Weisenthal, L. (June, 2001). Personal communication.

On June 09, 2001, George F. Grattan ( wrote:

"It's my understanding that while there's a great deal of debate on this- and occasional grumbling from non-asthmatic swimmers competing against those you are and use inhalers - there is "no" conclusive evidence than a non-asthmatic using an inhaler would improve his/her performance. I'm no coach or pulmonologist, but that squares with my own sense of how these medications work."

Dr. Larry Weisenthal replied as follows.

"There are different types of inhalers. The potential performance-enhancing ones contain so-called beta-agonists. Basically, most, but not all, have similar physiologic effects as ephedrine and pseudoephedrine ("Sudafed"), the class of drugs which cost Rick DeMont his 400 m freestyle gold medal in 1972 and cost the Romanian gymnast her gold medal in 2000.

The literature would suggest that ephedrine and pseudoephedrine ("Sudafed") are, indeed, performance-enhancing, while at least some of the beta-agonist inhalers may not be performance-enhancing. I believe that doping of age-group swimmers with over the counter medications such as Sudafed does indeed occur and serves as a terrible example to the young swimmer which may have long term effects on the young athlete's approach to athletic competition and to school, career, and life."

Abstract #1

Gill, N. D., Shield, A., Blazevich, A. J., Zhou, S., & Weatherby, R. P. (2000). Muscular and cardiorespiratory effects of pseudoephedrine in human athletes. British Journal of Clinical Pharmacology, 50, 205-213.

AIMS: Pseudoephedrine (PSE) is a readily available over-the-counter nasal decongestant which is structurally similar to amphetamine and is included on the International Olympic Committee's list of banned substances. However to date, little research has supported its putative ergogenic effect. This study investigated whether a 180 mg dose of PSE ingested 45 min prior to exercise enhanced short-term maximal exercise performance and/or altered related physiological variables.

METHODS: A randomized, double-blind, crossover study in 22 healthy male athletes.

RESULTS: Maximum torque (mean +/- s.d., n = 22) produced in an isometric knee extension exercise was 321.1+/-62.0 Nm (PSE) and 295.7+/-72.4 Nm (placebo), and peak power obtained on the 'all-out' 30 s cycle test was 1262.5+/-48.5 W (PSE) and 1228.4+/-47.1 W (placebo) (P<0.01, P<0.03, respectively). Subjects were estimated to be producing 96.9+/-2.4% of their maximal possible isometric leg extension force after PSE ingestion, but only 95.3+/-2.4% when PSE was not ingested. Bench press tasks and total work during the cycle test were not affected by the ingestion of PSE. Lung function was altered following ingestion of PSE (P<0.05) with FEV1 and FVC significantly increased (P<0.02, P<0.01, respectively) although the FEV1/FVC ratio was not altered. Heart rate was significantly elevated by the ingestion of PSE immediately following the 30 s cycle sprint (P<0.01) however, lactate concentration was not altered by the ingestion of PSE.

CONCLUSIONS: The administration of a 180 mg dose of PSE increased maximum torque, produced in an isometric knee extension and produced an improvement in peak power during maximal cycle performance, as well as improving lung function.

Abstract #2

Bell, D. G., & Jacobs, I. (1999). Combined caffeine and ephedrine ingestion improves run times of Canadian Forces Warrior Test. Aviation, Space and Environmental Medicine, 70, 325-329.

The ingestion of a combination of caffeine (C) and ephedrine (E) has been reported to prolong exercise time to exhaustion during cycle ergometry at 85% VO2max. The present study was undertaken to investigate whether this enhancement would occur in a field setting and if drug ingestion on 1 d would affect performance 1 d later. Two hours after ingesting either a combination of 375 mg of C and 75 mg E (C+E), or a placebo (P), 9 healthy male recreational runners completed six balanced and double-blind trials of the Canadian Forces Warrior Test (WT), a 3.2 km run wearing "fighting order" which weighed about 11 kg. The trials were performed in sets of two runs, i.e., two runs were done 24 h apart, and these sets were separated by a minimum of 7 d. The sets were: C+E trial on day 1 (D1), placebo on day 2 (P2); placebo first (P1), C+E second (D2); and placebo first (P3), placebo second (P4). In addition, 1 wk before the treatment trials the subjects performed a control trial WT. During the WT, heart rates (HR) were recorded every minute. Plasma C and E levels immediately before the WT were similar for both C+E trials, but were undetectable for all P trials. Run times (mean+/-SD) were 15.3+/-0.6, 15.4+/-0.9, 15.5+/-1.2, 15.4+/-0.9, 15.4+/-0.9, 14.8+/-0.7, and 14.6+/-0.8 min for control, P1, P2, P3, P4, D1, D2 trials, respectively. The two C+E trial run times were similar and both were significantly faster (p < 0.05) than control and all placebo trials. HR during the WT was significantly higher (p < 0.05) for the C+E trials compared with the other trials. WT performance was not impaired by C+E ingestion 24 h earlier. In conclusion, performance of the WT was improved by ingestion of C+E.

