• Maria Sharapova and the Pharmaceutical Quest for an Edge

    The following originally appeared on The Upshot (copyright 2016, The New York Times Company).

    It’s understandable that athletes at the highest end of the performance spectrum might look for any gain, any edge at all, that might help propel them to the top. Ego, fame and unbelievable amounts of money are at stake. But people all over the athletic spectrum are convinced that one supplement or another will make them healthier, faster or stronger, while other people seek a different sort of edge with drugs they hope will improve cognition.

    Maria Sharapova made news this week when she was suspended for using the “performance-enhancing” drug meldonium. I put that in quotes for a reason. Most Americans have probably never heard of this drug, let alone considered that someone would take it to improve their tennis. But there are a lot of healthy people, probably even people you know, who use a drug intended for ill people because they think it will give them an edge.

    Let’s start with meldonium. It works by increasing blood flow throughout the body. It’s mainly intended to treat ischemia, a condition that develops when parts of your body aren’t getting enough blood. Increased blood flow gets more oxygen moving around to muscles and other tissues.

    Of course, if you’re moving more blood and oxygen around, muscles all over the body might be better able to perform. Although the research on healthy people using the drug isn’t easy to parse, you can find reports from medical conferences that recommend doses for athletes. One page in a Russian medical journal that is now defunct is often cited as evidence of meldonium’s ability to improve performance.

    It doesn’t help that the Latvian drug maker itself says on its website that it is widely used “for the improvement of work capacity of healthy people at physical and mental overloads.” Meldonium is not approved by the Food and Drug Administration for use in the United States for any disorders.

    Drugs like EPO and steroids have a long track record of boosting athletic performance. But in general I’m baffled, although no longer surprised, by the widespread belief that drugs that help people who are ill will also improve those who are healthy.

    As my colleague Austin Frakt and I pointed out in two articles here on The Upshot, the gains often seen from pharmaceuticals are likely to be in those who need them the most. The less at risk you are, the less likely you are to see a benefit. Your chance of a side effect, however, remains unchanged.

    At my YouTube channel, I field more questions about supplements than about anything else. People are convinced that if a little vitamin C helps to protect your immune system, then mega doses of it will help you ward off illness. They won’t. Almost none of what you’ve been told about supplements by trainers, videos or diets has been proved in consistent, robust trials. When we do such trials, the supplements often fail. If they succeeded, all health care professionals would be recommending them.

    Additionally, supplements aren’t heavily regulated in the United States, so it’s shockingly likely that you aren’t even getting what you think you are.

    One recent craze in this area concerns nootropics: drugs or supplements that are supposed to improve cognitive function. Some are serious stuff and have a use in medicine, as meldonium has with ischemia. Modafinil, used in the treatment of narcolepsy, and piracetam, for dementia, are two of the most popular. We could also include stimulants used to treat disorders like attention deficit hyperactivity disorder, or A.D.H.D., in this group. Healthy people take these drugs to try to be brighter longer.

    It’s important to note that these beneficial effects have been proved only in people who have deficits. It has not been substantiated that their use in normal people gives them a real cognitive boost. A small 2013 randomized controlled trial looked at how modafinil affected creativity in otherwise healthy individuals. The results were mixed and not very convincing.

    A 2014 study also randomized healthy volunteers to take modafinil or a placebo. The most interesting outcome was the response latency on the Hayling Sentence Completion Test, which is thought to be highly sensitive to prefrontal executive function. Researchers found that those taking the drug took longer to complete sentences. That is, it made normal people slower — not what you’re looking for.

    If we pause to think about it, that’s probably what we want out of a drug for a condition like A.D.H.D. It makes people less impulsive. But that’s not what healthy people are taking it for.

    Collectively, a systematic review looked at all the studies. It found that methylphenidate, a stimulant used to treat A.D.H.D., had no real consistent enhancing effects. It did find that modafinil helped short-term sleep-deprived people maintain wakefulness, memory and an ability to get things done more than a placebo. But repeated doses of the drug couldn’t prevent deterioration of cognitive performance over a longer period of sleep deprivation. Of course, the same might be said about caffeine, without many of the significant side effects. The drugs carry significant risks.

    There has been a Cochrane review of piracetam. Researchers found 24 studies with almost 12,000 participants. There were no significant differences in cognition, immediate memory, delayed memory, speech, mental status or “global impression of change” in those who took the drug. Further, these studies were mostly on those who were cognitively impaired; there’s even less reason to think you’d see a difference in otherwise healthy people.

    There’s no magic here. We’ve become more and more successful at treating deficits and deficiencies in people. Those same therapies are not intended to improve healthy individuals. In our eternal quest to be better, however, many are willing to act without evidence in the hope they can leap ahead. Unfortunately, most of those people are getting all the harms of the substances they take, but few of the benefits.


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