L-carnitine Supplementation In Patients Research Articles

Survival benefit of l-carnitine supplementation in patients with cirrhosis.

l-Carnitine supplementation is effective in improving muscle cramps, hyperammonemia, and hepatic encephalopathy in patients with cirrhosis. However, limited evidence is available on the effect of l-carnitine supplementation on the survival of patients with cirrhosis. In this retrospective study, 674 patients with cirrhosis admitted to Gifu University Hospital or Chuno Kosei Hospital between October 2011 and December 2018 were enrolled. l-carnitine supplementation was defined as the use of l-carnitine for >30 consecutive days during the follow-up period. Propensity score matching was applied to create comparable groups between l-carnitine-treated and untreated patients. Mortality was evaluated using the Cox proportional hazards model. Among the patients, 93 were excluded. Of the remaining 581 patients, 71 (12%) received l-carnitine supplementation. Propensity matching identified 189 patients (63 l-carnitine-treated and 126 untreated patients) with comparable baseline characteristics in both groups. Of the matched patients, 33 (52%) l-carnitine-treated and 74 (59%) untreated patients died during the median follow-up period of 36.3 months. Overall survival was significantly higher in l-carnitine-treated patients than in untreated patients (hazard ratio [HR], 0.66; 95% CI, 0.43-0.99). A subgroup analysis showed that the survival benefit of l-carnitine supplementation was prominent in patients with Child-Pugh Class B or C (HR, 0.39; 95% CI, 0.23-0.68), serum albumin levels ≤3.5 g/dl (HR, 0.59; 95% CI, 0.37-0.95), and ammonia levels ≥90 mcg/dl (HR, 0.50; 95% CI, 0.26-0.97), and in those without sarcopenia (HR, 0.56; 95% CI, 0.35-0.90). l-Carnitine supplementation may improve survival in patients with cirrhosis.

Effects of l-carnitine supplementation in patients with childhood-onset epilepsy prescribed valproate

BackgroundThe benefits of carnitine supplementation in patients treated with valproate (VPA) are not clear. Therefore, we retrospectively explored the benefits of carnitine supplementation by analyzing laboratory data. MethodsWe measured the serum-free carnitine (FC), VPA, aspartate aminotransferase, alanine aminotransferase, amylase, and ammonia levels, and the platelet count, in 69 patients with childhood-onset epilepsy treated with VPA. Eight patients had received carnitine supplementation. The serum FC and acylcarnitine levels were measured using an enzyme cycling method. We compared laboratory values between patients with and without carnitine supplementation and analyzed the correlations between serum FC levels and laboratory values. ResultsThe serum FC levels were normal (median, 48.8 μmol/L; range: 41.9–68.3 μmol/L) in all eight patients with carnitine supplementation, but below normal in 32 of 61 patients without supplementation. The median serum amylase levels were lower in the patients with carnitine supplementation (median, 48 U/L; range: 27–149 U/L) than in those without (median, 7 U/L; range: 14–234 U/L). The platelet count and serum ammonia levels did not differ significantly between patients with and without supplementation. There was no significant correlation between the serum FC level and the platelet count, serum amylase level, or ammonia level. ConclusionsCarnitine supplementation helps maintain serum FC levels in patients treated with VPA. The lower serum amylase levels in patients with carnitine supplementation may reflect protective effects of carnitine against latent pancreatic injury.

Effect of L-carnitine on liver enzymes and biochemical factors in hepatic encephalopathy: A systematic review and meta-analysis.

