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. 2020 Apr 28;6(1):e000716. doi: 10.1136/bmjsem-2019-000716

Table 1.

Summary of included studies

Study Design Sample size Participants Main interventions Outcomes measured
Annaheim et al13 Double-blind, RCT with 4 arms: receiving high-dose rHuEPO, medium-dose rHuEPO, low-dose rHuEPO and placebo. 40 total; high-dose rHuEPO (n=10), medium-dose rHuEPO (n=10), low-dose rHuEPO (n=10), placebo (n=10). Healthy, endurance-trained men; none of the participants suffered from cardiovascular and ventilatory diseases or allergies; ferritin (30–400 µg/L), hct% <50%. rHuEPO or placebo (0.9% NaCl) injection every 2–3 days for 4 weeks; dosages were 10 000 IU, 5000 IU and 2500 IU for high-dose, medium-dose and low-dose groups, respectively; all subjects were given intravenously 100 mg of Fe-III-saccharate. Red cell parameters (hct%, Hb), plasma volume, VO2 max, time limit of constant-load test, maximum power, rate of perceived exertion, time to exhaustion.
Birkeland et al18 Double-blind, RCT with 2 arms: rHuEPO and placebo; matched for type of sport and training level. 20 total; rHuEPO (n=10), placebo (n=10). Healthy, well-trained male athletes (cycling, orienteering, running, triathlon, swimming, cross-country skiing) with normal haematological parameters, no history of thromboembolic disease and no risk factors for cardiovascular disease. rHuEPO (5000 U) or placebo (1 mL NaCl, 9 g/L) subcutaneous injection three times weekly for 30 days (4 weeks) or until hct% greater than or equal to 50%; all subjects were given iron supplementation with 270 mg/day Fe2+ in liquid formula. Hct%, Hb, VO2 max, serum EPO concentration, serum ferritin concentration, time course to soluble transferrin receptor levels.
Caillaud et al24 RCT with 2 arms: rHuEPO and placebo. 12 total; rHuEPO (n=6), placebo (n=6). Healthy aerobically trained men with no comorbidities. rHuEPO (50 U/kg) or placebo (0.9% NaCl) subcutaneous injection three times weekly for 4 weeks; all subjects given appropriate oral dose of iron sulfate, vitamin B9 and vitamin B12. Hct%, Hb, respiratory exchange ratio, substrate utilisation, body weight, % fat, max power, VO2 max, submaximal VO2, training load.
Connes et al20 Double-blind, RCT with 2 arms: rHuEPO and placebo. 16 total; rHuEPO (n=9), placebo (n=7). Endurance-trained men (cyclists, runners and triathletes). rHuEPO (50 IU/kg) or placebo (0.9% NaCl) subcutaneous injection three times weekly for 4 weeks; oral dose of 200 mg iron sulfate during 4 weeks. Hct%, Hb, VO2 max and POmax via incremental maximal exercise test vs submaximal exercise.
Heuberger et al6 Double-blind, RCT with 2 arms: rHuEPO and placebo. 49 total, 2 dropouts. 48 participants included in the analyses: rHuEPO (n=24), placebo (n=24). Healthy male cyclists, age 18–50. rHuEPO or placebo (0.9% NaCl) subcutaneous injection once weekly for 8 weeks; rHuEPO group received 5000 IU per injection for the first 4 rHuEPO injections; if Hb was below the target range, then dose increased to 6000 IU, 8000 IU or 10 000 IU; if it was in target range, dose decreased to 2000 IU, and if it was above target range placebo was administered; all subjects were given open-label, daily oral doses of 200 mg ferrous fumarate and 50 mg ascorbic acid. Hct%, Hb, VO2 max, POmax, lactate threshold VO2, lactate threshold power, ventilatory threshold, gross efficiency, heart rate, tidal volume, respiratory frequency, respiratory minute ventilation, respiratory quotient, average power output, average VO2, average heart rate, submaximal lactate, cycling economy, treatment-emergent adverse events.
