Scientists finally identify why statins can cause the 'painful' side effect in some people
A particular side effect experienced by some individuals taking cholesterol -lowering drugs, including statins, has baffled medical professionals since the 1980s. Yet recent research has revealed crucial underlying causes and mechanisms.
While uncommon, certain patients on statins may develop muscle pain, weakness, tenderness and exhaustion, potentially prompting them to discontinue the medication entirely, switch to an alternative treatment or modify their dose. This infrequent adverse reaction has remained a persistent medical enigma for decades , until recently, when researchers made significant breakthroughs . Scientific evidence suggests that, for a small number of people, particular statins can trigger uncontrolled calcium leakage from muscle cells by interfering with ryanodine receptors or depleting coenzyme Q10, resulting in muscle weakness. Nevertheless, numerous reported instances might actually stem from the nocebo effect, which isn't directly triggered by the medication itself but rather by patients' negative anticipation of adverse reactions. In Britain, the statins most commonly prescribed by doctors are Atorvastatin and Simvastatin . These medicines are frequently employed to manage elevated cholesterol levels and prevent cardiovascular disease. Atorvastatin is generally the preferred option for more intensive therapy, though alternative choices exist, including Rosuvastatin, Pravastatin, and Fluvastatin. Atorvastatin and other statins may trigger myalgia in certain people, reports the Mirror . Genuine muscle damage remains uncommon, and numerous patients encounter no adverse effects. The symptoms typically manifest as soreness or fatigue and, in exceptional circumstances, can progress to severe muscle breakdown . A fresh study by Columbia scientists, entitled 'Scientists finally uncover why statins cause muscle pain', now indicates that, at least for certain individuals, the adverse effects occur when statins attach to a protein in muscle cells, resulting in calcium ion leakage into the cells. The investigation suggests statins trigger spontaneous, erratic calcium releases from storage areas within muscle cells. 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.' Approximately seven to eight million adults across the UK take statins to help reduce their cholesterol levels and lower their risk of developing heart disease and suffering strokes. It's amongst the most commonly prescribed medications in Britain, with over five million people in England receiving prescriptions during 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. According to Marks, the calcium leak could account for the muscular side effects of statins by directly weakening the muscle or by triggering enzymes that break down muscle tissue. Marks also suggests statins could be redesigned to avoid binding the ryanodine receptor whilst maintaining their cholesterol-lowering properties. He is currently working with chemists to develop such a statin. Studies indicate that approximately 10% of people genuinely experience muscle pain from statins, but as many as 90% of the symptoms may not stem from the medication itself. Rather, they could be attributed to factors including ageing or physical activity. Medical professionals advise that if someone experiences muscle pain, they should consult their GP about potentially adjusting the dose or switching to an alternative statin to protect their heart health . Researchers continue to develop safer statins that won't damage muscles whilst remaining effective at preventing heart attacks and strokes. Although muscle pain is a recognised side effect, it's relatively rare and typically not caused by the statin itself. To address this, you might consider adjusting the dosage, switching to a different medication, or taking part in regular, moderate exercise. Physical activity can genuinely help minimise the adverse effects on muscles that trigger calcium leakage. Research conducted by Oxford Population Health scientists reveals that statin treatments are not responsible for muscle discomfort in more than 90% of patients experiencing such symptoms. The findings appeared in The Lancet and were shared at the European Society of Cardiology Congress. Should your GP have prescribed statins, avoid abruptly discontinuing the medication without consultation. Discuss alternative treatments, dosage adjustments, or whether symptoms might stem from other causes, including the 'nocebo effect' , with a medical professional. The NHS lists three rare side effects of statins, which include: muscle weakness loss of sensation or tingling in the nerve endings of the hands and feet tendon problems The health service says: 'It's rare, but statins can sometimes cause muscle inflammation 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 , 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 . See the Yellow Card Scheme website for more information.
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