Carnitine Group Research Articles

Effects of l-carnitine on frailty status in patients with liver cirrhosis: A randomized-controlled trial.

Frailty is a common complication in patients with liver cirrhosis, which is linked with augmented rates of morbidity and mortality. In this regard, timely nutritional assessment and intervention have gained scientific attention. L-carnitine may be a promising candidate with its potential to enhance energy metabolism, reduce inflammation, and act as an antioxidant. Therefore, we aimed to assess the impact of l-carnitine supplementation on frailty status and liver function in adults with liver cirrhosis. This double-blinded, randomized, controlled clinical trial study enrolled 77 patients with liver cirrhosis. Patients were randomly allocated into two groups: the control group (n = 42) and the l-carnitine group (n = 35). The l-carnitine group received 500 mg of l-carnitine orally three times a day for 8 weeks, while the control group did not receive any intervention. L-carnitine administration resulted in a significant decrease in alanine transaminase levels (p: 0.043) and partial thromboplastin time (p: 0.036). Furthermore, compared to the control group, l-carnitine treatment led to improvements in prothrombin time (p: 0.008) and international normalized ratio (p: 0.024). However, no significant improvement in the Liver Frailty Index, Freid Frailty Index, and Karnofsky Performance Status Scale (p > 0.05) was observed in the carnitine group after the 8-week intervention period. In conclusion, the administration of l-carnitine exhibited hepatoprotective properties and was correlated with lowered alanine transaminaselevels with improvement in coagulation status in liver cirrhosis patients. Nevertheless, our study indicated that the short-term use of l-carnitine might not significantly improve frailty in these patients.

P-071 The dichotomy of micronutrients in male fertility: doses matter - striking the right balance for optimal reproductive health

Abstract Study question What is the impact of escalating doses of common water-soluble antioxidant nutrients on semen parameters and fertility in healthy (CD1) and stressed (Gpx5-/-) mice? Summary answer High-dose supplementation of previously “thought-to-be-safe” common water-soluble antioxidant nutrients can cause significant DNA damage/impaired fertility in healthy mice. What is known already In assisted conception, men increasingly take preconceptual antioxidant supplements (even if they are generally healthy) to enhance the likelihood of a successful pregnancy. Recent published reviews suggest 79% of male fertility supplements include ingredients at dosages exceeding Food Safety Authorities’ Recommended Dietary Allowances (RDAs). While many fertility experts question the efficacy of such supplements, most still carry the notion that “dietary ingredients”, regardless of the doses given, pose little safety concerns. Moreover, without established RDAs for many natural substances such as carnitines, supplement makers often subscribe to the “more is better” philosophy, potentially compromising safety in their product formulations. Study design, size, duration This study evaluates escalating doses of common water-soluble antioxidant nutrients (Vitamin C, Zinc, Folate, and Carnitines) on redox status, semen parameters, genetic integrity, and fertility in healthy (CD1) and stressed (Gpx5 -/-) mice over 28 days. The treated groups (n = 6) were compared against pooled controls (n = 24). We analyzed the doses of these ingredients in commercial fertility supplements against our new “safety profiles” to highlight potential overdosing risks and asses the broader safety implications. Participants/materials, setting, methods Experimental ingredient exposure dosages were based on current US-FDA RDA/I declarations, commercial popularity, and/or use in clinical fertility settings. Animal dosage conversion calculations were based on standard pharmaceutical methodologies. Assessments of male mouse redox status and reproductive function included general sperm parameters (count, motility, viability, acrosome integrity), DNA parameters [oxidation (8-OHdG staining), fragmentation (TUNEL), decondensation (Toluidine Blue)], and blood analysis (total antioxidant capacity, glutathione, malondialdehyde). Pregnancy outcomes were assessed in Carnitine fed, CD1 mice. Main results and the role of chance In CD1 mice, escalating doses of individual micronutrients had minimal effect on semen parameters, except for a significant sperm count increase at the highest Carnitine dose. However, there were considerable adverse effects on sperm DNA integrity and blood plasma redox state. The high-dose Carnitine group notably exhibited reduced pregnancy rates, in terms of both impregnation and total pups born, compared to controls. Yet, there were no differences in the number of pups born or resorptions, per pregnant female, between the high-dose Carnitine group and controls. In GPX5-/- mice, general semen parameters were mostly unaffected. Intriguingly, Carnitine positively influenced sperm DNA integrity in this model, underscoring the established link between micronutrient deficiency, oxidative stress, and semen quality. In the analysis of 34 random male fertility supplements, almost every product contained at least one ingredient at a dose that was harmful according to our study. Alarmingly, 88% had at least two such ingredients, 68% had three or more, and roughly 33% contained four or more at doses considered unsafe. Limitations, reasons for caution Carnitines’ pungent odor may have affected the mating efficiency of carnitine exposed CD1 males. Due to synergy of action, antioxidants administered individually, even at the same dose, may exert a different biochemical profile than when in combination with other ingredients (as in most commercial formulations). Wider implications of the findings The majority of male fertility supplements often combine aggressive doses of antioxidant nutrients. Our results highlight the potential dangers that may arise from their use and provide a clear warning to fertility experts against routinely recommending random, unsubstantiated supplements, especially in the absence of prior oxidative stress assessment. Trial registration number not applicable

