Carnitine Group Research Articles

Effects of l-carnitine supplementation to suckling piglets on carcass and meat quality at market age

In a previous study, carnitine supplementation to piglets during the suckling period resulted in an increased total muscle fibre number at weaning in piglets of low birth weight. The objective of the present study was to investigate whether this effect is maintained until market age and whether this would attenuate the negative consequences of low birth weight on carcass and meat quality. Using a split-plot design with litter as block, sex as whole plot and treatment as subplot, the effects of early-postnatal l-carnitine supplementation on female and castrated male piglets of low birth weight were investigated on a total of 56 German Landrace piglets from 14 litters. From days 7 to 27 of age piglets were orally supplemented once daily with 400 mg of l-carnitine dissolved in 1 ml of water or received an equal volume of water without carnitine. From weaning (day 28) until slaughter (day 166 of age) all pigs were fed standard diets. At weaning, carnitine-supplemented piglets had a twofold increased concentration of free carnitine (P < 0.001) and a lower concentration of non-esterified fatty acids (P < 0.05) in blood plasma indicating that carnitine became bioavailable and increased fatty acid utilization during the period of supplementation. Growth performance was not influenced by treatment in any growth period. Dual-energy X-ray absorptiometry revealed no differences in body composition between groups in weeks 12, 16 and 20 of age. LW at slaughter, carcass weight, measures of meat yield and fat accretion, as well as body composition by chemical analyses and dissection of primal cuts did not differ between treatments. No differences between control and carnitine-treated pigs in total fibre number (P = 0.85) and fibre cross-sectional area (P = 0.68) in m. semitendinosus (ST) measured at slaughter could be observed. The carnitine group tended to exhibit a smaller proportion of slow-twitch oxidative fibres (P = 0.08), a greater proportion of fast-twitch glycolytic fibres (P = 0.11), and increased specific lactate dehydrogenase activity (P = 0.09) in ST indicating a more glycolytic muscle metabolism. Compared with the controls, a lower pH24 value was observed (P = 0.05) in ST muscle of carnitine-supplemented pigs, which – in castrates only – was associated with an increased drip loss (P < 0.01). Meat quality traits in m. longissimus were not influenced by treatment. In conclusion, our hypothesis that early-postnatal carnitine supplementation to piglets of low birth weight permanently increases myofibre number and improves later carcass and meat quality could not be confirmed by this experiment.

Effect of Lysine, Vitamin B6, and Carnitine Supplementation on the Lipid Profile of Male Patients With Hypertriglyceridemia: A 12-Week, Open-Label, Randomized, Placebo-Controlled Trial

BackgroundFat metabolism is known to be altered in hypertriglyceridemia. Fat oxidation requires carnitine, which can be obtained either from the diet (animal or dairy products) or through synthesis in the body using both lysine and vitamin B6. ObjectiveThe goal of this study was to investigate the effect of lysine, vitamin B6, and carnitine supplementation on both glycemia and the lipid profiles, specifically triglyceride (TG) levels, in men with hypertriglyceridemia. MethodsThis 12-week, randomized, placebo-controlled clinical trial was conducted at a Lebanese medical center. A total of 85 hypertriglyceridemic (TG> 150 mg/dL) male patients were randomized to 1 of 5 groups and given supplements of lysine (1 g/d), vitamin B6 (50 mg/d), lysine (1 g/d) + vitamin B6 (50 mg/d), carnitine (1 g/d), or placebo for 12 weeks. The lipid profile (TG, total cholesterol, LDL-C, and HDL-C) and fasting plasma glucose levels were assessed at baseline and at 6 and 12 weeks. ResultsAdults (∼50 years) Lebanese males from a low socioeconomic status in Beirut were given the appropriate supplements. Vitamin B6 supplementation was associated with a significant reduction in total cholesterol and HDL-C of ∼10%. In addition, plasma TG was reduced by 36.6 mg/dL at 6 weeks, whereas levels in the placebo group increased by 18 mg/dL; this difference failed to reach statistical significance. No major changes in the lipid profile were observed in the lysine and carnitine groups or when lysine was added to vitamin B6. ConclusionVitamin B6 supplementation in these male patients with hypertriglyceridemia reduced plasma total cholesterol and HDL-C concentrations.

