 There is now overwhelming evidence to support reducing LDL cholesterol, bad cholesterol, to reduce atherosclerotic cardiovascular disease, the number one killer. So why is adherence to cholesterol-lowering statin drug therapy such a major challenge? The majority of studies reported at least 40%, and as much as 80% of patients did not comply fully with statin treatment recommendations. Three quarters may flat out stop taking them, or sometimes up to nearly 90% discontinue treatment. When asked why, most former statin users or discontinuers cited muscle pain. A side effect is the primary reason for stopping the pills. By far, the most prevalent and important adverse events up to 72% of all statin side effects are statin-associated muscle symptoms. Taking coenzyme Q10 supplements is a treatment for statin-associated muscle symptoms was a good idea in theory, but they don't actually appear to help. Normally side effect symptoms go away when you stop the drug, but sometimes can linger a year or more. There's evidently growing evidence that statin intolerance is predominantly psychosocial, not pharmacological, meaning, wait, maybe it's mostly just in people's heads? Statins have developed a bad reputation with the public, one editorial read, a phenomenon driven largely by proliferation on the internet of bizarre and unscientific criticisms of these drugs. Maybe it's Google that leads to statin intolerance, but come on. People have been going off statins for decades before there even was an internet. What kind of data has doctors suggesting that patients are falsely misattributing normal aches and pains to be statin side effects? Well, if you take people who claim to have statin-related muscle pain and randomize them back and forth between statins and an identical-looking placebo in three-week blocks, they can't actually tell whether they're getting the real drug or the sugar pill. The problem with that study, though, is that it may take months to not only develop statin-induced muscle pain, but months before it goes away. I mean, so no wonder three weeks on, three weeks off may not be long enough for the participants to discern which is which. But these data are more convincing. 10,000 people were randomized to a statin or sugar pill for a few years. They had to stop the study early because so many more people were dying in the sugar pill group, and so everyone was then offered the statin. What they noted was that there was no excessive reports of muscle-related adverse effects among patients assigned to the statin over those assigned to the placebo, but then when the placebo phase was over and the people knew they were on a statin, then they reported more muscle side effects in those who knew they weren't. These results illustrate the so-called no-cebo effect, kind of like the opposite of the placebo effect. Placebo effects are positive consequences, falsely attributed to a treatment, whereas no-cebo effects are negative consequences, falsely attributed to a treatment, as was evidently seen here, as there was an excess rate of muscle-related adverse effects reported only when patients and their doctors were aware that statin therapy was being used, and not when it was being concealed. They hope these results will help assure both physicians and patients that most adverse events associated with statins are not actually caused by the drug, and should help counter exaggerated claims about statin-related side effects. As these kind of results from placebo-controlled randomized trials that are said to have shown it definitively that almost all the symptomatic adverse events that are attributed to statin therapy and routine practice are not actually caused by the drug. Now, only a few patients will believe this, that their statin-associated muscle symptoms are of psychogenic origin, meaning all just in their head, but their denial may have deadly consequences. Discontinuing statin treatment may be a life-threatening mistake. Here's the mortality of those who stopped their statins after having a possible adverse reaction compared to those who stuck with them. This translates into about one excess death for every 83 patients who discontinued treatment within a four-year period. So when there are media reports about statin side effects and people stop taking them, this could result in thousands of fatal and disabling heart attacks and strokes which would otherwise have been avoided. Seldom in the history of modern therapeutics have the substantial proven benefits of a treatment been compromised to such an extent by serious misrepresentations of the evidence for its safety. But is it a misrepresentation to suggest statin therapy caused the side effects enough to a fifth of patients? I mean, that is actually what you see in clinical practice. Between 10% to 25% of patients placed on statins complain of muscle problems. But because we don't see anywhere near those kinds of numbers in controlled trials, patients are accused of being confused. Why in clinical trials is the incidence of side effects from statins so low but out in the real world appear to be so high? For example, take this meta-analysis of clinical trials, finding muscle problems not in one in five, but only one in 2,000 patients. So, hey, maybe everyone over a certain age should be on them. But of course, every single one of those trials was funded by the statin manufacturers themselves. So, for example, how could the randomized controlled trials mis-detecting statin-related adverse side effects such as muscle pain by not asking? A review of 44 statin trials revealed that only one directly asked about muscle-related adverse effects so are the vast majority of side effects just being missed in all these trials? Or are the vast majority of side effects seen in clinical practice just some figment of patients' imagination? Bottom line, we don't know. But there's certainly an urgent need to figure it out.