Carnitine and COVID-19 Susceptibility and Severity: A Mendelian Randomization Study

Background: Carnitine, a potential substitute or supplementation for dexamethasone, might protect against COVID-19 based on its molecular functions. However, the correlation between carnitine and COVID-19 has not been explored yet, and whether there exists causation is unknown.Methods: A two-sample Mendelian randomization (MR) analysis was conducted to explore the causal relationship between carnitine level and COVID-19. Significant single nucleotide polymorphisms from genome-wide association study on carnitine (N = 7,824) were utilized as exposure instruments, and summary statistics of the susceptibility (N = 1,467,264), severity (N = 714,592) and hospitalization (N = 1,887,658) of COVID-19 were utilized as the outcome. The causal relationship was evaluated by multiplicative random effects inverse variance weighted (IVW) method, and further verified by another three MR methods including MR Egger, weighted median, and weighted mode, as well as extensive sensitivity analyses.Results: Genetically determined one standard deviation increase in carnitine amount was associated with lower susceptibility (OR: 0.38, 95% CI: 0.19–0.74, P: 4.77E−03) of COVID-19. Carnitine amount was also associated with lower severity and hospitalization of COVID-19 using another three MR methods, though the association was not significant using the IVW method but showed the same direction of effect. The results were robust under all sensitivity analyses.Conclusions: A genetic predisposition to high carnitine levels might reduce the susceptibility and severity of COVID-19. These results provide better understandings on the role of carnitine in the COVID-19 pathogenesis, and facilitate novel therapeutic targets for COVID-19 in future clinical trials.

Correlation between serum carnitine level and Soluble Receptors for Advance Glycation End Products(sRAGE) in Clomiphene Citrate Resistant- PCOS Women

The most frequently diagnosed condition in women at the age of reproduction is the polycystic ovarian syndrome (PCOS).it could be related to a complex endocrine condition, due to its heterogeneity and uncertainty about its etiology, as the clinical highlights of PCOS incorporate those related to reproductive signs such as decreased frequency of ovulation, irregular menstrual cycles, decreased fertility. Carnitine plays a substantial role in weight loss, glucose tolerance, insulin function and fatty acid metabolism. Thus carnitine plays a crucial role in controlling obesity, insulin resistance, oxidative stress that are associated with PCOS .While, AGEs are a diverse group of reactive molecules that are formed endogenously by non-enzymatic reactions of carbonyl group of carbohydrates with free amino groups of proteins, nucleic acids or lipids. The soluble form of receptors of AGE (sRAGE) could play an important role in management obesity, insulin resistance, hyperandrogenism, oxidative stress which could be related to PCOS. This study was aimed to investigate serum levels of carnitine & soluble receptors for advanced glycation end products (sRAGE) in clomiphene resistant PCOS .Besides assessing the correlation between serum levels of carnitine ,as well as, soluble receptors of AGE with hormonal ( LH, FSH& Testosterone) and metabolic ( serum glucose , serum insulin & HOMA-IR) markers in these patients . The study included thirty women with clomiphene resistant PCOS and thirty apparently healthy women, as a control .In order to measure serum total carnitine and serum soluble receptor of advance glycation end product (sRAGE in PCOS and control groups. The results of our study have shown a decreased serum levels of total carnitine in PCOS group in comparison with control group (48.05 and 59.73 nmol/ml, respectively), but there was no significant elevation in serum levels of sRAGE in patients group as compared with control group .In addition to a significant correlation between serum total carnitine and serum sRAGE levels (r=0.45, P-value=0.03). In conclusion serum total carnitine level was low in Clomiphene resistant-PCOS patients in comparison with control group. Although, sRAGE levels in clomiphene resistant- PCOS patients were not significantly different from the age and BMI-matching controls, but a significant correlation between serum total carnitine and sRAGE was detected. Key words: Poly cystic ovarian syndrome, soluble receptor of advance glycation end products (sRAGE) , SerumTotal Carnitine

The Association Between Serum Carnitine Level, Glucose Regulation, Body Fat and Nutrient Intake in Diabetic Individuals