We aimed to investigate the effect of L-carnitine on biochemical factors including ammonia, bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) in patients with hepatic encephalopathy (HE). A systematic search was carried out in Web of Science, PubMed, Scopus, and Cochrane Library databases to find articles related to the effect of L-carnitine supplementation in patients with HE, up to 7 February 2019. There was no language and time limitation. Meta-analyses were carried out using both the random and fixed effects models where appropriate, and I2 index was used to evaluate the heterogeneity. Search yielded 3462 publications. Nine randomized clinical trials with 779 patients were eligible. L-carnitine supplementation significantly reduced blood levels of ammonia. Furthermore, our results indicated that L-carnitine supplementation significantly reduced blood levels of bilirubin, AST, BUN, and Cr in patients with HE. Subgroup analysis demonstrated that L-carnitine significantly reduced ammonia in patients with all the ages, long and short duration of the supplementation, doses less or higher than 4000mg/day, any route of treatment (intravenous or oral), and in patients with any grade of the symptoms of HE. Moreover, we found that L-carnitine significantly increased circulating levels of albumin in HE patients. Present systematic review and meta-analysis revealed that L-carnitine supplementation significantly reduced blood levels of ammonia, bilirubin, AST, BUN, and Cr in HE patients. Moreover, we found that L-carnitine significantly increased circulating levels of albumin. However, further large-scale randomized clinical trials are needed.

L-Carnitine for the Treatment of Overt Hepatic Encephalopathy in Patients with Advanced Liver Cirrhosis.

Hepatic encephalopathy is a major complication in patients with advanced cirrhosis and is associated with poor prognosis. To evaluate the effectiveness of L-carnitine supplementation in patients with overt hepatic encephalopathy (OHE), outcomes were retrospectively analyzed in patients with OHE who were treated with intravenous branched-chain amino acids (BCAA), with or without intravenous L-carnitine. Twenty-six patients were treated with intravenous BCAA in addition to conventional agents such as lactulose and non-absorbable antibiotics (Group A), and 19 patients were treated with these agents plus intravenous L-carnitine (Group L). Changes in blood ammonia concentrations, hepatic coma grade and the Glasgow Coma Scale (GCS) were compared in the two groups. Recurrence-free survival (RFS) was evaluated in the two groups and in patients who were and were not administered oral L-carnitine supplementation. At baseline, GCS scores were significantly lower and deterioration in liver function greater in Group L. After 3 d of intravenous L-carnitine, however, GCS showed a significantly greater improvement in Group L than in Group A. Blood ammonia levels improved stably over time in Group L. Overall survival and RFS were similar in Group L and Group A, but median RFS was significantly longer in patients who did than did not receive oral L-carnitine supplementation (735 versus 497 d, p=0.03). Although these findings are preliminary, L-carnitine supplementation may be a therapeutic option for patients with OHE and disturbed consciousness.

The anti-wasting effects of L-carnitine supplementation on cancer: experimental data and clinical studies.

Cachexia is a paraneoplastic syndrome that affects the large majority of patients with end-stage cancer. No known therapy exists to effectively overcome the severe symptoms of cachexia, which include anorexia, weight loss and fatigue. This study considered the results of both experimental and clinical studies to evaluate the suitability of L-carnitine and its derivatives as potential therapies for cachexia in patients with cancer. All available English-language papers on the use of L-carnitine in patients with cachexia related to cancer, including reviews, case reports, case series, and clinical trials, were obtained by searching multiple databases, including all Elsevier publications, Web of Knowledge, PubMed, Scopus, clinical trials, and the Cochrane database of systematic reviews. The protective effects of L-carnitine were extracted from the literature review based on critical mechanisms involved in skeletal muscle loss, including increased proteolysis, impaired protein synthesis, myonuclear apoptosis, oxidative stress, and mitochondrial dysfunction. The results of this process favored L-carnitine supplementation in patients with cancer-related cachexia. Nitrogen balance was improved either through the increase of protein synthesis or by reduction in proteolysis, inhibiting apoptosis or reversing inflammatory processes. Although clinical studies are inconclusive, studies in animal models support L-carnitine administration to prevent oxidative stress and ameliorate mitochondrial function. L-carnitine supplementation leads to beneficial effects on several critical mechanisms involved in pathologic skeletal muscle loss and improved fatigue-related parameters in patients with cancer. However, more well-designed, double-blinded, randomized clinical trials are necessary to establish L-carnitine supplementation as a therapeutic strategy for cachexia.

