The Side Effects of Statins: Are They Worth It?

· ·

When statin-“intolerant” patients are challenged blindly, how many are really suffering muscle side effects?

Discuss
Languages

    Selecting a language opens the video on YouTube with captions enabled.

  • English
Republish

Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

In my last video, I tried to quantify the benefits of starting cholesterol-lowering statin drugs, but that’s only half the equation. The #1 reason people may refuse to take statins or stop taking them is a concern about side effects.

Statins are considered mandatory for secondary prevention, for those with known cardiovascular disease to prevent a second heart attack or stroke. But primary prevention, trying to prevent our first event, is more of a gray area. A hundred adults between the ages of 50 and 75 without known cardiovascular disease would have to be treated with a statin for 2.5 years to prevent one major adverse cardiovascular event, like a stroke or a heart attack. That’s the upside.

The downside, if you treated 10,000 such people for a year, the statins would be expected to cause 15 cases of muscle symptoms, 8 cases of liver dysfunction,12 cases of kidney dysfunction, and 14 more eye conditions, while at the same time preventing 19 heart attacks, 9 strokes, and 8 cardiovascular deaths. So, approximately the same risk of having a major side effect or a major benefit, but a benefit like preventing a heart attack or death is more important than avoiding a case of blurred vision. So, these reviewers suggest cardiovascular benefits of statins outweigh adverse effects in primary prevention. But wait; there were only 15 cases of muscle symptoms out of 10,000 people treated?

That is based on the clinical trials that found approximately one in 1000 users over a 10-year period develops serious muscle disease. Cases of muscle weakness or muscle breakdown are hard to miss, whereas the incidence of statin-induced muscle aches and pains is far more contentious. Such randomized controlled trials may seriously underestimate adverse effects like muscle pain, since industry-sponsored trials include these run-in periods before the study even starts to exclude people who can’t tolerate the drugs. So, no wonder they see such low rates in the actual trials, where all those folks who suffered never made it into the trials in the first place. Furthermore, the majority of clinical trials don’t systematically ask if people are experiencing side effects, since the trials are often run by the company that makes them. So, there’s an incentive to “don’t ask, don’t tell.”

Observational studies out in the real world, on the other hand, don’t find muscle symptoms in one in a thousand, but rather one in 10 or even one in five—that’s one or two hundred times higher rates than seen in the trials. Some have attributed this difference between observational and experimental studies to the nocebo effect, where patients experience side effects they are expecting, but it’s really all in their head. Or it could be because nearly all trials never actually asked, and even when they did ask, industry-sponsored trials are known to underreport, known to sweep adverse effects under the rug. Finally, statin trials have often excluded patients with a history of muscle problems, who may be in the population most at risk. How do we get to the bottom of this?

Well, if you rechallenge patients who claim to be statin-intolerant with the real thing or a placebo, you can see what proportion have muscle aches that are actually caused by the drugs, and when you do that, between 1/3 and 1/2 of patients consistently report muscle pain on statins, but not placebo. So, yes, a lot of people who think statins are causing their muscle pains are actually mistaken. But at the same time, a lot of people really are suffering because of these drugs. The European Atherosclerosis Society estimates the overall risk of developing statin-related muscle symptoms to be anywhere from one in 14 who go on statins to nearly one in 3.

Most trials also don’t systematically ask about other potential adverse effects––like fatigue, even though fatigue is among the most commonly reported problems by patients on statins. In a non-industry-funded trial on the effects of statins versus placebo on energy and fatigue with exertion, effectively four out of 10 treated women cited worsening in either energy levels or exertional fatigue.

What about effects on the brain? In 2012, the U.S. Food and Drug Administration issued a new warning for the labeling of statin drugs regarding potential adverse effects on cognition, including memory loss and confusion. That was based on early studies like these, but thankfully more recent evidence does not strongly support a link between statins and cognitive impairment. By 2015, putting all the relevant studies together, a systematic review concluded that statin therapy did not appear to be associated with cognitive impairment. But again, that’s from clinical trials.

What about statin use and dementia risk? Dozens of studies, involving a total of more than seven million patients, found that statin use was linked to lower risks of dementias, like Alzheimer’s disease. This could be because of the role cholesterol plays in the development of Alzheimer’s, as I’ve explored before. But it also could be due to things like “healthy user bias,” where people who diligently take statins may also engage in other health-promoting behaviors, and it’s those behaviors that reduce the risk, rather than the drugs themselves.