Carnitine (β-hydroxy-γ-trimethyl amino butyrate) is, a vitamin-like substance carrying long-chain fatty acids into the mitochondrial matrix. Due to its effect in energy metabolism, carnitine plays an important role in controlling diabetes and its complications. Studies on this topic have often focused on carnitine supplementation. This study was planned to investigate the relationship between serum carnitine level, glucose regulation and body fat in diabetic patients. A total of 64 people between the ages of 30-5, 32 patients with type 2 diabetes and 32 healthy subjects, were included in the study. Individual lipid profiles, glucose, insulin and serum carnitine levels were analyzed, anthropometric measurements were taken and 24-hour recall food consumption was recorded. As a result, blood glucose, insulin, triglyceride, VLDL-C, HDL-C and HOMA-IR were found to be higher in diabetic individuals than healthy group (p<0,05). Serum carnitine levels were found to be significantly lower in diabetic male (50,6±20,83 nmol/mL) than in healthy male (59,5±17,25 nmol/mL)(p<0,05). This difference was not statistically significant among female (p>0,05). It has been observed that intake of energy and macronutrients of diabetic individuals is generally lower than that of healthy individuals. Serum carnitine level was positively associated with polyunsaturated fatty acids and omega-6 fatty acid intake in male in the healthy group showed a negative correlation with fiber intake in female in the healthy group (p<0,05). There were negative correlations between serum carnitine level with body weight, body mass index and body fat mass in female in the healthy group (p<0,05). Individuals with diabetes are predisposed to dyslipidemia and insulin resistance. As a result; food consumption, and body fat affect individuals’ serum carnitine levels in type-2 diabetes. Since there is not enough study evaluating the relationship between anthropometric measurements of individuals and serum carnitine levels, it is thought that this result will guide future studies.

An Examination of Serum Acylcarnitine and Amino Acid Profiles at Different Time Point of Ketogenic Diet Therapy and Their Association of Ketogenic Diet Effectiveness

Background: This study aimed to identify metabolic parameters at different time points of ketogenic diet therapy (KDT) and investigate their association with response to KDT in pediatric drug-resistant epilepsy (DRE). Methods: Prospectively, twenty-nine patients (0.67~20 years old) with DRE received classic ketogenic diet with non-fasting, gradual KD initiation protocol (GRAD-KD) for 1 year were enrolled. A total of 22 patients remaining in study received blood examinations at baseline, 3rd, 6th, 9th, and 12th months of KDT. β-hydroxybutyrate, free carnitine, acylcarnitines, and amino acids were compared between responders (seizure reduction rate ≥ 50%) and non-responders (seizure reduction rate < 50%) to identify the effectiveness of KDT. Results: The 12-month retention rate was 76%. The responders after 12 months of KDT were 59% (13/22). The free carnitine level decreased significantly at 9th months (p < 0.001) but increased toward baseline without symptoms. Propionyl carnitine (C3), Isovaleryl carnitine (C5), 3-Hydroxyisovalerylcarnitine (C5:OH) and methylmalonyl carnitine (C4-DC) decreased but 3-hydroxybutyrylcarnitine (C4:OH) increased significantly at 12th months of KDT. The glycine level was persistently higher than baseline after KDT. KDT responders had lower baseline C3 and long-chain acylcarnitines, C14 and C18, as well as lower C5, C18, and leucine/isoleucine. Conclusions: KDT should be avoided in patients with non-ketotic hyperglycemia. Routine carnitine supplementation is not recommended because hypocarnitinemia was transient and asymptomatic during KDT. Better mitochondrial βoxidation function associates with greater KDT response.

Evaluation of Serum Level of Carnitine in Children with Acute Pyelonephritis (APN) Compared to Healthy Children

Aim: This cross sectional case-control study evaluated the serum carnitine level in children with urinary tract infection (UTI). Background: Acute pyelonephritis (APN), is a common bacterial infection of upper urinary tract in children which may also lead to renal damage and tubular atrophy. Activation of inflammatory mediator bedside alterations in the cytokines and generation of reactive oxygen species (ROS) play a striking role in the development of tissue damage after pyelonephritis. L-carnitine as one of the most potent natural antioxidant agent by inhibition of lipid peroxidation may protect cells and tissues from damage. Methods: A total of 30children with UTI (as a case group) and 30 healthy children (as a control group) which matched as age and sex were enrolled in this study. All children were evaluated and compared as age, sex, weight, body mass index (BMI) and serum carnitine level together. Serum carnitine level wasdetermined using serum carnitine ELISA kit. Results: Demographic and clinical data such as age, sex, weight and BMI were not statistically significant between two groups. The serum carnitine levels were significantly lower in case group with UTI than control group. Mean serum carnitine concentration in the case group and in control group was 36.56 ± 9.87 μmol/l and 62.8±21.35 respectively (P = 0.001). Conclusion: According to our study, it could be concluded that low serum L-carnitine level is linked to UTI in children. Therefore, further studies are needed to confirm our results.

