Pseudoephedrine is a sympathomimetic drug commonly found in nonprescription cold and flu medications. It is clinically useful in the treatment of mucosal congestion accompanying hay fever, allergic rhinitis, sinusitis, and other respiratory conditions. Pseudoephedrine is an α1 and β1 agonist similar in structure to ephedrine and amphetamines, and is listed as a banned substance by the International Olympic Committee for its classification as a stimulant. This drug has resulted in several positive drug tests in international athletic competitions in recent years. Cold and flu medications that do not contain pseudoephedrine are generally acceptable for athletes in international competition. Thus, its role as a possible ergogenic aid restricts the general clinical use of pseudoephedrine containing medications by athletes. Pseudoephedrine acts to increase heart rate (HR) and cardiac contractility. It is these chronotropic and inotropic effects that may lead to abuse of this drug during competition in an effort to attain an ergogenic effect. However, a therapeutic dose of pseudoephedrine, for treatment of mucosal congestion, should be considered separately than much greater doses used intentionally for ergogenic gain.
Although several studies have shown some increase in performance with the use of ephedrine and/or caffeine (1–3,5), there is very limited evidence of an ergogenic effect from pseudoephedrine. It has been shown that pseudoephedrine is without ergogenic effects during prolonged high-intensity exercise (9), during time to exhaustion tests (16), and during an incremental exercise test to exhaustion (6) and has limited ergogenic properties during a 30-s “all-out” cycle test (8). Thus, we saw a need to examine the effects of pseudoephedrine on two types of exercise: 1) maximal anaerobic exercise applicable to short-duration or intermittent high-intensity sport performance and 2) submaximal efficiency applicable to long-duration continuous sport performance.
The aim of the current investigation was to examine the effects of a therapeutic dose of pseudoephedrine on applied exercise performance, and for this reason, the following considerations were instrumental in the development this study. The normal therapeutic dose of 60-mg pseudoephedrine was used in this study as an appropriate representation of the dose typically taken by athletes in an attempt to treat symptoms from a common cold or flu. Although anaerobic cycle tests have been shown to be reliable, there is some debate as to what they measure. According to Inbar et al. (10), there is lack of agreement on the terminology used to describe the output of anaerobic tests. Nevertheless, peak power and total work are objective measures that may be compared between subjects and conditions. It is for this reason, and because the Wingate is the most commonly used anaerobic ergometric test, that the Wingate was used in this study. Efficiency of human muscle contraction has been defined as the ratio of energy output to energy consumption (12). Gross efficiency does not distinguish between energy consumption related to the work performed and basal energy consumption, and was calculated as the ratio of work output to total energy consumption (7,14,15).
Eleven moderately trained male subjects (Table 1) participated in this study (age = 29.0 ± 8.6 yr, V̇O2peak = 4.4 ± 0.8 L·min−1). An a priori power test was calculated on change in V̇O2 during steady-state cycling. For an effect size of 0.35 L·min−1, a standard deviation of 0.3 L·min−1 or less (7), α = 0.05, and β = 0.8, the sample size required was 8. Subjects were chosen from a variety of sports (running, N = 5; volleyball, N = 2; soccer, N = 1; rowing, N = 1; cycling, N = 1; rugby, N = 1). This study was delimited to male subjects to avoid possible confounding factors of hormonal fluctuation during the menstrual cycle. Written informed consent was obtained from all subjects before participation. No subject was on any medication, and none presented symptoms of any infection during the study. All the subjects in this study were pseudoephedrine naïve. The University of British Columbia Committee on Human Experimentation approved this study.
A randomized double-blinded crossover design was used. Subjects reported to the laboratory on three occasions. Each subject undertook both the drug (D) and placebo (P) conditions. On the first visit, anthropometric data were recorded, and subjects performed a baseline (B) Wingate test and a graded cycle test to exhaustion (V̇O2peak test). On the second and third visits, subjects ingested either 60-mg pseudoephedrine hydrochloride (from Sudafed©) or an identical placebo pill-containing cornstarch. Also on the second and third visits, after ingestion of the pseudoephedrine or placebo, subjects rested for 90 min and then performed the Wingate and cycling efficiency tests separated by 20 min of rest.