The Unexpected Effects of L-Carnitine Supplementation on Lipid Metabolism in Hemodialysis Patients

Background/Aims: There is a growing body of evidence that the long-term hemodialysis (HD) treatment leads to disturbances of carnitine homeostasis but the results of L-carnitine supplementation in HD patients have been conflicting. In the present prospective study, we investigated the effectiveness of intravenous L-carnitine in mitigating dialysis-related protein-energy wasting (PEW) based on pre-treatment albumin levels. Methods: Fifty patients (46% male, mean age 63±18.28 years, HD vintage 37.5 (7-288) months) received 1 g L-carnitine intravenously at the end of every HD session for 12 months. Clinical data were obtained from the medical records and charts. Intradialytic hypotension periods (defined as a decrease of systolic blood pressure by ≥ 20 mmHg) were recorded. Dietary habits were evaluated using a self-administered questionnaire prior to L-carnitine supplementation. Laboratory parameters were measured prior to the supplementation and controlled in 6-months intervals. Anthropometric measurements were performed prior to HD session, including „dry“ body weight and height, body mass index (BMI), and body composition analysis using bioimpedance spectroscopy. Malnutrition-inflammation score (MIS) was used as a scoring system representing the severity of PEW and an indicator of general functional capacity. Results: A significant increase in total cholesterol, predominantly on the account of LDL was found (p=0.005). Simultaneously, HDL decreased (p=0.001) while triglyceride levels remained unchanged. Although the rise in serum prealbumin could be observed, lean tissue index (LTI) decreased and fat tissue index (FTI) increased which resulted in reduction of the LTI/FTI ratio (p=0.002). When divided into two groups according to the pre-treatment albumin values (< 35 g/L or ≥35 g/L), patients from the higher albumin group showed significant increase in prealbumin (p=0.005), and improved MIS (p=0.03). Multivariate regression analysis showed that higher FTI after introduction of L-carnitine led to greater hemodynamic stability (OR 1.709, 95% CI 1.006-2.905, p=0.048). As there was no differences in HD treatment characteristics, primery kidney disease or residual diuresis we could conclude that positive energy balance (with an increase in prealbumin and FTI) eventually led to better hemodynamic stability. Conclusion: Our results show significant effects of L-carnitine supplementation on lipid metabolism. Further clinical trials, as well as experimental research are needed to define the role of lipid metabolism in CKD population. Significant benefits of L-carnitine supplementation in patients with better initial serum albumin levels suggest that this therapy should not be restricted to patients with the worst nutritional and overall status.

In vivo intracerebral administration of L-2-hydroxyglutaric acid provokes oxidative stress and histopathological alterations in striatum and cerebellum of adolescent rats

