Chicago—With approximately 30 million prescriptions for statins in the United States, many users complain of muscle pain, which—while usually mild—can cause them to discontinue the cholesterol-lowering medication.
A common response from some clinicians is to take vitamin D supplements to ease the muscle aches. A new Stanford University—led study found, however, that vitamin d supplementation did not have any meaningful impact on statin-associated muscle pain.
The report in the Journal of the American Medical Association Cardiology pointed out that while nonrandomized studies have reported 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—found otherwise.
For the randomized, double-blind trial, researchers had 2,083 participants take either 2,000 units of vitamin D supplements daily or a placebo. The results indicated that participants in both groups were similarly 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 to take actual 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," stated senior author Neil Stone, MD, a professor of medicine in cardiology and preventive medicine at Chicago's Northwestern University Feinberg School of Medicine and a Northwestern Medicine cardiologist. "So, it was very disappointing that vitamin D failed a rigorous test. Nevertheless, it's important to avoid using ineffective treatments and instead focus on research that can provide an answer."
The participants were men aged 50 years or older and women aged 55 years or older who were free of cancer and cardiovascular disease. The study subjects who initiated statin therapy after randomization were surveyed in early 2016, with the data analyzed in early 2022.
The researchers reported that statins were initiated by 1,033 vitamin D—assigned participants and 1,050 placebo-assigned participants. The mean age was 66.8 years, and 49% were women.
Specifically, over the follow-up period, statin-associated muscle symptoms (SAMS) were reported by 317 participants (31%) assigned vitamin D and 325 assigned placebo (31%). The adjusted odds ratio (OR) was 0.97 (95% CI, 0.80-1.18; P = .78).
The study noted that statins were discontinued by 137 participants (13%) assigned to vitamin D and 133 assigned to placebo (13%) with an adjusted OR of 1.04 (95% CI, 0.80-1.35; P = .78).
"Among participants with levels less than 20 ng/mL, SAMS were reported by 28 of 85 vitamin DÐassigned participants (33%) and 33 of 95 placebo-assigned participants (35%)," the authors added. "For those with levels less than 30 ng/ml, SAMS were reported by 88 of 330 vitamin—D assigned participants (27%) and 96 of 323 of placebo-assigned participants (30%)."
That led to the conclusion that vitamin D supplementation did not prevent SAMS or reduce statin discontinuation, with the authors pointing out that their results "were consistent across pretreatment 25-hydroxy vitamin D levels."
"We took advantage of a large placebo-controlled randomized trial to test whether vitamin D would reduce statin-associated muscle symptoms and help patients keep taking their statins," explained lead study author Mark Hlatky, MD, professor of health policy and cardiovascular medicine at Stanford University. "The placebo control in the study was important because if people think vitamin D is supposed to reduce their muscle pains, they just might feel better while taking it, even if vitamin D has no specific effect."
The 2,083 patients were among the larger cohort of participants in the VITamin D and Omega-3 Trial (VITAL). That study randomized nearly 26,000 participants to double-blind vitamin D supplementation to determine whether it would prevent cardiovascular disease and cancer.
"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," Dr. Hlatky explained. "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."
The authors suggested that pharmacies or other healthcare professionals confronted with patients who have difficulty with statins might analyze other medications they are taking, question whether or not they have associated metabolic or inflammatory conditions, discuss appropriate hydration, and also counsel them on pill anxiety.
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