‘Mystery’ statins side effect caused by cholesterol meds uncovered in new study

Scientists finally identify why statins can cause the ‘painful’ side effect in some people

A certain side effect that some people may get when taking cholesterol-lowering medication, such as statins, has puzzled doctors since the 1980s. However, recent studies have uncovered key causes and why they occur.

Although rare, some patients taking statins may experience muscle pain, weakness, tenderness and fatigue, which may lead to them coming off the medication altogether, swapping to a different kind or adjusting the dosage. This rare side effect has been a long-standing medical mystery for years, until recent developments uncovered by researchers.

Research indicates that, for a few people, some statins can cause muscle cells to leak calcium uncontrollably by messing with ryanodine receptors or reducing coenzyme Q10, which can make muscles weak. However, many of the reported cases might also be due to something called the nocebo effect, which is not directly caused by the drug but by the negative expectations of side effects.

In the UK, the statins doctors usually prescribe most often are Atorvastatin (Lipitor) and Simvastatin (Zocor). These medications are often used to help control high cholesterol and to stop heart disease. Atorvastatin is typically the first choice for stronger treatment, but there are other options, such as Rosuvastatin, Pravastatin, and Fluvastatin.

Atorvastatin (Lipitor) and other statins may cause myalgia (muscle pain, tenderness, or weakness) in some people. Actual muscle damage is rare, and many patients experience no side effects. The symptoms usually present as soreness or fatigue and, in rare cases, can lead to severe muscle breakdown (rhabdomyolysis).

What has recent research shown?

A new study by Columbia researchers, titled ‘Scientists finally uncover why statins cause muscle pain’, now suggests that, at least for some people, the side effects arise when statins bind to a protein in muscle cells, leading to a leak of calcium ions into the cells. The research suggests statins cause spontaneous, irregular releases of calcium from storage compartments in muscle cells. This, in turn, can cause damage, weakness, and pain.

A summary of the study reads: “A new discovery may explain why so many people abandon cholesterol-lowering statins because of muscle pain and weakness. Researchers found that certain statins can latch onto a key muscle protein and trigger a tiny but harmful calcium leak inside muscle cells. That leak may weaken muscles directly or activate processes that slowly break them down, offering a long-sought explanation for statin-related aches.”

Andrew Marks, chair of the Department of Physiology and Cellular Biophysics at the Vagelos College of Physicians and Surgeons, said: “It is unlikely that this explanation applies to everyone who experiences muscular side effects with statins, but even if it explains a small subset, that’s a lot of people we could help if we can resolve the issue.”

He added: “I’ve had patients who’ve been prescribed statins, and they refused to take them because of the side effects. It’s the most common reason patients quit statins, and it’s a very real problem that needs a solution.”

Around seven to eight million adults in the UK use statins to help lower their cholesterol and cut down the chances of getting heart disease and having a stroke. It’s one of the most frequently prescribed medicines in the country, with more than five million people in England receiving prescriptions in 2023/24.

A statement on the Columbia University Irving Medical Center website about the research reads: “Statins’ muscular side effects have puzzled researchers since the drugs hit the market in the late 80s. Statins are designed to lower cholesterol by binding to an enzyme involved in cholesterol synthesis. But statins also bind to other ‘off-target’ molecules, and some previous studies have suggested that muscular side effects occur when statins bind to a specific protein in muscle.

“With cryo-electron microscopy, a technique that can image molecules down to individual atoms, the researchers of the new study documented this binding and uncovered the precise details of the interaction.” The calcium leak could explain the muscular side effects of statins, Marks says, by weakening the muscle directly or by activating enzymes that degrade muscle tissue.

Marks also says statins could be redesigned so they do not bind the ryanodine receptor but retain their cholesterol-lowering ability. He is now collaborating with chemists to create such a statin.

What else is important to be aware of?

Research shows that around 10% of people really feel muscle pain from statins, but as much as 90% of the symptoms might not be from the medicine itself. Instead, they could be due to factors such as ageing or exercise.

Doctors recommend that if someone feels muscle pain, they should talk to their doctor about possibly changing the dose or trying a different statin to keep their heart safe. Scientists are still working on making safer statins that won’t hurt muscles but will still be good at stopping heart attacks and strokes.

Even though muscle pain is a known side effect, it’s uncommon and usually not caused by the statin itself. To help with this, you can try adjusting the dosage, switching to a different medication, or engaging in regular, moderate exercise. Exercise can really help reduce the bad effects on muscles that cause calcium to leak out.

According to a study led by researchers from Oxford Population Health, statin therapies are not the cause of muscle pain in over 90% of those who experience symptoms. The results were published in The Lancet and presented at the European Society of Cardiology Congress.

If you have been prescribed statins by your GP, do not just quit your medication suddenly. Talk to a doctor or healthcare provider about other options, changing the dosage, or if your symptoms might be caused by something else, like the “nocebo effect” (when you expect a side effect, you might actually feel it).

What does the NHS say?

The NHS lists three rare side effects of statins, which include:

• muscle weakness (myopathy)
• loss of sensation or tingling in the nerve endings of the hands and feet (peripheral neuropathy)
• tendon problems (tendons are tough cords of tissue that connect muscles to bones)

The health service says: “It’s rare, but statins can sometimes cause muscle inflammation (swelling) and damage. Speak to your doctor if you have muscle pain, tenderness or weakness that cannot be explained – for example, pain that is not caused by physical work. Your doctor may 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 there’s a big increase in the CK in your blood, your doctor may advise you to stop taking the statin. Regular exercise can sometimes lead to a rise in CK, so tell your doctor if you’ve been exercising a lot. Once the CK in your blood has come down to a level your doctor thinks is OK, they may suggest you start taking the statin again, but at a lower dose.”

The Yellow Card Scheme allows you to report suspected side effects from any type of medicine you’re taking. It’s run by a medicines safety watchdog called the Medicines and Healthcare products Regulatory Agency (MHRA). See the Yellow Card Scheme website for more information.