Serum Carnitine Levels Research Articles

Muscle Disease

On the basis of strong research evidence, Duchenne muscular dystrophy (DMD), the most common severe childhood form of muscular dystrophy, is an X-linked recessive disorder caused by out-of-frame mutations of the dystrophin gene. Thus, it is classified asa dystrophinopathy. The disease onset is before age 5 years. Patients with DMD present with progressive symmetrical limb-girdle muscle weakness and become wheelchair dependent after age 12 years. (2)(3). On the basis of some research evidence,cardiomyopathy and congestive heart failure are usually seen in the late teens in patients with DMD. Progressive scoliosis and respiratory in sufficiency often develop once wheelchair dependency occurs. Respiratory failure and cardiomyopathy are common causes of death, and few survive beyond the third decade of life. (2)(3)(4)(5)(6)(7). On the basis of some research evidence, prednisone at 0.75 mg/kg daily (maximum dose, 40 mg/d) or deflazacort at 0.9 mg/kg daily (maximum dose, 39 mg/d), a derivative of prednisolone (not available in the United States), as a single morning dose is recommended for DMD patients older than 5 years, which may prolong independent walking from a few months to 2 years. (2)(3)(16)(17). Based on some research evidence, treatment with angiotensin-converting enzyme inhibitors, b-blockers, and diuretics has been reported to be beneficial in DMD patients with cardiac abnormalities. (2)(3)(5)(18). Based on expert opinion, children with muscle weakness and increased serum creatine kinase levels may be associated with either genetic or acquired muscle disorders (Tables 1 and 3). (14)(15)

Potential Inhibitory Effects ofl-Carnitine Supplementation on Tissue Advanced Glycation End Products in Patients with Hemodialysis

Advanced glycation end products (AGEs) contribute to cardiovascular disease in patients with hemodialysis (HD). We have recently found that carnitine levels are inversely associated with skin AGE levels in HD patients. We examined whether L-carnitine supplementation reduced skin AGE levels in HD patients with carnitine deficiency. This was a single-center study. One hundred and two HD patients (total carnitine levels <50 μmol/L) were enrolled and randomized to either oral administration of L-carnitine (900 mg/day) (n=51) or control (n=51). After 6 months, metabolic and inflammatory variables, including serum levels of carnitine, were measured. Skin AGE levels were determined by evaluating skin auto-fluorescence with an AGE-reader. There were no significant differences of clinical variables at baseline between the control and L-carnitine therapy group. Thirty-two patients did not complete the assessment or treatment of the study. Oral L-carnitine supplementation for 6 months significantly increased low-density lipoprotein cholesterol (LDL-C), triglycerides, total, free, and acyl carnitine levels, while it decreased alanine transaminase, acyl/free carnitine ratio, β₂-microglobulin, and skin AGE values. Change in total carnitine values from baseline (Δtotal carnitine) and Δfree carnitine were inversely associated with Δskin AGE levels in L-carnitine-treated patients (p=0.036 and p=0.016, respectively). In multiple regression analysis, Δfree carnitine was a sole independent determinant of Δskin AGEs (R²=0.178). The present study demonstrated that oral L-carnitine supplementation significantly decreased skin AGE levels in HD patients with carnitine deficiency. These observations suggest that supplementation of L-carnitine might be a novel therapeutic strategy for preventing the accumulation of tissue AGEs in carnitine-deficient patients with HD.

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.

Randomized Double-Blind Placebo-Controlled Trial of Acetyl-L-Carnitine for the Prevention of Taxane-Induced Neuropathy in Women Undergoing Adjuvant Breast Cancer Therapy

Chemotherapy-induced peripheral neuropathy (CIPN) is common and leads to suboptimal treatment. Acetyl-L-carnitine (ALC) is a natural compound involved in neuronal protection. Studies have suggested ALC may be effective for the prevention and treatment of CIPN. A 24-week randomized double-blind trial comparing ALC (3,000 mg per day) with placebo in women undergoing adjuvant taxane-based chemotherapy was conducted. The primary objective was to determine if ALC prevents CIPN as measured by the 11-item neurotoxicity (NTX) component of the Functional Assessment of Cancer Therapy (FACT) -Taxane scale at 12 weeks. Secondary objectives included changes in 24-week end points, functional status (FACT-Trial Outcome Index [TOI]), fatigue (Functional Assessment of Chronic Illness Therapy [FACIT] -Fatigue), and NTX grade. A total of 409 patients were evaluable (208 received ALC; 201, placebo). In a multivariate linear regression, week-12 scores were 0.9 points lower (more CIPN) with ALC than placebo (95% CI, -2.2 to 0.4; P = .17), whereas week-24 scores were 1.8 points lower with ALC (95% CI, -3.2 to -0.4; P = .01). Patients receiving ALC were more likely to have a > 5-point decrease in FACT-NTX scores (38% v 28%; P = .05), and FACT-TOI scores were 3.5 points lower with ALC (P = .03). Grade 3 to 4 neurotoxicity was more frequent in the ALC arm (eight v one). No differences between arms were observed for FACIT-Fatigue or other toxicities. Serum carnitine level increased with ALC but remained stable with placebo. There was no evidence that ALC affected CIPN at 12 weeks; however, ALC significantly increased CIPN by 24 weeks. This is the first study to our knowledge showing that a nutritional supplement increased CIPN. Patients should be discouraged from using supplements without proven efficacy.

