L-carnitine Supplementation Research Articles

“Dose-Duration Dependent Changes Induced by Atrazine in the Ovary of Adult Albino Rat and the Possible Protective Role of L-Carnitine: Histological and Immunohistochemical Study”

Introduction: Atrazine (ATR) is the most common herbicide used in the world. Several studies show that ATR has many reproductive adverse effects. L-Carnitine (LC) is a flavonoid antioxidant.Aim of the Work: The goal of this research was to elucidate the structural and biochemical alterations induced by ATR in the ovary of the adult albino rats and to clarify the possible protective role of LC. Material and Methods: 70 adult female albino rats were separated into 6 groups; Control, LC (given 100 mg LC/kg/day for 30 days), ATR sub-chronic treated (given 6.5 mg ATR/kg/day for 30 days), ATR sub-acute treated (given 65 mg/kg/day for 14 days), Sub-chronic protected (given 6.5 mg ATR/kg/day +LC 100 mg/kg/day for 30 days), and Sub-acute protected (given 65 mg ATR/kg/day +LC 100 mg/kg/day for 14 days). All doses were administrated orally. Blood and tissue samples were obtained and processed for biochemical, histological, and immunohistochemical study. Statistical analysis was also done.Results: Serum luteinizing hormone (LH) and estradiol (E2), ovarian superoxide dismutase (SOD) and catalase (CAT) significantly decreased while the ovarian malondialdehyde MDA and nitric oxide (NO) significantly increased in ATR treated groups as compared to control group. Ovarian tissue of ATR treated groups showed significant increase in number of atretic follicles and loss zona pellucida continuity in PAS stain as compared to control group. Atresia was confirmed by significant increase in immuohistochemical study of P53 in ATR treated groups. Also, there was significant decrease in mitotic division in ATR treated groups confirmed by immuohistochemical study of Ki-67 as compared to control group. Moreover, there was significant difference between the two ATR treated groups in both biochemical and structural findings. While, these changes were less obvious in protected groups after administration of LC. Conclusion: supplementation of LC could have a beneficial effect against ATR-induced ovarian damage.

Microbiome Clusters Disclose Physiologic Variances in Dairy Cows Challenged by Calving and Lipopolysaccharides.

ABSTRACTDairy cows respond individually to stressful situations, even under similar feeding and housing conditions. The phenotypic responsiveness might trace back to their microbiome and its interactions with the host. This long-term study investigated the effects of calving, lipopolysaccharide (LPS)-induced inflammation, and l-carnitine supplementation on fecal bacteria and metabolites, dairy cow milk production, health, energy metabolism, and blood metabolites. Fifty-four multiparous Holstein dairy cows were examined over a defined period of life (168 days). The obtained data allowed a holistic analysis combining microbiome data such as 16S rRNA amplicon sequencing and fecal targeted metabolome (188 metabolites) with host parameters. The conducted analyses allowed the definition of three enterotype-like microbiome clusters in dairy cows which could be linked to the community diversity and dynamics over time. The microbiome clusters were discovered to be treatment independent, governed by Bifidobacterium (C-Bifi), unclassified (uncl.) Clostridiales (C-Clos), and unclassified Spirochaetaceae (C-Spiro). Animals between the clusters varied significantly in terms of illnesses, body weight, microbiome composition, and milk and blood parameters. C-Bifi animals were healthier and leaner with a less diverse but dynamic microbiome. C-Spiro animals were heavier, but the diversity of the static microbiome was higher. This pioneering study uncovered microbiome clusters in dairy cows, each contributing differently to animal health and productive performance and with a crucial role of Bifidobacterium.IMPORTANCE The health of dairy cows has to be carefully considered for sustainable and efficient animal production. The microbiome of animals plays an important role in the host’s nutrient supply and regulation of immune functions. We show that a certain composition of the fecal microbiome, called microbiome clusters, can be linked to an animal’s health at challenging life events such as calving and inflammation. Cows with a specific set of bacteria have coped better under these stressors than have others. This novel information has great potential for implementing microbiome clusters as a trait for sustainable breeding strategies.