Hypocarnitinemia and its effect on seizure control in adult patients with intractable epilepsy on the modified Atkins diet.

Previous studies have demonstrated the safety and efficacy of the modified Atkins diet (MAD) in attenuating seizures in patients with intractable epilepsy. MAD works by achieving ketosis, which is heavily dependent on the metabolic compound, carnitine, to facilitate the transport of long-chain fatty acids across the mitochondria for beta-oxidation. The effect of carnitine on ketogenic diet therapy is not well-defined in the current literature. Thus, the purpose of our study is to investigate the effects of hypocarnitinemia on the efficacy of MAD. A retrospective chart review was conducted, and 58 adults with epilepsy undergoing MAD were evaluated. Generalized linear mixed effects models were used to compare the low carnitine status with normal carnitine group in patient measures of body mass index, seizure frequency and severity, number of anti-seizure medications, beta-hydroxybutyrate, triglyceride, and carnitine levels across baseline, 3-9-month follow-up (timepoint 1), 1-2-year follow-up (timepoint 2), and 2+ year follow-up (timepoint 3). Our study revealed that 38.3% of adult patients with epilepsy following MAD experienced low free carnitine at some point through the course of diet therapy. Patients with hypocarnitinemia at timepoint 2 showed a significant percent seizure increase while seizures continued to decrease in the normal carnitine group. Fasting triglyceride levels at timepoint 1 were significantly increased in the low carnitine group compared to normal carnitine group. Change in BHB, BMI, seizure severity, and number of ASMs showcased no significant differences between the low and normal carnitine groups. It may be important for clinicians to monitor for hypocarnitinemia in adults on MAD and provide carnitine supplementation when low. Further investigations into carnitine and MAD may inform clinical decisions on carnitine supplementation to maximize the efficacy of MAD therapy.

Comparative study of the carnitine, Gensing, Dill, and Arginine effect in MDA, SOD, GSH levels in albino rats exposued to oxidative stress.

The aim of this study is to compare the effects of Carnitine, Gensing, Dill and Arginine in lipid peroxidation MDA and SOD, GSH antioxidant in normal and experimentally hydrogen peroxide H2O2 induced oxidative.
 Fifty male rats used in age 12-14 weeks in weights (300-325 g) divided randomly into 10 groups, included 5 in each group as following.
 Control, H2O2 , Carnitine , carnitine + H2O2 , Gensing , Gensing + H2O2 , Dill, Dill+ H2O2 ,Arginine , Arginine + H2O2 groups.
 Results showed:
 1-Treating normal rats with Carnitine, Gensing, Dill, Arginine, led to a significant increase (P≤0.05) in GSH level in all groups except Gensing group, and a significant decrease in MDA level in all groups except Carnitine group and no difference in SOD comparing to control group.
 2-Oxidative stress Induced by H2O2 led to significant increase in value (P≤ 0.05) in levels of MDA, comparing to control group. While there were a significant decrease in value (P≤0.05) in GSH, SOD.
 3-Treating rats exposure to oxidative stress with Carnitine, Gensing, Dill, Arginine, led to a significant decrease in value(P≤0.05) in MDA, While the treatment led to significant increase in GSH, , SOD comparing with H2O2 group.

