Dietary HMB and β-alanine co-supplementation does not improve in situ muscle function in sedentary, aged male rats

Abstract

This study evaluated the effects of dietary β-hydroxy-β-methylbutyrate (HMB) combined with β-alanine (β-Ala) in sedentary, aged male rats. It has been suggested that dietary HMB or β-Ala supplementation may mitigate age-related declines in muscle strength and fatigue resistance. A total of 20 aged Sprague-Dawley rats were studied. At age 20 months, 10 rats were administered a control, purified diet and 10 rats were administered a purified diet supplemented with both HMB and β-Ala (HMB+β-Ala) for 8 weeks (approximately equivalent to 3 and 2.4 g per day human dose). We measured medial gastrocnemius (MG) size, force, fatigability, and myosin composition. We also evaluated an array of protein markers related to muscle mitochondria, protein synthesis and breakdown, and autophagy. HMB+β-Ala had no significant effects on body weight, MG mass, force or fatigability, myosin composition, or muscle quality. Compared with control rats, those fed HMB+β-Ala exhibited a reduced (41%, P = 0.039) expression of muscle RING-finger protein 1 (MURF1), a common marker of protein degradation. Muscle from rats fed HMB+β-Ala also exhibited a 45% reduction (P = 0.023) in p70s6K phosphorylation following fatiguing stimulation. These data suggest that HMB+β-Ala at the dose studied may reduce muscle protein breakdown by reducing MURF1 expression, but has minimal effects on muscle function in this model of uncomplicated aging. They do not, however, rule out potential benefits of HMB+β-Ala co-supplementation at other doses or durations of supplementation in combination with exercise or in situations where extreme muscle protein breakdown and loss of mass occur (e.g., bedrest, cachexia, failure-to-thrive).

Inhibition of interleukin-6 decreases atrogene expression and ameliorates tail suspension-induced skeletal muscle atrophy

“…In the present study, pretreatment with HMB prevented muscle atrophy. Our data are consistent with those of previous studies, showing that HMB represses the expression of MuRF1 and atrogin-1 [ 8 – 10 ]. In a previous study, HMB did not repress the expression of MuRF1 and atrogin-1 and did not protect rats from skeletal muscle atrophy induced by monolateral hindlimb immobilization [ 49 ].…”

“…HMB also attenuated dexamethasone-induced muscle atrophy by regulating FOXO transcription factor and subsequent MuRF1 expression in rats [ 9 ]. In aged male rats, HMB reduced the expression of MuRF1 [ 10 ]. HMB has also been suggested to repress the expression of IL-6 [ 11 , 12 ].…”

Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention

“…Decreased protein breakdown observed in the elderly receiving a supplement of Similarly, Russ et al (2015) showed recently that HMB treatment combined with β-alanine in sedentary aged male rats (20 months) reduces muscle MuRF1 expression as compared to control rats. Similar data have been obtained in muscle cell cultures exposed to wasting treatments such as TNF-α, IFN-, and GCs (dexamethasone) (Aversa et al, 2012;Giron et al, 2015;Kimura et al, 2014a).…”

Age-related changes in skeletal muscle: changes to life-style as a therapy

“…In contrast, meta-analysis of protein supplementation studies (Xu et al 2014 ) showed no difference between the effect of protein supplementation and that of a placebo groups on muscle mass, protein synthesis and muscle strength in older men (Dirks et al 2014 ) or women (Zhu et al 2015 ). Furthermore, (Russ et al 2015a , b ) showed that protein supplementation attenuated muscle degradation through decreasing Murf1 expression, this did not translate to any functional benefits to muscles of old rats (Russ et al 2015b ). However these discrepancies may be explained by the times at which intake of protein occurred; Symons et al ( 2007 ) showed that a 90 g of protein meal in humans does not cause more protein synthesis than a 30 g meal in humans (Symons et al 2007 ).…”