PMID 32359762 Effects of l-carnitine supplementation on weight loss and body composition: A systematic review and meta-analysis of 37 randomized controlled clinical trials with dose-response analysis Meta-analysis · Clin Nutr ESPEN, 2020 37 randomized trials, 2,292 people - weight -1.21 kg, no significant difference in waist or body fat percentage, maximal at 2,000 mg/day.
Key summary
A meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. pooling as many randomized trials as possible on L-carnitine's effect on weight and body composition, and the first to add a dose-response analysis. Searching through January 2019, it included 37 trials (2,292 people). Weight differed by -1.21 kg (95% CI -1.73 to -0.68), BMI by -0.24 kg/m2 (95% CI -0.37 to -0.10), and fat mass by -2.08 kg (95% CI -3.44 to -0.72), with no significant difference in waist circumference or body fat percentage. Only the effect on weight was confirmed among high-quality trials. Weight reduction showed a non-linear dose-response relationship peaking at 2,000 mg/day. The authors concluded the effect was modest, especially in adults with overweight or obesity, and declared no conflict of interest.
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BACKGROUND AND AIM: Clinical evidence which investigated the effects of l-carnitine, a vitamin-like substance, on weight loss had led to inconsistent results. This study therefore aimed to examine the effect of l-carnitine supplementation on body weight and composition by including the maximum number of randomized controlled trials (RCTs) and to conduct a dose-response analysis, for the first time. METHODS AND RESULTS: Online databases were searched up to January 2019. In total, 37 RCTs (with 2292 participants) were eligible. Meta-analysis showed that l-carnitine supplementation significantly decreased body weight [Weighted mean difference (WMD) = -1.21 kg, 95% confidence interval (CI): -1.73, -0.68; P < 0.001], body mass index (BMI) (WMD = -0.24 kg/m2, 95% CI: -0.37, -0.10; P = 0.001), and fat mass (WMD = -2.08 kg, 95% CI: -3.44, -0.72; P = 0.003). No significant effect was seen for waist circumference (WC) and body fat percent. The meta-analysis of high-quality RCTs only confirmed the effect on body weight. A non-linear dose-response association was seen between l-carnitine supplementation and body weight reduction (P < 0.001) suggesting that ingestion of 2000 mg l-carnitine per day provides the maximum effect in adults. This association was not seen for BMI, WC and body fat percent. CONCLUSIONS: l-carnitine supplementation provides a modest reducing effect on body weight, BMI and fat mass, especially among adults with overweight/obesity. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 27335245 The effect of (L-)carnitine on weight loss in adults: a systematic review and meta-analysis of randomized controlled trials Meta-analysis · Obes Rev, 2016 Nine trials, 911 people - weight -1.33 kg, with the loss shrinking over longer use (p=0.002).
Key summary
A systematic review and meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of randomized carnitine trials on adult weight loss. Searching PubMed, Embase, CochraneAn international network that rigorously reviews and synthesizes evidence., and other sources, it included nine methodologically adequate trials (911 people). The carnitine groups lost more weight (-1.33 kg, 95% CI -2.09 to -0.57) and BMI (-0.47 kg/m2, 95% CI -0.88 to -0.05). Meta-regression on duration showed the size of the loss significantly decreased over time (p=0.002).
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This study provides a systematic review and meta-analysis of randomized controlled trials, which have examined the effect of the carnitine on adult weight loss. Relevant studies were identified by systematic search of PubMed, Embase, Cochrane Central Register of Controlled Trials and reference lists of relevant marker studies. Nine studies (total n = 911) of adequate methodological quality were included in the review. Trials with mean difference (MD) of 95% confidence interval (CI) were pooled using random effect model. Results from meta-analysis of eligible trials revealed that subjects who received carnitine lost significantly more weight (MD: -1.33 kg; 95% CI: -2.09 to -0.57) and showed a decrease in body mass index (MD: -0.47 kg m(-2) ; 95% CI: -0.88 to -0.05) compared with the control group. The results of meta-regression analysis of duration of consumption revealed that the magnitude of weight loss resulted by carnitine supplementation significantly decreased over time (p = 0.002). We conclude that receiving the carnitine resulted in weight loss. Using multiple-treatments meta-analysis of the drugs and non-pharmacotherapy options seem to be insightful areas for research. © 2016 World Obesity. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 11880112 Long-term administration of L-carnitine to humans: effect on skeletal muscle carnitine content and physical performance Clinical trial · Clin Chim Acta, 2002 Eight healthy men, 2 g twice a day for three months - no significant change in muscle carnitine, mitochondria, or exercise capacity.
