Oral Carnitine Supplementation Research Articles

Oral carnitine supplementation reduces body weight and insulin resistance in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial.

Oral carnitine supplementation reduces body weight and insulin resistance in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial.

Expression of concern: Oral carnitine supplementation influences mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial and The effects of coenzyme Q10 supplementation on gene expression related to insulin, lipid and inflammation in patients with polycystic ovary syndrome

Expression of concern: Oral carnitine supplementation influences mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial and The effects of coenzyme Q10 supplementation on gene expression related to insulin, lipid and inflammation in patients with polycystic ovary syndrome

Effect of Carnitine Supplementation in Pediatric Patients with Left Ventricular Dysfunction.

Carnitine is an essential amino acid involved in transporting fatty acids across the mitochondrial membrane. Fatty acids are a primary source of energy for the myocardium. Studies in adults demonstrated decreased carnitine levels in the ischemic myocardium, but subsequent exogenous carnitine supplementation showed improvement of myocardial metabolism and left ventricular function. However, only limited data regarding carnitine are available in pediatrics. A single-center retrospective, paired data study was conducted. Patients < 18years, left ventricular ejection fraction (LVEF) < 55% by echocardiography, and had received at least 7days of oral or intravenous carnitine supplementation between January 2018 and March 2021 are included in the study. Several endpoints and covariates were collected for each patient: before, one week after, one month after, and 6months after carnitine supplementation. Univariate analysis consisted of an analysis of variance (ANOVA), followed by an analysis of covariance (ANCOVA) to model LVEF while adjusting for other variables. 44 patients included in the final analyses. LVEF significantly improved from 50.5 to 56.6% (p < 0.01). When LVEF was adjusted for other interventions (mechanical ventilation, afterload reduction, diuretic therapy, spironolactone), the estimated means demonstrated a significant increase from 45.7 to 58.0% (p < 0.01). Free carnitine level increased significantly (p = 0.03), and N-terminal-pro-brain natriuretic peptide (p = 0.03), creatinine (p < 0.01), and lactate (p < 0.01) all significantly decreased over the study period. Carnitine supplementation in pediatric patients with left ventricular systolic dysfunction may be associated with an increase in LVEF and improvement in laboratory markers of myocardial stress and cardiac output.

Change in Anemia by Carnitine Supplementation in Patients Undergoing Peritoneal Dialysis: A Retrospective Observational Study.

Background: Carnitine supplementation improves various dialysis-related symptoms including erythropoietin-resistant anemia in patients who are undergoing hemodialysis. However, the utility of carnitine supplementation in patients who are undergoing peritoneal dialysis (PD) is not fully understood.Methods: Thirteen patients undergoing PD [mean age: 54.2 ± 14.8 years, males: 9/13 (69%)] administered oral carnitine supplementation (mean dose: 9.1 ± 3.3 mg/kg/day) for 4–6 months were retrospectively investigated. Changes in serum carnitine levels and other clinical variables including the erythropoietin resistance index (ERI) were analyzed after carnitine supplementation.Results: Carnitine supplementation increased serum total carnitine (48.5 ± 10.2 vs. 130.1 ± 37.2 μmol/L, P < 0.01), free carnitine (31.1 ± 8.3 vs. 83.1 ± 24.6 μmol/L, P < 0.01), and acyl carnitine (17.4 ± 2.8 vs. 46.9 ± 13.8, P < 0.01) levels. The acyl carnitine/free carnitine ratio was not affected (0.6 ± 0.1 vs. 0.6 ± 0.1, P = 0.75). Although the mean ERI was not affected by carnitine supplementation [13.7 ± 4.7 vs. 11.6 ± 3.4 IU/kg/(g/dL)/week, P = 0.28], the ERI change rate was significantly decreased (1.00 ± 0.00 vs. 0.87 ± 0.11, P < 0.01).Conclusion: Carnitine supplementation may improve erythropoietin resistance in patients who are undergoing PD.

