Carnitine Deficiency In Patients Research Articles

Research on the Clinical Practical Use of Pivoxil-Conjugated Antibodies and the Risk of Carnitine Deficiency Using Real-World Data.

In Japan, pivoxil-conjugated antibodies (PVs) are commonly used to treat infections. However, carnitine deficiency is a known adverse drug reaction associated with PV treatment. This study aimed to research the practical use of PV and assess the risk of carnitine deficiency in patients receiving PV compared to their amoxicillin (AM)-treated counterparts. The Pediatric Medical Information Collection System (P-MICS) served as the data source for this study. The study cohort comprised patients aged 0-15 years prescribed PV between April 2016 and March 2021. Data on the actual PV prescriptions were extracted for each patient. To evaluate the risk of carnitine deficiency, adverse events (AEs) were defined as carnitine deficiency and its associated symptoms. Propensity score matching was employed to compare the AE incidence between the PV and AM groups. The number of cases of PV prescriptions decreased year-on-year between 2016 and 2021, and >80% of prescriptions were dispensed in the clinic. The propensity score matching analysis demonstrated no statistically significant difference in the incidence of carnitine deficiency and its associated symptoms between the PV and AM groups. Our findings suggest that the risk of carnitine deficiency in children treated with PV is not significantly higher than that associated with other antibiotics.

Effectiveness of Propionyl-L-Carnitine Supplementation on Exercise Performance in Intermittent Claudication: A Systematic Review.

Lower extremity peripheral artery disease (PAD) affects 8.5 million people in the United States and more than 200 million worldwide. The most significant risk factors for PAD are hyperlipidemia, hypertension, diabetes mellitus, chronic kidney disease, and smoking. Intermittent claudication (IC) is the predominant symptom of PAD, but only about 10% of patients with PAD experience IC and are associated with reduced exercise capacity. The pathophysiology of IC is characterized by different degrees of stenosis and obstruction, with a progressive reduction in distal perfusion pressure and blood flow. Supervised exercise therapy is recommended as the initial therapy for IC, but the recommendations for medical treatment of IC vary significantly. Propionyl L-carnitine is an acyl derivative of levocarnitine (L-carnitine) and is indicated for patients with the peripheral arterial occlusive disease. It corrects secondary muscle carnitine deficiency in patients with PAD, significantly improving the walking capacity; its levels increase in serum and muscle. Thus, it is suggested to enhance blood flow and oxygen supply to the muscle tissue via improved endothelial function, thereby reducing hypoxia-induced cellular and biochemical disruptions.

Significance of Levocarnitine Treatment in Dialysis Patients.

Carnitine is a naturally occurring amino acid derivative that is involved in the transport of long-chain fatty acids to the mitochondrial matrix. There, these substrates undergo β-oxidation, producing energy. The major sources of carnitine are dietary intake, although carnitine is also endogenously synthesized in the liver and kidney. However, in patients on dialysis, serum carnitine levels progressively fall due to restricted dietary intake and deprivation of endogenous synthesis in the kidney. Furthermore, serum-free carnitine is removed by hemodialysis treatment because the molecular weight of carnitine is small (161 Da) and its protein binding rates are very low. Therefore, the dialysis procedure is a major cause of carnitine deficiency in patients undergoing hemodialysis. This deficiency may contribute to several clinical disorders in such patients. Symptoms of dialysis-related carnitine deficiency include erythropoiesis-stimulating agent-resistant anemia, myopathy, muscle weakness, and intradialytic muscle cramps and hypotension. However, levocarnitine administration might replenish the free carnitine and help to increase carnitine levels in muscle. This article reviews the previous research into levocarnitine therapy in patients on maintenance dialysis for the treatment of renal anemia, cardiac dysfunction, dyslipidemia, and muscle and dialytic symptoms, and it examines the efficacy of the therapeutic approach and related issues.

Association between carnitine deficiency and the erythropoietin resistance index in patients undergoing peritoneal dialysis: a cross-sectional observational study

Carnitine deficiency contributes to developing various pathological conditions, such as cardiac dysfunction, muscle weakness, and erythropoietin-resistant anemia in patients undergoing hemodialysis. However, a conclusion has not been reached concerning the prevalence and the effect of carnitine deficiency in patients undergoing peritoneal dialysis (PD). In this study, the prevalence of carnitine deficiency and the clinical factors associated with carnitine deficiency were investigated in 60 patients undergoing PD. The median age of the patients was 62.5 years (52.5–72.5 years), the proportion of male sex was 44/60 (73.3%), and the median PD period was 24 months (12–45 months). Carnitine deficiency (acyl carnitine/free carnitine ratio >0.4) was detected in 56/60 (93%) patients. Multiple regression analysis showed that the erythropoietin resistance index was independently associated with carnitine deficiency (β = 0.283, p = 0.04). These results suggest that carnitine plays pivotal roles in hematogenesis in patients undergoing PD.