Carnitine Supplementation Effects on Nonenzymatic Antioxidants in Young Rats Submitted to Exhaustive Exercise Stress

Previous studies have demonstrated that exercise stress increases oxidative stress in rats. However, antioxidant supplement therapy effects on reactive oxygen substances are conflicting. We evaluated the effects of carnitine on renal nonenzymatic antioxidants in young rats submitted to exhaustive exercise stress. Wistar rats were divided into 3 groups: (a) control group (not submitted to exercise stress), (b) exercise stress group, and (c) exercise stress and carnitine group. The rats from group 3 were treated with gavage administration of 1 ml of carnitine (5 mg·kg⁻¹) for 7 consecutive days. The animals from groups 2 and 3 were submitted to a bout of swimming exhaustive exercise stress. Kidney samples were analyzed for reactive substances to thiobarbituric acid by malondialdehyde (MDA), reduced glutathione (GSH), and vitamin-E levels. Carnitine treatment attenuated MDA increase caused by exercise stress (1: 0.16 ± 0.02 vs. 2: 0.34 ± 0.07 vs. 3: 0.1 ± 0.01 mmmol per milligram of protein; p < 0.0001). It also increased the renal levels of GSH (1: 23 ± 4 vs. 2: 23 ± 2 vs. 3: 58 ± 9 μmol per gram of protein; p < 0.0001); however, it did not change renal vitamin E (1: 24 ± 5 vs. 2: 27 ± 1 vs. 3: 28 ± 5 μM per gram of tissue; p < 0.001). In conclusion, carnitine improved oxidative stress and partially improved the nonenzymatic antioxidant activity in young rats submitted to exhaustive exercise stress.

Levo-carnitine supplementation normalizes skeletal muscle functions in type 2 diabetic rats

Levo-carnitine is known to improve skeletal muscle contractile functions in healthy humans and rats. It has also been claimed to correct metabolic derangements in type 2 diabetes mellitus (T2DM). This randomized control trial was designed to determine the effect of levo-carnitine on isometric contraction, force frequency relationship and fatigue of skeletal muscles along with oxidative stress in T2DM. Sprague-dawley rats (n=90) were randomly divided in three equal groups. Control group remained healthy while T2DM was induced in the diabetic and carnitine groups. Then, carnitine group was administered levo-carnitine 200mg/kg/day intraperitonealy for 6 days. At 28th day, extensor digitorum longus (EDL) muscles were removed and their functions were assessed using iWorx data acquisition unit (AHK/214). Blood obtained by intra-cardiac sampling at 28th day was used for estimation of serum malondialdehyde (MDA) levels. Regarding muscle parameters, no significant difference was found in maximum isometric twitch tension, time-to-peak twitch tension and time-to-relax to 50% of the peak twitch tension amongst the three groups. However, carnitine group showed significant improvement in maximum fused tetanic tension, maximum fused tetanic tension after fatigue protocol and recovery from fatigue after 5 minutes of rest period when compared with diabetic group. Serum MDA levels were reduced in carnitine group as compared to the diabetic group. These findings suggest that levo-carnitine supplementation reduces oxidative stress, improves work capacity and delays fatigue in T2DM.

Effects of Oral L-Carnitine Supplementation on Lipid Profile, Anemia, and Quality of Life in Chronic Renal Disease Patients under Hemodialysis: A Randomized, Double-Blinded, Placebo-Controlled Trial.

In patients on maintenance hemodialysis several factors reduce the body stored carnitine which could lead to dyslipidemia, anemia, and general health in these patients. We evaluated the effect of oral L-carnitine supplementation on lipid profiles, anemia, and quality of life (QOL) in hemodialysis patients. In a randomized, double-blinded, placebo-controlled trial, end-stage renal disease (ESRD) patients on hemodialysis received either L-carnitine 1 g/d (n = 24) or placebo (27 patients) for 16 weeks. At the end of the study, there was a significant decrease in triglyceride (−31.1 ± 38.7 mg/dL, P = 0.001) and a significant increase in HDL (3.7 ± 2.8 mg/dL, P < 0.001) levels in the carnitine group. Decrease in total cholesterol (−6.6 ± 16.0 mg/dL, P = 0.075) and increase in hemoglobin (0.7 ± 1.7 g/dL, P = 0.081) concentrations in the carnitine group were not significant. There was no statistically significant changes in LDL in any group (P > 0.05). Erythropoietin dose was significantly decreased in both the carnitine (−4750 ± 5772 mg, P = 0.001) and the placebo group (−2000 ± 4296 mg, P < 0.05). No improvement was observed in QOL scores of two groups. In ESRD patients under maintenance hemodialysis, oral L-carnitine supplementation may reduce triglyceride and cholesterol and increase HDL and hemoglobin and subsequently reduce needed erythropoietin dose without effect on QOL.

