How the Atrogin-1 Gene May Cause Muscle Pain for Statin Users (2022)

Statins are a group of cholesterol-lowering medications. While greatly beneficial to many people working to manage hyperlipidemia, like all drugs, statins come with the risk of side effects. So-called statin-associated muscle symptoms (SAMS)—including myalgia (generalized muscle pain) and myopathy (diseases that cause muscle weakness)—are notable ones.

Muscle pain associated with statins may be mild and uncomfortable or significant enough to impact daily life. In rare cases, the impact of these drugs on the muscles can be serious.

How the Atrogin-1 Gene May Cause Muscle Pain for Statin Users (1)

Symptoms

SAMS can vary in frequency and severity. The following are the three most common forms of statin-related muscle pain:

  • Myalgia:This type of muscle pain usually feels like mild soreness in the shoulders, arms, hips or thighs. Myalgia also often comes with mild feelings of weakness.
  • Myositis:Myositis, a type of myopathy, causes muscle pain and inflammation, as well as an elevation in CK (a muscle enzyme) levels in the blood. The presence of CK in the blood is an indicator of muscle damage.
  • Rhabdomyolysis:While fortunately very rare, this severe type of myopathy is a life-threatening condition characterized by the breakdown of muscle tissue that causes muscle fiber contents to be released into the blood, potentially causing kidney damage.

Muscle problems related to statin therapy usually begin within a few weeks to a few months after beginning treatment. While statin-related myalgia, myositis, and rhabdomyolysis will resolve once you stop taking statins, rhabdomyolysis may result in irreversible muscle damage.

Additionally, a 2016 study showed statin-associated autoimmune myopathies are also a side effect of statins. This serious muscle wasting condition is rare and occurs in a fraction of patients.

Causes

While there are several theories as to why statins may cause muscle pain, none have been confirmed.

Research has shown that the gene atrogin-1 may be the source of muscle pain in those taking statins. This gene turns on at the beginning stages of the breakdown of muscle, which is associated with illnesses such as cancer, sepsis, and AIDS. (When the atrogin-1 gene is not active, muscle wasting does not occur.)

Research has also shown that people taking Mevacor (lovastatin) have higher levels of atrogin-1 than those not taking the drug. When the drug is removed from the cells, it does not appear to cause muscle damage. In the future, this may allow your healthcare professional to identify if you are at risk for statin-related muscle pain. Additionally, scientists may be able to manipulate this gene, or others involved, to prevent muscle damage caused by statins.

Another theory is that statins can potentially interfere with the production of CoQ10, a coenzyme in the muscles. CoQ10 assists the muscles in using the energy they need to function properly. Research has suggested thattaking CoQ10 supplementsmight lower your chances of experiencing statin-related myopathy, but available data is still not sufficient enough to back this up.

High-dosesimvastatin(brand name Zocor) appears to present a higher risk for muscle pain than otherstatin drugs. The risk appears to be significantly lower with Lescol (fluvastatin), Pravachol (pravastatin) and Crestor (rosuvastatin). As such, it's recommended that the dosage of simvastatin be limited to 40 milligrams (mg) per day, which can reduce the risk of muscle problems.

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Risk Factors

About 5% to 10% of patients taking statins experience SAMS or mild muscle pain. Your risk of experiencing SAMS while taking statins is increased if you:

  • Are older than 80
  • Are female
  • Have a smaller body frame
  • Drink alcohol excessively
  • Have certain conditions like hypothyroidism
  • Have had prior muscle problems
  • Consume large amounts of grapefruit or cranberry juice

Statin-related muscle problems are more likely to occur in people who exercise vigorously, especially if they begin to do so at a rapid rate rather than slowly building up intensity.

It is also more common in people taking a variety of other medications, including Lopid (gemfibrozil), as well as steroids, cyclosporine, or niacin.

Furthermore, studies have also shown that people with vitamin D deficiency also tend to experience muscle problems with statins more frequently than others. Some experts have reported that administering vitamin D to these people helps ease these symptoms.

People who have the muscle diseaseamyotrophic lateral sclerosis (ALS) are also at higher risk for muscle pain while taking statins.

Diagnosis and Treatment

Millions of Americans take statins because they effectively target all aspects of one's lipid profileby lowering low-density lipoprotein (LDL) cholesterol and triglycerides while raising high-density lipoprotein (HDL) cholesterol. They also reduce the chance of stroke and heart attack.

Because of these benefits, the decision to stop taking statins because of related muscle pain is carefully considered.

If you have started statins and experience muscle pain, see your healthcare provider. While it may be likely that it is indeed the drug that is causing your discomfort, they will consider the possibility of other causes as well.