EP.68Carnitine deficiency in patients with Duchenne muscular dystrophy requiring long-term tube feeding and heart function improvement by carnitine replacement

Carnitine deficiency and the effects of long-term carnitine supplementation were investigated in 4 patients with Duchenne muscular dystrophy (DMD) requiring long-term feeding tube. All the patients were tube-fed for 40 months or longer and were on enteral nutrition without supplemented carnitine. They had carnitine deficiency or free carnitine levels that were below normal levels. They were administered 1,500 mg of carnitine replacement daily for 6 years. Their free carnitine levels normalized 1 month after initiating carnitine replacement therapy. However, although patients showed improvement with long-term carnitine replacement therapy, their ejection fraction (EF) was significantly low at baseline and continued to decrease until 2 years of carnitine replacement but tended to increase at 3 years and onward after initiating carnitine replacement therapy. It is unlikely that EF improves in the clinical course of DMD; therefore, it was considered an effect of long-term carnitine replacement therapy. The most common cause of death in patients with DMD is heart failure. Thus, the results of this study suggested that carnitine supplementation improves vital prognosis in patients with DMD.

Incidence of carnitine deficiency in patients with cancer pain: A pilot study.

Carnitine deficiency is reportedly associated with increased pain sensation in diabetes mellitus and fibromyalgia, but the association between serum carnitine concentration and cancer pain has not been fully elucidated. We investigated the incidence of carnitine deficiency in patients with cancer pain, and examined the effect of the patients' demographic and clinical characteristics on pain intensity and carnitine deficiency. The serum carnitine concentration was measured in 50 patients with cancer pain receiving non-steroidal anti-inflammatory drugs, but not opioids. Multivariate regression analysis was used to determine the association of carnitine concentration, pain intensity, age and gender with hemoglobin and C-reactive protein (CRP) concentrations. Carnitine deficiency was detected in 9 of the patients (18.0%) and found to be significantly correlated with an elevated CRP concentration (P=0.039). In conclusion, although there does not appear to be an association between carnitine deficiency and cancer pain, it may be affected by inflammation or infection.

Carnitine Deficiency and Improvement of Muscle Cramp by Administration of Carnitine in Patients with Liver Cirrhosis

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.

Carnitine deficiency presenting with a decreased mental state in a patient with amyotrophic lateral sclerosis receiving long-term tube feeding: a case report

IntroductionL-carnitine is an important metabolic mediator involved in fatty acid transport. It is obtained from the diet, particularly from animal products, such as red meat. Previous reports have revealed that long-term tube feeding with a commercial product containing no or low levels of carnitine can lead to an altered mental state caused by hyperammonemia.Case presentationA 72-year-old Japanese man had a 12-year history of amyotrophic lateral sclerosis. He was bedridden and had required mechanical ventilation and enteral tube feeding for 10 years at home. His main enteral solution was a commercial product that contained low carnitine levels, and he sometimes received coffee and homemade products such as miso soup. Our patient’s ability to communicate gradually deteriorated over a period of one year. His serum total carnitine level was abnormally low, at 26.7μmol/L (normal range, 45 to 91μmol/L), but his ammonium level was normal. His mental state improved dramatically after starting L-carnitine supplementation (600mg twice daily).ConclusionThis case highlights the importance of avoiding carnitine deficiency in patients with amyotrophic lateral sclerosis undergoing long-term tube feeding. These patients experience progressive muscle atrophy that might cause impaired carnitine storage and might manifest as communication difficulties. Carnitine deficiency can be misdiagnosed as a progression of systemic muscle atrophy. Clinicians should be aware of this disorder and should consider periodically measuring carnitine levels, regardless of the patient’s serum ammonium levels.

Carnitine Deficiency and its Possible Risk Factors in TB Patients: First Report

To assess carnitine serum levels and possible risk factors of its deficiency in patients with TB. All newly diagnosed TB patients admitted to an infectious diseases ward were recruited. Demographic, clinical and paraclinical characteristics of the patients were collected. Total carnitine serum concentrations were measured. To investigate factors that can predict carnitine deficiency, logistic regression analysis with odds ratio and 95% CI was performed. The mean ± standard deviation of carnitine serum levels of patients was 43.77 ± 32.92 µmol/l. Carnitine deficiency was detected in 47.7% of the study population. According to the final model of multivariate logistic regression analysis, increased serum triglyceride levels and hypoalbuminemia were identified as predictive factors of carnitine deficiency in TB patients aged over 35 years old. Nearly half of Iranian patients with TB were carnitine-deficient. Increased serum triglyceride levels and hypoalbuminemia were identified as independent risk factors of carnitine deficiency in patients aged over 35 years. Considering malnutrition as a major risk factor of TB and the safety of carnitine supplementation, use of carnitine as an adjunctive modality instead of other standard interventions may show beneficial effects in patients with TB.

