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Carnitine

Nutrient Name: Carnitine.
Synonyms:L-Carnitine, levocarnitine; vitamin BT.
Forms: Acetyl-L-carnitine (ALC),L-acetylcarnatine (LAC); propionyl-L-caritine (PLC),L-propionylcarnitine (LPC).
Related Substance:D-Carnitine (synthetic isomer).

Summary Table
nutrient description

Chemistry and Forms

Carnitine (3-hydroxy-4N-trimethylammoniumbutanoate) is a naturally occurring quaternary amine. Forms include acetyl-L-carnitine (ALC;L-acetylcarnitine, LAC) and propionyl-L-carnitine (PLC;L-propionylcarnitine, LPC).

Physiology and Function

Carnitine (levocarnitine,L-carnitine) is considered to be a nonessential amino acid, although in certain situations it is considered conditionally essential (e.g., dialysis patients, premature and very-low-birth-weight infants, coronary artery disease). The highest concentrations of carnitine are found in the heart, muscles, liver, and kidney. The major biochemical function of carnitine is to act as a transmembrane carrier of long-chain fatty acids to the interior of mitochondria. It plays a major role in the utilization of fats in energy production at the mitochondrial level through the beta-oxidation of branched-chain amino acids and ketoacids. Carnitine also participates in transportation of acyl-coenzyme A (CoA) compounds. The activated long-chain fatty acyl-CoA esters in the cytosol are able to be transported to the mitochondrial matrix only by combining with carnitine. Beta-oxidation, the primary metabolic process by which fatty acids, branched-chain amino acids, and ketoacids (as acyl-coA esters) are used as fuel for cellular energy, occurs in the mitochondria. Thus, carnitine functions as an important physiological mediator of fatty acid and protein metabolism. Carnitine also enables hepatic detoxification and excretion of chemicals, including drugs, and improves glucose disposal and may reduce insulin resistance. Carnitine is instrumental in the production and release of acetylcholine.

Carnitine from dietary sources is rapidly absorbed from the intestinal tract by both passive and active transport. Although it exhibits vitamin-like properties, carnitine is a small amino acid derivative that can be synthesized de novo in the liver, brain, and kidneys using lysine and methionine in a process requiring vitamins C, B6, and niacin. Exogenous intake may be necessary during periods of increased demand or increased loss. Acetyl-L-carnitine (ALC), the acetylated derivative ofL-carnitine, is particularly localized in muscles, brain, and testicles.

nutrient in clinical practice

Known or Potential Therapeutic Uses

Carnitine's central role in muscle function and fat metabolism has drawn the attention of clinicians and researchers to clinical applications related to these roles. Carnitine is proposed for increasing endurance and improving cardiac performance based on its known action of enhancing the efficiency of energy production in muscle tissue in general and the myocardium in particular. Human research has focused on therapeutic application of carnitine, especially as propionyl-L-carnitine (PLC), in the treatment of angina, myocardial insufficiency, peripheral claudication, and other conditions related to arterial insufficiency. CardiacL-carnitine content, essential for mitochondrial fatty acid transport and adenosine triphosphate (ATP)–diphosphate (ADP) exchange, decreases during ischemia. Furthermore, acetyl-L-carnitine (ALC) has been administered for slowing, and even partially reversing, nerve and brain deterioration associated with the aging process. Thus, the primary potential clinical uses for carnitine include claudication, Alzheimer's disease, myocardial insufficiency, and renal dialysis. Hyperlipidemia, male infertility, athletic performance, and weight loss have also been the subjects of therapeutic claims and evolving investigations, although results have been more mixed.

During pregnancy, infancy, and breastfeeding (i.e., situations of high energy demands), the physiological need forL-carnitine can exceed the capacity for endogenous synthesis. Consequently,L-carnitine is often used as a supplement with breast milk or infant formula for low-birth-weight (LBW) infants (either preterm or full term).

Possible Uses

Attention deficit–hyperactivity disorder (ADHD), alcohol dependence, Alzheimer's disease, angina pectoris, anorexia nervosa, arrhythmias, atherosclerosis, athletic performance (enhancement), cardiac ischemia, cardiac surgery (recovery), cataracts, chronic fatigue syndrome, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF; propionyl-L-carnitine), dementia, depression in elderly (acetyl-L-carnitine), diabetes mellitus, diabetic cardiac autonomic neuropathy, erectile dysfunction, human immunodeficiency virus (HIV) infection, hyperactivity in fragile X syndrome, hypercholesterolemia, hyperthyroidism, hypertriglyceridemia, infertility (male), intermittent claudication, myocardial infarction, myocardial insufficiency (e.g., CHF or cardiomyopathy), Peyronie's disease, Raynaud's disease, renal dialysis, seizure disorders, weight loss.

