Actovegin is a biological drug that has been used for the treatment of sports muscle injuries. Several in vitro studies have shed light on potential mechanisms of action and the drug has consistently demonstrated its potential to reduce return from injury time for muscle tears in elite athletes. Yet it was banned for a time under the International Olympic Committee (IOC) as a blood doping agent, this ban was based on presumptuous conclusions and subsequently lifted after no indisputable evidence could be provided. This editorial aims to provide readers with some of the key, objective facts relating to Actovegin and then based on this, will offer an informed opinion on its role in sports medicine. We also hope to highlight the importance of evidence-based medicine, particularly in the volatile field of Sports Medicine, and the need for facts, not fiction

Brock, James

Kwan, Alvin

Lee, Paul

Nokes, Len

Smith, Paul M.

Journal of Tissue Science & Engineering

Paul YF Lee

Alvin P Kwan

Paul M Smith

James Brock

Len Nokes

Crossref

Actovegin Equals to Performance Enhancing Drug Doping: Fact or Fiction?

Cardiff Metropolitan Research Repository (DSpace)

Volume 7 • Issue 3 • 1000179J Tissue Sci Eng, an open access journalISSN: 2157-7552Short Communication OMICS InternationalJournal of Tissue Science & EngineeringJournal of Tissue Science & EngineeringISSN: 2157-7552Lee et al., J Tissue Sci Eng 2016, 7:3DOI: 10.4172/2157-7552.1000179IntroductionActovegin is a biological drug that has been used for the treatment of sports muscle injuries. Several in vitro studies have shed light on potential mechanisms of action and the drug has consistently demonstrated its potential to reduce return from injury time for muscle tears in elite athletes. Yet it was banned for a time under the International Olympic Committee (IOC) as a blood doping agent, this ban was based on presumptuous conclusions and subsequently lifted after no indisputable evidence could be provided. This editorial aims to provide readers with some of the key, objective facts relating to Actovegin and then based on this, will offer an infromed opinion on its role in sports medicine. We also hope to highlight the importance of evidence-based medicine, particularly in the volatile field of Sports Medicine, and the need for facts, not fiction.ActoveginActovegin (Takeda Pharmaceutical Company Ltd, Osaka, Japan) is a biological drug produced from deproteinised haemodialysate of calf serum. Its high standard of quality control and long 50-year history of clinical evidence has provided much evidence to support its efficacy [1]. Functioning in a similar vain to other calf blood derivatives, it can be compared to foetal bovine serum (FBS) which is well known for its established role in maintaining cell viability in in vitro tissue culture methods. Thus, Actovegin may be considered as a highly controlled and approved form of FBS with an excellent track record for human use in the clinical setting.In Vitro EvidenceThe active component and mechanism of Actovegin has yet to be identified, its effects are likely due to a mixture of ingredients instead of a single active compound. Study has shown the drug to not contain peptide, growth factor or hormone-like substances [2]. Further, in vitro evidence suggests that Actovegin promotes oxidative metabolism and shifts the redox-balance of cells to produce more oxidized substrates, possibly protecting against hypoxic cell injury [2]. This mechanism can be logically extrapolated to the first few hours of muscle injury where the goal of any therapeutic intervention would be to interrupt the process of cell damaging events, and therefore importantly preserve cell viability at the injury site. In vitro evidence has also pointed towards Actovegin’s protective effect on injured cell types ranging from neuroblastoma cells [3], neutrophils [4] and renal cells [5]. It has also been postulated that Actovegin could have a beneficial effect as an injective therapy for osteoarthritis [6].One of the properties of Actovegin is to promote oxidation and energy production in cell cultures, its efficacy is assumed to benefit post-ischemic metabolic events clinically. A recent in vitro study has made unsubstantiated, optimistic claims about the potential performance enhancing qualities of Actovegin for clinical use [7]. Søndergård et al. inflicted cell membrane injuries to the muscle cells with a cytotoxic detergent, Saponin then treated the cell culture with Actovegin and analysed mitochondrial activity of the cells. They concluded that as the Actovegin groups had higher mitochondrial activity, it must be able to enhance sports performance and failed to consider the fact that Actovegin may also have membrane stabilizing properties which stabilized cells and allowed the mitochondria to function normally. As discussed in the previous section, Actovegin is a drug that has been proven to have protective effects on ischemic cells. Therefore, it is important that we highlight here that the study by Søndergård et al. should be viewed as an in vitro cell membrane injury study and not a performance analysis. Care must be taken when extrapolating conclusions from in vitro evidence, as results will