Key summary
A trial giving eight healthy adult men 2 g of L-carnitine twice a day for three months, with muscle biopsies and exercise tests before, immediately after, and two months after stopping. The abstract mentions no placeboAn inert dummy treatment used as the comparison baseline. group. Total muscle carnitine went from 4.10 to 4.79 and then 4.19 µmol/g with no significant difference, and maximal oxygen uptake, maximal power, mitochondrial enzyme activity, and fiber composition were unchanged. The authors concluded that long-term oral use in healthy adults is not associated with a significant increase in muscle carnitine, mitochondrial proliferation, or physical performance.
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BACKGROUND: Long-term administration of high oral doses of L-carnitine on the skeletal muscle composition and the physical performance has not been studied in humans. METHODS: Eight healthy male adults were treated with 2 x 2 g of L-carnitine per day for 3 months. Muscle biopsies and exercise tests were performed before, immediately after, and 2 months after the treatment. Exercise tests were performed using a bicycle ergometer for 10 min at 20%, 40%, and 60% of the individual maximal workload (P(max)), respectively, until exhaustion. RESULTS: There were no significant differences between V(O(2)max), RER(max), and P(max) between the three time points investigated. At submaximal intensities, the only difference to the pretreatment values was a 5% increase in V(O(2)) at 20% and 40% of P(max) 2 months after the cessation of the treatment. The total carnitine content in the skeletal muscle was 4.10 +/- 0.82 micromol/g before, 4.79 +/- 1.19 micromol/g immediately after, and 4.19 +/- 0.61 micromol/g wet weight 2 months after the treatment (no significant difference). Activities of the two mitochondrial enzymes citrate synthase and cytochrome oxidase, as well as the skeletal muscle fiber composition also remained unaffected by the administration of L-carnitine. CONCLUSIONS: Long-term oral treatment of healthy adults with L-carnitine is not associated with a significant increase in the muscle carnitine content, mitochondrial proliferation, or physical performance. Beneficial effects of the long-term treatment with L-carnitine on the physical performance of healthy adults cannot be explained by an increase in the carnitine muscle stores. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 7808246 Carnitine supplementation: effect on muscle carnitine and glycogen content during exercise Randomized trial · Med Sci Sports Exerc, 1994 6 g/day for 7 and 14 days - blood carnitine rose, but muscle content and fat oxidized during exercise did not change.
Key summary
A trial of carnitine supplementation's effect on muscle carnitine and glycogen during cycling at 70% of maximal oxygen uptake. After 7 and 14 days of 6 g/day, researchers took muscle biopsies and measured respiration. Resting serum carnitine rose, but muscle carnitine concentration was unaffected, and respiratory exchange ratio, carbohydrate and fat oxidized, and glycogen showed no differences. The authors read this as increased serum carnitine neither raising muscle content nor altering lipid oxidation, with an adequate amount already present within the mitochondria to support lipid oxidation.
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This study investigated the effects of L-carnitine supplementation on muscle carnitine and glycogen content during submaximal exercise (EX). Triglycerides were evaluated by a fat feeding (90 g fat) and 3 h later subjects cycled for 60 min at 70% VO2max (CON). Muscle biopsies were obtained preexercise and after 30 and 60 min of EX. Blood samples were taken prior to and every 15 min of exercise. Subjects randomly completed two additional trials following 7 and 14 d of carnitine supplementation (6 g.d-1). During one of the two trials, subjects received 2000 units of heparin 15 min prior to EX to elevate FFA (CNhep); no heparin was administered during the other trial (CN). There were no differences in VO2, respiratory exchange ratio, heart rate, or g.min-1 of CHO and fat oxidized among the three trials. At rest serum total acid soluble (TASC) and free (FC) carnitine increased with supplementation (TASC; CON, 71.3 +/- 2.9; CN, 92.8 +/- 5.4; CNhep, 109.8 +/- 3.5 mumol.l-1) (FC; CON, 44.1 +/- 2.7; CN, 66.1 +/- 5.3; CNhep, 77.1 +/- 4.1 mumol.l-1). During EX, TASC remained stable, while FC decreased and short-chain acylcarnitine (SCAC) increased (P < 0.05). Muscle carnitine concentration at rest was unaffected by supplementation. During EX, muscle TASC did not change, FC decreased, and SCAC increased significantly in all three trials. Pre-EX and post-EX muscle glycogens were not different. Increased availability of serum carnitine does not result in an increase in muscle carnitine content nor does it alter lipid oxidation. It appears that there is an adequate amount of carnitine present within the mitochondria to support lipid oxidation. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 21224234 Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans Randomized controlled trial · J Physiol, 2011 14 men, 2 g L-carnitine L-tartrate plus 80 g carbohydrate twice a day for 24 weeks - total muscle carnitine up 21%, work output up 11%.
