Serum Carnitine Concentrations Research Articles

Serum Carnitine Concentrations and Cardiac Function in Pediatric, Adolescent and Young Adult Oncology Patients Receiving High-Dose Anthracyclines

OBJECTIVE Anthracycline chemotherapy agents have significant dose-dependent cardiotoxic effects. ­Carnitine, a non-essential amino acid, is involved in long chain fatty acid oxidation, and carnitine deficiency can result in cardiomyopathy and cardiac arrhythmias. If administered concurrently with chemotherapy, carnitine supplementation could be a potential strategy to prevent cardiotoxicity. However, the association between serum carnitine concentrations and anthracycline cardiotoxicity during cancer treatment in the childhood, adolescent, and young adult (CAYA) age range has not been established. METHODS This prospective pilot cohort study characterized changes in serum carnitine concentrations and cardiac function before, during, and approximately 1 year after large-dose anthracycline therapy in newly diagnosed CAYA cancer patients. RESULTS Among 21 patients with a mean cumulative anthracycline dose exposure of 409 mg/m2 of ­doxorubicin equivalents, left ventricular ejection fraction and relative wall thickness decreased, indicating an overall decline in cardiac function. A reversible decrease in serum carnitine concentrations was also observed. A non-statistically significant positive correlation was observed; for every 1 mmol/L decrease in serum carnitine concentration, there was a 0.09% decrease in LVEF (p = 0.2). CONCLUSIONS These findings from this small pilot study suggest that there may be a relationship between serum carnitine concentrations and cardiac function after anthracycline therapy that should be evaluated in larger studies.

The influence of a maternal vegan diet on carnitine and vitamin B2 concentrations in human milk.

The maternal diet greatly influences the nutritional composition of human milk. With the rise of vegan diets by lactating mothers, there are concerns about the nutritional adequacy of their milk. Two important nutrients, vitamin B2 and carnitine, are mostly ingested via animal products. We investigated the influence of a vegan diet on the vitamin B2 and carnitine concentrations in milk and serum of lactating women. In this case-control study, 25 lactating mothers following an exclusive vegan diet were comparted to 25 healthy lactating mothers with an omnivorous diet without use of supplements. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry were used to measure vitamin B2 and carnitine concentrations, respectively. A linear regression model was used to determine differences in human milk and serum concentrations between study groups. Vitamin B2 concentrations in human milk and serum did not differ between study groups. While the human milk free carnitine (C0) and acetyl carnitine (C2) concentrations did not differ between study groups, serum carnitine concentrations were lower in participants following a vegan diet than in omnivorous women (p < 0.0001). A maternal vegan diet did not affect human milk concentration of vitamin B2 and carnitine. Breastfed infants of mothers following an exclusive vegan diet therefore are likely not at increased risk of developing a vitamin B2 or carnitine deficiency.

Identifying Genetic Variants and Metabolites Associated with Rapid Estimated Glomerular Filtration Rate Decline in Korea Based on Genome-Metabolomic Integrative Analysis.

Identifying the predisposing factors to chronic or end-stage kidney disease is essential to preventing or slowing kidney function decline. Therefore, here, we investigated the genetic variants related to a rapid decline in the estimated glomerular filtration rate (eGFR) (i.e., a loss of >5 mL/min/1.73 m2 per year) and verified the relationships between variant-related diseases and metabolic pathway signaling in patients with chronic kidney disease. We conducted a genome-wide association study that included participants with diabetes, hypertension, and rapid eGFR decline from two Korean data sources (N = 115 and 69 for the discovery and the validation cohorts, respectively). We identified a novel susceptibility locus: 4q32.3 (rs10009742 in the MARCHF1 gene, beta = −3.540, P = 4.11 × 10−8). Fine-mapping revealed 19 credible, causal single-nucleotide polymorphisms, including rs10009742. The pimelylcarnitine and octadecenoyl carnitine serum concentrations were associated with rs10009742 (beta = 0.030, P = 7.10 × 10−5, false discovery rate (FDR) = 0.01; beta = 0.167, P = 8.11 × 10−4, FDR = 0.08). Our results suggest that MARCHF1 is associated with a rapid eGFR decline in patients with hypertension and diabetes. Furthermore, MARCHF1 affects the pimelylcarnitine metabolite concentration, which may mediate chronic kidney disease progression by inducing oxidative stress in the endoplasmic reticulum.