Ninot et al21 Double-blind, RCT with 3 arms: rHuEPO, placebo and no treatment. 17 total; rHuEPO (n=6), placebo (n=5), no treatment (n=6). Endurance-trained men, same middle-class socioeconomic background, no psychiatric disorder or acute medical illness, no negative life events occurring over a 3-month period, no comorbidities. rHuEPO or placebo (0.9% NaCl) subcutaneous injection three times weekly for 6 weeks; rHuEPO group was given 50 U/kg three times weekly for the first 4 weeks followed by 20 U/kg three times weekly for the remaining 2 weeks; treatment was stopped if hct% ≥50%; all subjects were given a daily oral dose of 200 mg of iron sulfate during the 6 weeks of injections. Hct%; Hb; psychological measures of global self-esteem, physical self-worth and 4 physical subdomains (physical condition, sport competence, physical strength and attractive body) using the Physical Self Inventory-6 Scale; VO2 max, training load.
Rasmussen et al22 Double-blind, crossover RCT with 2 arms: rHuEPO and placebo. 15 total;
3 days group (n=7), 3 months group (n=8); however, participants from the 3 months group were excluded due to the lack of placebo.
Healthy men, age 18–34. rHuEPO (30 000 IU) or placebo (saline) subcutaneous injection once daily for three consecutive days; washout period of 3 months. Hct%, VO2 max, respiratory frequency, tidal volume, EPO assay, blood glucose and lactate content, voluntary activation, RPE, visual perception, visual memory, selective attention, mental concentration, visual scanning abilities, perceptual speed.
Sieljacks et al15 Single-blind, RCT with 4 arms: sedentary placebo, sedentary rHuEPO, training placebo and training rHuEPO. 38 total, 2 dropouts; sedentary placebo (n=9), training placebo (n=10), sedentary rHuEPO (n=9), training rHuEPO (n=8). Healthy, non-smoking, untrained men, age 18–35; BMI: 18–29 kg/m2, BP: <135/85 mm Hg, hct%: <45%, VO2 max:<50 mL/kg/min. rHuEPO or placebo (isotonic saline) subcutaneous injection once weekly for 10 weeks; dosing variable; all subjects were given 100 mg of oral iron daily. Hct%, Hb, reticulocytes, mean cell volume, VO2 max, wattmax, total training workload and estimated energy consumption.
Thomsen et al19 Single-blind, controlled clinical trial with 2 arms: rHuEPO and placebo. 16 total; rHuEPO (n=8), placebo (n=8). Healthy men of reasonable age, weight and height. rHuEPO (5000 IU) or placebo (saline) subcutaneous injection every other day for the first 2 weeks, 3 injections on three consecutive days for the third week, 1 injection weekly for weeks 4–13; all subjects were given 100 mg iron daily for 2 weeks prior and throughout treatment. Hct%, Hb, VO2 max, time to exhaustion, VO2, VCO2, SaO2 (arterial oxygen saturation).
Wilkerson et al23 Double-blind, RCT with 2 arms: experimental and placebo. 15 total; rHuEPO (n=8), placebo (n=7). Healthy men, age 25±4 years, recreationally active, no hypertension or hct% baseline. rHuEPO (150 IU/kg) or placebo (saline) subcutaneous injection once weekly for 4 weeks; all subjects given appropriate iron tablets and vitamin C tablets. Hct%, Hb, blood pressure, VO2 consumption rate, pulmonary gas exchange, ventilation, lactate levels, pulmonary VO2, heart rate, peak VO2, time to exhaustion, peak power output.

BMI, body mass index; BP, blood pressure; EPO, erythropoietin; Hb, haemoglobin concentration; hct%, haematocrit percentage; IU/kg, IU per kilogram body mass; POmax, maximal power output; RCT, randomised controlled trial; rHuEPO, recombinant human erythropoietin; RPE, Borg Scale Rating of Perceived Exhaustion; VO2 max, maximal oxygen consumption.