L-Carnitine Tartrate Supplementation for 5 Weeks Improves Exercise Recovery in Men and Women: A Randomized, Double-Blind, Placebo-Controlled Trial.

L-carnitine tartrate has been shown to improve relatively short-term recovery among athletes. However, there is a lack of research on the longer-term effects in the general population. Objective: The primary objectives of this randomized double-blind, placebo-controlled trial were to evaluate the effects of daily L-carnitine tartrate supplementation for 5 weeks on recovery and fatigue. Method: In this study, eighty participants, 21- to 65-years-old, were recruited. Participants were split into two groups of forty participants each, a placebo, and a L-carnitine Tartrate group. Seventy-three participants completed a maintenance exercise training program that culminated in a high-volume exercise challenge. Results: Compared to placebo, L-carnitine tartrate supplementation was able to improve perceived recovery and soreness (p = 0.021), and lower serum creatine kinase (p = 0.016). In addition, L-carnitine tartrate supplementation was able to blunt declines in strength and power compared to placebo following an exercise challenge. Two sub-analyses indicated that these results were independent of gender and age. Interestingly, serum superoxide dismutase levels increased significantly among those supplementing with L-carnitine tartrate. Conclusions: These findings agree with previous observations among healthy adult subjects and demonstrate that L-carnitine tartrate supplementation beyond 35 days is beneficial for improving recovery and reducing fatigue following exercise across gender and age.

Myths and reality of L-carnitine (3-Hydroxy 4-N trimethylammonium butyrate) supplementation and its chemistry: A systematic review

L-carnitine, an amino acid derivative, is naturally synthesized in human bodies in very few amounts and can also be taken as a dietary supplement. This amino acid derivative is very popular among various medical drugs and in gym dietary nutrients. In addition, it plays an intense role in brain functioning, in the generation of energy, known to provide more oxygen for muscles and improve stamina, strength, and power. Besides its various applications, several myths are reported but do not have adequate scientific evidence to date. This review aims to investigate the effects of L-Carnitine as a drug and the myths related to it. This paper contains significant facts about L-Carnitine, i.e., its benefits, side effects, and myths. It will give a clear idea about L-Carnitine and its applications. This review paper discussed the characteristics of L-carnitine, which finds vast applications and benefits. This review paper has also discussed the most recent finding of L-Carnitine promoting atherosclerosis by way of trimethylamine N-oxide Meta organismal pathway along with its solution on trial bases. L-Carnitine has many applications in the clinic and personalized medicine; hence, it has an excellent scope for future works, which requires the trials of its applications on a large scale.

Effect of Oral Supplementation with L-Carnitine on Performance Time in a 5000 m Race and Responses of Free Fatty Acid and Carnitine Concentrations in Trained-Endurance Athletes

This study was designed to determine the effect of oral supplementation with L-carnitine on the performance time in a 5000 m race. In addition, free fatty acid, blood carnitine, lactate, and glucose responses to the race following the supplementation period were measured. Twenty male trained-endurance athletes were randomly divided into two groups (L-carnitine, n = 10 (22.13 ± 2.66 yrs) or placebo, n = 10 (21.63 ± 2.23 yrs)). The study was performed with a randomized, double-blind, placebo-controlled parallel-group, in which participants ingested an L-carnitine supplement or a placebo 2 × 1.5 g/day for 3 weeks. Athletes completed a 5000 m race before and after the supplementation period. Blood samples were collected from each athlete before and after the race, preand post-supplementation to measure the physiological responses. Data showed that there were no differences in performance time before (p=0.624) and after (p=0.407) supplementation period between groups and within a group (p>0.05). No differences existed in physiological responses between groups after supplementation before beginning the race (p>0.05), except for the blood carnitine level, which was significantly higher in the L-carnitine than the placebo (P=0.001) group. After the finish of the race, however, data showed better physiological responses in response to L-carnitine supplementation compared to the placebo group (p<0.05). In conclusion, although L-carnitine supplementation increases blood carnitine concentration, it has no beneficial effect on performance time of 5000 m race probably due to the short duration of the race; it might also have no ergogenic effect.

