Refereed Papers
2007Lamboley, C.R., D. Royer, and I.J. Dionne, 2007 Effects of ß-hydroxy-ß-methylbutyrate (HMB) on aerobic performance components and body composition in college students, Int. J. Sport Nutr. Exerc. Metab. 17:56-69 Placebo-controlled study in college students.
HMB supplementation significantly increased maximal oxygen consumption.
HMB supplementation significantly increased maximal oxygen consumption.
view abstract2001Vukovich, M.D. and G.D. Dreifort, 2001 The effect of ß-hydroxy-ß-methylbutyrate (HMB) on VO2 peak and lactate threshold in endurance-trained cyclists, J. Strength and Conditioning Res. 15:491-497 Double-blind switchback study with HMB, leucine, and placebo.
This study showed that HMB supplementation increased the cyclists endurance as measured by VO2 peak and lactate threshold.
This study showed that HMB supplementation increased the cyclists endurance as measured by VO2 peak and lactate threshold.
2000Knitter, A., L. Panton, J.A. Rathmacher, A. Peterson and R. Sharp, 2000 Effects of ß-hydroxy-ß-methylbutyrate (HMB) on muscle damage after a prolonged run, J. Appl. Physiol. 89:1340-1344 This double-blind randomized study in male and female runners showed that HMB reduced muscle damage after a prolonged run. Decreasing the amount of muscle damage caused by running may decrease the DOMS soreness many long-distance runners experience.
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.
2008Nunes, 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.
2007Eley, 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.
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.
2005Smith, 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.
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.
A combination of HMB/KIC, 3 and .3 grams, respectively, was shown to reduce exercise-induced muscle damage.
2004Smith, 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.
These studies showed HMB inhibits activation of a major protease pathway in muscle thus inhibiting protein degradation in muscle.
2001Vukovich, 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.
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.
2000Slater, 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.
Results indicated that HMB does not alter testosterone levels and infer that the HMB acts through a different mechanism.
2005Baxter, J.H., J.L. Carlos, J. Thurmond, R.N. Rehani, J. Bultman, and D. Frost, 2005 Dietary toxicity of calcium ß-hydroxy-ß-methylbutyrate (CaHMB), Food & Chem. Toxicology 43:1731-1741 Toxicity study conducted in rats fed up to five percent HMB in the diet.
The data showed that HMB at five percent of the diet can be considered the NOAEL (no observed adverse effect level). This amounted to ~3.5 and ~4.1 g/kg body weight intake per day in male and female rats, respectively. (Like a normal human consuming about 300 g per day.)
The data showed that HMB at five percent of the diet can be considered the NOAEL (no observed adverse effect level). This amounted to ~3.5 and ~4.1 g/kg body weight intake per day in male and female rats, respectively. (Like a normal human consuming about 300 g per day.)
2000Nissen, S., R.L. Sharp, L. Panton, M. Vukovich, S. Trappe, and J.C. Fuller, Jr., 2000 ß-Hydroxy-ß-methylbutyrate (HMB) supplementation in humans is safe and may decrease cardiovascular risk factors, J. Nutr. 130:1937-1945 A summary of safety data from nine double-blind randomized clinical trials including both men and women and young and elderly adults.
HMB supplementation was shown to have no adverse or untoward effects. This summary also shows that HMB supplementation has positive effects on LDL cholesterol (-7.3 percent) and systolic blood pressure (-4.4 mm Hg).
HMB supplementation was shown to have no adverse or untoward effects. This summary also shows that HMB supplementation has positive effects on LDL cholesterol (-7.3 percent) and systolic blood pressure (-4.4 mm Hg).
Gallagher, P.M., J.A. Carrithers, M.P. Godard, K.E. Schulze, and S.W. Trappe, 2000 ß-Hydroxy-ß-methylbutyrate (HMB) ingestion, Part II: effects on hematology, hepatic and renal function, Med. & Sci. in Sports & Exer. 32:2116-2119 Double-blind randomized study with male weightlifters.
In this eight-week study, consuming up to six grams of HMB per day was shown to have no adverse effects on measures of hematology and hepatic and renal function.
In this eight-week study, consuming up to six grams of HMB per day was shown to have no adverse effects on measures of hematology and hepatic and renal function.
2009Thomson, J.S., Watson, P.E., and D.S. Rowlands, 2009 Effects of nine weeks of beta-hydroxy-beta- methylbutyrate supplementation on strength and body composition in resistance trained men, J. Strength Cond. Res. 23:827-835
In this 9-week, randomized, double-blind, placebo-controlled study, HMB increased lean mass, decreased fat mass and resulted in a substantial increase in lower body strength.
