New uses for carnitine

Well-documented in the sports nutrition arena, L-carnitine research suggests new avenues of clinical efficacy ranging from cardiovascular health to weight loss to ageing. Barbara Anan Kogan, OD, investigates

Carnitine enjoys a robust body of research to support its role as ?the energy nutrient.? Although long the purview of body builders and other elite athletes, L-carnitine?s safety has been validated to the point where it is routinely added to infant formulations.

Carnitine?s multi-functional uses have reached the ears of the National Institutes of Health, which recently sponsored a workshop with the Institutes of Child Health and Development, the Center for Complementary and Alternative Medicine (NCCAM), and the Office of Dietary Supplements. Nearly 200 people attended to explore the uses of L-carnitine that go beyond the sports nutrition field.

?Two days for this workshop were needed to expand research interests, particularly collaboration between centres and researchers,? says carnitine scientific planning committee member Irini Manoli, MD. Potential applications include kidney disease, cardiovascular conditions, immunity, ageing and male infertility.

Because a nutrient?s absorption abilities are vital in manifesting physiological changes, among the first items on the agenda was to confirm carnitine?s bioavailability. ?Acetyl-L-carnitine, an acyl-carnitine ester, is quantitatively and functionally most significant with absorption of 0.5 to 6g of dietary L-carnitine at 54 to 87 per cent and an absolute bioavailability of 14 to 18 per cent,? says Charles J Rebouche, PhD, from the University of Iowa. ?Renal absorption of LC is highly efficient at 90 to 99 per cent with evidence for renal tubular secretion of both LC and ALC.?

Italy?s Sigma Tau SpA?s Menotti Calvani, MD, studied 1,038 cardiovascular disease patients with end-stage renal disease and hemodialysis, who, after being administered intravenous L-carnitine as an essential nutrient replacement, increased red blood cell count. The mitochondria have an integral role in the carnitine pathway as they regulate lipid and glucose metabolism.

?It is important to note L-carnitine was approved by the FDA for primary and secondary deficiency under the FDA?s Center for Drug Evaluation and Regulation?s metabolic and endocrine drug products in 1999 for this disease,? Calvani points out.

Research demonstrates L-carnitine?s support of a healthy heart muscle, which can lead to reduced mortality
The heart obtains some 70 per cent of its energy from fat breakdown. Because L-carnitine is central to the formation of energy from fat, the heart is therefore dependent on L-carnitine for most of its energy production. Research demonstrates L-carnitine?s support of a healthy heart muscle, which can lead to reduced mortality among those who have previously suffered heart attacks. 1

One of the fundamental roles of L-carnitine is to transport long-chain fatty acids across the membrane of the mitochondria, the cellular organelle responsible for most ATP synthesis and hence energy production. Although fatty acids need to enter the mitochondria for oxidation, the fatty acids by themselves are unable to penetrate the inner mitochondrial membrane. A transport system consisting of L-carnitine and at least three enzymes shuttles the long-chain fatty acids into the mitochondria. A study published in the August 2004 issue of Metabolism demonstrates that Lonza?s L-Carnipure brand of L-carnitine can increase fatty acid oxidation in healthy adults.2 The human study, of 4.5g/day L-carnitine L-tartrate for 10 days on 12 slightly overweight adults, confirm that L-Carnipure carries long-chain fatty acids into the mitochondria where they are oxidised for energy. Its ability to generate energy from fat makes carnitine useful as part of a weight management program.

?This is great news to all people who exercise, those who undergo a weight management program and those who have a high energy demand,? says lead researcher Klaus D Wutzke.

In related research, limited fatty acid oxidation is found in those with carnitine deficiencies.3 Paediatric patients benefited from an injection for toxic organic acid accumulation causing secondary carnitine deficiencies. Philadelphia?s Children?s Hospital at the University of Pennsylvania?s Charles A Stanley, MD, finds limited fatty acid oxidation and is seen as a cardiomyopathy or hypoglycaemia in infancy and excessive dosing of pivalate conjugated antibiotics.

Ageing and sexual health
In delaying ageing by reversing oxidative mitochondrial decay with acetyl carnitine and lipoic acid, 30-year carnitine researcher Bruce Ames, PhD, found feeding old rats acetyl carnitine with lipoic acid restores the velocity of the reaction for ALC transferral and mitochondrial function mimicking oxidation, and lowers oxidants and neuron RNA oxidation.

