Oral Administration Of L-carnitine Research Articles

Chronic oral administration of L-carnitine induces testicular injury: in vivo evidence.

While L-carnitine is commonly used to treat oligoasthenozoospermia, concerns have been raised regarding its potential harm to spermatogenesis. This study aims to investigate the potential testicular toxicity of long-term oral administration of L-carnitine. In this study, we refer to the clinical adult dosage and mode of L-carnitine administration, and after converting to mouse doses, mice were daily intragastrical administered L-carnitine to investigate whether it was harmful to the testis. The investigation involved assessing its potential testicular toxicity through histopathological staining, sperm motility analysis, and quantitative real-time PCR. Our results showed that L-carnitine increased sperm motility after 14days of continuous administration, but increased luminal exfoliated spermatogenic cells occurred in the testis, and TUNEL results showed increased apoptotic cells. Compared with the control group, the mRNA expression of the spermatogenic cell marker at each stage was decreased in mice treated for 14 consecutive days of L-carnitine. After 50days of continuous administration followed by 14days of drug withdrawal, the total sperm motility of mice was almost 0, and a large number of abnormal eosinophilic spermatogenic cells appeared in the testis. These indicate that oral L-carnitine for more than 14 days impairs spermatogenesis in mice, and sudden discontinuation of administration results in substantial death of established spermatogenic cell populations. Our findings suggest that chronic oral administration of L-carnitine impairs spermatogenic function in the testis. The oral administration of L-carnitine to enhance sperm motility should not exceed the 2/5 point of the spermatogenic cycle.

Additional L-Carnitine Reduced the Risk of Hospitalization in Patients with Overt Hepatic Encephalopathy on Rifaximin

Background: Data regarding the additional effect on the recurrence of hepatic encephalopathy (HE) after oral L-carnitine administration are scarce. Objective: This study aimed to assess the additional effects of L-carnitine in patients who were receiving rifaximin for HE. Methods: This randomized study comprised a screening visit and a 12-week treatment period. Patients who fulfilled the eligibility criteria were randomized to either group A (additional rifaximin) or group B (additional L-carnitine and rifaximin). Group A received 1,200 mg/day of rifaximin. Group B received 1,500 mg/day of L-carnitine and rifaximin at 1,200 mg/day. The endpoints were the changes in the portal systemic encephalopathy (PSE) index and the admission rate from the baseline for the duration of the study in both groups. Results: Eighty-three patients were randomized to either group A (n = 42) or group B (n = 41). In group A, the PSE index decreased from 0.35 ± 0.09 at baseline to 0.27 ± 0.11 on the final evaluation day (p = 0.001). In group B, the PSE index decreased from 0.37 ± 0.09 at baseline to 0.24 ± 0.11 on the final evaluation day (p = 0.001). Although there was not a significant reduction in the PSE index in group A compared to that in group B (p = 0.202), the admission rates were 30.9% and 9.8% in groups A and B, respectively. Additional L-carnitine significantly reduced the admission rate (p = 0.028). Conclusion: L-Carnitine addition reduced the risk of hospitalization for patients who received rifaximin for HE.

The effect of adding L-Carnitine to the GnRH-antagonist protocol on assisted reproductive technology outcome in women with polycystic ovarian syndrome: a randomized clinical trial

