Pros and cons of Carnitine and L-carnitine, Linus ing Institute

[Guest guest]

[Ed. note: A relatively rare, but significant side effect of carnitine and acetyl-l-carnitine use for those who have it is a condition known as fish-odor syndrome. See below.]

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 500 mg to 2,000 mg/day.

Acetyl-L-carnitine is available without a prescription as a nutritional supplement. In addition to providing L-carnitine, it provides acetyl groups, which may be used in the formation of the neurotransmitter, acetylcholine. Supplemental doses usually range from 500 mg to 2,000 mg/day (6).

Age-related declines in mitochondrial function and increases in mitochondrial oxidant production are thought to be important contributors to the adverse affects of aging. Tissue L-carnitine levels have been found to decline with age in humans and animals (7). Feeding aged rats acetyl-L-carnitine (ALCAR) reversed age-related declines in tissue L-carnitine levels and reversed a number of age-related changes in mitochondrial function, but high doses of ALCAR increased liver mitochondrial oxidant production (8). More recently, a series of studies in aged rats found that supplementation with either ALCAR or alpha-lipoic acid, a mitochondrial cofactor and antioxidant, improved mitochondrial energy metabolism, decreased oxidative stress, and improved memory (9, 10). Interestingly, supplementation with the combination of ALCAR and alpha-lipoic acid resulted in significantly greater improvement than either compound alone. While these findings are very exciting, the researchers involved caution that these studies used relatively high doses of the compounds and only for a short time (one month). It is not yet known whether taking relatively high doses of these two naturally occurring substances will benefit rats in the long-term or will have similar effects in humans. Clinical trials in humans are planned, but it will be several years before the results are available.

HIV/AIDS

One of the hallmarks of infection with the retrovirus, HIV, is a progressive decline in the numbers of critical immune cells known as CD4 T lymphocytes (CD4 cells), ultimately leading to the development of AIDS. Lymphocytes of HIV-infected individuals inappropriately undergo programmed cell death (apoptosis). Limited evidence in cell culture experiments and in humans suggests that L-carnitine supplementation may help slow or prevent HIV-induced lymphocyte apoptosis. In an uncontrolled trial, 11 asymptomatic HIV-infected patients, who had refused antiretroviral treatment despite progressively declining CD4 cell counts, were treated with 6 grams/day of L-carnitine intravenously for 4 months (35). After 4 months of L-carnitine therapy, CD4 cell counts increased significantly and markers of lymphocyte apoptosis decreased, although there was no significant change in plasma levels of the HIV virus (viremia). Long-term outcomes were not reported in these patients. In a more recent study, 20 HIV-infected individuals were randomly assigned to receive the antiretroviral agents, zidovudine (AZT) and didanosine (DDI), with or without supplemental L-carnitine (36). Although CD4 cell counts and plasma HIV levels were not different between the two groups after 7 months of therapy, indicators of CD4 cell apoptosis were significantly lower in the group taking L-carnitine.

Some antiretroviral agents (nucleoside analogues) used to treat HIV-infection appear to cause a secondary L-carnitine deficiency that may lead to some of their toxic side effects (see Drug interactions) (2). A small cross-sectional study found that nerve concentrations of acetyl-L-carnitine were significantly lower in HIV patients who developed peripheral neuropathy while taking nucleoside analogues than in control subjects (37). Ten out of 16 HIV patients with painful neuropathies reported improvement after 3 weeks of intravenous or intramuscular acetyl-L-carnitine treatment (38). Although more controlled research is needed before conclusions can be drawn, L-carnitine supplementation may be a beneficial adjunct to antiretroviral therapy in some HIV-infected individuals.

Toxicity

In general L-carnitine appears to be well tolerated. Toxic effects related to L-carnitine overdose have not been reported. L-carnitine supplementation may cause mild gastrointestinal symptoms, including nausea, vomiting, abdominal cramps and diarrhea. Supplements providing more than 3,000 mg/day may cause a "fishy" body odor. Acetyl-L-carnitine has been reported to increase agitation in some Alzheimer's disease patients and to increase seizure frequency and/or severity in some individuals with seizure disorders (6). Only the L-isomer of carnitine is biologically active. The D-isomer may actually compete with L-carnitine for absorption and transport, increasing the risk of L-carnitine deficiency (1). Supplements containing a mixture of the D-, and L-isomers (D,L-carnitine) were associated with muscle weakness in patients with kidney disease. Controlled studies examining the safety of L-carnitine supplementation in pregnant and breastfeeding women are lacking (6).

Drug Interactions

The anticonvulsant, valproic acid, and nucleoside analogues, used in the treatment of HIV infection, including zidovudine (AZT), didanosine (ddI), zalcitabine (ddC) and stavudine (d4T), may produce secondary L-carnitine deficiencies. Pivalic acid-containing antibiotics used in Europe (pivampicillin, pivmecillinam and pivcephalexin) may also produce secondary L-carnitine deficiencies (3, 6). The cancer chemotherapy agents, ifosfamide and cisplatin, may increase the risk of secondary L-carnitine deficiency, and there is limited evidence that L-carnitine supplementation may help prevent cardiomyopathy induced by doxorubicin (adriamycin) therapy (2).

http://lpi.oregonstate.edu/infocenter/othernuts/carnitine/

FISH ODOR SYNDROME (TRIMETHYLAMINURIA)

Gabe Mirkin, M.D.

Many foods that you eat are loaded with choline and carnitine, two nutrients that your body uses to keep you healthy. Choline and carnitine that are not absorbed in your upper intestinal tract, pass to your colon where bacteria ferment these two chemicals to form trimethylamine which smells like rotten fish. This chemical is absorbed from the colon into the bloodstream and travels to the liver which breaks trimethylamine down to odorless trimethylamine N-oxide which is then excreted in the urine. However, some people inherit a condition in which they lack the liver enzyme that breaks down the fishy-smelling trimethylamine to its odorless product and their breath, sweat, tears, saliva, urine and vaginal secretions smell like rotting fish.

To be able to remain in society, these people must restrict foods that contain lots of choline and carnitine, such as fish and meats. They may also benefit from short courses of metronidazole, an antibiotic that kills the bacteria normally found in the colon to cause trimethylamine to form.

HU Rehman. Fish odour syndrome.Postgraduate Medical Journal, 1999, Vol 75, Iss 886, pp 451-452.