Chronic L-Carnitine Supplementation on Exercise Performance, Blood Lactate, and Exercise-Induced Oxidative Stress in Resistance-Trained Males

Chronic L-Carnitine Supplementation on Exercise Performance, Blood Lactate, and Exercise-Induced Oxidative Stress in Resistance-Trained Males

Increased dietary methionine levels and supplemental L-carnitine do not prevent the development of white striping in broiler chickens

The present experiment investigated the effect of dietary methionine levels and supplemental L-carnitine on live performance, carcass and organ yields, meat quality attributes, serum lipid metabolites, and occurrence of white striping in broiler chickens. The study comprised of 4 experimental groups with a 2 × 2 factorial arrangement of dietary methionine levels (100 and 125 % of requirement) and L-carnitine supplementation (0 and 100 mg/kg). Each experimental group comprised of 8 replicates; each replicate randomly received 15 one-d-old broiler chickens. Corn-soybean meal-based basal diets were formulated for 100 % and 125 % dietary methionine levels for starter, grower, finisher, and withdrawal growth phases. Supplemental L-carnitine and/or 125 % dietary methionine levels improved the overall feed conversion ratio of broiler chickens (P = 0.022). Increasing dietary methionine levels increased the breast weight (P = 0.022) and yield (P = 0.023) at d 49. At d 49, L-carnitine supplementation reduced the absolute abdominal fat weight (P = 0.050). Dietary methionine and supplemental L-carnitine did not affect the meat quality and development of white striping at d 39 and 49. While dietary methionine levels had no effect on serum triglyceride and total cholesterol levels, L-carnitine supplementation lowered (P = 0.027) the serum total cholesterol levels of broilers. In conclusion, increased dietary methionine levels and L-carnitine supplementation failed to inhibit the development of white striping on breast fillets of broiler chickens.

Possible correlation between increased serum free carnitine levels and increased skeletal muscle mass following HCV eradication by direct acting antivirals

We aimed to evaluate factors associated with changes in skeletal muscle mass in hepatitis C virus (HCV)-infected patients after treatment with direct-acting antivirals (DAAs). Consecutive HCV-infected patients after treatment with DAA were recruited into the study. Patients who achieved sustained virological response (SVR); and had complete clinical information, preserved serum samples at baseline and SVR48, and skeletal muscle mass evaluations based on the psoas muscle mass index (PMI) on computed tomography at baseline and ≥ 12 months were included. Altogether, 70.7% of patients (41/58) showed increased PMI after DAA therapy, and mean relative PMI was significantly higher after DAA therapy than at baseline. There were no significant associations between baseline clinical factors routinely examined in clinical practice and increased PMI. Among factors reported to be associated with skeletal muscle loss in patients with chronic liver disease, serum zinc levels and total and free carnitine levels increased significantly after DAA therapy and only changes in serum free carnitine levels were significantly associated with an increased PMI (r = 0305, P = 0.020). In conclusion, increased skeletal muscle mass after successful HCV eradication by DAAs was significantly associated with increased serum-free carnitine levels. l-carnitine supplementation may be beneficial in patients with low skeletal muscle mass after DAA.

Role of Carnitine in Non-alcoholic Fatty Liver Disease and Other Related Diseases: An Update.

Carnitine is an amino acid-derived substance that coordinates a wide range of biological processes. Such functions include transport of long-chain fatty acids from the cytoplasm to the mitochondrial matrix, regulation of acetyl-CoA/CoA, control of inter-organellar acyl traffic, and protection against oxidative stress. Recent studies have found that carnitine plays an important role in several diseases, including non-alcoholic fatty liver disease (NAFLD). However, its effect is still controversial, and its mechanism is not clear. Herein, this review provides current knowledge on the biological functions of carnitine, the “multiple hit” impact of carnitine on the NAFLD progression, and the downstream mechanisms. Based on the “multiple hit” hypothesis, carnitine inhibits β-oxidation, improves mitochondrial dysfunction, and reduces insulin resistance to ameliorate NAFLD. L-carnitine may have therapeutic role in liver diseases including non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, alcoholic fatty liver disease, and viral hepatitis. We also discuss the prospects of L-carnitine supplementation as a therapeutic strategy in NAFLD and related diseases, and the factors limiting its widespread use.