A study published in the April 2004 Urology demonstrates L-carnitine plus its metabolite, acetyl-L-carnitine, can treat symptoms of male ageing, including sexual dysfunction, depressed mood and fatigue.4 The six-month, randomised, placebo-controlled study followed 120 men from 60-74 years old. One group was given 160mg/day testosterone undecanoate, the other 2g/day L-carnitine plus 2g/day acetyl-L-carnitine.

Testosterone and carnitines significantly improved the peak systolic velocity, resistive index of cavernosal penile arteries, nocturnal penile tumescence, International Index of Erectile Function score, Depression Melancholia score, and fatigue scale score. The carnitines proved significantly more active than testosterone in improving nocturnal penile tumescence and the Erectile Function score.

Along the same lines, L-carnitine and acetyl-L-carnitine are found in high concentrations in the epididymal tissue, sperm and seminal fluid, which lends the obvious rationale for carnitine?s use for improving sperm quality. Specifically, studies have shown that 3g/day L-carnitine is associated with significant increases in sperm concentration and count, percentage of motile sperm and the percentage of sperm with rapid linear progression.5,6,7,8

Acetyl-L-carnitine is readily converted into an important neurotransmitter known as acetylcholine, which is known to be profoundly deficient in the brains of Alzheimer?s patients. It is for these reasons that acetyl-L-carnitine has been evaluated in dementia studies.

Ames reported on clinical trials with acetyl-L-carnitine conducted by the University of California-Berkeley and Oakland?s Children?s Hospital. He reported significant efficacy in the treatment of both mild cognitive impairment and Alzheimer?s disease when compared with the placebo, as well as spatial memory improvement in older rats that were administered acetyl-L-carnitine.

Researchers at the University of California, San Diego, found a striking reduction in the rate of mental decline in younger Alzheimer?s patients taking 3g/day acetyl-L-carnitine HCl over the one-year evaluation.9 However, researchers are confounded in rationalising why late-onset Alzheimer?s patients tend to progress more rapidly.

Diabetes and weight loss
Carnitine workshop scientific planning committee member and chief of the Endocrine Section at NCCAM Marc R Blackman, MD, finds, ?There are enough pre-clinical and human studies to suggest that carnitine can alter mitochondrial functions via antioxidant, anti-apoptotic and/or other mechanisms. Although carnitine has been reported to reduce total body fat, to date we do not know if it decreases (metabolically active) abdominal fat in animals or humans. It is important to determine whether carnitine increases insulin sensitivity and glucose tolerance and also improves insulin actions at the vascular level.?

Italy?s Catholic University?s Instituto di Medicine Interna, Geltrude Mingrone, MD, PhD, studied the mature onset of diabetes in youth, and found that when the lowest dose of L-carnitine was administered to diabetics, glucose reuptake improved with storage vs loss through oxidation. Using Sigma Tau?s CARNITOR IV brand L-carnitine, insulin sensitivity improved by 50 per cent on type 2 diabetics and with constant Carnitor injection for insulin-resistant diabetics.

In Blackman?s opinion, ?These are worthy areas of inquiry insofar as they may suggest novel uses of carnitine in management of patients with insulin resistance. The opportunities for further productive research in this area are many.?

Barbara Anan Kogan, OD, has an ophthalmology practice in Washington, DC.
Respond: [email protected]
All correspondence will be forwarded to the author.

1. Davini P, et al. Controlled study on L-carnitine therapeutic efficacy in post-infarction. Drugs Exper Clin Res 1992;18(8):355.
2. Wutzke KD, Lorenz H. The effect of L-carnitine on fat oxidation, protein turnover, and body composition in slightly overweight subjects. Metabolism 2004 Aug; 53(8):1002-6.
3. Lohninger A, et al. Carnitine deficiency causes downregulation of carnitine acyltransferase genes. 3rd ISSFAL Congress 1998, p220.
4. Cavallini G, et al. Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging. Urology 2004 Apr; 63(4):641-6.
5. Costa M, et al. L-carnitine in idiopathic asthenozoospermia: a multicenter study. Italian Study Group on Carnitine and Male Infertility. Andrologia 1994 May-Jun; 26(3):155-9.
6. Vitali G, et al. Carnitine supplementation in human idiopathic asthenospermia: clinical results. Drugs Exp Clin Res 1995; 21(4):157-9.
7. Mioic S, et al. 16th World Congress on fertility and sterility and 54th annual meeting of the Amer Soc Rep Med 1996. San Francisco.
8. Mioic S, et al. Amer Soc Andrology, 25th annual meeting 2000. Boston.
9. Thal LJ, et al. A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer?s disease. Neurology 1996; 47:705-11.

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