Serum Carnitine Research Articles

The effect of oral L‐carnitine supplementation on the lipid profiles of hyperlipidaemic children

To investigate the carnitine status and the effect of carnitine supplementation on serum lipid profiles in children with hyperlipoproteinaemia, a clinical open trial was conducted at Hacettepe University Ihsan Dogramaci Children's Hospital, Section of Nutrition and Metabolism. Patients were given carnitine at a dose of 100 mg/kg/d for 12 wk. Blood samples for the determination of lipid profile and carnitine levels and urine samples for carnitine levels were obtained on admission, at week 4 and week 12 of the study period. A total of 41 children were enrolled in the study: 20 patients had type II heterozygotes, eight patients had type II homozygotes, three patients had type III, six patients had type V and four patients had secondary hyperlipidaemias. Serum and urine carnitine levels were within normal limits on admission. No significant correlations were found between serum carnitine levels and serum lipid profiles. Serum HDL and apolipoprotein A-I decreased significantly during the 12 wk of intervention in type II heterozygotes. In type II homozygotes, total cholesterol and LDL levels at weeks 4 and 12 increased significantly compared to initial levels. No significant change was noted for lipid parameters in hyperlipoproteinaemia type V. The results of this trial demonstrated that carnitine supplementation was of no benefit for children with hyperlipidaemias, especially in primary hyperlipoproteinaemia type II heterozygotes, homozygotes and type V.

Muscle carnitine in hypo‐ and hyperthyroidism

Weakness is common in both hyper- and hypothyroidism, and skeletal muscle L-carnitine may play a role in this regard, as suggested by studies indicating abnormal levels of carnitine in serum and urine of patients with thyroid dysfunction. Skeletal muscle samples were obtained for carnitine analysis from control subjects, and from hyperthyroid and hypothyroid patients before and after treatment. There was a significant reduction in carnitine, especially the esterified portion, in hyperthyroid individuals, with a return to normal as euthyroid status was regained. In hypothyroid patients, there was a trend for carnitine to be lower than normal and for improvement once euthyroid status was attained. Our data indicate that muscle carnitine levels are affected by both hypo- and hyperthyroidism. A decrease in muscle carnitine in both conditions may contribute to thyroid myopathy.

L-Carnitine Supplementation does not Promote Weight Loss in Ovariectomized Rats Despite Endurance Exercise

In this five-week study, we tested the hypotheses that free access to a maintenance diet supplemented with L-carnitine (L-C) would reduce body fat in adult, sedentary, ovariectomized (OVX) rats, and that there would be an additive effect of L-C on weight reduction in swim-trained animals. As expected, serum carnitine was higher in rats fed the L-C diet, and the OVX-induced weight gain and abdominal fat were counteracted by swimming. L-C supplementation did not reduce the weight gain or abdominal fat in these adult female rats, Moreover, though not reaching statistical significance, rats that were fed L-C demonstrated a tendency for greater weight gain than their basal-fed counterparts despite no difference in energy intake. If the results of this study on ovariectomized rats can be translated to postmenopausal women, moderate intensity exercise may be recommended, but L-C supplementation, with no energy restriction, may be contraindicated as a weight loss method in this cohort.

Hipoglucemia sin cetosis. Caso clínico

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a rare disease, inherited as autosomal-recessive trait, with variable clinical presentation including severe hypoglycaemia, cardiomyopathy, sudden infant death, progressive liver failure, 'Reye like' syndrome, neuromyopathy, muscle weakness and rhabdomyolysis. We report a 3 years old male patient admitted to our emergency department with vomiting, hypotonia and prostration, after a common respiratory infection. The presence of hypoketotic hypoglycaemia and elevated liver enzymes in the admission motivated a metabolic study. We found an abnormal low lactate/pyruvate ratio, decreased serum carnitine and dicarboxylic aciduria leading to the diagnosis of a fatty acid oxidation disorder (LCHADD). The molecular study of HADHA gene revealed homozygosity for the G1528C mutation in the patient DNA, and heterozygosity in both parents. The diagnosis of a fatty acid oxidation disorder must be considered in the presence of vomiting associated with excessive prostration specially if there is hypoketotic hypoglycaemia or familiar sudden infant death history. Physicians should be aware about these conditions and for the importance of measuring both glycaemia and ketone bodies during the evaluation of high risk situations.