Your practitioner will likely also test your blood for increased creatine kinase (CK) levels—an indicator of rhabdomyolysis. If detected, statins will be stopped right away.

However, if your only symptoms are pain and/or a minor increase in CK blood levels, your healthcare provider may decide that the benefits of continuing with statin therapy outweigh the cons. They may suggest stopping treatment only briefly until the problem resolves, or not at all.

Sometimes switching to a different type of statin can resolve muscle-related pain and side effects, so your practitioner may recommend this if you're in search of relief.

While there aren't proven pain relief mechanisms for statin-related muscle pain, you may also find that gentle exercise and stretching may help.

A Word From Verywell

While statins are proven to help reduce cholesterol, they come with a variety of risks and side effects. Besides muscle pain, these can include liver damage, digestive problems, increased blood sugar, memory loss and confusion.

As with any drug, you should bring up any concerns you have with your healthcare provider to ensure that this is still the right treatment plan for you, and you should never stop taking a prescribed medication without your practitioner's OK.

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  2. MedlinePlus. Creatine Kinase.

  3. MedlinePlus. Rhabdomyolysis.

  4. Lee D, Goldberg A. Atrogin1/MAFbx: what atrophy, hypertrophy, and cardiac failure have in common. Circ Res. 2011;109(2):123-6. doi:10.1161/CIRCRESAHA.111.248872

  5. Di stasi SL, Macleod TD, Winters JD, Binder-macleod SA. Effects of statins on skeletal muscle: a perspective for physical therapists. Phys Ther. 2010;90(10):1530-42. doi:10.2522/ptj.20090251

  6. Qu H, Guo M, Chai H, Wang WT, Gao ZY, Shi DZ.Effects of coenzyme Q10 on statin-induced myopathy: an updated meta-analysis of randomized controlled trials.J Am Heart Assoc. 2018;7(19):e009835. doi:10.1161/JAHA.118.009835

  7. Thompson PD, Panza G, Zaleski A, Taylor B. Statin-associated side effects. J Am Coll Cardiol. 2016;67(20):2395-2410. doi:10.1016/j.jacc.2016.02.071

  8. Ward NC, Watts GF, Eckel RH. Statin toxicity. Circ Res. 2019;124(2):328-350. doi:10.1161/CIRCRESAHA.118.312782

  9. Stroes E, Thompson P, Corsini A et al. Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management.Eur Heart J. 2015;36(17):1012-1022. doi:10.1093/eurheartj/ehv043

  10. Semple, SJ. Statin therapy, myopathy and exercise–a case report.Lipids Health Dis. 2012;11(40). doi:10.1186/1476-511X-11-40

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  12. Gupta A, Thompson PD. The relationship of vitamin D deficiency to statin myopathy. Atherosclerosis. 2011;215(1):23-9. doi:10.1016/j.atherosclerosis.2010.11.039

  13. Golomb BA, Verden A, Messner AK, Koslik HJ, Hoffman KB. Amyotrophic lateral sclerosis associated with statin use: A disproportionality analysis of the FDA's adverse event reporting system. Drug Saf. 2018;41(4):403-413. doi:10.1007/s40264-017-0620-4

  14. Salami JA, Warraich H, Valero-elizondo J, et al. National trends in statin use and expenditures in the U.S. adult population From 2002 to 2013: Insights from the Medical Expenditure Panel Survey. JAMA Cardiol. 2017;2(1):56-65. doi:10.1001/jamacardio.2016.4700

  15. Harvard Medical School. Harvard Health Publishing. Managing statin muscle pain.

Additional Reading

FAQs

How do statins cause muscle pain? ›

The researchers suggest that in most people, muscle cells can tolerate this calcium leak. However, in people already susceptible due to their genes or lifestyle, the leak caused by statins may overwhelm the muscle cells, giving rise to muscle pain and weakness.

Which gene predicts risk for muscle toxicity with simvastatin use? ›

Statins inhibit the activity of this enzyme. It has been demonstrated in multiple studies that genetic variants in the HMGCR gene are important determinants for statin efficacy [68–74].

What kind of muscle pain is associated with statins? ›

Statin-related muscle pain, if it happens at all, usually happens within the first few months after you start the drug or raise the dose. You may feel a constant soreness or weakness in your shoulders, thighs, hips, or calves. If you're like most people, it'll affect both sides of your body equally.

How do statins cause myositis? ›

Any factor that increases the serum concentration of a statin has the potential to increase the risk of myopathy. Therefore, factors that affect the pharma- cokinetics of statins, leading to increased concentra- tions of the drugs in blood or tissue, may predispose to myopathy.

