Abstract
Carnitine deficiency is prevalent in patients undergoing hemodialysis, and it could result in lowered muscle strength. So far, the effect of treatment with levocarnitine on lower limb muscle strength has not been well described. This observational study examined the association between treatment with levocarnitine with the change in knee extensor strength (KES) in hemodialysis patients. Eligible patients were selected from the participants enrolled in a prospective cohort study for whom muscle strength was measured annually. We identified 104 eligible patients for this analysis. During the one-year period between 2014 to 2015, 67 patients were treated with intravenous levocarnitine (1000 mg per shot, thrice weekly), whereas 37 patients were not. The change in KES was significantly higher (p = 0.01) in the carnitine group [0.02 (0.01–0.04) kgf/kg] as compared to the non-carnitine group [−0.02 (−0.04 to 0.01) kgf/kg]. Multivariable-adjusted regression analysis showed the positive association between the change in KES and the treatment with levocarnitine remained significant after adjustment for the baseline KES and other potential confounders. Thus, treatment with intravenous levocarnitine was independently and positively associated with the change in KES among hemodialysis patients. Further clinical trials are needed to provide more solid evidence.
Highlights
A large number of hemodialysis patients suffer from sarcopenia and decreased muscle strength which are closely related to impaired activity of daily living (ADL) [1] and high mortality rate [2,3,4]
In addition to the role in fatty acid ß-oxidation, carnitine is known to exert other potentially protective effects against muscle wasting [13]: the effect on insulin-like growth factor 1 (IGF-1) regulating the synthesis and degradation of body proteins, the effect on cytokines linking to inflammation, the effect on caspase 3 resulting in proteolysis and myonuclear apoptosis, the effect on oxidative stress, and the effect on mitochondrial dysfunction mediated by peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α
We examined whether the observed between-group difference in the one-year change in knee extensor strength was attributable to the levocarnitine treatment by using the multivariable-adjusted linear regression model which included age, sex, duration of hemodialysis, diabetic kidney disease or not, prior cardiovascular disease (CVD), and knee extensor strength at the beginning of the period as potential confounders (Table 2)
Summary
A large number of hemodialysis patients suffer from sarcopenia and decreased muscle strength which are closely related to impaired activity of daily living (ADL) [1] and high mortality rate [2,3,4]. Carnitine deficiency may contribute to sarcopenia, lowered muscle strength, decreased cardiac function, anemia, and other complications of hemodialysis patients [10,11]. In addition to the role in fatty acid ß-oxidation, carnitine is known to exert other potentially protective effects against muscle wasting [13]: the effect on insulin-like growth factor 1 (IGF-1) regulating the synthesis and degradation of body proteins, the effect on cytokines linking to inflammation, the effect on caspase 3 resulting in proteolysis and myonuclear apoptosis, the effect on oxidative stress, and the effect on mitochondrial dysfunction mediated by peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α. Induction of autophagy by carnitine restores mitochondrial dysfunction in mice [14] All these effects of carnitine are potentially protective against decreased muscle mass and strength. No study is available in the literature that examined the effect of levocarnitine on muscle strength of lower extremity, which is important for independence of ADL [26]
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