L-carnitine in the secondary prevention of cardiovascular disease: systematic review and meta-analysis. Mayo Clin Proc ; European multicenter study on priopionyl-L-carnitine in intermittent claudication.
J Am Coll Cardiol ; Propionyl-L-carnitine improves exercise performance and functional status in patients with claudication. Am J Med ; A systematic review and meta-analysis of propionyl-L-carnitine effects on exercise performance in patients with claudication. Vasc Med ; Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis.
Nat Med ; L-carnitine supplementation for the treatment of fatigue and depressed mood in cancer patients with carnitine deficiency: a preliminary analysis. Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients. Br J Cancer ; Carnitine in type 2 diabetes. Carnitine increases glucose disposal in humans. L-carnitine improves glucose disposal in type 2 diabetic patients. Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials.
Diabetes Care ; Acetyl-L-carnitine for the treatment of HIV lipoatrophy. L-carnitine and acetyl-L-carnitine in the treatment of complications associated with HIV infection and antiretroviral therapy.
Mitochondrion ; Effect of L-carnitine on human immunodeficiency virus-1 infection-associated apoptosis: a pilot study. Blood ; Acetyl-L-carnitine administration increases insulin-like growth factor 1 levels in asymptomatic HIVinfected subjects: correlation with its suppressive effect on lymphocyte apoptosis and ceramide generation. Clin Immunol ; J Peripher Nerv Syst ; Plasma carnitine in HIV-associated neuropathy.
AIDS ; Acetyl-l-carnitine in the treatment of painful antiretroviral neuropathy in human immunodeficiency virus patients: an open label study. Carnitine depletion in peripheral blood mononuclear cells from patients with AIDS: effect of oral L-carnitine. L-carnitine for the treatment of highly active antiretroviral therapy-related hypertriglyceridemia in HIV-infected adults. L-carnitine in the treatment of HIV-associated lipodystrophy syndrome. HIV Med Carnitine replacement in end-stage renal disease and hemodialysis.
Effects of L-carnitine supplementation in maintenance hemodialysis patients: a systematic review. J Am Soc Nephrol ; Free L-carnitine in human semen: its variability in different andrologic pathologies. Fertil Steril ; L-carnitine levels in the seminal plasma of fertile and infertile men: correlation with sperm quality.
Int J Fertil Womens Med ; L-carnitine in idiopathic asthenozoospermia: a multicenter study. Italian study group on carnitine and male infertility. Andrologia ; Carnitine supplementation in human idiopathic asthenospermia: clinical results.
Drugs Exp Clin Res ; Effects of treatment with carnitines in infertile patients with prostato-vesiculo-epididymitis. Hum Reprod ; Use of carnitine therapy in selected cases of male factor infertility: a double-blind crossover trial. The role of carnitine in the male reproductive system. Carnitine for the treatment of idiopathic asthenospermia: a randomized, double-blind, placebo-controlled trial.
Fertil Steril ;85 5 Pivalate-generating prodrugs and carnitine homeostasis in man. Treating a serious condition with supplement can sometimes be hazardous. Anyone with symptoms or a diagnosis of a serious disease people should seek conventional treatment from a qualified medical professional.
Many athletes and gym enthusiasts use carnitine, and it is available over the counter as a sports or health supplement. The hypothesis is that carnitine supplementation improves exercise performance in healthy athletes through various mechanisms. A rordent study, published in , suggested that carnitine may reduce oxidative stress during exercise. Researchers who gave L-carnitine to older patients with chronic obstructive pulmonary disease COPD alongside exercise testing found that exercise capacity improved in the eight men who completed the experiment.
People should be especially sure to inform their doctor before using it as a supplement if they have:. Carnitine can interact with phenobarbital, valproic acid, phenytoin, carbamazepine, and some antibiotics , but there is no evidence that these can lead to a deficiency. The Linus Pauling Institute recommend that anyone who does decide to take carnitine supplements should consider acetyl-L-carnitine at mg to 1, mg a day. In this Honest Nutrition feature, we explore the practice of "clean eating," and why this concept has been a controversial one for researchers.