not necessarily translate. In fact more care must be taken in concluding whether or not any substance will improve performance in humans from in vitro studies. This misleading conclusion may have contributed to the fictitious hype with article exposure and media attention, thus having a detrimental effect on science and medical research. Legality and Ergogenic PotentialIn December, 2000, the IOC banned the use of Actovegin as an ergogenic substance after noting its prolific use at the Sydney Olympic Games and that year’s Tour de France [8]. The ban was lifted however, 2 months later after no indisputable evidence was provided demonstrating Actovegin had performance enhancing potential. The current stance from World Anti Doping Agency (WADA) is that Actovegin is legal under 50 mL every 6 h. However, 50 mL is 25 fold higher than the amount injected for a muscle tear and that is without concentrating the drug; making these guidelines somewhat ill-informed. Further, neither intravenous nor intramuscular injections of Actovegin are prohibited in or out of competition according to latest search in Global Drug Reference Online, which is approved by UK Anti-Doping (UKAD), the Canadian Centre for Ethics in Sport (CCES), the United States Anti-Doping Agency (USADA) and WADA [9,10].A study of 567 diabetic patients showed no improvement in muscle strength or condition was found after maximal Actovegin infusion for 160 days [11]. Further, Lee et al. performed another, more recent blinded, crossover peak aerobic capacity study in healthy human participants [12]. Lee et al. provide definitive clinical evidence that Actovegin did not improve aerobic capacity compared to saline control in humans. No significant differences were observed in peak values *Corresponding author: Paul YF Lee, South Wales Orthopaedic Research Network, Welshbone, Cardiff, United Kingdom, Tel: +447764614688; E-mail: paul@welshbone.com Received September 21, 2016; Accepted October 13, 2016; Published October 23, 2016Citation: Lee PYF, Kwan AP, Smith PM, Brock J, Nokes L (2016) Actovegin Equals to Performance Enhancing Drug Doping: Fact or Fiction? J Tissue Sci Eng 7: 179. doi:10.4172/2157-7552.1000179Copyright: © 2016 Lee PYF, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Actovegin Equals to Performance Enhancing Drug Doping: Fact or Fiction?Paul YF Lee1,2, Alvin P Kwan2, Paul M Smith3, James Brock1 and Len Nokes21South Wales Orthopaedic Research Network, Welshbone, Cardiff, UK2Actovegin Research Group, Health, Technology and the Digital World, School of engineering, Cardiff University3School of Sport, Cardiff Metropolitan UniversityCitation: Lee PYF, Kwan AP, Smith PM, Brock J, Nokes L (2016) Actovegin Equals to Performance Enhancing Drug Doping: Fact or Fiction? J Tissue Sci Eng 7: 179. doi:10.4172/2157-7552.1000179Page 2 of 2Volume 7 • Issue 3 • 1000179J Tissue Sci Eng, an open access journalISSN: 2157-7552for aerobic power. Additionally, values of gross and net efficiency, and calorific energy equivalents associated with VO2 were similar. Therefore, in brief, results from this study provide definitive clinical evidence that Actovegin in its maximum permitted dose does not improved human peak aerobic capacity. Thus, showing the claims by Sondergard et al. do not extrapolate to a human population. Interestingly, in a recent series of studies with human macrophages using RT-PCR and flow cytometry, they have tentatively demonstrated a possible role of Actovegin as an anti-inflammatory agent, which is consistent with the finding that Actovegin can reduce the recovery time in mild muscle injuries.Muscle Injuries - Current Strategies and IssuesMuscle injuries are common in sports, recently different injection treatment options such as growth factors have demonstrated encouraging results, however, with their anabolic properties, interventions that utilize growth factors, autologous blood or autologous conditioned serum are unfeasible therapeutic options for professional athletes, being banned by WADA [10]. Interventions such as Platelet Rich Plasma (PRP) and Autologous Conditioning Serum (ACS) have become popular augmentative therapies in Sports Medicine, being proposed to facilitate muscle healing by optimizing provision of growth factors from promising animal study [13-15]. However, again these results do not necessarily translate to human trial. Reurink et al. in a recent, double-blind, randomized placebo controlled trial, showed no clinical or statistical difference between PRP and placebo treated groups [15]. This study did highlight the heterogeneity in PRP preparation protocol, distinct lack of consistency in quality control and thus, variation between individual PRP injections. This is an issue we as authors have highlighted previously [6]. The information thus suggests that there is a lack of an effective, legally utilizable option for professional athletes to treat acute muscle injuries. It also dictates that that use of blood products as biological drugs for muscular injury is nothing new and the Actovegin is a logical option.Clinical EvidenceThe use of Actovegin as an intramuscular injection therapy for acute muscle tears was first documented by Pfister and Koller [16]. They