ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 40 of 41
УЖМБС 2017, 2(3): 229–244
Physical training and Sport

Tivortin Aspartate: a New Safe and Effective Non-Prohibited Medical Drug for Stimulation the Performance of Athletes

Gunina L. M.1, Vinnichuk Yu. D.1, Dmitriev A. V.2, Vysochina N. L.1, Bezuglaya V. V.1, Nosach E. V.3

The need to increase sport achievements in the setting of ever-increasing competition and approximation of the functional capabilities of the human body to the border of reserve mechanisms make us seek new ways to stimulate physical performance and psycho-emotional stability of athletes. One of the most promising areas for improving the results of training and competitive activities of athletes is the use of pharmacological agents which are not prohibited by WADA. At the present time the substances that are on L-arginine based, in the form of food supplements firmly took their place in the pharmacological support of children’s and youth sport and high performance sport. Materials and Methods. Studies of the safety and efficacy of Tivortin aspartate (L-arginine aspartate) were conducted in skilled male athletes aged 18 to 26, represented the different groups of sports – cyclic (track and field athletics, middle distance running) and endurance (weightlifting) ones. The study involved 69 healthy skilled (first-rate and sub-master sportsmen) athletes who were on a special preparatory stage of the preparatory period of the annual macrocycle in the standard training mode. All study participants had no manifestations of any acute respiratory viral infections and the history of diseases of cardio-respiratory, endocrine, digestive, excretory systems with clinical manifestations. The athletes signed Informed Consent, in which they confirmed their voluntary consent to participate in the study after acquaintance with all its features that could affect their free decision. The study was randomized, blind and placebo-controlled. Randomization of the athletes within both groups (Group 1 – 36 track and field athletes, Group 2 – 33 weightlifters) was conducted before the signing the Informed Consent. By simple randomization within the groups, 4 subgroups of athletes (2 main and 2 control) were formed; they did not have statistically significant differences in the initial clinic and anamnestic, anthropologic and demographic, pedagogical, qualification and gender characteristics. Treatment groups included 46 athletes, of them 24 middle distance runners and 22 weightlifters, and 23 athletes as controls (12 runners and 11 weightlifters). Tivortin aspartate as a 20 % oral solution at a daily dose of 40 ml, divided into two 20 ml administrations, was used immediately after meals for 21 study days. Before and after the study, all athletes underwent complete physical examination by a specialist in sports medicine, including an assessment of the functional state of the cardio-respiratory system; laboratory diagnostics, psychophysiological testing with the calculation of the stress factor and evaluation of the incidence of side effects and subjective complaints in the athletes during the drug administration were conducted as well. Laboratory parameters included standard measures of hematological (white blood cell, platelet and red blood cell counts, hemoglobin content, hematocrit, mean absolute and average hemoglobin concentration in red blood cells, mean volume and anisocytosis of red blood cells) and biochemical homeostasis (total protein, bilirubin, urea, creatinine, glucose, cholesterol and triglycerides, potassium, sodium, ionized calcium, magnesium and phosphorus; activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transaminase, α-amylase, alkaline phosphatase; serum iron content, total iron binding capacity of serum and transferrin saturation; activated partial thromboplastin time). Moreover, prooxidant-antioxidant balance (PAB) in the erythrocyte membranes was studied based on the malonic dialdehyde/reduced glutathione ratio. The special pedagogical performance measures were also studied: for runners – PWC170 and running time for simulated competitive distances of 800 m and 1500 m, for weightlifters – the height of the bar lift in jumping and snatching and the timing of these exercises. Results. The data obtained clearly indicate the absence of subjective complaints, objective significant