Effects and molecular mechanism of exogenous L-carnitine on excessive endoplasmic reticulum stress-mediated hepatic pyroptosis in severely scald rats

Effects and molecular mechanism of exogenous L-carnitine on excessive endoplasmic reticulum stress-mediated hepatic pyroptosis in severely scald rats

The protective effect of L-carnitine supplementation on retinopathy of prematurity: A retrospective cohort study

Background/Aim: Retinopathy of prematurity (ROP) is important morbidity in premature infants and is the most common preventable cause of blindness in childhood. Carnitine is a key molecule in energy metabolism and in oxidation of fatty acids, which are the main structural component of phospholipid membrane of the brain and retinal cells. Premature babies are born with insufficient carnitine pools. This study aimed to evaluate the effect of carnitine replacement on ROP in premature infants aged < 34 gestational weeks. Methods: Premature infant records between 2014 and 2019 were retrospectively examined. All premature infants at gestational ages < 34 weeks were included. Data from the two groups who received/did not receive carnitine supplementation in total parenteral nutrition (TPN) over two consecutive time periods and whose ROP examination was complete were recorded retrospectively. Fifty-eight out of 125 infants were in the carnitine group, and 67 formed the non-carnitine group (CG and NCG, respectively). The morbidity data from subjects, especially those with ROP, who received (CG) and did not receive carnitine (NCG), were compared. Results: Of the 125 infants enrolled, no significant differences in gestational age (P = 0.323) or birth weight (P = 0.597) between the groups was found. The Cox regression analysis revealed that carnitine replacement in the premature infant was a protective factor for ROP (P=0.045, B= −0.933, hazard ratio 0.393, 95% confidence interval 0.158–0.978). Conclusion: Carnitine supplementation may offer protection from developing ROP during exposure to oxygen in premature infants.

Association between Levocarnitine Treatment and the Change in Knee Extensor Strength in Patients Undergoing Hemodialysis: A Post-Hoc Analysis of the Osaka Dialysis Complication Study (ODCS).

Carnitine deficiency is prevalent in patients undergoing hemodialysis, and it could result in lowered muscle strength. So far, the effect of treatment with levocarnitine on lower limb muscle strength has not been well described. This observational study examined the association between treatment with levocarnitine with the change in knee extensor strength (KES) in hemodialysis patients. Eligible patients were selected from the participants enrolled in a prospective cohort study for whom muscle strength was measured annually. We identified 104 eligible patients for this analysis. During the one-year period between 2014 to 2015, 67 patients were treated with intravenous levocarnitine (1000 mg per shot, thrice weekly), whereas 37 patients were not. The change in KES was significantly higher (p = 0.01) in the carnitine group [0.02 (0.01–0.04) kgf/kg] as compared to the non-carnitine group [−0.02 (−0.04 to 0.01) kgf/kg]. Multivariable-adjusted regression analysis showed the positive association between the change in KES and the treatment with levocarnitine remained significant after adjustment for the baseline KES and other potential confounders. Thus, treatment with intravenous levocarnitine was independently and positively associated with the change in KES among hemodialysis patients. Further clinical trials are needed to provide more solid evidence.

L-Carnitine improves follicular survival and function in ovarian grafts in the mouse.

Ovarian tissue transplantation is performed to preserve fertility in patients undergoing chemotherapy and radiotherapy. However, the ischemia-reperfusion injury which occurs after the ovarian tissue transplantation causes follicular depletion and apoptosis. l -Carnitine has antioxidant and anti-inflammation properties. Therefore, we aimed to investigate the beneficial effect of l -carnitine on mouse ovaries following heterotopic autotransplantation. Mice were randomly divided into three groups (six mice per group): control, autografted and autografted+l -carnitine (200mg/kg daily intraperitoneal injections). Seven days after ovary autografting, the serum levels of malondialdehyde (MDA), total antioxidant capacity, tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-10 were measured. Ovary histology, serum concentrations of progesterone and estradiol were also measured 28days after autotransplantation. Data were analysed using one-way analysis of variance (ANOVA) and Tukey test, and the means were considered significantly different at P Key results: In the autografted+l -carnitine group, the total volume of the ovary, the volume of the cortex, the number of follicles, the serum concentrations of IL-10, estradiol and progesterone significantly increased compared to the autografted group. In the autografted+l -carnitine group, serum concentrations of IL-6, TNF-α and MDA were significantly decreased compared to the autografted group. Our results indicated that l -carnitine can ameliorate the consequences of ischemia-reperfusion on the mice ovarian tissue following autotransplantation. l -carnitine improves the structure and function of transplanted ovaries.