Adopting a Mediterranean-style eating pattern with low, but not moderate, unprocessed, lean red meat intake reduces fasting serum trimethylamine N-oxide (TMAO) in adults who are overweight or obese.

A Mediterranean-style eating pattern (MED-EP) may include moderate red meat intake. However, it is unknown if the pro-atherogenic metabolite trimethylamine N-oxide (TMAO) is affected by the amount of red meat consumed with a MED-EP. The results presented are from a secondary, retrospective objective of an investigator-blinded, randomized, crossover, controlled feeding trial (two 5-wk interventions separated by a 4-wk washout) to determine if a MED-EP with 200g unprocessed lean red meat/wk (MED-CONTROL) reduces circulating TMAO concentrations compared to a MED-EP with 500g unprocessed lean red meat/wk (MED-RED). Participants were 27 women and 12 men (n=39 total) who were either overweight or obese (BMI: 30.5 ± 0.3 kg/m2 mean ± SEM). Serum samples were obtained following an overnight fast both before (pre) and after (post) each intervention. Fasting serum TMAO, choline, carnitine, and betaine concentrations were measured using a targeted Liquid chromatography-mass spectrometry. Data were analyzed to assess if (a) TMAO and related metabolites differed by intervention, and (b) if changes in TMAO were associated with changes in Framingham 10-year risk score. Serum TMAO was lower post-intervention following MED-CONTROL compared to MED-RED intervention (post-MED-CONTROL 3.1 ± 0.2 µM vs. post-MED-RED 5.0 ± 0.5 µM, p<0.001), and decreased following MED-CONTROL (pre- vs post-MED-CONTROL, p = 0.025). Exploratory analysis using mixed model analysis of covariance identified a positive association between changes in TMAO and changes in HOMA-IR (p = 0.036). These results suggest that lower amounts of red meat intake leads to lower TMAO concentrations in the context of a MED-EP.

Causal Inference of Carnitine on Blood Pressure and potential mediation by uric acid: A mendelian randomization analysis

BackgroundDietary change alters blood pressure (BP) but the specific causal dietary elements are unclear. Given previous observational data suggesting serum carnitine or uric acid affect BP, we investigated the role of serum carnitine and serum uric acid concentrations on BP, and considered mediation by lipids and insulin resistance using two-sample bi-directional Mendelian randomization (MR) analysis. MethodsWe performed MR to characterize bi-directional causal relationships of carnitine or uric acid on cardiometabolic traits. We performed two-sample MR using genome-wide association summary data from separate large-scale genomic analyses of carnitine, uric acid, BP, lipids, and glycemic traits. We used inverse variance weighted (IVW) meta-analysis and MR Egger regression to test for causal relations in the absence and presence of pleiotropy, respectively, and performed sensitivity analyses to identify confounders and intermediates. ResultsIn our analysis, carnitine was directly, causally associated with systolic BP (IVW effect = 0.2, causal p-value = 0.03) but not diastolic BP (IVW causal p = 0.1). Our findings additionally support direct and indirect relationships of carnitine on TG and on uric acid. No causal associations of carnitine were found with glycemic traits. Uric acid was not associated with BP, nor TG. ConclusionTwo-sample bi-directional MR demonstrated an unconfounded causal effect of carnitine, but not uric acid, on systolic but not diastolic BP, suggesting a role of carnitine in arterial stiffness. Carnitine, but not uric acid, also has direct and indirect effects on TG but are independent of the causal effect of carnitine on systolic BP.

Serum carnitine concentration and the acyl to free carnitine ratio in nondialysis chronic kidney disease and hemodialysis patients.

