Plasma L-carnitine Research Articles

Plasma L-carnitine levels of obese and non-obese polycystic ovary syndrome patients

It is well-known that plasma L-carnitine concentrations are significantly decreased in obese individuals. A study showed that L-carnitine concentrations are significantly lower in lean PCOS patients than in lean healthy women. Thus, it has been suggested that lowered L-carnitine is associated with PCOS. This study also showed that the women with PCOS had significantly lower L-carnitine levels than those of the healthy controls. In addition, this study hypothesised that low L-carnitine levels in PCOS patients were associated with obesity and/or insulin resistance. Moreover, plasma L-carnitine concentrations were found to be statistically similar in PCOS patients and healthy controls, when controlled for obesity. This study implied that L-carnitine could be used as an adjunctive therapy in the management of insulin resistance or obesity in women who have PCOS. Further research might be planned to clarify the clinical effects of L-carnitine administration in PCOS patients with insulin resistance and/or obesity.

Diabetes is Associated with Higher Trimethylamine N-oxide Plasma Levels.

Recent studies have revealed strong associations between systemic trimethylamine N-oxide (TMAO) levels, atherosclerosis and cardiovascular risk. In addition, plasma L-carnitine levels in patients with high TMAO concentrations predicted an increased risk for cardiovascular disease and incident major adverse cardiac events. The aim of the present study was to investigate the relation between TMAO and L-carnitine plasma levels and diabetes. Blood plasma samples were collected from 12 and 20 weeks old db/db mice and patients undergoing percutaneous coronary intervention. Diabetic compared to non-diabetic db/L mice presented 10-fold higher TMAO, but lower L-carnitine plasma concentrations at 12 weeks of age. After 8 weeks of observation, diabetic db/db mice had significantly increased body weight, insulin resistance and TMAO concentration in comparison to non-diabetic control. In 191 patients undergoing percutaneous coronary intervention the median (interquartile range) plasma concentration of TMAO was 1.8 (1.2-2.6) µmol/L. Analysis of the samples showed a bivariate association of TMAO level with age, total cholesterol and L-carnitine. The multivariate linear regression analysis revealed that, in addition to L-carnitine as the strongest predictor of log transformed TMAO (p<0.001), the parameters of age, diabetes status and body mass index (BMI) were independently associated with increased log transformed TMAO levels (p<0.01).Our data provide evidence that age, diabetes and BMI are associated with higher TMAO levels independently of L-carnitine. These data support the hypothesis of TMAO as a cardiovascular risk marker and warrant further investigation of TMAO for diabetes research applications.

Probiotic supplementation and trimethylamine-N-oxide production following a high-fat diet.

The objective of this study was to test the hypothesis that the multi-strain probiotic VSL#3 would attenuate the increase in fasting plasma concentrations of trimethylamine-N-oxide (TMAO) following a high-fat diet. Nineteen healthy, non-obese males (18-30 years) participated in the present study. Following a 2-week eucaloric control diet, subjects were randomized to either VSL#3 (900 billion live bacteria) or placebo (cornstarch) during the consumption of a hypercaloric (+1,000 kcalday(-1) ), high-fat diet (55% fat) for 4 weeks. Plasma TMAO, L-carnitine, choline, and betaine (UPLC-MS/MS) were measured at baseline and following a high-fat diet. Plasma TMAO significantly increased 89% ± 66% vs. 115% ± 61% in both the VSL#3 and placebo groups, respectively; however, the magnitude of change in plasma TMAO was not different (P > 0.05) between them. Plasma L-carnitine, choline, and betaine concentrations did not increase following the high-fat diet in either group. A high-fat diet increases plasma TMAO in healthy, normal-weight, young males. However, VSL#3 treatment does not appear to influence plasma TMAO concentrations following a high-fat diet. Future studies are needed to determine whether other therapeutic strategies can attenuate the production of TMAO.

Multiplexed separations for biomarker discovery in metabolomics: Elucidating adaptive responses to exercise training.