Beneficial effects of levo-carnitine on lipid metabolism and cardiac function in neonatal streptozotocin rat model of diabetes

Levo-carnitine (L-carnitine) facilitates the transport of long chain fatty acyl co-enzyme A (CoA) across the mitochondrial membrane for eventual oxidation and energy production. Carnitine deficiency results in free fatty acid accumulation and contributes to cardiovascular complications in experimental diabetes. In this condition, oral carnitine supplementation provides cardio-protection by its various metabolic effects. The beneficial effects of six weeks treatment with L-carnitine (600 mg/kg day orally) were studied in neonatal streptozotocin (STZ) diabetic rats. STZ (90 mg/kg) was administered to five day old rats and after fourteen weeks of STZ administration, the rats showed hyperglycemia, hyperinsulinemia, hypercholesterolemia, hypertriglyceridemia and associated cardiac defects like hypertension and bradycardia. L-carnitine treatment for six weeks after induction of diabetes and associated complications significantly lowered cholesterol and triglyceride levels and normalized blood pressure and heart rate; however the treatment was not found to produce beneficial effects against hyperglycemia and hyperinsulinemia in diabetic rats. The L-carnitine treatment may have fulfilled the carnitine deficiency and have improved the lipid metabolism and subsequently the cardiac function in diabetic rats. The study suggest that long term treatment with L-carnitine not only prevents but also partially reverses the diabetes-associated lipid metabolism and cardiac function abnormalities in neonatal STZ diabetic rats.

Oral carnitine supplementation influences mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial

Introduction: Limited data are available assessing the effects of oral carnitine supplementation on mental health parameters and biomarkers of oxidative stress of women with polycystic ovary syndrome (PCOS).This study was designed to determine the effects of oral carnitine supplementation on mental health parameters and biomarkers of oxidative stress in women with PCOS.Methods: In the current randomized, double-blind, placebo-controlled trial, 60 patients diagnosed with PCOS were randomized to take either 250 mg carnitine supplements (n = 30) or placebo (n = 30) for 12 weeks.Results: After 12 weeks’ intervention, compared with the placebo, carnitine supplementation resulted in a significant improvement in Beck Depression Inventory total score (−2.7 ± 2.3 versus −0.2 ± 0.7, p < 0.001), General Health Questionnaire scores (−6.9 ± 4.9 versus −0.9 ± 1.5, p < 0.001) and Depression Anxiety and Stress Scale scores (−8.7 ± 5.9 versus −1.2 ± 2.9, p = 0.001). In addition, changes in plasma total antioxidant capacity (TAC) (+84.1 ± 151.8 versus +4.6 ± 64.5 mmol/L, p = 0.01), malondialdehyde (MDA) (−0.4 ± 1.0 versus +0.5 ± 1.5 μmol/L, p = 0.01) and MDA/TAC ratio (−0.0005 ± 0.0010 versus +0.0006 ± 0.0019, p = 0.003) in the supplemented group were significantly different from the changes in these indicators in the placebo group.Conclusions: Overall, our study demonstrated that carnitine supplementation for 12 weeks among patients with PCOS had favorable effects on parameters of mental health and biomarkers of oxidative stress.

Enhancing Glycogen Resynthesis after Acute Oral Carnitine Supplementation in Human Exercised Skeletal Muscle

Enhancing Glycogen Resynthesis after Acute Oral Carnitine Supplementation in Human Exercised Skeletal Muscle

Oral carnitine supplementation reduces body weight and insulin resistance in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.