92 UTILISATION OF ENDOGENOUS FATTY ACID STORES FOR ENERGY PRODUCTION IN BOVINE PRE-IMPLANTATION EMBRYOS

Current embryo culture media are based on the carbohydrate metabolism of embryos. However, little is known about the metabolism of endogenous lipids. This is surprising given the high intracellular lipid densities of embryos of some species and the potential for ATP production via β-oxidation. L-carnitine is a β-oxidation co-factor that is absent in most culture media. The aim of this study is to investigate the influence of carnitine supplementation ± carbohydrates on bovine embryo development. Abattoir-derived cattle cumulus–oocyte complexes were cultured and fertilised (Sutton-McDowall et al. 2006 Biol. Reprod. 74, 881–888). Post-fertilisation (24 h), presumptive zygotes were transferred into an amino acid-free cleavage media ± carbohydrates (glucose, lactate and pyruvate) ±5 mM carnitine and cultured for 4 days. The absence of carbohydrates during culture resulted in embryos arresting at the 2- and 4-cell stages. Remarkably, +carnitine significantly increased development to the morula stage compared with +carbohydrates alone (20.4 ± 3% vs 4.7 ± 2.5% morula development; P &lt; 0.001). The combination of carbohydrates and carnitine supplementation further improved embryo development, with 14-fold more embryos reaching the morula stage after culture in the +carbohydrates +carnitine group compared with the +carbohydrates group (+carbohydrates = 3.1 ± 1.9 vs +carbohydrates +carnitine = 43.8 ± 9.1% morula development; P &lt; 0.05). The beneficial effects of carnitine supplementation on embryo development were reversed when embryos were cultured in presence of etomoxir, a non-reversible inhibitor of the rate-limiting enzyme of β-oxidation (development to 8-cell stage; +carnitine = 33.9 ± 8% vs +carnitine +etomoxir = 19.2 ± 4.9%; P &lt; 0.05). Intracellular lipid content of embryos +carnitine was determined by culturing presumptive zygotes in media -carbohydrates ± carnitine for 24 h. Lipid content of embryos was determined by measuring BODIPY 493/503 dye fluorescence. Carnitine supplementation reduced fluorescence intensity 1.8-fold (P &lt; 0.001). Adenosine triphosphate and ATP:ADP levels were measured in embryos after 24 h of culture ± carbohydrates ± carnitine. While there was a trend for +carnitine to increase ATP levels (P = 0.09), ADP levels were higher and ATP:ADP ratio were 1.9-fold lower (main effect, P &lt; 0.05) compared with embryos cultured in –carnitine. This indicates +carnitine embryos were more metabolically active, with higher rates of ATP-ADP conversion. We have shown carnitine supplementation supports pre-compaction embryo development and there is an additive effect of +carnitine +carbohydrate on early embryo development. This is most likely through increased β-oxidation levels within embryos. Current disparities between in vivo and in vitro embryo production, in particular increased lipid content (Romek et al. 2010 Theriogenology 74, 265–276) and decreased developmental potential of in vitro-produced embryos, may be an artefact resulting from limited lipid oxidation in vitro.

Clinical Effects of Carnitin Supplementation on Hypoglycemia, Apnea and Sepsis in Very Low Birth Weight Neonates

Background Systemic carnitine deficiency may present with apnea, hypotonia, and poor growth. Premature infants often manifest these symptoms and are at risk of developing carnitine deficiency because of immaturity of the biosynthetic pathway, lack of sufficient predelivery transplacental transport, and lack of sufficient exogenous supplementation. Objective This study was undertaken to examine the effect of carnitine supplementation on hypoglycemia, apnea and sepsis in premature infants. Methods In this clinical study 60 preterm infants less than <1500 g birth weight were enrolled. The subjects in the carnitine group received 20 mg/kg/day oral supplemental by nasogastric tube in addition to routine nursing care within 96 hours of birth. Episodes of apnea, hypoglycemia and sepsis were the primary outcome measures recorded. The control group received routine nursing care. Results Episodes of apnea and the hypoglycemia were similar between the two groups. (P=0.55 and 0.69 respectively). Conclusion: In this study treatment with carnitine supplementation had no effect on apnea, hypoglycemia and sepsis in very low birth weight neonates.

A comparison of the efficacy of 5-fluorouracil/triamcinolone, carnitine and dexamethasone therapy on wound healing in tracheal injury: potential for preventing tracheal stenosis?

