Effect of HMB on fuel utilization, membrane stability and creatine kinase content of cultured muscle cells

Beta-hydroxy beta-methyl-butyrate (HMB) enhances the gains in muscle strength and lean mass associated with resistance training (J Nutr Biochem, 1997; 8:300-311). To study the underlying mechanism for this action, myoblasts from two cell lines, H9C2 and C2C12, derived, respectively, from heart and skeletal muscles, were differentiated in culture to myotubes and exposed (2 to 4 days) to 0-6 mM HMB. The following parameters were examined; beta-oxidation of palmitate, medium content of lactate dehydrogenase (LDH) and creatine kinase (CK) activity of cell homogenates. HMB treatment increased beta-oxidation of palmitate by 30% (P<0.001). It decreased LDH release from myotubes by 25% (p<0.05). Inclusion of HMB in the differentiation medium also increased cellular expression of CK by 25% (p<0.01). The data suggest that HMB exerts several effects on muscle cells. 1) it increases the cell's oxidative capacity. This action outlasts HMB removal from the culture medium and might involve changes in oxidative enzymes. Increased fat oxidation by muscle may contribute to gains in lean body mass. 2) HMB appears to exert a "stabilizing" effect on myotube membranes as evidenced by the decrease in LDH leak into the medium. This effect may be particularly beneficial during strength training as it would protect against some of the associated cellular injury. Finally, the effect of HMB on cellular CK, an established differentiation marker, suggests that it might enhance expression of muscle-specific proteins.