Free Papers Compiled

INTRODUCTION:Preliminary studies suggestive of Acetyl-L-carnitine treatment have positive effects on patients depression with respects to fatigability and cognitive functions and also negative symptoms in patients diagnosed with schizophrenia.AIMThe aim of the study is to assess the effect of Acetyl-L carnitine as an add on therapy in patients with schizophrenia.OBJECTIVESTo assess the response of acetyl-L-carnitine as an augmented treatment in reduction of negative symptoms, cognitive decline severity in patients of schizophrenia.METHODOLOGY:Seventy five patients diagnosed with schizophrenia according to the DSM-5 criteria were selected for the study after meeting the inclusion criteria and written informed consent. Fifteen patients were dropped from the study due to multiple reasons, finally 60 patients completed the pre and post analysis. Two groups of the patients were taken randomly from Hospital, which were drug naïve psychotic patients. Both the groups were chosen according to inclusion and exclusion criteria as mentioned earlier. After analysis it was found that both the groups were comparable with respect to age, sex, education, occupation, marital status, family type and economic status ensuring more homogeneity among the groups as compared to previous studies (p value >0.05). After randomization, 30 patients were assigned for olanzepine group, and 30 for olanzepine + acetyl l carnitine group. All the patients were assessed with PANSS, MoCA, GAF at the baseline and follow up.Post analysis was done after 6 weeks of treatment. Baseline and follow up data was compared.RESULTS:Both group is very much significant in comparison with intra group. The two group medication is working fine. But the efficacy of ALC is unknown when comparing both groups.CONCLUSION:The results of the current study in conjunction with the results of other methodologically similar studies suggest that ALC can be used as an additional medication with the active ingredient olanzapine. There is no significant difference in effect of olanzapine mono-therapy vs. olanzapine augmented Acetyl-L-carnitine in patients with schizophrenia. Both group shows similar pattern in reduction of negative symptoms, cognitive decline severity in patients of schizophrenia.

Acetyl-L-Carnitine Ameliorates Metabolic and Endocrine Alterations in Women with PCOS: A Double-Blind Randomized Clinical Trial.

Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder and the main cause of infertility in women of reproductive age. Affected women suffer from insulin resistance and present with an intense stress response. Treatment with insulin sensitizers alone and in combination is used to ameliorate the signs and symptoms associated with the disease. This study was designed to compare the endocrine and metabolic parameters as well as subjective and objective measures of stress in women with PCOS before and after treatment with acetyl-L-carnitine (ALC) and metformin plus pioglitazone. A total of 147 women with PCOS were randomly assigned into two groups: the combo group (n = 72) received a combination of metformin, pioglitazone, and ALC (500mg, 15mg, and 1500mg, respectively), twice daily; the Met + Pio group (n = 75) received metformin plus pioglitazone (500mg, 15mg, respectively) and placebo (citric acid plus calcium carbonate), twice daily for 12weeks. Medications were discontinued when pregnancy was confirmed. The Perceived Stress Scale (PSS14) and Profile of Mood States (POMS) were employed as subjective measures of stress. The endocrine and metabolic functions of women with PCOS were assessed by measuring insulin, leutinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and adiponectin levels in fasting blood samples. Insulin resistance was calculated by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Women at baseline had significantly elevated circulating concentration of insulin and low level of adiponectin. Treatment decreased insulin in both groups; however, the combo group showed a significant decrease (p = 0.001). Serum adiponectin level was raised significantly after treatment in both groups (p < 0.001). HOMA-IR also decreased in both groups (both p < 0.001). Testosterone, FSH, and LH significantly improved in both groups. LH also decreased in both groups; however, the change was significant only in the combo (metformin plus pioglitazone plus ALC) group (p = 0.013). Interestingly, there was a significant improvement in body circumference (p < 0.001) in the combo group. The PSS scores of the patients improved significantly (p < 0.001) in the combo group. Interestingly, regular menstrual cycles were found (97.2%) in the carnitine group, but in only 12.9% of the other group. We conclude that addition of ALC therapy is superior to metformin plus pioglitazone in ameliorating insulin resistance, polycystic ovaries, menstrual irregularities, and hypoadiponectinemia in women with PCOS. Trial registration: clinicalTrial.gov NCT04113889. Registered 3 October, 2019. https://clinicaltrials.gov/ct2/show/NCT04113889 .