Relative Carnitine Deficiency in Autism

A random retrospective chart review was conducted to document serum carnitine levels on 100 children with autism. Concurrently drawn serum pyruvate, lactate, ammonia, and alanine levels were also available in many of these children. Values of free and total carnitine (p < 0.001), and pyruvate (p = 0.006) were significantly reduced while ammonia and alanine levels were considerably elevated (p < 0.001) in our autistic subjects. The relative carnitine deficiency in these patients, accompanied by slight elevations in lactate and significant elevations in alanine and ammonia levels, is suggestive of mild mitochondrial dysfunction. It is hypothesized that a mitochondrial defect may be the origin of the carnitine deficiency in these autistic children.

Serum carnitine levels in patients with homozygous beta thalassemia: a possible new role for carnitine?

Carnitine (beta-hydroxy-gamma-trimethylaminobutyric acid) facilitates the transfer of activated long-chain fatty acids from the cytoplasm to the mitochondria, the site of their beta-oxidation. Carnitine deficiency results in a reduced usage of fatty acids in energy production and therefore the appearance of clinical symptoms such as myalgia and muscle weakness. In the present study, serum carnitine levels were measured in 45 children and 20 adults with homozygous beta thalassemia. A decrease in serum carnitine levels (total, free and acyl) was found, without any evidence of disorder in the process of mitochondrial beta-oxidation. The possible cause of this finding could be related to a reduced hepatic carnitine biosynthesis. In patients with homozygous beta thalassemia, the reduction of serum carnitine levels might play an important role in the appearance of muscular dysfunction. It is possible that L : -carnitine administration in these patients might improve or even resolve the aforementioned symptom.

Primary carnitine deficiency: adult onset lipid storage myopathy with a mild clinical course

We studied two adult patients with myalgia and muscular fatigability during prolonged physical exercise. Serum creatine kinase was increased and muscle biopsy revealed a lipid storage myopathy affecting predominantly the type I fibres. Skeletal muscle carnitine content was reduced to 15% and 21% of the normal mean values, while serum carnitine levels were either normal or decreased. Four months of oral therapy with L-carnitine (3 g per day) resolved the clinical symptoms completely in both patients, and a subsequent muscle biopsy confirmed a marked reduction of lipid storage, along with increased muscle carnitine levels. The analysis of renal carnitine excretion and the exclusion of possible secondary carnitine deficiencies in both patients are compatible with mild defects of the carnitine transporter in one patient and of carnitine biosynthesis in the other. Since myalgia and muscular fatigue are frequent but unspecified complaints of otherwise clinically unremarkable adult patients, it is important to identify myopathies associated with primary carnitine deficiency because they may be amenable to treatment.

Serum Carnitine Levels in Newborns with Perinatal Asphyxia and Relation to Neurologic Prognosis

Neonatal hypoxic encephalopathy is one of the major causes of permanent neurological sequel. This study was conducted to investigate serum total, free and acylcarnitine levels in asphyxiated newborns with or without encephalopathy. Serum total, free and acylcarnitine levels were investigated in 21 newborns with and seven asphyxiated newborns without signs of encephalopathy. The newborns with encephalopathy were further divided into grade 1, 2 and 3 encephalopathy groups. Serum total and acylcarnitine concentrations of the whole encephalopathy group were significantly lower than the non-encephalopathy group ( p =0.042 for both). Serum total and acylcarnitine concentrations of grade 3 encephalopathy group were significantly lower than the non-encephalopathy group ( p =0.014 and p =0.040, respectively). No significant differences were noticed for free carnitine levels. Total carnitine levels were positively correlated with birth weight and 10th minute apgar score, whereas acylcarnitine levels were found to correlate with cord blood pH and free carnitine levels with birth weight. Cord blood pH, and total carnitine levels were found to be the most significant determinants of the neurological outcome at one year of age. It was emphasized that carnitine deficiency could occur in severely affected asphyxiated newborns and it is related to the outcome at one year of age.

