Corticosteroids such as dexamethason and prednison are powerful anti-inflammatories, but they also cause muscles to atrophy – and that's less good new
Corticosteroids such as dexamethason and prednison are powerful anti-inflammatories, but they also cause muscles to atrophy – and that’s less good news. Should you ever need to use corticosteroids, it might be worth considering using HMB. According to researchers at Pusan National University in South Korea, HMB can reduce muscle atrophy caused by corticosteroids.
HMB is a metabolite of leucine, and muscle cells have a kind of inbuilt sensor for this amino acid. The more leucine muscle cells ‘see’, the more they do their best to grow.
HMB has a similar effect on muscle cells, but we don’t know exactly how HMB actually works. A not particularly new theory suggests that it’s not leucine that muscle cells ‘see’, but its metabolite HMB. Recent studies suggest however that HMB and leucine induce muscle growth in two different ways.
The Koreans wanted to know whether patients who had to take corticosteroids would retain muscle mass by taking either leucine or HMB. They performed an animal study in which they gave rats dexamethasone, a corticosteroid, for 5 days. Dexamethasone is five times stronger than prednisone. A control group [Con] was given no active substances.
One group of rats was given only dexamethasone. [Dexa]
Another group was given a hefty dose of leucine on top of this. [Dexa + Leu] The human equivalent of this dose would be about 8 g per day, based on a person weighing 80 kg.
Another group of rats was given a modest dose of HMB in addition to the dexamethasone. The human equivalent of this dose would be about 2 g per day. [Dexa +HMB 150]
Yet another group of rats was given a hefty dose of HMB in addition to the dexamethasone. The human equivalent of this dose would be about 8 g per day. [Dexa + HMB 600]
Less muscle loss
At the end of the five days the dexamethasone had reduced the weight of the rats’ gastrocnemius muscle, but HMB supplementation had reduced the level of atrophy. The figure below shows the weight of the gastrocnemius as a proportion of the rats’ bodyweight.
Dexamethason also reduced the rats’ muscle strength and boosted the concentration of creatine kinase in the blood. The latter is an indication of muscle damage.
The Koreans think that HMB sabotages the forkhead box protein O1 [FOXO1]. The receptor to which corticosteroid hormones attach themselves doesn’t function properly without this protein.
“Our in vivo data show that HMB protects against glucocorticoid-induced muscle atrophy and suggest that HMB supplementation be considered a potential treatment for muscle atrophy”, the Koreans write.
?-Hydroxy ?-methylbutyrate improves dexamethasone-induced muscle atrophy by modulating the muscle degradation pathway in SD rat.
Skeletal muscle atrophy results from various conditions including high levels of glucocorticoids, and ?-hydroxy ?-methylbutyrate (HMB; a metabolite of leucine) is a potent therapeutical supplement used to treat various muscle disorders. Recent studies have demonstrated that HMB inhibits dexamethasone-induced atrophy in cultured myotubes, but its effect on dexamethasone-induced muscle atrophy has not been determined in vivo. In the present study, we investigated the effect of HMB on dexamethasone-induced muscle atrophy in rats. Treatment with dexamethasone weakened grip strengths and increased muscle damage as determined by increased serum creatine kinase levels and by histological analysis. Dexamethasone treatment also reduced both soleus and gastrocnemius muscle masses. However, HMB supplementation significantly prevented reductions in grip strengths, reduced muscle damage, and prevented muscle mass and protein concentration decrease in soleus muscle. Biochemical analysis demonstrated that dexamethasone markedly increased levels of MuRF1 protein, which causes the ubiquitination and degradation of MyHC. Indeed, dexamethasone treatment decreased MyHC protein expression and increased the ubiquitinated-MyHC to MyHC ratio. However, HMB supplementation caused the down-regulations of MuRF1 protein and of ubiquitinated-MyHC. Furthermore, additional experiments provided evidence that HMB supplementation inhibited the nuclear translocation of FOXO1 induced by dexamethasone, and showed increased MyoD expression in the nuclear fractions of soleus muscles. These findings suggest that HMB supplementation attenuates dexamethasone-induced muscle wasting by regulating FOXO1 transcription factor and subsequent MuRF1 expression. Accordingly, our results suggest that HMB supplementation could be used to prevent steroid myopathy.
PMID: 25032690 [PubMed – in process] PMCID: PMC4102592