Key summary
A randomized double-blind trial of whether adding carbohydrate to raise insulin lets muscle carnitine rise. Fourteen healthy men took either 80 g of carbohydrate alone or 2 g of L-carnitine L-tartrate with 80 g of carbohydrate twice a day for 24 weeks. Total muscle carnitine rose 21% in the carnitine group and was unchanged in controls. At 50% intensity they used 55% less muscle glycogen than controls, and at 80% muscle lactate was 44% lower. Work output in the performance trial rose 11% from baseline while controls showed no change. The authors described this as the first demonstration that human muscle total carnitine can be increased by dietary means.
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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. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 34959912 Effect of Acute and Chronic Oral l-Carnitine Supplementation on Exercise Performance Based on the Exercise Intensity: A Systematic Review Systematic review · Nutrients, 2021 11 trials - improvement reported at high intensity, no significant improvement at moderate intensity. No pooled meta-analysisA statistical synthesis combining results of multiple studies into one conclusion..
Key summary
A systematic review of acute and chronic oral L-carnitine by exercise intensity. Of 220 articles, 11 were included, with chronic use at 1-3 g/day for 4-24 weeks and acute doses of 3-4 g. High-intensity performance was assessed in nine studies and moderate-intensity in six. The authors summarized that 3-4 g taken 60-90 minutes before testing or 2-2.72 g/day for 9-24 weeks improved high-intensity performance, while moderate performance did not improve. They reported no funding and no conflict of interest.
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l-Carnitine (l-C) and any of its forms (glycine-propionyl l-Carnitine (GPL-C) or l-Carnitine l-tartrate (l-CLT)) has been frequently recommended as a supplement to improve sports performance due to, among others, its role in fat metabolism and in maintaining the mitochondrial acetyl-CoA/CoA ratio. The main aim of the present systematic review was to determine the effects of oral l-C supplementation on moderate- (50-79% V˙O2 max) and high-intensity (≥80% V˙O2 max) exercise performance and to show the effective doses and ideal timing of its intake. A structured search was performed according to the PRISMA® statement and the PICOS guidelines in the Web of Science (WOS) and Scopus databases, including selected data obtained up to 24 October 2021. The search included studies where l-C or glycine-propionyl l-Carnitine (GPL-C) supplementation was compared with a placebo in an identical situation and tested its effects on high and/or low-moderate performance. The trials that used the supplementation of l-C together with additional supplements were eliminated. There were no applied filters on physical fitness level, race, or age of the participants. The methodological quality of studies was evaluated by the McMaster Critical Review Form. Of the 220 articles obtained, 11 were finally included in this systematic review. Six studies used l-C, while three studies used l-CLT, and two others combined the molecule propionyl l-Carnitine (PL-C) with GPL-C. Five studies analyzed chronic supplementation (4-24 weeks) and six studies used an acute administration (<7 days). The administration doses in this chronic supplementation varied from 1 to 3 g/day; in acute supplementation, oral l-C supplementation doses ranged from 3 to 4 g. On the one hand, the effects of oral l-C supplementation on high-intensity exercise performance variables were analyzed in nine studies. Four of them measured the effects of chronic supplementation (lower rating of perceived exertion (RPE) after 30 min at 80% V˙O2 max on cycle ergometer and higher work capacity in "all-out" tests, peak power in a Wingate test, and the number of repetitions and volume lifted in leg press exercises), and five studies analyzed the effects of acute supplementation (lower RPE after graded exercise test on the treadmill until exhaustion and higher peak and average power in the Wingate cycle ergometer test). On the other hand, the effects of l-C supplementation on moderate exercise performance variables were observed in six studies. Out of those, three measured the effect of an acute supplementation, and three described the effect of a chronic supplementation, but no significant improvements on performance were found. In summary, l-C supplementation with 3 to 4 g ingested between 60 and 90 min before testing or 2 to 2.72 g/day for 9 to 24 weeks improved high-intensity exercise performance. However, chronic or acute l-C or GPL-C supplementation did not present improvements on moderate exercise performance. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 32958033 The bright and the dark sides of L-carnitine supplementation: a systematic review Systematic review · J Int Soc Sports Nutr, 2020 11 studies of 12 weeks or more in healthy people - muscle carnitine rose with carbohydrate, performance effects were conditional, fasting TMAO rose.