Objective This study aimed to investigate the effect of adding L-Carnitine to the gonadotropins on ART outcome in frozen-thawed embryo transfer cycles among PCOS women. Methods In this randomized clinical trial, 83 patients with PCOS were randomized to either L-Carnitine supplemented (n = 42) or control (n = 41) groups. The L-Carnitine group was given 3000 mg of oral L-Carnitine daily until the final day of ovulation. The numbers of metaphase II (MII) oocytes, 2-pronuclears (2PNs), oocyte maturity rate, fertilization rate, fertilization proportion as well as implantation, chemical and clinical pregnancy rates were compared between the two groups. Results Even though the duration of stimulation and endometrial thickness were comparable between groups (p > .05), serum estradiol level on the day of oocyte triggering, was significantly higher in the L-Carnitine group compared to the control group (p < .05). In contrast, the number of retrieved and MII oocytes as well as the number of 2PNs and obtained embryos were similar between groups (p > .05). Moreover, oocyte maturity rate (0.85 ± 0.38 vs. 1.02 ± 0.90), fertilization proportion (0.62 ± 0.44 vs. 0.80 ± 0.86), fertilization rate (0.70 ± 0.22 vs. 0.76 ± 0.19) along with implantation rate (18.1 vs. 13.7%), chemical (26.8 vs. 30.7%) and clinical (24.3 vs. 25.6%) pregnancy rates, were all comparable between L-Carnitine and control groups respectively (p > .05). Conclusions Our result showed that oral L-Carnitine administration during induction of ovulation among PCOS women could not improve laboratory and pregnancy outcome.

L-carnitine reduces hospital admissions in patients with hepatic encephalopathy.

The aim of this study was to determine whether oral L-carnitine administration reduces the blood ammonia concentration and number of hospital admissions for hepatic encephalopathy in patients with advanced cirrhosis. Of 68 patients with hepatic encephalopathy treated with oral L-carnitine supplementation from April 2013 to March 2016, we enrolled 19 patients who had received full standard treatment. We analyzed blood ammonia concentration, number of hospital admissions, and prognosis to determine how effective L-carnitine was in achieving mid-term to long-term suppression of recurrent hepatic encephalopathy. Median blood ammonia concentrations at the start, 1 week, 12 weeks, 24 weeks, and 48 weeks were 159, 79, 75, and 82 μg/dL, respectively. Blood ammonia concentrations 12 week, 24 weeks, and 48 weeks after L-carnitine administration were significantly lower than those at the start (P < 0.0001, respectively). During the 3 years prior to oral L-carnitine administration, the enrolled patients were hospitalized a total of 29 times for hepatic encephalopathy. However, during the 3 years following oral L-carnitine administration, they were admitted a total of six times for hepatic encephalopathy (P < 0.001). Median survival time was 40.9 months. Child-Pugh scores before and after oral L-carnitine administration differed significantly, whereas liver reserve function, nutritional status, and muscle index did not change significantly. Oral L-carnitine administration is effective and free of adverse effects in patients with hyperammonemia and reduces the number of hospital admissions for hepatic encephalopathy.

Supplementation with L-Carnitine Rescues Sperm Epigenetic Changes in Asthenospermic Male Semen with Altered Acetyl-L-Carnitine Levels

Objective: To investigate the relationship between the concentration of L-carnitine in semen and sperm parameters and investigate the epigenetic profile in sperm cell after L-carnitine usage. Methods: From February 2017 to February 2018, 46 semen samples from asthenospermic males and 41 semen samples from healthy donors were acquired. Motility parameters were assessed using computer-assisted sperm analysis (CASA, n = 78) and the DNA fragmentation index (DFI) was evaluated through flow cytometry (n = 86), %DFI = % cells outside main population. Other oxidative stress markers, such as reactive oxygen species (ROS) levels (n = 86) and the mitochondria DNA copy numbers, were detected (n = 78). The concentration of L-carnitine and acetyl-L-carnitine was detected (n = 82), and methylation was analyzed (n = 30). After that, we collected 13 fresh semen samples from asthenospermic males and 23 fresh semen samples from healthy donors. These samples were used in a freeze-thaw model that was used to determine whether adding L-carnitine could change sperm progressive motility (n = 23), apoptosis index (n = 9), and methylation analysis (n = 7). In total, we have done 13 asthenospermia samples for Western blot, and except for the poor Western result, we analyzed 6 samples for H3K9ac detection, 7 samples for H3K9m3 and H3K27m3 detection, and immunofluorescence (n = 3). Finally, we had recruited 30 volunteers, and they were given oral administration of L-carnitine for 3 months and then collected semen samples at different time points for methylation analysis. Results: The concentration of acetyl-L-carnitine is negatively correlated with the %DFI value (r2 = 0.1090; P = 0.0026), and the concentration of acetyl-L-carnitine is positively correlated with sperm forward motility (r2 = 0.0543; P = 0.0458) and ROS (r2 = 0.1854;P Conclusion: L-carnitine can reduce the %DFI and also affect the methylation of the histone modification marker in sperm as a possible epigenetic regulator.