reported a reduction in recovery time from 8.3 weeks to 5.5 weeks in treatment groups. However, their partially blinded case control study of 103 patients received several criticisms. Patients were recruited from different levels of sport and thus treatment regime and rehabilitation protocols were therefore not standardised. Further, Actovegin was mixed with local anaesthetic, which could have altered its pharmacodynamic and kinetic properties. Finally, the outcome scores were made on subjective observation by patients and clinicians with no pre-injury data to compare with.Since this study there has been limited supporting evidence for its role in the treatment of muscle injuries. Lee et al. have published a study on the effects of standalone Actovegin therapy, reporting a reduction in return to play time in injured, professional footballers of 8 days when compared to physiotherapy alone (p=0.033) [17]. This study using players from the same elite football club allowed for standardization of intervention, physical fitness and rehabilitation protocols. ConclusionThe evidence provided in this editorial delivers updated evidence that hopefully can dispel the shroud of criticism that has surrounded Actovegin. The in vitro evidence provides insight into the mechanism by which this biological drug is improving cell oxidative metabolism and its role in shifting redox balance to maintain cell viability. The clinical evidence provided has highlighted the importance of care in extrapolating in vitro findings, which do not necessarily extrapolate clinically. Further, clinical evidence has demonstrated  that standalone Actovegin therapy is safe and effective to treat muscle injuries in elite sports professionals [17]. It is important therefore, particularly in a volatile field such as Sports Medicine, that an evidence based medicine approach is taken throughout and treatments are not judged on anecdotal and subjective opinion. Current evidence is suggestive that Actovegin is a non-ergogenic, safe and potentially beneficial biological drug for the treatment of sports related muscle injury in elite athletes. Further research will tease out mechanisms and identify active ingredients, while clinical trials could confirm efficacy and establish a dose-response relationship. We should remain cautious in generating facts over anecdotal fiction and tailor the use of any intervention to an individual athlete’s need above anything else.References1. Buchmayer F, Pleiner J, Elmlinger MW, Lauer G, Nell G, et al. (2011) Actovegin®: A biological drug for more than 5 decades. Wien Med Wochenschr 161: 80-88.2. Schonwald D, Sixt B, Machicao F, Marx E, Haedenkamp G, et al. (1991) Enhanced proliferation of coronary endothelial cells in response to growth factors is synergized by hemodialysate compounds in vitro. Res Exp Med (Berl) 191: 259-272.3. Yurinskaya MM, Vinokurov MG, Grachev SV, Astashkin EI (2014) Actovegin reduces the hydrogen peroxide-induced cell apoptosis of SK-N-SH neuroblastoma by means of p38MAPK and PI-3K inhibition. Dokl Biol Sci 456: 215-217.4. Gulevsky AK, Moiseyeva NN, Gorina OL (2011) Influence of low molecular (below 5 KD) fraction from cord blood and actovegin on phagocytic activity of frozen-thawed neutrophils.Cryo Letters 32: 131-140.5. Gulevsky AK, Trifonova AV, Lavrik AA (2011) Stimulating effect of cord blood fraction below 5 kDa and actovegin on cell growth of permanent cell lines. Cell and Tissue Biology 5: 144-150. 6. Lee P, Brock J (2016) Intra-articular injections for osteoarthritis: From bench to bedside, can we teach old drugs new tricks? J Arthritis 5: 3. 7. Søndergård SD, Dela F, Helge JW, Larsen S (2016) Actovegin, a non-prohibited drug increases oxidative capacity in human skeletal muscle. Eur J Sport Sci 16: 801-807.8. Tsitsimpikou C, Tsiokanos A, Tsarouhas K, Schamasch P, Fitch KD, et al. (2009) Medication use by athletes at the Athens 2004 Summer Olympic Games. Clin J Sport Med 19: 33-38.9. Global DRO (2016) The global drug reference online. 10. World Anti-Doping Agency (2016) Prohibited list 2016.11. Ziegler D, Movsesyan L, Mankovsky B, Gurieva I, Abylaiuly Z, et al. (2009) Treatment of symptomatic polyneuropathy with actovegin in type 2 diabetic patients. Diabetes Care 32: 1479-1484.12. Lee P, Nokes L, Smith PM (2012) No effect of intravenous Actovegin® on peak aerobic capacity. Int J Sports Med 33: 305-309.13. Moraes VY, Lenza M, Tamaoki MJ, Faloppa F, Belloti JC (2014) Platelet-rich therapies for musculoskeletal soft tissue injuries. The Cochrane Database of Systematic Reviews 4: CD01007. 14. Mosca MJ, Rodeo SA (2015) Platelet-rich plasma for muscle injuries: Game over or time out? Curr Rev Musculoskelet Med 8: 145-153.15. Reurink G, Goudswaard GJ, Moen MH, Weir A, Verhaar JA, et al. (2015) Rationale, secondary outcome scores and 1 year follow-up of a randomised trial of platelet-rich plasma injections in acute hamstring muscle injury: the Dutch Hamstring Injection Therapy study. Br J Sports Med 49: 1206-1212. 16. Pfister A, Koller W (1990) [Treatment of fresh muscle injury].Sportverletz Sportschaden 4: 41-44.17. Lee P, Rattenberry A, Connelly S, Nokes L (2011) Our experience on Actovegin, is it cutting edge? Int J Sports Med 32: 237-241.