High efficiency separations are needed to enhance selectivity, mass spectral quality, and quantitative performance in metabolomic studies. However, low sample throughput and complicated data preprocessing remain major bottlenecks to biomarker discovery. We introduce an accelerated data workflow to identify plasma metabolite signatures of exercise responsiveness when using multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS). This multiplexed separation platform takes advantage of customizable serial injections to enhance sample throughput and data fidelity based on temporally resolved ion signals derived from seven different sample segments analyzed within a single run. MSI-CE-MS was applied to explore the adaptive metabolic responses of a cohort of overweight/obese women (BMI > 25, n = 9) performing a 6-wk high-intensity interval training intervention using a repeated measures/cross-over study design. Venous blood samples were collected from each subject at three time intervals (baseline, postexercise, recovery) in their naïve and trained states while completing standardized cycling trials at the same absolute workload. Complementary statistical methods were used to classify dynamic changes in plasma metabolism associated with strenuous exercise and training status. Positive adaptations to exercise were associated with training-induced upregulation in plasma l-carnitine at rest due to improved muscle oxidative capacity, and greater antioxidant capacity as reflected by lower circulating glutathionyl-l-cysteine mixed disulfide. Attenuation in plasma hypoxanthine and higher O-acetyl-l-carnitine levels postexercise also indicated lower energetic stress for trained women.

Determination of trimethylamine-N-oxide in combination with L-carnitine and γ-butyrobetaine in human plasma by UPLC/MS/MS.

An ultra-high-performance liquid chromatography-mass spectrometry (UPLC/MS/MS) method was developed and validated for the quantification of trimethylamine-N-oxide (TMAO) simultaneously with TMAO-related molecules L-carnitine and γ-butyrobetaine (GBB) in human blood plasma. The separation of analytes was achieved using a Hydrophilic interaction liquid chromatography (HILIC)-type column with ammonium acetate-acetonitrile as the mobile phase. TMAO determination was validated according to valid US Food and Drug Administration guidelines. The developed method was successfully applied to plasma samples from healthy volunteers.

Effect of craniotomy on oxidative stress and its effect on plasma L-carnitine levels.

to investigate the impact of craniotomy on oxidative stress and its effect on levels of plasma L-carnitine (LC). plasma levels of reactive oxygen species, superoxide dismutase (SOD), glutathion peroxidase (GSH-Px), catalase (CAT), total antioxidative capacity (T-AOC), and thiobarbituric acid reactive substances (TBARS) were measured in 34 patients (26 males and 8 females, mean age 47.7 ± 6.7 years) before and after craniotomy. Plasma levels of LC, acetyl-L-carnitine (ALC), and propionyl-L-carnitine (PLC) were also measured before and after the craniotomy. the plasma concentrations of SOD, GSH-Px, CAT, and T-AOC within the first 4 h after craniotomy were lower than their baseline values (P < 0.05). There were no statistically significant differences in the mean plasma levels of SOD, GSH-Px, CAT, or T-AOC between the baseline and 24 h post-operative values. The level of TBARS at 4 h after the craniotomy was lower than the pre-operative level (P < 0.05), but the 24 h post-operative value was similar to the baseline concentration (P > 0.05). Plasma levels of LC, ALC, and PLC were lower after the craniotomy (P < 0.05), but these levels returned to the baseline levels 24 h after the operation. craniotomy and the associated procedures for surgery/anesthesia temporarily reduce antioxidant activity and plasma levels of L-carnitine.

Simultaneous determination of N(1)-methylnicotinamide, L-carnitine, and creatinine in human plasma and urine by liquid chromatography with mass spectrometry for assessing the activities of multiple renal cationic transporters.

Organic cation transporters are responsible for the disposition of various endogenous and therapeutic agents in humans; thus, there is a great need for the development of a simple assay for simultaneous assessment of the activities of multiple transporters. Using liquid chromatography-mass spectrometry (LC/MS), we developed an assay that allows for simultaneous quantitation of plasma and urinary levels of N(1)-methylnicotinamide (a substrate of hOCT2/hMATEs), L-carnitine (a substrate of hOCTN2), and creatinine (an indicator of glomerular filtration). Samples were diluted with ultrapure water, deproteinized with trichloroacetic acid, filtered, and then injected on a cation exchange column. The analytes were separated with a gradient LC technique and detected by MS. The total assay time was less than 8 min. The lower detection limits for N(1)-methylnicotinamide, L-carnitine, and creatinine were 2, 10, and 24 ng/mL, respectively. Recovery of the analytes was almost complete. A preliminary clinical study conducted in 25 healthy subjects revealed that the mean±SD for the renal clearance (CLR) of N(1)-methylnicotinamide (272.7±81.0 mL/min) far exceeded the glomerular filtration rate (116.3±19.6 mL/min), indicating the involvement of active tubular secretion, while the mean CLR of clearance of L-carnitine was close to nil (1.5±1.4 mL/min), indicating almost complete tubular reabsorption. The present method is potentially useful for clinical studies on the genetic control of cationic transporter activities and the transporter-mediated drug interactions.

