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Update on Vitamin D

Walter Royal, III, MD

In recent years there has been an accumulation of evidence that suggests vitamin D may have a role in preventing the occurrence of MS and perhaps in the treatment of the disease. The first clinical description of rickets, the clinical syndrome that is now recognized to occur as a result of vitamin D deficiency, was made in the 17th century. However, it was not until almost three hundred years later that vitamin D was identified. Vitamin D is a fat-soluble vitamin. It is ingested in the diet as a precursor form and is normally converted to an active form by a process that involves chemical reactions triggered by ultraviolet light produced by the sun and by enzymes that are primarily produced by liver and kidney cells, but also by immune cells. A product of this reaction is 25-hydroxy vitamin D, which can be measured in blood to determine whether a person has normal levels or is deficient in vitamin D.

Since its discovery, the primary effects of vitamin D had been ascribed to the maintenance of bone health. However, it is now apparent that the vitamin also has important effects on the function of the immune system. With respect to MS, vitamin D deficiency has been linked with an increased risk of developing the disease. This was initially shown in a study performed in a cohort of nurses in which it was found that an increased intake of vitamin D, either in the diet or in the form of supplements, was associated with a lower risk of MS. The results of this study were supported by the findings of a subsequent study in which analysis of blood samples from military personnel showed that individuals who had the highest levels of vitamin D had the lowest risk of developing the disease, and the risk increased with progressively lower levels of vitamin D.

Subsequently, a large number of studies have provided further information regarding the effects of vitamin D in MS. These include evidence that higher vitamin D levels are associated with lower numbers of new lesions as well as less brain atrophy on MRI. Higher vitamin D levels were not clearly associated with a lower chance of relapses, but people with MS were found to be less likely to develop worse disability. Such information suggests that vitamin D supplementation would likely result in people obtaining such beneficial effects. Unfortunately, so far it has not been demonstrated from clinical trials that taking vitamin D supplements, which can be purchased over the counter, can have a beneficial effect on a person’s course of MS. It has been found from such studies, however, that supplementation can have effects of immune function in a manner that can be expected to be beneficial to people with MS.

There are many potential reasons why it has been difficult so far to show a definite benefit from taking vitamin D supplements in MS. These include the fact that there is strong evidence for benefit from vitamin D in MS and with respect to overall health, so it is difficult to ethically justify a clinical trial where one of the study groups is given placebo instead of vitamin D. Also, for people who are in a clinical trial, it is difficult to monitor the amount of vitamin D that is otherwise being ingested in the diet since there are many sources of the vitamin in addition to its availability as a supplement.

Finally, we have learned from studies that involved currently approved MS drugs that clinical trials that are designed to study potential MS therapies require larger numbers of people than what have been enrolled in vitamin D treatment trials to date. It can be difficult to enroll the required number of people for such studies. However, there are randomized, controlled clinical trials that are currently planned or underway that will examine larger numbers of people. These studies will also formally examine specific questions such as the effects of a higher versus a lower dose of vitamin D and whether such doses are safe and well tolerated. Observation studies in which people were not randomized to take a particular treatment, suggest that vitamin D can be effective when it is administered in combination with one of the FDA-approved disease modifying therapies. This will also be studied in a clinical trial in which people will be randomly assigned to take a specific dose of vitamin D with their standard MS drug.

As we await information from these studies, people with MS are advised to take vitamin D supplements and have their vitamin D levels checked at regular intervals. The daily dose of vitamin D that will be optimal for people to take will be learned from clinical trials. It is currently recommended that the average person take up to 2,000 international units (IU) of vitamin D in combination with 1,000-1,200 milligrams (mg) of calcium. Low calcium levels impede the body’s normal use of vitamin D and can promote a false increase in vitamin D levels.

However, common recommended doses of vitamin D in people with MS are between 1,000-4,000 IU of vitamin D3 per day, with individuals treated with doses within this range being very unlikely to develop complications related to toxicity from taking the vitamin. It is possible to check blood levels of 25-hydroxy vitamin D and to use the result as a guide for how much vitamin D should be taken. A normal range for 25-hydroxy vitamin D level in blood is 30-74 nanograms per milliliter (ng/ml). Levels between 20-30 ng/ml are referred to as insufficient, and vitamin D deficiency is defined as levels less than 20 ng/ml.

People with MS should discuss their vitamin D levels with their health care provider, including testing and approaches to ensure adequate levels. Additional information related to vitamin D and MS can be found on the websites of the National MS Society and National Institutes of Health Office of Dietary Supplements.