L-Carnitine as a Diet Supplement in Patients With Type II Diabetes.

Introduction: L-Carnitine is a very important component of the human body which is involved in cardiac function and generally in the proper functioning of the muscular system. Also, it contributes to the proper use of glucose by the cell, thereby improving the regulation of glucose metabolism of the diabetic patient and preventing complications such as fatigue, insomnia, and mental activity. In this paper we would like to show the therapeutic effect of L-carnitine on type II diabetic patients after 2 g/day oral administration of L-carnitine.Methods: In this study 181 Greek patients, 84 men and 97 women, aged 50-65 years, Type II diabetics, were administered L-carnitine for six months. All of them were euglycemic, under the proposed treatment, with no diabetic complications or cardiovascular problems. They were under the Mediterranean diet trying to keep their body mass index (BMI) constant. They were neither smokers nor alcohol drinkers. They were administered 2 g/day L-carnitine, orally, once daily for six months, on an empty stomach. The blood tests included fasting glucose, glycated hemoglobin (HBA1c), total cholesterol, and triglycerides and they were performed before, three months after, and six months after the treatment initiation. We also evaluated their tiredness, insomnia, and mental activity at these time points; the participants were given forms to fill out (regarding the distance they are able to brisk walk thrice/week, the duration of their calm uninterrupted sleep and their performance in a cognitive screening test, respectively) and based on the results of their answers, they were allocated to graded groups and scale analysis was performed in each one of them.Results: Fasting glucose mean decrease was 17.51 after three months of medication (p<0.05); the decrease though noted after six months was not statistically significant. HbA1c showed a statistically significant mean decrease in both three- and six-month milestones (0.335, p<0.05 and 0.623, p<0.05 respectively). Changes noted in cholesterol levels were not statistically significant. Triglyceride measurements showed a significant decrease; -15.38 after three months (p<0.05) and -31.39 after six months of treatment (p<0.05). Finally, significant changes were found in both time periods for tiredness (three months: -0.49, p<0.05, six months: -0.88, p<0.05), insomnia (three months: -0.49, p<0.05, six months: -0.88, p<0.05), and mental activity (three months: +0.25, p<0.05, six months: +0.89, p<0.05).Conclusion: L-Carnitine could be a valuable dietary supplement in patients with type II diabetes who follow a Mediterranean diet and are under recommended treatment. Research in this field though is at an early stage and more studies should be performed.

Down-Regulation of Mitochondrial Metabolism after Tendon Release Primes Lipid Accumulation in Rotator Cuff Muscle

Atrophy and fat accumulation are debilitating aspects of muscle diseases and are rarely prevented. Using a vertical approach combining anatomic techniques with omics methodology in a tenotomy-induced sheep model of rotator cuff disease, we tested whether mitochondrial dysfunction is implicated in muscle wasting and perturbed lipid metabolism, speculating that both can be prevented by the stimulation of β-oxidation with l-carnitine. The infraspinatus muscle lost 22% of its volume over the first 6 weeks after tenotomy before the area-percentage of lipid increased from 8% to 18% at week 16. Atrophy was associated with the down-regulation of mitochondrial transcripts and protein and a slow-to-fast shift in muscle composition. Correspondingly, amino acid levels were increased 2 weeks after tendon release, when the levels of high-energy phosphates and glycerophospholipids were lowered. l-Carnitine administration (0.9 g/kg per day) prevented atrophy over the first 2 weeks, and mitigated alterations of glutamate, glycerophospholipids, and carnitine levels in released muscle, but did not prevent the level decrease in high-energy phosphates or protein constituents of mitochondrial respiration, promoting the accumulation of longer lipids with an increasing saturation. We conclude that the early phase of infraspinatus muscle degeneration after tendon release involves the elimination of oxidative characteristics associated with an aberrant accumulation of lipid species but is largely unrelated to the prevention of atrophy with oral l-carnitine administration.

