All studies were randomised placebo-controlled trials and were conducted in a double blind crossover fashion. Each protocol of the 16 studies included in this meta-analysis required the participants to abstain from use of stimulants before the trials and some studies had a pre-planned meal.
Table 1 shows the characteristics of the 16 studies included in the meta-analysis. Where data were presented only in figures [ 7 , 24 ], authors were directly contacted for the raw data. If these were not available, the figures were enlarged and values were calculated using a ruler [ 26 ]. The meta-analysis was carried out using the RevMan [ 27 ] software. The inverse-variance random-effects model for meta-analyses was used as it proportionately weights studies based on the magnitude of their standard errors [ 28 ] and accounts for heterogeneity across trials [ 29 ].
To account for the crossover design of the included studies, data for experimental and placebo conditions were analysed in the manner of a parallel group trial [ 28 ]. Study heterogeneity is represented by the I 2 statistic which is the variation of effects that could be attributed to differences across studies rather than to chance.
The 16 analysed studies included participants. One 6. Mean ages ranged from 18 to 38 years, with only one study [ 22 ] allowing participants up to 60 years. Participants were either competitive athletes or volunteers with an interest in sport.
Effects were generally positively or negatively trivial across parameters with the exception of HR which showed a small positive effect in favour of PSE ingestion. Subgroups, chosen by a median split, revealed important trends Table 3.
In terms of the other parameters studied, there were trivial improvements in time trial performance, a trivial reduction in RPE and trivial decreases in GLU and LAC levels during exercise. It could be argued that these equivocal findings suggest a meta-analysis would better wait until a larger number of studies have been performed, thus leading to a more robust conclusion. However, the intriguing subgroup analyses argue against this. Effect sizes tended to be larger in just those athletes of most concern to anti-doping agencies younger and well-trained athletes.
They also suggest an optimal time and activity to take the drug, indicating PSE is most effectively administered less than 90 min before a short bout of exercise of less than 25 min. However, this was accompanied by a larger effect on increasing HR. A recent study looking at neuromuscular performance effects using these more effective higher PSE doses mg noted adverse side effects such as tachycardia and heart palpitations 24 h after exercise [ 18 ].
This suggests it will be increasingly difficult to get ethical approval to test the most effective doses of PSE, making it important to carry out the most complete analysis of the studies that have already been performed. The initial search for our systematic review was carried out at approximately the same time as that of the recent systematic review by Trinh et al. However, the studies deemed appropriate for detailed analysis were different. Whilst our search confirmed and agreed with the many of the studies chosen by Trinh et al.
As our enhanced sample enabled the meta-analysis that Trinh et al. Both reviews focused on the performance effects of PSE using a randomised-controlled trial approach. This biased our search to include only those studies that focused on sports events with an aerobic component.
This approach ruled out one article included by Trinh et al. It also ruled out a recent study published after both systematic searches.
No effects were seen except in the highest dose studied mg where PSE seemingly increased lower body muscle contraction velocity. Trinh et al.
We feel that, at least in part, this conclusion is based on the combination of a flawed search strategy and an overly restrictive view of which articles to select from that search.
We found seven additional papers omitted by Trinh et al. On this basis, these studies could, in principle, fit the criteria used by Trinh et al. These articles are highlighted in Table 1 and owing to their importance to our final meta-analysis, it is crucial that we justify their inclusion individually see discussion in Table 4.
Given that Trinh et al. Crucially, all seven studies excluded showed no effect of PSE on performance. This may not be related to a dose effect as three studies [ 6 , 8 , 22 ] were at low clinically approved doses and four were at supratherapeutic doses [ 19 , 20 , 23 , 24 ]. Of the 10 studies included by Trinh et al.
However, adding the seven omitted studies would significantly weaken this argument as only 3 out of 7 high dose studies demonstrate a positive effect of PSE. Therefore, although there is clearly an increase in HR during exercise due to PSE, we are more equivocal than Trinh et al. Including these new articles does, however, strongly favour the conclusion that when taken at clinically recommended doses, PSE has only a very minor effect on HR and no ergogenic effect in terms of performance.
Our analysis suggests that only at high doses does PSE have the potential to enhance sports performance. It also sheds some light on to the possible mechanism that could be operating. The subgroup analyses showed that the biggest effect sizes were seen at high doses and in athletes with high maximal oxygen uptake VO 2 max. Three individual studies showed a performance effect [ 13 , 14 , 15 ]. Gill et al. Similarly, Pritchard-Peschek et al.
Given that studies that showed no performance increase showed at least as large and as significant HR increases during exercise, it seems unlikely that—in and of itself—changes in HR underpin any performance enhancement.
In relation to RPE, GLU, and LAC levels in exercise, a lack of data is more challenging to overcome with only between five and seven studies reporting sufficient information. We observed a small, trivial decrease in all of these parameters. However, it is worth exploring the individual studies, as the statistical power of pairing individuals in a crossover study is lost during a meta-analysis.
For RPE, none of the five studies included showed meaningful differences between PSE and placebo [ 8 , 12 , 15 , 22 , 23 ]. An additional study did not report values, but did state that there were no significant differences [ 7 ]. Glucose levels were not significantly different in four of the five studies included in the meta-analysis [ 6 , 7 , 14 , 23 ]. An additional study, not part of the analysis as it reported no values, again stated a lack of any PSE effect on GLU [ 25 ].
This was one of the few studies that also showed a performance effect decreased time in cycling TT. Interestingly in this case, it was the pre-exercise GLU level that correlated with the increased performance in the cycling time trial. Lactate levels did not significantly change in five of the seven studies included in the meta-analysis [ 7 , 13 , 14 , 15 , 23 ].