Frequency of Depression and its Correlation with Serum Carnitine Level in HIV/AIDS Patients

There are some evidences regarding beneficial effects of carnitine in improvement of depression symptoms. Incidence of depression is significantly higher among HIV positive individuals compared to HIV negative populations. Also carnitine deficiency is prevalent in HIV positive individuals. In a cross-sectional study correlation between serum carnitine level and depression severity based on the Beck Depression Inventory questionnaire was assessed in 100 HIV/AIDS (42 males and 58 females) patients. According to the Beck Depression Inventory definitions, 31%, 16%, and 21% of the patients experienced mild, moderate, and severe depression, respectively. The mean ± SD serum concentration of total carnitine in the patients was 37.96 ± 26.08 (µmol/L). Fifty-four (54%) patients were categorized as carnitine deficient. A non-statistically significant negative correlation between patients' depression scores and total levels of serum carnitine was found. Considering the prevalence of depression among HIV/AIDS patients and probable role of carnitine in the pathogenesis of depressive disorders, more studies are needed to reveal correlation between depression and the body storage of carnitine.

Evidence for a Positive Association Between Serum Carnitine and Free Testosterone Levels in Uremic Men with Hemodialysis

Low free testosterone levels are associated with sexual dysfunction and an increased risk of cardiovascular disease in male hemodialysis patients. Carnitine deficiency is frequently observed in hemodialysis patients as well. However, the relationship between carnitine and testosterone levels remains unknown. In this study, we examined whether carnitine deficiency was independently associated with low free testosterone levels in male hemodialysis patients. Nineteen male hemodialysis patients underwent determinations of blood chemistries, including serum levels of free testosterone, carnitine, and pentosidine, one of the well-characterized advanced glycation end products. Mean free testosterone levels in hemodialysis patients were significantly lower than those in healthy controls (4.67±2.69 vs. 9.50±3.67 pg/mL, p<0.001). Univariate analysis revealed that carnitine (p=0.023), pentosidine (inversely, p=0.027), blood glucose (inversely, p=0.032), creatinine (p=0.026) levels, and statin use (inversely, p=0.034) were correlated with free testosterone values. Multiple stepwise regression analysis revealed that carnitine (p=0.001) and statin use (inversely, p=0.002) were the independent determinants of age-adjusted free testosterone levels in hemodialysis patients (r² =0.612). The present study gives the first evidence that decreased carnitine levels were independently associated with low free testosterone values in male hemodialysis patients. Our study suggests that decreased carnitine levels may be a novel therapeutic target for uremic men with hemodialysis.

Primary carnitine deficiency: novel mutations and insights into the cardiac phenotype

Solute carrier family 22 member 5 (SLC22A5) encodes a sodium-dependent ion transporter responsible for shuffling carnitine across the plasma membrane. This process provides energy for the heart, among other organs allowing beta-oxidation of fatty acids. Mutations in SLC22A5 result in primary carnitine deficiency (PCD), a disorder that manifests with cardiac, skeletal, or metabolic symptoms. We hereby describe two novel mutations in SLC22A5 in two Lebanese families associated exclusively with a cardiac phenotype. The frequency of the cardiac, metabolic and skeletal symptoms in PCD patients remains undefined. All the reported eight PCD patients belonging to five different Lebanese families have an exclusive cardiac phenotype. Carnitine levels appear to be directly linked to the type and position of the mutation and the severity of the phenotypic presentation does not seem to be associated with serum carnitine levels. A comprehensive review of 61 literature-reported PCD cases revealed an exclusive cardiac manifestation frequency at 62.3% with a very low likelihood of simultaneous occurrence of cardiac and metabolic manifestation.