The Effect of Different l-Carnitine Administration Routes on the Development of Atherosclerosis in ApoE Knockout Mice.

l-Carnitine (LC) is abundant in red meat and is widely added to health supplements and food. This study focuses on the adverse effects of oral supplementation of 1.3% LC in ApoE-/- mice and whether the parenteral administration of LC (subcutaneously, sub) has any impact on the development of atherosclerosis. Mice are randomly divided into three groups (n=15). All mice are fed a high-fat diet (HFD). The number of Ly6Chi monocytes; degree of atherosclerosis; plasma LC, γ-butyrobetaine (γBB), and trimethylamine-N-oxide (TMAO) levels; and microbial community composition are analyzed. Compared with the HFD and HFD±LC (sub) groups, the number of Ly6Chi monocytes, atherosclerotic plaque area, and plasma γBB and TMAO levels are increased in the HFD±LC (oral) group (p<0.001). Plasma LC levels in the HFD±LC (sub) group are higher than those in other groups. The levels of γBB, TMAO, and Ly6Chi monocytes are positively correlated with atherosclerotic plaque area (p<0.01), and TMAO is positively correlated with Bacteroidetes and negatively correlated with Firmicutes at the phylum level. In contrast with oral LC administration, subcutaneous LC administration, which bypasses its conversion to TMAO in the liver, does not have a detrimental effect on the development of atherosclerosis in male ApoE-/- mice. Taking LC parenterally may be preferable among patients who require LC supplementation.

Oral administration of l-carnitine improves the clinical outcome of fertility in patients with IVF treatment

Age-dependent decline of mitochondrial function has been proposed to be a main cause of decline of embryo quality. Then, l-carnitine plays important roles in reducing the membranous toxicity of free-fatty acids by forming acyl-carnitine and promoting β-oxidation, preventing cell damage. Recent research revealed that l-carnitine played important roles in vitro in oocyte growth, oocyte maturation and embryo development. However, such beneficial effects of l-carnitine in vivo have yet to be verified. The effect of oral l-carnitine supplementation on embryo quality and implantation potential was examined. A total of 214 patients were included in this study. They all previously received in vitro fertilization-embryo transfer (IVF-ET) and failed to conceive. Then they were administered l-carnitine for 82 days on average and underwent IVF-ET again. There were no significant differences in the total number of retrieved oocytes, and their maturation and fertilization rates between before and after l-carnitine administration. The quality of embryos on Days 3 and 5 after insemination was improved following l-carnitine administration (p < .05) in cycles after l-carnitine administration compared with previous cycles. Healthy neonates were born after IVF-ET following l-carnitine administration. Our data suggested that oral administration of l-carnitine to fertility patients improved the developmental competence of their oocytes after insemination.

Comparison of the Effects of Varicocelectomy and Oral L-carnitine on Sperm Parameters in Infertile Men with Varicocele.

Varicocele is defined as dilated and twisted veins of the pampiniform plexus in the spermatic cord. It is the most common cause of male infertility. There are various medical and surgical procedures for the treatment of this disease. This study was aimed to compare the effects of oral administration of L-Carnitine and varicocelectomy on spermogram parameters. This study was conducted as a double blind clinical trial without randomization. Inclusion criteria were, all married infertile men with varicocele. Patients chose their treatment personally and spermogram was carried out for all patients before and after the third and sixth months of treatment. Then, the sperm parameters of the two groups were compared using repeated measures ANOVA. In our study, trend of sperm count in the surgery group changed from 22 to 28.61 million (vs 34.6 to 45.37 in L-Carnitine group), motility changed from 21.74 to 35.38 percent (vs 33.9 to 47.48 in L-Carnitine group), normal sperm morphology changed from 46.25 to 60 percent (vs 56.61 to 69.7 in L-Carnitine group) and volume of semen changed from 3.5 to 4.17 cc (vs 2.95 to 4.33 in L-Carnitine group). These values were not statistically different between the two groups. Based on the results of this study, we can say that medicinal treatment by administration of oral L-Carnitine is as effective as varicocelectomy in improving semen parameters and can be used as an alternative to surgery for varicocele grade II.