The aim of the study was to investigate the efficacy of 5-flourouracil/triamcinolone acetonide (5-FU/TA), carnitine and dexamethasone on wound healing in an animal model of tracheal injury. Twenty-eight rats underwent surgical injury of the tracheal mucosa and perichondrium under general anesthesia, and were randomized into four groups. Group I (the control group) received nothing after tracheal trauma. Group II received intratracheal 5 mg 5-FU/TA combined with 0.2 ml sodium hyaluronic acid once. Group III received intraperitoneal carnitine 100 mg/kg/day for 20 days. Group IV received intramuscular dexamethasone 0.1 mg/day for 20 days. After 1 month, the levels of superoxide dismutase enzyme activity (SOD) and levels of malondialdehide (MDA) and nitric oxide (NO) in serum were measured and the tracheal specimens were harvested for histopathologic examination. SOD was significantly lower in the carnitine group compared to the control group. A statistically significant decrease in MDA levels were observed in the 5-FU/TA and carnitine groups compared to the control group. NO levels were significantly lower in the 5-FU/TA group, but significantly higher in the dexamethasone group, compared to the control group. The fibrotic tissue volumes of tracheal specimens were significantly lower in both the 5-FU/TA and carnitine groups than those of the control group, but trended toward higher volumes in the dexamethasone group when compared to controls. We concluded that 5-FU/TA and carnitine diminish the occurrence of tracheal stenosis (TS) secondary to experimentally induced tracheal trauma.

Prevention of free fatty acid‐induced hepatic lipotoxicity by carnitine via reversal of mitochondrial dysfunction

Mitochondria are the main sites for fatty acid oxidation and play a central role in lipotoxicity and nonalcoholic steatohepatitis. We investigated whether carnitine prevents free fatty acid (FFA)-induced lipotoxicity in vitro and in vivo. HepG2 cells were incubated with FFA, along with carnitine and carnitine complexes. Mitochondrial β-oxidation, transmembrane potential, intracellular ATP levels and changes in mitochondrial copy number and morphology were analysed. Otsuka Long-Evans Tokushima Fatty and Long-Evans Tokushima Otsuka rats were segregated into three experimental groups and fed for 8 weeks with (i) normal chow, (ii) a methionine choline-deficient (MCD) diet or (iii) an L-carnitine-supplemented MCD diet. Carnitine prevented FFA-induced apoptosis (16% vs. 3%, P < 0.05). FFA treatment resulted in swollen mitochondria with increased inner matrix density and loss of cristae. However, mitochondria co-treated with carnitine had normal ultrastructure. The mitochondrial DNA copy number was higher in the carnitine treatment group than in the palmitic acid treatment group (375 vs. 221 copies, P < 0.05). The carnitine group showed higher mitochondrial β-oxidation than did the control and palmitic acid treatment groups (597 vs. 432 and 395 ccpm, P < 0.05). Carnitine treatment increased the mRNA expression of carnitine palmitoyltransferase 1A and peroxisome proliferator-activated receptor-γ, and carnitine-lipoic acid further augmented the mRNA expression. In the in vivo model, carnitine-treated rats showed lower alanine transaminase levels and lesser lobular inflammation than did the MCD-treated rats. Carnitine and carnitine-lipoic acid prevent lipotoxicity by increasing mitochondrial β-oxidation and reducing intracellular oxidative stress.

Roles of PYK2 and caveolin-1 in alcoholic cardiomyopathy and the effect of drug intervention

To explore the protein expressions of PYK2 (protein-rich tyrosine kinase-2) and caveolin-1 in alcoholic cardiomyopathy (ACM) dog model and the effect of early drug intervention. A total of 28 adult dogs were randomly divided into 4 groups: (i): alcohol-fed; (ii): alcohol plus valsartan, an angiotensin receptor blocker (ARB); (iii): alcohol plus carnitine; (iv): control group. At Month 6, the cardiac functions of all animals were evaluated by echocardiography. The concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in cardiac tissue were detected by chronometry. The protein expressions of collagen types I and III were determined by ELISA (enzyme-linked immunosorbent assay) while those of PYK2 and caveolin-1 evaluated by immunohistochemistry. The internal relationship of PYK2, caveolin-1, MDA and collagen types I & III was analyzed. Compared with the control group, the contents of SOD and GSH-Px significantly decreased in the alcohol, valsartan and carnitine groups while MDA significantly increased in the alcohol and carnitine groups. The relative contents in each group were as follows: MDA [alcohol: (28 ± 5) U/mg Pro; valsartan: (33 ± 13) U/mg Pro; carnitine: (33 ± 10) U/mg Pro], GSH-Px [alcohol: (188 ± 37) U/g Pro; valsartan: (362 ± 29) U/g Pro; carnitine: (282 ± 29) U/g Pro and MDA [alcohol: (19.4 ± 3.0) nmol/mg Pro; carnitine: (10.8 ± 2.1) nmol/mg Pro]. Compared with the control group, the concentration of collagen typeI significantly increased in the alcohol, valsartan and carnitine groups. In the alcohol-fed group, the protein expression of PYK2 gradually increased with the progression of ACM while that of caveolin-1 stayed at a low level. Through the interventions of valsartan and carnitine, the protein expression of PYK2 significantly increased while that of caveolin-1 significantly decreased (all P < 0.01). Alcohol promotes the myocardial oxidative stress and fibrosis through an elevated expression of PYK2 and a lowered expression of caveolin-1. Then a deterioration of cardiac structures and functions occur.

