Written by Peter Renner, Markus Horneber and the CAM-Cancer Consortium.
Updated January 29, 2015

L-Carnitine

What is it?

What is it?

L-carnitine (LC) is a naturally occurring compound which is present in humans, most animal species, numerous microorganisms and plants.1 Together with its short-, medium- and long-chain esters, collectively referred to as acylcarnitines, LC forms the major component of the body’s carnitine pool. Other carnitine compounds include acyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC).

The vital metabolic functions of LC are to facilitate the transport of fatty acids (acyl groups) as acylcarnitines across the mitochondrial membrane for beta-oxidation, to maintaining adequate mitochondrial levels of free coenzyme A and to buffer excess acetyl-coenzyme A.2 Further functions are: regulation of apoptosis and inflammation, protection from free radicals and modulation of proteins, cellular stress response and gene expression.3-6

Humans obtain LC both from endogenous synthesis and their diet. Meat, fish and dairy products are rich in LC and therefore valuable dietary sources; a well-balanced Western diet provides about 100-300mg LC per day.7 However, in healthy adults with a balanced diet not all of the consumed LC is absorbed intestinally because the body is capable of synthesizing the amount it requires.

Ratios of tissue-to-plasma levels of LC and ALC are high, with a hundredfold difference between concentrations in skeletal muscle and blood plasma. Blood plasma contains both free (~80%) and esterified LC, usually in the form of ALC (20%) and plasma levels of total (free + esterified) LC are kept within narrow limits (40-50 micromole/L in healthy adults).8, 9

Circulating LC is excreted via the kidneys as LC or ALC. Renal tubules contain a highly efficient LC transport system that re-absorbs more than 98% of the LC in the glomerular filtrate. This mechanism is effective in conserving LC body stores even during LC-poor diets. If tubular reabsorption is affected by kidney disease, or inhibited by other compounds or drugs, the increased urinary loss can result in depletion of LC body stores.8

Scientific and other names

Carnitine was named from the Latin word for flesh (‘carno’) because it was first discovered in muscle tissue. Carnitine is a trimethylated amino acid and its chemical name is (3R)-3-hydroxy-4-(trimethylazaniumyl) butanoate (IUPAC). Carnitine contains a chiral centre and exists in two enantiomeric forms. L-carnitine is the biologically active enantiomer of carnitine. Other names used include: levocarnitine, carnitor, carnitene, karnitin and vitamin BT.

Ingredients

The majority of carnitine supplements contain LC. However, compounds containing the esterized forms ALC and PLC are also available over the counter.

Application and dosage

As LC is not regarded as an essential nutrient, no values for dietary reference intake or recommended daily allowance have been set. For supplementation or pharmacological purposes, LC is available as capsules, tablets or powder for oral use and as solutions for intravenous administration. Typical doses investigated in clinical trials have ranged from 250mg to 6g per day.

History/providers

Carnitine was discovered in 1905, isolated from muscle tissue.1 Its chemical structure and major physiological functions were elucidated in the 1920s–1950s and investigations from the 1960s onwards have  led to the uncovering of its biosynthetic pathway, transport mechanisms and deficiency syndromes.10 Today, leading manufacturers use prokaryotic biotransformation processes analogous to the natural biosynthetic pathway of carnitine, which yield pure LC with high efficiency.11

Claims of efficacy and alleged indications

Supplementation with LC is claimed to protect organs from chemo- and radiotherapy-related toxicities and to counteract cancer-related fatigue (CrF)and cancer anorexia-cachexia syndrome (CACS).

Mechanisms of action

The following explanations for the molecular mechanisms of action of LC are currently under discussion:

  1. Results from animal studies indicate that cancer-related cachexia is associated with liver-acinus lipid-metabolism zonation and decreased activity of carnitine palmitoyl transferases (CPT I and CPT II)12.Signs of cachexia have been found to be ameliorated in mice by modulating the expression and activity of CPTs and by regulating cytokines.13, 14 This is in line with findings that malnourished and cachectic patients have reduced plasma concentrations and stores of carnitine in the body.15-18 However, observations in carnitine-deficient patients with lower carnitine stores suggest that these did not affect resting energy expenditure or total food intake.19
  2. Long-chain fatty acids are the most energy-rich substrates for beta-oxidation, and increased skeletal muscle LC content has been reported to delay muscular fatigue in rats20.It could be speculated that increases in ALC levels would have a significant impact on energy production, thus reducing fatigue.
  3. Findings in rats suggest that ALC could protect nervous tissue from chemotherapy-induced toxicity, through protein kinase C-related signalling pathways, by modulating the activities of nerve growth- and glial-derived neurotrophic factors,21, 22 and by protecting the mitochondria of peripheral nerves.23
  4. Animal studies also suggest that LC and PLC could decrease the duration and severity of radiation-induced mucositis because of their capacity to scavenge reactive oxygen species, activate antioxidant enzymes and protect DNA from cleavage.24, 25
  5. There is evidence from rats that carnitine deficiency might aggravate carboplatin nephropathy26 and that patients with decreased dietary carnitine uptake develop carnitine deficiency when treated repeatedly with chemotherapy, including platinum derivatives.27, 29
  6. There is evidence from two mouse models with carcinogen-induced cancers that dietary carnitine might inhibit the development of precancerous and neoplastic lesions.30, 31

Prevalence of use

There are no data available on the prevalence of use of carnitine in cancer patients.

Legal issues

In the USA,LC is approved by the Food and Drug Administration for the treatment of carnitine deficiencies and according to the Office of Dietary Supplements, LC and ALC are approved dietary supplements.7 In the EU,LC and PLC are approved for use in foodstuffs for particular nutritional uses.51

Costs and expenditures

Good quality LC supplements cost about €0.30 per 1000mg. Taking into account typical daily doses of 10–50mg/kg, costs for a 70kg patient could amount to anything between €8.00 and €30.00 per month.

Citation Peter Renner, Markus Horneber, CAM-Cancer Consortium. L-Carnitine [online document]. http://ws.cam-cancer.org/The-Summaries/Dietary-approaches/L-Carnitine. January 29, 2015.

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