Propionyl l-carnitine: intermittent claudication and peripheral arterial disease

Peripheral arterial disease (PAD) is a clinical manifestation of underlying aorto-iliac and leg atherosclerosis that is characterized by different stages of stenosis and obstruction. It affects approximately 12% of the adult population and about 20% of people over the age of 70 years, and is associated with increased cardiovascular (CV) and cerebrovascular morbidity. Intermittent claudication (IC) is the major symptom of PAD; it is defined as cramping leg pain (in the buttock, thigh, or calf) while/after clim bing one or two flights of stairs, or during walking. The goals of IC management are to: slow the progression of local and systemic atherosclerosis, prevent major fatal and nonfatal CV events (myocardial infarction and stroke), improve walking capacity, prevent and reduce resting pain and cutaneous lesions. Propionyl L-carnitine is an acyl derivative of levocarnitine (L-carnitine) and is indicated for patients with peripheral arterial occlusive disease. It corrects secondary muscle carnitine deficiency in patients with PAD, significantly improving the walking capacity; it is a free radical that produces positive effects on endothelial function; it protects from oxidative stress; and it enhances most measures of quality of life. The recent Trans-Atlantic Inter-Society Consensus II update recommends the use of propionyl L-carnitine in combination with physical training to improve the symptoms associated with PAD.

Carnitine deficiency and l-carnitine supplementation in lysinuric protein intolerance

The aim of the study was to investigate the prevalence and mechanisms of development of carnitine deficiency in patients with lysinuric protein intolerance (LPI). In our cohort of 37 Finnish patients with LPI, 8 (8-52 years of age) have been diagnosed with hypocarnitinemia. Their free and total serum carnitine levels, acyl carnitine profiles, renal function, diet, and medication were compared with the data from 8 age- and sex-matched patients with LPI not treated with carnitine supplementation. In patients with LPI, hypocarnitinemia was strongly associated with female sex, renal insufficiency, and the use of ammonia-scavenging drugs. Of the 8 hypocarnitinemic patients, 3 complained of muscle weakness, and their symptoms disappeared during carnitine supplementation. Oral lysine supplementation did not correct hypocarnitinemia in our patients. The patients with LPI are at considerable risk for carnitine deficiency. Supplementation of hypocarnitinemic LPI patients with oral l-carnitine improved serum total carnitine values, but the ratio of free and total carnitine remained subnormal in all supplemented patients except one. Furthermore, decreased ratio of free and total serum carnitine was common even in LPI patients with normal total serum carnitine concentration.

Cardiac involvement in children with coeliac disease and the effect of gluten free diet on cardiac performance

Background. The association between coeliac disease (CD) and several other disorders is well established [ [1] Dewar D.H. Clinical features and diagnosis of celiac disease. Gastroenterology. 2005; 128: S19-S24 Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar ]. Idiopathic dilated cardiomyopathy and autoimmune myocarditis have been recently described in association with or as a presenting feature of CD in adult [ 2 Curione M. Carnitine deficiency in patients with celiac disease and idiopathic dilated cardiomyiopathy. Nutr Metab Cardiovasc Dis. 2005; 15: 279-283 Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar , 3 Frustaci A. Celiac disease associated with autoimmune myocarditis. Circulation. 2002; 105: 2611-2618 Crossref PubMed Scopus (152) Google Scholar ]. No evidence-based data is available for this issue in children.

Debate Forum: Levocarnitine Therapy Is Rational and Justified in Selected Dialysis Patients