Effects of l-carnitine Supplement on Serum Amyloid A and Vascular Inflammation Markers in Hemodialysis Patients: A Randomized Controlled Trial

We studied the effects of l-carnitine supplement on serum amyloid A (SAA), a systemic inflammation marker, and vascular inflammation markers in hemodialysis patients. This was a randomized, double-blind, placebo-controlled trial. The study was performed in Soodeh Hemodialysis Center in Islamshahr, Iran. We included 36 hemodialysis patients (15 men and 21 women). The patients on hemodialysis were randomly assigned to either a carnitine or a placebo group. Patients in the carnitine group received 1,000 mg/day oral l-carnitine for 12 weeks, whereas patients in the placebo group received a corresponding placebo during the study. Serum free carnitine, SAA, soluble intercellular adhesion molecule type 1, soluble intercellular adhesion molecule type 2, soluble vascular cell adhesion molecule type 1, sE-selectin, sP-selectin, and oxidized low-density lipoprotein were measured at baseline and at the end of week 12 of the study. Mean serum free carnitine concentration increased significantly to 150% of baseline in the carnitine group at the end of week 12 (P < .001), whereas serum SAA showed a significant 32% decrease (P < .001). No significant changes were observed in the serum concentrations of free carnitine and SAA in the placebo group during the study. There were no significant differences between the two groups in mean changes in serum soluble intercellular adhesion molecule type 1, soluble intercellular adhesion molecule type 2, soluble vascular cell adhesion molecule type 1, sE-selectin, sP-selectin, and oxidized low-density lipoprotein concentrations. The study indicates that l-carnitine supplement reduces serum SAA, which is a risk factor for cardiovascular diseases in hemodialysis patients, but has no effect on vascular inflammation markers.

Chronic oral ingestion of l‐carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans

We have previously shown that insulin increases muscle total carnitine (TC) content during acute i.v. l-carnitine infusion. Here we determined the effects of chronic l-carnitine and carbohydrate (CHO; to elevate serum insulin) ingestion on muscle TC content and exercise metabolism and performance in humans. On three visits, each separated by 12 weeks, 14 healthy male volunteers (age 25.9 ± 2.1 years, BMI 23.0 ± 0.8 kg m−2) performed an exercise test comprising 30 min cycling at 50% , 30 min at 80% , then a 30 min work output performance trial. Muscle biopsies were obtained at rest and after exercise at 50% and 80% on each occasion. Following visit one, volunteers ingested either 80 g of CHO (Control) or 2 g of l-carnitine-l-tartrate and 80 g of CHO (Carnitine) twice daily for 24 weeks in a randomised, double blind manner. All significant effects reported occurred after 24 weeks. Muscle TC increased from basal by 21% in Carnitine (P < 0.05), and was unchanged in Control. At 50% , the Carnitine group utilised 55% less muscle glycogen compared to Control (P < 0.05) and 31% less pyruvate dehydrogenase complex (PDC) activation compared to before supplementation (P < 0.05). Conversely, at 80% , muscle PDC activation was 38% higher (P < 0.05), acetylcarnitine content showed a trend to be 16% greater (P < 0.10), muscle lactate content was 44% lower (P < 0.05) and the muscle PCr/ATP ratio was better maintained (P < 0.05) in Carnitine compared to Control. The Carnitine group increased work output 11% from baseline in the performance trial, while Control showed no change. This is the first demonstration that human muscle TC can be increased by dietary means and results in muscle glycogen sparing during low intensity exercise (consistent with an increase in lipid utilisation) and a better matching of glycolytic, PDC and mitochondrial flux during high intensity exercise, thereby reducing muscle anaerobic ATP production. Furthermore, these changes were associated with an improvement in exercise performance.