Actovegin equal to performance enhancing drug doping: fact or fiction?

Lee, Paul Yuh Feng

Kwan, Alvin P. L.

Nokes, Leonard Derek Martin

Online Research @ Cardiff

This is a n  Op e n  Acces s  doc u m e n t  dow nloa d e d  fro m  ORCA, Ca r diff U nive r si ty 'sins ti t u tion al r e posi to ry: h t t p s://o rc a .c a r diff.ac.uk/id/e p rin t/95 8 3 2/This  is t h e  a u t ho r’s ve r sion  of a  wo rk  t h a t  w as  s u b mi t t e d  to  / a c c e p t e d  forp u blica tion.Cit a tion  for  final p u blish e d  ve r sion:Le e,  Paul Yuh Fe n g,  Kwan,  Alvin P. L., S mi th,  Pa ul M.,  Brock, Jam e s  a n dN ok es,  Leon a r d  Der ek  M a r tin  ORCID: h t t p s://orcid.o rg/00 0 0-0 0 0 2-9 5 0 4-8 0 2 82 0 1 6.  Actovegin  e q u als  p e rfo r m a nc e  e n h a n cing  d r u g  doping:  fac t  o r  fiction.Jour n al of Tissu e  Scie nc e  a n d  En gine e rin g  7  (3) , 1 7 9.  1 0 .41 7 2/21 5 7-7 5 5 2.10 0 0 1 7 9  file P u blish e r s  p a g e:  Ple a s e  no t e:  Ch a n g e s  m a d e  a s  a  r e s ul t  of p u blishing  p roc e s s e s  s uc h  a s  copy-e di ting,for m a t ting  a n d  p a g e  n u m b e r s  m ay no t  b e  r eflec t e d  in t his  ve r sion.  For  t h ed efini tive  ve r sion  of t his  p u blica tion,  ple a s e  r ef e r  to  t h e  p u blish e d  sou rc e.  Youa r e  a dvise d  to  cons ul t  t h e  p u blish e r’s ve r sion  if you  wish  to  ci t e  t his  p a p er.This ve r sion  is b ein g  m a d e  av ailable  in  a cco r d a n c e  wit h  p u blish e r  policie s.S e e  h t t p://o rc a .cf.ac.uk/policies.h t ml for  u s a g e  policies.  Copyrigh t  a n d  m o r al  r i gh t sfor  p u blica tions  m a d e  available  in ORCA a r e  r e t ain e d  by t h e  copyrig h thold e r s .Volume 7 • Issue 3 • 1000179J Tissue Sci Eng, an open access journalISSN: 2157-7552Short Communication OMICS InternationalJournal of Tissue Science & EngineeringJournal of Tissue Science & EngineeringISSN: 2157-7552Lee et al., J Tissue Sci Eng 2016, 7:3DOI: 10.4172/2157-7552.1000179IntroductionActovegin is a biological drug that has been used for the treatment of sports muscle injuries. Several in vitro studies have shed light on potential mechanisms of action and the drug has consistently demonstrated its potential to reduce return to injury time for muscle tears in elite athletes. Yet it was banned for a time under the International Olympic Committee (IOC) as a blood doping agent, this ban was based on presumptuous conclusions and subsequently lifted after no indisputable evidence could be provided. This editorial hopes to provide readers with some of the key, objective facts relating to Actovegin and then based on this, will offer an opinion on its role in sports medicine. We also hope to highlight the importance of evidence-based medicine, particularly in the volatile field of Sports Medicine, and the need for facts, not fiction.ActoveginActovegin (Takeda Pharmaceutical Company Ltd, Osaka, Japan) is a biological drug produced from deproteinised haemodialysate of calf serum. Its high standard of quality control and long 50-year history of clinical evidence have provided much evidence to support its efficacy [1]. Functioning in a similar vain to other calf blood derivatives, it can be compared to foetal bovine serum (FBS) which is well known for its established role in maintaining cell viability in in vitro tissue culture methods. Thus, Actovegin may be considered as a highly controlled and approved form of FBS with an excellent track record for human use in the clinical setting.In Vitro EvidenceThe active component and mechanism of Actovegin has yet to be identified, its effects are likely due to a mixture of ingredients instead of a single active compound. Study has shown the drug to not contain peptide, growth factor or hormone-like substances [2]. Further, in vitro evidence suggests that Actovegin promotes oxidative metabolism and shifts the redox-balance of cells to produce more oxidized substrates, possibly protecting against hypoxic cell injury [2]. This mechanism can be logically extrapolated