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  1. #1
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    Statins and Muscle Pain

    Statins and Muscle Pain: What Are the Odds?
    BerkeleyWellness.com
    April 4, 2019

    Deaths from coronary artery disease have plummeted in recent decades, and cholesterol-lowering statin drugs have played a major role in this success story. So why do many people fear statins and refuse to take them—or start and then stop taking them?

    One in four Americans over age 40 now take a statin, but about one in ten stop because of symptoms they attribute, often mistakenly, to the drugs, according to a recent Scientific Statement from the American Heart Association (AHA), which attempts to set the record straight about statin safety.

    A continuum of muscle problems
    The clearest risk from statins is muscle damage resulting in weakness, tenderness, or pain. These symptoms commonly occur in large muscles in the legs, chest, upper arms, shoulders, or lower back, but can occur elsewhere. Statin-related muscle inflammation and damage occur on a continuum. Most often the problem is mild and manifests itself as muscle discomfort or weakness. More serious muscle damage causes moderate to severe pain. The most serious (and least common) muscle disorder caused by statins, called rhabdomyolysis, can also damage the kidneys and lead to kidney failure.

    If you take a statin and develop musculoskeletal pain, it’s natural to blame the drug. But such pain is common, especially in middle-aged and older people, and can have many causes. In fact, most clinical trials have found that nearly as many people taking a placebo report muscle problems as do those taking statins. According to the AHA’s analysis of clinical trials:

    • Fewer than 1 in 100 statin users develop muscle pain (myalgia) of any degree, compared to a placebo.
    • Fewer than 1 in 1,000 develop muscle symptoms accompanied by elevated blood markers for muscle damage (myopathy).
    • About 1 in 10,000 develop rhabdomyolysis.

    However, some researchers believe that participants in statin trials have not been representative of the general population, so the results may underestimate the true prevalence of statin-related side effects. And with only one exception, the trials were not specifically designed to examine the effect of statins on muscles.

    In contrast, in large observational studies as well as clinical practice, anywhere from 5 to 20 percent of people (or possibly even more) report muscle symptoms that are ascribed to statins, according to Ronald Krauss, MD, director of Atherosclerosis Research at Children’s Hospital Oakland Research Institute and a member of our Editorial Board, “and that is likely an underestimate of more subtle effects of statins on muscle biology.”

    The symptoms usually begin within the first few weeks or months of treatment (or after an interacting drug is started) but sometimes start later, and in some cases can be precipitated by increased physical activity.

    Risk factors and nocebo effect
    Many factors can increase the risk of statin-related muscle damage:

    • High statin dose.
    • Being over 75 (because of coexisting medical conditions and use of multiple drugs).
    • Being female or of East Asian descent.
    • Any disease affecting kidney or liver function.
    • Excessive alcohol intake.
    • A family history of statin intolerance.
    • Certain medical conditions, such as hypothyroidism.
    • Taking certain other medications, such as some antibiotic, antifungal, or HIV drugs.
    • Regularly drinking grapefruit juice.This inhibits an enzyme in the small intestine that metabolizes certain drugs, including some statins (notably simvastatin, atorvastatin, and lovastatin), thus boosting blood levels of them and increasing the risk of statin-related myopathy.

    The AHA places new emphasis on the fact that statin users may experience muscle pain because of the “nocebo” (Latin for “I will harm”) effect. That occurs when negative expectations and fears about statins’ risks—aroused by media reports, warnings in package inserts, word of mouth from statin users, and rumors on the internet—become a self-fulfilling prophecy. The nocebo effect is the flip side of the placebo effect, in which positive expectations contribute to benefits. Symptoms related to a nocebo effect are real (not imagined), can be severe, and should never be dismissed by doctors and other health care providers, according to the AHA.

    Evaluating other concerns
    Another established adverse effect of statins is a modestly increased risk of developing type 2 diabetes, especially in women and in people who already have risk factors for it, such as being sedentary or obese. According to the AHA, clinical trials indicate that statins may increase the risk by 10 to 20 percent over five years, which works out to about 2 extra cases of diabetes per year in 1,000 statin users in the general population.

