It still remains to be seen if Chris Froome will face sanctions for an adverse analytical finding in which he exceeding the maximum limit of 1,000ng/ml of salbutamol in his urine.
In the meantime, many have questioned whether any dosage of salbutamol from an inhaler could realistically offer any performance advantage, as a great number of studies suggest that those using salbutamol enjoy no advantage over non-asthmatic peers.
Speaking with Cyclist, the World Anti-Doping Agency explains that it places a maximum limit on salbutamol because it considers that the substance can, in certain cases, act as an anabolic agent that can increase muscle mass.
‘There have been several studies, including animal models, showing that beta-2 agonists such as salbutamol can have an effect on muscle mass,’ says Olivier Rabin, senior director of science and international relationships at WADA.
However the actual upper limit is based on clinical guidelines from manufacturers, not specific anti-doping research. There is also no testing that shows inhaled salbutamol to show benefits for athletes. How exactly exceeding this limit of salbutamol could indicate unfair performance gains is, therefore, not as obvious as it might seem.
Potential enhancement
‘We know that taking salbutamol inhalation of 800 micrograms per 12 hours is not performance enhancing,’ says Rabin. Indeed, all research points to normal therapeutic use of inhaled salbutamol offering no performance gains. This is the reason why WADA removed the necessity for a TUE (theraputic use exemption) for normal use of the drug. Determining what dosage would be required to bring about a performance gain isn’t obvious, though.
Studies that have demonstrated anabolic effects of salbutamol have been done with animals, not humans, so it is highly likely that there is no identifiable quantity of salbutamol that would indicate a performance benefit.
The dosages indicated for use with a normal inhaler are relatively tiny. For innstance, if someone were admitted to hospital in the UK with a severe exacerbation (an asthma attack), the patient might expect a 2,500 microgram dosage every two hours – far exceeding the WADA maximum.
An inhaler is less likely to deliver a performance enhancing dose of salbutamol
This would generally be done with nebulisation, where a high volume of salbutamol in aerosol form is inhaled through a mask.
A cyclist could require this dosage in the event of a serious attack and in such cases an athlete could be granted a TUE even after the incident. ‘If an athlete had to use another form [eg nebulisation] of salbutamol in cases of asthma exacerbation, for example, it’s possible to have a TUE for higher doses of salbutamol,’ Rabin says.
Any nebulisation of salbutamol requires a TUE, as would any oral tablets. That’s because these forms of the drug would be ‘systemic’, rather than an inhaler, which acts locally on the muscles in the lungs.
Therein lies the key distinction in what WADA wants to allow, and what it wants to prohibit.
Systemic use and nebulisation
‘We have an upper limit because we have multiple publications showing that systemic use of beta-2 agonists, including salbutamol, can be performance enhancing,’ Rabin explains.
‘Systemic use’ usually means injection or ingestion of a pill – a form that delivers it directly into the gastrointestinal tract or blood system, rather than inhalation. However, inhalation can also result in ingestion.
‘When people inhale salbutamol a fraction is going to go into the lungs but a significant fraction is also going to go to the gastrointenstinal tract [it is swallowed], which would be similar to an oral intake,’ Rabin explains. ‘So the minute you really significantly increase the inhaled dose of a salbutamol a good fraction of it is going to end up being a systemic route.
‘This is particularly true when people use nebulisation of salbutamol. Nebulisation exposes you to potentially higher nasal intake of salbutamol,’ he adds.
Respiratory specialist Dr James Hull of The Royal Brompton Hospital in Chelsea published a paper late last year that spoke of ‘an apparent and worrying increase in the use of nebulised bronchodilator therapy in athletes’.
Dr Hull suggested that this could become more common as teams ‘opt to avoid using an oral corticosteroid (ie, to prevent accusation of use for performance gain).’
Why 800 micrograms?
As mentioned previously, the maximum limit is based on clinical advice from manufacturers.
Manufacturers set this limit not to prevent anabolic benefits, but rather to help prevent poor management of asthma. If relying too heavily on salbutamol rather than seeking appropriate treatment such as corticosteroids there is a significant risk of exacerbation of the condition.
‘We took [the upper limit] from a combination of what is a clinical practice of salbutamol and what is a potential muscular benefit of use of salbutamol,’ says Rabin.
To an extent this is geared toward the health of an athlete, as much as doping. ’As you know the world anti-doping code takes into account the protection of the health of the athletes,’ says Rabin.
‘Always keep in mind that from a sporting point of view you’re dealing with top competitive athletes and you need to know that the asthma is controlled and you can allow the athlete to compete.’
WADA makes clear that while the health of athletes is a concern, doping restrictions are primarily about performance gains not controlling medical practice, which is beyond its remit.
‘It’s not the medical practice that we’re trying to control, it’s fundamentally that beta-2 agonists can be performance enhancing in high doses,’ says Rabin.
WADA’s policy, then, stems above all from an interpretation of the research surrounding salbutamol and its anabolic properties. In some senses it’s a lot to hinge on research that remains theoretical only. But WADA is well-equipped to make the call.
‘We have some of the leading experts in respiratory physiology and pharmacology working with us,’ Rabin says. ‘So we are very confident that what is established today is adequate.’