Key summary
A systematic review of studies giving healthy people oral L-carnitine alone for at least 12 weeks. Of 1,024 articles, 11 were included, at 1-4 g/day for 12 or 24 weeks. Taken with carbohydrate, it effectively raised total skeletal muscle carnitine. Twenty-four weeks did not affect muscle strength in healthy aged women, but significantly improved muscle mass, physical effort tolerance, and cognitive function in centenarians. Fasting plasma TMAO also rose, without association with changes in the inflammatory or oxidative stress markers measured. The authors called for long-term studies on the cardiovascular system and declared no competing interests.
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BACKGROUND: L-carnitine (LC) is used as a supplement by recreationally-active, competitive and highly trained athletes. This systematic review aims to evaluate the effect of prolonged LC supplementation on metabolism and metabolic modifications. METHODS: A literature search was conducted in the MEDLINE (via PubMed) and Web of Science databases from the inception up February 2020. Eligibility criteria included studies on healthy human subjects, treated for at least 12 weeks with LC administered orally, with no drugs or any other multi-ingredient supplements co-ingestion. RESULTS: The initial search retrieved 1024 articles, and a total of 11 studies were finally included after applying inclusion and exclusion criteria. All the selected studies were conducted with healthy human subjects, with supplemented dose ranging from 1 g to 4 g per day for either 12 or 24 weeks. LC supplementation, in combination with carbohydrates (CHO) effectively elevated total carnitine content in skeletal muscle. Twenty-four-weeks of LC supplementation did not affect muscle strength in healthy aged women, but significantly increased muscle mass, improved physical effort tolerance and cognitive function in centenarians. LC supplementation was also noted to induce an increase of fasting plasma trimethylamine-N-oxide (TMAO) levels, which was not associated with modification of determined inflammatory nor oxidative stress markers. CONCLUSION: Prolonged LC supplementation in specific conditions may affect physical performance. On the other hand, LC supplementation elevates fasting plasma TMAO, compound supposed to be pro-atherogenic. Therefore, additional studies focusing on long-term supplementation and its longitudinal effect on the cardiovascular system are needed. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based on this text and the full-text quotes below.
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The work was funded by Poland's National Science Centre (not industry).
"Funding This work was supported by National Science Centre in Poland, grant number 2014/15/B/NZ7/00893."
The authors declared no competing interests.
"Competing interests The authors declare that they have no competing interests."
※ Quotes machine-checked against the open full text in PMC (CC BY 4.0, 2026-11-07) View original ↗ PMID 22989098 Systemic primary carnitine deficiency: an overview of clinical manifestations, diagnosis, and management Expert review · Orphanet J Rare Dis, 2012 Overview of primary deficiency - oral 50-400 mg/kg/day in three doses, with favorable long-term prognosis while staying on it.
Key summary
A review of the clinical features, diagnosis, and management of systemic primary carnitine deficiency. It presents with hypoketotic hypoglycemia and hepatomegaly in infants, myopathy and cardiomyopathy in childhood, and cardiomyopathy, arrhythmias, or fatigability in adulthood. Diagnosis rests on low plasma free carnitine (<5 μM, normal 25-50 μM), reduced fibroblast transport, and SLC22A5 testing. US frequency is about 1 in 50,000 from newborn screening. Primary treatment is oral levocarnitine at 50-400 mg/kg/day in three doses, and long-term prognosis is favorable while patients remain on it. The authors declared no competing interests.