The Effect of Carnitine Supplementation on Blood Ammonia Level in Epilepsy Children Treated with Valproic Acid: A Randomized Controlled Trial

Background: Long-term use of valproic acid is associated with a high level of blood ammonia related to carnitine deficiency. This study investigates the effect of carnitine supplementation on blood ammonia levels in children with epilepsy who have been treated with valproic acid for more than six months.Materials and Methods: This was a randomized, double-blind, placebo-controlled trial study where children with epilepsy who were treated with valproic acid were randomly allocated to the carnitine supplementation and control group. All children were followed for month, and then measured for blood ammonia level. Blood ammonia levels of both groups were compared using an Independent t-test with a significant of p&lt;0.05.Results: Total of 32 children with epilepsy were enrolled as subjects in this study, with 16 children in carnitine group, and 16 children in control group. Among the subjects, 50% were male and 50% were female, with a mean age of 6.5 years old. The average duration of epilepsy in the carnitine and control group were 41.7 months and 36.9 months, respectively (p=0.419). The duration of valproic acid therapy in the carnitine and control group were 33.1 months and 27.6 months, respectively (p=0.483). The level of blood ammonia in carnitine and control group were 44.6 mg/dL and 81.4 mg/dL, respectively (p=0.007).Conclusion: The level of blood ammonia in a carnitine group was significantly lower than in a control group. It is recommended to give carnitine supplementation in epileptic children treating with long-term valproic acid.Keywords: ammonia, carnitine, epilepsy, seizure, valproic acid

Effects of early supplement of exogenous L-carnitine on renal function in severely scalded rats

Objective: To explore the effects of early exogenous L-carnitine supplementation on renal function in severely scalded rats. Methods: According to the random number table, sixty-six adult female Sprague-Dawly rats were divided into healthy control group (n=6), scald alone group (n=30), and scald+ carnitine group (n=30). In the latter two groups, the rats were inflicted with full-thickness scald of 30% total body surface area on the back, and the lactated Ringer's solution was injected through the tail vein for resuscitation immediately after scald. At post injury hour (PIH) 1, rats in scald+ carnitine group were intraperitoneally injected with 100 mg/mL L-carnitine solution 400 mg/kg, while rats in scald alone group were intraperitoneally injected with the same volume of normal saline. Rats in these two groups were injected once every 24 hours thereafter. Six rats were taken from each of scald alone group and scald+ carnitine group to collect the renal tissue and abdominal aorta blood at PIH 6, 12, 24, 48, and 72, respectively. The serum content of total protein, albumin, urea nitrogen, creatinine, and cystatin C were determined by the automatic biochemical analyzer. Renal tissue was stained with hematoxylin-eosin to observe histopathological changes. Rats in healthy control group did not undergo any treatment, and their renal tissue and blood sample were extracted and analyzed in the same way as those of severely scalded rats. Data were statistically analyzed with one-way analysis of variance and Bonferroni method. Results: (1) The serum content of total protein and albumin of rats in scald alone group at each time point after injury was significantly lower than that in healthy control group (P<0.05). The serum content of total protein of rats in scald+ carnitine group was significantly higher than that in scald alone group at PIH 12 and 24 (P<0.05), and the serum content of albumin of rats in scald+ carnitine group was significantly higher than that in scald alone group at PIH 12 (P<0.05). The serum content of total protein and albumin of rats in scald alone group and scald+ carnitine group showed a trend of decrease followed by an increase, with the lowest value at PIH 24. (2) The serum content of urea nitrogen and creatinine of rats in scald alone group at each time point after injury was significantly higher than that of healthy control group (P<0.05). The serum content of urea nitrogen of rats in scald+ carnitine group was significantly lower than that in scald alone group at PIH 6, 48, and 72 (P<0.05). The serum content of creatinine of rats in scald+ carnitine group was significantly lower than that in scald alone group at PIH 12, 24, 48, and 72 (P<0.05). The serum content of urea nitrogen and creatinine of rats in scald alone group and scald+ carnitine group showed a trend of increase followed by a decrease, with the peak value at PIH 12. (3) The serum content of cystatin C of rats in scald alone group at PIH 6, 12, 24, 48, and 72 was (0.250±0.030), (0.330±0.070), (0.300±0.060), (0.240±0.060), and (0.190±0.030) mg/L, and the content at the first 4 time points were significantly higher than (0.170±0.020) mg/L of healthy control group (P<0.05). At PIH 24, the serum content of cystatin C of rats in scald+ carnitine group was (0.210±0.040) mg/L, which was significantly lower than that of scald alone group (P<0.05). The serum content of cystatin C of rats in scald alone group and scald+ carnitine group showed a trend of increase followed by a decrease, with the peak value at PIH 12. (4) The renal tissue of rats in healthy control group was almost normal, and the degree of renal tissue injury of rats in scald+ carnitine group was lighter than that in scald alone group at each time point after injury. At PIH 24, the renal tissue of rats in scald alone group showed extensive swelling of the renal tubular epithelial cells, vacuolar degeneration and necrosis, loss of brush borders, and nuclear shrinkage; more than 2/3 of the renal tubular cell nuclei disappeared, the tubular lumen was narrowed, necrotic exfoliated cells could be seen in the lumen, and edema and inflammatory cell infiltration could be seen in the renal interstitial. Compared with those of scald alone group, significantly reduced severity of edema and necrosis of renal tubular epithelial cells, as well as less inflammatory cell infiltration were observed in the renal tissue of rats in scald+ carnitine group. Conclusions: Early supplement of L-carnitine in severely scalded rats can reduce the damage of renal cells, accelerate the restoration of the content of total protein, albumin, urea nitrogen, creatinine, and cystatin C, thereby maintaining the stability of renal function metabolism level.

