Wednesday, 4 June 2014

Let’s (not) Get Physical: the Effect of Spironolactone on Muscle Strength in the Elderly

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Life expectancy has increased continuously over the past several decades, and with it, a host of new age-related ailments have emerged as contemporary medical issues. Muscle function decreases with age, leaving increasing numbers of elderly people incapable of being physically independent. This not only has devastating personal effects but is also a major public health issue. In a recent study, researchers investigated whether blocking the hormone aldosterone may help counter the effects of physical impairment with age.

Aldosterone is a hormone best known from the role it plays in the regulation of blood pressure, but it has also been associated with muscle weakness. This makes sense, considering that aldosterone also lowers levels of magnesium and potassium – two minerals that are essential for muscle contractility. Thus lower levels of aldosterone may promote restoring muscle function.

How can we keep aldosterone levels low? The production of aldosterone in the body is a complex interplay between hormones and enzymes. Medication can be targeted to interfere with it at different stages. One way to influence aldosterone levels is to inhibit the creation of a hormone that would otherwise stimulate its production. These so-called angiotensin-converting enzyme blockers (ACE blockers) are usually prescribed to treat high blood pressure and heart failure. Interestingly, some studies reported additional positive effects on muscle strength and physical fitness in elderly.  But the results not conclusive: some studies did not find any positive effect on muscle strength. Furthermore, ACE blockers seem to fail at reducing aldosterone levels over longer time periods. However, long-term efficacy is a crucial factor for improving muscle function. 

Image Source: Shutterstock Copyright: Tish1

Another way to interfere with aldosterone is to block aldosterone receptors directly. This is exactly what a drug called spironolactone does. It blocks receptors in the kidneys, heart and blood vessels that are usually targeted by aldosterone. Because aldosterone can only act when it has the possibility to bind to its receptors, any competition for those receptors blocks its action. Recent studies suggest however that blocking the aldosterone receptors by means of spironolactone may be superior to ACE inhibitors when it comes to blocking the specific effects of aldosterone. For example, spironolactone seems to be more effective than ACE inhibitors in keeping magnesium and potassium levels in muscles high – a highly desired effect for improving muscle strength. Spironolactone may thus be a promising medication to counter the decline in muscle function in elderly.

In line with this, physical fitness of heart failure patients improves after they’re treated with spironolactone. However, one must consider that spironolactone is well-known as an effective medication for high blood pressure and heart failure. Therefore, its positive effect on physical performance may simply be caused by better overall health after treatment rather than by a direct effect of spironolactone on muscle strength. To understand whether the intake of spironolactone may have a beneficial effect on muscle strength in elderly who do not suffer from heart failure, a research team from the University of Dundee recruited 120 patients aged 65 and older. The patients had self-reported difficulties in performing daily activities, but did not suffer from heart conditions or high blood pressure. Half of the participants received a daily dose of spironolactone over a period of 20 weeks, while the other half of the patient group received a placebo – a pill that resembled spironolactone but which was medically inert. The researchers considered various factors of interest, including objective and subjective physical function. Subjective physical functioning was measured by self-reports. Objective physical function was assessed by the distance that participants could walk within 6 minutes, a simple but widely-used, reliable measure of exercise performance in the elderly.

The results were surprising: the treatment with spironolactone did not increase the distance that participants could walk within 6 minutes, suggesting that the intake of spironolactone did not enhance their muscle functioning. In contrast to the objective findings, the self-report measures showed another picture: after 20 weeks, only those participants who had been treated with spironolactone reported an improvement in quality of life. Whether this effect was caused by a pain-relieving effect or by other pharmacological benefits associated with spironolactone is not known; further studies are required to clarify these results.

Despite the fact that the results could not confirm any positive effect of spironolactone on muscle strength, this should not be interpreted as a definite exclusion of its efficacy as a counteragent for age-related muscle decline. Rather, the findings demonstrate that spironolactone was well tolerated in participants without heart failure and improved their quality of life. This provides encouragement to test the drug at higher doses and for longer treatment durations. Future studies are needed to determine whether these advanced treatments can cause the desired physiological effects, but the current findings help to define them.

This summary by Jenny-Charlotte Baumeister was shortlisted for Access to Understanding 2014 and was commended by the judges. It describes research published in the following article, selected for inclusion in the competition by the Chief Scientist Office of the Scottish Executive:

PMCID: PMC3695565
L.A. Burton, D. Sumukadas, M.D. Witham, A.D. Struthers & M.E.T. McMurdo.
The American Journal of Medicine (2013) 126(7), 590-597.

Access to Understanding entrants are asked to write a plain English summary of a research article. For Access to Understanding 2014 there were 10 articles to choose from, selected by the Europe PMC fundersThe articles are all available from Europe PMC, are free to read and download, and were supported by one or more of the Europe PMC funders.

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