Dietary L‐carnitine alters gene expression in skeletal muscle of piglets

Carnitine improves protein accretion, muscle mass, and protein:fat accretion in piglets. The underlying mechanisms, however, are largely unknown. To gain insight into mechanisms through which carnitine exerts these effects, we fed piglets either a control or a carnitine-supplemented diet, and analyzed the transcriptome in skeletal muscle. Carnitine concentrations in plasma and muscle were about four-fold higher in the carnitine group when compared to the control group. Transcript profiling revealed 211 genes to be differentially expressed in muscle by carnitine supplementation. The identified genes were mainly involved in molecular processes such as cytoskeletal protein binding, insulin-like growth factor (IGF) binding, transcription factor activity, and insulin receptor binding. Identified genes with the molecular function transcription factor activity encoded primarily transcription factors, most of which were down-regulated by carnitine, including pro-apoptotic transcription factors such as proto-oncogene c-fos, proto-oncogene c-jun and activating transcription factor 3. Furthermore, atrophy-related genes such as atrogin-1, MuRF1, and DRE1 were significantly down-regulated by carnitine. IGF signalling and insulin signalling were identified as significantly up-regulated regulatory pathways in the carnitine group. Carnitine may have beneficial effects on skeletal muscle mass through stimulating the anabolic IGF-1 pathway and suppressing pro-apoptotic and atrophy-related genes, which are involved in apoptosis of muscle fibers and proteolysis of muscle proteins, respectively.

Effects of L-Carnitine supplement on plasma coagulation and anticoagulation factors in hemodialysis patients

Background: Hypercoagulability is an important risk factor for thrombosis and its complications in hemodialysis patients. This study was designed to investigate the effects of l-carnitine supplement on plasma coagulation and anticoagulation factors in hemodialysis patients. Methods: Thirty-six hemodialysis patients were randomly assigned to either a carnitine or a placebo group. Patients in the carnitine group received 1000 mg/day oral l-carnitine for 12 weeks, whereas patients in the placebo group received a corresponding placebo. At baseline and the end of week 12, 5 mL blood was collected after a 12- to 14-hour fast and plasma fibrinogen concentration, activity of plasma protein C, coagulation factors V, VII, IX, and serum concentrations of tissue plasminogen activator (tPA), plasminogen activator inhibitor type-1 (PAI-1), free carnitine, and C-reactive protein (CRP) were measured. Results: In the carnitine group, mean serum free carnitine concentration increased significantly to 150% of baseline (p < 0.001), whereas plasma fibrinogen and serum CRP had 98 mg/dL (p < 0.01) and 41% (p < 0.01) significant decreases, respectively, at the end of week 12 compared with baseline. The reductions were significant compared with the placebo group (p < 0.05). No significant differences were observed between the two groups with regard to mean changes of the activity of plasma protein C, coagulation factors V, VII, IX, and serum PAI-1 to tPA ratio. Conclusion: l-Carnitine supplement reduces serum CRP, a marker of systemic inflammation, and plasma fibrinogen, an inflammation-related coagulation factor, in hemodialysis patients. Therefore, l-carnitine may play an effective role in preventing cardiovascular diseases in these patients.

Preliminary Study Comparing the Effects of Locally and Systemically Applied L-Carnitine on the Healing of Full-Thickness Skin Defects

L-carnitine as an endogenous cofactor has a role in the regulation of energy flow between different oxidative sources. The purpose of this study is to investigate that the clinical and histopathologic effects of L-carnitine locally and systemically on secondary healing in wounds of full thickness defects. We also measured the effects of L-carnitine on wound tensile strength as mechanical. sixty adult male Sprague-Dawley rats were divided into three groups randomly; group 1 (control group, n = 20), group 2 (local experimental group, n = 20), group 3 (systemic experimental group, n = 20). Group 1 was not given any pharmacologic agents. L-carnitine was administered locally in the group 2, and systemically in group 3 for a total of 14 days. The healing days of all groups were recorded. On the 7th, 10th,14th and 21st postoperative days, biopsy specimens, including tissue samples both from healing wound sites and sur-rounding healthy skin were evaluated for neovascularization, inflammation, the amount of collagen deposit, fibroblast migration and re-epithelization. Tensile strength was measured in the samples which completed healing on the 30th day. The results were evaluated by nonparametric Kruskall-Wallis test followed by Mann Whitney-U test. the mean clinical healing days were 18.25 days, 16.5 days, 15 days for the control group, local experimental and systemic group, respectively. The differences between groups were statistically significant (p < 0.005). Mean tensile strength values were 762.10 centinewton (cN), 801.69 cN and 786.13 cN for the control group, local experimental group and systemic experimental group, respectively. There were no statistically significant differences between groups (p > 0.05). There was no statistically significant difference in the histopathologic ex-amination on the 7th, 10th, 14th and 21st days in the neovascularization, inflammation and fibroblast migration. Collagen deposit was most prevalent in the systemic experimental group and was least in the control group. Complete wound closure rate was observed on the 7th day in the systemic administration group, on the 10th day in local administration group and on the 14th day in the control group. Re-epithelization thickness in the systemic carnitine group was more than the other groups. L-carnitine administered locally or systemically has positive effects on wound healing rate and tensile strength in rats.