Carnitine for Body Composition in Hemodialysis Patients

Background: Authors and colleagues have continued clinical research for hemodialysis patients. Currently, a pilot study presents intervention of carnitine for changes of the body composition. Subjects and Methods: Subjects were six patients on hemodialysis with intervention of carnitine (group 1). Average data were 74.3 years, 65.4 kg, 22.6 in BMI. As levocarnitine, L-Cartin FF injection 1000 mg was administered three times a week for six months. Group 2 has six control patients for age-, sex-, body weight, BMI-matched (group 2). Body composition of muscle and fat tissues were measured by InBody 770 on 0 and 6 months. Results: In group 1, muscle volume and skeletal muscle showed increasing tendency without statistical significance. In contrast, there were significant decreases of body fat volume (22.3 kg vs 20.5 kg, 39.0% vs 35.8%) (p&lt;0.05). No significant differences were found in hemoglobin, total protein, albumin and Cardio-Thoracic Ratio (CTR) of chest X-ray. Group 2 showed no significant changes. Discussion and Conclusion: Hemodialysis patients often have muscular reduction. Previous reports showed improved lean body mass by carnitine administration, which may support our result. These results from current pilot study would be expected to become useful reference data in the pathophysiological investigation in patients on hemodialysis.

L-Carnitine Improves Postoperative Liver Function in Hepatectomized Patients.

The effect of perioperative treatment with l-carnitine in hepatectomized patients is unclear. The objective of the current study is to evaluate the short-term outcomes after liver cancer surgery in patients treated with l-carnitine compared with nontreated patients. Patients with primary liver malignancies scheduled to undergo a hepatectomy were randomly assigned to receive either perioperative treatment with l-carnitine (carnitine group) or usual intake (control group). The primary endpoint of this study was the short-term outcome after liver surgery. The study participants were randomly assigned into 2 groups: 106 patients in the control group and 102 patients in the perioperative l-carnitine supplementation group. The restoration of serum ammonia levels, prothrombin time, and peripheral neutrophil count at 3 days after the operation was significantly faster in the carnitine group than in the control group. Fewer patients in the carnitine group developed grade B posthepatic liver failure, according to the grading system of the International Study Group of Liver Surgery, than patients in the control group (20% vs 76%). The length of hospitalization was significantly shorter in patients in the carnitine group than in those in the control group. We found that perioperative treatment with l-carnitine was significantly better than ordinary treatment in reducing postoperative serum ammonia levels, suggesting that l-carnitine may serve as a pivotal regulator of liver injury and repair and result in shorter postoperative hospitalization (ClinicalTrials.gov trial registration no. NCT03021876).

Oolong Tea Extract and Citrus Peel Polymethoxyflavones Reduce Transformation of l-Carnitine to Trimethylamine-N-Oxide and Decrease Vascular Inflammation in l-Carnitine Feeding Mice.

Carnitine, a dietary quaternary amine mainly from red meat, is metabolized to trimethylamine (TMA) by gut microbiota and subsequently oxidized to trimethylamine-N-oxide (TMAO) by host hepatic enzymes, flavin monooxygenases (FMOs). The objective of this study aims to investigate the effects of flavonoids from oolong tea and citrus peels on reducing TMAO formation and protecting vascular inflammation in carnitine-feeding mice. The results showed that mice treated with 1.3% carnitine in drinking water significantly (p < 0.05) increased the plasma levels of TMAO compared to control group, whereas the plasma TMAO was remarkedly reduced by flavonoids used. Meanwhile, these dietary phenolic compounds significantly (p < 0.05) decreased hepatic FMO3 mRNA levels compared to carnitine only group. Additionally, oolong tea extract decreased mRNA levels of vascular inflammatory markers such as tissue necrosis factor-alpha (TNF-α), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Polymethoxyflavones significantly lowered the expression of VCAM-1 and showed a decreasing trend in TNF-α and E-selectin mRNA expression compared to the carnitine group. Genus-level analysis of the gut microbiota in the cecum showed that these dietary phenolic compounds induced an increase in the relative abundances of Bacteroides. Oolong tea extract-treated group up-regulated Lactobacillus genus, compared to the carnitine only group. Administration of polymethoxyflavones increased Akkermansia in mice.