Limited data are available for evaluating the effects of oral carnitine supplementation on weight loss and metabolic profiles of women with polycystic ovary syndrome (PCOS). This study was designed to determine the effects of oral carnitine supplementation on weight loss, and glycaemic and lipid profiles in women with PCOS. In a prospective, randomized, double-blind, placebo-controlled trial, 60 overweight patients diagnosed with PCOS were randomized to receive either 250 mg carnitine supplements (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were obtained at the beginning and the end of the study to quantify parameters of glucose homoeostasis and lipid concentrations. At the end of the 12 weeks, taking carnitine supplements resulted in a significant reduction in weight (-2·7 ± 1·5 vs +0·1 ± 1·8 kg, P < 0·001), BMI (-1·1 ± 0·6 vs +0·1 ± 0·7 kg/m(2) , P < 0·001), waist circumference (WC) (-2·0 ± 1·3 vs -0·3 ± 2·0 cm, P < 0·001) and hip circumference (HC) (-2·5 ± 1·5 vs -0·3 ± 1·8 cm, P < 0·001) compared with placebo. In addition, compared with placebo, carnitine administration in women with PCOS led to a significant reduction in fasting plasma glucose (-0·38 ± 0·36 vs +0·11 ± 0·97 mmol/l, P = 0·01), serum insulin levels (-14·39 ± 25·80 vs +3·01 ± 37·25 pmol/l, P = 0·04), homoeostasis model of assessment-insulin resistance (-0·61 ± 1·03 vs +0·11 ± 1·43, P = 0·04) and dehydroepiandrosterone sulphate (-3·64 ± 7·00 vs -0·59 ± 3·20 μmol/l, P = 0·03). Overall, 12 weeks of carnitine administration in PCOS women resulted in reductions in weight, BMI, WC and HC, and beneficial effects on glycaemic control; however, it did not affect lipid profiles or free testosterone.

Acquired encephalopathy associated with carnitine deficiency after cefditoren pivoxil administration

We describe a 47-year-old woman who presented with palinopsia and subacute altered mental change after cefditoren pivoxil administration. The patient showed characteristic clinical manifestations of hypocarnitinemia, which affected her state of consciousness and she had radiologic findings that revealed metabolic encephalopathy with cytotoxic edema in the right occipital area and intracranial hemorrhages in right occipital and left frontal areas. Follow-up imaging after oral carnitine supplementation demonstrated complete resolution of the bilateral frontal subcortical T2 high-intensity lesions. Carnitine deficiency due to cefditoren pivoxil treatment may present as metabolic encephalopathy in adults. This possibility should be considered with the differential diagnosis of encephalopathies, and carnitine levels should be checked in patients treated with cefditoren pivoxil.

Transient carnitine transport defect with cholestatic jaundice: report of one case in a premature baby

Carnitine (β-hydroxy-γ-trimethylaminobutyric acid) is involved in the transport of long-chain fatty acids into the mitochondrial matrix and the removal of potentially toxic acylcarnitine esters. Transient carnitine transport defect is a rare condition in newborns reported in 1/90,000 live births. In this paper, we describe a case of transient carnitine transport defect found in a premature baby who had prolonged cholestatic jaundice and poor weight gain, and who responded dramatically to oral carnitine supplementation.

Effects of Exercise Intensity and Altered Substrate Availability on Cardiovascular and Metabolic Responses to Exercise After Oral Carnitine Supplementation in Athletes

The effects of 15 d of supplementation with L-carnitine L-tartrate (LC) on metabolic responses to graded-intensity exercise under conditions of altered substrate availability were examined. Fifteen endurance-trained male athletes undertook exercise trials after a 2-d high-carbohydrate diet (60% CHO, 25% fat) at baseline (D0), on Day 14 (D14), and after a single day of high fat intake (15% CHO, 70% fat) on Day 15 (D15) in a double-blind, placebo-controlled, pair-matched design. Treatment consisted of 3 g LC (2 g L-carnitine/d; n = 8) or placebo (P, n = 7) for 15 d. Exercise trials consisted of 80 min of continuous cycling comprising 20-min periods at each of 20%, 40%, 60%, and 80% VO2peak. There was no significant difference between whole-body rates of CHO and fat oxidation at any workload between D0 and D14 trials for either the P or LC group. Both groups displayed increased fat and reduced carbohydrate oxidation between the D14 and D15 trials (p < .05). During the D15 trial, heart rate (p < .05 for 20%, 40%, and 60% workloads) and blood glucose concentration (p < .05 for 40% and 60% workloads) were lower during exercise in the LC group than in P. These responses suggest that LC may induce subtle changes in substrate handling in metabolically active tissues when fatty-acid availability is increased, but it does not affect whole-body substrate utilization during short-duration exercise at the intensities studied.

Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control

In addition to its essential role in permitting mitochondrial import and oxidation of long chain fatty acids, carnitine also functions as an acyl group acceptor that facilitates mitochondrial export of excess carbons in the form of acylcarnitines. Recent evidence suggests carnitine requirements increase under conditions of sustained metabolic stress. Accordingly, we hypothesized that carnitine insufficiency might contribute to mitochondrial dysfunction and obesity-related impairments in glucose tolerance. Consistent with this prediction whole body carnitine diminution was identified as a common feature of insulin-resistant states such as advanced age, genetic diabetes, and diet-induced obesity. In rodents fed a lifelong (12 month) high fat diet, compromised carnitine status corresponded with increased skeletal muscle accumulation of acylcarnitine esters and diminished hepatic expression of carnitine biosynthetic genes. Diminished carnitine reserves in muscle of obese rats was accompanied by marked perturbations in mitochondrial fuel metabolism, including low rates of complete fatty acid oxidation, elevated incomplete beta-oxidation, and impaired substrate switching from fatty acid to pyruvate. These mitochondrial abnormalities were reversed by 8 weeks of oral carnitine supplementation, in concert with increased tissue efflux and urinary excretion of acetylcarnitine and improvement of whole body glucose tolerance. Acetylcarnitine is produced by the mitochondrial matrix enzyme, carnitine acetyltransferase (CrAT). A role for this enzyme in combating glucose intolerance was further supported by the finding that CrAT overexpression in primary human skeletal myocytes increased glucose uptake and attenuated lipid-induced suppression of glucose oxidation. These results implicate carnitine insufficiency and reduced CrAT activity as reversible components of the metabolic syndrome.

Carbohydrate, Protein, and Fat Metabolism during Exercise after Oral Carnitine Supplementation in Humans

Twenty nonvegetarian active males were pair-matched and randomly assigned to receive 2 g of L-carnitine L-tartrate (LC) or placebo per day for 2 wk. Participants exercised for 90 min at 70% VO2max after 2 days of a prescribed diet (M +/- SD: 13.6 +/- 1.6 MJ, 57% carbohydrate, 15% protein, 26% fat, 2% alcohol) before and after supplementation. Results indicated no change in carbohydrate oxidation, nitrogen excretion, branched-chain amino acid oxidation, or plasma urea during exercise between the beginning and end of supplementation in either group. After 2 wk of LC supplementation the plasma ammonia response to exercise tended to be suppressed (0 vs. 2 wk at 60 min exercise, 97 +/- 26 vs. 80 +/- 9, and 90 min exercise, 116 +/- 47 vs. 87 +/- 25 micromol/L), with no change in the placebo group. The data indicate that 2 wk of LC supplementation does not affect fat, carbohydrate, and protein contribution to metabolism during prolonged moderate-intensity cycling exercise. The tendency toward suppressed ammonia accumulation, however, indicates that oral LC supplementation might have the potential to reduce the metabolic stress of exercise or alter ammonia production or removal, which warrants further investigation.

Metabolic profiling of PPARα −/− mice reveals defects in carnitine and amino acid homeostasis that are partially reversed by oral carnitine supplementation

Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a master transcriptional regulator of beta-oxidation and a prominent target of hypolipidemic drugs. To gain deeper insights into the systemic consequences of impaired fat catabolism, we used quantitative, mass spectrometry-based metabolic profiling to investigate the fed-to-fasted transition in PPARalpha(+/+) and PPARalpha(-/-) mice. Compared to PPARalpha(+/+) animals, acylcarnitine profiles of PPARalpha(-/-) mice revealed 2- to 4-fold accumulation of long-chain species in the plasma, whereas short-chain species were reduced by as much as 69% in plasma, liver, and skeletal muscle. These results reflect a metabolic bottleneck downstream of carnitine palmitoyltransferase-1, a mitochondrial enzyme that catalyzes the first step in beta-oxidation. Organic and amino acid profiles of starved PPARalpha(-/-) mice suggested compromised citric acid cycle flux, enhanced urea cycle activity, and increased amino acid catabolism. PPARalpha(-/-) mice had 40-50% lower plasma and tissue levels of free carnitine, corresponding with diminished hepatic expression of genes involved in carnitine biosynthesis and transport. One week of oral carnitine supplementation conferred partial metabolic recovery in the PPARalpha(-/-) mice. In summary, comprehensive metabolic profiling revealed novel biomarkers of defective fat oxidation, while also highlighting the potential value of supplemental carnitine as a therapy and diagnostic tool for metabolic disorders.