Effects of l-carnitine supplementation in patients with childhood-onset epilepsy prescribed valproate

BackgroundThe benefits of carnitine supplementation in patients treated with valproate (VPA) are not clear. Therefore, we retrospectively explored the benefits of carnitine supplementation by analyzing laboratory data. MethodsWe measured the serum-free carnitine (FC), VPA, aspartate aminotransferase, alanine aminotransferase, amylase, and ammonia levels, and the platelet count, in 69 patients with childhood-onset epilepsy treated with VPA. Eight patients had received carnitine supplementation. The serum FC and acylcarnitine levels were measured using an enzyme cycling method. We compared laboratory values between patients with and without carnitine supplementation and analyzed the correlations between serum FC levels and laboratory values. ResultsThe serum FC levels were normal (median, 48.8 μmol/L; range: 41.9–68.3 μmol/L) in all eight patients with carnitine supplementation, but below normal in 32 of 61 patients without supplementation. The median serum amylase levels were lower in the patients with carnitine supplementation (median, 48 U/L; range: 27–149 U/L) than in those without (median, 7 U/L; range: 14–234 U/L). The platelet count and serum ammonia levels did not differ significantly between patients with and without supplementation. There was no significant correlation between the serum FC level and the platelet count, serum amylase level, or ammonia level. ConclusionsCarnitine supplementation helps maintain serum FC levels in patients treated with VPA. The lower serum amylase levels in patients with carnitine supplementation may reflect protective effects of carnitine against latent pancreatic injury.

Association between plasma L-carnitine and the risk of cognitive impairment in patients with acute ischemic stroke

Background and Aims: L-carnitine has been shown to exert neuroprotective effects against cerebral ischemia, mainly through improving mitochondrial function and reducing inflammation. L-carnitine supplementation has also been promoted to enhance cognitive function. However, the relationship between L-carnitine and cognitive impairment after ischemic stroke has been sparsely studied. We aimed to evaluate the prospective association between plasma levels of L-carnitine and post-stroke cognitive impairment.

Effects of dietary l-carnitine supplementation on the response to an inflammatory challenge in mid-lactating dairy cows: Hepatic mRNA abundance of genes involved in fatty acid metabolism

This study aimed at characterizing the effects of dietary l-carnitine supplementation on hepatic fatty acid (FA) metabolism during inflammation in mid-lactating cows. Fifty-three pluriparous Holstein dairy cows were randomly assigned to either a control (CON, n = 26) or an l-carnitine supplemented (CAR; n = 27) group. The CAR cows received 125 g of a rumen-protected l-carnitine product per cow per day (corresponding to 25 g of l-carnitine/cow per day) from d 42 antepartum (AP) until the end of the trial on d 126 postpartum (PP). Aside from the supplementation, the same basal diets were fed in the dry period and during lactation to all cows. In mid lactation, each cow was immune-challenged by a single intravenous injection of 0.5 μg of LPS/kg of BW at d 111 PP. Blood samples were collected before and after LPS administration. The mRNA abundance of in total 39 genes related to FA metabolism was assessed in liver biopsies taken at d -11, 1, and 14 relative to LPS (d 111 PP) and also on d 42 AP as an individual covariate using microfluidics integrated fluidic circuit chips (96.96 dynamic arrays). In addition to the concentrations of 3 selected proteins related to FA metabolism, acetyl-CoA carboxylase α (ACACA), 5' AMP-activated protein kinase (AMPK), and solute carrier family 25 member 20 (SLC25A20) were assessed by a capillary Western blot method in liver biopsies from d -11 and 1 relative to LPS from 11 cows each of CAR and CON. On d -11 relative to LPS, differences between the mRNA abundance in CON and CAR were limited to acyl-CoA dehydrogenase (ACAD) very-long-chain (ACADVL) with greater mRNA abundance in the CAR than in the CON group. The liver fat content decreased from d -11 to d 1 relative to the LPS injection and remained at the lower level until d 14 in both groups. One day after the LPS challenge, lower mRNA abundance of carnitine palmitoyltransferase 1 (CPT1), CPT2, ACADVL, ACAD short-chain (ACADS), and solute carrier family 22 member 5 (SLC22A5) were observed in the CAR group as compared with the CON group. However, the mRNA abundance of protein kinase AMP-activated noncatalytic subunit gamma 1 (PRKAG1), ACAD medium-chain (ACADM), ACACA, and FA binding protein 1 (FABP1) were greater in the CAR group than in the CON group on d 1 relative to LPS. Two weeks after the LPS challenge, differences between the groups were no longer detectable. The altered mRNA abundance before and 1 d after LPS pointed to increased transport of FA into hepatic mitochondria during systemic inflammation in both groups. The protein abundance of AMPK was lower in CAR than in CON before the LPS administration. The protein abundance of SLC25A20 was neither changing with time nor treatment and the ACACA protein abundance was only affected by time. In conclusion, l-carnitine supplementation temporally altered the hepatic mRNA abundance of some genes related to mitochondrial biogenesis and very-low-density lipoprotein export in response to an inflammatory challenge, but with largely lacking effects before and 2 wk after LPS.