Effects of l‐carnitine supplement on serum inflammatory cytokines, C‐reactive protein, lipoprotein (a), and oxidative stress in hemodialysis patients with Lp (a) hyperlipoproteinemia

Inflammation, oxidative stress, and high concentration of serum lipoprotein (a) [Lp (a)] are common complications in hemodialysis patients. The present study was designed to investigate the effects of L-carnitine supplement on serum inflammatory cytokines, C-reactive protein (CRP), Lp (a), and oxidative stress in hemodialysis patients with Lp (a) hyperlipoproteinemia [hyper Lp (a)]. This was an unblinded, randomized clinical trial. Thirty-six hyper Lp (a) hemodialysis patients (23 men and 13 women) were randomly assigned to either a carnitine or control group. Patients in the carnitine group received 1000 mg/d oral L-carnitine for 12 weeks, whereas patients in the control group did not receive any L-carnitine supplement. At baseline and the end of week 12, 5 mL of blood were collected after a 12- to 14-hours fast and serum free carnitine, CRP, interleukin-1β, interleukin-6 (IL-6), tumor necrosis factor-α, Lp (a), and oxidized low-density lipoprotein were measured. Serum free carnitine concentration increased significantly by 86% in the carnitine group at the end of week 12 compared with baseline (P<0.001), while serum CRP and IL-6 showed a significant decrease of 29% (P<0.05) and 61% (P<0.001), respectively. No significant changes were observed in serum free carnitine, CRP, and IL-6 in the control group. There were no significant differences between the two groups in mean changes of serum interleukin-1β, tumor necrosis factor-α, Lp (a), and oxidized low-density lipoprotein concentrations. L-carnitine supplement reduces inflammation in hemodialysis patients, but has no effect on hyper Lp (a) and oxidative stress.

Effects of Carnitine on Peripheral Blood Mitochondrial DNA Copy Number and Liver Function in Non-Alcoholic Fatty Liver Disease

Functional and anatomical abnormalities of mitochondria play an important role in developing steatohepatitis. Carnitine is essential for enhanced mitochondrial beta oxidation through the transfer of long-chain fatty acids into the mitochondria. We examined the impact of carnitine complex on liver function and peripheral blood mitochondria copy number in NAFLD patients. Forty-five NAFLD patients were enrolled. Patients were categorized into the carnitine complex-administered group and control group. Before and 3 months after drug administration, a liver function test and peripheral blood mitochondrial DNA and 8-oxo-dG quantitive analysis were conducted. In carnitine treatment group, ALT, AST, and total bilirubin were reduced after medication. There was no difference in AST, ALT, and total bilirubin between before and after treatment in control group. In carnitine group, peripheral mitochondrial DNA copy number was significantly increased from 158.8+/-69.5 copy to 241.6+/-180.6 copy (p=0.025). While in control group the mitochondrial copy number was slightly reduced from 205.5+/-142.3 to 150.0+/-109.7. 8-oxo-dG level was also tended to decrease in carnitine group (p=0.23) and tended to increase in control group (p=0.07). In NAFLD, the carnitine improved liver profile and peripheral blood mitochondrial DNA copy number. This results suggest that carnitine activate the mitochondria, thereby contributing to the improvement of NAFLD.

Failure of carnitine in improving hepatic nitrogen content in alcoholic and non-alcoholic malnourished rats

AIMS:To investigate the effect of carnitine supplementation on alcoholic malnourished rats' hepatic nitrogen content.METHODS:Malnourished rats, on 50% protein‐calorie restriction with free access to water (malnutrition group) and malnourished rats under the same conditions with free access to a 20% alcohol/water solution (alcohol group) were studied. After the undernourishment period (4 weeks with or without alcohol), both groups were randomly divided into two subgroups, one of them nutritionally recovered for 28 days with free access to a normal diet and water (recovery groups) and the other re‐fed with free access to diet and water plus carnitine (0.1 g/g body weight/day by gavage) (carnitine groups). No alcohol intake was allowed during the recovery period.RESULTS:The results showed: i) no difference between the alcohol/no alcohol groups, with or without carnitine, regarding body weight gain, diet consumption, urinary nitrogen excretion, plasma free fatty acids, lysine, methionine, and glycine. ii) Liver nitrogen content was highest in the carnitine recovery non‐alcoholic group (from 1.7 to 3.3 g/100 g, P<0.05) and lowest in alcoholic animals (about 1.5 g/100g). iii) Hepatic fat content (∼10 g/100 g, P>.05) was highest in the alcoholic animals.CONCLUSION:Carnitine supplementation did not induce better nutritional recovery.