Mechanisms of impaired fatty acid metabolism may not be the same in nondialysis and hemodialysis patients. Correlations between the serum-free carnitine concentration (FC), acylcarnitine concentration (AC), acyl to free carnitine ratio (AC/FC), and estimated glomerular filtration rate (eGFR) in the nondialysis population and the duration of hemodialysis in hemodialysis patients were investigated. As the eGFR decreased, the FC and AC increased, and as the duration of hemodialysis became longer, the FC and AC decreased. The AC/FC increased consistently as the eGFR decreased and the duration of hemodialysis increased. As an exception, the AC/FC decreased in the patients with a hemodialysis duration less than 90 days, which was not explained by carnitine removal by hemodialysis. In nondialysis patients, a functional, rather than an absolute, carnitine deficiency is a main cause of impaired fatty acid metabolism. Long-term hemodialysis exacerbates absolute carnitine deficiency, whereas hemodialysis treatment may improve impaired fatty acid metabolism.

Evaluation of Serum Level of Carnitine in Children with Acute Pyelonephritis (APN) Compared to Healthy Children.

This cross-sectional case-control study evaluated the serum carnitine level in children with urinary tract infection (UTI). Acute pyelonephritis (APN) is a common bacterial infection of the upper urinary tract in children which may also lead to renal damage and tubular atrophy. Activation of inflammatory mediator bedside alterations in the cytokines and generation of reactive oxygen species (ROS) play a striking role in the development of tissue damage after pyelonephritis. L-carnitine as one of the most potent natural antioxidant agents by inhibition of lipid peroxidation may protect cells and tissues from damage. A total of 30 children with UTI (as a case group) and 30 healthy children (as a control group) which matched in terms of age and sex were enrolled in this study. All children were evaluated and compared with respect to age, sex, weight, body mass index (BMI) and serum carnitine level. Serum carnitine level was determined using serum carnitine ELISA kit. Demographic and clinical data such as age, sex, weight and BMI were not statistically significant between the two groups. The serum carnitine levels were significantly lower in the case group with UTI than the control group. Mean serum carnitine concentration in the case group and in the control group was 36.56 ± 9.87 μmol/l and 62.8±21.35, respectively (P = 0.001). According to our study, it could be concluded that low serum L-carnitine level is linked to UTI in children. Therefore, further studies are needed to confirm our results.

Effect of L-carnitine on health-related quality of life in patients with liver cirrhosis.

L-carnitine (4-N-trimethylammonium-3-hydroxybutyric acid) is the physiologically active form of carnitine and is a natural compound that has been shown to exhibit antioxidant activity. L-carnitine is used as a supplementary treatment in patients with cirrhosis with hepatic encephalopathy, hyperammonemia or muscle cramps. In the present study, the effect of L-carnitine supplementation on health-related quality of life in 30 patients with cirrhosis was prospectively examined. L-carnitine (1,800 mg/day) was administered orally for 6 months. To assess the effects of L-carnitine on chronic fatigue, patients filled out a self-report questionnaire regarding their physical and mental health. The levels of total and free carnitine, and acylcarnitine were found to be significantly higher 1, 3 and 6 months after therapy initiation compared with before treatment. Serum albumin levels were significantly increased 3 and 6 months after initiation of therapy. L-carnitine supplementation significantly increased the BAP/d-ROM ratio, a marker of antioxidant status in patients with cirrhosis. Changes in serum carnitine concentrations were positively correlated with changes in serum albumin levels (R2=0.369; P=0.012), but not with changes in serum ammonia levels (R2= 0.005; P=0.78). Total and mental health scores improved significantly, and physical scores improved marginally 3 and 6 months after initiation of L-carnitine. These findings may be attributed to the enhanced serum albumin levels and oxidative stress rather than the reduced serum ammonia levels. Based on these results, it is suggested that L-carnitine can potentially alleviate chronic fatigue, along with the increased BAP/d-ROM ratio, which were involved in increased oxidative stress in patients with cirrhosis. The specific mechanisms by which L-carnitine ameliorates chronic fatigue is not fully understood and requires further investigation.

Serum Metabolic Signatures of Chronic Limb-Threatening Ischemia in Patients with Peripheral Artery Disease.