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Systemic primary carnitine deficiency (CDSP) is an autosomal recessive disorder of carnitine transportation. The clinical manifestations of CDSP can vary widely with respect to age of onset, organ involvement, and severity of symptoms, but are typically characterized by episodes of hypoketotic hypoglycemia, hepatomegaly, elevated transaminases, and hyperammonemia in infants; skeletal myopathy, elevated creatine kinase (CK), and cardiomyopathy in childhood; or cardiomyopathy, arrhythmias, or fatigability in adulthood. The diagnosis can be suspected on newborn screening, but is established by demonstration of low plasma free carnitine concentration (<5 μM, normal 25-50 μM), reduced fibroblast carnitine transport (<10% of controls), and molecular testing of the SLC22A5 gene. The incidence of CDSP varies depending on ethnicity; however the frequency in the United States is estimated to be approximately 1 in 50,000 individuals based on newborn screening data. CDSP is caused by recessive mutations in the SLC22A5 gene. This gene encodes organic cation transporter type 2 (OCTN2) which transport carnitine across cell membranes. Over 100 mutations have been reported in this gene with the c.136C > T (p.P46S) mutation being the most frequent mutation identified. CDSP should be differentiated from secondary causes of carnitine deficiency such as various organic acidemias and fatty acid oxidation defects. CDSP is an autosomal recessive condition; therefore the recurrence risk in each pregnancy is 25%. Carrier screening for at-risk individuals and family members should be obtained by performing targeted mutation analysis of the SLC22A5 gene since plasma carnitine analysis is not a sufficient methodology for determining carrier status. Antenatal diagnosis for pregnancies at increased risk of CDSP is possible by molecular genetic testing of extracted DNA from chorionic villus sampling or amniocentesis if both mutations in SLC22A5 gene are known. Once the diagnosis of CDSP is established in an individual, an echocardiogram, electrocardiogram, CK concentration, liver transaminanses measurement, and pre-prandial blood sugar levels, should be performed for baseline assessment. Primary treatment involves supplementation of oral levocarnitine (L-carnitine) at a dose of 50-400 mg/kg/day divided into three doses. No formal surveillance guidelines for individuals with CDSP have been established to date, however the following screening recommendations are suggested: annual echocardiogram and electrocardiogram, frequent plasma carnitine levels, and CK and liver transaminases measurement can be considered during acute illness. Adult women with CDSP who are planning to or are pregnant should meet with a metabolic or genetic specialist ideally before conception to discuss management of carnitine levels during pregnancy since carnitine levels are typically lower during pregnancy. The prognosis for individuals with CDSP depends on the age, presentation, and severity of symptoms at the time of diagnosis; however the long-term prognosis is favorable as long as individuals remain on carnitine supplementation. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 31373028 Increased risk of sudden death in untreated primary carnitine deficiency Observational study · J Inherit Metab Dis, 2020 Six of 53 sudden deaths under age 45 in the Faroe Islands had untreated primary deficiency - odds ratio 54.3.
Key summary
In the Faroe Islands, where primary carnitine deficiency has a high prevalence of 1:300, investigators reviewed all medico-legal sudden deaths under age 45 from 1979 to 2012. Genetic analysis of stored material from 53 of 65 cases found six homozygous for the c.95A>G mutation (11.3%, 95% CI 5-23%). Against a background prevalence of 0.23%, the odds ratio was 54.3 (95% CI 21-138), and among the 11 women five were homozygous, an odds ratio of 348.8. This is an association against the background population, not a randomized comparison of treatment.
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Primary carnitine deficiency (PCD) affects fatty acid oxidation and is associated with cardiomyopathy and cardiac arrhythmia, but the risk of sudden death in PCD is unknown. The Faroe Islands have a high prevalence of PCD, 1:300. This study systematically investigated a possible association between untreated PCD and sudden death in young Faroese subjects. We investigated all medico-legal cases of sudden death between 1979 and 2012 among subjects below the age of 45. Stored biomaterial was examined with molecular genetic analysis to reveal PCD. We compared the prevalence of PCD among sudden death cases with that of the background population (0.23%) to calculate the odds ratio (OR) for sudden death with PCD. Biomaterial was available and genetically analyzed from 53 of 65 sudden death cases (82%) in the Faroe Islands. Six (one male and five females) of the 53 cases were homozygous for the PCD related c.95A>G mutation-a prevalence of 11.3% (95% CI 5%-23%) and an OR of 54.3 (95% CI 21-138, P < .0001) for the association between sudden death and untreated PCD. Only 11 of the 53 sudden death cases were women-of whom five were homozygous for the c.95A>G mutation (45.5%) yielding an OR of 348.8 (95% CI 94-1287, P < .0001) for the association between sudden death and untreated PCD in females. This study showed a strong association between sudden death and untreated PCD, especially in females. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 30219858 L-Carnitine Improves Skeletal Muscle Fat Oxidation in Primary Carnitine Deficiency Clinical trial · J Clin Endocrinol Metab, 2018 Eight adults with primary deficiency paused for four days - fatty acid oxidation during exercise fell from 12.3 to 8.5 µmol/kg/min (P=0.008).
Key summary
Comparing eight adults homozygous for c.95A>G with 10 healthy controls, this study used isotopes to measure energy metabolism during one hour of cycling, with patients tested on carnitine and after a four-day pause. Fatty acid oxidation was 12.3 on treatment and 8.5 µmol/kg/min off it (P=0.008), and even on treatment stayed below the 29.5 of healthy controls (P<0.001). The authors suggested treatment may not only prevent cardiac complications but also boost skeletal muscle fat metabolism during exercise. These are results in deficient patients and cannot serve as evidence about fat oxidation in healthy people.
