Aim: We measured carnitine levels in patients with carnitine including dialysis patients, and examined whether administration of L-carnitine improved muscle symptoms. Methods: We measured carnitine levels in 27 patients with liver cirrhosis who were receiving treatment in our hospital, and administered L-carnitine (600 mg - 1800 mg) to patients having muscle cramps for approximately one month and examined the presence/absence of the symptom. We measured carnitine concentration before and after dialysis, before dialysis after the administration to eight dialysis patients, before and after the administration to 19 nondialytic patients. Results: The total carnitine levels before the dialysis of dialysis patients were an average of 42.2 μmol/L and fell to 17.7 μmol/L after more dialysis, but it was increased to 155 μmol/L after the administration of L-carnitine. In the nondialytic patients, the total carnitine levels were significantly increased from 71.7 μmol/L to 101.7 μmol/L after the administration of L-carnitine (P = 0.038). For symptomatic patients, significant improvement of muscle clamps was observed in the L-carnitine administrated group when compared with the non-administrated group (P = 0.0002). Conclusions: Total carnitine levels were low even before dialysis in the dialysis patients with liver cirrhosis in particular and they further decreased after the dialysis. Administration of L-carnitine increased the total carnitine levels and improved the symptom. Based on these results, we conclude that L-carnitine is useful for carnitine deficiency in patients with liver cirrhosis.
In recent years, we occasionally come across some reports that carnitine is useful for improving blood ammonia and cognitive function in hepatic cirrhosis patients with latent hepatic encephalopathy [
This was a randomized, double-blind, placebo-controlled study.
The serum carnitine concentrations in 27 patients with hepatic cirrhosis who are outpatients at our hospital were measured by using the enzyme cycling method (total carnitine reference value 45.0 - 91.0 μmol/L, free carnitine reference value 36 - 74 μmol/L, acylcarnitines reference value 6 - 23 μmol/L). LC (600 - 1800 mg) was administered to patients with cramps for 1 month, and the presence or absence of the symptom was examined. Serum carnitine concentrations were measured before and after dialysis and after LC administration in 8 dialysis patients, and before and after administration in 19 non-dialysis patients. In 17 patients with the symptom, the serum carnitine concentrations following administration were measured 1 month later. The study was reviewed and approved by the ethics committee established in the Masuko Memorial Hospital. The patients were given explanation on the study, for which written consents were obtained.
The 27 patients consisted of 8 dialysis and 19 non-dialysis patients, with no differences in the background factors (age, sex, cause, Child-Pugh grade, complication by liver cancer, implementation of dialysis, and with or without administration of branched-chain amino acids, hereinafter referred to as BCAAs, formulation) between the two groups. A significant difference was noted in serum total carnitine concentrations (
Baseline participant characteristics | |||
---|---|---|---|
Hemodialysis n = 8 | Non-hemodialysis n = 19 | P value | |
Age mean ± S.D. | 62 ± 11 | 66 ± 9 | 0.32* |
Sex male/female | 5/3 | 12/7 | 1.00** |
Etiology (Alco/HBVHCV//nonBnonC/other) | 0/0/7/0/1 | 6/2/10/1/2 | 0.10** |
Child-pugh grade (A/B/C) | 4/4/0 | 10/5/4 | 0.38** |
Child-pugh score mean ± S.D. | 6.5 ± 1.2 | 7.1 ± 2.7 | 0.43** |
HCC complication (%) | 7 (88) | 12 (63) | 0.36** |
Total-carnitine mean ± S.D. μmol/L | 42.2 ± 19.5 | 70.5 ± 20.7 | 0.004* |
BCAA treatment (%) | 4 (50) | 11 (58) | 1.00** |
L-carnitine treatment (%) | 5 (63) | 11 (63) | 1.00** |
Cr mean ± S.D. mg/dL | 8.9 ± 2.8 | 0.9 ± 0.4 | <0.0001* |
*Student’s t test; **Fisher’s exact test.
13 patients) of the patients, while the symptom did not disappear in the absence of LC administration, showing a significant difference between the two groups (P = 0.0002) (
With respect to test methods, the paired t-test and Student’s t-test were used for paired continuous variable data and unpaired continuous variable data, respectively, and the chi-square test or the Fisher’s exact test was used for categorical variable data. All tests were two-sided, and difference levels of p < 0.05 were considered statistically significant.
The total carnitine concentration of 6 dialysis patients whose serum carnitine concentrations were measured was a subnormal 42.2 ± 19.5 μmol/L before dialysis and 17.7 ± 6.5 μmol/L after dialysis, showing significant decrease (P = 0.011). Free carnitine levels decreased significantly from 27.0 ± 13.2 μmol/L before dialysis to 11.2 ± 25.4 μmol/L after dialysis (P = 0.009); acylcarnitine levels decreased significantly from 15.2 ± 6.2 μmol/L to 5.8 ± 1.9 μmol/L (P = 0.021) (
In the non-dialysis patients, no significant differences was observed in patient backgrounds (age, sex, cause, Child-Pugh grade, complication by liver cancer, total carnitine concentration, and with or without BCAAs administration) between the LC group of 12 patients and non-administration group of 7 patients. By Child-Pugh grades, serum total carnitine showed little variation (grade A, 67.4 ± 20.4 μmol/L; grade B, 51.6 ± 18.8 μmol/L;
Incidence on muscle cramp | ||||
---|---|---|---|---|
Total patients n = 27 | Hemodialysis n = 8 | Non-hempdialysis n = 19 | P value | |
Muscle cramp (%) | 18 (67) | 4 (50) | 14 (74) | 0.3748 |
Improvements on muscle cramp | |||
---|---|---|---|
L-carnitine n = 13 | Non-L-carnitine n = 4 | P value | |
Disappearance of muscle cramp (%) | 12/13 (92) | 0/4 (-) | 0.0002* |
Hemodialysis | 3/3 (100) | 0/1 (-) | 0.2500 |
Non-hemodialysis | 9/10 (90) | 0/3 (-) | 0.0140* |
grade C, 71.6 ± 28.1 μmol/L); free carnitine also exhibited little variation (grade A, 51.6 ± 16.8 μmol/L; grade B, 56.3 ± 10. 9 μmol/L; grade C, 55.0 ± 18.9 μmol/L); and acylcarnitine also showed little variation (grade A, 15.8 ± 8.9 μmol/L; grade B, 18.3 ± 9.9 μmol/L; grade C, 16.6 ± 10.5 μmol/L), neither of which showed a significant difference (
Takayanagi reported that carnitine was an amino acid derivative with low molecular weight and played an important role in energy metabolism [
The cases that we examined in this study were likely to have been those of secondary carnitine deficiency. The symptom of cramps in patients with hepatic cirrhosis is occasionally encountered in clinical practice, and switching therapeutic drugs from BCAA formulations or BCAA granules to oral nutrients for liver failure may improve the symptom [