to the first few hours of muscle injury where the goal of any therapeutic intervention would be to interrupt the process of cell damaging events, and therefore importantly preserve cell viability at the injury site. In vitro evidence has also pointed towards Actovegin’s protective effect on injured cell types ranging from neuroblastoma cells [3], neutrophils [4] and renal cells [5]. It has also been postulated that Actovegin could have a beneficial effect as an injective therapy for osteoarthritis [6].One of the properties of Actovegin is to promote oxidation and energy production in cell cultures, its efficacy is assumed to benefit post-ischemic metabolic events clinically. A recent in vitro study has made unsubstantiated, optimistic claims about the potential performance enhancing qualities of Actovegin for clinical use [7]. Søndergård et al. inflicted cell membrane injuries to the muscle cells with a cytotoxic detergent, Saponin then treated the cell culture with Actovegin and analysed mitochondrial activity of the cells. They concluded that as the Actovegin groups had higher mitochondrial activity, it must be able to enhance sports performance and failed to consider the fact that Actovegin may also have membrane stabilizing properties which stabilized cells and allowed the mitochondria to function normally. As discussed it the previous section, Actovegin is a drug that has been proven to have protective effects on ischemic cells. Therefore, it is important that we highlight here that the study by Søndergård et al. should be viewed as an in vitro cell membrane injury study and not a performance analysis. Care must be taken when extrapolating conclusions from in vitro evidence, as results will not necessarily translate. In fact more care must be taken in concluding whether or not any substance will improve performance in humans from in vitro studies. This misleading conclusion may have contributed to the fictitious hype with article exposure and media attention, thus having a detrimental effect on science and medical research. Legality and Ergogenic PotentialIn December, 2000, the IOC banned the use of Actovegin as an ergogenic substance after noting its prolific use at the Sydney Olympic Games and that year’s Tour de France [8]. The ban was lifted however, 2 months later after no indisputable evidence was provided demonstrating Actovegin had performance enhancing potential. The current stance from World Anti Doping Agency (WADA) is that Actovegin is legal under 50 mL every 6 h. However, 50 mL is 25 fold higher than the amount injected for a muscle tear and that is without concentrating the drug; making these guidelines somewhat ill-informed. Further, neither intravenous nor intramuscular injections of Actovegin are prohibited in or out of competition according to latest search in Global Drug Reference Online, which is approved by UK Anti-Doping (UKAD), the Canadian Centre for Ethics in Sport (CCES), the United States Anti-Doping Agency (USADA) and WADA [9,10].A study of 567 diabetic patients showed no improvement in muscle strength or condition was found after maximal Actovegin infusion for 160 days [11]. Further, Lee et al. performed another, more recent blinded, crossover peak aerobic capacity study in healthy human participants [12]. Lee et al. provide definitive clinical evidence that Actovegin did not improve aerobic capacity compared to saline control in humans. No significant differences were observed in peak values for aerobic power. Additionally, values of gross and net efficiency, and calorific energy equivalents associated with VO2 were similar. Therefore, *Corresponding author: Paul YF Lee, South Wales Orthopaedic Research Network, Welshbone, Cardiff, United Kingdom, Tel: +447764614688; E-mail: paul@welshbone.com Received September 21, 2016; Accepted October 13, 2016; Published October 23, 2016Citation: Lee PYF, Kwan AP, Smith PM, Brock J, Nokes L (2016) Actovegin Equals to Performance Enhancing Drug Doping: Fact or Fiction? J Tissue Sci Eng 7: 179. doi:10.4172/2157-7552.1000179Copyright: © 2016 Lee