    For people who already have diabetes, statins may cause a small increase in blood sugar. Since people with diabetes are at high risk for cardiovascular disease, the benefit of statin therapy outweighs this side effect.

    The AHA states that there may be a slightly increased risk of hemorrhagic stroke (caused by a rupture of an artery in the brain) in people who have already had one, but the benefit in reducing ischemic strokes (far more common, caused by blood clots) and heart attacks generally outweighs that risk.

    Liver damage used to be a major concern, but research has found that statin-related liver problems are rare and seldom progress to serious disease. Statins may cause a dose-related rise in blood markers for liver damage in about 1 percent of people, but this alone does not indicate clinically significant liver injury. Liver damage from statin drugs occurs in about 1 in 100,000 people, according to the AHA. In statin users, symptoms such as unusual fatigue, loss of appetite, or yellowing of the skin or whites of the eyes, particularly in people with pre-existing liver disease, require medical attention.

    The paper also reviewed the research on other reported or rumored side effects and safety concerns - including neurological problems, cognitive impairment, peripheral neuropathy, cataracts, cancer, erectile dysfunction, kidney problems, and tendon ruptures—and found no convincing evidence that statins increased these risks.

    Restarting statins: good news
    A Harvard study looked at what happens in the real world when people develop statin-related problems. Published in the Annals of Internal Medicine in 2013, it analyzed medical records of 108,000 people taking statins. During an eight-year period, about half discontinued the drugs at least temporarily, most often for unknown reasons or because they thought the drug was no longer necessary. Nearly one-fifth of all patients reported adverse effects, usually muscle pain, which often led to stopping the drugs. Seven people developed rhabdomyolysis.

    The key finding was that among the 11,000 people who reported stopping statins because of adverse effects, more than 90 percent of those who were re-challenged with a lower dose or different statin were able to continue it long term. This suggests that the adverse effects were not caused by statins, were mild enough to be tolerable, or went away when patients switched to a lower dose or different statin. Thus, the study concluded, most people who have adverse effects should not give up on statins.

    In 2017, a second study by the same researchers in the same journal found that among 28,000 people who reported adverse reactions to statins, 71 percent were able to continue taking the same or a different statin. After four years, those who continued taking statins had a 10 to 20 percent lower risk ofcardiovascular events or death from any cause than those who stopped the drugs.

    Our advice
    If you’re taking a statin and develop muscle weakness, tenderness, or pain, consult your doctor. The statin may not be to blame, or other factors may be involved. If the statin is the cause, the symptoms should go away within days or weeks after the drug is stopped. If you continue the drug, the damage may progress and become severe and even possibly lead to rhabdomyolysis. If you suddenly begin to pass dark urine, that can be a sign of rhabdomyolysis, so get immediate medical attention.

    Besides doing a physical exam, your doctor will test your blood level of creatine kinase, an enzyme that can indicate muscle damage. Your doctor should also make sure that other drugs you’re taking are not boosting the blood level of your statin. Depending on these and other factors, along with the severity of your symptoms, you may be advised to continue the statin, perhaps at a lower dose, to see if the symptoms go away, or to switch to another statin. That often helps.

    Keep in mind that statins are not a substitute for heart-healthy lifestyle changes such as improved diet, exercise, and weight control. Such steps may allow you to take a lower statin dose—or may even make the drug unnecessary in the first place.

    CoQ10 for Statin Users
    Some statin users take coenzyme Q10 (CoQ10) supplements as a way to prevent or treat statin-related muscle problems. Made by the body, this vitamin-like substance is essential for energy production and is a powerful antioxidant.

    Statins work by inhibiting an enzyme in the liver that’s integral to cholesterol production. This enzyme is also involved in the production of CoQ10, so statins reduce blood levels of it as well (certain other drugs, such as some beta-blockers and antidepressants, also reduce CoQ10). It’s not known if statins’ effect on CoQ10 contributes to their adverse effects.