In the Alzheimer’s video, I profiled Dr. Dean Ornish’s landmark 2024 study showing that a whole food plant-based diet and other healthy lifestyle behaviors could apparently reverse the progression of early-stage Alzheimer’s disease, similar to his previous work showing that a similar plant-based diet and lifestyle could reverse the progression of heart disease. But it doesn’t have to be all or nothing.

In the Lyon Diet Heart Study, heart attack survivors were randomized to advice to eat a more Mediterranean-style diet rich in plant-based omega-3s, or to just continue to eat whatever their doctors told them to eat. And the dietary advice group ate more bread, more fruit, less ham and sausage and other meat, less butter and cream. And though they didn’t significantly change their fish consumption, they did eat more of a provided butterless spread enriched with plant-based omega-3s––like the kind found in flaxseeds and walnuts. And check out those survival curves. Over the next five years, only about 5% of the people in the diet group suffered a fatal or nonfatal heart attack, compared to more than 20% of the control group.

As health professionals, the pharmaceutical industries, and research funding and regulatory agencies are almost totally focused on lowering cholesterol levels using drugs. It is heartening to see a well-conducted study find that relatively simple dietary changes achieved greater reductions in the risk of all-cause mortality and heart disease mortality in a secondary prevention trial than any of the drug studies to date. Diet beat out drugs when it came to death. Despite the striking findings—we’re talking 70% reduction in the risk of premature death from just eating more plant foods and less meat and dairy—few cardiologists may even be aware of the study, even though it was published in one of the most prestigious medical journals in the world.

Please consider volunteering to help out on the site.

Motion graphics by Avo Media

Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

In my last video, I tried to quantify the benefits of starting cholesterol-lowering statin drugs, but that’s only half the equation. The #1 reason people may refuse to take statins or stop taking them is a concern about side effects.

Statins are considered mandatory for secondary prevention, for those with known cardiovascular disease to prevent a second heart attack or stroke. But primary prevention, trying to prevent our first event, is more of a gray area. A hundred adults between the ages of 50 and 75 without known cardiovascular disease would have to be treated with a statin for 2.5 years to prevent one major adverse cardiovascular event, like a stroke or a heart attack. That’s the upside.

The downside, if you treated 10,000 such people for a year, the statins would be expected to cause 15 cases of muscle symptoms, 8 cases of liver dysfunction,12 cases of kidney dysfunction, and 14 more eye conditions, while at the same time preventing 19 heart attacks, 9 strokes, and 8 cardiovascular deaths. So, approximately the same risk of having a major side effect or a major benefit, but a benefit like preventing a heart attack or death is more important than avoiding a case of blurred vision. So, these reviewers suggest cardiovascular benefits of statins outweigh adverse effects in primary prevention. But wait; there were only 15 cases of muscle symptoms out of 10,000 people treated?

That is based on the clinical trials that found approximately one in 1000 users over a 10-year period develops serious muscle disease. Cases of muscle weakness or muscle breakdown are hard to miss, whereas the incidence of statin-induced muscle aches and pains is far more contentious. Such randomized controlled trials may seriously underestimate adverse effects like muscle pain, since industry-sponsored trials include these run-in periods before the study even starts to exclude people who can’t tolerate the drugs. So, no wonder they see such low rates in the actual trials, where all those folks who suffered never made it into the trials in the first place. Furthermore, the majority of clinical trials don’t systematically ask if people are experiencing side effects, since the trials are often run by the company that makes them. So, there’s an incentive to “don’t ask, don’t tell.”

Observational studies out in the real world, on the other hand, don’t find muscle symptoms in one in a thousand, but rather one in 10 or even one in five—that’s one or two hundred times higher rates than seen in the trials. Some have attributed this difference between observational and experimental studies to the nocebo effect, where patients experience side effects they are expecting, but it’s really all in their head. Or it could be because nearly all trials never actually asked, and even when they did ask, industry-sponsored trials are known to underreport, known to sweep adverse effects under the rug. Finally, statin trials have often excluded patients with a history of muscle problems, who may be in the population most at risk. How do we get to the bottom of this?