A recent study found several phthalates and other plasticizers in food items from leading fast-food chains, highlighting the need for more regulation.
This article looks at the causes of postprandial somnolence, or food coma, and explains how people who often feel sleepy after eating can cope with…. Hot water bottles can help to relieve aches and pains. Learn more here. New research in mice examines the impact of a Western diet on cognitive decline and neurodegenerative disorders. Carnitine: What are the benefits and risks? Medically reviewed by Debra Rose Wilson, Ph.
What is it? Requirements Food sources As a therapy For athletic performance Risks Carnitine is present in almost every cell in the body. A randomized , double-blind , placebo -controlled trial in 28 older women ages, years found no effect of L-carnitine supplementation 1.
One major limitation of this study beyond its retrospective design is that patients who received L-carnitine had a significantly different clinical presentation; in particular, liver dysfunction was significantly more severe in these patients than in those who were not supplemented Muscle cramps are involuntary and painful contractions of skeletal muscles.
Two uncontrolled studies conducted in participants with cirrhosis found that L-carnitine supplementation was safe to use at doses of 0. However, whether supplemental L-carnitine can be efficacious to limit the incidence of muscle cramps in patients with cirrhosis remains unknown.
An open-label , non-randomized trial in 69 patients with either type 1 or type 2 diabetes mellitus found a reduction in the incidence of muscle cramps and an improvement in the quality of life of those prescribed 0. In contrast, there is little evidence to date to suggest that supplemental L-carnitine could reduce muscle cramps in patients undergoing hemodialysis Well-designed trials are necessary to examine whether L-carnitine could be helpful in the management of cramps.
Interest in the potential of L-carnitine supplementation to improve athletic performance is related to its important roles in energy metabolism. However, the content carnitine in skeletal muscle, phosphocreatine, ATP , glycogen , and lactate, as well as measures of physical performance during exercise were equivalent between vegetarians and omnivores.
While L-carnitine supplementation normalized plasma carnitine concentration in vegetarians to that observed in omnivores, there was no effect on energy metabolism and physical performance compared to no supplementation and between vegetarians and omnivores The normal rate of L-carnitine biosynthesis in humans ranges from 0.
Thus, a 70 kg 1b person would synthesize between 11 and 34 mg of carnitine per day. Meat, poultry, fish, and dairy products are the richest sources of L-carnitine, while fruit, vegetables, and grains contain relatively little L-carnitine.
Non-milk-based infant formulas e. Some carnitine-rich foods and their carnitine content in milligrams mg are listed in Table 1. Intravenous L-carnitine is available by prescription only for the treatment of primary and secondary L-carnitine deficiencies Oral L-carnitine is available by prescription for the treatment of primary and secondary L-carnitine deficiencies It is also available without a prescription as a nutritional supplement ; supplemental doses usually range from 0.
In addition to providing L-carnitine, it provides acetyl groups that may be used in the formation of the neurotransmitter , acetylcholine. Supplemental doses usually range from 0. It is, however, available without prescription as a nutritional supplement. See Figure 1 for the chemical structures of L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine.
In general, L-carnitine appears to be well tolerated; no toxic effects have been reported in relation to intakes of high doses of L-carnitine. L-Carnitine supplementation may cause mild gastrointestinal symptoms, including nausea, vomiting, abdominal cramps, and diarrhea. Despite claims that L-carnitine or ALCAR might increase seizures in some individuals with seizure disorders , these are not supported by any scientific evidence Only the L- isomer of carnitine is biologically active; the D-isomer may actually compete with L-carnitine for absorption and transport, thereby increasing the risk of L-carnitine deficiency 4.
Supplements containing a mixture of the D- and L-isomers D,L-carnitine have been associated with muscle weakness in patients with kidney disease. Long-term studies examining the safety of ALCAR supplementation in pregnant and breast-feeding women are lacking Pivalic acid combines with L-carnitine and is excreted in the urine as pivaloylcarnitine, thereby increasing L-carnitine losses see also Secondary carnitine deficiency.