    Research on the effect of CoQ10 supplements in statin users has produced conflicting results. While a 2015 meta-analysis of clinical trials, published in Mayo Clinic Proceedings, found that CoQ10 worked no better than a placebo in reducing statin-related muscle problems, a meta-analysis in the Journal of the American Heart Association in October 2018 concluded that CoQ10 can indeed help reduce such problems.

    Also see our interview with Ronald Krauss, MD, on this subject.

  2. #2
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    Re: Statins and Muscle Pain

    I tried two statins and persevered with both of them. I had severe back pain with both and this was certainly not a "nocebo" effect in my case since before I tried them I had no knowledge of side-effects.

    Moreover, the pain started within a few days of starting the medication, not weeks or months), and it stopped within a few days of discontinuing the medication.

    Nothing mitigated or moderated the pain. I tried acetaminophen medications, ibuprofen medications, naproxen, heating pads, and nothing helped. It was bad enough that even standing, sitting, lying down, or walking was painful and when I was able to fall asleep the pain woke me up again.

    After the second attempt, I just told my doctor I couldn't tolerate these medications.

    I don't want to present my experience as typical - it's just my experience. But I do think the side effects are understated:

    The clearest risk from statins is muscle damage resulting in weakness, tenderness, or pain. These symptoms commonly occur in large muscles in the legs, chest, upper arms, shoulders, or lower back, but can occur elsewhere. Statin-related muscle inflammation and damage occur on a continuum. Most often the problem is mild and manifests itself as muscle discomfort or weakness. More serious muscle damage causes moderate to severe pain.

  3. #3
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    Re: Statins and Muscle Pain

    Well from having been on quite a few statins I agree with you. I guess acccording to this report we are exceptions

    We've discussed them before and they are not the only cholesterol reducing meds and I recall trying one being told it wasn't a statin and it was actually worse. I also have had sever muscle pains, spasms and severe leg cramping when you wake up in the middle of the night clutching your leg hoping it will subside at the verge and sometimes at the point of actual tears when it can last for minutes. Funny how this has never happened except as a teenager when I had growth spurts. But none were as severe or prolonged as on every single trial. And the effect seemed cumulatively worsening with every attempt.

    Statins are a big money maker for big pharma. Period. It is one of the most unneccesarily prescribed medication like blood pressure meds for some weird reason.

    I have muscle tenderness from inactivity and other conditions as hyper sensitivity but not one episode similar off statins in many years. My doc and cardiologist know, and although they think preventatively they would like my levels lower it's now a fact "Don't go there. Don't mention it because it's not going to happen." And they are respectful of that fact. The Testosterone injections and weight loss have helped lower my levels and thats good enough for me.

    The report seems to omit (unless I missed it) theat the muscle damamge caused can also be permanent and irreversable! Curious as to who funded this research. Not you?

    Doesn't mean they aren't helping many people but I bet there are many that suffer in spite of it because their doctor tells them they have to be on it and suck it up living with the pain as a simple fact of life because they have to.

    Disclaimer: Personal opinion and experience. Never stop any medication based on other people's experiences and opinions. If the hat fits and you feel like it could be the cause of your problems then discuss it firmly with your doctor and never be afraid to confront and ask for justification. Doctors are human too and also can be biased by being fed the wrong information.
    ​"A real friend is one who walks in when the rest of the world walks out." ~ Walter Winchell

  4. #4
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    Re: Statins and Muscle Pain

    I am actually on one that works: Olestyr.

    I was originally prescribed it in a low does by my gastroenterologist to help with digestion after my right hemicolectomy (I think it's also used for Irritable Bowel Syndrome and similar conditions).

    Since I had no side effects with it, when my doctor was last reviewing my medication history and my bad effects with statins, I said what if we just increase the dose and kill two birds with one stone?

    I think the problem is that many in the medical profession tend to believe it's statins or nothing but that doesn't seem to be the case. It's working for me so far.

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