Actovegin

Actovegin is a highly filtered extract obtained from calf blood which enhances aerobic oxidation in mammals.[1] This improves absorption of glucose and oxygen uptake in tissue,[1] which may enhance physical performance and stamina.

Actovegin made headlines from 2009 to 2011 when Canadian sports doctor Anthony Galea was charged with illegally providing professional athletes with a number of performance-enhancing drugs, including Actovegin.[2][3] As revealed by later testimony by riders, it was also regularly used by Lance Armstrong and the members of his U.S. Postal Service Pro Cycling Team on the 2000 Tour de France to enhance their performance.[4] Recent study has proven that Actovegin does not improve human peak performance.[5] Actovegin can be useful to treat muscle injuries.[6]

Mechanism of action

According to Gulevsky, et al., Actovegin "is highly purified hemodialysate extracted from vealer blood by ultrafiltration."[1]

Actovegin has been shown to improve the transport of glucose over a plasma membrane and the uptake of oxygen by tissues.[1] This can lead to aerobic oxidation, which provides a cell with access to more energy and potentially enhances its function.[1] Actovegin has large amounts of superoxide dismutase enzymes and magnesium.[7]

Uses and side effects

Nycomed, a Swiss drug company which manufactures Actovegin,[8] claims it can be used for circulation and nutrition disturbances, skin grafting, burns, and wound-healing impairment.[9] Actovegin has also been used as a performance enhancer.[10]

It has been investigated for use in treatment of polyneuropathy in diabetes,[11] and for stroke.[12] One study found that when tissues suffer from hypoxia caused circulation abnormalities, Actovegin helps capillaries improve circulation by enhancing the neogenic mechanism in blood vessels.[7]

There are reports suggesting that Actovegin have ergogenic ability, but this has been ruled out by a high quality scientific study.<[5]

Manufacturing process

Actovegin is a deproteinated, pyrogen- and antigen-free hemodialysate of calf blood. It is manufactured from calf blood in several steps by ultrafiltration: here, the manufacturer uses different cut off sieves: first, an ultrafiltration step employing a cut off of 6 kD is performed, followed by a vacuum distillation step and removal of the precipitate by filtration (0.45 urn) and titration to pH 6.8. Afterwards, the product is subjected to sterile filtration with prefilters of 0.2 pm and 0.45 pm and stored at 2-6 °C for more than 14 days and subsequently filtered (0.45 pm) and again titrated to pH 6.8. After subsequent pH titration steps, the product is again subject to filtration (7 pm and 0.2 pm) and another ultrafiltration step with a lOkDa cut off, followed by sterile filtration with prefilters of 0.45 pm and 0.2 pm. After another storage period at 2-6 °C for more than 56 days, the final precipitate is removed by filtration (0.45 pm) and diluted to a nominal concentration to 200 mg/ml dry weight. Finally, deproteinization is completed by sterile filtration with prefilters of 0.2 pm and 0.45 pm. The analysis of the final product shows that it contains a mixture of natural substances: both inorganic components like common blood electrolytes (e.g. chloride, phosphate, sodium, potassium, calcium, and magnesium, several sources for nitrogen, amino acids, peptides, glucose, acetate and lactate) and organic components like amino acids, a number oligopeptides, nucleosides, glycosphingolipids and products of the intermediary metabolism.[13]

Counterindications

Anaphylactic shock has been observed in at least one patient treated with actovegin[14] but was likely due to infection, i.e. septic shock instead of anaphylactic shock, unrelated to actovegin administration.

Market approvals

As of July 2011, the drug was not approved for sale, importation, or use in the United States.[15] Although, being unscheduled, it is legal to possess and use. It is an unapproved drug in Canada as well.