Patients affected by L-2-hydroxyglutaric aciduria (L-2-HGA) are biochemically characterized by elevated L-2-hydroxyglutaric acid (L-2-HG) concentrations in cerebrospinal fluid, plasma, and urine due to a blockage in the conversion of L-2-HG to α-ketoglutaric acid. Neurological symptoms associated with basal ganglia and cerebelar abnormalities whose pathophysiology is still unknown are typical of this neurometabolic disorder. In the present study we evaluated the early effects (30min after injection) of an acute in vivo intrastriatal and intracerebellar L-2-HG administration on redox homeostasis in rat striatum and cerebellum, respectively. Histological analyses of these brain structures were also carried out 7 days after L-2-HG treatment (long-term effects). L-2-HG significantly decreased the concentrations of reduced (GSH) and total glutathione (tGS), as well as of glutathione peroxidase (GPx) and reductase (GR) activities, but did not change the activities of superoxide dismutase and catalase in striatum. Furthermore, the concentrations of oxidized glutathione (GSSG) and malondialdehyde (MDA), as well as 2′,7′-dichlorofluorescein (DCFH) oxidation and hydrogen peroxide (H2O2) production, were increased, whereas carbonyl formation and nitrate plus nitrite concentrations were not altered by L-2-HG injection. It was also found that the melatonin, ascorbic acid plus α-tocopherol, and creatine totally prevented most of these effects, whereas N-acetylcysteine, the noncompetitive glutamate NMDA antagonist MK-801, and the nitric oxide synthase inhibitor L-NAME were not able to normalize the redox alterations elicited by L-2-HG in striatum. L-2-HG intracerebellar injection similarly provoked a decrease of antioxidant defenses (GSH, tGS, GPx, and GR) and an increase of the concentrations of GSSG, MDA, and H2O2 in cerebellum. These results strongly indicate that the major accumulating metabolite in L-2-HGA induce oxidative stress by decreasing the antioxidant defenses and enhancing reactive oxygen species in striatum and cerebellum of adolescent rats. Regarding the histopathological findings, L-2-HG caused intense vacuolation, lymphocyte and macrophage infiltrates, eosinophilic granular bodies, and necrosis in striatum. Immunohistochemistry revealed that L-2-HG treatment provoked an increase of GFAP and a decrease of NeuN immunostaining, indicating reactive astroglyosis and reduction of neuronal population, respectively, in striatum. Similar macrophage infiltrates, associated with less intense vacuolation and lymphocytic infiltration, were observed in cerebellum. However, we did not observe necrosis, eosinophilic granular bodies, and alteration of GFAP and NeuN content in L-2-HG-teated cerebellum. From the biochemical and histological findings, it is presumed that L-2-HG provokes striatal and cerebellar damage in vivo possibly through oxidative stress induction. Therefore, we postulate that antioxidants may serve as adjuvant therapy allied to the current treatment based on a protein-restricted diet and riboflavin and L-carnitine supplementation in patients affected by L-2-HGA.

L-carnitine supplementation in patients with HIV/AIDS and fatigue: a double-blind, placebo-controlled pilot study.

BackgroundThe purpose of this study was to determine the effect of L-carnitine supplementation on fatigue in patients with terminal human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS).MethodsIn this randomized, double-blind, placebo-controlled, parallel-group study, patients who had end-stage HIV/AIDS with carnitine deficiency and fatigue received 3 g of oral L-carnitine or placebo for 2 weeks, followed by a 2-week, open-label phase with the same amount of L-carnitine for all patients. The primary outcome was the degree of fatigue according to the Brief Fatigue Inventory. Secondary outcomes included serum carnitine and lactate levels, physical, emotional, social, and functional well-being, performance status, mood, and CD4 count.ResultsEighteen patients in the treatment arm and 17 in the placebo arm completed the trial. At the end of the double-blind phase, total and free carnitine levels in the treatment arm rose from 28±9 to 48±17 nM/L (P<0.001) and from 24±8 to 40±13 nM/L (P<0.001) respectively, with no changes in the placebo arm. The primary outcome, ie, fatigue measured at the end of the blinded phase, did not improve. Secondary outcomes of function, quality of life, and mood did not show improvement either. The secondary outcome of serum lactate decreased from baseline in the treatment group (1.45±0.76 to 1.28±0.52 mmol/L) and increased in the placebo group (1.38±0.62 to 1.84±0.74 mmol/L; P<0.005).ConclusionOur study suggests that 3 g of oral L-carnitine supplementation for 2 weeks in terminally ill HIV/AIDS patients does not improve fatigue. This study might help to determine the dose and duration of treatment used in future clinical trials, as higher doses and/or longer periods of supplementation might be needed in order to detect an improvement. The reduction in serum lactate levels suggests a potential role for L-carnitine supplementation in patients undergoing certain types of antiretroviral therapy. This study contributes evidence-based data to the field of alternative and complementary medicine, a multibillion dollar industry in which controlled studies are not the norm.