The role of rabbit seminal plasma natural antioxidants in the realization of spermatozoid activity after ionizing irradiation

Aim. To investigate the effects of X-rays on the content of rabbit seminal plasma L-carnitine and α-tocopherol, as well as physiological parameters of spermatozoid in 10, 30 and 90 days after whole body irradiation of animals in the dose range of 0.1–2.0 Gy. Methods. White rabbits-males Soviet Shinshila were irradiated by X-rays. Physiological parameters of sperm were evaluated by light microscopy, and the content of natural antioxidants was determined using liquid chromatograph “Agilent 1200”. Results. It was shown that low doses of ionizing radiation (0.1 Gy and 0.5 Gy) in 10 days after irradiation lead to the increase of the L-carnitine level in seminal plasma, whereas at 1.0 Gy and 2.0 Gy its concentration decreases. In additional, there is a decrease in the seminal plasma α-tocopherol content with a minimum of 2.0 Gy, although a dose of 0.1 Gy dose not cause changes in the index. The L-carnitine level is no longer different from the control for a dose 0.1 Gy in one month after rabbit irradiation, while the α-tocopherol concentration continues to decrease. Conclusions. The increasing of L-carnitine level in the rabbit’s seminal plasma at 0.1 Gy and 0.5 Gy contributes to increased motility and a radio-stimulating effect on sperm. Radiation-induced depletion of the α-tocopherol pool in semen disappears at a later period. Keywords: ionizing radiation, rabbits, seminal plasma, natural antioxidants

Usefulness of Carnitine Supplementation for the Complications of Liver Cirrhosis

Carnitine is a vitamin-like substance that regulates lipid metabolism and energy production. Carnitine homeostasis is mainly regulated by dietary intake and biosynthesis in the organs, including the skeletal muscle and the liver. Therefore, liver cirrhotic patients with reduced food intake, malnutrition, biosynthetic disorder, and poor storage capacity of carnitine in the skeletal muscle and liver are more likely to experience carnitine deficiency. In particular, liver cirrhotic patients with sarcopenia are at a high risk for developing carnitine deficiency. Carnitine deficiency impairs the important metabolic processes of the liver, such as gluconeogenesis, fatty acid metabolism, albumin biosynthesis, and ammonia detoxification by the urea cycle, and causes hypoalbuminemia and hyperammonemia. Carnitine deficiency should be suspected in liver cirrhotic patients with severe malaise, hepatic encephalopathy, sarcopenia, muscle cramps, and so on. Importantly, the blood carnitine level does not always decrease in patients with liver cirrhosis, and it sometimes exceeds the normal level. Therefore, patients with liver cirrhosis should be treated as if they are in a state of relative carnitine deficiency at the liver, skeletal muscle, and mitochondrial levels, even if the blood carnitine level is not decreased. Recent clinical trials have revealed the effectiveness of carnitine supplementation for the complications of liver cirrhosis, such as hepatic encephalopathy, sarcopenia, and muscle cramps. In conclusion, carnitine deficiency is not always rare in liver cirrhosis, and it requires constant attention in the daily medical care of this disease. Carnitine supplementation might be an important strategy for improving the quality of life of patients with liver cirrhosis.

P1588CAN L-CARNITINE SUPPLEMENTATION IMPROVE CARDIOPULMONARY FUNCTION? A RANDOMIZED CONTROLLED TRIAL IN HEMODIALYSIS PATIENTS

Background and Aims It is well known that L-Carnitine is a cardioprotective agent, which balances cardiac energy metabolism, by promoting mitochondrial β-oxidation and facilitating transport of long chain fatty acids into the mitochondrial matrix. It has been shown that L-Carnitine level in plasma and tissue is lower in hemodialysis patients and they may lose the benefits of this substance. As far as our knowledge, the effect of L-Carnitine on cardiopulmonary function has not been evaluated by ergospirometry up to now. The aim of this randomized clinical trial was to assess the effects of L-carnitine supplementation on cardiopulmonary Function in hemodialysis patients through ergospirometry. Method This randomized clinical trial was conducted on 46 chronic hemodialysis patients. The patients were divided into two groups. In both groups ergospirometry parameters (VE Max, VO2-Max, VCO2 Max, AT, VE/VCO2 Slope) were recorded for a 3-month period. During this period, one group received L-Carnitine at doses of 2 gr/day orally and the other group received only placebo. After three months, all of the mentioned parameters were rechecked and statistical analysis performed by SPSS software. Results Only CRP was different between the two groups increasing in placebo group significantly after 3 months (P = 0.018). No significant difference was detected in Cardiopulmonary factors. In terms of ergospirometry factors, PET-CO2 was the only parameter significantly increased in the treatment group (P = 0.026). Conclusion The present results indicate that L-Carnitine can improve cardiopulmonary function among hemodialysis patients.