L-carnitine ameliorates the liver inflammatory response by regulating carnitine palmitoyltransferase I-dependent PPARγ signaling.

The liver is crucial for systemic inflammation in cancer cachexia. Previous studies have shown that L-carnitine, as the key regulator of lipid metabolism, exerts an anti-inflammatory effect in several diseases, and ameliorates the symptoms of cachexia by regulating the expression and activity of carnitine palmitoyltransferase (CPT) in the liver. However, the effect of L-carnitine on the liver inflammatory response in cancer cachexia remains to be elucidated. The aim of the present study was to examine the role of the CPT I-dependent peroxisome proliferator-activated receptor (PPAR)γ signaling pathway in the ameliorative effect of L-carnitine on the liver inflammatory response. This was investigated in a colon-26 tumor-bearing mouse model with cancer cachexia. Liver sections were immunohistochemically analyzed, and mRNA and protein levels of representative molecules of the CPT-associated PPARγ signaling pathway were assessed using PCR and western blot analysis, respectively. The results showed that oral administration of L-carnitine in these mice improved hepatocyte necrosis, liver cell cord derangement and hydropic or fatty degeneration of the liver cells in the liver tissues, decreased serum levels of malondialdehyde, increased serum levels of superoxide dismutase and glutathione peroxidase, and elevated the expression levels of PPARα and PPARγ at the mRNA and protein levels. These changes induced by L-carnitine were reversed by treatment with etomoxir, an inhibitor of CPT I. The inhibitory effect of L-carnitine on the increased expression level of nuclear factor (NF)-κB p65 in the peripheral blood mononuclear cells was markedly weakened by GW9662, a selective inhibitor of PPAR-γ. GW9662 also eliminated the inhibitory effect of L-carnitine on the expression of cyclooxygenase-2 (Cox-2) in the liver, and on the serum expression levels of pro-inflammatory prostaglandin E2, C-reactive protein, tumor necrosis factor-α and interleukin-6 in the cancer cachexia model mice. This reversing effect of GW9662 on L-carnitine was restored by pyrrolidine dithiocarbamate, a specific inhibitor of NF-κB signaling. Taken together, these results demonstrated that L-carnitine ameliorated liver inflammation and serum pro-inflammatory markers in cancer cachexia through regulating CPT I-dependent PPARγ signaling, including the downstream molecules of NF-κB p65 and Cox-2.