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CONTEXT: Primary carnitine deficiency (PCD) is an inborn error of fatty acid metabolism. Patients with PCD are risk for sudden heart failure upon fasting or illness if they are not treated with daily l-carnitine. OBJECTIVE: To investigate energy metabolism during exercise in patients with PCD with and without l-carnitine treatment. DESIGN: Interventional study. SETTING: Hospital exercise laboratories and department of cardiology. PARTICIPANTS: Eight adults with PCD who were homozygous for the c.95A>G (p.N32S) mutation and 10 healthy age- and sex-matched controls. INTERVENTION: Four-day pause in l-carnitine treatment. MAIN OUTCOME MEASURES: Total fatty acid and palmitate oxidation rates during 1-hour submaximal cycle ergometer exercise assessed with stable isotope method (U13C-palmitate and 2H2-d-glucose) and indirect calorimetry with and without l-carnitine. RESULTS: Total fatty acid oxidation rate was higher in patients with l-carnitine treatment during exercise than without treatment [12.3 (SD, 3.7) vs 8.5 (SD, 4.6) µmol × kg-1 × min-1; P = 0.008]. However, the fatty acid oxidation rate was still lower in patients treated with l-carnitine than in the healthy controls [29.5 (SD, 10.1) µmol × kg-1 × min-1; P < 0.001] and in the l-carnitine group without treatment it was less than one third of that in the healthy controls (P < 0.001). In line with this, the palmitate oxidation rates during exercise were lower in the no-treatment period [144 (SD, 66) µmol × kg-1 × min-1] than during treatment [204 (SD, 84) µmol × kg-1 × min-1; P = 0.004) . CONCLUSIONS: The results indicate that patients with PCD have limited fat oxidation during exercise. l-Carnitine treatment in asymptomatic patients with PCD may not only prevent cardiac complications but also boost skeletal muscle fat metabolism during exercise. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 33713287 Effect of L-carnitine supplementation on renal anemia in patients on hemodialysis: a meta-analysis Meta-analysis · Int Urol Nephrol, 2021 18 trials in 1,090 hemodialysis patients - lower ESA requirement, no difference in hemoglobin or hematocrit, long-term outcomes unclear.
Key summary
A meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of randomized L-carnitine trials for renal anemia in hemodialysis patients, covering 18 trials (1,090 people). Plasma free carnitine rose (mean difference 140.53, 95% CI 102.22 to 178.85), while the erythropoietin responsiveness index (-2.72, 95% CI -3.20 to -2.24) and required agent dose (-1.70, 95% CI -2.04 to -1.36) fell. Hemoglobin (0.18, 95% CI -0.20 to 0.55) and hematocrit (1.07, 95% CI -0.73 to 2.87) showed no significant difference. The authors supported use while saying the relationship with long-term outcomes remains unclear and more high-quality trials are needed.
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BACKGROUND: L-carnitine is an amino acid derivative that is thought to be helpful for treating renal anemia in hemodialysis patients. However, the mechanism remains to be fully elucidated. METHODS: A literature search was performed on PubMed, Embase, and Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) and conduct a meta-analysis for investigating the effect of L-carnitine in the treatment of renal anemia in participants receiving hemodialysis. RESULTS: A total of 18 eligible trials with 1090 participants were included in this study. L-carnitine can significantly increase plasma free L-carnitine levels (mean difference [MD]: 140.53, 95% confidence interval [CI] 102.22-178.85; P < 0.00001), decrease the erythropoietin responsiveness index (ERI; MD: -2.72, 95% CI -3.20 to -2.24; P < 0.00001) and the required erythropoiesis-stimulating agent (ESA) doses (MD: -1.70, 95% CI -2.04 to -1.36; P < 0.00001). However, the use of L-carnitine was not associated with a higher hemoglobin level (MD: 0.18, 95% CI -0.20 to 0.55; P = 0.35) and hematocrit level (MD: 1.07, 95% CI -0.73 to 2.87; P = 0.24). In subgroup analyses, the effects of L-carnitine supplementation on renal anemia in patients on hemodialysis were independent of the treatment duration and intervention routes. CONCLUSION: The present meta-analysis indicated that L-carnitine therapy significantly increased plasma L-carnitine concentrations, improved the response to ESA, decreased the required ESA doses in patients receiving hemodialysis, and maintained hemoglobin and hematocrit levels. L-carnitine supplementation should be supported in hemodialysis patients. However, the relationship between L-carnitine treatment and long-term outcomes is still unclear. Further high-quality RCTs are needed to verify our findings. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 12908852 Pharmacokinetics of L-carnitine Pharmacokinetic review · Clin Pharmacokinet, 2003 Absolute bioavailabilityThe fraction of an ingested substance that actually reaches the blood and tissues to act. is 5-18% at oral doses of 1-6 g and up to 75% from food - larger doses are absorbed less efficiently.
