Effects of prolonged low doses of recombinant human erythropoietin during submaximal and maximal exercise

Abstract

The aim of this study was to characterise the effect of prolonged low doses of recombinant erythropoietin (r-HuEPO) on the responses to submaximal and maximal exercise. Volunteer recreational athletes ( n=21) were divided into three groups: r-HuEPO+intravenous iron (EPO+IV, n=7), r-HuEPO+oral iron (EPO+OR, n=9) and placebo ( n=5). During the 12 week study, r-HuEPO or saline injections were given three times a week for the first 8 weeks and for the final 4 weeks the subjects were monitored but no injections were administered. The r-HuEPO doses were 50 IU x kg(-1) body mass for 3 weeks and 20 IU x kg(-1) body mass for the next 5 weeks. An exercise test comprising three submaximal intensities and then increments to elicit maximal aerobic power (VO2max ) was conducted during weeks 0, 4, 8 and 12. During week 0, the mean intensity of the submaximal stages was 60%, 72% and 81%. Blood taken at rest was analysed twice a week for haematocrit (Hct). The relative increases in at weeks 4, 8 and 12 were 7.7%, 9.7% and 4.5%, respectively, for the EPO+IV group; 6.0%, 4.7% and 3.1% for the EPO+OR group; and -0.5%, -0.1% and -1.0% for the placebo group, where the improvements at week 12 for the EPO+IV and EPO+OR groups remained significantly above week 0 values. The Hct was significantly elevated by 0.06 and 0.07 units at week 3 in the EPO+IV and EPO+OR groups, respectively, and was stable during the 5 weeks of low-dose r-HuEPO. After 8 weeks of r-HuEPO use, plasma lactate concentration tended to be lower at exercise intensities ranging from 60% to 100%. This study confirmed the ability of low doses of r-HuEPO to maintain Hct and at elevated levels.

Current markers of the Athlete Blood Passport do not flag microdose EPO doping

“…Our findings agree with reticulocyte data published by Russell et al (2002) who injected (subcutaneously) 20 IU/kg thrice weekly (i.e., *4,500 IU per week) for 5 weeks. During what they termed a 'maintenance phase' the reticulocyte percentages in treated subjects were indistinguishable from baseline values (and placebo subjects).…”

“…In subsequent phases, this dosage increased to 3,000 IU per week (20 IU/kg), 4,500 IU per week (30 IU/kg) and peaked at 6,000 IU per week (40 IU/kg) for several subjects. This dosage/frequency combination spanned a range shown previously to enhance maximal oxygen uptake: 20-40 IU/kg (Berglund and Ekblom 1991); 20-50 IU/kg (Russell et al 2002); 60 IU/kg (Thomsen et al 2007), however our focus was not on physiological but rather haematological endpoints. As such, our incremental approach deliberately contrasted with previous studies that began with a more aggressive treatment strategy; we surmised that in an environment where rhEPO is unreservedly acknowledged to be performance enhancing and thus highly coveted, an athlete selecting a doping regimen would place greater emphasis on finding the highest dosage which evaded detection, rather than the lowest dosage which yielded a performance enhancement.…”

Prolonged administration of recombinant human erythropoietin increases submaximal performance more than maximal aerobic capacity

“…The presented increase in VO 2 max of 9.1 and 8.1% after 4 and 11 weeks, respectively, falls in line with previously published data ranging from 6 to 9% (Audran et al 1999;Birkeland et al 2000;Parisotto et al 2001;Russell et al 2002). In these studies, however, rHuEpo was injected at a much higher frequency than in the present study, and the treatment period was considerably shorter, i.e.…”

“…They injected 20-40 IU kg ¡1 body mass for a period of up to 6 weeks and demonstrated an increase in [Hb] and concomitant also in VO 2 max. Subsequently several other groups have conWrmed that injecting between 50-200 IU kg ¡1 at a frequency of about three times a week for 10-30 days increases VO 2 max (Audran et al 1999;Birkeland et al 2000;Parisotto et al 2001), and also lower dosages (20-50 IU kg ¡1 ) have been shown to induce similar results (Russell et al 2002). Although VO 2 max is a commonly used measure for aerobic performance, it was recently shown in top professional cyclists (all with several remarkable international victories) that VO 2 max varied from 65.5 to 82.5 ml kg ¡1 min ¡1 (Lucia et al 2002).…”

Faster oxygen uptake kinetics at the onset of submaximal cycling exercise following 4�weeks recombinant human erythropoietin (r-HuEPO) treatment

“…For trained-endurance athletes, maximal O 2 consumption (VȮ 2,max ) is one of the key factors determining performance in endurance events, and for such athletes O 2 supply rather than metabolic capacity is a key factor limiting the level of VȮ 2,max [38]. The benefits of increased red blood cell mass following administration of recombinant human erythropoietin (rHuEPO) on VȮ 2,max have been studied in recreationallevel athletes [2,10,30] and investigators have reported VȮ 2,max increases of 6-11% after 4 weeks of r-HuEPO administration.…”