Mechanisms underlying the anti-wasting effect of l-carnitine supplementation under pathologic conditions: evidence from experimental and clinical studies

Loss of skeletal muscle mass, also known as muscle wasting or muscle atrophy, is a common symptom of several chronic diseases, such as cancer and infectious diseases. Due to the strong negative impact of muscle loss on patient's prognosis and quality of life, the development of efficacious treatment approaches to combat muscle wasting are of great importance. In order to evaluate the suitability of L-carnitine (LC) as an anti-wasting agent for clinical purposes the present review comprehensively summarizes the results from animal and clinical studies showing the effects of supplementation with LC or LC derivatives (acetyl-LC, propionyl-LC) on critical mechanisms involved in skeletal muscle loss under pathologic conditions, such as increased proteolysis, impaired protein synthesis, myonuclear apoptosis, inflammation, oxidative stress, and mitochondrial dysfunction. Evidence from both animal and clinical studies exists that LC supplementation causes an improved nitrogen balance either due to increased protein synthesis or reduced protein degradation, an inhibition of apoptosis and an abrogation of inflammatory processes under pathologic conditions. Furthermore, strong evidence has been provided, at least from animal studies, that LC supplementation prevents oxidative stress and ameliorates mitochondrial function, whereas results from a very low number of available clinical studies in this regard are inconclusive. In conclusion, LC supplementation beneficially influences several critical mechanisms involved in pathologic skeletal muscle loss that may at least partially explain the anti-catabolic effects and the improvement of fatigue-related parameters following LC supplementation in patients with chronic diseases. However, more suitable clinical trials (double-blinded, randomized, placebo-controlled, large-scale) are necessary in order to establish LC supplementation as strategy for anti-wasting therapy.

Effectiveness of l-carnitine supplementation in patients with erythropoietin-resistant anemia

Whilst L-carnitine (LC) supplementation is recommended for the treatment of EPO-resistant anemia, the extent of effectiveness has been shown to vary considerably. Previous work by Reuter et al (2008) demonstrated a significant association between EPO-resistance and carnitine pool composition; based on these findings, it is hypothesized that patients who have a high EPO resistance index (ERI) are more likely to respond to LC supplementation. Preliminary assessment of this hypothesis was conducted as retrospective analysis, using prospectively-defined criteria, of data from 2 randomized, double-blind, placebo-controlled trials. HD patients were administered LC (20 mg/kg/wk/dialysis i.v.) or placebo for 24 weeks, with EPO dose and hemoglobin data assessed at Weeks 0, 12 & 24. Patients were classified as High (>0.02 μg/kg/wk/gHb) or Low ERI based on baseline data. Treatment effectiveness was analyzed using %baseline ERI for all patients (Low ERI & High ERI) and for High ERI patients only. 77 patients (38 LC/39 placebo) were included in the analysis, of which 22 (14 LC/8 placebo) were classified as High ERI. Analysis of all patient data indicated no significant differences between Week 0, 12 & 24 %baseline ERI for neither the LC nor placebo groups, whereas analysis of High ERI patient data indicated a significant reduction in %baseline ERI at Week 12 & 24 compared to Week 0 ( p =0.004) for the LC treatment group, with no significant placebo treatment effect. Similarly, analysis of %baseline ERI area-under-the-curve from 0–24°weeks indicated no significant treatment effects when all patients were included in the analysis, whereas for High ERI patients, significantly lower values were demonstrated for LC vs placebo ( p =0.016). These findings suggest that High ERI patients may receive the most benefit from LC supplementation. It is proposed that LC treatment results in an improvement in CPT activity via normalization of the LC/acylcarnitine ratio, thereby resulting in stabilization of the RBC membrane and improvement in anemia. A randomized, double-blind, placebo-controlled study is being conducted to investigate this further.

Dynamic adaptive changes of the serum carnitine esters during and after L-carnitine supplementation in patients with maintenance haemodialysis