The Wingate tests were performed on a Monark cycle ergometer with a resistance of 0.075 kg·kg−1 body weight. Power was recorded in W every 5 s. Peak power was taken as the highest 5-s block, and minimum power was taken as the lowest 5-s block. Total work performed during the 30-s Wingate test was recorded in kilojoules. Fatigue index was calculated as the difference between peak power and minimum power divided by peak power and expressed as a percentage.
Measurement of V̇O2peak and submaximal V̇O2.
The graded exercise test was performed on an electronically braked cycle ergometer (Quinton Excalibur, Lode, Groningen, The Netherlands). Subjects started at 0 W and increased at a rate of 30 W·min−1 and were encouraged to maintain pedal speed above 90 rev·min−1. The test stopped when they experienced volitional fatigue and could not maintain this pedaling rate for 15–20 s. All subjects achieved a respiratory quotient (RQ) > 1.10. Expired gases were collected and analyzed (Ametek, Pittsburgh, PA), and ventilation was measured (Flo-1B, Physio-Dyne Fitness Instrument Technologies, Quogue, NY) and averaged every 15 s. HR was measured by telemetry (Polar Vantage XL, Kempele, Finland) and averaged every 15 s. Peak oxygen uptake (V̇O2peak) was calculated as the average of the four highest consecutive readings. Peak power achieved at the end of the test was recorded.
Oxygen uptake (V̇O2) was measured during steady-state exercise on the electronically braked cycle ergometer. On the second and third visits to the laboratory, in a randomized order, and separated by 5 min of rest, subjects cycled for 10 min at 40% and 60% of the peak power achieved in their graded exercise test. Data collected were averaged over the last 5 min of the steady-state cycle tests.
Calculation of cycling gross efficiency.
During the steady state cycle ergometer tests, energy expenditure (kcal·min−1) was calculated from V̇O2 (L·min−1) by using the table developed by Lusk (11) and RQ values for each subject. Power output (W) on the cycle ergometer was converted to work output (kcal·min−1). Gross efficiency (%) was calculated as the ratio of work output to energy expenditure.
A repeated measures one-factor ANOVA was used to analyze the Wingate data (peak power, total work, and fatigue index). Paired t-tests were used to analyze the cycling efficiency data (V̇O2, HR, V̇E, and RQ) with α = 0.05. A Bonferroni adjustment was used to reduce to possibility of Type I error.
There were no significant differences in peak power (Fig. 1; 860 ± 154, 926 ± 124, and 908 ± 118 W F (2, 30) = 0.73, P = 0.48), total work (20 ± 3, 21 ± 3, and 21 ± 2 kJ F (2,30) = 0.08, P = 0.92), or fatigue index (39 ± 8, 45 ± 5, and 43 ± 4%F (2,30) = 2.97, P = 0.06) on the Wingate test in any of the three conditions B, D, and P, respectively (Table 2). No significant differences were found between D and P for gross efficiency (Fig. 2) HR, V̇O2, V̇E, or RQ at either intensity (40% and 60% peak power) during the cycling efficiency test (Table 3). The cycling efficiency tests at 40% and 60% peak power corresponded to 58 ± 8% and 78 ± 11% of V̇O2peak, respectively.
Our results show that a therapeutic dose of pseudoephedrine is not associated with change in performance of a maximal anaerobic test or a submaximal aerobic efficiency test. These findings are consistent with several previous studies on the effects of sympathomimetics on performance (6,9,16) and oppose the findings of other studies involving pseudoephedrine (8) and ephedrine (1–3,5).
It has been shown in previous studies that pseudoephedrine has no effect on peak oxygen uptake (6,16) or time to exhaustion (16). However, data on oxygen consumption during submaximal performance with the use of pseudoephedrine are not available. Athletes commonly perform at intensities below V̇O2peak, and therefore the cycling efficiency tests were chosen in this study as a representative measure of oxygen consumption during exercise performance. It is reasonable to assume that a drug such as pseudoephedrine, which is banned as a stimulant, might affect short-duration, high-intensity performance. The Wingate test was used for this reason and as a comparison to the findings of Gill et al. (8) of improved peak power during a 30-s cycle sprint after ingestion of pseudoephedrine.
