Scientists May Finally Know Why Statins Cause Muscle Pain

By Pat Anson

Many people stop taking cholesterol-lowering statins because they experience painful muscle cramps, weakness, and fatigue. I know, because I was one of them.

I started taking statins in my 40’s on the advice of our family physician, because of mildly elevated cholesterol and a family history of coronary artery disease. Soon I was having stinging cramps in my legs overnight, which were painful enough to wake me up. 

My doctor was skeptical that statins were the cause, but switched me from Lipitor to Vytorin and finally to Crestor. The muscle cramps continued. Only when I stopped taking statins did the symptoms disappear.

“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,” says Andrew Marks, MD, Professor and Chair of the Department of Physiology and Cellular Biophysics at Columbia University.

To find a solution, first you need to identify the cause, and Marks and his colleagues have finally discovered why about 10% of people on statins experience those muscular side effects.

Their research, recently published in The Journal of Clinical Investigation, found that a widely-used statin called simvastatin (Zocor) binds to a protein in muscle cells, which causes a leak of calcium ions inside the cells.

Using an electron microscope, researchers watched simvastatin molecules bind to two locations in a muscle protein called the ryanodine receptor, which opened a channel in the receptor that allowed calcium to flow through. 

Marks says the calcium leak could be weakening the muscle directly or by activating enzymes that degrade muscle tissue.

“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,” Marks said in a press release.

The electron images suggest that statins could be redesigned so they don’t bind to the ryanodine receptor, but retain their cholesterol-lowering ability. 

Marks is now collaborating with chemists to create such a statin. He owns stock in RyCarma Therapeutics, a company developing compounds that target the ryanodine receptor.

Plugging the calcium leak could be another option: Statin-induced calcium leaks in laboratory mice can be closed with an experimental drug developed by Marks for other muscle conditions involving calcium leaks.

“These drugs are currently being tested in people with rare muscle diseases. If it shows efficacy in those patients, we can test it in statin-induced myopathies,” Marks says.

The first statin was approved by the FDA in 1987, but it took the agency nearly three decades to listen to patients like me and update warning labels on statins in 2014, cautioning that statins can cause myopathy. In rare instances, the FDA says statins can also cause liver injury, diabetes and memory loss.   

Cheap Drugs May Prevent Migraine Just as Effectively as Expensive Ones

By Pat Anson, PNN Editor

Two drugs commonly used to treat depression and high cholesterol are just as effective at preventing migraine as CGRP inhibitors, according to a large new study.

They are also a heck of a lot cheaper.  

Researchers at the Norwegian Center for Headache Research analyzed the prescription drug history of over 100,000 migraine patients in Norway from 2010 to 2020. Their goal was to see if patients reduced their use of medications used to treat acute migraine pain – such as triptan – once they started taking drugs used to prevent migraine.

“When the withdrawal of acute migraine medicines changed little after starting preventive medicines, or people stopped quickly on the preventive medicines, the preventive medicine was interpreted as having little effect,” explained lead investigator Marte-Helen Bjørk, MD, a Professor in the Department of Clinical Medicine, University of Bergen.

“If the preventive medicine was used on long, uninterrupted periods, and we saw a decrease in the consumption of acute medicines, we interpreted the preventive medicine as having good effect.”

Beta blockers are often the first drugs used to prevent migraine attacks, but Bjørk and her colleagues found that three other medications were associated with lesser use of triptans: amitriptyline, simvastatin and CGRP inhibitors.

Amitriptyline is a tricyclic antidepressant that is mostly taken for depression, while simvastatin is a statin used to treat high cholesterol. Both drugs are also used off-label for migraine prevention.

CGRP inhibitors are a relatively new class of medication that block calcitonin gene-related peptides, a protein that binds to nerve receptors in the brain and triggers migraine pain. Since 2018, the FDA has approved over half a dozen CGRP medications, which are considered the biggest innovation in migraine treatment in decades.

However, CGRP drugs are not cheap. Eight doses of Nurtec, a tablet taken daily to prevent and treat migraine, can cost over $1,000, while the listed price for Emgality is $679 for a self-injectable syringe used once a month for migraine prevention. Prices will vary for patients, depending on insurance and whether they qualify for a patient assistance program.

By comparison, amitriptyline and simvastatin are screaming bargains. A bottle of 30 simvastatin tablets will cost about $14, while amitriptyline costs about $13 for a supply of 28 tablets.

When it comes to reducing triptan use, amitriptyline, simvastatin and the CGRP inhibitors performed about the same. During the first 90 days of treatment, nearly 57% of patients taking simvastatin reduced their triptan use, compared to 53% of patients taking amitriptyline and 55% of those taking CGRP medicines.

The study findings, recently published in the European Journal of Neurology, show that patients taking beta blockers, topiramate or clonidine were more likely to keep taking triptans.

“Our analysis shows that some established and cheaper medicines can have a similar treatment effect as the more expensive ones. This may be of great significance both for the patient group and Norwegian health care” says Bjørk, who has already started work on a clinical trial to see if other cholesterol-lowering drugs can prevent migraine.

Migraine affects about 1 billion people worldwide and 39 million in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound. Women are three times more likely to suffer from migraines than men.