Peripheral artery disease (PAD) is characterized by the atherosclerotic narrowing of lower limb vessels, leading to ischemic muscle pain in older persons. Some patients experience progression to advanced chronic limb-threatening ischemia (CLTI) with poor long-term survivorship. Herein, we performed serum metabolomics to reveal the mechanisms of PAD pathophysiology that may improve its diagnosis and prognosis to CLTI complementary to the ankle–brachial index (ABI) and clinical presentations. Non-targeted metabolite profiling of serum was performed by multisegment injection–capillary electrophoresis–mass spectrometry (MSI–CE–MS) from age and sex-matched, non-diabetic, PAD participants who were recruited and clinically stratified based on the Rutherford classification into CLTI (n = 18) and intermittent claudication (IC, n = 20). Compared to the non-PAD controls (n = 20), PAD patients had lower serum concentrations of creatine, histidine, lysine, oxoproline, monomethylarginine, as well as higher circulating phenylacetylglutamine (p < 0.05). Importantly, CLTI cases exhibited higher serum concentrations of carnitine, creatinine, cystine and trimethylamine-N-oxide along with lower circulating fatty acids relative to well matched IC patients. Most serum metabolites associated with PAD progression were also correlated with ABI (r = ±0.24−0.59, p < 0.05), whereas the ratio of stearic acid to carnitine, and arginine to propionylcarnitine differentiated CLTI from IC with good accuracy (AUC = 0.87, p = 4.0 × 10−5). This work provides new biochemical insights into PAD progression for the early detection and surveillance of high-risk patients who may require peripheral vascular intervention to prevent amputation and premature death.

A simple and precise method for measurement of serum free carnitine and acylcarnitines by isotope dilution HILIC-ESI-MS/MS

Recent studies have found that carnitine and acylcarnitines (AcyCNs) are potential biomarkers for many metabolic diseases, including inherited disorders, diabetes and coronary atherosclerotic artery disease (CAD). Here we presented and validated a method for measurement of free carnitine and twelve AcyCNs in human serum by using electrospray ionization tandem mass spectrometry (ESI-MS/MS). Serum samples were mixed with isotopic labeled internal standards and extracted with isopropanol. Carnitine and AcyCNs were separated within 5min by isocratic elution on a hydrophilic interaction liquid chromatographic column (HILIC) and detected with electrospray ionization (ESI) in positive ion mode with multiple reaction monitor (MRM) mode. This method was linear in response with correlation coefficients higher than 0.999. Analytical recoveries were 89.4%–105.4% with an average of 98.7%. The intra-run and total imprecisions were 0.9–4.7% and 1.5–14.1%, respectively. Stability tests showed that all the compounds were stable in serum for at least 6 month at −80 °C, but unstable when stored at room temperature (RM) and 4 °C.Serum carnitine and AcyCNs concentrations of 472 apparently healthy subjects were analyzed. Significant associations between the metabolites and traditional CAD risk factors were observed. The established HILIC–ESI-MS/MS method was simple, precise, and sensitive and may be used as an efficient tool in CAD risk assessment and research.

Serum Trimethylamine N-oxide, Carnitine, Choline, and Betaine in Relation to Colorectal Cancer Risk in the Alpha Tocopherol, Beta Carotene Cancer Prevention Study.

Background: Trimethylamine N-oxide (TMAO), a choline-derived metabolite produced by gut microbiota, and its biomarker precursors have not been adequately evaluated in relation to colorectal cancer risk.Methods: We investigated the relationship between serum concentrations of TMAO and its biomarker precursors (choline, carnitine, and betaine) and incident colorectal cancer risk in a nested case-control study of male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We measured biomarker concentrations in baseline fasting serum samples from 644 incident colorectal cancer cases and 644 controls using LC/MS-MS. Logistic regression models estimated the ORs and 95% confidence interval (CI) for colorectal cancer by quartile (Q) of serum TMAO, choline, carnitine, and betaine concentrations.Results: Men with higher serum choline at ATBC baseline had approximately 3-fold greater risk of developing colorectal cancer over the ensuing (median ± IQR) 14 ± 10 years (in fully adjusted models, Q4 vs. Q1, OR, 3.22; 95% CI, 2.24-4.61; Ptrend < 0.0001). The prognostic value of serum choline for prediction of incident colorectal cancer was similarly robust for proximal, distal, and rectal colon cancers (all P < 0.0001). The association between serum TMAO, carnitine, or betaine and colorectal cancer risk was not statistically significant (P = 0.25, 0.71, and 0.61, respectively).Conclusions: Higher serum choline concentration (but not TMAO, carnitine, or betaine) was associated with increased risk of colorectal cancer.Impact: Serum choline levels showed strong prognostic value for prediction of incident colorectal cancer risk across all anatomical subsites, suggesting a role of altered choline metabolism in colorectal cancer pathogenesis. Cancer Epidemiol Biomarkers Prev; 26(6); 945-52. ©2017 AACR.