Low serum carnitine in HIV-infected children on antiretroviral treatment

HIV-infection and antiretroviral therapies are associated with energy dysfunction and lipid metabolism in adults. Our aim was to detect a possible carnitine deficiency in HIV-infected children on antiretroviral treatments. We analysed the relation among serum carnitine, its amino-acid precursors (methionine and lysine), clinical evaluation and antiretroviral therapy. Cross-sectional study performed in a tertiary care hospital. A total of 79 HIV-infected children on antiretroviral therapy, monitored prospectively in our hospital. Antiretroviral therapy included nucleoside analogues plus protease inhibitors and/or non-nucleoside analogues. Carnitine was analysed by an enzymatic-spectrometric procedure, and amino acids by ion exchange chromatography. Reference values of carnitine and amino acids were established in apparently healthy children who underwent presurgical analysis for minor surgery. Serum free and total carnitine, acylcarnitines, methionine and lysine were significantly lower in HIV-infected children compared with our reference values for similar ages (P<0.0001; Student's t-test). Low carnitine values were observed in 37% of our HIV-infected children. A significantly positive correlation was observed between serum total carnitine and methionine or lysine (P<0.0001 and P=0.005, respectively; Pearson test). No relation was observed between serum carnitine and clinical stage of HIV infection, immunological or nutritional status or lipodystrophy. Free and total carnitine were significantly lower (P=0.002 and 0.033, respectively) in HIV-infected patients on protease inhibitors (N=56) compared with those on other treatments (N=23). Low serum carnitine concentration was observed in 37% of our HIV-infected children on antiretroviral therapy. Malabsorption or defective synthesis may also account for the low serum carnitine values detected in these patients.

Carnitine and Choline Supplementation with Exercise Alter Carnitine Profiles, Biochemical Markers of Fat Metabolism and Serum Leptin Concentration in Healthy Women

We sought to determine the effects of supplementary choline, carnitine and a combination of the two with or without exercise on serum and urinary carnitine and biochemical markers of fatty acid oxidation in healthy humans. Nineteen women were placed in three groups: 1) placebo, choline or carnitine preloading period of 1 wk followed by 2) supplementation with choline plus carnitine during wk 2-wk 3 and 3) all groups exercised in wk 3. Although there were no changes in the placebo group, serum and urinary carnitine decreased in the choline-supplemented group during wk 1. Introduction of carnitine to the choline group restored serum and urinary carnitine. Serum and urinary carnitine increased during wk 1 in the carnitine-supplemented group and, although the introduction of choline to this group depressed serum and urinary carnitine, they remained significantly greater than control. Serum beta-hydroxybutyrate and serum as well as urinary acetylcarnitine were elevated by the supplements. A mild exercise regimen increased the concentration of serum beta-hydroxybutyrate, and serum and urinary acylcarnitines; it also decreased serum leptin concentrations in all groups. The effects of supplements were sustained until wk 2 after cessation of choline plus carnitine supplementation and exercise. We conclude that the choline-induced decrease in serum and urinary carnitine is buffered by carnitine preloading, and these supplements shift tissue partitioning of carnitine that favors fat mobilization, incomplete oxidation of fatty acids and disposal of their carbons in urine as acylcarnitines in humans.

Miopatía por déficit de carnitina: un caso de diagnóstico tardío

Myopathies caused by lipidic metabolism alterations are very infrequent. Carnitine deficiency-associated myopathies are included in this group. Two main types of carnitine deficiency syndromes have been delineated: a predominantly myopathic form, with normal serum and low muscle carnitine levels, and a systemic form, with encephalopathy, hepatic dysfunction, muscle weakness and low muscle, liver and serum carnitine levels. Both types have typical lipid stores in muscle biopsy. We describe the case of a myopathic form of carnitine deficiency. Due to the age of the patient, this is an unusual case, with an unfavourable evolution. Therapeutic measures used in these patients have included prednisone, carnitine replacement and a low-fat with medium chain tryglycerides and high-carbohydrate diet. However, in none of the patients responding to therapy, a significative increase in muscle carnitine has been demonstrated.