EFFECT OF ORAL L-CARINITINE ADMINISTRATION ON PRODUCTIVE AND REPRODUCTIVE PERFORMANCES OF CROSSBREED CATTLE

The objective of this study was to evaluate the effects of oral L-carnitine (LC) administration on milk yield and composition, estrous activity and reproduction performance of crossbreed cows. A total of 30 crossbreed cows at early post-partum, weighing 432.7±23.5 kg LBW, aging 3.5-4 years and in 1-3 parities were divided into two similar groups according to LBW and age. Cows in the 1st group were fed a basal diet and was considered as a control group (G1). While, cows in the 2nd group (G2) were fed the same diet and treated orally with 3 g LC/cow/day for 120 days postpartum. Cows were machine milked and milk yield was calculated as actual (AMY) or 4% fat corrected milk (FCMY) yield. Milk composition and somatic cell count (SCC) were determined. Estrus was detect and cows in heat were artificially inseminated. Then, number and length of estrous cycles from calving up to conception was recorded. Postpartum 1st estrus (PPFEI) and 1st service (PPFSI) intervals, number of services per conception (NSC), service period length (SPL), days open (DO) and conception rate (CR%) were calculated. Pregnancy was diagnosed by rectal palpation on day 60 post-insemination. Results show that daily milk yield as AMY or FCMY of cows increased (P<0.05) by about 19.3% in G2 than in G1. Percentage of fat and protein in milk increased (P<0.05), while SCC decreased (P<0.05) by about 16.9% in milk of G2 as compared to G1. Average number of estrus cases and estrous cycles/cow was lower (P<0.05) in G2 than in G1. Average P4 concentration and P4 peak during the estrous cycle was higher (P<0.05) in G2 than in G1. Average P4 concentration during PPFEI was lower (P<0.05) in G2 than in G1. Average of PPFEI, PPFSI, SPL, DO and NSC were lower (P<0.05) in G2 than in G1. CR was higher (P<0.05) in G2 (93.33%) than in G1 (66.67%). In conclusion, the present study indicated beneficial effects of L-carnitine treatment (3 g/cow) for 120 days during early lactation period on milk production and reproductive performance of crossbreed cows during the first four months of lactation.

Effects of Levocarnitine on Brachial-Ankle Pulse Wave Velocity in Hemodialysis Patients: A Randomized Controlled Trial

Background and Aims: Atherosclerotic cardiovascular disease is the most common cause of mortality in patients with end-stage kidney disease. Chronic kidney disease patients often exhibit a deficiency in l-carnitine due to loss during hemodialysis (HD). We studied the effects of l-carnitine supplementation on brachial-ankle pulse wave velocity (baPWV), a marker of atherosclerosis, in HD patients. Methods: This was a prospective, open-label, randomized, parallel controlled, multi-center trial testing the anti-atherosclerotic efficacy of oral l-carnitine administration (20 mg/kg/day). HD patients (n = 176, mean age, 67.2 ± 10.3 years old; mean duration of HD, 54 ± 51 months) with plasma free l-carnitine deficiency (<40 μmol/L) were randomly assigned to the oral l-carnitine group (n = 88) or control group (n = 88) and monitored during 12 months of treatment. Results: There were no significant differences in baseline clinical variables between the l-carnitine and control groups. l-carnitine supplementation for 12 months significantly increased total, free, and acyl carnitine levels, and reduced the acyl/free carnitine ratio. The baPWV value decreased from 2085 ± 478 cm/s at baseline to 1972 ± 440 cm/s after six months (p < 0.05) to 1933 ± 363 cm/s after 12 months (p < 0.001) of l-carnitine administration, while no significant changes in baPWV were observed in the control group. Baseline baPWV was the only factor significantly correlated with the decrease in baPWV. Conclusions: l-carnitine supplementation significantly reduced baPWV in HD patients. l-carnitine may be a novel therapeutic strategy for preventing the progression of atherosclerotic cardiovascular disease.

PP131-MON: Darbepoetin Alfa Dose Reduced Effect by the Oral Administration of L-Carnitine in Elderly Dialysis Patients

PP131-MON: Darbepoetin Alfa Dose Reduced Effect by the Oral Administration of L-Carnitine in Elderly Dialysis Patients

The effect of long-term oral L-carnitine administration on insulin sensitivity, glucose disposal, plasma concentrations of leptin and acylcarnitines, and urinary acylcarnitine excretion in warmblood horses