Consequently, prolonged use of pivalic acid-containing antibiotics, including pivampicillin, pivmecillinam, pivcephalexin, and cefditoren pivoxil Spectracef , can lead to secondary L-carnitine deficiency The anticonvulsant valproic acid Depakene interferes with L-carnitine biosynthesis in the liver and forms with L-carnitine a valproylcarnitine ester that is excreted in the urine.
However, L-carnitine supplements are necessary only in a subset of patients taking valproic acid. There is insufficient evidence to suggest that nucleoside analogs used in the treatment of HIV infection i. Originally written in by: Jane Higdon, Ph. Updated in April by: Victoria J. Drake, Ph. Updated in July by: Barbara Delage, Ph. Reviewed in December by: Tory M. Hagen, Ph. Rebouche CJ. Modern Nutrition in Health and Disease.
Fraenkel G, Friedman S. Vitam Horm. De Grandis D, Minardi C. Acetyl-L-carnitine levacecarnine in the treatment of diabetic neuropathy. A long-term, randomised, double-blind, placebo-controlled study. Drugs R D. L - -Carnitine and its precursor, gamma-butyrobetaine. Nutraceuticals in Health and Disease Prevention.
New York: Marcel Dekker, Inc. Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism. Ann N Y Acad Sci. Baltimore; Ascorbic acid and carnitine biosynthesis. Am J Clin Nutr. Evans AM, Fornasini G. Pharmacokinetics of L-carnitine. Clin Pharmacokinet. Carnitine status of lactoovovegetarians and strict vegetarian adults and children.
Metabolic fate of dietary carnitine in human adults: identification and quantification of urinary and fecal metabolites. J Nutr. Uptake of L-carnitine, D-carnitine and acetyl-L-carnitine by isolated guinea-pig enterocytes. Biochim Biophys Acta. Renal adaptation to dietary carnitine in humans. Present Knowledge in Nutrition. McGrane MM. Carbohydrate metabolism--synthesis and oxidation.
In: Stipanuk MH, ed. Biochemical and Physiological Aspects of Human Nutrition. Philadelphia: W. Saunders Co; The antioxidant properties of carnitine in vitro.
Cell Mol Biol Lett. Age-dependent decrease of carnitine content in muscle of mice and humans. Biochem Biophys Res Commun. Downregulation of carnitine acyltransferases and organic cation transporter OCTN2 in mononuclear cells in healthy elderly and patients with myelodysplastic syndromes.
J Mol Med Berl. Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Acetyl-L-carnitine supplementation to old rats partially reverts the age-related mitochondrial decay of soleus muscle by activating peroxisome proliferator-activated receptor gamma coactivator-1alpha-dependent mitochondrial biogenesis.
Rejuvenation Res. Acetyl-l-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 CPT1 activity in interfibrillar mitochondria without changing the l-carnitine content in the rat heart.
Mech Ageing Dev. Oxidative stress-mediated macromolecular damage and dwindle in antioxidant status in aged rat brain regions: role of L-carnitine and DL-alpha-lipoic acid. Clin Chim Acta. Age-associated deficit of mitochondrial oxidative phosphorylation in skeletal muscle: role of carnitine and lipoic acid. Mol Cell Biochem.
Supplementation of L-carnitine improves mitochondrial enzymes in heart and skeletal muscle of aged rats. Exp Aging Res. Savitha S, Panneerselvam C. Mitochondrial membrane damage during aging process in rat heart: potential efficacy of L-carnitine and DL alpha lipoic acid. Efficacy of levo carnitine and alpha lipoic acid in ameliorating the decline in mitochondrial enzymes during aging.
Clin Nutr. Sethumadhavan S, Chinnakannu P. Carnitine and lipoic Acid alleviates protein oxidation in heart mitochondria during aging process. Sundaram K, Panneerselvam KS.
Oxidative stress and DNA single strand breaks in skeletal muscle of aged rats: role of carnitine and lipoicacid. L-carnitine and alpha-lipoic acid improve age-associated decline in mitochondrial respiratory chain activity of rat heart muscle.