Protective effects of carnitine in an experimental ischemia–reperfusion injury

Background/Aims: We aimed to determine the role of exogenous carnitine to prevent ischemia–reperfusion damage in liver tissue in experimental model. Methods: Rats were divided into four groups as Sham (SG), 30% Hepatectomy (HG), ischemia–reperfusion +30% hepatectomy (IRHG) and ischemia–reperfusion+30% hepatectomy+carnitine (IRHCG). Serum AST, ALT and GGT levels have been determined in systemic blood samples (post-hepatic vena cava) and liver tissue and serum carnitine levels in blood samples from portal vein (pre-hepatic blood samples). Results: Serum carnitine levels were significantly higher in IRHCG compared to SG (P < 0.01). Each of the serum AST, ALT and GGT levels were statistically higher in HG, IRHG and IRHCG than SG (P < 0.001). While these values in IRHG were also higher than those in HG (P < 0.001), in IRHCG enzyme levels were significantly lower than IRHG (P < 0.001). Liver tissue damage was less in IRHCG than IRHG statistically (P < 0.001). Conclusions: This animal model implies that exogenous carnitine supplementation may be helpful in preventing free oxygen radical damage and inflammatory reactions in liver tissue.

Rapid diagnosis of organic acidemias and fatty-acid oxidation defects by quantitative electrospray tandem-MS acyl-carnitine analysis in plasma.

The analysis of circulating free carnitine and acyl-carnitines provides a powerful selective screening tool for genetic defects in mitochondrial fatty acid oxidation and defects in the catabolism of branched chain amino acids. Using electrospray tandem mass spectrometry (ESI/MS/MS) we developed a sensitive quantitative analysis of free carnitine and acyl-carnitines in plasma and/or serum. This method was evaluated by analyzing 250 control samples and 103 samples of patients suffering from twelve different defects in either mitochondrial fatty acid oxidation or the catabolism of branched chain amino acids. The reproducibility of the method was acceptable with a day-to-day coefficient of variation ranging from 6-15% for free carnitine and the different acylcarnitines. Except for one patient with a mild form of short chain acyl CoA dehydrogenase (SCAD) deficiency and a single sample from a patient with a mild form of multiple acyl CoA dehydrogenase (MAD) deficiency all patient samples were clearly abnormal under a wide variety of clinical conditions, illustrating the high sensitivity and specificity of the method.

Clinical and demographic predictors of exercise capacity in end-stage renal disease.

Patients on maintenance hemodialysis therapy for end-stage renal disease have reduced exercise tolerance. Multiple processes related to uremia and hemodialysis have been implicated in the pathophysiology of this impairment. However, limited data are available to identify the separate and combined effects of clinical factors on the degree of impairment for individuals within this population. For this purpose, data from 193 patients who had undergone exercise testing for two clinical trials were retrospectively analyzed. Univariate and multiple linear regression analyses were used to identify demographic and clinical correlates of peak exercise oxygen uptake (VO2). Peak VO2 averaged 18.5 +/- 6.4 mL/min/kg. On univariate analysis, peak VO2 correlated positively with male sex and hemoglobin, serum albumin, and serum creatinine concentrations and correlated negatively with dialytic age and diagnosis of diabetes or chronic heart failure. In a multiple linear regression model, sex, hemoglobin concentration, age, and diagnosis of diabetes each remained statistically significant. Together, factors included in the model accounted for 41% of the variability in peak VO2 (P = 0.0001). Among factors not correlating significantly with peak VO2 were resting blood pressure, serum carnitine level, and urea clearance assessed by Kt/V. Findings show the range of exercise impairment among clinically stable ambulatory hemodialysis patients, which may be sufficient to interfere with normal daily activities for many of these patients. Although this impairment may be broadly attributable to physiological consequences of uremia, the degree of impairment for individual patients is predicted by demographic factors, coexistent disease, and factors potentially modified by medical therapeutics.

SERUM CARNITINE LEVELS OF PEDIATRIC CANCER PATIENTS

Secondary carnitine deficiency may occur in some diseases including malnutrition. The present study examined the serum carnitine levels of children with cancer and their relationship with nutritional status. Fifty-one (mean age: 104 - 23 months) patients with cancer were evaluated at diagnosis and 3 months after the initiation of the treatment. There were significant differences between the mean carnitine levels of patients before and during the treatment ( p : .004). Although initial carnitine levels of patients were similar to those in control groups, there was a significant difference between the mean carnitine levels of patients and those of the control group at the third month ( p : .02). The prevalence of malnutrition at the third month of the treatment (43%) was higher from the prevalence at diagnosis (33%) but this was not significant. No significant relationship was found between carnitine levels and nutritional status of patients either at diagnosis or during treatment. These results showed that inadequate intake of carnitine or its precursors could not be responsible for decrease in carnitine levels. Metabolic changes that result from therapy and/or from neoplastic process may be responsible for the decrease in carnitine levels. Detailed studies, including measurements of fractions of carnitine and urinary carnitine excretion according to individual drug, are necessary to determine real cause of this decrease.

