MTI Biotech

How HMB Works


Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein...

The authors studied muscle protein synthesis (MPS) and muscle protein breakdown (MPB) in young males supplemented with CaHMB.  Similar to their previous study with HMB free acid, CaHMB provided a comparable stimulation of MPS and suppression of MPB.  The pro-anabolic properties of CaHMB were shown to include activation of mTORc1.  Therefore, both CaHMB and HMB free acid have similar effects on muscle protein turnover despite the differences reported in bioavailability.


Conversion of leucine to beta-hydroxy-beta-methylbutyrate by alpha-keto isocaproate dioxygenase...

This significant study performed in skeletal muscle cells shows that leucine’s stimulation of protein synthesis in muscle is through conversion to HMB.  While previous studies had speculated that much of the effect of leucine was due to its downstream metabolite HMB, this study is the first to actually demonstrate this effect in living cells.


Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein...

Skeletal muscle protein turnover was measured in healthy young men in response to an oral dose of either 2.4 g of HMB in free acid form or 3.4 g of leucine. While both HMB and leucine stimulated muscle protein synthesis, HMB was also shown to attenuate muscle protein breakdown (-57%). The authors concluded that HMB induces anabolic effects in skeletal muscle that are distinct and/or additive to the effects of leucine.


β-Hydroxy-β-methylbutyrate (HMB) prevents dexamethasone-induced myotube atrophy.

This study used a model cell culture system that represents what happens in an animal or human.  Glucocorticoids, such as dexamethasone used in this study, cause increased muscle protein degradation and decreased protein synthesis which result in a loss of muscle.  HMB attenuated the negative effects of dexamethasone on protein degradation and protein synthesis and thus prevented the muscle loss.

Beta-hydroxy-beta-methyl-butyrate blunts negative age-related changes in body composition...

In a study using sedentary rats of multiple age groups, from young to old, HMB supplementation was shown to maintain muscle mass as the rats aged.  HMB simultaneously decreased fat mass in older rats.  Thus, HMB supplementation may be useful in blunting the effects of sarcopenia (muscle loss with aging) in humans, even without a stimulus such as regular exercise.

Metabolic and functional effects of beta-hydroxy-beta-methylbutyrate (HMB) supplementation in...

In this study utilizing rats, HMB was shown to improve muscle tetonic force after 4 weeks of oral supplementation. HMB also decreased muscle fatigue as measured by muscle tension developed over successive contractions.  Additionally, HMB increased glycogen, ATP, and citrate synthase activity in these muscles which may have been why the HMB-supplemented rats had increased tetonic force and fatigue resistance.


Beta-hydroxy-beta-methylbutyrate (HMB) stimulates myogenic cell proliferation, differentiation...

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.

Mechanism of attenuation by beta-hydroxy-beta-methylbutyrate of muscle protein degradation induced..

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.

Acute and timing effects of beta-hydroxy-beta-methylbutyrate (HMB) on indirect markers of skeletal..

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.

Effect of beta-hydroxy-beta-methylbutyrate (HMB) on protein metabolism in whole body and in...

In this study tissue as well as whole body protein turnover was studied in rats after HMB administration.  This study demonstrated that HMB inhibits proteasome dependent proteolysis in skeletal muscle and decreases whole body protein turnover.


Beta-hydroxy-beta-methylbutyrate supplementation reduces tumor growth and tumor cell proliferation..

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.

Mechanism of attenuation of muscle protein degradation induced by tumor necrosis factor-alpha and...

The author's first paper detailed HMB effect on maintaining 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 dependent 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.


Signaling pathways initiated by beta-hydroxy-beta-methylbutyrate to attenuate the depression of...

Protein synthesis studies were conducted in a cachectic mouse model and in muscle cell cultures.   The results demonstrate that HMB simulates protein synthesis in muscle by multiple mechanisms including the mTOR/p70S6k pathway.  Many of these mechanisms 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.


Attenuation of proteasome-induced proteolysis in skeletal muscle by {beta}-hydroxy-{beta...

This study was conducted in a mouse model of cancer tumor growth. HMB was shown to maintain lean body mass and attenuate protein degradation through down regulation of the increased expression of key regulatory components of the ubiquitin-proteasome proteolytic pathway.  HMB also stimulated protein synthesis.

Supplementation with beta-hydroxy-beta-methylbutyrate (HMB) and alpha-ketoisocaproic acid (KIC)...

This counterbalanced, crossover study in 6 non-resistance trained males given either a placebo or HMB/KIC (3 grams HMB and 0.3 grams KIC) showed that his combination reduced exercise-induced muscle damage.


Mechanism of the attenuation of proteolysis-inducing factor stimulated protein degradation in...

This In vitro study of chemical markers of proteolytic functions in muscle cell cultures showed that HMB inhibits activation of a major protease pathway in muscle, thus inhibiting protein degradation in muscle.


beta-hydroxy-beta-methylbutyrate (HMB) kinetics and the influence of glucose ingestion in humans.

In 2 randomized trials the blood levels of HMB were examined after eight males took either 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.


Beta-hydroxy beta-methylbutyrate (HMB) supplementation does not influence the urinary testosterone..

In this case study of six males taking HMB, the results demonstrated that HMB does not alter testosterone levels and infer that HMB acts through a mechanism other than testosterone.

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