Oral carnitine supplementation improves dyslipidemia in hemodialysis patients

Oral carnitine supplementation improves dyslipidemia in hemodialysis patients

Legal pre-event nutritional supplements to assist energy metabolism

Physical training and proper nutrition are paramount for success in sport. A key tissue is skeletal muscle, as the metabolic pathways that produce energy or ATP allow the muscles to complete the many activities critical to success in sport. The energy-producing pathways must rapidly respond to the need for ATP during sport and produce energy at a faster rate or for a longer duration through training and proper nutrition which should translate into improved performance in sport activities. There is also continual interest in the possibility that nutritional supplements could further improve muscle metabolism and the provision of energy during sport. Most legal sports supplements do not improve performance following oral ingestion. However, three legal supplements that have received significant attention over the years include creatine, carnitine and sodium bicarbonate. The ingestion of large amounts of creatine for 4-6 days increases skeletal muscle creatine and phosphocreatine contents. The majority of the experimental evidence suggests that creatine supplementation can improve short-term exercise performance, especially in sports that require repeated short-term sprints. It may also augment the accretion of skeletal muscle when taken in combination with a resistance-exercise training programme. Supplementary carnitine has been touted to increase the uptake and oxidation of fat in the mitochondria. However, muscle carnitine levels are not augmented following oral carnitine supplementation and the majority of well-controlled studies have reported no effect of carnitine on enhancing fat oxidation, Vo(2max) or prolonged endurance exercise performance. The ingestion of sodium bicarbonate before intense exercise decreases the blood [H+] to potentially assist the efflux of H+ from the muscle and temper the metabolic acidosis associated with intense exercise. Many studies have reported performance increases in laboratory-based cycling tests and simulated running races in the field following sodium bicarbonate ingestion where the need for ATP from substrate phosphorylation is high. However, other studies have reported no benefit and the incidence of negative side effects is high.

Carnitine for the treatment of idiopathic asthenospermia: a randomized, double-blind, placebo-controlled trial

To determine the effect of oral carnitine supplementation on the semen parameters of men with idiopathic asthenospermia. Prospective, randomized, double-blind placebo-controlled study. Academic tertiary referral centers. Male patients presenting with infertility and with sperm motility of 10%-50% were selected. Patients were randomized to 24-week treatment arms of oral carnitine (2,000 mg L-carnitine and 1,000 mg L-acetyl-carnitine per day) or placebo. Sperm motility and total motile sperm counts at baseline, 12 weeks, and 24 weeks. Seminal plasma and sperm free, acetyl, and total L-carnitine levels at baseline and at week 24. Twenty-one patients entered the study, with 12 patients in the carnitine arm and 9 in the placebo arm. There were no significant differences in baseline semen parameters between the carnitine and placebo arms. There was no statistically significant or clinically significant increase in motility or total motile sperm counts between baseline, 12 week, or 24 weeks in the carnitine or placebo arms. Carnitine supplementation demonstrated no clinically or statistically significant effect on sperm motility or total motile sperm counts in men with idiopathic asthenospermia.

