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. Injecting it into the blood track is not allowed. Local utilisation is allowed in countries like Canada and Sweden. Doctors like Hans-Wilhelm Müller-Wohlfahrt and Richard Steadman think Actovegin should be allowed in general. Others think there is not enough research, and persons from the World Anti-Doping Agency like Olivier Rabin is sceptical that it is having more than a placebo effect.[2][3]

Actovegin made headlines from 2009 to 2011 when Canadian sports doctor Anthony Galea was charged with drug smuggling, conspiring to lie to federal agents, unlawful possession with intent to distribute and practising medicine without a licence in the United States. Galea pleaded guilty of bringing misbranded and unapproved drugs, including Nutropin, a human growth hormone, and Actovegin, into the United States. The discipline committee for the College of Physicians and Surgeons of Ontario (CPSO) suspended Galeas license for 9 months for professional misconduct.[4] [5][6][7]

Actovegin made headlines again in 2016, stemming from a 2011 incident, when American former professional athlete and fashion designer Nick Brandt-Sorenson was charged with a one count misdemeanor by the United States Department of Justice involving misbranding Actovegin into interstate commerce.[8][9][10][11] Afterwards in 2016, USADA banned the working artist and fashion designer Nick Brandt-Sorenson for life after his third anti-doping offense of being uncooperative.[12]

On 08 Sept 2011, Swiss NYCOMED Actovegin® was awarded “Medication of the Year” in Ukraine, with sincere congratulations expressed by the Head of Committee on Public Health Supreme Council of Ukraine, the Minister of Public Health of Ukraine Aleksandr Anischenko and the Chairman of State Administration of Ukraine for Medicinal Products Aleksey Soloviov.[13]

As revealed by later testimony by riders, Actovegin 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.[14] One small-scale trial found that Actovegin did not improve human peak performance, at least in the short-term. [15] Actovegin can be useful to treat muscle injuries, .[16]

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.[17]

Uses and side effects

Nycomed, a Swiss drug company which manufactures Actovegin,[18] claims it can be used for circulation and nutrition disturbances, skin grafting, burns, and wound-healing impairment.[19] Actovegin has also been used as a performance enhancer.[20]

It has been investigated for use in treatment of polyneuropathy in diabetes,[21] and for stroke.[22][23] 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.[17]

Anaphylactic shock has been observed in at least one patient treated with actovegin.[24]

There are reports suggesting that Actovegin have ergogenic ability, however one small trial found no apparent benefit from short-term use. [15]

Two studies certified Actovegin to have an anti-inflammatory effect. One of the two studies certified Actovegin to reduce Progressive muscular atrophy-induced inflammation in human cells.[25][26]

Another study certified Actovegin to have a positive impact on the growth of muscle cells.[27][28]

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 using various precipitation techniques and filters. The analysis of the final product shows that it contains a mixture of natural substances: both inorganic components such as 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 such as amino acids, a number oligopeptides, nucleosides, glycosphingolipids and products of the intermediary metabolism.[29]

Market approvals

As of July 2011, the drug was not approved for sale, importation, or use in the United States.[30] It is an unapproved drug in Canada as well.

References
  1. 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. Dopingfund in Göteborg, Polizei stellt Ermittlungen ein
  3. The doctor they call 'Healing Hans', ESPN, 2011-12-16.
  4. Fish, Mike (December 16, 2011). "Anthony Galea receives no jail time". ESPN. Retrieved December 16, 2011.
  5. 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.
  6. Schmidt, Michael S.; Austen, Ian (2009-12-17). "Doctor Under Investigation Is Charged in Canada". The New York Times. Retrieved 2009-12-17.
  7. Canadian regulatory body suspends Dr. Anthony Galea for nine months following U.S. sports doping scandal, Daily News, 2017-12-06.
  8. "Former Pro Cyclist Pleads Guilty Misbranded/Non FDA Approved Drug Importation". Partnership for Safe Medicines. 2016-03-24. Retrieved 2023-03-01.
  9. "Former Pro Cyclist Pleads Guilty To Importing, Selling Performance Enhancing Drugs". www.cbsnews.com. 16 March 2016. Retrieved 2023-03-01.
  10. companies (2016-04-18). "Fitness app Strava faces an uproar over an elite cycling user linked to doping". Los Angeles Times. Retrieved 2023-03-01.
  11. Flax, Peter (2016-03-28). "Who is Thorfinn-Sassquatch? The mysterious case of a Los Angeles Strava legend". CyclingTips. Retrieved 2023-03-01.
  12. "L.A. cyclist who sold performance-enhancing drugs to be sentenced today". Daily News. 2016-07-20. Retrieved 2023-03-01.
  13. "Actovegin And Other NYCOMED Products Called The Medicines Of The Year at PANACEA-2011". www.newswire.com (Press release). Retrieved 2023-03-06.
  14. USADA v. Armstrong, Reasoned decision, section IV B 3.e (pp. 42–45) (USADA 10 October 2012).Text
  15. Lee P, Nokes L, Smith PM (2012). "No effect of intravenous Actovegin® on peak aerobic capacity". Int J Sports Med. 33 (4): 305–9. doi:10.1055/s-0031-1291322. PMID 22318562. S2CID 2760688.
  16. 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. S2CID 28641277.
  17. 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.
  18. "Nycomed May Invest 35 Million Euros in Ukrainian Production Capacities." The Pharma Letter. 3 May 2011. Accessed 2011-09-16.
  19. "Actovegin." Nycomed. 2011. Accessed 2011-09-16.
  20. 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. S2CID 40623178.
  21. 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. PMC 2713653. PMID 9470838.
  22. 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. S2CID 8234398.
  23. Guekht, A; Skoog, I; Edmundson, S; Zakharov, V; Korczyn, AD (2017). "ARTEMIDA Trial (A Randomized Trial of Efficacy, 12 Months International Double-Blind Actovegin): A Randomized Controlled Trial to Assess the Efficacy of Actovegin in Poststroke Cognitive Impairment". Stroke. 48 (5): 1262–1270. doi:10.1161/STROKEAHA.116.014321. PMC 5404405. PMID 28432265.
  24. 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.
  25. "Comprehensive Analytics of Actovegin® and Its Effect on Muscle Cells". 11 September 2017. {{cite journal}}: Cite journal requires |journal= (help)
  26. Reichl, F. X.; Högg, C.; Liu, F.; Schwarz, M.; Teupser, D.; Hickel, R.; Bloch, W.; Schweikl, H.; Thomas, P.; Summer, B. (July 2020). "Actovegin® reduces PMA-induced inflammation on human cells". European Journal of Applied Physiology. 120 (7): 1671–1680. doi:10.1007/s00421-020-04398-2. PMC 8497287. PMID 32447451.
  27. Reichl, F. X.; Holdt, L. M.; Teupser, D.; Schütze, G.; Metcalfe, A. J.; Hickel, R.; Högg, C.; Bloch, W. (2017). "Comprehensive Analytics of Actovegin® and Its Effect on Muscle Cells". International Journal of Sports Medicine. 38 (11): 809–818. doi:10.1055/s-0043-115738. PMID 28895623.
  28. Fiedler, Matthias (29 April 2021). "The eternal medicine man". Der Spiegel (in German).
  29. Buchmayer F, Pleiner J, Elmlinger MW, Lauer G, Nell G, Sitte HH (2011). "Actovegin: a biological drug for more than 5 decades". Wien Med Wochenschr. 161 (3–4): 80–8. doi:10.1007/s10354-011-0865-y. PMID 21404144. S2CID 20989513.
  30. 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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