shifts in standard laboratory parameters and the functional state of athletes under the influence of the course of taking Tivortin aspartate, which suggests its high safety profile. In this case, the drug has a positive effect on the PAB with a decrease in malonic dialdehyde content in the erythrocyte membranes from 3.380±0.281 to 2.962±0.038 nmol/10-6 per erythrocyte (p <0.05), and an increase in reduced glutathione content by 16.3% in the controls. Similar figures in weightlifters are 3.345±0.082 vs. 3.144±0.076 nmol/10-6 for erythrocyte (p <0.05) and 25.5% as compared to controls. Under the influence of Tivortin aspartate, the severity of psychophysiological stress also significantly decreases by 9.5 points, while this measure in the controls increases by 3.59 points (p <0.05) in track and field athletes and changes to 4.52 and 2.86 points, respectively, in weightlifters. At the same time, there is a significant increase in performance measures of athletes: PWC170 in runners increases by 21.8 % vs. controls, in which this measure increases by only 9.62 % at the end of the study; and the time for passing the competitive distances of 800 m and 1500 m is reduced by 3.74 and 4.14 sec, respectively, versus the values of the runners of the control group (p <0.05). Similarly, the performance measures of weightlifters are changed. Conclusions. We believe that the rise in the performance of runners in the course of administration of Tivortin aspartate is primarily achieved by increasing the oxygen transport function of the blood by reducing its viscosity and improving the structural and functional state of erythrocytes. In weightlifters, the observed increase in performance is caused mainly by increasing the height of the bar lift and reducing the time of exercise and by the optimization of intermuscular and neuromuscular interaction during the normalization of lipid peroxidation processes in the membranes of nerve cells under the influence of L-arginine.

Keywords: sport, work capacity, ergogenic medical drugs, L-arginine, Tivortin aspartate, oxidative homeostasis, psychophysiological stress

Full text: PDF (Rus) 444K

  1. Bankova VV, Prischepova NF, Avratinskiy OI. [A method for assessing the pathological changes in the plasma membrane in children with various diseases]. Patologicheskaya fiziologiya i eksperimentalnaya terapiya. 1987; 3: 78-81. [Russian].
  2. Vinogradov VE. Stimulation of efficiency and recovery processes in the training and competitive activities of qualified athletes: monograph. Kiev: PNP "Slavutich-Delfin"; 2009. 367 s. [Russian].
  3. Gunina Larisa. [Anabolic agents in sports: the mechanism of doping and side effects]. Nauka v olimpiyskom sporte. 2015; 4: 41-8. [Russian].
  4. Gunina LM, Oliynik SA, Ivanov SV. [Changes in blood indices and prooxidant-antioxidant balance in erythrocyte membranes under the influence of Rithmokor with intense physical activity]. Medichna himiya. 2007; 9 (1): 95-9. [Ukrainian].
  5. Gunina LM, Visochina NL. [Methodology for correction of stress in athletes]. Proceedings of the 8-td International Scientific and Practical Conference "Achievements of Higher School-2013". Sofiya, Bolgariya; 2013. s. 61-3. [Ukrainian].
  6. Gunina LM. [Interconnection of aggregation properties of erythrocytes, structural and functional state of their membranes and physical performance of athletes for oxidative stress]. Krovoobig ta gemostaz. 2010; 3: 15-8. [Ukrainian].
  7. Gunina LM, Olishevsky SV, Cherednichenko OO, Golovashchenko RV, Bezugla VV. [Rationale for the possibility of using the "Cardonat" metabolic drug for high-skilled angling]. Sportivna meditsina. 2010; 1-2: 92-7. [Russian].
  8. Gunina LM, Konyushok SO, Palamarchuk OP, Dzhurenko NY, Grek GP. [One of the aspects of the mechanism of the Chinese lemongrass is the indicators of the special trained weightlifters]. Sportivna meditsina. 2008; 2: 102-7. [Russian].
  9. Evdokimov BS. Evaluation of the level of special physical fitness of a weightlifter. Weightlifting: a collection of articles. Moskva: Fizkultura i sport; 1971. s. 118-22. [Russian].
  10. Ivanchenko VA, Ivanchenko AM, Ivanchenko TP. Supersatisfaction and success in business for everyone. SPb: Komplekt; 1994. 262 s. [Russian].
  11. Karpman VL, Belotserkovsky ZB, Gudkov IA. Testing in sports medicine. Moskva: Fizkultura i sport; 1988. 208 s. [Russian].