Effective dosing of L-carnitine in the secondary prevention of cardiovascular disease: a systematic review and meta-analysis.

BackgroundL-carnitine supplementation has been associated with a significant reduction in all-cause mortality, ventricular arrhythmia, and angina in the setting of acute myocardial infarction (MI). However, on account of strict homeostatic regulation of plasma L-carnitine concentrations, higher doses of L-carnitine supplementation may not provide additional therapeutic benefits. This study aims to evaluate the effects of various oral maintenance dosages of L-carnitine on all-cause mortality and cardiovascular morbidities in the setting of acute MI.MethodsAfter a systematic review of several major electronic databases (PubMed, EMBASE, and the Cochrane Library) up to November 2013, a meta-analysis of five controlled trials (n = 3108) was conducted to determine the effects of L-carnitine on all-cause mortality and cardiovascular morbidities in the setting of acute MI.ResultsThe interaction test yielded no significant differences between the effects of the four daily oral maintenance dosages of L-carnitine (i.e., 2 g, 3 g, 4 g, and 6 g) on all-cause mortality (risk ratio [RR] = 0.77, 95% CI [0.57-1.03], P = 0.08) with a statistically insignificant trend favoring the 3 g dose (RR = 0.48) over the lower 2 g dose (RR = 0.62), which was favored over the higher 4 g and 6 g doses (RR = 0.78, 0.78). There was no significant differences between the effects of the daily oral maintenance dosages of 2 g and 6 g on heart failure (RR = 0.53, 95% CI [0.25-1.13], P = 0.10), unstable angina (RR = 0.90, 95% CI [0.51-1.58], P = 0.71), or myocardial reinfarction (RR = 0.74, 95% CI [0.30-1.80], P = 0.50).ConclusionsThere appears to be no significant marginal benefit in terms of all-cause mortality, heart failure, unstable angina, or myocardial reinfarction in the setting of acute MI for oral L-carnitine maintenance doses of greater or less than 3 g per day.

Impact on L-carnitine Homeostasis of Short-term Treatment with the Pivalate Prodrug Tenofovir Dipivoxil

Pivalate-generating prodrugs have been suggested to cause clinically significant hypocarnitinaemia. Tenofovir dipivoxil, a novel ester prodrug of tenofovir, can be used for treatment for hepatitis B and HIV infection and it was necessary to evaluate the effect of its treatment on carnitine homeostasis. We sought to investigate the effect of Class 1 drug tenofovir dipivoxil on endogenous L-carnitine level during a 72-hr test in healthy Chinese volunteers and to establish a suitable dose of L-carnitine nutritional supplement for patients who were administered short-term tenofovir dipivoxil tablets for treatment for hepatitis B and herpes simplex virus infection. Tenofovir dipivoxil was administered in one of eight dosing regimens (single dose 150, 300 and 600mg, multiple dose 300, 450, and 600mg, multiple dose 450 (600) mg tenofovir dipivoxil and 0.5g L-carnitine) to gender-balanced groups of 84 healthy Chinese volunteers. Plasma concentrations of L-carnitine were quantified before, during and after treatment. Plasma L-carnitine concentrations fell during tenofovir dipivoxil dosing. The nadir in L-carnitine concentration was dependent on the dose of tenofovir dipivoxil and it decreased from 6.1±0.6 to 4.4±0.8μg/ml, 6.1±1.8 to 3.3±1.2μg/ml, 6.2±0.6 to 2.5±0.5μg/ml for single doses of 150, 300, 600mg tenofovir dipivoxil tablets and from 6.0±1.4 to 2.1±1.5μg/ml, 6.2±0.4 to 0.9±0.5μg/ml for multiple doses of 450, 600mg tenofovir dipivoxil tablets, respectively. Short-term administration of tenofovir dipivoxil results in hypocarnitinaemia and increased losses of carnitine in resulting of minor adverse events of decreased food appetite, nausea, abdominal distention and muscle weakness.