Age-dependent upregulation of p53 and cytochrome c release and susceptibility to apoptosis in skeletal muscle fiber of aged rats: role of carnitine and lipoic acid. Free Radic Biol Med. Neuronal mitochondrial amelioration by feeding acetyl-L-carnitine and lipoic acid to aged rats.
J Cell Mol Med. Low carnitine intake and altered lipid metabolism in infants. American Academy of Pediatrics, Committee on Nutrition. Soy protein-based formulas: recommendations for use in infant feeding. Functional and molecular studies in primary carnitine deficiency.
Hum Mutat. Systemic primary carnitine deficiency: an overview of clinical manifestations, diagnosis, and management. Orphanet J Rare Dis. Disorders of mitochondrial long-chain fatty acid oxidation and the carnitine shuttle.
Rev Endocr Metab Disord. Primary and secondary carnitine deficiency syndromes. J Child Neurol. Diagnosis and treatment of renal tubular disorders. Semin Nephrol. However acetyl-L-carnitine was not found to benefit young men suffering Down's Syndrome [ ].
Human skeletal and cardiac muscles contain relatively high concentrations of carnitine received from the plasma, since they are incapable of carnitine biosynthesis [ 1 ].
The heart is one of the organs most affected in carnitine-acylcarnitine carrier CAC deficiency [ ]. This pathway is the major source of energy for the heart [ ]. Cardiomyopathy, cardiac arrhythmia, likely due to the accumulation of long-chain fatty acids and acylcarnitines that cannot be oxidized , cardiac insufficiency and respiratory distress arise from CAC deficiency [ ].
Carnitine deficiency has been associated with heart failure [ 5 ]. The mechanism s underlying the effects of L-carnitine LC in cardiovascular diseases are not well clarified. Miguel-Carrasco et al. In opposition to the reported beneficial effects of carnitine overload, Diaz et al. In addition, carnitine supplementation increased contracture of the heart shortly after reperfusion. Diaz and colleagues concluded that in conditions where it does not increase glucose oxidation, carnitine supplementation worsens both injury and recovery of contractile function after transient ischemia in perfused rat heart [ ].
L-carnitine has been shown to have favorable effects in patients with severe cardiovascular disorders, such as coronary heart disease, chronic heart failure and peripheral vascular disease [ — ].
In patients with chronic heart disease, administration of L-carnitine over 12 months led to attenuation of left ventricular dilatation and prevented ventricular remodeling while reducing incidence of chronic heart failure and death [ ]. In ischemia, L-carnitine reduces myocardial injury mainly through improving carbohydrate metabolism and by reducing the toxicity of high free fatty acid levels [ ].
The protective effect of L-carnitine on ST-elevation myocardial infarction has been documented. Following an acute myocardial infarction prompt L-carnitine administration and subsequent maintenance therapy attenuates progressive left ventricular dilatation [ ]. L-carnitine reduces early mortality but not overall risk of death or heart failure at 6 months [ ].
L-carnitine supplementation also prevents ventricular enlargement and dysfunction, reduces the infarct size and cardiac biomarkers, and diminishes the total number of cardiac events including cardiac deaths and nonfatal infarction [ , ]. Xue and colleagues suggest that the beneficial effects of L-carnitine in cardiovascular disease are due to the resumption of normal oxidative metabolism and restoration of myocardial energy reserves [ , ].
Carnitine has been widely recommended as a supplement in cardiovascular disease. However, it should be noted as mentioned previously, in conditions where it does not increase glucose oxidation, carnitine supplementation worsens both injury and recovery of contractile function after transient ischemia in the perfused rat heart [ ]. Myopathy can be seen with biochemically defined defects in mitochondrial substrate transport or utilization, including the myopathic form of carnitine deficiency; CPT II deficiency which most often presents with exercise intolerance and myoglobinuria and is discussed below [ ].