  12. Kuramshin SF. [The construction of a stage of direct precompetitive training (ENPP) of highly qualified athletes to the main competitions of the season]. Physical culture as a kind of culture: a collection of scientific papers. Voronezh: Izdatelstvo VGPU; 2003. s. 173-7. [Russian].
  13. Makarova GA. Pharmacological support of sports activities: real effectiveness and controversial issues. Moskva: Sovetskiy sport; 2013. 231 s. [Russian].
  14. Markelova IA, Balykova LA, Ivanskiy SA. [The use of metabolic therapy to optimize the tolerance of young athletes to physical activity]. Pediatriya. 2008; 87 (2): 51-5. [Russian].
  15. Mikheev AA. Theory and methodology of vibration training in sports (biological and pedagogical justification of dosed vibro-training): monograph. Moskva: Sovetskiy sport; 2011. 615 s. [Russian].
  16. Mohan R, Glesson M, Greenhaff PL. Biochemistry of muscular activity and physical training. Kiev: Olimpiyskaya literatura; 2001. 296 s. [Russian].
  17. Mutaeva IS, Kuznetsov AS, Konovalov IE, Khalikov GZ. [Evaluation of the functional readiness of athletes training for endurance]. Fundamental Researche. 2013; 6 (2): 440-4. [Russian].
  18. Oleshko VG. Modeling the process of training and selection of athletes in power sports. Kiev: DMP "Polimed"; 2005. 254 s. [Ukrainian].
  19. Platonov Vladimir. [Overtraining in sports]. Nauka v olimpiyskom sporte. 2015; 1: 19-34. [Russian].
  20. Sokunova SF, Konovalova LV, Vavilov VV. [The use of interval hypoxic training in seasonal training of runners at medium distances]. Uchenyie zapiski universiteta imeni PF Lesgafta. 2009; 5: 86-9. [Russian].
  21. Solodkov AS. [Physical fitness athletes and general principles of its correction]. Uchenyie zapiski universiteta imeni PF Lesgafta. 2014; 3 (109): 148-57. [Russian].
  22. Shvets NI, Davydov VV. [Age features of changes in the glutathione system in the heart of rats with immobilization stress]. Ukrayinskiy biohimichniy zhurnal. 2008; 80 (6): 74-8. [Ukrainian].
  23. Aguiar AF, Balvedi MC, Buzzachera CF, Altimari LR, Lozovoy MA, Bigliassi M, Januário RS, et al. L-Arginine supplementation does not enhance blood flow and muscle performance in healthy and physically active older women. Eur J Nutr. 2016; 55 (6): 2053-62.
  24. Alvares TS, Conte-Junior CA, Silva JT, Paschoalin VM. L-arginine does not improve biochemical and hormonal response in trained runners after 4 weeks of supplementation. Nutr Res. 2014; 34 (1): 31-9.
  25. Álvares TS, Meirelles CM, Bhambhani YN, Paschoalin VM, Gomes PS. L-Arginine as a potential ergogenic aid in healthy subjects. Sports Med. 2011; 41 (3): 233-48.
  26. Arsic A, Vucic V, Glibetic M, Popovic T, Debeljak-Martacic J, Cubrilo D, Ahmetovic Z, et al. Redox balance in elite female athletes: differences based on sport types. J Sports Med Phys Fitness. 2016; 56 (1-2): 1-8.
  27. Bohdanovs'ka NV, Kotsiuruba AV, Malikov MV. Nitric oxide synthesis during different stages of competition period in well-trained athletes. Fiziol J. 2011; 57 (4): 82-9.
  28. Brun JF, Varlet-Marie E, Raynaud de Mauverger E. Hematocrit and hematocrit viscosity ratio during exercise in athletes: Even closer to predicted optimal values? Clin Hemorheol Microcirc. 2016; 64 (4): 777-87.
  29. Busardò FP, Frati P, Sanzo MD, Napoletano S, Pinchi E, Zaami S, Fineschi V. The impact of nandrolone decanoate on the central nervous system. Curr Neuropharmacol. 2015; 13 (1): 122-31.