Background: Insulin resistance in horses is an emerging field of interest as it is thought to be a contributing factor in the pathogenesis of many equine conditions.Objectives: The objectives of the present study were to determine the effects of long-term oral administration of L-carnitine on insulin sensitivity, glucose disposal, plasma leptin concentrations and acylcarnitine spectrum both in plasma and urine.Animals and methods: Six 3-year-old healthy warmblood geldings were used. In a double blind 2 × 2 Latin square design at a dosage of 100 mg/kg body weight (BW)/day for 28 days the effects of oral supplementation of L-carnitine (as fumarate) were assessed. Glucose disposal and insulin sensitivity were measured by means of the euglycemic-hyperinsulinemic clamp technique. Radioimmunoassays were used to determine plasma leptin and insulin concentrations. Electrospray tandem mass spectrometry was used to assess acylcarnitines both in plasma and urine. Statistical analysis was performed using a linear mixed-effects model and P values <0.05 were considered significant.Results: Long-term L-carnitine administration did not affect insulin sensitivity. Plasma leptin and free carnitine concentrations in plasma and urine increased significantly (P = 0.047 and 0.000, respectively) following L-carnitine administration as well as short-chain acylcarnitines in plasma and urinary excretion of short- and medium-chain acylcarnitines.Conclusion and clinical relevance: Given the effects of oral administration of L-carnitine further clinical study is necessary in order to assess the potential beneficial effects in equine patients suffering from metabolic myopathies such as acquired multiple acyl-CoA dehydrogenase deficiency.Impact for human medicine: The current study supports the treatment rationale of short-chain acyl-CoA dehydrogenase deficiency in humans with L-carnitine at an oral dosage of 100 mg/kg BW/day.

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.

Positive influence ofl-carnitine on the different muscle fibres types of racing pigeons

Succinate dehydrogenase (SDH), Ca(2+) ATPase, Lactate dehydrogenase (LDH), are involved in energy metabolism. These enzymes can be used as indicators of the energy capacity of aerobic cells. The study investigated the effects of L-carnitine supplementation on M. pectoralis superficialis, M. pectoralis profundus, M. extensor carpi radialis muscle and M. flexor carpi ulnaris. Twenty-eight racing pigeons hatched at the same time were divided randomly into three groups. Eight pigeons, which were used as the control group, were sacrificed at 92-day old. The remaining twenty pigeons continued training until they reached 157-day old, with half the pigeons getting 25 mg/head/day of L-carnitine, while the other half given the same amount of water. The pigeons were assessed by histochemical methods and reverse transcription polymerase chain reaction (RT-PCR). To assess influence of L-carnitine on muscle fibre composition and the performance of three genes' mRNA, this study applied SDH localization, SDH, Ca(2+) ATPase and LDH mRNA expression to examine the results after oral administration of L-carnitine in vivo in racing pigeons. The results showed that L-carnitine significantly elevated the amount of white muscle fibre type IIa (p < 0.05). The mRNA expression quantities of SDH and LDH gene was higher via RT-PCR method. However, the expression of Ca(2+) ATPase remains similar. In conclusion, appropriate oral administration of L-carnitine of 25 mg/pigeon/day will result in an improvement of muscles related to flying.

Effects of Oral L-Carnitine Administration in Narcolepsy Patients: A Randomized, Double-Blind, Cross-Over and Placebo-Controlled Trial

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement (REM) sleep abnormalities. A genome-wide association study (GWAS) identified a novel narcolepsy-related single nucleotide polymorphism (SNP), which is located adjacent to the carnitine palmitoyltransferase 1B (CPT1B) gene encoding an enzyme involved in β-oxidation of long-chain fatty acids. The mRNA expression levels of CPT1B were associated with this SNP. In addition, we recently reported that acylcarnitine levels were abnormally low in narcolepsy patients. To assess the efficacy of oral l-carnitine for the treatment of narcolepsy, we performed a clinical trial administering l-carnitine (510 mg/day) to patients with the disease. The study design was a randomized, double-blind, cross-over and placebo-controlled trial. Thirty narcolepsy patients were enrolled in our study. Two patients were withdrawn and 28 patients were included in the statistical analysis (15 males and 13 females, all with HLA-DQB1*06:02). l-carnitine treatment significantly improved the total time for dozing off during the daytime, calculated from the sleep logs, compared with that of placebo-treated periods. l-carnitine efficiently increased serum acylcarnitine levels, and reduced serum triglycerides concentration. Differences in the Japanese version of the Epworth Sleepiness Scale (ESS) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) vitality and mental health subscales did not reach statistical significance between l-carnitine and placebo. This study suggests that oral l-carnitine can be effective in reducing excessive daytime sleepiness in narcolepsy patients.Trial RegistrationUniversity hospital Medical Information Network (UMIN) UMIN000003760