PYF, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Actovegin Equals to Performance Enhancing Drug Doping: Fact or Fiction?Paul YF Lee*, Alvin P Kwan, Paul M Smith, James Brock and Len NokesSouth Wales Orthopaedic Research Network, Welshbone, Cardiff, UKCitation: Lee PYF, Kwan AP, Smith PM, Brock J, Nokes L (2016) Actovegin Equals to Performance Enhancing Drug Doping: Fact or Fiction? J Tissue Sci Eng 7: 179. doi:10.4172/2157-7552.1000179Page 2 of 2Volume 7 • Issue 3 • 1000179J Tissue Sci Eng, an open access journalISSN: 2157-7552in brief, results from this study provide definitive clinical evidence that Actovegin in its maximum permitted dose does not improved human peak aerobic capacity. Thus, showing the claims by Sondergard et al. does not extrapolate to a human population. Interestingly, in a recent series of studies with human macrophages using RT-PCR and flow cytometry, they have tentatively demonstrated a possible role of Actovegin as an anti-inflammatory agent, which is consistent with the finding that Actovegin can reduce the recovery time in mild muscle injuries.Muscle Injuries - Current Strategies and IssuesMuscle injuries are common in sports, recently different injection treatment options such as growth factors have demonstrated encouraging results, however, with their anabolic properties, interventions that utilize growth factors, autologous blood or autologous conditioned serum are unfeasible therapeutic options for professional athletes, being banned by WADA [10]. Interventions such as Platelet Rich Plasma (PRP) and Autologous Conditioning Serum (ACS) have become popular augmentative therapies in Sports Medicine, being proposed to facilitate muscle healing by optimizing provision of growth factors from promising animal study [13-15]. However, again these results do not necessarily translate to human trial. Reurink et al. in a recent, double-blind, randomized placebo controlled trial, showed no clinical or statistical difference between PRP and placebo treated groups [15]. This study did highlight the heterogeneity in PRP preparation protocol, distinct lack of consistency in quality control and thus, variation between individual PRP injections. This is an issue we as authors have highlighted previously [6]. The information thus provided suggests that there is a lack of an effective, legally utilizable option for professional athletes to treat acute muscle injuries. It also dictates that the use of blood products as biological drugs for muscular injury is nothing new and the Actovegin is a logical option.Clinical EvidenceThe use of Actovegin as an intramuscular injection therapy for acute muscle tears was first documented by Pfister and Koller [16]. They reported a reduction in recovery time from 8.3 weeks to 5.5 weeks in treatment groups. However, their partially blinded case control study of 103 patients received several criticisms. Patients were recruited from different levels of sport and thus treatment regime and rehabilitation protocols were therefore not standardised. Further, Actovegin was mixed with local anaesthetic, which could have altered its pharmacodynamic and kinetic properties. Finally, the outcome scores were made on subjective observation by patients and clinicians with no pre-injury data to compare with.Since this study there has been limited supporting evidence for its role in the treatment of muscle injuries. Lee et al. have published a study on the effects of standalone Actovegin therapy, reporting a reduction in return to play time in injured, professional footballers of 8 days when compared to physiotherapy alone (p=0.033) [17]. This study using players from the same elite football club allowed for standardization of intervention, physical fitness and rehabilitation protocol. ConclusionThe evidence provided in this editorial delivers updated evidence that hopefully can dispel the shroud of criticism that has surrounded Actovegin. The in vitro evidence provides insight into the mechanism by which this biological drug is improving cell oxidative metabolism and its role in shifting redox balance to