  30. Chang CY, Wang MC, Miyagawa T, Chen ZY, Lin FH, Chen KH, Liu GS, Tseng CL. Preparation of arginine-glycine-aspartic acid-modified biopolymeric nanoparticles containing epigalloccatechin-3-gallate for targeting vascular endothelial cells to inhibit corneal neovascularization. Int J Nanomedicine. 2016; 12: 279-94.
  31. Circu ML, Aw TY. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med. 2010; 48 (6): 749-62.
  32. Djordjevic D, Cubrilo D, Macura M, Barudzic N, Djuric D, Jakovljevic V. The influence of training status on oxidative stress in young male handball players. Mol Cell Biochem. 2011; 351 (1-2): 251-9.
  33. Esposito S, Deventer K, Geldof L, Van Eenoo P. In vitro models for metabolic studies of small peptide hormones in sport drug testing. J Pept Sci. 2015; 21 (1): 1-9.
  34. Forbes SC, Harber V, Bell GJ. The acute effects of L-arginine on hormonal and metabolic responses during submaximal exercise in trained cyclists. Int J Sport Nutr Exerc Metab. 2013; 23 (4): 369-77.
  35. Fukuda S, Nojima J, Motoki Y, Yamaguti K, Nakatomi Y, Okawa N, Fujiwara K, et al. A potential biomarker for fatigue: Oxidative stress and anti-oxidative activity. Biol Psychol. 2016; 118: 88-93.
  36. Goto C, Nishioka K, Umemura T, Jitsuiki D, Sakagutchi A, Kawamura M, Chayama K, et al. Acute moderate-intensity exercise induces vasodilation through an increase in nitric oxide bioavailiability in humans. Am J Hypertens. 2007; 20 (8): 825-30.
  37. Ikeda T, Yoshitomi Y, Saito H, Shimasaki T, Yamaya H, Kobata T, Ishigaki Y, et al. Regulation of soluble Flt-1 (VEGFR-1) production by hnRNP D and protein arginine methylation. Mol Cell Biochem. 2016; 413 (1-2): 155-64.
  38. Jones AM, Vanhatalo A, Bailey SJ. Influence of dietary nitrate supplementation on exercise tolerance and performance. Nestle Nutr Inst Workshop Ser. 2013; 75: 27-40.
  39. Khanmohammadi N, Movahedin M, Safari M, Sameni HR, Yousefi B, Jafari B, Zarbakhsh S. Effect of L-carnitine on in vitro developmental rate, the zona pellucida and hatching of blastocysts and their cell numbers in mouse embryos. Int J Reprod Biomed (Yazd). 2016; 14 (10): 649-56.
  40. Little JP, Forbes SC, Candow DG, Cornish SM, Chilibeck PD. Creatine, arginine alpha-ketoglutarate, amino acids, and medium-chain triglycerides and endurance and performance. Int J Sport Nutr Exerc Metab. 2008; 18 (5): 493-508.
  41. Lomonosova YN, Shenkman BS, Kalamkarov GR, Kostrominova TY, Nemirovskaya TL. L-arginine supplementation protects exercise performance and structural integrity of muscle fibers after a single bout of eccentric exercise in rats. PLos One. 2014; 9 (4): e94448.
  42. Lorin J, Zeller M, Guilland JC, Cottin Y, Vergely C, Rochette L. Arginine and nitric oxide synthase: regulatory mechanisms and cardiovascular aspects. Mol Nutr Food Res. 2014; 58 (1): 10-6.
  43. Matelot D, Schnell F, Khodor N, Endjah N, Kervio G, Carrault G, Thillaye du Boullay N, Carre F. Does Deep Bradycardia Increase the Risk of Arrhythmias and Syncope in Endurance Athletes? Int J Sports Med. 2016; 37 (10): 792-8.
  44. Maravelias C, Dona A, Stefanidou M, Spiliopoulou C. Adverse effects of anabolic steroids in athletes. A constant threat. Toxicol Lett. 2005.15; 158 (3): 167-75.
