The use of carnitine in oncology

DNA moleculeNeoplastic diseases are the second cause of death. Each year about 90 thousand people die because of cancer. It is estimated that this number will keep growing, becoming in the near future, the first cause of death before 65 years of age for both women and men. Tumors are a serious health and social problem of the 21st century.

Currently, chemotherapy is commonly used as a method of treatment of different types of human tumors. Unfortunately, the clinical usefulness of this method is limited by multiple organ toxicity. The toxic effects of chemotherapy result from the mechanisms not involved in their anticancer activity.

Many recent research has shown that some of the today commonly used anticancer drugs, such as doxorubicin, cisplatin, carboplatin or ifosfamide, interfere with the absorption, synthesis and excretion of carnitine in the non-tumor tissues, resulting in a secondary carnitine deficiency.

Carnitine is a naturally occurring in the organism quaternary ammonium compound. Carnitine plays an important role in the transportation of long-chain fatty acids from cytoplasm into mitochondria, where the process of beta-oxidation takes place. The human body synthesizes only 25% of carnitine. The remaining 75% must be taken from the diet. The main source in the diet are meat and dairy products.

The low level of carnitine in serum of patients in the terminal stages of cancer, is also affected by reduced intake of carnitine in the diet and the increased urinary excretion by the kidneys, as well as impaired endogenous production.

Recent studies have shown that carnitine deficiency can be reversed by the substitution therapy. Such substitution has no effect on the anticancer therapeutic efficacy.

One of the chemotherapeutic drugs used in cancer therapy is doxorubicin. This drug contributes to the development of cardiomyopathy, myocardial infarction, through inhibition of gene expression of fatty acid-binding protein, what interfere with beta-oxidation in cells. Consequently, this leads to a deficiency of ATP in heart cells.

There were conducted many studies in rats, which aim was to prove the beneficial effects of carnitine supplementation during doxorubicin therapy. The animals treated with carnitine at the same time, had a higher ejection fraction and the higher pressure in the left ventricle than the rats, that received only doxorubicin. The studies proved also, that the rats treated with additional carnitine, synthesize significantly more heat shock proteins than animals treated with doxorubicin alone.

The researchers suggest that carnitine reduces inhibition of oxygen uptake and formation of ATP and by inducing the formation of heat-shock proteins, enhances the protective mechanisms in the heart cells, which reduces the incidence of doxorubicin-induced cardiomyopathy.

The results suggest that carnitine reduces the incidence of cardiomyopathy. Considering the above facts and inability to replace anticancer drugs with other substances, it will be important to include carnitine supplementation in the basic scheme of anticancer therapy. By reducing organ toxicity of cytostatics, it will be possible to use higher doses of this drugs, that would destroy more cancer cells, and therefore increase patient’s chances of survival.

Writen by: Agnieszka Grzechnik, Krzysztof Grzechnik, Justyna Podgórska

Source:
1. Mohamed M. Sayed-Ahmed. Role of carnitine in cancer chemotherapy-induced multiple organ toxicity. Saudi Pharmaceutical Journal (2010) 18, 195–206
2. Sayed-Ahmed, M.M., Al-Shabanah, O.A., Hafez, M.M., Aleisa,A.M., Al-Rejaie, S.S., 2010. Inhibition of gene expression of heart fatty acid binding protein and organic cation/carnitine transporter in doxorubicin cardiomyopathic rat model. Eur. J. Pharmacol. 640, 143–149.
3. Waldner, R., Laschan, C., Lohninger, A., Gessner, M., Tu¨ chler, H., Huemer, M., Spiegel, W., Karlic, H., 2006. Effects of doxorubicincontaining chemotherapy and a combination with L-carnitine on oxidative metabolism in patients with non Hodgkin lymphoma. J. Cancer Res. Clin. Oncol.132, 121–128.
4. Yoon, H.R., Hong, Y.M., Boriack, R.L., Bennett, M.J., 2003. Effect of L-carnitine supplementation on cardiac carnitine palmitoyltransferase activities and plasma carnitine concentrations in adriamycin-treated rats. Pediatr. Res. 53, 788–792.

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