How HMB Works
2009Holecek, M., Muthny, T., Kovarik, M., and L. Sispera, 2009 Effect of beta-hydroxy-beta-methylbutyrate (HMB) on protein metabolism in whole body and in selected tissues, Food Chem. Toxicol. 47:255-259 In this study tissue as well as whole body protein turnover was studied in rats after HMB administration. This study demonstrated that HMB inhibits proteosome dependant proteolysis in skeletal muscle and decreases whold body protein turnover.
Kornasio, R., I. Riederer, G. Butler-Browne, V. Mouly, Z. Uni, and O. Halevy, 2009 β-Hydroxy-β-methylbutyrate (HMB) stimulates myogenic cell proliferation, differentiation and survival via the MAPK/ERK and PI3K/Akt pathways, Biochim. Biophys. Acta 1793:755-763
This in vitro study of HMB on muscle cells showed that HMB affects myoblast differentiation and survival similar to IGF-1 and suggests that HMB has a positive role in preventing muscle wasting.
Russell, S.T., and M.J. Tisdale, 2009 Mechanism of attenuation by β-hydroxy-β-methylbutyrate of muscle protein degradation induced by lipopolysaccharide, Mol. Cell. Biochem. 330:171-179
Lipopolysaccharide (LPS) was used to simulate an endotoxemia model of muscle wasting in cultured muscle cells. HMB was shown to attenuate the LPS-induced protein degradation. HMB attenuated the activation of caspase-3/-8, activation of dsRNA-dependant protein kinase, and production of reactive oxygen species. This study further defined the mechanism whereby HMB may attenuate protein degradation in muscle wasting.
Wilson, J.M., J. Kim, S. Lee, J.A. Rathmacher, B. Dalmau, J.D. Kingsley, H. Koch, A.H. Manninen, R. Saadat, and L.B. Panton, 2009 Acute and timing effects of beta-hydroxy-beta-methylbutyrate (HMB) on indirect markers of skeletal muscle damage, Nutrition & Metabolism 6:6
HMB supplementation was given either pre- (60 min to allow blood levels to increase) or post-exercise to college-aged men performing acute isometric exercise by maximal voluntary contraction of the quadriceps and hamstrings. Taking HMB pre-exercise prevented an increase in lactate dehydrogenase (LDH), an indicator of muscle damage. Therefore this study indicated there was an advantage to taking HMB pre-exercise.
2008
Nunes, E.A., Kuczera, D., Brito, G.A., Bonatto, S.J., Yamazaki, R.K., Tanhoffer, R.A., Mund, R.C., Kryczyk, M., and L.C. Fernandes, 2008 β-Hydroxy-β-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. 28:487-493 This 8-week study using a rat tumor model showed that oral HMB attenuated the cachexic weight loss caused by the tumor, resulted in decreased tumor weight, and improved glucose and glycogen metabolism. Therefore, HMB at commonly used dosages maintained healthy tissues while helping inhibit the tumor tissue growth.
Eley, H.L., Russell, S.T., and M.J. Tisdale, 2008 Attenuation of depression of muscle protein synthesis induced by lipopolysaccharide, tumor necrosis factor, and angiotensin II by β-hydroxy-β-methylbutyrate, Am. J. Physiol. Endocrinol. Metab. 295:E1409-E1416
Lipopolysaccharide, tumor nucrosis factor-α and angiotensin II are catabolic in nature and depress protein synthesis. In cultured muscle cells HMB attenuated the decrease in protein synthesis by stimulating factors involved in the mTOR/p70 pathway.
Eley, H.L., Russell, S.T., and M.J. Tisdale, 2008 Mechanism of attenuation of muscle protein degradation induced by tumor necrosis factor-α and angiotensin II by β-hydroxy-β-methylbutyrate., Am. J. Physiol. Endocrinol. Metab. 295:E1417-E1426
The author's first paper detailed HMB effect on maintianing protein synthesis even after administration of lipopolysaccharide, TNF-α and angiotensin II. This second set of experiments in cultured muscle cells showed that HMB attenuated a specific pathway involving caspase 3 and 8, PKR (RNA dependant protein kinase), and reactive oxygen species (ROS) known to activate the ubiquitin-protease pathway. These data provide evidence as to why HMB is effective in maintaining and building muscle mass in a wide range of conditions such as AIDS, cachexia and aging.
2007
Eley, H.L., Russell, S.T., Baxter, J.H., Mukerji, P., and M.J. Tisdale, 2007 Signaling pathways initiated by ß-hydroxy-ß-methylbutyrate to attenuate the depression of protein synthesis in skeletal muscle in response to cachectic stimuli, Am. J. Physiol. Endocrinol. Metab. 293:E923-E931 Protein synthesis studies conducted in a cachectic mouse model and in muscle cell culture.
The results demonstrate that HMB simulates protein synthesis in muscle by multiple mechanisms including the mTOR/p70S6k pathway. Many of these features are also shared with leucine. However, HMB is more potent than leucine in attenuating the development of cachexia and is better tolerated by oral administration.
2005
Smith, H.J., P. Mukerji, and M.J. Tisdale., 2005 Attenuation of proteasome-induced proteolysis in skeletal muscle by ß-hydroxy-ß-methylbutyrate (HMB) in cancer-induced muscle loss, Cancer Res. 65:277-283 Study conducted in a mouse model of cancer tumor growth.
HMB preserves lean body mass and attenuates protein degradation through down regulation of the increased expression of key regulatory components of the ubiquitin-proteasome proteolytic pathway, togetherwith stimulation of protein synthesis.
Van Someren, K.A., A.J. Edwards, and G. Howatson, 2005 Supplementation with ß-hydroxy-ß-methylbutyrate (HMB) and α-Ketoisocaproic Acid (KIC) reduced signs and symptoms of exercise-induced muscle damage in man, Int. J. Sport Nutr. & Exer. Met. 15:413-424 Counterbalanced crossover study in 6 nonresistance trained males given either a placebo or HMB/KIC.
A combination of HMB/KIC, 3 and .3 grams, respectively, was shown to reduce exercise-induced muscle damage.
2004
Smith, H.J., S.M. Wyke, and M.J. Tisdale, 2004 Mechanism of the attenuation of proteolysis-inducing factor stimulated protein degradation in muscle by ß-hydroxy-ß-methylbutyrate, Cancer Res. 64:8731-8735 In vitro study of chemical markers of proteolytic functions in muscle cell cultures.
These studies showed HMB inhibits activation of a major protease pathway in muscle thus inhibiting protein degradation in muscle.
2001
Vukovich, M.D., G. Slater, M.B. Macchi, M.J. Turner, K. Fallon, T. Boston, and J. Rathmacher, 2001 ß-Hydroxy-ß-methylbutyrate (HMB) kinetics and the influence of glucose ingestion in humans, J. Nutr. Biochem. 12:631-639 Randomized trials in which eight males took HMB, HMB plus glucose, glucose alone, or placebo.
These metabolic studies showed that the half-life of HMB in plasma is about 2.5 hours and that up to 85 percent of the HMB ingested is retained in the body. Simultaneous glucose ingestion did not affect the percentage of HMB retained.
2000
Slater, G.J., P.A. Logan, T. Boston, C.J. Gore, A. Stenhouse, and A.G. Hahn, 2000 ß-Hydroxy-ß-methylbutyrate (HMB) supplementation does not influence the urinary testosterone:epitestosterone ratio in healthy males, J. Sci. Med. Sport 3:79-83 Case studies of six males taking HMB.
Results indicated that HMB does not alter testosterone levels and infer that the HMB acts through a different mechanism.
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