Carnitine-related hypoglycemia caused by 3\xa0days of pivalate antibiotic therapy in a patient with severe muscular dystrophy: a case report

BackgroundLong-term treatment with antibiotics containing pivalic acid may decrease serum carnitine concentration and can sometimes be associated with severe hypoglycemia and encephalopathy in infants. Little has been reported, however, on severe hypocarnitinemia induced by acute administration in older children.Case presentationWe describe a 6-year-old Japanese girl with Fukuyama-type congenital muscular dystrophy who lost consciousness after 3 days of treatment with an antibiotic containing pivalic acid (cefditoren pivoxil). Investigations at the onset of unconsciousness revealed hypoglycemia (free plasma glucose concentration: 31 mg/dL) and hypocarnitinemia (serum free carnitine concentration: 6.2 μmol/L). Intravenous administration of glucose rapidly improved her symptoms without any complications. Serum free carnitine concentration was 29.0 μmol/L immediately prior to the initiation of cefditoren pivoxil. Computed tomography scanning showed severe peripheral skeletal muscle atrophy, indicating the likelihood of decreased carnitine stores in skeletal muscle.ConclusionsAlthough serum carnitine concentration can appear deceptively normal, skeletal muscle carnitine stores can be reduced in patients with severe muscular atrophy. Even a short course of a pivalate-containing antibiotic can lead to life-threatening hypocarnitinemia in older children with severe muscular dystrophy.

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.

Intravenous Carnitine Administration in Addition to Parenteral Nutrition With Lipid Emulsion May Decrease the Inflammatory Reaction in Postoperative Surgical Patients.

BackgroundA prospective randomized study was performed to investigate the validity of intravenous carnitine administration during postoperative parenteral nutrition (PN) with lipid emulsion.MethodsPatients undergoing surgery for gastric or colorectal cancer were enrolled in the study and were randomly divided into two groups (n = 8 in each group): 1) group L, who received a peripheral PN (PPN) solution of 7.5% glucose, 30% amino acid, and 20% lipid emulsion; and 2) group LC, who received the same PPN solution, as well as carnitine intravenously. PPN was performed from postoperative day (POD) 1 to POD4. Clinical and laboratory parameters were compared between the two groups; statistical significance was set at P < 0.05.ResultsSerum carnitine concentrations were significantly higher in group LC on POD3 (P < 0.01) and POD7 (P = 0.01). Postoperative changes in laboratory parameters and morbidity were comparable between the two groups. However, the decrease in C-reactive protein from POD3 to POD7 was significantly greater in group LC than in group L (P = 0.011).ConclusionThe results show that intravenous carnitine administration in addition to PN is safe and may be beneficial for recovery from postoperative inflammatory reactions.

