Vitamin D as add-on therapy for multiple sclerosis

Integrative Medicine

An estimated 300,000 to 400,000 Americans have multiple sclerosis (MS), a chronic neurologic condition with a variable natural history. Most patients have the relapsing–remitting form when first diagnosed. Multiple sclerosis is considered to be an immune-mediated disease that affects the myelin sheath of neurons.

Environmental, infectious, and genetic factors have been identified as potential risk factors for developing the disease. Lower levels of vitamin D were first implicated as a contributing factor more than 30 years ago because MS prevalence increases further away from the equator, while vitamin D levels similarly decline. 

Observational studies

Several epidemiologic studies have suggested that the risk of developing MS is inversely related to vitamin D intake or circulating levels of the vitamin. Data from the observational Nurses’ Health Studies show that women with the highest vitamin D intake had a 33% lower risk of MS than those with the lowest intake. Women taking at least 400 IU daily of a vitamin D supplement had a 41% lower risk of MS compared with those not taking the supplement. 

Observational studies have also suggested that the risk of relapse may be higher when levels are lower. One population-based cohort study of 145 patients with relapsing–remitting MS had 25-hydroxyvitamin D levels measured twice yearly over a 2-year period. A 9% to 12% reduction in the risk of a MS relapse was reported with every 10 nmol/L (4 ng/ml) increase in vitamin D levels. A 2014 study identified higher vitamin D levels early in the course of MS predicted a lower relapse rate and fewer new active lesions over a 12-month period. 

Clinical trials

In addition to its proposed use for the prevention and treatment of MS, vitamin D has also been proposed to benefit cardiovascular disease and diabetes, among other conditions. Unfortunately, all of these potential uses are based on observational studies and not on high-quality randomized clinical trials. This is a significant consideration with MS given its variable course in many patients. 

The published clinical studies of vitamin D for MS have included both controlled and uncontrolled designs. Trials generally used cholecalciferol (vitamin D3) in dosages varying between 5,000 and 20,000 IU daily. In general, the studies have included fewer than 50 patients who were followed for 6 to 12 months. Although some studies have assessed relapse rates, most have evaluated biomarkers for MS activity.

Fortunately, multiple clinical trials are under way to formally evaluate the effect of vitamin D3 in varying dosages as an add-on therapy. As an example, a 2-year study is recruiting participants between the ages of 18 and 50 years who are taking glatiramer acetate for relapsing–remitting MS. The primary aim is to evaluate the proportion of participants experiencing a relapse while receiving either 600 IU of vitamin D3 or 5,000 IU of vitamin D3 as an add-on therapy. The study will assess changes in health-related quality of life as well as in brain parenchymal volume, cortical thickness, and gray matter volume. In addition, an ongoing French study is evaluating whether the use of cholecalciferol in high-risk patients with clinically isolated syndrome (first neurologic episode) can delay the formal diagnosis of MS.

What to tell patients

Studies have been conflicting as to the potential benefit of vitamin D supplements in preventing or treating multiple sclerosis. Although patients may decide to take this supplement, including in high dosages, they should be counseled to discuss this decision with their neurologist and request that a vitamin D level be obtained to ensure that a deficiency is not present.