It was anticipated that D might elevate submaximal HR during the steady state cycling efficiency tests compared with P, consistent with the actions of a β1 agonist. This has been demonstrated in previous studies with the administration the sympathomimetic drugs pseudoephedrine (6) and ephedrine (1,3,4). However, in this study the marginally higher HR in D versus P were not significant. These findings are consistent with a previous study involving pseudoephedrine (16). We believe that this reflects the dose of pseudoephedrine used in this study. Although it is possible that a larger dose of pseudoephedrine could act as a stimulant to increase HR, the therapeutic dose used in this study clearly had no such effect on HR.
There have been several studies showing an ergogenic effect of ephedrine, which is a sympathomimetic drug similar to pseudoephedrine. Although pseudoephedrine is an α1 and β1 agonist, ephedrine is an α1, β1, and β2 agonist, which could cause the added effect of bronchodilation. Bell and colleagues (4,5) have shown an increased time to exhaustion and faster run times (1,3) with ephedrine in combination with caffeine. Ephedrine on its own has been shown to reduce 10-km run times (3) and increase peak power output during a Wingate test (2). However, Sidney and Lefcoe (13) examined the effects of ingestion of 24-mg ephedrine on treadmill effort and physical performance, and reported that ephedrine had no significant effect on peak oxygen uptake, anaerobic capacity as measured by time taken to sprint up stairs, or aerobic endurance as measured by time to exhaustion at 85% of maximal HR. It is possible these conflicting findings are due to differences in dose of ephedrine. Bell and colleagues (1,4,5) used a dose of 0.8 mg·kg−1, 1.0 mg·kg−1, or 75 mg ephedrine, which is significantly higher than the dose of 24 mg used by Sidney and Lefcoe (13).
To date, most of the studies examining the effects of pseudoephedrine on exercise suggest that an ergogenic effect is unlikely. Recently, however, Gill et al. (8) have found evidence of significantly greater peak power on an all-out 30-s cycle test and an increased isometric knee extension torque after ingestion of 180-mg pseudoephedrine. Several other studies involving the administration of pseudoephedrine have shown no ergogenic effect (6,9,16).
It is clear from two studies in particular that pseudoephedrine does not improve maximal aerobic performance. Swain et al. (16) examined the effects of 1 mg·kg−1 and 2 mg·kg−1 doses of pseudoephedrine on a graded cycling test to exhaustion. No ergogenic effect on peak oxygen uptake or time to exhaustion was found for either dose when compared to placebo. Similarly, Clemons and Crosby (6) found no difference in performance (peak oxygen uptake) on a graded treadmill test (Bruce protocol) between 60-mg pseudoephedrine and placebo. It has also been shown that pseudoephedrine does not improve sustained, high-intensity exercise. In a study by Gillies et al. (9), subjects performed a 40-km cycling time trial after ingestion of 120-mg pseudoephedrine or placebo with no difference in trial times.
The results of this study show that pseudoephedrine, when taken at the therapeutic dose of 60 mg, has no further stimulant effect in combination with exercise than exercise has alone. We believe that an ergogenic effect was not demonstrated in our study because a relatively low dose of 60 mg was used. This dose corresponds to the amount that would normally be used by athletes to battle the symptoms of a common cold, rather than a much larger dose that might be used in an attempt to gain an ergogenic effect. No assumption should be made about the effects of pseudoephedrine taken at a dose much greater than that used to combat the effects of the common cold or flu.
We conclude that 60-mg pseudoephedrine has no ergogenic effect in healthy athletes when performing either maximal anaerobic or submaximal aerobic tasks. We concur with the statement of Gillies et al. (9) that “the aim of doping control in international competition should be the elimination from competition of athletes who willfully use drugs with a known ergogenic effect to enhance their performances.” We believe that the findings of this study indicate that a therapeutic dose of pseudoephedrine does not act as an ergogenic aid during the performance of a Wingate test or cycling at 40% and 60% peak power. Its classification as a banned drug for athletic competition may not be appropriate.
The authors wish to thank Diana Jespersen for her technical assistance with this study.
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Keywords:©2003The American College of Sports Medicine
ERGOGENIC; WINGATE; BANNED SUBSTANCE; STIMULANT; EXERCISE