Effects of carnitine supplementation on muscle metabolism by the use of magnetic resonance spectroscopy and near-infrared spectroscopy in end-stage renal disease.
OBJECTIVE
A defect in skeletal muscle mitochondrial metabolism develops in patients with chronic renal failure on haemodialysis. Treatment with carnitine, a compound essential for normal mitochondrial function, has been suggested to have significant benefits in such patients, so we carried out a study to see if carnitine acts by improving muscle bioenergetics and function.


METHODS
In a phase II randomised double-blind trial, patients with end-stage renal disease received placebo or intravenous L-carnitine (20 mg/kg dry body weight three times weekly after haemodialysis) for 16 weeks (n = 13 in each group). 31P magnetic resonance spectroscopy, 1H magnetic resonance imaging and near-infrared spectroscopy were used to measure muscle bioenergetics and function at baseline and at 16 weeks.


RESULTS
There were no significant differences between groups at baseline. Mean plasma carnitine rose 10-fold in the carnitine group but was unchanged in the placebo group. L-carnitine had no statistically significant effect on any of the parameters measured. The rate of proton efflux from muscle, as a measure of tissue perfusion, was low in both groups and was not affected by treatment.


CONCLUSIONS
The study failed to show any significant effect of 16 weeks' L-carnitine supplementation on these objective measures of muscle metabolism and function. Slow proton efflux from muscle provides evidence supporting low blood flow and, therefore, decreased oxygen availability, as an underlying mechanism for muscle mitochondrial dysfunction in this disorder.
Vaux
E C
EC
Oxford Kidney Unit, Churchill Hospital, Headington, UK.
Taylor
D J
DJ
Altmann
P
P
Rajagopalan
B
B
Graham
K
K
Cooper
R
R
Bonomo
Y
Y
Styles
P
P
D001774:Blood Chemical Analysis; D002331:Carnitine / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism / Q000628:therapy; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D018908:Muscle Weakness / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D006435:Renal Dialysis; D019265:Spectroscopy, Near-Infrared
D002331:Carnitine