Dietary interventions and nutritional supplements for heart failure: a systematic appraisal and evidence map.

To appraise meta-analytically determined effect of dietary interventions and nutritional supplements on heart failure (HF)-related outcomes, and create an evidence map to visualize the findings and certainty of evidence. Online databases were systematically searched for meta-analyses of randomized controlled trials (RCTs) evaluating the effect of dietary interventions and nutritional supplements on HF outcomes and incidence. These were then updated if new RCTs were available. Estimates were pooled using a random-effects model and reported as risk ratios (RRs) or mean differences with 95% confidence intervals. We identified 14 relevant meta-analyses, to which 21 new RCTs were added. The total evidence base reviewed included 122 RCTs (n=176 097 participants) assessing 14 interventions. We found that coenzyme Q10 was associated with lower all-cause mortality [RR 0.69 (0.50-0.96); I2 = 0%; low certainty of evidence] in HF patients. Incident HF risk was reduced with Mediterranean diet [RR 0.45 (0.26-0.79); I2 = 0%; low certainty of evidence]. Vitamin E supplementation was associated with a small but significant increase in the risk of HF hospitalization [RR 1.21 (1.04-1.40); I2=0%; moderate certainty of evidence]. There was moderate certainty of evidence that thiamine, vitamin D, iron, and L-carnitine supplementation had a beneficial effect on left ventricular ejection fraction. Coenzyme Q10 may reduce all-cause mortality in HF patients, while a Mediterranean diet may reduce the risk of incident HF; however, the low certainty of evidence warrants the need for further RCTs to confirm a definite clinical role. RCT data were lacking for several common interventions including intermittent fasting, caffeine, DASH diet, and ketogenic diet. More research is needed to fill the knowledge gap.

The effects of L-carnitine supplement on anemia in hemodialysis patients: A randomized clinical trial study

BACKGROUND: There is no general consensus about the effect of L-carnitine (LC) on anemic factors in hemodialysis patients. In this clinical trial, the effect of LC on anemia was investigated in these patients. METHODS: In a double-blinded clinical trial, hemodialysis patients admitted to the dialysis department of Tohid Hospital in Sanandaj, Iran, in 2017, were randomly divided into two groups of intervention (n = 40) and placebo (n = 40). Individuals in the intervention group received a dose of 1 g/day of LC, and the other group received placebo tablets of the same form for 12 weeks. Anemia factors were evaluated in both groups before and after the intervention. The data were analyzed using t-test and analysis of covariance (ANCOVA). RESULTS: The LC supplementation increased hemoglobin (Hb) in hemodialysis patients (P = 0.043). Moreover, the mean corpuscular volume (MCV) level was decreased under the effect of LC (P 0.050). CONCLUSION: The effect of LC supplement on Hb, serum ferritin, and MCV levels in hemodialysis patients was significant. Therefore, LC can be used to treat anemia in this group of patients.