Abstract #3

Swain, R. A., Harsha, D. M., Baenziger, J., Saywell, R. M. Jr. (1997). Do pseudoephedrine or phenylpropanolamine improve maximum oxygen uptake and time to exhaustion? Clinical Journal of Sport Medicine, 7, 168-173.

OBJECTIVE: To study the effects of over-the-counter dosages of the pure alpha 1-agonists pseudoephedrine (PSE) and phenylpropanolamine (PPA) on selected parameters of exercise performance, and to establish a range of corresponding drug levels in the urine of the athletes who use these drugs.

DESIGN: Placebo-controlled, randomized, double-blinded, multiple-dose trial. SETTING: The National Institute of Fitness and Sport, the Department of Family Medicine, Indiana University, and the Sports Medicine Lab, Department of Pathology, Indiana University, Indianapolis, Indiana.

PARTICIPANTS: A convenience sample of 20 male cyclists, aged 18-35, from the local cycling community. Inclusion criteria required cycling at least 50 miles a week, no chronic medical problems, and not taking any medications. Subjects were recruited by local ads and word of mouth.

INTERVENTION: Patients were randomized to one of two groups of 10 subjects. Each subject in both groups performed three separate bicycle ergometer tests after ingestion of varying dosages of alpha 1-agonists. One group performed tests after receiving placebo, 0.33 mg/kg PPA, and 0.66 mg/kg PPA, whereas the other group received placebo, 1 mg/kg PSE, and 2 mg/kg PSE. A minimum 1-week washout period was required between tests. Urine for drug testing was collected 1 h before, immediately afterward, and the next morning after testing. Drug testing was performed by gas GC/MCD at a facility approved by the International Olympic Committee.

MAIN OUTCOME MEASURES: Maximum oxygen uptake (VO2max), time to exhaustion, urine drug levels of PSE and PPA, peak blood pressures (BPs), peak pulse, and Borg scale (rating of perceived exertion or RPE).

MAIN RESULTS: In the PPA group, the 0.33-mg/kg dose resulted in insignificant changes in peak systolic BP (+5.4 mm Hg, p = 0.260), peak diastolic BP (-1.6 mm Hg, p = 0.622), peak pulse (-2.2 beats/min, p = 0.12), peak Borg (RPE = -0.10 (p = 0.823), time to exhaustion (-16.9 s, p = 0.287), and VO2max (+0.50 ml/kg/min, p = 0.71). No significant change was noted in any study variable at the 0.66-mg/kg PPA dose, and some effects were dissimilar to the lower PPA dose effects. Peak systolic BP increased 2.8 mm Hg (p = 0.617), diastolic BP decreased 1.6 mm Hg (p = 0.634), peak pulse increased 1.4 beats/min (p = 0.504), peak Borg RPE decreased 0.80 (p = 0.210), time to exhaustion decreased 2.6 s (p = 0.861), and VO2max decreased 2.92 ml/kg/min (p = 0.14). In the 1-mg/kg PSE group, there was a significant increase in peak systolic BP (+10.6 mm Hg, p = 0.029). No significant changes occurred in peak diastolic BP (+2.4 mm Hg, p = 0.333), peak pulse (+2.2 beats/min, p = 0.306), peak RPE (+0.2, p = 0.62), time to exhaustion (+21.4 s, p = 0.289), and VO2max (+2.29 ml/kg/min, p = 0.31). In the 2-mg/kg PSE dose trial, there were insignificant changes in peak systolic BP of +2.4 mm Hg (p = 0.559), +3.8 mm Hg in peak diastolic BP (p = 0.106), +1.6 beats/min in peak pulse (p = 0.586), -0.1 in peak Borg RPE scales (p = 0.76), -10.4 s in time to exhaustion (p = 0.41), and +1.79 ml/kg/min in VO2max (p = 0.43). Urine drug levels in those subjects receiving 1 mg/kg PSE ranged from 7-55 micrograms/ml before performance and 30-128 micrograms/ ml after performance to 7-35 micrograms/ml the next morning. Levels in those receiving 2 mg/kg ranged from 5-160 micrograms/ml before performance and 44-200 micrograms/ml after performance to 8-44 micrograms/ml the next day. In the PPA 0.33-mg/kg dose trials, the levels ranged 1-36 micrograms/ml before performance and 9-50 micrograms/ml after performance to < 1-14 micrograms/ml the next morning. In the PPA 0.66-mg/kg dose trials, the levels were 4-52 micrograms/ml before performance, 8-80 micrograms/ml after performance, and 6-74 micrograms/ml the next day.