maintain cell viability. The clinical evidence provided has highlighted the importance of care in extrapolating in vitro findings, which do not necessarily extrapolate clinically. Further, the clinical evidence has suggested that standalone Actovegin therapy is safe and effective to treat muscle injuries in elite sports professionals [17]. It is important therefore, particularly in a volatile field such as Sports Medicine, that an evidence based medicine approach is taken throughout and treatments are not judged on anecdotal and subjective opinion. Current evidence is suggestive that Actovegin is a non-ergogenic, safe and potentially beneficial biological drug for the treatment of sports related muscle injury in elite athletes. Further research will tease out mechanisms and identify active ingredients, while clinical trials could confirm efficacy and establish a dose-response relationship. We should remain cautious in generating facts over anecdotal fiction and tailor the use of any intervention to an individual athlete’s need above anything else.References1. Buchmayer F, Pleiner J, Elmlinger MW, Lauer G, Nell G, et al. (2011) Actovegin®: A biological drug for more than 5 decades. Wien Med Wochenschr 161: 80-88.2. Schonwald D, Sixt B, Machicao F, Marx E, Haedenkamp G, et al. (1991) Enhanced proliferation of coronary endothelial cells in response to growth factors is synergized by hemodialysate compounds in vitro. Res Exp Med (Berl) 191: 259-272.3. Yurinskaya MM, Vinokurov MG, Grachev SV, Astashkin EI (2014) Actovegin reduces the hydrogen peroxide-induced cell apoptosis of SK-N-SH neuroblastoma by means of p38MAPK and PI-3K inhibition. Dokl Biol Sci 456: 215-217.4. Gulevsky AK, Moiseyeva NN, Gorina OL (2011) Influence of low molecular (below 5 KD) fraction from cord blood and actovegin on phagocytic activity of frozen-thawed neutrophils.Cryo Letters 32: 131-140.5. Gulevsky AK, Trifonova AV, Lavrik AA (2011) Stimulating effect of cord blood fraction below 5 kDa and actovegin on cell growth of permanent cell lines. Cell and Tissue Biology 5: 144-150. 6. Lee P, Brock J (2016) Intra-articular injections for osteoarthritis: From bench to bedside, can we teach old drugs new tricks? J Arthritis 5: 3. 7. Søndergård SD, Dela F, Helge JW, Larsen S (2016) Actovegin, a non-prohibited drug increases oxidative capacity in human skeletal muscle. Eur J Sport Sci 16: 801-807.8. Tsitsimpikou C, Tsiokanos A, Tsarouhas K, Schamasch P, Fitch KD, et al. (2009) Medication use by athletes at the Athens 2004 Summer Olympic Games. Clin J Sport Med 19: 33-38.9. Global DRO (2016) The global drug reference online. 10. World Anti-Doping Agency (2016) Prohibited list 2016.11. Ziegler D, Movsesyan L, Mankovsky B, Gurieva I, Abylaiuly Z, et al. (2009) Treatment of symptomatic polyneuropathy with actovegin in type 2 diabetic patients. Diabetes Care 32: 1479-1484.12. Lee P, Nokes L, Smith PM (2012) No effect of intravenous Actovegin® on peak aerobic capacity. Int J Sports Med 33: 305-309.13. Moraes VY, Lenza M, Tamaoki MJ, Faloppa F, Belloti JC (2014) Platelet-rich therapies for musculoskeletal soft tissue injuries. The Cochrane Database of Systematic Reviews 4: CD01007. 14. Mosca MJ, Rodeo SA (2015) Platelet-rich plasma for muscle injuries: Game over or time out? Curr Rev Musculoskelet Med 8: 145-153.15. Reurink G, Goudswaard GJ, Moen MH, Weir A, Verhaar JA, et al. (2015) Rationale, secondary outcome scores and 1 year follow-up of a randomised trial of platelet-rich plasma injections in acute hamstring muscle injury: the Dutch Hamstring Injection Therapy study. Br J Sports Med 49: 1206-1212. 16. Pfister A, Koller W (1990) [Treatment of fresh muscle injury].Sportverletz Sportschaden 4: 41-44.17. Lee P, Rattenberry A, Connelly S, Nokes L (2011) Our experience on Actovegin, is it cutting edge? Int J Sports Med 32: 237-241.

Actovegin equals performance enhancing drug doping: fact or fiction

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Actovegin equal to performance enhancing drug doping: fact or fiction?

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