Patients with Duchenne dystrophy and Becker dystrophy showed lower carnitine levels in muscle biopsies than controls [ ] though these levels were higher than in patients suffering primary carnitine deficiency as a result of severe muscle damage [ 1 ].
CPT II Type 1 "muscle" phenotype, which is the most frequent clinical presentation, is characterized by recurrent episodes of muscle pain, rhabdomyolysis a potentially fatal disease that occurs suddenly and with great force destroying skeletal muscle and myoglobinuria. Cyclosporin A induced nephrotoxicity has been discussed above. Valproic acid VPA is a broad-spectrum anti-epileptic drug [ ].
VPA is used to treat psychiatric disorders and as such there is an association with accidental or deliberate overdose, the incidence of which is increasing [ , ]. Benefits of oral L-carnitine in relation to VPA-associated deficiency and related adverse effects have been reported [ — ]. Carnitine supplementation during VPA therapy in high-risk patients is now recommended by some, especially by pediatricians [ ]. L-carnitine therapy could also be valuable in those patients who develop VPA-induced hepatotoxicity or VPA-induced hyperammonaemic encephalopathy [ ].
Al-Majed and colleagues [ ] found that carnitine deficiency and oxidative stress are risk factors during development of cisplatin CDDP -induced cardiomyopathy and that carnitine supplementation, using propionyl-l-carnitine, prevents the progression of CDDP-induced cardiotoxicity. Adverse effects of aging are, in part, attributed to decreases in mitochondrial function and increases mitochondrial oxidant production [ ]. L -carnitine levels in tissues have been found to decline with age [ ].
Acetyl- L -carnitine ALCA fed to aged rats was shown to reverse age-related declines in tissue L -carnitine levels and also reversed a number of age-related changes in liver mitochondrial function; however, high doses of ALCA increased liver mitochondrial oxidant production [ ]. Liu et al. ALCA, together with alpha-lipoic acid, was shown to improve mitochondrial energy metabolism and decrease oxidative stress leading to improved memory in aged rats [ , ].
Several studies have reported that supplementing rats with both L -carnitine and alpha-lipoic acid halts age-related increases in reactive oxygen species ROS , lipid peroxidation, protein carbonylation, and DNA strand breaks in heart, skeletal muscle and brain, concomitant with improvement in mitochondrial enzyme and respiratory chain activities [ — ]. In a clinical trial of Levocarnitine-treated elderly patients [ ], there was significant improvement in total fat mass, total muscle mass, total cholesterol, LDL-C, HDL-C, triglycerides, apoA1, and apoB with concomitant decreases in physical and mental fatigue.
These data suggest that administration of levocarnitine to healthy elderly subjects may result in reduction of total fat mass, and increase of total muscle mass, may be reduce fatigue and serum lipids.
Carnitine levels decrease with age [ ]. Patano and colleagues suggest that this decrease in energy availability might compromise osteoblast activity and bone remodeling in an age-related manner [ ]. Patano et al.
Using an aging ovariectomized rat model they found supplementation of L-carnitine can influence bone density and slow the rate of bone turnover by slowing bone loss and improving bone microstructural properties through decreasing bone turnover [ ]. The study reported that benefits of carnitine are comparable with other drugs of choice in terms of effectiveness in preventing BMD loss due to aging.
Colluci and colleagues [ ] used an in vitro model to suggest that carnitine supplementation in the elderly may stimulate osteoblast activity and decrease age-related bone loss. Dry eye is a common disease of the ocular surface that is associated with corneal surface irregularity and blurred vision [ — ].
In artificial tear formulations, L-carnitine is considered a "compatible solute". Use of carnitine in artificial tears has demonstrated rapid and consistent improvements in signs and symptoms in patients with dry eye [ ] suggesting an intrinsic homeostatic role for carnitine in the eye [ ].
Recently, Pescosolido and colleagues [ ] evaluated the presence of carnitine in tears of dry eye patients and suggested that the damage incurred on the ocular surface of dry eye patients may, in part, be due to a lack of carnitine in the tear film of these patients relative to the ocular surface cells and suggested use of solutions containing carnitine to reduce this damage. Increased tear osmolarity in dry eye disease has been found to stimulate production of inflammatory cytokines and matrix metalloproteinases by ocular surface epithelial cells [ ].