CONCLUSIONS: We found no significant differences between trials in maximum oxygen uptake (VO2max), peak or progression of Borg Scale (RPE), maximum systolic and diastolic BPs, peak pulse, or t

Abstract #4

Norris, S. R., Petersen, S. R., & Jones, R. L. (1996). The effect of salbutamol on performance in endurance cyclists. European Journal of Applied Physiology and Occupational Physiology, 73, 364-368.

The effect of salbutamol (S) on cycling performance was examined in 15 highly trained non-asthmatic male cyclists. A double-blind, randomized cross-over design was used with S or placebo (P) administered using a metered-dose inhaler and a spacer device 20 min before each testing session. The S dose was 400 micrograms (four puffs), which is twice the normal therapeutic level. Subjects were habituated to all the laboratory procedures in the week prior to actual data collection. The subjects performed four tests under S and P conditions on separate days over 2 weeks. These included measurement of maximal O2 uptake (VO2max) (cycle ergometry) with assessment of pulmonary function before and after, a submaximal (90% of ventilatory threshold) square-wave work transition from a base of unloaded cycling, a 60-s modified Wingate test, and a simulated 20 km time trial. No significant differences were observed in any of the dependent variables related to aerobic endurance or cycling performance between the S and P conditions. These results support other findings that an acute dose (400 micrograms) of S has no performance-enhancing properties.

Abstract #5

Fleck, S. J., Lucia, A., Storms, W. W., Wallach, J. M., Vint, P. F., & Zimmerman, S. D. (1993). Effects of acute inhalation of albuterol on submaximal and maximal VO2 and blood lactate. International Journal of Sports Medicine, 14, 239-243.

The acute effects of inhaled albuterol, a selective beta-2 adrenergic agonist, on measures of endurance cycling performance and pulmonary function were assessed in 21 competitive road cyclists. A 5 step methacholine challenge revealed all cyclists to be non-asthmatic. Albuterol (A) total dose 360 micrograms or a saline placebo (P) was administered by inhaler, in 4 metered doses of 90 micrograms each, 15 minutes before cycle ergometry exercise. Heart rate, whole blood lactate, perceived exertion and VO2 were determined at the submaximal workloads of 150, 200, 225, 250, 275, 300 watts and at max.

Pulmonary function tests determining forced vital capacity, forced expiratory volume during the first second of expiration, forced mid-expiratory flow and maximal voluntary ventilation were performed prior to and 10 minutes after inhalation; and 5, 10 and 15 minutes after termination of the exercise protocol. Heart rate was significantly greater during the A compared to the P treatment at 200 (150.8 +/- 2.5 vs 146.7 +/- 2.8 beats per minute), 225 (159.7 +/- 2.4 vs 154.6 +/- 2.7 beats per minute) and 250 watts (166.9 +/- 2.4 vs 164.4 +/- 2.6 beats per minute). Whole blood lactate was significantly greater during the A compared to the P treatment at 275 watts (4.7 +/- 0.3 vs 4.2 +/- 0.4 mM). No other significant differences were found between the 2 treatments at any time point. These data indicate that the acute effect of albuterol inhalation at twice the recommended dosage has no positive effect on endurance performance measures or pulmonary function in athletes who are not asthmatic.

Abstract #6

Meeuwisse, W. H., McKenzie, D. C., Hopkins, S. R., & Road, J. D. (1992). The effect of salbutamol on performance in elite nonasthmatic athletes. Medicine and Science of Sports and Exercise, 24, 1161-1166.

The effect of salbutamol on performance was studied in seven male nonasthmatic highly trained (VO2max > or = 60 ml/kg/min) cyclists. Salbutamol (S = 2 puffs = 200 micrograms) or placebo (P) was administered by metered-dose inhaler, through a spacer device, 20 min prior to testing in a double-blind, randomized cross-over design. Testing sessions on a cycle ergometer included the measurement of maximal oxygen uptake (VO2max), peak power, maximal heart rate, and pulmonary function. A timed sprint to exhaustion was performed after 45 min of exercise at 70% of VO2max, and a Wingate anaerobic test was used to measure total work and peak power. There was a nonsignificant decrease in VO2max (P = 63.5 +/- 3.2; S = 62.6 +/- 3.3 ml/kg/min). No difference was found in peak power, maximum heart rate, endurance sprint time, Wingate peak power, or total work. After an anticipated baseline increase was taken into account, the pattern of change in FEV1 over time did not differ between salbutamol and placebo. It was concluded that a therapeutic dose of aerosol salbutamol does not have an ergogenic effect in elite nonasthmatic athletes, and it is therefore recommended that inhaled salbutamol continue to be permitted in international competition for individuals with exercise induced bronchospasm.

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