The decreased level of plasma carnitine in patients with epilepsy

Antiepileptic drugs (AEDs) have long been known to affect carnitine metabolism, dropping the plasma free carnitine. Valproate (VPA) was considered to be the strongest carnitine-reducing agent. VPA-induced hyperammonemic encephalopathy and hepatotoxicity are well known, and pre-existing carnitine deficiency can be a predisposing factor, especially in congenital metabolic disorders. Several studies have shown that carnitine supplementation in patients receiving VPA to result in subjective and objective improvements and to prevent VPA-induced hepatotoxicity and encephalopathy, in parallel with increases in carnitine serum concentrations. Level of free plasma carnitine <20 micromol/l (syn. carnitine deficiency) in patients with epilepsy (in 15-30% of cases) may occur not only with administration of VPA but with administration of other AEDs (phenobarbital, phenytoin, carbamazepine) and low nutritional intake of carnitine. Some findings indicate that the number of AEDs used is a risk factor for carnitine deficiency. It was established that body weight, height and multidrug therapy are significantly associated with low level of free plasma in epileptic patients. Carnitine deficiency can have severe consequences; but most epileptic patients suffering from it are asymptomatic. Although carnitine deficiency is not uncommon among patients receiving AEDs, it seems not necessary to routinely monitor carnitine levels in epileptic ambulatory patients, this is reasonable only in groups of risk. L-carnitine supplementation is clearly indicated in case of VPA-induced hepatotoxicity (i.v. administration) VPA overdose (i.v. administration), primary carnitine-transporter defect and is strongly recommended in specific secondary carnitine deficiency syndromes, symptomatic VPA-associated hyperammonemia, infants and young children receiving VPA, especially those younger than 2 years, patients with a complex neurologic disorder, who are receiving multiple AEDs, patients who have risk factors for hepatotoxicity and carnitine insufficiency. In the absence of double blind trials, clinical practice is based on empiric observation, clinical experience, and theory. Well-designed studies of specific and general uses of L-carnitine replacement therapy in patients with epilepsy are needed.

Relationship of Serum Carnitine Level with Falls and Gait Disturbance in the Elderly.

Gait disturbance and falls are serious events that can impair activities of daily living (ADL) in the elderly. On the other hand, carnitine plays essential roles in energy production, and carnitine deficiency leads to low activity levels. We examined whether a lower serum carnitine concentration was correlated with falls and gait disturbances in the elderly. We performed a cross-sectional study. One hundred and ninety-eight elderly patients (male, 83; female, 115; 81 ± 6 years old) were enrolled in this study. Physical performance (hand grip strength, leg strength, walking speed, one-leg standing time, and tandem gait steps) and frailty status (The Edmonton Frail Scale: EFS) were evaluated. The serum total, free, and acylated carnitine levels were measured using an enzyme cycling method. We then investigated the associations between the serum carnitine level, history of falls, and the results of these physical examinations. Of the 198 subjects, 56 (28%) had a history of falls within the past one year. The patients with a history of falls had lower serum total carnitine and free carnitine levels than those without a history of falls. Regarding the physical performance results, the patients with a history of falls had higher EFS scores, a weaker hand grip strength, a slower walking speed, a shorter one-leg standing time, and a smaller number of tandem gait steps than those without a history of falls. A logistic regression analysis showed that the low serum total carnitine concentration was identified as an independent factor associated with a history of falls, a slow walking speed after adjustments for age, sex and modified EFS. A low serum carnitine level is associated with a history of falls and gait disturbances in elderly people.

Acyl/free carnitine ratio is a risk factor for hepatic steatosis after pancreatoduodenectomy and total pancreatectomy

ObjectivesHepatic steatosis, one of the most frequent long-term complications of pancreatectomy, influences not only hepatic function but also survival rate. However, its risk factors and pathogenesis have not been established. The purpose of this study was to clarify the risk factors for hepatic steatosis after pancreatectomy. MethodsIn this retrospective study of 21 patients who had undergone pancreatectomy (19 cases of pancreatoduodenectomy and 2 cases of total pancreatectomy), serum carnitine concentrations, fractions of carnitine, and hepatic attenuation on computed tomography images were analyzed with the aim of identifying risk factors for hepatic steatosis. ResultsThirteen (61.9%) of the 21 patients were diagnosed as having hypocarnitinemia after pancreatectomy. Average hepatic attenuation was as low as 42.2HU (±21.3 SD). A high ratio of acyl/free carnitine was associated with less pronounced hepatic attenuation according to both univariate (P < 0.001) and multivariate (P = 0.020) regression analyses. ConclusionsThe serum carnitine concentrations were low after pancreatectomy in some patients. The statistical analyses suggest that a high ratio of acyl/free carnitine is an independent risk factor for hepatic steatosis after pancreatectomy.