Deficiency Symptoms

Carnitine deficiency is characterized by inadequate tissue levels, resulting in impaired tissue fatty acid oxidation. Other symptoms of a relative deficiency may include elevated blood lipids, abnormal liver function, chronic muscle weakness, reduced energy, impaired glucose control, cardiomyopathy, encephalopathy, and recurrent episodes of coma. 1

Absolute carnitine deficiency is unlikely because of endogenous synthesis. Primary systemic carnitine deficiency is caused by a defect in the specific high-affinity carnitine transporter, which is expressed in most tissues and is responsible for bringing carnitine into the cytosol. This carnitine uptake defect is rare and is characterized by progressive infantile-onset carnitine-responsive cardiomyopathy, weakness, recurrent hypoglycemic hypoketotic encephalopathy, and failure to thrive. 2 Several inherited metabolic disorders, especially organic acidurias and disorders of beta-oxidation, can cause secondary carnitine deficiency. 3,4

Carnitine deficiency can result from numerous factors, independently or in combination, and will contribute to further sequelae and increased risk factors. Deficiency can result from high fat diets and insufficient supply of precursors for synthesis (methionine, lysine, niacin, vitamins C and B6). Individuals who have a limited intake of meat and dairy products tend to have lowerL-carnitine intakes. However, even long-term vegans usually do not display signs of carnitine deficiency. Seizure disorders, diabetes mellitus, cirrhosis, illness, and infection (e.g., HIV), strenuous exercise, trauma, pregnancy and lactation, and other conditions characterized by increased physiological stress are associated with decreased carnitine levels. A carnitine deficiency can also result from oxygen deprivation, which can occur in some cardiac conditions. 5 Carnitine deficiency may play a role in the development of retinopathy, hyperlipidemia, neuropathy, or complications of diabetes. 6 Many prescription medications may also have an adverse effect on carnitine levels and functions.

Dietary Sources

As implied by its name, carnitine is primarily found in foods of animal origin, and to a lesser extent, in foods of plant origin. Meat, milk, eggs, and dairy products are the richest sources of dietary carnitine intake, with beef being the most abundant. Generally, the redder the meat, the higher is the carnitine content. Cereals, fruit, and vegetables are relatively poor dietary sources.

Nutrient Preparations Available

Carnitine is administered as one of three salts ofL-carnitine:L-carnitine (for heart and other conditions), propionyl-L-carnitine (for heart conditions), and acetyl-L-carnitine (for Alzheimer's disease). The dosage is the same for all three forms, typically 500 mg to 1 g three times daily.

  • Note:   Only pureL-carnitine should be used as a supplement or therapeutic agent.

Dextrocarnitine (D-carnitine), or theDL-mixture, may interfere with the normal function of the levo (L-) isomer and produce signs of deficiency.

Dosage Forms Available

Capsule, powder, tablet.

Source Materials for Nutrient Preparations

Synthesized.

Dosage Range

Adult

  • Dietary:   No dietary reference intake (DRI) or recommended dietary allowance (RDA) has been established for carnitine. The average omnivorous diet provides approximately 100 to 300 mg of carnitine per day.
  • Supplemental/Maintenance:   1500 to 4000 mg per day in divided doses, when supplementation is indicated. Optimal levels of intake have not been established.
  • Pharmacological/Therapeutic:   150 mg to 1 g three times daily.
  • Toxic:   No toxicities have been reported or suspected as being associated with carnitine.

Pediatric (<18 Years)

  • Dietary:   No DRI or RDA has been established for carnitine.
  • Supplemental/Maintenance:   Usually not necessary, although often administered to LBW infants (preterm or full term) with breast milk or infant formula and in children receiving long-term total parenteral nutrition (TPN). Optimal levels of intake have not been established.
  • Pharmacological/Therapeutic:   50 mg to 1 g three times daily. One clinical trial involving children diagnosed with ADHD used 50 mg/kg twice daily, up to a maximum of 4 g daily. 7
  • Toxic:   No reported adverse effects have been specifically related to children.

safety profile

Overview

L-Carnitine is quite safe, with no significant adverse effects reported, even at high doses.

Nutrient Adverse Effects

General Adverse Effects

Rarely, gastrointestinal (GI) complaints such as nausea and vomiting have been reported with the use ofL-carnitine. 8 Sleeplessness may occur if taken before bed.

Pregnancy and Nursing

Adverse effects are not predicted, and reports are lacking. However, the lack of controlled studies involving pregnant or lactating women prevents any claims of safety and suggests that supplementation should be avoided during such life stages.

Infants and Children

Adverse effects are not predicted, and reports are lacking. Supplementation is not recommended unless otherwise indicated as essential.

Contraindications

Individuals with low or borderline-low thyroid levels should avoid carnitine supplementation because it may impair the action of thyroid hormone. 9,10This proposed effect is primarily extrapolated from research involving patients being treated for goiter with exogenous hormone.