Which statins are less likely to cause muscle pain? ›

Is muscle pain a side effect of all statins? Even though all statins are similar chemically, they have some minor differences that could impact how likely they are to cause muscle pain. Simvastatin is the most likely to cause muscle pain, and fluvastatin is the least likely.

Does CoQ10 help with muscle pain from statins? ›

In a study published in the American Journal of Cardiology , researchers indicate that using CoQ10 supplements seemed to decrease the muscle breakdown, pain, and discomfort of people taking statins. However, a recent study in Atherosclerosis suggests that CoQ10 does not improve muscle pain in people taking statins.

Which statin has highest risk of myopathy? ›

The incidence of myopathy was highest with Simvastatin 40 mg (50%) and lowest with Fluvastatin XL 80 mg (8%) and Rosuvastatin 10 mg (10.8%). The relatively high rate of statin induced myopathy in our population may point to the importance of genetic factors.

How can statin myopathy be prevented? ›

There are 6 key principles in the management of patients with goal-inhibiting statin intolerance: ensuring a valid indication, identifying risk factors for intolerance, ensuring the patient is informed of the benefits and risks, encouraging nondrug therapies/not advocating for supplements to prevent statin-associated ...

How can statin induced myopathy be prevented? ›

The prevention of statin-related myopathy involves using the lowest statin dose required to achieve therapeutic goals and avoiding polytherapy with drugs known to increase systemic exposure and myopathy risk.

Which muscles are most affected by statins? ›

Within a month of starting statin therapy, they may feel aches or weakness in the large muscles of their arms, shoulders, thighs or buttocks on both sides of the body. About 5 to 10% of people who try statins are affected. It's more common in the elderly, in women and in those taking the more potent statins.

What can you take instead of statins? ›

7 cholesterol-lowering alternatives to statins
  • Fibrates. Mostly used for lowering triglyceride levels in patients whose levels are very high and could cause pancreatitis. ...
  • Plant stanols and sterols. ...
  • Cholestyramine and other bile acid-binding resins. ...
  • Niacin. ...
  • Policosanol. ...
  • Red yeast rice extract (RYRE) ...
  • Natural products.

Can statins cause permanent muscle damage? ›

Symptoms tend to disappear within 3 months after you stop taking statins, with no permanent damage in most cases. But a 2018 study suggests that in rare cases, some muscle damage isn't reversible. Moderate exercise, as opposed to intense physical activity, also may help eliminate myopathy symptoms.

Can statins trigger an autoimmune disease? ›

Johns Hopkins researchers have discovered how statins, the most commonly prescribed class of medication in the United States, appear to trigger a rare but serious autoimmune muscle disease in a small portion of the 30 million Americans who take the cholesterol-lowering drugs.

Can statin induced myositis be reversed? ›

While there is no cure for this chronic, disabling condition, many patients can successfully be treated with anti-inflammatory medications.

Can muscle pain caused by statins be reversed? ›

The damage is typically reversible once the person stops taking the statin. More rarely still, a severe type of muscle damage called rhabdomyolysis may occur, in an estimated 2–3 in 100,000 people taking this type of drug per year.

What is the safest most effective statin drug? ›

Simvastatin and pravastatin had the best safety profile, according to this review. Overall, the researchers found a 9 percent increased risk of type 2 diabetes in people taking statins.

What statin is best tolerated? ›

Among individual statins, simvastatin and pravastatin seem safer and more tolerable than other statins.

Is there a natural substitute for statins? ›

Natural alternatives to statins include soy products like tofu and edamame. According to the Centers for Disease Control and Prevention, more than 35 million Americans have high LDL, also known as bad cholesterol. This greatly increases your risk for heart disease and stroke.

What happens if you don't take CoQ10 with statins? ›

Some studies have shown that statins decrease the concentration of CoQ10 in both muscle tissue and in the bloodstream. The hypothesis is that, if you decrease the CoQ10 levels, you reduce the production of energy in muscle cells and they won't function as well, leading to muscle aches, weakness or inflammation.

How much CoQ10 should I take for statin muscle pain? ›

For people taking statin medications, the typical dosage recommendation for CoQ10 is 30–200 mg per day ( 13 ).

Do I need CoQ10 if I don't take a statin? ›

Just because you are on a statin does not necessarily mean you should take a coenzyme Q10 supplement. Also, if you are experiencing side effects, such as muscle aches, that seem to be associated with your statin use, bring that to your doctor's attention, as well.

How long after stopping statins does muscle pain stop? ›

Explain to interested patients that muscle pain and weakness are known side effects of statin therapy. In most patients, they resolve quickly when the drugs are stopped. Explain that this study reported on a small number of patients in whom symptoms persisted for six months after statins were discontinued.