Key summary
A review of L-carnitine pharmacokinetics. The body's pool is maintained by dietary absorption, biosynthesis, and renal reabsorption (98-99%). Absolute bioavailabilityThe fraction of an ingested substance that actually reaches the blood and tissues to act. is 5-18% at oral doses of 1-6 g while dietary carnitine may reach 75%, so supplemental or pharmacological doses are absorbed less efficiently than the smaller amounts in a normal diet. The reabsorption threshold is similar to the normal plasma level, so renal clearance rises after exogenous dosing. Dialysis patients can develop secondary deficiency through loss across the dialyser.
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L-Carnitine is a naturally occurring compound that facilitates the transport of fatty acids into mitochondria for beta-oxidation. Exogenous L-carnitine is used clinically for the treatment of carnitine deficiency disorders and a range of other conditions. In humans, the endogenous carnitine pool, which comprises free L-carnitine and a range of short-, medium- and long-chain esters, is maintained by absorption of L-carnitine from dietary sources, biosynthesis within the body and extensive renal tubular reabsorption from glomerular filtrate. In addition, carrier-mediated transport ensures high tissue-to-plasma concentration ratios in tissues that depend critically on fatty acid oxidation. The absorption of L-carnitine after oral administration occurs partly via carrier-mediated transport and partly by passive diffusion. After oral doses of 1-6g, the absolute bioavailability is 5-18%. In contrast, the bioavailability of dietary L-carnitine may be as high as 75%. Therefore, pharmacological or supplemental doses of L-carnitine are absorbed less efficiently than the relatively smaller amounts present within a normal diet.L-Carnitine and its short-chain esters do not bind to plasma proteins and, although blood cells contain L-carnitine, the rate of distribution between erythrocytes and plasma is extremely slow in whole blood. After intravenous administration, the initial distribution volume of L-carnitine is typically about 0.2-0.3 L/kg, which corresponds to extracellular fluid volume. There are at least three distinct pharmacokinetic compartments for L-carnitine, with the slowest equilibrating pool comprising skeletal and cardiac muscle.L-Carnitine is eliminated from the body mainly via urinary excretion. Under baseline conditions, the renal clearance of L-carnitine (1-3 mL/min) is substantially less than glomerular filtration rate (GFR), indicating extensive (98-99%) tubular reabsorption. The threshold concentration for tubular reabsorption (above which the fractional reabsorption begins to decline) is about 40-60 micromol/L, which is similar to the endogenous plasma L-carnitine level. Therefore, the renal clearance of L-carnitine increases after exogenous administration, approaching GFR after high intravenous doses. Patients with primary carnitine deficiency display alterations in the renal handling of L-carnitine and/or the transport of the compound into muscle tissue. Similarly, many forms of secondary carnitine deficiency, including some drug-induced disorders, arise from impaired renal tubular reabsorption. Patients with end-stage renal disease undergoing dialysis can develop a secondary carnitine deficiency due to the unrestricted loss of L-carnitine through the dialyser, and L-carnitine has been used for treatment of some patients during long-term haemodialysis. Recent studies have started to shed light on the pharmacokinetics of L-carnitine when used in haemodialysis patients. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 23563705 Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis Animal and observational study · Nat Med, 2013 In mice, carnitine sped atherosclerosis via TMAO; among 2,595 people, plasma carnitine predicted risk only with high TMAO.
Key summary
A study reporting the pathway by which gut microbes convert dietary L-carnitine into TMAO. In mice, chronic carnitine supplementation raised TMA and TMAO synthesis and increased atherosclerosis, which did not occur with intestinal microbiota suppressed. Omnivores produced more TMAO than vegans or vegetarians after carnitine ingestion. Among 2,595 people undergoing cardiac evaluation, plasma carnitine predicted cardiovascular disease and major adverse cardiac events only in those with high TMAO. It was funded by the NIH among others, and the disclosure in its PMC full text lists some authors as co-inventors on patents related to cardiovascular diagnostics and therapeutics. Per the full text's competing-interest disclosure, lead authors are co-inventors on cardiovascular diagnostic and therapeutic patents.
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Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based on this text and the full-text quotes below.
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The corresponding author Hazen and a colleague declared they are co-inventors on their institution's cardiovascular diagnostic and therapeutic patents, an interest on the side arguing TMAO risk.
"Drs. Hazen and Smith are named as co-inventors on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics."