Rowlands, D.S., and J.S. Thomson, 2009 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. 23:836-846
This recent meta-analysis was conducted on the effects of HMB in younger men participating in resistance-training programs. The data were broken into trained and untrained subject groups. The authors concluded that HMB supplementation resulted in clear overall increases in strength in men entering a resistance training program, but that the benefit of HMB in trained athletes was smaller.
Baier, S., Johannsen, D., Abumrad, N., Rathmacher, J. A., Nissen S. and P. Flakoll, 2009 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 33:71-82 In this year long double-blind, placebo-controlled study in the elderly, daily supplementation with HMB, arginine, and lysine increased lean mass and protein turnover.
Kraemer W.J., Hatfield D.L., Volek J.S., Fragala M.S., Vingren J.L., Anderson J.M., Spiering B.A., Thomas G.A., Ho J.Y., Quann E.E., Izquierdo M., Hakkinen K., and C.M. Maresh, 2009 Effects of amino acids supplement on physiological adaptations to resistance training, Med. & Sci. in Sports & Exerc. 41:1111-1121
This randomized, double-blind, placebo-controlled study tested the effects of EAS Muscle Armor® (main ingredients HMB, arginine and glutamine) in resistance-training men in a 12 week study. This study showed that supplementation with Muscle Armor® doubled the effects of the training on lean mass and increased fat loss compared with placebo supplementation. Muscle Armor® beneficially improved hormonal markers associated with intense resistance exercise and increasing lean mass. Muscle Armor® also resulted in greater increases in strength, power, thigh circumference, and decreased indicators of muscle damage.
2008Wilson, G.J., J.M. Wilson, and A.H. Manninen, 2008 Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: A review, Nutr. Metab. (Lond) 5:1 This independent, peer-reviewed paper discusses the critical details of HMB studies and the variables affecting the results of these studies. Included is a review of the current research showing how HMB works (metabolic mechanisms). This paper concludes that collectively there is not only clinical data, but also mechanistic data supporting HMB's effect on increasing muscle mass and strength.
2007Kuhls, D.A., J.A. Rathmacher, M.D. Musngi, D.A. Frisch, J. Nielson, A. Barber, A.D. MacIntyre, J.E. Coates, and J.J. Fildes, 2007 ß-Hydroxy-ß-methylbutyrate (HMB) supplementation in critically ill trauma patients, J. Trauma Inj. Infect. & Crit. Care 62:125-131 Placebo-controlled, double-blind clinical study of HMB in critically injured patients.
Data from this study suggest that HMB can improve nitrogen balance in severely injured trauma patients.
Data from this study suggest that HMB can improve nitrogen balance in severely injured trauma patients.
O’Connor, D.M. and M.J. Crowe, 2007 Effects of six weeks of ß-hydroxy-ß-methylbutyrate (HMB) and HMB/creatine supplementation on strength, power, and anthropometry of highly trained athletes, J. Strength Cond. Res. 21:419-423
Subjects’ ethical backgrounds prevented this study from being conducted as a double-blind, placebo-controlled study; however, a placebo treatment was utilized.
Using skin-fold data reported in this paper, calculations of lean mass change show a numerical increase in lean tissue with HMB supplementation. This calculation was however not reported in the paper.
Nissen, S.L., 2007 ß-Hydroxy-ß-methylbutyrate. In J.A. Driskell (Ed.) Sports Nutrition: Fats and Proteins, Boca Raton: CRC Press 12:221-241 This chapter in the CRC series of desk references for professional nutritionists and trainers discusses the origins, mechanisms, uses, safety and results of HMB supplementation in both healthy individuals and those experiencing unwanted muscle loss.
2004Flakoll, P., R. Sharp, S. Baier, D. Levenhagen, C. Carr, and S. Nissen, 2004 Effect of ß-hydroxy-ß-methylbutyrate (HMB), arginine, and lysine supplementation on strength, functionality, body composition, and protein metabolism in elderly women, Nutrition 20:445-451 Two double-blind, randomized, placebo-controlled clinical studies in elderly women. Data from two independent studies demonstrate that a nutritional mixture of HMB, arginine, and lysine can enhance whole body protein synthesis and improve functionality in elderly women.
2003Ransone, J., K. Neighbors, R. LeFavi, and J. Chromiak, 2003 The effect of ß-hydroxy-ß-methylbutyrate (HMB) on muscular strength and body composition in collegiate football players, J. Strength Cond. Res. 17:34-39 Double-blind randomized crossover study in 35 training collegiate football players.
This study was performed with highly trained athletes undergoing an intense training program. Although this study failed to show significant differences, HMB-supplemented subjects gained more lean and lost body fat.
This study was performed with highly trained athletes undergoing an intense training program. Although this study failed to show significant differences, HMB-supplemented subjects gained more lean and lost body fat.