Age and Sex Dependency of Carnitine Concentration in Human Serum and Skeletal Muscle

Carnitine plays an essential role in fatty acid metabolism. It can be synthesized in the liver, but additional intestinal resorption is necessary (1). Carnitine mediates the transport of activated acyl residues via the carnitine palmityl transferase system into mitochondria for β-oxidation (2). Whereas primary carnitine deficiency is attributable to mutations in OCTN2 [a carnitine transporter of plasma membranes (3)], several other conditions can cause secondary deficiency (4). The leading symptom of either primary or secondary carnitine deficiency is weakness of skeletal muscles. In addition to these pathologic conditions in some animal models, a physiologic decline of carnitine concentration with aging has been reported (5)(6). In addition to increasing muscular carnitine concentrations (6), oral treatment with l-carnitine or its acetyl ester has also been shown to restore many of physiologic impairments that accompany aging (7)(8)(9)(10). These data indicate the important role of carnitine in the aging process, at least in mice and rats. For human skeletal muscle, confusing results exist with respect to the age dependency of carnitine content: Whereas Costell et al. (5) found a “drastic” age-dependent decrease of carnitine in human skeletal muscle and Gonzalez-Crespo et al. (11) detected reduced free carnitine concentrations in elderly patients undergoing hip surgery, an age-dependent decrease in carnitine concentration could not be confirmed by Starling et al. (12). The answer to the question of whether carnitine in human muscle is also age dependent is hampered by the different populations investigated and the different methods used. No reliable data exist concerning the sex dependency of a possible age-dependent variation. The present study seeks to clarify whether carnitine concentrations in human skeletal muscle and serum depend on age and sex. The physiologic relevance is discussed. Analysis of carnitine in serum was performed in samples from healthy …

Degenerative Disorders of the Central Nervous System

Degenerative Disorders of the Central Nervous System

Anesthetics and cardiocentesis increase urinary carnitine excretion in rats and guinea pigs

Our interest in carnitine homeostasis lead us to determine effects of several commonly used anesthetics and blood sampling procedures on serum and urinary carnitine concentrations. Serum and urine samples were collected from male rats and guinea pigs prior to and after anesthesia with and without cardiocentesis and assayed for carnitine and acylcarnitine. Methoxyflurane alone increased urinary carnitine excretion in guinea pigs but not in rats. Methoxyflurane plus cardiocentesis increased urinary carnitine and acylcarnitine in both species, and isoflurane mimicked methoxyflurane in rats. Cardiocentesis with phenobarbital or pentobarbital increased carnitine and acylcarnitine in serum but not in urine. Ketamine plus acepromazine increased total carnitine only in the serum of rats. A combination of ketamine and xylazine increased serum carnitine and urinary acylcarnitine. It is concluded that anesthesia and cardiocentesis increased serum and urinary carnitine and acylcarnitines differently depending on the species and the anesthetic administered.

LOW SERUM CARNITINE CONCENTRATIONS IN HEALTHY CHILDREN WITH IRON DEFICIENCY ANEMIA

Carnitine is not only obtained from animal-derived foods but also synthesized in the body. It plays an important role in the energy metabolism of many tissues, including heart and skeletal muscles. Iron is known to be essential for the biosynthesis of carnitine. Although many conditions are well known to cause secondary carnitine deficiency, iron deficiency, which is a very common condition in children, is not well studied as a cause of secondary carnitine deficiency in humans. This study demonstrates the coexistence of iron deficiency and low carnitine levels in otherwise healthy children. The mean carnitine concentration of 18 otherwise healthy children with iron deficiency anemia was significantly lower compared to the mean carnitine concentration of healthy children without iron deficiency anemia. Based on the evidence about the effect of low iron on carnitine stores in experimental animals, we proposed that low serum carnitine levels in these children may be secondary to iron deficiency. However, further studies need to be done to further clarify this relationship.

A Case of Anorexia Nervosa with Serum Carnitine Deficiency and High Creatine Phosphokinase Concentration during Nutritional Rehabilitation

A Case of Anorexia Nervosa with Serum Carnitine Deficiency and High Creatine Phosphokinase Concentration during Nutritional Rehabilitation