※ Quotes machine-checked against the open full text in PMC (PMC 학술 연구용 텍스트 마이닝 허용, 2026-11-07) View original ↗ PMID 30485835 L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women Clinical study · Ann Nutr Metab, 2019 24 weeks in healthy aged women - plasma TMAO up tenfold, with no change in lipid, inflammatory, or vascular markers.
Key summary
A study of whether L-carnitine supplementation changes serum atherosclerosis markers over 24 weeks in healthy aged women. Plasma free carnitine and TMAO rose, with TMAO up tenfold. C-reactive protein, interleukin-6, tumour necrosis factor-alpha, selectins, adhesion molecules, and lipid markers were unaffected. These are blood markers over 24 weeks, not cardiovascular events.
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BACKGROUND: L-carnitine can be metabolized to trimethylamine N-oxide (TMAO), a molecule that promotes atherogenesis through its interaction with macrophages and lipid metabolism. OBJECTIVE: The aim of the present study was to assess whether L-carnitine supplementation may promote changes in selected serum biomarkers of atherosclerosis. METHODS: Before the start, in the mid-point and after completing the 24-weeks supplementation protocol, fasting blood samples were taken from the antecubital vein. Plasma free L-carnitine and TMAO were determined by the UPLC/MS/MS method. Serum proteins were determined by the enzyme immunoassay method using commercially available kits. Total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides have been determined using standard automatic analyzer. RESULTS: L-carnitine supplementation elevated fasting plasma carnitine in the mid-point of our study and it remained increased until the end of supplementation period. Moreover, it induced tenfold increase in plasma TMAO concentration but did not affect serum C-reactive protein, interleukin-6, tumour necrosis factor-α, L-selectin, P-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 or lipid profile markers. CONCLUSION: We demonstrated that -although oral L-carnitine supplementation significantly -increased plasma TMAO concentration, no lipid profile changes or other markers of adverse cardiovascular events were detected in healthy aged women over the period of 24 weeks. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 31167879 Assessment of Causal Direction Between Gut Microbiota-Dependent Metabolites and Cardiometabolic Health: A Bidirectional Mendelian Randomization Analysis Mendelian randomization · Diabetes, 2019 Genetically higher TMAO and carnitine were not linked to coronary disease, MI, or stroke - supporting diabetes and kidney disease raising TMAO.
Key summary
A bidirectional Mendelian randomization analysis using genetic variants to test whether TMAO and its precursors cause cardiometabolic disease. After Bonferroni correction, genetically predicted higher TMAO and carnitine were not associated with type 2 diabetes, atrial fibrillationAn irregular, rapid heart rhythm arising in the atria., coronary artery disease, myocardial infarctionA heart attack - death of heart muscle from blocked blood flow., stroke, or chronic kidney disease. Conversely, type 2 diabetes and chronic kidney disease were causally associated with higher TMAO. The authors suggested observational evidence for cardiovascular disease may be due to confounding or reverse causality. It did not directly test carnitine supplements.
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We examined the causal direction between gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) or its predecessors and cardiometabolic diseases, such as risk of type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), myocardial infarction (MI), stroke, atrial fibrillation (AF), and chronic kidney disease (CKD). We used genetic variants as instruments to test the causal associations. Genetically predicted higher TMAO and carnitine were not associated with higher odds of T2DM, AF, CAD, MI, stroke, and CKD after Bonferroni correction (P ≤ 0.0005). However, we observed that genetically increased choline showed a suggestive association with higher risk of T2DM (odds ratio 1.84 [95% CI 1.00-3.42] per 10 units, P = 0.05). In contrast, genetically predicted higher betaine (0.68 [0.48-0.95] per 10 units, P = 0.023) was suggestively associated with a lower risk of T2DM. We observed a suggestive association of genetically increased choline with a lower level of body fat percentage (β ± SE -0.28 ± 0.11, P = 0.013) but a higher estimated glomerular filtration rate (0.10 ± 0.05, P = 0.034). We further found that T2DM (0.130 ± 0.036, P < 0.0001) and CKD (0.483 ± 0.168, P = 0.004) were causally associated with higher TMAO levels. Our Mendelian randomization findings support that T2DM and kidney disease increase TMAO levels and that observational evidence for cardiovascular diseases may be due to confounding or reverse causality. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ FDA (openFDA) CARNITOR (levocarnitine oral) - drug label (primary deficiency indication, bioavailability, renal precaution, warfarin interaction, adverse reactions)
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View original ↗ FDA (openFDA) CARNITOR (levocarnitine injection) - drug label (deficiency in dialysis patients, dosing, clinical outcomes not determined)
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