However, they did significantly decrease in two studies [ 19 , 24 ]. In one study, LAC levels were not reported, the authors nonetheless stating there was no significant change [ 25 ].
Given that only 3 of the 16 studies included in our analysis showed a performance benefit, it is worth exploring in detail, which secondary parameters changed in these studies to see if this can inform mechanism. These are consistent with the well-characterised role of PSE in stimulating the sympathetic nervous system and acting as a bronchodilator [ 33 ]. This is unlikely to explain the effect on peak power observed here, nor is a small increase in FVC and FEV likely to improve sports performance in endurance events given the lack of consistent ergogenic effect of drugs that are far more effective in increasing lung function such as salbutamol [ 34 ].
Hodges et al. However, no other measured parameters HR, LAC, GLU, arterial O 2 partial pressure, arterial carbon dioxide partial pressure and arterial oxygen saturation were significantly altered. Pritchard-Peschek et al. PSE is more lipid soluble and is therefore more accessible to the central nervous system. Consequently, it can, in principle, act as both a peripheral or central stimulant. However, the biochemical, physiological, and psychological data in our systematic review and meta-analysis fail to give a consistent explanation to underpin a possible ergogenic mechanism.
Heart rate did increase, however, in most studies there was no accompanying performance benefit; indeed in some studies which showed a performance benefit, there is no significant heart rate change. However, other studies show no metabolite changes even when there is a performance benefit. The WADA Prohibited List may include any substance that satisfies any two of the following three criteria: i it has the potential to enhance or enhances sport performance; ii it represents an actual or potential health risk to the athlete; iii it violates the spirit of sport.
Apparently, PSE fulfilled these criteria and was banned until , did not fulfil them between and when it was removed from the banned list , and then fulfilled them again after when it returned to the banned list. Currently, PSE is only banned in competition.
Even given the biological variability of single point measurements, this level is high enough that it should not be possible to produce a positive urine test if an athlete discontinues a therapeutic dose of PSE more than 24 h before competition. However, it is possible, though not guaranteed, to exceed these levels within 24 h of taking PSE at the normal therapeutic dose [ 9 ], and it is impossible not to exceed them when on a supratherapeutic dose [ 24 ].
The program indicated clear abuse of this substance with high concentrations in a number of sports and regions. In addition, available literature shows scientific evidence of the performance-enhancing effects of pseudoephedrine beyond certain doses. Some increase in PSE use would be expected when the ban was lifted given that the best drug to treat nasal decongestion in competition was now freely available to athletes without the threat of sanction.
Presumably, the geographic and sport-specific nature of the increase argued against this more benign interpretation. Subsequent research in the s further differentiated the two drugs on the basis of their potential for adverse cardiovascular effects, when it was shown that the dose of pseudoephedrine required to raise diastolic blood pressure above 90mmHg was three times higher than that of ephedrine.
So it was concluded that pseudoephedrine 60mg was the optimal single adult dose which achieved maximal nasal decongestion with minimal cardiovascular or other unwanted effects. More recently, a large, placebo-controlled study of patients with nasal congestion associated with acute upper respiratory tract infection URTI showed significantly greater improvement in NAR following single and multiple doses of pseudoephedrine 60mg over three days, with accompanying subjective improvements.
Pseudoephedrine is not totally free from stimulatory effects on the CNS: sleep disturbance and, rarely, hallucinations have been reported. Nasal congestion rarely occurs in isolation — in either allergic rhinitis or common cold sufferers. Antihistamines and intranasal corticosteroids form the mainstay of treatment for allergic rhinitis, with intranasal steroids superior to antihistamines in relieving nasal blockage and most other symptoms.
In cold and influenza remedies, pseudoephedrine has been combined with a wide range of other agents, but an analgesic is almost universal — usually paracetamol.
The additive effect of paracetamol 1,mg and pseudoephedrine 60mg has been demonstrated in a double blind study in URTI patients. Professor Eccles, one of the investigators in the study, explains that, although paracetamol caused slight worsening of nasal congestion, pseudoephedrine appeared slightly to enhance the analgesic effects of paracetamol.
The widespread limitations introduced on sales of pseudoephedrine followed an increase in methamphetamine use in the US, UK and elsewhere during the early s. For Olympic athletes, the advice about taking oral products containing pseudoephedrine is clear-cut. WADA advises them to stop taking such products 24 hours before in-competition periods. Some experts question the need for pseudoephedrine to be on the banned list at all.
It was off the banned list altogether from — One recent placebo-controlled study of the effects of pseudoephedrine 2. Professor Eccles suggests that the restriction is less to do with performance enhancement and more to do with potential drug test confusion with other substances with similar structures, such as ephedrine and methamphetamine.
He concludes that pseudoephedrine is a tough product to challenge as a nasal decongestant. Any action to take account of the methamphetamine issue should be proportional, otherwise we will be depriving the general public of a safe and effective oral decongestant. Access provided by. Pseudoephedrine is a tough product to challenge as a nasal decongestant Although pseudoephedrine has had its fair share of negative publicity in recent years, Jenny Bryan looks at why it is still one of the best decongestants around.
Chinese import Pseudoephedrine treatment is thought to date back thousands of years, and Ephedra sinica — a Himalayan shrub from which ephedrine and its stereoisomer, pseudoephedrine, are derived — was recommended for use in colds, fever and asthma in an early Chinese pharmacopoeia.
A prescription is not required to purchase these products. View more on Pseudoephedrine Regulations View more about our active ingredients. The procedure may vary state by state, but generally to purchase a product containing the ingredient pseudoephedrine at a store with a pharmacy, you will need to do the following:.
Only the products below are found at the pharmacy counter.
0コメント