Fish Oil and the Pan-PPAR Agonist Tetradecylthioacetic Acid Affect the Amino Acid and Carnitine Metabolism in Rats

Peroxisome proliferator-activated receptors (PPARs) are important in the regulation of lipid and glucose metabolism. Recent studies have shown that PPARα-activation by WY 14,643 regulates the metabolism of amino acids. We investigated the effect of PPAR activation on plasma amino acid levels using two PPARα activators with different ligand binding properties, tetradecylthioacetic acid (TTA) and fish oil, where the pan-PPAR agonist TTA is a more potent ligand than omega-3 polyunsaturated fatty acids. In addition, plasma L-carnitine esters were investigated to reflect cellular fatty acid catabolism. Male Wistar rats (Rattus norvegicus) were fed a high-fat (25% w/w) diet including TTA (0.375%, w/w), fish oil (10%, w/w) or a combination of both. The rats were fed for 50 weeks, and although TTA and fish oil had hypotriglyceridemic effects in these animals, only TTA lowered the body weight gain compared to high fat control animals. Distinct dietary effects of fish oil and TTA were observed on plasma amino acid composition. Administration of TTA led to increased plasma levels of the majority of amino acids, except arginine and lysine, which were reduced. Fish oil however, increased plasma levels of only a few amino acids, and the combination showed an intermediate or TTA-dominated effect. On the other hand, TTA and fish oil additively reduced plasma levels of the L-carnitine precursor γ-butyrobetaine, as well as the carnitine esters acetylcarnitine, propionylcarnitine, valeryl/isovalerylcarnitine, and octanoylcarnitine. These data suggest that while both fish oil and TTA affect lipid metabolism, strong PPARα activation is required to obtain effects on amino acid plasma levels. TTA and fish oil may influence amino acid metabolism through different metabolic mechanisms.

Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis

Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk.

L-carnitine and cancer cachexia. I. L-carnitine distribution and metabolic disorders in cancer cachexia

Cancer cachexia (CC), a progressive loss of body mass, is associated with decreased energy production. Abnormally low levels of L-carnitine (LC) in skeletal muscle means that mitochondrial β-oxidation of long-chain fatty acids (LCFA) does not occur efficiently in patients with CC. We assessed the influence of CC on LC distribution and the effects of parenteral lipid emulsions on plasma LC levels and urinary excretion. Fifty patients with CC were randomly assigned to total parenteral nutrition (TPN) with long-chain triglycerides (LCTs), or LCTs plus medium-chain triglycerides (MCTs) as 50/50. Patients were further separated into those with body-mass index (BMI) ≤ 19 kg/m(2) and BMI >19 kg/m(2). Plasma concentrations of total LC (TC) and free LC (FC) and their urinary excretion were measured, along with skeletal muscle LC levels. On average, plasma FC and TC were higher than reference values in all patients. Patients with BMI ≤ 19 kg/m(2) had lower plasma FC and TC than those with BMI >19 kg/m(2). Skeletal muscle FC in the BMI ≤ 19 kg/m(2) group was lower than reference value, but within the normal range in others. LC and FC urinary excretion was higher than reference values. Plasma LC and its urinary excretion were higher in patients administered pure LCTs relative to those given MCTs/LCTs. A decrease in skeletal muscle LC in cancer patients with CC (BMI ≤ 19 kg/m(2)) correlates with an increase in its plasma levels and increased renal excretion. A diet of MCTs/LCTs reduces LC release from muscle to plasma and urine more effectively than LCTs.

