Tuesday, August 18, 2015

Can we Reduce Muscle Cramps in Patients with Cirrhosis?

Can we Reduce Muscle Cramps in Patients with Cirrhosis?
Kristine Novak

L-carnitine appears to be safe and effective for reducing muscle cramps in patients with cirrhosis, researchers report in the August issue of Clinical Gastroenterology and Hepatology.

Many patients with cirrhosis develop frequent muscle cramps, which reduce their quality of lifeL-carnitine (L-beta-hydroxy-gamma-N-trimethyl aminobutyric acid) is an amino acid that transports long-chain fatty acids across the mitochondrial membrane, and has been proposed to provide energy for skeletal muscle. Hiroyuki Nakanishi et al evaluated its effects on muscle cramps in a prospective study.

Consecutive patients with cirrhosis and muscle cramps were given L-carnitine (300 mg) 3 times/day (900 mg/day total, n = 19) or 4 times/day (1200 mg/day total, n = 23) for 8 weeks. The frequency of muscle cramps was assessed by questionnaires, and the degree of muscle cramping was assessed by the visual analogue scale (VAS).

The VAS is a horizontal, 100 mm line with word descriptors at each end (left, totally without pain and right, unbearable pain). Patients mark points on the line the point that best indicates their current state. The VAS score is then determined by measuring millimeters from the left end of the line to the marked points.

At the end of the 8 week study period, muscle cramps decreased in 88.1% of all subjects; 28.6% of patients had no cramps at al.

Overall VAS scores decreased significantly, from a mean value of 69.9±22.5 at baseline to 26.2±29.1 after 8 weeks.

Muscle cramps were reduced in 43.5% of patients in the 1200 mg/day group and 10.5% in the 900 mg/day group. At the end of the 8-week study period, mean VAS scores were 9.9±13.5 in the 1200 mg/day group and 39.6±31.9 in the 900 mg/day group (see figure).

Nakanishi et al did not observe any adverse events.

VAS scores before and after 8 weeks of L-carnitine. Black lines indicate the 1200 mg group, gray the 900 mg group. (A) Overall, the mean VAS score was reduced significantly from 69.9 ± 22.5 to 26.2 ± 29.1 after 8 weeks of therapy. (B) VAS scores after 8 weeks were significantly lower in 1200 mg group than in 900 mg group

Why do patients with cirrhosis develop cramps, and why might L-carnitine reduce them? An analysis of skeletal muscle biopsies from patients with cirrhosis and found reductions in ATP, phosphocreatine, and total adenine nucleotides. Deficiencies in ATP result in insufficient dissociation of myosin from actin, and thereby prolonged muscle contraction and cramping.

Carnitine transports long-chain acyl groups from fatty acids into the mitochondrial matrix, so they can be broken down through β-oxidation to acetyl CoA to obtain usable energy via the citric acid cycle.

This process provides ATP for heart and skeletal muscles. Nakanishi et al propose that some patients with cirrhosis could have carnitine deficiency. Larger, randomized, controlled studies are necessary to further evaluate the efficacy of L-carnitine in reducing muscle cramps in patients with cirrhosis and other disorders.

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