Protective effects of L-carnitine on behavioral alterations and neuroinflammation in striatum of glutaryl-COA dehydrogenase deficient mice

Glutaric acidemia type 1 (GA1) is caused by glutaryl-CoA dehydrogenase deficiency that leads to a blockage in the metabolic route of the amino acids lysine and tryptophan and subsequent accumulation of glutaric acid (GA), 3-hydroxyglutaric acids and glutarylcarnitine (C5DC). Patients predominantly manifest neurological symptoms, associated with acute striatal degeneration, as well as progressive cortical and striatum injury whose pathogenesis is not yet fully established. Current treatment includes protein/lysine restriction and l-carnitine supplementation of (L-car). The aim of this work was to evaluate behavior parameters and pro-inflammatory factors (cytokines IL-1β, TNF-α and cathepsin-D levels), as well as the anti-inflammatory cytokine IL10 in striatum of knockout mice (Gcdh−/-) and wild type (WT) mice submitted to a normal or a high Lys diet. The potential protective effects of L-car treatment on these parameters were also evaluated. Gcdh−/- mice showed behavioral changes, including lower motor activity (decreased number of crossings) and exploratory activity (reduced number of rearings). Also, Gcdh−/- mice had significantly higher concentrations of glutarylcarnitine (C5DC) in blood and cathepsin-D (CATD), interleukin IL-1β and tumor factor necrosis alpha (TNF-α) in striatum than WT mice. Noteworthy, L-car treatment prevented most behavioral alterations, normalized CATD levels and attenuated IL-1β levels in striatum of Gcdh−/- mice. Finally, IL-1β was positively correlated with CATD and C5DC levels and L-car was negatively correlated with CATD. Our results demonstrate behavioral changes and a pro-inflammatory status in striatum of the animal model of GA1 and, most importantly, L-car showed important protective effects on these alterations.

Exogenous L-carnitine ameliorates burn-induced cellular and mitochondrial injury of hepatocytes by restoring CPT1 activity

BackgroundImpaired hepatic fatty acid metabolism and persistent mitochondrial dysfunction are phenomena commonly associated with liver failure. Decreased serum levels of L-carnitine, a amino acid derivative involved in fatty-acid and energy metabolism, have been reported in severe burn patients. The current study aimed to evaluate the effects of L-carnitine supplementation on mitochondrial damage and other hepatocyte injuries following severe burns and the related mechanisms.MethodsSerum carnitine and other indicators of hepatocytic injury, including AST, ALT, LDH, TG, and OCT, were analyzed in severe burn patients and healthy controls. A burn model was established on the back skin of rats; thereafter, carnitine was administered, and serum levels of the above indicators were evaluated along with Oil Red O and TUNEL staining, transmission electron microscopy, and assessment of mitochondrial membrane potential and carnitine palmitoyltransferase 1 (CPT1) activity and expression levels in the liver. HepG2 cells pretreated with the CPT1 inhibitor etomoxir were treated with or without carnitine for 24 h. Next, the above indicators were examined, and apoptotic cells were analyzed via flow cytometry. High-throughput sequencing of rat liver tissues identified several differentially expressed genes (Fabp4, Acacb, Acsm5, and Pnpla3) were confirmed using RT-qPCR.ResultsSubstantially decreased serum levels of carnitine and increased levels of AST, ALT, LDH, and OCT were detected in severe burn patients and the burn model rats. Accumulation of TG, evident mitochondrial shrinkage, altered mitochondrial membrane potential, decreased ketogenesis, and reduced CPT1 activity were detected in the liver tissue of the burned rats. Carnitine administration recovered CPT1 activity and improved all indicators related to cellular and fatty acid metabolism and mitochondrial injury. Inhibition of CPT1 activity with etomoxir induced hepatocyte injuries similar to those in burn patients and burned rats; carnitine supplementation restored CPT1 activity and ameliorated these injuries. The expression levels of the differentially expressed genes Fabp4, Acacb, Acsm5, and Pnpla3 in the liver tissue from burned rats and etomoxir-treated hepatocytes were also restored by treatment with exogenous carnitine.ConclusionExogenous carnitine exerts protective effects against severe burn-induced cellular, fatty-acid metabolism, and mitochondrial dysfunction of hepatocytes by restoring CPT1 activity.