The Effect of Chemotherapy on Serum Carnitine Levels and Fatigue in Chemotherapy Naive Medical Oncology Patients: A Pilot Study. Carnitine, Chemotherapy and Fatigue

Abstract Background: Fatigue, a highly prevalent side-effect of anticancer therapy, poses a significant burden on patient quality of life. Carnitine deficiency has been implicated in the development of fatigue during chemotherapy. Methods: This pilot study aimed to evaluate the relationship between chemotherapy-related fatigue and serum carnitine (total, free- and acyl: free carnitine ratio) in 35 chemotherapy-naive oncology patients at baseline, 6 and12 weeks. Results: Carnitine deficiency, based on acyl: free carnitine ratio, was detected in three patients at baseline but this did not persist to the next time point. Carnitine deficiency was not detected in any other participant throughout this study and levels of carnitine were not correlated with fatigue during the study period. Conclusion: A relationship between carnitine status and fatigue was not found at the time points measured. Further research is required to confirm these results in a larger medical oncology population.

Decreased serum carnitine is independently correlated with increased tissue accumulation levels of advanced glycation end products in haemodialysis patients

There is accumulating evidence that advanced glycation end products (AGE) play a role in cardiovascular disease (CVD) in patients with haemodialysis (HD). Carnitine deficiency is frequently observed in HD patients, which may also contribute to CVD. In this study, we examined whether carnitine deficiency was independently associated with increased tissue accumulation levels of AGE in HD patients. One hundred and twenty-nine HD patients underwent determinations of blood chemistries including serum level of carnitine. Tissue AGE levels were evaluated by measuring skin autofluorescence with an AGE-reader. Serum carnitine levels were significantly lower, while skin AGE levels were significantly higher in HD patients compared with healthy controls (P < 0.001). In univariate analysis, β(2)-microglobulin (β(2)-MG) and carnitine (inversely) were correlated with skin AGE levels. Multiple stepwise regression analysis revealed that carnitine levels were one of the independent determinants of skin AGE levels (P = 0.024). When β(2)-MG-adjusted skin AGE levels were stratified by serum carnitine levels, a statistical significance and dose-response relationship were observed (P = 0.043). Furthermore, skin AGE levels were one of the independent determinants of serum carnitine levels as well (P = 0.012). The present study demonstrated that decreased carnitine levels were independently associated with increased skin AGE levels in HD patients. Since carnitine is reported to inhibit the formation of AGE in vitro, our study suggests that supplementation of carnitine may be a therapeutic target for preventing the accumulation of tissue AGE and subsequently reducing the risk of CVD in HD patients.

Evaluation of Serum Level of Carnitine in HIV-Positive Individuals and its Possible Explanatory Factors

Aims: This cross-sectional study evaluated the status of serum carnitine level and its possible explanatory factors in Iranian HIV-positive patients. Materials &amp; methods: During a 1-year period, 210 HIV-positive patients older than 18 years of age were enrolled in the study. Serum carnitine concentrations of the patients were measured using radioimmunoassay kits. Probable correlations between the patients’ demographic and clinical characteristics with their serum levels of carnitine were determined in this study. Results: In comparison with normal serum concentration of carnitine in a healthy population, 63.45% of the patients had carnitine deficiency. Receiving antiretroviral regimen, duration of HIV infection, receiving fibrate drugs, serum total cholesterol, fasting blood sugar and serum triglyceride had significant correlations with serum level of carnitine of the patients. Conclusion: The results of the present study showed that carnitine deficiency is prevalent in Iranian HIV/AIDS patients. Nutritional risk assessment of HIV-positive individuals at first visit and in the follow-up is essential.

Enzymes involved in l-carnitine biosynthesis are expressed by small intestinal enterocytes in mice: Implications for gut health

BackgroundCarnitine is essential for mitochondrial β-oxidation of long-chain fatty acids. Deficiency of carnitine leads to severe gut atrophy, ulceration and inflammation in animal models of carnitine deficiency. Genetic studies in large populations have linked mutations in the carnitine transporters OCTN1 and OCTN2 with Crohn's disease (CD), while other studies at the same time have failed to show a similar association and report normal serum carnitine levels in CD patients. MethodsIn this report, we have studied the expression of carnitine-synthesizing enzymes in intestinal epithelial cells to determine the capability of these cells to synthesize carnitine de novo. We studied expression of five enzymes involved in carnitine biosynthesis, namely 6-N-trimethyllysine dioxygenase (TMLD), 4-trimethylaminobutyraldehyde dehydrogenase (TMABADH), serine hydroxymethyltransferase 1 and 2 (SHMT1 and 2) and γ-butyrobetaine hydroxylase (BBH) by real-time PCR in mice (C3H strain). We also measured activity of γ-BBH in the intestine using an ex vivo assay and localized its expression by in situ hybridization. ResultsOur investigations show that mouse intestinal epithelium expresses all five enzymes required for de novo carnitine biosynthesis; the expression is localized mainly in villous surface epithelial cells throughout the intestine. The final rate-limiting enzyme γ-BBH is highly active in the small intestine; its activity was 9.7±3.5pmol/mg/min, compared to 22.7±7.3pmol/mg/min in the liver. ConclusionsWe conclude that mouse gut epithelium is able to synthesize carnitine de novo. This capacity to synthesize carnitine in the intestine may play an important role in gut health and can help explain lack of clinical carnitine deficiency signs in subjects with mutations with OCTN transporters.