Nissen, S. and R. Sharp, 2003 The efficacy of dietary supplements in accentuating the muscle mass and strength gains achieved with resistance exercise: A meta-analysis, J. Appl. Physiol. 94:651-659 A meta-analysis of dietary supplements used to increase lean and strength which shows few supplements used as ergogenic aids have two or more peer-reviewed studies. Only HMB and creatine have been shown to significantly increase lean and strength gains with exercise.
2001Vukovich, M.D., N.B. Stubbs and R.M. Bohlken, 2001 Body composition in 70-year-old adults responds to dietary ß-hydroxy-ß-methylbutyrate (HMB) similarly to that of young adults, J. Nutr. 131:2049-2052 Double-blind randomized study in elderly men and women participating in a weight training exercise program.
In this study, HMB tended to increase muscle strength and lean mass while significantly increasing fat loss over this eight-week study in older adults.
In this study, HMB tended to increase muscle strength and lean mass while significantly increasing fat loss over this eight-week study in older adults.
Jówko, E., P. Ostaszewski, M. Jank, J. Sacharuk, A. Zieniewicz, J. Wilczak, and S. Nissen, 2001 Creatine and ß-hydroxy-ß-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight training program, Nutrition 17:558-566 Double-blind randomized study in weight training males.
This is the first major study to show that HMB combined with creatine supplementation results in even greater strength and lean gains than either HMB or creatine supplementation alone.
This is the first major study to show that HMB combined with creatine supplementation results in even greater strength and lean gains than either HMB or creatine supplementation alone.
Slater, G., D. Jenkins, P. Logan, H. Lee, M. Vukovich, J.A. Rathmacher and A.G. Hahn, 2001 ß-Hydroxy-ß-methylbutyrate (HMB) supplementation does not affect changes in strength or body composition during resistance training in trained men, Int. J. Sport Nutr. & Exer. Met. 11:384-396 Double-blind randomized study in trained male athletes undergoing a weight training program.
In highly trained athletes, HMB numerically increased strength and lean, but the increase was not significantly greater than that of the placebo group.
In highly trained athletes, HMB numerically increased strength and lean, but the increase was not significantly greater than that of the placebo group.
2000Panton, L.B., J.A. Rathmacher, S. Baier, and S. Nissen, 2000 Nutritional supplementation of the leucine metabolite ß-hydroxy-ß-methylbutyrate (HMB) during resistance training, Nutrition 16:734-739 Two double-blind randomized studies including males and females and trained and untrained weightlifters.
Two separate studies showed that regardless of gender or prior training, HMB increases strength and minimizes muscle damage when combined with a four-week resistance-training program.
Two separate studies showed that regardless of gender or prior training, HMB increases strength and minimizes muscle damage when combined with a four-week resistance-training program.
Gallagher, P.M., J.A. Carrithers, M.P. Godard, K.E. Schulze, and S.W. Trappe, 2000 ß-Hydroxy-ß-methylbutyrate (HMB) ingestion, Part I: effects on strength and fat free mass, Med. & Sci. in Sports & Exer. 32:2109-2115 Double-blind randomized study with male weightlifters.
In this study, either three or six grams of HMB were consumed per day. HMB increased lean mass, peak muscle torques, and decreased plasma CPK after resistance training with no added benefit seen from consuming the higher level.
In this study, either three or six grams of HMB were consumed per day. HMB increased lean mass, peak muscle torques, and decreased plasma CPK after resistance training with no added benefit seen from consuming the higher level.
1999Kreider, R.B., M. Ferreira, M. Wilson, and A.L. Almada, 1999 Effects of calcium ß-hydroxy-ß-methylbutyrate (HMB) supplementation during resistance training on markers of catabolism, body composition, and strength, Int. J. Sports Med. 20:503-509 Randomized placebo-controlled study of 40 experienced, resistance-trained males.
In this four-week study, trained athletes consumed either three or six grams of HMB per day. While not statistically significant, HMB consumption resulted in numerically greater lean and strength gains.
In this four-week study, trained athletes consumed either three or six grams of HMB per day. While not statistically significant, HMB consumption resulted in numerically greater lean and strength gains.
1996Nissen, S., R. Sharp, M. Ray, J.A. Rathmacher, D. Rice, J.C. Fuller, Jr., A.S. Connelly and N. Abumrad, 1996 Effect of the leucine metabolite ß-hydroxy-ß-methylbutyrate (HMB) on muscle metabolism during resistance-exercise training, J. Appl. Physiol. 81:2095-2104 Two double-blind randomized studies in weight training males.
In these separate studies, one for three weeks and one for seven weeks, it was found that feeding three grams of HMB to exercising humans increased lean mass, strength, and reduced muscle damage.
In these separate studies, one for three weeks and one for seven weeks, it was found that feeding three grams of HMB to exercising humans increased lean mass, strength, and reduced muscle damage.