Beneficial effects of combination therapy of intradialytic parenteral nutrition and oral l-carnitine administration

According to the review article on nutritional support in hemodialysis patients by Bossola et al. [1], intradialytic parenteral nutrition (IDPN) seems to improve nutritional parameters such as serum albumin and body weight, but the effects of IDPN on long-term survival remain controversial. IDPN can provide energy of 7–8 kcal/kg/day and protein of 0.3–0.4 g/kg/day at best, and in order to attain the recommended nutritional requirements, spontaneous oral intake must reach [0.8 g/kg/day for protein and [20 kcal/kg/day for energy [2]. Therefore, the effects of IDPN on nutritional status often seem uncertain. In some patients, the loss of muscle mass occurs despite IDPN. We report here our experience of the use of L-carnitine in combination with IDPN in patients on chronic hemodialysis. Our IDPN therapy consisted of 200 ml of 6.1 % amino acids solution, 200 ml of 50 % dextrose solution, and 100 ml of 20 % soy lipid solution. Total energy intake including IDPN ranged from 30 to 35 kcal/kg/day. These were infused through the blood line throughout each entire dialysis session. In 6 patients whose nutritional conditions, such as body weight and muscle mass, had not improved by IDPN for 6 months, oral L-carnitine of 300 mg was additionally administered 20 min before each dialysis session. Body composition by bioimpedance method, serum levels of high-sensitivity C-reactive protein (hs-CRP) and albumin were evaluated every 3 months for 1 year. The effects of L-carnitine added to IDPN were shown in Table 1. During the 6 months on IDPN therapy alone, the fat mass significantly increased, while the muscle mass significantly decreased. With additive L-carnitine administration, however, the muscle mass significantly increased at month 3. Serum albumin levels increased in 2 patients, decreased in 3, and did not change in one. The reason of such inconsistent changes of serum albumin remains unknown. Six months after L-carnitine administration, we found a significant decrease in serum hs-CRP level, which persisted 1 year after L-carnitine administration. However, its clinical impacts may be modest, because serum hs-CRP level before L-carnitine administration was low at 0.051 mg/dL. Many studies have indicated that hemodialysis is a protein-catabolic procedure, and hemodialysis itself may be a cause of malnutrition leading to a loss of lean M. Tsunoda (&) Department of Nephrology and Dialysis, H. N. Medic Sapporo-Higashi, 1-26, Kita-19 Higashi-7, Higashi-ku, Sapporo 065-0019, Japan e-mail: tndmstk@hnmedic.jp

Effect of oxidative stress during repeated ovulation on the structure and functions of the ovary, oocytes, and their mitochondria

We previously reported that superoxide generated in the ovary induces apoptosis of granulosa cells to break down follicular walls, thereby supporting ovulation in rodents, and suggested that oxidative stress underlies the mechanism of ovarian aging. To test this hypothesis, we successfully induced ovulation repeatedly in mice by sequentially administrating pregnant mare serum gonadotropin, human chorionic gonadotropin, and prostaglandin F2α. Kinetic analysis revealed that the number of ovulated oocytes decreased significantly with repeated cycles of ovulation with a concomitant decrease in the gene expression of mitochondrial transcription factor A and nuclear respiratory factor 1 and an increase in oocytes having abnormally distributed mitochondria. Repeated ovulation decreased the amounts of mitochondrial DNA and increased 8-hydroxydeoxyguanosine in oocytes. Cell culture analysis of the in vivo fertilized oocytes revealed that their maturation from two cells to blastocyst was inhibited significantly by repeated ovulation. All these events induced by repeated ovulation were suppressed by oral administration of L-carnitine. These results suggest that oxidative stress associated with ovulation underlies the mechanism of ovarian aging and that L-carnitine may have therapeutic potential in patients with infertility and increased incidence of aneuploidy and to suppress impaired maturation of zygotes frequently observed in childbearing at an advanced age.