Studies on transdermal delivery of sinomenine hydrochloride through mouse skin treated by microneedle arrays

Objective To analyze the correlation of seminal plasma free testosterone and free L-carnitine with semen density,vitality,and motility,so as to investigate their effects on male fertility and their roles in the examination and treatment of male infertility.Methods Using chemiluminescence immunoassay method,LC-MS-MS and computer-assisted semen analysis system,we examined the seminal levels of free testosterone,free L-carnitine and sperm density,vitality,and motility in 192 infertile males(normozoospermia,n=36;oligozoospermia,n=48;asthenozoospermia,n=60;and oligoasthenozoospermia,n=48).The difference of free testosterone and free L-carnitine levels between different groups was analyzed,and the correlation of their levels with semen density,vitality,and motility was also analyzed using the SPSS 13.0 statistical software.Results The levels of free testosterone and free L-carnitine in the seminal plasma of the normozoospermia men were significantly higher than those of others(P0.05).Correlation analysis showed that there was positive correlation between seminal free testosterone with the sperm density(r=0.427,P0.05),seminal free L-carnitine with the sperm density(r=0.318,P0.01),and seminal free L-carnitine with sperm vitality,motility(r=0.641,P0.01;r=0.568,P0.01).Conclusion Seminal free testosterone level is correlated with the sperm density,and seminal free L-carnitine level is correlated with sperm density,motility and vitality;both levels can be taken as a biochemical index for the clinical diagnosis and treatment of male infertility.

Plasma pharmacokinetics and gastrointestinal transit of a new Propionyl-l-Carnitine controlled release formulation

Propionyl-l-carnitine is a naturally occurring analogue of l-carnitine (LC) produced in the body. PLC administration has shown beneficial effects in cardiovascular pathologies. In ulcerative colitis (UC), oral PLC treatment increased clinical presentation and positively influenced colon histology. In the present study, the MMX Multi Matrix System® (MMX™) was used as drug delivery strategy for targeted PLC colon delivery.A pharmacoscintigraphic study (n = 6 healthy volunteers) described release characteristics of two MMX-PLC-HCl controlled release 500 mg tablets. A pharmacokinetic (PK) parallel group study (n = 24) determined safety, plasma PLC concentrations and PK parameters after single and multiple doses.Gastrointestinal transit was slow and variable. The colon was the main site of PLC release and absorption. After single 500 or 1000 mg PLC doses plasma PLC and LC increased up to 2.6 and 1.2–1.3-fold compared to baseline. Multiple doses of 500 and 1000 mg twice a day over 7 days did not significantly increase maximum plasma concentrations of PLC or LC with respect to concentrations achieved after single dose administration.The colon is the main site of PLC release and absorption from MMX-PLC tablets. A daily dose of 500 mg to 1000 mg PLC twice a day was well tolerated, justifying further studies in patients with pathologies of the distal gastrointestinal tract to evaluate the efficacy of the MMX-PLC formulation.

Mildronate treatment alters γ-butyrobetaine and l-carnitine concentrations in healthy volunteers

In this study, we aimed to investigate the effects of long-term administration of the cardioprotective drug mildronate on the concentrations of l-carnitine and γ-butyrobetaine in healthy volunteers. Mildronate was administered perorally, at a dosage of 500mg, twice daily. Plasma and urine samples were collected weekly. Daily meat consumption within an average, non-vegetarian diet was monitored. l-Carnitine, γ-butyrobetaine and mildronate concentrations were measured using the UPLC/MS/MS method. After 4 weeks, the average concentrations of l-carnitine in plasma significantly decreased by 18%. The plasma concentrations of γ-butyrobetaine increased about two-fold, and this effect was statistically significant in both the male and female groups. In urine samples, a significant increase in l-carnitine and γ-butyrobetaine levels was observed, which provides evidence for increased excretion of both substances during the mildronate treatment. At the end of the treatment period, the plasma concentration of mildronate was 20µm on average. There were no significant differences between the effects observed in female and male volunteers. Meat consumption partially reduced the l-carnitine-lowering effects induced by mildronate. Long-term administration of mildronate significantly lowers l-carnitine plasma concentrations in non-vegetarian, healthy volunteers.

Single Dose Administration of L-Carnitine Improves Antioxidant Activities in Healthy Subjects