  45. McConnell AK, Romer LM. Respiratory muscle training in healthy humans: resolving the controversy. Int J Sports Med. 2004; 25 (4): 284-93.
  46. Morton JP, Kayani AC, McArdle A, Drust B. The exercise-induced stress response of skeletal muscle, with specific emphasis on humans. Sports Med. 2009; 39 (8): 643-62.
  47. Mujika I, Pereira da Silveira F, Nosaka K. Blood markers of recovery from Ironman distance races in an elite triathlete. J Sports Med Phys Fitness. 2017; 57 (8): 1057‒61.
  48. Olver TD, Ferguson BS, Laughlin M. Molecular Mechanisms for Exercise Training-Induced Changes in Vascular Structure and Function: Skeletal Muscle, Cardiac Muscle, and the Brain. Prog Mol Biol Transl Sci. 2015; 135: 227‒57.
  49. Ostadhadi S, Khan MI, Norouzi-Javidan A, Chamanara M, Jazaeri F, Zolfaghari S, Dehpour AR. Involvement of NMDA receptors and L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effects of topiramate in mice forced swimming test. Brain Res Bull. 2016; 122: 62-70.
  50. Padovani F, Duffy J, Hegner M. Microrheological Coagulation Assay Exploiting Micromechanical Resonators. Anal Chem. 2017; 89 (1):751-8.
  51. Powers SK, Grinton S, Lawler J, Criswell D, Dodd S. High intensity exercise training-induced metabolic alterations in respiratory muscles. Respir Physiol. 1992; 89 (2): 169-77.
  52. Ranjbar K, Rahmani-Nia F, Shahabpour E. Aerobic training and l-arginine supplementation promotes rat heart and hindleg muscles arteriogenesis after myocardial infarction. J Physiol Biochem. 2016; 72 (3): 393-404.
  53. Ranucci M, Laddomada T, Ranucci M, Baryshnikova E. Blood viscosity during coagulation at different shear rates. Physiol Rep. 2014; 2 (7): pii: e12065.
  54. Rowlands DC, Nelson AR, Raymond F, Metairon S, Mansourian R, Clarke J, Stellingwerff T, Phillips SM. Protein-leucine ingestion activates a regenerative inflammo-myogenic transcriptome in skeletal muscle following intense endurance exercise. Physiol Genomics. 2016; 48 (1): 21-32.
  55. Silva EPJr, Borges LS, Mendes-da-Silva C, Hirabara SM, Lambertucci RH. L-arginine supplementation improves rats' antioxidant system and exercise performance. Free Radic Res. 2017; 51 (3): 281-293.
  56. Sunaga A, Masuda M, Fujita M, Iida O, Kanda T, Matsuda Y, Morozumi T, et al. Cardiac iodine-123-metaiodobenzylguanidine scintigraphy may be useful to identify pathologic from physiologic sinus bradycardia. Pacing Clin Electrophysiol. 2017; 40 (6): 632‒37.
  57. Sunderland KL, Greer F, Morales J. VO2max and ventilator threshold of trained cyclists are not affected by 28-day l-arginine supplementation. J Strength Cond Res. 2011; 25 (3): 833‒7.
  58. Suzuki J, Reardon C. L-arginine supplementation causes additional effects on exercise-induced angiogenesis and VEGF expression in the heart and hind-leg muscles of middle-aged rats. J Physiol Sci. 2006; 56 (1): 39-44.
  59. Vassilakopoulos T, Deckman G, Kebbewar M, Rallis G, Harfouche R, Hussain SN. Regulation of nitric oxide production in limb and ventilatory muscles during chronic exercise training. Am J Physiol Lung Cell Mol Physiol. 2003; 284 (3): L452-7.
  60. Wang S, Qi Y, Yu L, Zhang L, Chao F, Huang W, Huang R, et al. Endogenous nitric oxide regulates blood vessel growth factors, capillaries in the cortex, and memory retention in Sprague-Dawley rats. Am J Transl Res. 2016; 8 (12): 5271-85.