Serum carnitine levels and levocarnitine supplementation in institutionalized Huntington’s disease patients

Along with antioxidant properties, carnitine is an important regulator of lipid metabolism in humans. While beneficial effects of carnitine have been demonstrated in animal models of Huntington's disease (HD), metabolism of carnitine has not been studied in humans with this illness. In this retrospective database review from 23 patients admitted to a HD-specialized nursing home unit, we found a relatively high prevalence of hypocarnitinemia (6 cases, 26%). Our review suggests that catabolism and chronic valproate use predisposed our patients to develop hypocarnitinemia. The patients with low serum carnitine levels who received levocarnitine supplementation, during a mean period of 7.3 months, showed improvement in motor, cognitive and behavioral measures. We hypothesize that observed improvement related to the resolution of reversible metabolic encephalopathy and myopathy associated with secondary carnitine deficiency. In conclusion, notwithstanding its limitations, this is the first study to report measurements of carnitine levels in HD patients, revealing relatively high prevalence of hypocarnitinemia in our population. Our findings suggest that HD patients with hypocarnitinemia may benefit from low-dose levocarnitine supplementation. Further studies of carnitine metabolism and supplementation in HD patients are warranted.

L-Carnitine Improves the Asthma Control in Children with Moderate Persistent Asthma

The objective. was to investigate L-Carnitine level and the effects of its supplementation in children with moderate persistent Asthma. Methods. Free and total serum carnitine levels were measured in 50 children having moderate persistent asthma and 50 healthy control children. The patients group was randomly divided into two subgroups. Subgroup A was supplemented with L-carnitine for 6 months while subgroup B was used as a placebo controls. Both subgroups were assessed by pulmonary function tests (PFT) and childhood-asthma control test (C-ACT) before and 6 months after carnitine supplementation. Results. Total and free carnitine levels were significantly lower in patient group than in control group. PFT and C-ACT showed significant improvements in asthmatic children supplemented with L-carnitine than in those who were not supplemented. Conclusion. L-carnitine levels were initially lower in moderate persistent asthmatic children as compared to healthy control children. Asthmatic children who received L-carnitine supplementation showed statistically significant improvement of C-ACT and PFT.

Fatigue and serum carnitine levels in chronic liver disease

Fatigue and serum carnitine levels in chronic liver disease

Carnitine and coenzyme Q10 levels in individuals with Prader–Willi syndrome

Carnitine deficiency or coenzyme Q10 (CoQ10) deficiency may present with hypotonia, poor growth, easy fatigability, and apnea. This constellation of findings can also be seen in individuals with Prader-Willi syndrome (PWS). Animal studies indicate that increased fat mass due to obesity negatively correlates with both carnitine and CoQ10 levels in skeletal muscle. Increased body fat and obesity are characteristic of individuals with PWS. Currently, there is no documentation of serum carnitine levels, and only one study investigating plasma CoQ10 levels, in individuals with PWS. Fasting serum carnitine and plasma CoQ10 levels were measured in 40 individuals with molecularly confirmed PWS (ages 1-27 years; 19 F/21 M), 11 individuals with early-onset morbid obesity of unknown etiology (ages 3-13 years; 5 F/6 M), and 35 control siblings from both groups (ages 1-24 years; 19 F/16 M). There were no significant differences among the three groups in either total carnitine, free carnitine, or CoQ10 levels. However, individuals with PWS had higher serum levels of carnitine esters (P = 0.013) and higher ester-to-free carnitine ratios (P = 0.0096) than controls suggesting a possible underlying impairment of peripheral carnitine utilization and mitochondrial energy metabolism in some individuals with PWS. Serum sampling identified no significant differences in total and free carnitine or CoQ10 levels between individuals with PWS, obese individuals, and sibling control groups. Muscle biopsy or measurement in leukocytes or cultured skin fibroblasts could be a better method to identify abnormalities in carnitine and CoQ10 metabolism in individuals with PWS than peripheral blood sampling.

