Statin-related muscle symptoms are common and can lead to the discontinuation of prescribed statin therapy. So cardiologist Mark Hlatky and colleagues conducted a randomized, placebo-controlled, double-blind clinical trial of vitamin D supplementation. Some clinicians have recommended vitamin D to patients taking statins to help with muscle aches, but a new study shows the vitamin has no effect.
Some clinicians have recommended vitamin D supplements to patients taking statins to alleviate muscle aches, but a new study shows the vitamin has no significant impact. Patients who take statins to lower high cholesterol levels frequently complain of muscle pains, which can cause them to discontinue the highly effective medication and increase their risk of a heart attack or stroke.
Some clinicians have recommended vitamin D supplements to patients taking statins to alleviate muscle aches, but a new study from Northwestern University, Harvard University, and Stanford University found the vitamin had no significant impact.
The findings will be published in JAMA Cardiology.
Although non-randomized studies have found vitamin D to be an effective treatment for statin-associated muscle symptoms, the new study, the first randomized clinical trial to look at the effect of vitamin D on statin-associated muscle symptoms, was large enough to rule out any significant benefits.
We had high hopes that vitamin D would be effective because in our clinic and across the country, statin-associated muscle symptoms were a major reason why so many patients stopped taking their statin medication.Dr. Neil Stone
In the randomized, double-blind trial, 2,083 participants ingested either 2,000 units of vitamin D supplements daily or a placebo. The study found participants in both categories were equally likely to develop muscle symptoms and discontinue statin therapy. Over 4.8 years of follow-up, statin-related muscle pain was reported by 31% of the participants assigned vitamin D and 31% assigned a placebo.
“We had high hopes that vitamin D would be effective because in our clinic and across the country, statin-associated muscle symptoms were a major reason why so many patients stopped taking their statin medication,” said senior author Dr. Neil Stone, a Northwestern Medicine cardiologist and professor of medicine in cardiology and preventive medicine at Northwestern University Feinberg School of Medicine. “As a result, the failure of vitamin D to pass a rigorous test was extremely disappointing. Nonetheless, it is critical to avoid ineffective treatments and instead concentrate on research that can provide an answer.”
Statins and vitamin D supplements are two of the most commonly used medications among adults in the United States. Statins are prescribed to approximately 30 to 35 million Americans, and approximately half of the population aged 60 and older takes a vitamin D supplement.
“We used a large placebo-controlled randomized trial to see if vitamin D could reduce statin-associated muscle symptoms and keep patients on their statins,” said lead study author Dr. Mark Hlatky, a Stanford professor of health policy and cardiovascular medicine. “The placebo control in the study was important because if people believe vitamin D is supposed to relieve muscle pain, they may simply feel better while taking it, even if vitamin D has no specific effect.”
Trial was a sub study within a larger clinical trial
The 2,083 patients were part of a larger cohort in the VITamin D and Omega-3 Trial (VITAL), which randomly assigned nearly 26,000 people to double-blind vitamin D supplementation to see if it could prevent cardiovascular disease and cancer. This gave researchers a one-of-a-kind opportunity to see if vitamin D reduces muscle symptoms in participants who started taking statins during the follow-up period of the larger VITAL trial. The average age of the study participants was 67, with 51% being female.
“Randomized clinical trials are important because many very good ideas don’t work as well as we had hoped when they are put to the test,” Hlatky said. “Statistical associations do not prove a cause-and-effect relationship. Low levels of vitamin D are associated with many medical problems, but it turns out that giving people vitamin D does not generally fix those problems.”
For patients who report statin-associated muscle pains
Dr. Stone noted that sometimes the key to understanding patients who struggle with statins is analyzing other medications they’re taking, determining whether or not they have associated metabolic or inflammatory conditions, counseling them on their ability to hydrate adequately, and, most importantly, discussing “pill anxiety.”
“For those who are having problems with statins, a systematic evaluation by a physician with experience in dealing with these issues is still very important,” Stone said.
The idea for this substudy came from conversations between study co-author Dr. Pedro Gonzalez, then a resident at Northwestern Memorial Hospital, and Dr. Stone, who runs a large lipid clinic at Northwestern.