L-carnitine Supplementation Enhances Nuclear and Cytoplasmic Maturation Rates of Sheep Oocytes In Vitro

The aim of the present study was to determine the effectiveness of l-carnitine (LC) supplementation on nuclear and cytoplasmic maturation rates of sheep oocytes. In experiment 1, oocytes were maturated for 24 hours in tissue culture medium 199 supplemented with LC at doses of 0.3 mg/mL, 0.6 mg/mL, and 0.9 mg/mL. In experiment 2, oocytes were maturated and fertilized in a media supplemented with LC at a dose of 0.3 mg/mL and incubated with 5x106 sperm/mL for 12 hours. The treatment group consisted of LC supplementation only in maturation medium (P1), only in fertilization medium (P2), and in both maturation and fertilization media (P3). In experiment 3, sperm motility patterns were assessed using CASA after being exposed to fertilization medium supplemented with LC at a dose of 0.3 mg/mL for 0 and 3 hours. Our results showed that supplementation of LC at a dose of 0.3 mg/mL significantly (p<0.05) increased the percentage of oocytes reaching metaphase II (86.7±4.1%) compared to those supplemented with LA at doses of 0, 0.6, and 0.9 mg/mL (73.6±1.2%, 81.4±1.3%, and 70.5±1.6%, respectively). The LC treatment in the fertilization medium only did not influence the number of two pronuclear formations (62.1±2.5%) compared to supplementation either in the maturation medium only (72.0±4.7%) or a combination of both in maturation and fertilization media (68.2±2.7%) (p<0.05). Further results after 3 hours of incubation compared to the control group showed the total motility (24.8±2.04% vs. 17.49±2.37%), progressive motility (14.17±2.03% vs. 6.49±1.64%), and curvilinear velocity (VCL) (119.70±3.73% vs. 71.15±10.59%) (p<0.05) were increased in the fertilization medium containing LC but it did not improve the fertilization rate. It is concluded that supplementation of LC at a dose of 0.3 mg/mL in the maturation medium only could better improve the nuclear and cytoplasmic maturation rates of sheep oocytes.

Effects of Reducing L-Carnitine Supplementation on Carnitine Kinetics and Cardiac Function in Hemodialysis Patients: A Multicenter, Single-Blind, Placebo-Controlled, Randomized Clinical Trial.

L-carnitine (LC) supplementation improves cardiac function in hemodialysis (HD) patients. However, whether reducing LC supplementation affects carnitine kinetics and cardiac function in HD patients treated with LC remains unclear. Fifty-nine HD patients previously treated with intravenous LC 1000 mg per HD session (three times weekly) were allocated to three groups: LC injection three times weekly, once weekly, and placebo, and prospectively followed up for six months. Carnitine fractions were assessed by enzyme cycling methods. Plasma and red blood cell (RBC) acylcarnitines were profiled using tandem mass spectrometry. Cardiac function was evaluated using echocardiography and plasma B-type natriuretic peptide (BNP) levels. Reducing LC administration to once weekly significantly decreased plasma carnitine fractions and RBC-free carnitine levels during the study period, which were further decreased in the placebo group (p < 0.001). Plasma BNP levels were significantly elevated in the placebo group (p = 0.03). Furthermore, changes in RBC (C16 + C18:1)/C2 acylcarnitine ratio were positively correlated with changes in plasma BNP levels (β = 0.389, p = 0.005). Reducing LC administration for six months significantly decreased both plasma and RBC carnitine levels, while the full termination of LC increased plasma BNP levels; however, it did not influence cardiac function in HD patients.