References

  1. 1 2 3 4 5 Gulevsky, Alexander Kirillovich; Abakumova, Yelena Sergeevna; Moiseyeva, Natalya Nikolaevna; Ivanov, Yevgeniy Gennadievich (2011). "Influence of Cord Blood Fraction (below 5 kDa) on Reparative Processes during Subchronic Ulcerative Gastropathy". Ulcers. 2011: 1–9. doi:10.1155/2011/214124.
  2. ↑ Doheny, Kathleen. "FAQ on Actovegin: An Expert Explains How the Drug May Enhance Athletic Performance." WebMD Health News. December 16, 2009. Accessed 2011-09-16.
  3. ↑ Schmidt, Michael S.; Austen, Ian (2009-12-17). "Doctor Under Investigation Is Charged in Canada.". The New York Times. Retrieved 2009-12-17.
  4. ↑ USADA v. Armstrong, Reasoned decision, section IV B 3.e (pp. 42–45) (USADA 10 October 2012). Text
  5. 1 2 Buchmayer, Florian; Pleiner, Johannes; W. Elmlinger, Martin; Sitte, Harald H. (2010). "Actovegin: a Biological Drug for more than 5 Decades". Wien Med Wochenschr. 55 (15) – via Center for Physiology and Pharmacology.
  6. ↑ Lee, P.; Rattenberry, A.; Connelly, S.; Nokes, L. (2011). "Our Experience on Actovegin, is it Cutting Edge?". International Journal of Sports Medicine. 32 (4): 237–41. doi:10.1055/s-0030-1269862. PMID 21271496.
  7. 1 2 Nordvik, B. "Actovegin. New Aspects of Clinical Application." In Collected Book of Research and Practice Articles. S. A. Rumyantseva, ed. St. Petersburg, Russia: MAPO, 2002, p. 280.
  8. ↑ "Nycomed May Invest 35 Million Euros in Ukrainian Production Capacities." The Pharma Letter. 3 May 2011. Accessed 2011-09-16.
  9. ↑ "Actovegin." Nycomed. 2011. Accessed 2011-09-16.
  10. ↑ Tsitsimpikou, Christina; Tsiokanos, Athanasios; Tsarouhas, Konstantinos; Schamasch, Patrick; Fitch, Kenneth D; Valasiadis, Dimitrios; Jamurtas, Athanasios (2009). "Medication Use by Athletes at the Athens 2004 Summer Olympic Games". Clinical Journal of Sport Medicine. 19 (1): 33–8. doi:10.1097/JSM.0b013e31818f169e. PMID 19124981.
  11. ↑ Ziegler, D.; Movsesyan, L.; Mankovsky, B.; Gurieva, I.; Abylaiuly, Z.; Strokov, I. (1997). "Treatment of Symptomatic Polyneuropathy With Actovegin in Type 2 Diabetic Patients". Diabetes Care. 33 (11): 1809–14. doi:10.2337/dc09-0545. PMID 9470838.
  12. ↑ Derev’yannykh, E. A.; Bel’skaya, G. N.; Knoll, E. A.; Krylova, L. G.; Popov, D. V. (2008). "Experience in the use of actovegin in the treatment of patients with cognitive disorders in the acute period of stroke". Neuroscience and Behavioral Physiology. 38 (8): 873–5. doi:10.1007/s11055-008-9051-0. PMID 18802768.
  13. ↑ Sitte, Harald H. (2010-05-12). "Actovegin: a Biological Drug for more than 5 Decades - Get Actovegin". Wien Med Wochenschr. doi:10.1007/s10354-011-0865-y. Retrieved 2016-09-07.
  14. ↑ Maillo, Luis (2008). "Anaphylactic Shock with Multiorgan Failure in a Cyclist after Intravenous Administration of Actovegin". Annals of Internal Medicine. 148 (5): 407. doi:10.7326/0003-4819-148-5-200803040-00022. PMID 18316765.
  15. ↑ Kovaleski, Serge. "Canadian Doctor Tied to Professional Athletes Guilty of Drug Charge." New York Times. July 6, 2011. Accessed 2011-09-16.
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