Carnitine is a metabolic cofactor which is essential for normal fatty acid metabolism. Patients with chronic kidney disease on dialysis have been shown both to suffer from disordered fatty acid metabolism and to have a significant deficiency in plasma and tissue carnitine. Aberrant fatty acid metabolism has been associated with a number of cellular abnormalities such as increased mitochondrial permeability (a promoter of apoptosis), insulin resistance, and enhanced generation of free radicals. These cellular abnormalities have, in turn, been correlated with pathological clinical conditions common in dialysis patients including cardiomyopathy with attendant hypotension and resistance to the therapeutic effect of recombinant human erythropoietin (EPO). In 1999, the Food and Drug Administration approved levocarnitine injection for the prevention and treatment of carnitine deficiency in patients on dialysis based on documentation of free plasma carnitine levels in dialysis patients similar to other serious carnitine deficiency states for which treatment was required. Data analysis performed by expert panels convened by both the American Association of Kidney Patients and, subsequently, the National Kidney Foundation recommended a trial of levocarnitine therapy for specific subsets of dialysis patients including those with EPO resistance, dialysis-related hypotension, cardiomyopathy and muscle weakness. In 2003, the Centers for Medicare and Medicaid services convened a Medical Advisory Committee which established reimbursement on a national level for carnitine-deficient dialysis patients who had either dialysis-related hypotension or EPO resistance. Recently, a correlation between reductions in hospitalization rates of dialysis patients receiving levocarnitine therapy has been demonstrated in a large retrospective study. Despite data-based recommendations and national reimbursement, only a small minority of dialysis patients have been prescribed a therapeutic trial of levocarnitine. Whereas the reasons for the reluctance of nephrologists to prescribe this therapeutic trial are unclear, possible explanations include a lack of appreciation of the pivotal role played by carnitine in cellular metabolism and the strength of evidence for a substantial deficiency of carnitine in dialysis patients, an underestimation of the prognostic import of EPO resistance and dialysis-related hypotension, inadequate dissemination of the clinical trial data supporting the use of levocarnitine in dialysis patients, and the heterogeneous clinical response of dialysis patients to levocarnitine therapy. Difficulties in documenting both initial eligibility and evidence of improvement as a result of therapy may also be a contributing factor. This paper discusses the biological role of carnitine and its particular relevance to dialysis patients. Clinical trial data concerning an effect of therapy on EPO resistance and dialysis-related hypotension are summarized along with a discussion of the logic behind the use of levocarnitine in dialysis. Finally, the difficulties posed by a reimbursement policy based on clinical as opposed to laboratory endpoints and a heterogeneous response to therapy are addressed.

Carnitine deficiency in patients with coeliac disease and idiopathic dilated cardiomyopathy

Idiopathic dilated cardiomyopathy (IDCM) and coeliac disease (CD) are two pathological conditions which may lead, by different mechanisms, to malabsorption of various micronutrients, including carnitine, active in cardiac metabolism. The aim of the present investigation was primarily to evaluate differences in serum concentrations of total carnitine between IDCM patients and patients with IDCM associated with CD and then also to evaluate, in the latter, the effect of a gluten-free diet on serum concentrations of total carnitine. Serum carnitine was determined by enzymatic spectrophotometric assay in three groups of individuals: group A, 10 patients (5 males, 5 females), mean age 46.5+/-10.8 years, presenting isolated IDCM; group B, 3 patients (2 males, 1 female), mean age 34+/-8 years, with IDCM+CD; and group C, 10 healthy subjects (5 males, 5 females), mean age 38.6+/-11.1 years. All patients with IDCM belonged to class NYHA I-II. Mean concentrations of total serum carnitine in the group of patients with isolated IDCM (group A) were found to be lower than in the controls (group C). The concentrations in patients with IDCM associated with CD (group B) were lower than in the control group and also lower than in the isolated IDCM (group A). After 2 years on a gluten-free diet, patients presenting IDCM associated with CD showed a progressive increase in mean serum carnitine levels compared to values observed prior to the diet. Patients presenting IDCM associated with CD show a greater decrease in serum total carnitine levels than patients presenting the isolated form of IDCM. A gluten-free diet, in these patients, leads to a progressive increase in serum levels of this substance.

Levocarnitine and Dialysis: A Review

Among the various metabolic abnormalities documented in dialysis patients are abnormalities related to the metabolism of fatty acids. Aberrant fatty-acid metabolism has been associated with the promotion of free-radical production, insulin resistance, and cellular apoptosis. These processes have been identified as important contributors to the morbidity experienced by dialysis patients. There is evidence that levocarnitine supplementation can modify the deleterious effects of defective fatty-acid metabolism. Patients receiving hemodialysis and, to a lesser degree, peritoneal dialysis have been shown to be carnitine deficient, as manifested by reduced levels of plasma free carnitine and an increase in the acyl:free carnitine ratio. Cardiac and skeletal muscles are particularly dependent on fatty-acid metabolism for the generation of energy. A number of clinical abnormalities have been correlated with a low plasma carnitine status in dialysis patients. Clinical trials have examined the efficacy of levocarnitine therapy in a number of conditions common in dialysis patients, including skeletal-muscle weakness and fatigue, cardiomyopathy, dialysis-related hypotension, hyperlipidemia, and anemia poorly responsive to recombinant human erythropoietin therapy (rHuEPO). This review examines the evidence for carnitine deficiency in patients requiring dialysis, and documents the results of relevant clinical trials of levocarnitine therapy in this population. Consensus recommendations by expert panels are summarized and contrasted with present guidelines for access to levocarnitine therapy by dialysis patients.