Background. Here we report the serum carnitine ester profile during and after 1g iv/day L-carnitine supplementation in haemodialysis patients. Materials and methods. Seven patients were studied over 29 weeks. After a control day, 12 weeks of replacement therapy was introduced followed by 17 weeks of washout period. The serum acylcarnitine concentrations were determined by isotope dilution ESI MS/MS technique. Results. At baseline significantly decreased free carnitine (48%, p < 0.01) and a 1.5–16-fold elevation of 16 out of 27 acylcarnitines were detected in HD patients compared with the controls. On the last day of L-carnitine supplementation a 1.6–4.8-fold increase was observed in the acylcarnitine levels compared with day 0; the increase-profile was achieved in four different patterns. The increase rate was rapid and early saturable for C5, C5OH, C6DC, C8:1, C10DC and C18:2 esters, slower for C2, C4, C6, C18 and C18:1 esters, it was slowest and reached a late plateau for C3, C8DC, C14:2, C16 and C16:1, and finally almost gradual increase was seen for 11 acylcarnitines. Three months after the cessation of carnitine treatment marked concentration drops were found for almost all acylcarnitines (by 11–74 % of week 12, p < 0.05); the values further decreased over the five remaining weeks of the observation period. Conclusion. Carnitine administration affected the levels of circulating esters in different dynamics and kinetics suggesting a regulated, non-random adaptive reallocation of nutrients. A considerable washout was achieved 3 months after discontinuation of the supplementation; however, the profile still was suggestive for presence of rest of accumulated supplement.

L-Carnitine Supplementation in Patients with Advanced Cancer and Carnitine Deficiency: A Double-Blind, Placebo-Controlled Study

Carnitine deficiency is prevalent in populations with chronic illness, including cancer. In a recent open-label study, L-carnitine supplementation was well tolerated and appeared to improve fatigue and other outcomes in cancer patients. To further evaluate this finding, adult patients with advanced cancer, carnitine deficiency (free carnitine more than 35 μmol/L for males or less than 25 μmol/L for females, or acyl/free carnitine ratio of more than 0.4), moderate to severe fatigue, and a Karnofsky Performance Status (KPS) score of 50 or more, were randomly assigned to receive either L-carnitine (0.5 g/day for two days, followed by 1 g/day for two days, and then 2 g/day for 10 days) or placebo. This double-blind phase was followed by an open-label phase, during which all patients received L-carnitine supplementation for two weeks. Outcomes included the fatigue subscale of the Functional Assessment of Cancer Therapy-Anemia (FACT-An), the Linear Analog Scale Assessments (LASA), the Mini-Mental State Exam (MMSE), and the KPS. Twenty-nine patients (12 placebo, 17 L-carnitine) were included in the intent-to-treat (ITT) analysis. From baseline to the end of the double-blind phase, serum total and free L-carnitine increased from 32.9 ± 3.8 to 56.6 ± 20.5 ( P = 0.004), and from 22.9 ± 19.4 to 45.3 ± 17.2 ( P = 0.004), respectively, in the L-carnitine-treated group, and from 28.2 ± 10.2 to 36.2 ± 8.7 ( P = ns), and from 22.6 ± 7.9 to 28.7 ± 8.6 ( P = ns) in the placebo group, respectively. The planned ITT analysis revealed no significant improvement in any of the study's endpoints, and these negative findings were not different when data from two patients who did not adhere to the protocol were eliminated. However, an exploratory covariate analysis that excluded these two protocol violators and included outcome data from both the double-blind and open-label phases demonstrated significantly improved fatigue on the FACT-An fatigue subscale ( P < 0.03), and significantly improved FACT-An functional well-being subscale ( P < 0.03), and KPS ( P < 0.003), in the group that started with L-carnitine during the double-blind phase. These data do not support the conclusion that L-carnitine in the doses tested reverses cancer-related fatigue in carnitine-deficient patients. However, L-carnitine supplementation does increase L-carnitine serum levels, and the positive findings in an exploratory analysis justify a larger study to determine if this strategy could be of benefit for a subpopulation of cancer patients.