L‐carnitine and cancer cachexia: Clinical and experimental aspects

Cancer cachexia is a multifaceted syndrome characterized, among many symptoms, by extensive muscle wasting. Chronic systemic inflammation, partly triggered and sustained by cytokines, as well as increased oxidative stress contributes to the pathogenesis of this complex metabolic disorder. l-carnitine plays a central role in the metabolism of fatty acids and shows important antioxidant and anti-inflammatory properties. Systemic carnitine depletion has been described in several diseases, and it is characterized by fatigue, muscle weakness, and decreased tolerance to metabolic stress. In cachectic cancer patients, low serum carnitine levels have been reported, and this change has been suggested to play an important contributory role in the development of cachexia. Based on these data, carnitine supplementation has been tested in preliminary studies concerning human cachexia, resulting in improved fatigue and quality of life. We present here a review of clinical and experimental evidence regarding the use of carnitine supplementation in the management of cancer cachexia.

Carnitine serum levels and levocarnitine administration in multiple sclerosis patients treated with natalizumab

Carnitine serum levels and levocarnitine administration in multiple sclerosis patients treated with natalizumab

Carnitine and Metabolic Correlates in Hospitalized Psychiatric Patients

Carnitine deficiency may be encountered in the context of chronic psychiatric illness, particularly with the chronic use of valproic acid. Despite the importance of carnitine in lipid metabolism and mitochondrial function, its metabolic effects have not been studied in a psychiatric population. To raise awareness regarding the possible metabolic implications of carnitine homeostasis in psychiatric patients. Retrospective database review in a subgroup of 23 patients with documented hypo carnitinemia. Statistical analysis revealed a negative correlation between serum carnitine levels and lipid levels. Initial fasting plasma glucose levels correlated positively with acylcarnitine/free carnitine ratios, suggesting unfavorable secondary effects of carnitine insufficiency, which resolved once carnitine was supplemented. Carnitine is a plausible substrate for future investigations of metabolic status in psychiatric patients. Further studies are needed to evaluate whether serum carnitine levels may be useful as a marker for psychiatric patients at risk for developing metabolic syndrome, and whether carnitine supplementation may reduce that risk. (Journal of Psychiatric Practice 2011;17:35-40).

Serum carnitine concentrations in different glomerular diseases with normal renal function.

Serum carnitine concentrations are known to decrease in patients on regular hemodialysis and to increase in chronic renal failure. However, there is little information available concerning serum levels of carnitine in different glomerular diseases in patients whose renal functions have not yet deteriorated. In this study, we measured serum carnitine concentrations in 40 pediatric patients with idiopathic nephrotic syndrome, IgA nephropathy, non-IgA glomerulonephritis, focal segmental glomerular sclerosis, and normal controls. The results showed that there were no significant differences in the serum-free and total carnitine concentrations (S-FCC and S-TCC, respectively) between patients with different glomerular diseases and the controls. Of interest was the statistically weak correlations of both S-TCC and S-FCC with BUN in these patients, despite their normal renal functions. The ratio of S-FCC to S-TCC was significantly higher as compared with that of the controls. These findings suggest that serum carnitine concentrations are not affected by the types of glomerular lesions and that serum levels of carnitine depend mostly on the glomerular excretory capacity of urea nitrogens, even when the renal functions have not yet deteriorated. The increase in the ratio of S-FCC to S-TCC may be an early reflection of changes in the serum carnitine profiles of these patients.

Simultaneous Determination of Free and Total Carnitine in Human Serum by HPLC with UV Detection

A simple and reliable high-performance liquid chromatographic (HPLC) method for simultaneous determination of free and total carnitine in human serum has been developed, and its clinical significance has been investigated. After proteins in serum were precipitated, carnitine in serum was derivatized to form its ester. HPLC separation of the sample solution was performed on a SiO(2) column and detected by UV absorbance at 260 nm. A mobile phase composed of acetonitrile-citric acid-triethanolamine was found to be the most suitable for this separation. The free and total carnitine levels in serum were studied in 347 subjects. The method proved to be linear in the range of carnitine from 5 micromol/L to 400 micromol/L. The relative standard deviations of within-assay for free and total carnitine analyses were 3.36% and 1.97%, respectively; and between-assay for free and total carnitine analyses were 3.34% and 1.77%, respectively. The average recovery was 98.2% for free carnitine and 96.3% for total carnitine, respectively. The method has been applied to the simultaneous determination of free and total carnitine in serum. Statistics analysis showed that total and free carnitine levels of males were higher than that of females (p < 0.01) while acylcarnitine level had no statistically significant difference (p > 0.05).