title: Actovegin, a non-prohibited drug increases oxidative capacity in human skeletal muscle.
abstract: Actovegin, a deproteinized haemodialysate of calf blood, is suggested to have ergogenic properties, but this potential effect has never been investigated in human skeletal muscle. To investigate this purported ergogenic effect, we measured the mitochondrial respiratory capacity in permeabilized human skeletal muscle fibres acutely exposed to Actovegin in a low and in a high dose. We found that Actovegin, in the presence of complex I-linked substrates increased the oxidative phosphorylation (OXPHOS) capacity significantly in a concentration-dependent manner (19 ± 3, 31 ± 4 and 45 ± 4 pmol/mg/s). Maximal OXPHOS capacity with complex I and II-linked substrate was increased when the fibres were exposed to the high dose of Actovegin (62 ± 6 and 77 ± 6 pmol/mg/s) (p < .05). The respiratory capacity of the electron transfer system as well as Vmax and Km were also increased in a concentration-dependent manner after Actovegin exposure (70 ± 6, 79 ± 6 and 88 ± 7 pmol/mg/s; 13 ± 2, 25 ± 3 and 37 ± 4 pmol/mg/s; 0.08 ± 0.02, 0.21 ± 0.03 and 0.36 ± 0.03 mM, respectively) (p < .05). In summary, we report for the first time that Actovegin has a marked effect on mitochondrial oxidative function in human skeletal muscle. Mitochondrial adaptations like this are also seen after a training program in human subjects. Whether this improvement translates into an ergogenic effect in athletes and thus reiterates the need to include Actovegin on the World Anti-Doping Agency's active list remains to be investigated.
authors.affiliation: a Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Stine D
authors.initials: SD
authors.lastname: Søndergård
authors.affiliation: a Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Flemming
authors.initials: F
authors.lastname: Dela
authors.affiliation: a Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Jørn W
authors.initials: JW
authors.lastname: Helge
authors.affiliation: a Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Larsen
mesh_terms: D000328:Adult; D004300:Doping in Sports; D006418:Heme / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D012119:Respiration / Q000187:drug effects
chemical_list: D006418:Heme; C015646:Actovegin
keywords: Actovegin; human skeletal muscle; mitochondrial oxidative capacity; non-prohibited drug