Cardio-protective effects of carnitine in streptozotocin-induced diabetic rats

BackgroundStreptozotocin-induced diabetes (STZ-D) in rats has been associated with carnitine deficiency, bradycardia and left ventricular enlargement.AimThe purpose of this study was to determine whether oral carnitine supplementation would normalize carnitine levels and cardiac function in STZ-D rats.MethodsWistar rats (48) were made hyperglycemic by STZ at 26 weeks of age. Same age normal Wistar rats (24) were used for comparison. Echocardiograms were performed at baseline 2, 6, 10, and 18 weeks after STZ administration in all animals. HbA1c, serum carnitine and free fatty acids (FFA) were measured at the same times. Since STZ-D rats become carnitine deficient, 15 STZ-D rats received supplemental oral carnitine for 16 weeks.ResultsThe heart rates for the STZ-D rats (290 ± 19 bpm) were less than control rats (324 ± 20 bpm) (p < 0.05). After 4 weeks of oral carnitine supplementation, the serum carnitine and heart rates of the STZ-D rats returned to normal. Dobutamine stress increased the heart rates of all study animals, but the increase in STZ-D rats (141 ± 8 bpm) was greater than controls (79 ± 8 bpm) (p < 0.05). The heart rates of STZ-D rats given oral carnitine, however, were no different than controls (94 ± 9 bpm). The left ventricular mass/body weight ratio (LVM/BW) in the diabetic animals (2.7 ± 0.5) was greater than control animals (2.2 ± 0.3) (p < 0.05) after 18 weeks of diabetes. In contrast, the LVM/BW (2.3 ± .2) of the STZ-D animals receiving supplemental carnitine was the same as the control animals at 18 weeks.ConclusionThus, supplemental oral carnitine in STZ-D rats normalized serum carnitine, heart rate regulation and left ventricular size. These findings suggest a metabolic mechanism for the cardiac dysfunction noted in this diabetic animal model.

Oral carnitine supplementation increases sperm motility in asthenozoospermic men with normal sperm phospholipid hydroperoxide glutathione peroxidase levels

To clarify the role of carnitine supplementation in idiopathic asthenozoospermia and to look for a rationale for its use in asthenozoospermic patients. Blind clinical study. Academic. Thirty asthenozoospermic patients divided in two groups according to phospholipid hydroperoxide glutathione peroxidase (PHGPx) levels. Placebo for 3 months, then oral L-carnitine (2 g/day) for 3 months; semen samples were collected at baseline, after placebo, after carnitine administration, and again after 3 months with no drugs. Evaluation of seminal parameters and determination of seminal PHGPx levels, measured as rescued activity. When asthenozoospermic subjects were divided in two groups on the basis of PHGPx levels, we observed an improvement of mean sperm motility only in the group of patients with normal PHGPx levels. Phospholipid hydroperoxide glutathione peroxidase has an important role in male infertility, and carnitine treatment might improve sperm motility in the presence of normal mitochondrial function.

Carnitine transport: pathophysiology and metabolism of known molecular defects.

Early-onset dilatative and/or hypertrophic cardiomyopathy with episodic hypoglycaemic coma and very low serum and tissue concentrations of carnitine should alert the clinician to the probability of the plasmalemmal high-affinity carnitine transporter defect. The diagnosis can be established by demonstration of impaired carnitine uptake in cultured skin fibroblasts or lymphoblasts and confirmed by mutation analysis of the human OCTN2 gene in the affected child and obligate heterozygote parents. The institution of high-dose oral carnitine supplementation reverses the pathology in this otherwise lethal autosomal recessive disease of childhood, and carnitine therapy from birth in prospectively screened siblings may altogether prevent the development of the clinical phenotype. Heterozygotes may be at risk for cardiomyopathy in later adult life, particularly in the presence of additional risk factors such as hypertension and competitive pharmacological agents. OCTN2 belongs to a family of organic cation/carnitine transporters that function primarily in the elimination of cationic drugs and other xenobiotics in kidney, intestine, liver and placenta. The high- and low-affinity human carnitine transporters, OCTN2 and OCTN1, are multifunctional polyspecific organic cation transporters; therefore, defects in these transporters may have widespread implications for the absorption and/or elimination of a number of key pharmacological agents such as cephalosporins, verapamil, quinidine and valproic acid. A third organic/cation carnitine transporter with high specificity for carnitine, Octn3, has been cloned in mice. The juvenile visceral steatosis (jvs) mouse serves as an excellent clinical, biochemical and molecular model for the high-affinity carnitine transporter OCTN2 defect and is due to a spontaneous point mutation in the murine Octn2 gene on mouse chromosome 11, which is syntenic to the human locus at 5q31 that harbours the human OCTN2 gene.