Analysing hypoglycin A, methylenecyclopropylacetic acid conjugates and acylcarnitines in blood to confirm the diagnosis and improve our understanding of atypical myopathy

SummaryOwing to recent methodological validation studies, we have now the opportunity to determine hypoglycin A, methylenecyclopropylacetic acid–carnitine and acylcarnitines concentrations in equine serum. These analytes are essential to confirm the diagnosis of atypical myopathy but also to improve our understanding of the pathophysiology of the disease. In particular, they might help elucidate why some horses seem more resistant to hypoglycin A poisoning.

Carnitine dynamics and their effects on hyperammonemia in cirrhotic Japanese patients

Supplementation with levocarnitine preparations has been reported to improve hepatic encephalopathy, but no detailed investigations have addressed the dynamics of carnitine or its supplementation indication in cirrhosis patients. We studied carnitine dynamics in cirrhotic patients by measuring serum and liver tissue carnitine levels and tested the effects of levocarnitine supplementation on concurrent hyperammonemia. In a pilot cohort of seven patients with liver cirrhosis and five patients without cirrhosis, the serum and liver carnitine concentrations were measured. Then the serum carnitine fractions were analyzed in 70 liver cirrhosis patients. Among them, a levocarnitine preparation (1800mg/day) was supplemented orally for 3months in 27 patients with refractory hyperammonemia, and the effects were evaluated. A significant correlation was observed between serum and liver tissue carnitine concentrations (r = 0.69, P <0.05). The serum total carnitine concentration was 68.4 ± 4.7μmol/L, the free carnitine concentration was 53.2 ± 2.6μmol/L, and the acylcarnitine concentration was 13.2 ± 1.1μmol/L in 70 cirrhotic patients (reference values are 45-91, 36-74, 6-23μmol/L, respectively). There was no correlation between blood ammonia and serum carnitine concentrations. The serum carnitine concentration rose with levocarnitine supplementation, reaching steady state after 1month and, in parallel, refractory hyperammonemia was significantly improved. The cut-off level for a 20% decrease in blood ammonia was identified as 62.0μmol/L total carnitine concentration by receiver-operating characteristic curve analysis, with an area under the curve of 0.69. Serum carnitine concentrations were within standard levels in the majority of liver cirrhosis patients. In patients with concurrent hyperammonemia, the levocarnitine supplementation reduced blood ammonia levels.

Serum carnitine concentration is decreased in patients with Lyme borreliosis.

Lyme borreliosis (LB) is a serious infectious disease. Carnitine plays a crucial role in metabolism and inflammatory responses. Carnitine may be important in improving neuronal dysfunction and loss of neurons. To evaluate serum carnitine concentration in adult patients with various clinical types of LB. Groups: 1) patients with erythema migrans (EM, n=16), 2) neuroborreliosis (NB, n=10), 3) post-Lyme disease (PLD, n=22) and healthy controls (HC, n=32). Total (TC) and free (FC) carnitine were determined with the spectrophotometric method. TC levels (44.9±10.4, 28.0±8.4, 35.9±15.6 μmol/L) in the EM, NB and PLD patients were lower than in HC (54.0±11.4 μmol/L), p < 0.001. FC levels (32.7±7.7, 23.6±6.8, 26.3±11.2 μmol/L) in the EM, NB and PLD patients were lower than in HC (40.5±7.6 μmol/L), p < 0.001. AC levels (12.2±5.2, 4.4±2.6, 9.6±7.4 μmol/L) in the EM, NB and PLD patients were lower in the NB and PLD patients than in HC (13.5±8.40 μmol/L), p <0.001. AC/FC ratio was 0.31±0.14, 0.18±0.09, 0.39±0.33 in the EM, NB and PLD patients. LB patients exhibit a significant decrease of their serum carnitine concentrations. The largest changes were in the NB and PLD patients. To prevent late complications of the disease a possibility of early supplementation with carnitine should be considered. Further studies are required to explain the pathophysiological significance of our findings.