Cardiovascular Disease Protective Effect of Allicin Through Gut Microbiota Modulation (FS07-08-19)

ObjectivesRed meat consumption can promote atherosclerosis since the gut microbiota can metabolize L-carnitine from meat into trimethylamine N-oxide (TMAO) which is a causative risk for cardiovascular disease. Garlic has long been associated with health benefits. Allicin is a major bioactive compound typically found in blend fresh garlic. It possesses the antibacterial, anti-oxidant, and cholesterol-lowering effects. The aim of this study is to investigate the effect allicin on the gut microbiota and its metabolites on cardiovascular disease by using the long-term carnitine treatment ApoE (-/-) mice model. Methods8-week old male ApoE (-/-) mice were divided into 4 groups: (1) Control, (2) 1.3% Carnitine, (3) Allicin (10 mg/kg), and (4) 1.3% Carnitine + Allicin (10 mg/kg). After 15 weeks, we performed the carnitine challenge test by oral gavage of d9-carnitine to evaluate the TMAO production ability of the gut microbiota. The serum was analyzed for carnitine, trimethylamine (TMA) and TMAO levels by using LC-MS/MS. Other biochemistry was checked by an automatic blood analyzer. Morphological changes of aortic plaque formation were observed using oil red staining. The gut microbiome was analyzed by using 16S rDNA amplicon sequencing in Illumina Miseq platform. ResultsThe results showed that allicin supplementation in the carnitine group exhibited the reduction of aortic lesion up to 34.2% as compared with carnitine group without allicin supplementation (P < 0.01). The carnitine challenge test indicated the d9-TMAO level of carnitine with allicin supplementation group tend to be reduced compared with carnitine-fed mice. Principal coordinate analysis of the feces microbiota composition was significantly different (ADONIS: P < 0.001) for each group. The linear discriminant analysis (LDA) effect size (LEfSe) results demonstrated that Akkermansia was enriched in the carnitine-fed group. In contrast, the carnitine-fed mice with allicin supplementation were abundance with Lachnospiraceae. ConclusionsAllicin may exhibit the cardiovascular disease protective effect through modulation of gut microbiota-TMAO-atherosclerosis pathway. Funding SourcesMOST 107-2321-B-002 -017 -. Supporting Tables, Images and/or Graphs▪▪▪

Speculation of the Cytotoxic Effect of Cisplatin Either Necrosis or Apoptosis and the Possible Antagonist Protective Role of Acetyl L-Carnitine, In vitro Study

Background: Cisplatin is one of mostly used chemotherapeutic drugs. Eventhough, cisplatin drawbacks limit its use. Acetyl L- Carnitine is a neuro-protective and anti-oxidant agents as well as it has anti-apoptotic properties.Aim of the study: this study was designed to evaluate the mechanism of Cisplatin to influence tissue in the pathway of apoptosis or the pathway of necrosis and the protective role of Acetyl-L-Carnitine against cytotoxicity induced by Cisplatin in the dental pulp. Material and methods: Total of 30 male albino rats (250-300 grams) were divided equally into three groups where saline was given to the control group (Group I), Cisplatin was injected into group II the (Cisplatin Group), and L- Carnitine was given to the Group III (L- Carnitine group + Cisplatin) before the injection of Cisplatin. After sacrificing the rats one week later, the extraction and preparation of their jaws were carried out in order to examine their dental pulp histologically histologically and immunohistochemically. Results: The light microscopic results showed degeneration in the dental pulp tissue of group II animals represented by cytoplasmic vacuolization, idiopathic calcification, hyaline and fatty degeneration. While group III showed normal dental pulp tissues with dilated blood vessels. Immunohistochemical examination showed significant differences in group II when compared to control group for both Bax (p=0.0002) and TNF-α (p=0.0029). No significant differences appeared in group III when compared to control group for both Bax and TNF-α. Significant differences were evident in comparison between group II and group III for both Bax (p=0.0015) and TNF-α (p=0.000001).Conclusion: Cisplatin has a devastating effect on dental pulp tissues via both the apoptosis and necrosis pathways. L-Carnitine had a protective effect against the cytotoxicity of Cisplatin.