The effect of antioxidants on post-thawed Angora goat ( Capra hircus ancryrensis) sperm parameters, lipid peroxidation and antioxidant activities

The aim of this study was to determine the effects of the antioxidants curcumin, inositol and carnitine on microscopic seminal parameters, lipid peroxidation (LPO) and the antioxidant activities of sperm, following the freeze-thawing of Angora goat semen. Ejaculates were collected via artificial vagina from three Angora goats and microscopically evaluated and pooled at 37 °C. The pooled semen samples were diluted in a Tris-based extender, including curcumin (2.5, 5 or 10 mM), inositol (2.5, 5 or 10 mM), carnitine (2.5, 5 or 10 mM) and no antioxidant (control). The diluted semen was slowly (at a rate of 0.2–0.3 °C/min) cooled to 5 °C and then cryopreserved in 0.25 mL French straws. Frozen straws were thawed individually at 37 °C for 20 s in a water bath, for microscopic sperm evaluation. The freezing extender supplemented with 2.5 mM curcumin led to higher percentage of computer-assisted semen analyzer (CASA) sperm motility (65 ± 3%), when compared to the control, inositol and the 10 mM carnitine ( P < 0.01) groups, following the freeze-thawing process. The addition of antioxidants did not provide any significant effect on the percentages of post-thaw subjective analyses and CASA progressive motilities, as well as sperm motility characteristics (VAP, VSL, LIN and ALH), compared to the controls. Freezing extenders with antioxidants at three different doses led to lower percentages of acrosome and total sperm abnormalities, when compared to the controls ( P < 0.001). However, the addition of 5 mM inositol did not induce any difference in total sperm abnormalities, when compared to the controls. The antioxidants also did not show any effectiveness in the elimination of malondialdehyde (MDA) formation and the maintenance of glutathione peroxidase (GSH-PX) activity, when compared to the controls. Superoxide dismutase (SOD) activity was found to be higher in the presence of curcumin at all three dose levels and carnitine at 5 mM, compared to the other groups. Glutathione (GSH) concentration was demonstrated to be maintained at a higher level with the addition of inositol, compared to the other groups. However, these differences in SOD and GSH levels were not significant, compared to the controls. All the antioxidants at all three dose levels resulted in a better protection of the sperm morphology (except for 5 mM inositol with respect to the total sperm abnormalities), compared to the control samples. According to CASA, the best post-thawing sperm motility rate was recorded when the freezing extender was supplemented with 2.5 mM curcumin. Further studies are required to obtain more conclusive results regarding the characterization of microscopic and oxidative stress parameters in cryopreserved goat sperm, using the different antioxidants.

Effects of simvastatin and carnitine versus simvastatin on lipoprotein(a) and apoprotein(a) in type 2 diabetes mellitus

Aim: The aim of the present study was to compare the effects of simvastatin and L-carnitine coadministration versus simvastatin monotherapy on lipid profile, lipoprotein(a) (Lp(a)) and apoprotein(a) (Apo(a)) levels in type II diabetic patients. Patients/methods: In this double-blind, randomized clinical trial, 75 patients were assigned to one of two treatment groups for 4 months. Group A received simvastatin monotherapy; group B received L-carnitine and simvastatin. The following variables were assessed at baseline, after washout and at 1, 2, 3 and 4 months of treatment: body mass index, fasting plasma glucose, glycated hemoglobin, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, Apolipoprotein A1, Apo B, lipoprotein(a) and apoprotein(a). Results: At the end of treatment in the carnitine and simvastatin combined group compared with the simvastatin alone group, we observed a significant decrease in glycemia (p < 0.001), tryglicerides (p < 0.001), Apo B (p < 0.05), Lp(a) (p < 0.05), apo(a) (p < 0.05), while HDL significantly increased (p < 0.05). Conclusions: The coadministration of carnitine and simvastatin resulted in a significant reduction in Lp(a) and apo(a) and may represent a new therapeutic option in reducing plasma Lp(a) levels, LDL cholesterol and Apo B100.