How long does it take for statin myopathy to resolve? ›

For most patients, myopathy symptoms induced by statin therapy resolve relatively quickly; however, the results of the PRIMO study showed that it may take up to 2 months for resolution of symptoms.

When should I stop taking statins with elevated CK? ›

Statin treatment should be discontinued immediately if an elevated CK level is found (i.e. CK >10 x upper limit of normal6), or where myopathy is suspected or diagnosed. If there is a moderate rise in the CK level (i.e. 3-10 x upper limit of normal) then monitor CK levels weekly and seek specialist advice.

What is the best way to treat drug induced myositis? ›

Treatment
  1. Corticosteroids. Drugs such as prednisone can be very effective in controlling polymyositis symptoms. ...
  2. Corticosteroid-sparing agents. When used in combination with a corticosteroid, these drugs can decrease the dose and potential side effects of the corticosteroid. ...
  3. Rituximab (Rituxan).
Jul 2, 2022

Does exercise help myopathy? ›

Exercise programmes to improve muscle strength, endurance and cardiovascular fitness have an important role in the overall management of patients with myopathy.

Do most cardiologists take statins? ›

What a Cardiologist Wants You to Know. About 35 million people take statins in the United States, but research says only 55% of those who are recommended to take a statin are taking one.

What blood tests check for statin damage? ›

Your doctor will carry out a blood test to measure a substance in your blood called creatine kinase (CK), which is released into the blood when your muscles are inflamed or damaged. If the level of CK in your blood is more than 5 times the normal level, your doctor may advise you to stop taking the statin.

What is the new cholesterol drug that is not a statin? ›

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and bempedoic acid (BDA) are some of the newer non-statin medications available within the United States (US) for the management of cholesterol.

Is there a cholesterol medicine that is not a statin? ›

There are many non-statin medications your doctor might prescribe: Bile acid-binding resins, like cholestyramine (Locholest, Prevalite, Questran), colesevelam (WelChol), and colestipol (Colestid) stick to cholesterol-rich bile acids in your intestines and lower your LDL levels.

What is the newest statin on the market? ›

Known as Vascepa, the medication is derived from omega-3 fish oil. It is the first of its kind to be approved by the FDA to help lower the risk of cardiovascular events in patients with high blood fat who are already on statin therapy.

How do you fix statin muscle damage? ›

Although there are no proven remedies for statin-related muscle pain, the following may help.
  1. Exercise. ...
  2. Ramp up your lifestyle changes. ...
  3. Have a thyroid blood test. ...
  4. Take supplements. ...
  5. Change your prescription. ...
  6. Image: © Christophe Bourloton/Thinkstock.

Do statins cause neurological problems? ›

Neurological side effects

The FDA warns on statin labels that some people have developed memory loss or confusion while taking statins. These side effects reverse once you stop taking the medication.

Do statins destroy muscles? ›

In rare cases, statins are known to cause a severe muscle condition called rhabdomyolysis, in which skeletal muscle tissue is destroyed, leading to serious complications.

What autoimmune diseases cause muscle pain? ›

Myositis (my-o-SY-tis) is a rare type of autoimmune disease that inflames and weakens muscle fibers. Autoimmune diseases occur when the body's own immune system attacks itself. In the case of myositis, the immune system attacks healthy muscle tissue, which results in inflammation, swelling, pain, and eventual weakness.

How long after taking statins does muscle pain start? ›

Within a month of starting statin therapy, they may feel aches or weakness in the large muscles of their arms, shoulders, thighs or buttocks on both sides of the body. About 5 to 10% of people who try statins are affected. It's more common in the elderly, in women and in those taking the more potent statins.

Can muscle damage from statins be reversed? ›

Often the only way to halt the effects of statins on your muscle cells is to stop taking the medications. Symptoms tend to disappear within 3 months after you stop taking statins, with no permanent damage in most cases. But a 2018 study suggests that in rare cases, some muscle damage isn't reversible.

What can you take instead of statins? ›

7 cholesterol-lowering alternatives to statins
  • Fibrates. Mostly used for lowering triglyceride levels in patients whose levels are very high and could cause pancreatitis. ...
  • Plant stanols and sterols. ...
  • Cholestyramine and other bile acid-binding resins. ...
  • Niacin. ...
  • Policosanol. ...
  • Red yeast rice extract (RYRE) ...
  • Natural products.

What is the safest statin to take? ›

Simvastatin and pravastatin had the best safety profile, according to this review. Overall, the researchers found a 9 percent increased risk of type 2 diabetes in people taking statins.

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