Monday, April 18, 2011

Actovegin: a biological drug for more than 5 decades

Abstract

Actovegin® is a biological drug manufactured from a natural source: it is a calf blood hemodialysate. Its therapeutic benefits stem from a variety of pharmacodynamic actions that can be summarized to a common goal, i.e. the enhancement of cellular metabolism; this results from an insulin-like activity mediated by Inositol-phospho-oligosaccharides. Actovegin®

Actovegin-Ergogenic Aid or Not
results in beneficial effects in several pathophysiological clinical settings including malfunction of the blood circulation and trophic disturbances in the brain, impairment of peripheral blood circulation and associated diseases, dermal transplants and acute and chronic wounds. Here, we give an overview of the pharmacodynamic actions of calf-blood hemidialysate and its beneficial effects in a variety of clinical settings.

By Chad Robertson B.Sc (KIN), B.Sc (PHARM)

There has been a great deal of hype in the media of late regarding the drug Actovegin after reports that a world renown physician who treated Tiger Woods is under investigation for apparently using it. My intentions of this article is to educate the public on the pharmacological properties of Actovegin and how to derive the same clinical applications using natural nutrients. As reported, Actovegin is a protein free blood derived extract from calf used for treating dementia, cerebrovascular insufficiency, and periperal vascular resistance. It is manufactured by a European based pharmaceutical company, Nycomed Austria

Properties of Actovegin

An extensive Medline literature search revealed older German and Russian studies focusing on Actovegin's physiologic effects on glucose metabolism and cerebral circulation. There are no reports on its use in improving athletic performance and scant reviews for it's treatment of sports related injuries. Nevertheless, since its introduction, the athletic community has realized the potential of Actovegin to increase mitochondrial ATP energy production through increased glucose and oxygen utilization.

Improvement of glucose metabolism

Jacob S et. al. (1996) was one of the first to show that Actovegin stimulated the uptake of glucose into adipocytes by inositol-phosphate-oligosaccharides (IPO), a key component of Actovegin. IPO is thought to possess insulin-mimicking effects by regulating glucose carrier activity 1, 2. Improvements in glucose tolerance occurs without affecting endogenous serum insulin levels and this effect was seen in diabetics rather than those with normal carbohydrate metabolism 3.

Increase peripheral blood flow

Restrictions in peripheral blood flow due to arterial occlusive disease results in muscle pain during rest and exercise. A study was undertaken to determine the effects of intravenous (IV), intraarterial (IA) Actovegin administration and physical exercise on peripheral arterial occlusive disease 4.

Over a four week period, patients who received IA injections achieved a pain free walking distance of 44.9% compared to 37.8% in the IV group. However, physical exercise showed improvements in pain free walking distance of 66.9% although the results were not considered significant compared to IA Actovegin.

Hypoxic states and dementia

The parietal cortex is responsible for processing visual information and spatial directed attention and shrinkage to the area leads to dementia. It appears Actovegin improves the cognitive processing in the parietal cortex in age associated memory impairment 5. Kanowski S et. al. 1995 showed improvements in organic brain syndrome patients in social behavior and mental performance with injections of Actovegin compared to placebo 6.

Actovegin improves energy metabolism in hypoxia by increasing uptake of glucose and oxygen 7.

Sports injuries

Rapid recovery times from sports related injuries are important for athletes. Local injections of Actovegin has been shown to significantly shorten recovery time in muscle injury compared to placebo 8.

How does Actovegin compare to ACS

Autologous Conditioned Serum (ACS) is produced by physical and chemical stimulation of whole blood to increase the concentration of specific growth factors such as FGF-2, TGF-beta1 and HGF. During muscle regeneration, a host of growth factor are involved in the repair process but FGF-2, TGF-beta 1, and HGF are key regulators of muscle satellite cell activation. Wright-Carpenter et.al. 2004 compared the effects of ACS against Actovegin/Traumeel (control) for muscle strains. Local injections of ACS shortened recovery time to healing (as shown on MRI scans) and showed an almost complete regression of edema and bleeding after 14 days compared to the control group which only possessed mild effects 9.

Comparison to alternative products

It is interesting to note how Actovegin's biochemical and physiological properties compares to other products currently used in similiar disease states.

R-Lipoic Acid

Actovegin has been proposed to increase glucose utilization by regulating glucose transporter protein (GLUT-1). Lipoic acid mimics insulin action by affecting GLUT-1 and GLUT-4 10. Glut-1 involves glucose transport into red blood cells and the brain whereas Glut-4 transports glucose into fat and muscle cells and has a greater impact on blood sugar levels than Glut-1.

Skeletal muscle depends on insulin to transport glucose into myocytes where it is used to produce energy. During exercise, muscle contractions upregulate expression of GLUT-4 thereby reducing blood sugar levels and overcoming insulin resistant skeletal muscle 11. Another important property of Lipoic acid is it's ability to strengthen antioxidant defenses by increasing glutathione and protect against exercise induced oxidative stress 12.

Taurine

The hypoglycemic properties of taurine appear to be much greater after glucose supplementation rather than administration before a glucose challenge 13. Taurine acts by stimulating the secretion of insulin from pancreatic beta cells in addition to protecting it from lipid peroxidation through it's antioxidant action. Taurine's antioxidant property also extends to skeletal muscles where it may enhance exercise performance by attenuating damage to muscle tissues induced by exercise 14.

Vinpocetine

Vinpocetine, a derivative from the periwinkle plant, has been used as a nootropic to enhance mental function and as a drug to treat cerebral ischemia. Like Actovegin, vinpocetine can increase cerebral blood flow in ischemic stroke patients especially in areas which concentrated the drug the most 15. However, it's effect on the metabolic rate of glucose in the brain is minimal and the clinical use of vinpocetine in dementia is not conclusive 16.

Conclusion

Similiarities exists between Actovegin and the natural products lipoic acid, taurine and vinpocetine to improve blood flow and increase glucose disposal. Current well designed studies on it's use in sport injuries and enhancement of performance has yet to be conducted.



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