Precautions and Warnings

DL-Carnitine may produce muscle weakness; theDisomer should be avoided because it may interfere with the activity ofL-carnitine and thus is potentially toxic.

interactions review

Strategic Considerations

The activity of carnitine suggests significant potential in preventing and treating many conditions, particularly in supporting healthy cardiovascular function. Combination therapy with a statin drug can be particularly effective in reducing lipoprotein(a) levels, especially in patients with type 2 diabetes. However, several common medications and drug classes can increase carnitine excretion or interfere with its activity. Continued development of carnitine therapy in treatment of ischemic disease is probable given its potential to limit anoxic damage while simultaneously reducing peripheral arterial resistance. 11 Furthermore, it may inhibit platelet-activating factor (PAF), thus potentially contributing an antithrombotic effect. Arterial insufficiency can decrease carnitine content of heart muscle cells. Carnitine is used conventionally in critical care and cancer surgery and has been found to benefit elderly and other high-risk patients undergoing elective cardiac surgery. 12

In regard to neurological conditions and carnitine, emerging evidence supports further research into its value in treating individuals with Alzheimer's disease. 13 Anticonvulsant medications tend to increase carnitine excretion, thus suggesting a potential role for coadministration in seizure disorders. Its immune-enhancing activity and potential efficacy during infections is countered by the adverse effects exerted on it by some chemotherapeutic agents and antiviral drugs, especially antiretroviral nucleoside analogs. Carnitine inhibits entry of thyroid hormone into certain cells and can be used to prevent adverse effects of thyroid therapy for goiter. 9,10

nutrient-drug interactions
Allopurinol
Doxorubicin and Related Anthracycline Chemotherapy
Isotretinoin and Related Retinoids
Levothyroxine and Related Thyroid Hormones
Nitroglycerin and Related Nitrates
Pivalate Prodrugs
Simvastatin and Related HMG-COA Reductase Inhibitors (Statins)
Valproic Acid and Related Anticonvulsant Medications
Zidovudine (AZT) and Related Antiretroviral Agents, Reverse-Transcriptase Inhibitor (Nucleoside)
theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Calcium Channel Blockers
Cisplatin, Ifosfamide, and Related Chemotherapy
Gentamicin
Propranolol and Related Beta-1-Adrenoceptor Antagonists (Beta-1-Adrenergic Blocking Agents)

Propranolol and Related Beta-1-Adrenoceptor Antagonists (Beta-1 Adrenergic Blocking Agents). Propranolol (Betachron, Inderal LA, Innopran XL, Inderal) Related: Acebutolol (Sectral), atenolol (Tenormin), atenolol combination drugs: atenolol and chlortalidone (Co- Tendione, Tenoretic), atenolol and nifedipine (Beta-Adalat, Tenif), sotalol (Betapace, Betapace AF, Sorine); betaxolol (Kerlone), bisoprolol (Zebeta), carteolol (cartrol), esmolol (Brevibloc), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol XL); combination drug: metoprolol and hydrochlorothiazide (Lopressor HCT), nadolol (Corgard), nebivolol (Nebilet), oxprenolol (Trasicor), penbutolol (Levatol), pindolol (Visken), propranolol combination drug: propranolol and bendrofluazide (Inderex), timolol (Blocadren)

Many studies have demonstrated the value of L-carnitine in the prevention and treatment of cardiovascular disorders. Ferro et al. 94 reported on the case of a 52-year-old man with dilated cardiomyopathy in whom concomitant treatment with L-carnitine and propranolol restored cardiac function, with a 50% reduction in mitral EPSS (E point septal separation), from 20 to 10 mm, and a decrease from 60 to 57 mm in diastolic diameter. These clinicians concluded that their “experience suggests promising benefits in adopting beta blockers combined with L-carnitine therapy in myocardial failure secondary to dilated cardiomyopathy.”

After reviewing the literature on the treatment of hypertrophic cardiomyopathy, Ferro et al. 94 also proposed that the protective action of beta-blocking agents against chronic catecholamine stimulation may be enhanced by the combination with L-carnitine. Notably, L-carnitine plays a synergistic role by acting as an important source of energy because of fatty acid oxidation and by avoiding the accumulation of lipids in the blood plasma and myocardium.

Physicians prescribing beta-blocker therapy are advised to discuss with their patients the potential benefits of concomitant carnitine. L-Carnitine and L-propionyl-carnitine are the forms most frequently used for prevention and treatment of cardiovascular conditions, with typical therapeutic dosages in the range of 1 to 3 g per day.

nutrient-nutrient interactions
Alpha-Lipoic Acid
Coenzyme Q10, Fish Oil, Magnesium, and Taurine
herb-nutrient interactions
Hawthorn
Citations and Reference Literature
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