MO641IMPACT OF MAGNESIUM AND L-CARNITINE ADMINISTRATION ON 3-YEAR SURVIVAL IN DIABETIC PATIENTS WITH END-STAGE RENAL DISEASE

Abstract Background and Aims According to population registries, the survival of diabetic patients with end-stage-renal disease (ESRD) remains low today. In this context, it is reasonable to develop new therapeutic strategies based on advances in science of the important role of magnesium (Mg) and L-carnitine deficiency (via inflammation and endothelial dysfunction) in mechanisms of cardiovascular remodeling, high morbidity and mortality rates. Thus, the purpose of the present study was to evaluate the effect of Mg and L-carnitine supplementation on 3-year survival and development of the cardiovascular complications in diabetic hemodialysis (HD) patients. Method 48 type 2 diabetic ESRD patients were included in this prospective cohort study (male/female, 29/19; age, 59.9±0.6 years; HD duration, 34.8±4.8 month; diabetes mellitus duration, 174.7±7.1 month). The study was performed in accordance with the provisions of the Declaration of Helsinki last revision. Depending on the treatment programme, patients were divided into two groups: the 1st (main) group (n=24) in addition to basic treatment (hypoglycemic, antihypertensive therapy, according to indications - correction of anemia, hyperparathyroidism, hyperphosphatemia) was treated by combination of magnesium aspartate (0.5 g/day orally) and L-carnitine (1 g/day parenterally after each HD session (three times weekly); the 2nd (comparison) group (n=24) was only on the basic therapy. Complex treatment lasted 12-months; administration of L-carnitine was performed continuously throughout the year, while magnesium aspartate – by three 2-months’ courses/year. The follow up period in both groups was 36 months. Quantitative data are expressed as means±SEM, qualitative ones – as %. Kaplan-Meier method and Log-rank test were used to estimate survival of HD patients, χ2-test – to compare the frequency values. Results The cumulative proportion of survivors at the end of follow-up was 60.4%; however, after 36 months, the survival rate of diabetic HD patients who received a combination of magnesium aspartate and L-carnitine as part of their modified treatment was significantly higher (75 vs. 45.8%; Log-rank=2.07, p=0.038) compared to patients who were on basic therapy (Figure). Survival time in main and comparison groups was 31.9±1.7 and 26.4±2.2 months respectively. It is noteworthy, that throughout the year (from 10 to 22 months), no completed events were recorded in subjects who underwent Mg and L-carnitine supplementation. Conclusion (1) The combined use of magnesium aspartate and L-carnitine in addition to the basic 12-month treatment provides an effective reduction of cardiovascular complications and promotes 3-year survival of diabetic HD patients. (2) The results obtained substantiate the advisability of using repeated courses of Mg and L-carnitine administration 1 years after the end of the primary modified treatment to improve the prognosis in these ESRD patients.

Effect of L-carnitine supplementation on lipid profile and apolipoproteins in children on hemodialysis: a randomized placebo-controlled clinical trial

Cardiovascular disease (CVD) is the leading cause of death in children with chronic kidney disease (CKD) and accounts for 40% of all deaths among pediatric patients with stage5 chronic kidney disease (CKD5). Dyslipidemia is common in children with CKD and is considered one of the major causes of CVD in these patients. As carnitine plays a key role in lipid metabolism and because plasma levels are reduced in hemodialysis patients, the aim of this study was to determine the effects of L-carnitine supplementation on serum lipid profiles, apolipoproteins, and free carnitine (FC) levels. A total of 30 children on hemodialysis (6-18 years) were enrolled and 24 completed the study. Twelve patients received 50 mg/kg/day L-carnitine, while the other 12 patients received placebo for 10 weeks. Serum FC, total cholesterol (TC), LDL-C, HDL-C, TG, Apolipoprotein B (ApoB), and Apolipoprotein A1 (ApoA1) were determined at the baseline and after the intervention. One-way repeated measures analysis was used to evaluate the effects of L-carnitine supplementation. Oral L-carnitine supplementation led to decreased ApoB levels and ApoB/ApoA1 ratio, but these changes were not significant compared to placebo. Meanwhile, L-carnitine supplementation significantly reduced serum LDL-C and TC and increased serum FC compared to placebo. No significant changes were observed in serum TG and HDL-C levels. Given the significant reduction in LDL-C and TC levels, L-carnitine supplementation had positive effects on improving hyperlipidemia in children receiving hemodialysis. For more decisive results, studies with longer duration of L-carnitine therapy on children receiving hemodialysis with significant dyslipidemia are recommended. We registered the present trial in the Iranian Registry of Clinical Trials website (available at: http://www.irct.ir , identifier: IRCT20170202032367N2).