Safety, Tolerability and Symptom Outcomes Associated with l-Carnitine Supplementation in Patients with Cancer, Fatigue, and Carnitine Deficiency: A Phase I/II Study

Carnitine deficiency is among the many metabolic disturbances that may contribute to fatigue in patients with cancer. Administration of exogenous l-carnitine may hold promise as a treatment for this common symptom. Little is known about l-carnitine safety, tolerability, and dose-response in patients with cancer. We conducted a Phase I/II open-label trial to assess the safety and tolerability of exogenous l-carnitine and clarify the safe dose range associated with symptom effects for future controlled trials. Adult patients with advanced cancer, carnitine deficiency (free carnitine <35 for males or <25 μM/L for females, or acyl/free carnitine ratio >0.4), moderate to severe fatigue, and a Karnofsky Performance Status (KPS) score ≥50 were entered by groups of at least three into a standard maximum tolerated dose design. Each successive group received a higher dose of l-carnitine (250, 750, 1250, 1750, 2250, 2750, 3000 mg/day, respectively), administered in two daily doses for 7 days. To compare symptom outcomes before and after supplementation, patients completed validated measures of fatigue (Brief Fatigue Inventory [BFI]), depressed mood (Center for Epidemiologic Studies Depression Scale [CES-D]), quality of sleep (Epworth Sleeplessness Scale [ESS]), and KPS at baseline and 1 week later. Of the 38 patients screened for carnitine levels, 29 were deficient (76%). Twenty-seven patients participated (“intention to treat, ITT”) (17 males, 10 females), and 21 completed the study (“completers”); 17 of these patients (“responders,” mean ± [SD] age = 57.9 ± 15) had increased carnitine levels at the end of the supplementation period. The highest dose achieved was 3000 mg/day. No patient experienced significant side effects and no toxicities were noted. Analysis of all the patients accrued (ITT, n = 27) showed a total carnitine increase from 32.8 ± 10 to 54.3 ± 23 μM/L ( P < 0.001) and free carnitine increase from 26.8 ± 8 to 44.1 ± 17 μM/L ( P < 0.001). BFI decreased significantly, from 66 ± 12 to 39.7 ± 26 ( P < 0.001); ESS decreased from 12.9 ± 12 to 9 ± 6 ( P = 0.001); and CES-D decreased from 29.2 ± 12 to 19 ± 12 ( P < 0.001). A separate analysis of the 17 “responders” showed a dose-response relationship for total- ( r = 0.54, P = 0.03), free-carnitine ( r = 0.56, P = 0.02) levels, and fatigue (BFI) scores ( r = −0.61, P = 0.01). These findings suggest that l-carnitine may be safely administered at doses up to 3000 mg/day and that positive effects may be more likely at relatively higher doses in this range. This study provides the basis for the design of future placebo-controlled studies of l-carnitine supplementation for cancer-related fatigue.

L-carnitine supplementation in patients with cystic acne on isotretinoin therapy

Background Patients with cystic acne (CA) on Isotretinoin (Iso) therapy might present muscular symptoms as side effect of the drug. Myalgia, weakness, hypotension are also some of the main characteristics of carnitine (car) deficiency.Methods Two hundred and thirty (N=230) patients with CA were treated with Isotretinoin (0.5 mg/kg per 24 h). All the patients were requested to visit our out-patient department at the onset of muscular symptoms. Laboratory tests including car (total, free, acylcarnitine) were determined in blood and urine before treatment, at the onset of muscular symptoms and after the end of a 45 day study. Fifty percent of the patients with muscular involvement received L-carnitine (100 mg/kg per 24 h per os) (group C) and 50% placebo (group P).Results Their laboratory tests showed the well known increases of their liver enzymes and lipids, whereas car blood levels were remarkably decreased at the onset of their muscular symptoms and or at the end of the study. Their supplementation with L-car, in patients of group C (N=20) without Iso discontinuation or reduction, resulted in the disappearance of their muscular symptoms within 5–6 days and normalisation not only of the increased levels of their liver enzymes but also those of car, at the 45 day of their therapy. Additionally, the patients who received placebo (group P, N=20) continued complaining for mualgias. The rest of the patients (group A, N=190) did not experience any muscular symptoms, their laboratory tests showed elevation of liver enzymes and lipids and a decrease in car levels in the blood whereas a remarkable increase of car excretion was determined in their urine.Conclusions Iso therapy decreases car blood levels in patients with CA. l-car supplementation might treat liver and muscular side effects of the drug. These hopeful preliminary results need further investigation.