L-carnitine has been used as a supplement to treat cardiovascular or liver disease. However, there has been little information about the effect of L-carnitine on anti-oxidation capability in healthy human subjects. This study was designed to investigate the correlation between plasma L-carnitine concentration and antioxidant activity. Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Plasma concentration of L-carnitine was detected by HPLC. The baseline concentration of L-carnitine was 39.14 ± 5.65 µmol/L. After single oral administration, the maximum plasma concentration (C(max)) and area under the curve (AUC(0-∞)) were 84.7 ± 25.2 µmol/L and 2,676.4 ± 708.3 µmol/L·h, respectively. The half-life and the time required to reach the C(max) was 60.3 ± 15.0 min and 3.4 ± 0.46 h, respectively. There was a gradual increase in plasma concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase and total antioxidative capacity (T-AOC) in the first 3.5 h following L-carnitine administration. The plasma concentrations of SOD, GSH-Px, catalase and T-AOC returned to baseline levels within 24 h. A positive correlation was found between L-carnitine concentration and the antioxidant index of SOD (r = 0.992, P < 0.01), GSH-Px (r = 0.932, P < 0.01), catalase (r = 0.972, P < 0.01) or T-AOC (r = 0.934, P < 0.01). In conclusion, L-carnitine increases activities of antioxidant enzymes and the total antioxidant capacity in healthy subjects. It may be useful as a supplementary therapy for chronic illnesses involving excessive oxidative stress.

Relationship Between Plasma L-carnitine Concentration and Production Performance in Hybrid Beef Cattle and Holstein Cows Sired by Different Strain Bulls

Relationship Between Plasma L-carnitine Concentration and Production Performance in Hybrid Beef Cattle and Holstein Cows Sired by Different Strain Bulls

Pharmacological use of l-carnitine in uremic anemia: Has its full potential been exploited?

Anemia is one of the most frequent complications of kidney failure and a common cause of morbidity in dialysis patients. A number of clinical studies have suggested that l-carnitine (LC), a naturally occurring compound involved in bioenergetic processes, may alleviate the anemia of hemodialysis patients. Since LC deficiency is commonly present in dialysis patients, LC has been described as a “conditional vitamin”. However, the use of LC supplementation in dialysis remains controversial as well as its mode of action in preventing anemia. Recent literature shows that to fully exploit its pharmacological potential, LC may have to be administered at doses that achieve supra-physiological levels of LC in plasma and target organs. However, this concept has not been fully investigated in uremic patients. In this article, we will review the use of LC in dialysis patients, and provide a rationale for the anti-anemic action of LC based on biophysical, metabolic and antiapoptotic effects of this compound on erythropoiesis and the function of mature, circulating erythrocytes. The discussion will be focused on experimental and clinical data that support the concept that supra-physiological concentrations of LC may improve the anemic condition of dialysis patients, as would be expected from a “conditional drug” rather than a “conditional vitamin”.

The effect of training on plasma L-carnitine metabolism in purebred Arabian horses

1. Dynamic change of free serum L-carnitine concentration in relation to age, sex, and exercise in Anglo-Arabian Thoroughbred horses Francesca Arfuso, Claudia Giannetto, Elisabetta Giudice, Francesco Fazio, Giuseppe Piccione Journal of Equine Veterinary Science CrossRef

Endogenous plasma carnitine pool composition and response to erythropoietin treatment in chronic haemodialysis patients

Anaemia is a common complication associated with haemodialysis and is usually managed by treatment with recombinant human erythropoietin (rHuEPO). However, many patients remain hyporesponsive to rHuEPO treatment despite adequate iron therapy. The effect of L-carnitine administration on rHuEPO dose and/or haematocrit in haemodialysis patients has been previously reported with equivocal results. This study examined the relationship between endogenous carnitine pool composition and rHuEPO requirements in long-term haemodialysis patients. Pre-dialysis blood samples were collected from 87 patients and analysed for plasma L-carnitine and individual acylcarnitine levels by LCMS/MS. As an indication of rHuEPO responsiveness, erythropoietin resistance index (ERI) was calculated as rHuEPO dose/kg/week normalized for haemoglobin levels. A significant negative correlation between L-carnitine levels and ERI was found (P = 0.0421). All patients categorized as high ERI (>0.02 microg/kg/week/gHb) exhibited subnormal L-carnitine levels (<30 microM); conversely, patients with normal L-carnitine levels (>30 microM) displayed low ERI values (<0.02 microg/kg/week/gHb). More importantly, the ratio of non-acetyl acylcarnitines/total carnitine was significantly positively correlated with ERI (P = 0.0062). These data illustrate the relationship between carnitine levels and response to rHuEPO treatment in haemodialysis patients, in particular, the importance of the proportion of long-chain acylcarnitines within the plasma carnitine pool. This proportion may be more indicative of the response to L-carnitine supplementation than absolute L-carnitine levels alone.