Tears of patients with dry eye show significantly increased osmolarity, with a mean value of mOsm compared with mOsm in healthy controls [ ]. Corrales and colleagues [ ] showed that osmoprotectants such as L-carnitine reduce activation of mitogen-activated protein MAP kinases, the phosphorylation of which leads to an increased expression of cytokines, chemokines and matrix metalloproteases [ ]. These factors mediate and control immune and inflammatory responses.
Dysregulation of these factors in the eye can lead to corneal melting and scarring with deleterious consequences. Under hyperosmolar conditions, L-carnitine was found to protect against stress activation of corneal epithelial cells by reducing levels of kinase [ ]. Peluso et al. Chorioretinopathy emerges during early childhood as granular pigmentation of the central fundus with or without pigment clumping which may progress to chorioretinal atrophy, high myopia, posterior staphyloma and low vision [ ].
Current treatment includes a low fat, high carbohydrate diet and avoidance of fasting which dramatically improves prognosis allowing long term survival. However the dietary impact is controversial [ ]. Roomets et al.
They further suggest that accumulation of 3-hydroxylated intermediates of long-chain fatty acids may contribute to the pathogenesis of retinopathy in MTP deficiencies [ ]. Carnitine as a nutritional supplement has, since the s, been promoted as beneficial in a number of disorders of human carnitine deficiency of impaired fatty acid oxidation, suggesting that nutritional or pharmacologic supplements of carnitine might be beneficial in some disorders [ ].
However it should be noted that according to Stanley [ ], over the past 40 years, there have been only two clear examples of disorders directly due carnitine deficiency that have provided evidence of unequivocal benefit from carnitine treatment. Most healthy people, including vegetarians, produce and gain sufficient carnitine from their diets.
Carnitine is thus considered a "conditionally essential" nutrient since individuals' requirements might exceed dietary intake during specific disease states.
The increase of L-carnitine in plasma via oral administration, even up to and exceeding 2 mg, is limited, since L-carnitine has a very poor absorption and bioavailability, a very high renal clearance, and active uptake into tissues.
Despite this, in a number of disease states much work has been done regarding the effects of prophylactic levels of carnitine though some controversy and misconceptions relating to its use in general nutrition need to be addressed. Carnitine is a natural compound, free from toxicity when given in oral doses up to several grams and thus supplements are often recommended in primary and secondary deficiencies.
Since carnitine is readily excreted, supplemental ingestion is well tolerated. Evidence from both rodent and human studies supports health-related benefits when used as a therapeutic agent.
Kendler BS: Carnitine: an overview of its role in preventive medicine. Prev Med. Int Pediatr. Google Scholar. Rebouche CJ: Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism.
Ann N Y Acad Sci. Rebouche CJ, Chenard CA: Metabolic fate of dietary carnitine in human adults: identification and quantification of urinary and fecal metabolites.
J Nutr. CAS Google Scholar. Nutr Clin Pract. Article Google Scholar. Rebouche CJ: Carnitine function and requirements during the life cycle. Faseb J. Am J Clin Nutr. Biochem J. Clin Biochem. Am J Kidney Dis. Annu Rev Nutr. Ahmad S: L-carnitine in dialysis patients. Semin Dial. Breningstall GN: Carnitine deficiency syndromes. Pediatr Neurol. J Physiol Pharmacol. J Cell Biochem. Biochim Biophys Acta. Biochem Biophys Res Commun. Nephrology Carlton. Mol Genet Metab. J Inherit Metab Dis. Hum Mutat.
J Child Neurol. Hum Mol Genet. Nat Genet. Ann Nutr Metab. J Biol Chem. Lab Invest. Vermeire S, Rutgeerts P: Current status of genetics research in inflammatory bowel disease.
Genes Immun. Annu Rev Physiol.
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