Muscle carnitine deficiency in patients with severe peripheral vascular disease: Brevetti G, Angelini C, Rosa M, et al. Circulation 1991;84:1490–1495

Muscle carnitine deficiency in patients with severe peripheral vascular disease: Brevetti G, Angelini C, Rosa M, et al. Circulation 1991;84:1490–1495

Muscle Carnitine deficiency in patients with severe peripheral vascular disease : Brevetti G, Corrado A, Maurizio R, et al. Circulation 84:4, 1991

Muscle Carnitine deficiency in patients with severe peripheral vascular disease : Brevetti G, Corrado A, Maurizio R, et al. Circulation 84:4, 1991

Muscle carnitine deficiency in patients with severe peripheral vascular disease.

This study was designed to evaluate the effect of severe peripheral arterial insufficiency on carnitine concentrations and carnitine acetyltransferase and palmitoyltransferase activities in the ischemic skeletal muscles of patients with severe peripheral vascular disease. Nine biopsy specimens of ischemic muscles were obtained from five patients undergoing reconstructive vascular surgery. Biopsies from 35 normal subjects served as controls. Ischemic muscles showed a significant reduction in total carnitine from the control value of 20.9 +/- 5.2 to 11.6 +/- 6.2 nmol/mg noncollagen protein (p less than 0.01). A significantly lower free carnitine and acylcarnitine content contributed to this reduction. Similarly, carnitine acetyltransferase activity was reduced in the ischemic muscles from the control value of 102.1 +/- 41.2 to 52.9 +/- 22.1 nmol/min/mg noncollagen protein (p less than 0.01). On the contrary, carnitine palmitoyltransferase activity did not show any change (0.29 +/- 0.05 nmol/min/mg noncollagen protein in the ischemic muscles and 0.28 +/- 0.07 nmol/min/mg noncollagen protein in controls). Carnitine, acylcarnitines, and enzyme activities were also measured in the ischemic muscles in four additional patients 2 days after intravenous administration of L-propionylcarnitine (1.5 g as a single bolus followed by an infusion of 1 mg/kg/min for 30 minutes). Treatment restored normal levels of carnitine and its esters in the ischemic muscles but did not affect enzyme activities. Demonstration of carnitine deficiency in severe peripheral vascular disease substantiates previous findings showing the efficacy of carnitine supplementation to ischemic muscles. Furthermore, the feasibility of restoring carnitine homeostasis with L-propionylcarnitine provides the basis for clinical trials aimed at assessing the efficacy of this carnitine ester in the treatment of peripheral vascular disease.

A case of carbamylphosphate synthetase-I deficiency associated with secondary carnitine deficiency —l-carnitine treatment of CPS-I deficiency

We describe a male infant with congenital hyperammonaemia due to partial carbamylphosphate synthetase-I (CPS-I) deficiency. At 21 days of age, he had convulsions and at 53 days of age hyperammonaemic coma. Therapy with sodium benzoate, L-arginine, essential amino acids, L-carnitine and peritoneal dialysis lowered the blood ammonia levels, and his clinical manifestations improved. The CPS-I activity in liver tissue obtained by open biopsy was about 25.6% of normal values. The serum and urine free carnitine levels in the patient decreased during the hyperammonaemic crisis and were low at 7 months of age. After oral administration of L-carnitine (10 mg/kg per day) at 7 months of age, the mean blood ammonia levels decreased significantly, accompanied by an increase in serum and urine free carnitine levels. We propose the use of L-carnitine therapy to prevent secondary carnitine deficiency in patients with CPS-I deficiency as well as ornithine transcarbamylase (OTC) deficiency.

Renal handling of carnitine in children with carnitine deficiency and hyperammonemia associated with valproate therapy

Free and acylcarnitine in serum and urine samples were measured in five patients with hyperammonemia associated with anticonvulsant therapy including sodium valproate, of whom three had a Reye-like syndrome. All had considerable reduction in serum free carnitine and slight increase of acylcarnitine concentrations, suggesting increased conversion of free to acylcarnitine by valproate administration. Urinary excretion of both free and acylcarnitine was increased, accompanied by depressed reabsorption of free carnitine and decreased acylcarnitine/free carnitine clearance ratio. These results indicate a decreased threshold for free carnitine. The combination of these several factors may be responsible for carnitine deficiency in patients with hyperammonemia taking valproate.