Well, if you rechallenge patients who claim to be statin-intolerant with the real thing or a placebo, you can see what proportion have muscle aches that are actually caused by the drugs, and when you do that, between 1/3 and 1/2 of patients consistently report muscle pain on statins, but not placebo. So, yes, a lot of people who think statins are causing their muscle pains are actually mistaken. But at the same time, a lot of people really are suffering because of these drugs. The European Atherosclerosis Society estimates the overall risk of developing statin-related muscle symptoms to be anywhere from one in 14 who go on statins to nearly one in 3.

Most trials also don’t systematically ask about other potential adverse effects––like fatigue, even though fatigue is among the most commonly reported problems by patients on statins. In a non-industry-funded trial on the effects of statins versus placebo on energy and fatigue with exertion, effectively four out of 10 treated women cited worsening in either energy levels or exertional fatigue.

What about effects on the brain? In 2012, the U.S. Food and Drug Administration issued a new warning for the labeling of statin drugs regarding potential adverse effects on cognition, including memory loss and confusion. That was based on early studies like these, but thankfully more recent evidence does not strongly support a link between statins and cognitive impairment. By 2015, putting all the relevant studies together, a systematic review concluded that statin therapy did not appear to be associated with cognitive impairment. But again, that’s from clinical trials.

What about statin use and dementia risk? Dozens of studies, involving a total of more than seven million patients, found that statin use was linked to lower risks of dementias, like Alzheimer’s disease. This could be because of the role cholesterol plays in the development of Alzheimer’s, as I’ve explored before. But it also could be due to things like “healthy user bias,” where people who diligently take statins may also engage in other health-promoting behaviors, and it’s those behaviors that reduce the risk, rather than the drugs themselves.

In the Alzheimer’s video, I profiled Dr. Dean Ornish’s landmark 2024 study showing that a whole food plant-based diet and other healthy lifestyle behaviors could apparently reverse the progression of early-stage Alzheimer’s disease, similar to his previous work showing that a similar plant-based diet and lifestyle could reverse the progression of heart disease. But it doesn’t have to be all or nothing.

In the Lyon Diet Heart Study, heart attack survivors were randomized to advice to eat a more Mediterranean-style diet rich in plant-based omega-3s, or to just continue to eat whatever their doctors told them to eat. And the dietary advice group ate more bread, more fruit, less ham and sausage and other meat, less butter and cream. And though they didn’t significantly change their fish consumption, they did eat more of a provided butterless spread enriched with plant-based omega-3s––like the kind found in flaxseeds and walnuts. And check out those survival curves. Over the next five years, only about 5% of the people in the diet group suffered a fatal or nonfatal heart attack, compared to more than 20% of the control group.

As health professionals, the pharmaceutical industries, and research funding and regulatory agencies are almost totally focused on lowering cholesterol levels using drugs. It is heartening to see a well-conducted study find that relatively simple dietary changes achieved greater reductions in the risk of all-cause mortality and heart disease mortality in a secondary prevention trial than any of the drug studies to date. Diet beat out drugs when it came to death. Despite the striking findings—we’re talking 70% reduction in the risk of premature death from just eating more plant foods and less meat and dairy—few cardiologists may even be aware of the study, even though it was published in one of the most prestigious medical journals in the world.

Please consider volunteering to help out on the site.

Motion graphics by Avo Media

Doctor's Note

This is the third video in an extended series on the critically important topic of how to lower LDL cholesterol, the primary driver of our primary killer. In this series, we take a deep dive into how to lower cholesterol through diet. We’ll explore the Portfolio Diet, plant sterols, and cholesterol-lowering supplements, foods, herbs, and spices, then conclude with my Portfolio Plus Powder recipe “cooking” video.

If you don’t want to wait for all the videos to be released over time, we’ve compiled all the information into my latest book, Lower Cholesterol Naturally with Food, available as a softcover, ebook, and audiobook.

If you missed either of the first two videos, check out Why Isn’t Everyone on Cholesterol-Lowering Statin Drugs? and How Effective Are Statins?. The next in the series is What Is the Best Statin Cholesterol-Lowering Drug?.

If you haven't yet, you can subscribe to our free newsletter. With your subscription, you'll also get notifications for just-released blogs and videos. Check out our information page about our translated resources.

Subscribe to our free newsletter and receive the preface and new author’s note from Dr. Greger's How Not Die: Revised and Updated.

Previous Video

How Effective Are Statins?

Pin It on Pinterest

Share This