted into α-ketoisocaproate (KIC), which is further metabolized into either isovaleryl-CoA or HMB. Under normal conditions, the majority of KIC is converted into isovaleryl-CoA, while only approximately 5% of leucine is metabolized to HMB. This implies that, in order to reach pharmacological levels of HMB, this compound needs to be administered directly, rather than via increasing leucine dosage. ... HMB exerts its effects through protective, anticatabolic mechanisms and directly influences protein synthesis. HMB has also been shown to stabilize the muscle cell membrane, to modulate protein degradation and to up-regulate protein synthesis [68].
1 2 Szcześniak KA, Ostaszewski P, Fuller JC, Ciecierska A, Sadkowski T (tháng 6 năm 2015). “Dietary supplementation of β-hydroxy-β-methylbutyrate in animals – a review”. Journal of Animal Physiology and Animal Nutrition 99 (3): 405–417. PMID25099672. doi:10.1111/jpn.12234. Cholesterol is a major component of the cell membrane, and sarcolemma is the one that relies mainly on de novo synthesis of cholesterol. This is important under stressful conditions when muscle cells may lack the capacity to produce adequate amounts of the cholesterol that is essential to proper functioning of cell membranes. Many biochemical studies have shown that HMB may be a precursor of cholesterol synthesis (Bachhawat et al., 1955; Bloch et al., 1954; Coon et al., 1955; Adamson and Greenberg, 1955; Gey et al., 1957). According to pertinent literature, HMB carbon is incorporated into cholesterol. Therefore, increased intramuscular HMB concentrations may provide readily available substrate for the cholesterol synthesis that is needed to form and stabilize the sarcolemma. ... It is known that HMB supplementation decreases post-exercise levels of enzymes, indicating muscle damage, such as creatinine phosphokinase (CK) and lactate dehydrogenase (LDH), which suggests an enhancement of the muscle cell membrane function. This was shown in numerous studies in humans undergoing both resistance and endurance training (Wilson et al., 2013) ... In theory, HMB use as a precursor to cholesterol could aid in stabilizing muscle cell membranes; however, this has not been confirmed by research studies. The effect of HMB on protein metabolism may in fact help stabilize muscle structure more than any effect HMB may have on cholesterol metabolism in the cell.
↑ “2017–18 NCAA Banned Drugs” (PDF). National Collegiate Athletic Association. Bản gốc lưu trữ (PDF) ngày 17 tháng 12 năm 2017. Truy cập ngày 17 tháng 12 năm 2017.
1 2 Cruz-Jentoft AJ (tháng 5 năm 2017). “Beta-hydroxy-beta-methyl butyrate (HMB): From experimental data to clinical evidence in sarcopenia”. Current Protein & Peptide Science 18 (7): 668–672. PMID28554316. doi:10.2174/1389203718666170529105026. HMB is widely used as an ergogenic supplement by young athletes. ... This study shows that in healthy older adult, HMB supplementation may preserve muscle mass during 10 days of bed rest. These results are encouraging, but need to be confirmed by other groups.
↑ Mullin GE (tháng 2 năm 2014). “Nutrition supplements for athletes: potential application to malnutrition”. Nutrition in Clinical Practice 29 (1): 146–147. PMID24336486. doi:10.1177/0884533613516130. There are a number of nutrition products on the market that are touted to improve sports performance. HMB appears to be the most promising and to have clinical applications to improve muscle mass and function. Continued research using this nutraceutical to prevent and/or improve malnutrition in the setting of muscle wasting is warranted.
1 2 Mochamat, Cuhls H, Marinova M, Kaasa S, Stieber C, Conrad R, Radbruch L, Mücke M (tháng 7 năm 2016). “A systematic review on the role of vitamins, minerals, proteins, and other supplements for the treatment of cachexia in cancer: a European Palliative Care Research Centre cachexia project”. Journal of Cachexia, Sarcopenia and Muscle 8 (1): 25–39. PMC5326814. PMID27897391. doi:10.1002/jcsm.12127. Looking at studies with proteins and other dietary supplements the combination of HMB, arginine, and glutamine showed interesting results ... In one study, 32 patients gained an average of about 2 kg of body weight.[21] This study was one of three studies confirming the positive effects of this combination in a variety of diagnoses/conditions such as HIV/AIDS patients and healthy adults.[40] Another study, on a far larger sample base of around 470 cancer patients, found no significant difference with regard to LBM after 8 weeks however a strong trend in the direction of an increase in LBM as measured by both bio-impedance and skin-fold measurements.[22] In summary, the effect of the combination of HMB, arginine, and glutamine on weight gain should be investigated in further studies on cancer patients investigating time periods of several months.
↑ Rahman A, Wilund K, Fitschen PJ, Jeejeebhoy K, Agarwala R, Drover JW, Mourtzakis M (tháng 7 năm 2014). “Elderly persons with ICU-acquired weakness: the potential role for β-hydroxy-β-methylbutyrate (HMB) supplementation?”. JPEN. Journal of Parenteral and Enteral Nutrition 38 (5): 567–575. PMID24072740. doi:10.1177/0148607113502545. More than 20 publications in humans have demonstrated benefit with HMB supplementation associated with increased lean body mass without fat gain, improved markers of muscle strength, and decreased onset of muscle soreness with training and reduced markers of muscle damage. ... One proposed cellular mechanism for HMB is principally through stabilization of the cholesterol membrane in muscle cells. HMB is metabolized to β-hydroxy-β-methylglutaryl-coenzyme A (HMG-CoA) in the cytosol of muscle cells, which in turn is converted to cholesterol. ... Muscle produces its own cholesterol to maintain the integrity of the cell membrane, typically from HMG-CoA, because it cannot supply its cholesterol needs via absorption from the circulation.