Comparing the protective effect of L-carnitine, chromium, and vitamin D with metformin on kidney parameters, lipid profiles, and antioxidant indices in streptozotocin-diabetic rats

Introduction: Type 1 diabetes mellitus is believed to be caused by decline of insulin secretion because of destruction of the pancreatic β cell, which is characterized with symptoms such as hyperglycemia, polyuria, polydipsia, weight loss, and other symptoms. Due to the lack of sufficient data about protective effect of L -carnitine, chromium, and vitamin D as compared with metformin on biochemical indices in streptozotocin-diabetic rats, it seems necessary to determine the effects of these medications on diabetes. Materials and Methods: Sixty Wistar rats were divided into 12 diabetic and healthy groups, and 10 groups of witness, metformin )150 mg/kg(, L -carnitine )200 mg/kg(, and chromium )2 mg/kg(, vitamin D (0.06 µg) and a group treated with simultaneous combined therapy of L -carnitine, chromium, and vitamin D. Diabetes mellitus was induced by streptozotocin. Rats with glucose levels of more than 300 mg/dL were considered as diabetic. After 30 days of treatment, the serum concentrations of renal parameters, lipid profile, malondialdehyde, and activity of superoxide dismutase were measured in the studied groups. Results: Malondialdehyde had a significant decrease in all diabetic groups but an increase in nondiabetic metformin and L -carnitine groups (P L -carnitine, chromium, and vitamin D (P L -carnitine, chromium treatment, and combined group showed a significant decrease (P L -carnitine, chromium, and vitamin D such as metformin seemed appropriate, which had the hypoglycemic, antilipidemic, and antioxidant effects.

Impact of pretreatment with carnitine and tadalafil on contrast-induced nephropathy in CKD patients

Objective: The present study assesses whether phosphodiesterase type 5 (PDE-5) inhibitor or carnitine exert nephroprotective effects against clinical contrast-induced nephropathy (CIN).Materials and Methods: The present study consisted of three groups of CKD patients. The first group was control group, who were treated with N-acetyl-L-cysteine 1 day before and on the day of radiocontrast administration. The second one was carnitine group, where the patients were infused with carnitine over 10 min 2 h prior to the radiocontrast administration and 24 h post CT. The third one was PDE-5 inhibitor group, where patients were given tadalafil 2 h prior to the administration of the radiocontrast and in the subsequent day. Urine and blood samples were collected before and at the following time sequence: 2, 6, 12, 24, 48, and 120 h after the contrast administration, for creatinine and NGAL determination.Results: Pretreated with N-acetyl-L-cysteine prior to administration of contrast media (CM) to CKD patients caused a significant increase in urinary but not of plasma neutrophil gelatinase-associated lipocalin (NGAL) and serum creatinine (SCr). In contrast, pretreatment with carnitine prevented the increase in urinary NGAL and reduced SCr below basal levels. Similarly, tadalafil administration diminished the elevation of CM-induced urinary NGAL.Conclusions: These results indicate that carnitine and PDE-5 inhibitors may comprise potential therapeutic maneuvers for CIN.

Atorvastatin and carnitine combination versus atorvastatin alone impacts on the lipid profile of haemodialyzed patients: A randomised clinical trial

Introduction: Dyslipidemia is one of the most common problems in hemodialysis patients and healthcare system. Some studies have suggested the use of carnitine in the treatment of dyslipidemia in hemodialysis patients. This study was carried out aiming to evaluate the effect of atorvastatin and carnitine combination versus atorvastatin alone on the lipid profile of hemodialyzed patients. Methods: In this clinical trial, 50 hemodialysis patients referred to the educational centres of Tabriz University of Medical Sciences, Tabriz, Iran, for haemodialysis were enrolled. Patients were randomly assigned into two groups. In the first group, patients were treated with carnitine (1000 mg three times daily) and atorvastatin (10-80 mg/day based on the baseline lipid profile of the patients) and in the second group, the patients were treated with atorvastatin alone for six months. The levels of triglyceride (TG), cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and haemoglobin before and after intervention were compared. The side effects of carnitine administration were also evaluated. Results: Results showed that TG, cholesterol, and LDL levels were significantly lower in the carnitine group compared to those in the other group at the end of study (P &lt; 0.050). In addition, HDL and haemoglobin levels were significantly higher in the carnitine group in comparison to the other group (P &lt; 0.050). No major side effects of carnitine were observed among the patients. Conclusion: The use of carnitine plus atorvastatin combination is an effective and safe method in the treatment of dyslipidemia in patients undergoing hemodialysis without imposing significant side effects.