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Higher Vitamin D Levels Associated With Lower MS Risk

  • Authors: News Author: Caroline Cassels
    CME Author: Désirée Lie, MD, MSEd
  • CME Released: 12/20/2006
  • Valid for credit through: 12/20/2007
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Target Audience and Goal Statement

This article is intended for primary care clinicians, neurologists, and other specialists who care for patients at risk for MS.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  • Describe the association between vitamin D levels and risk of MS.
  • Identify the level of protection of vitamin D against MS risk in different subgroups.


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  • Caroline Cassels

    Caroline Cassels is a Senior Journalist for Medscape Neurology & Neurosurgery. A medical and health journalist for 20 years, Caroline has written extensively for both physician and consumer audiences. She helped launch and was the editor of Health Digest, an award-winning Canadian consumer health publication. She was also national editor of the Heart & Stroke Foundation of Canada's Web site before joining Medscape Neurology & Neurosurgery in 2005. She is the recipient of the 2008 American Academy of Neurology Journalism Fellowship Award. She can be contacted at [email protected]


    Disclosure: Caroline Cassels has disclosed no relevant financial relationships.

CME Author(s)

  • Désirée Lie, MD, MSEd

    Clinical Professor, Family Medicine, University of California, Orange; Director, Division of Faculty Development, UCI Medical Center, Orange, California


    Disclosure: Désirée Lie, MD, MSEd, has disclosed no relevant financial relationships.

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Higher Vitamin D Levels Associated With Lower MS Risk

Authors: News Author: Caroline Cassels CME Author: Désirée Lie, MD, MSEdFaculty and Disclosures

CME Released: 12/20/2006

Valid for credit through: 12/20/2007


December 20, 2006 — High circulating serum levels of vitamin D have been linked to a significantly lower risk of multiple sclerosis (MS), a new study suggests.

In the first large-scale prospective study to investigate the relationship between vitamin D levels and MS, researchers at the Harvard School of Public Health found that healthy young adults with the highest 25-hydroxyvitamin D levels had a 62% reduction in MS risk compared with their counterparts with the lowest levels.

"This study provides very encouraging results. For the first time we can envision the possibility of MS prevention," principal investigator Alberto Ascherio, MD, DrPH, told Medscape.

The study is published in the December 20 issue of JAMA.

Racial Paradox in African Americans

The study population included more than 7 million active-duty US military personnel with at least 1 serum sample stored in the US Department of Defense Serum Repository (DoDSR).

The purpose of DoDSR is to routinely screen military personnel for human immunodeficiency virus and other worldwide deployment-related blood tests. The samples are then catalogued and stored. Typically military personnel provide 1 sample at service entry and, on average, every 2 years thereafter.

Between 1992 and 2004, a total of 257 US Army and Navy personnel with at least 2 serum samples stored in the repository were diagnosed with MS. Study participants were matched with control subjects by age, sex, race/ethnicity, date of sample collection, and branch of military service. Each case was matched with 2 control subjects.

To guard against potential confounding due to race, its influence on MS risk, and the effect of skin color on vitamin D levels, separate analyses were conducted in whites, blacks, and Hispanics.

Dr. Ascherio pointed out that African Americans have a lower MS risk than whites, which is largely attributed to genetic factors. Paradoxically, they also have lower 25-hydroxyvitamin D levels, mostly because of darker skin pigmentation, which decreases UV-B-induced subcutaneous production of vitamin D.

Vitamin D status was estimated by averaging 25-hydroxyvitamin D levels of 2 or more serum samples collected before the date of initial MS symptoms. Individuals were divided into quintiles according to average levels.

Age May Play a Role

The investigators found that among whites, MS risk declined with increasing vitamin D levels, which was 62% lower among individuals in the top quintile of vitamin D concentration (approximately 100 nmol/L) than those in the lowest quintile (approximately 63 nmol/L).

Furthermore, they report this association was strongest among individuals who were younger than 20 years at study entry. This finding, said Dr. Ascherio, suggests that vitamin D levels earlier in life may be critical in providing protection against MS.

"Most MS literature suggests vitamin D in adolescents and young adults may be particularly important. Our study certainly suggests vitamin D levels before age 20 is important in MS prevention. If this is true, any potential intervention to prevent MS would likely be most effective if targeted towards young people under age 20," he said.

No significant association between vitamin D levels and MS was found among blacks or Hispanics, possibly because of the smaller sample size and lower vitamin D levels in these groups. In addition, no significant differences were found between men and women.

Clinical Recommendations Premature

While this study demonstrates a strong association between increased MS risk and low vitamin D levels, Dr. Ascherio said any recommendations advising patients to use vitamin D supplementation to reduce their risk would be "premature."

"Before we can recommend vitamin D supplementation, we need to conduct a large-scale trial to confirm a protective effect and to determine whether supplementation is the optimal way of increasing vitamin D levels," Dr. Ascherio said. "A logical target group would be individuals with a strong family history of the disease. Such individuals have a 20- to 30-fold increased risk of MS compared to individuals with no family history."

Nevertheless, Dr. Ascherio added, this study reinforces the importance of guarding against vitamin D deficiency. "This is a very common condition and we would certainly recommend physicians screen their patients to make sure they are not vitamin D–deficient," he said.

Excellent Research

Asked by Medscape to comment on the study, John Noseworthy, MD, professor and former chair of the department of neurology at the Mayo Clinic College of Medicine in Rochester, Minnesota, said it is an "extremely well done piece of research that provides the research community with an important observation."

"This study provides strong support that vitamin D deficiency may indeed play a contributing role in either causing or triggering MS," Dr. Noseworthy said. "If [this finding is] confirmed, it may afford physicians the opportunity to modify MS risk for the first time. You can't do anything about your patients' genetic profile, but relative low levels of vitamin D are something we can influence."

JAMA. 2006;296:2832-2838.

Clinical Context

According to the authors, MS is one of the most common neurologic diseases in young adults. It affects 350,000 individuals in the United States and 2 million people worldwide. There is a multifold increase in incidence with increasing latitude with an associated genetic predisposition. Environmental factors such as sunlight and vitamin D have been proposed as etiologic mechanisms, according to the authors.

Currently, the Institute of Medicine recommendation for vitamin D supplementation is 200 U/day for adults younger than 50 years; highest dose considered safe is 2000 U/day. Levels of 25-hydroxyvitamin D higher than 25 nnmol/L have traditionally been considered adequate, according to the authors, and almost half of whites and two thirds of blacks in the United States have levels less than 70 nmol/L. However, a review by Bischooff-Ferrari and colleagues published in the July 2006 issue of the American Journal of Clinical Nutrition suggests that levels of 90 to 100 nmol/L are optimal for bone mineralization and fracture prevention.

This prospective, nested case-control study of more than 7 million US military personnel who have serum stored examines the association between vitamin D levels and risk of MS over a mean of 4.4 years.

Study Highlights

  • Samples were from more than 7 million US military personnel who have at least 1 serum sample stored.
  • Serum was collected an average of every 2 years from personnel.
  • Included were active personnel in the US Army and Navy who were evaluated by the Physical Evaluation Boards for a diagnosis of MS (coded) between 1992 and 2004.
  • Medical records were extracted and reviewed by 2 trained personnel.
  • Cases were classified as definite or probable MS.
  • Definite MS was diagnosed if determined by a neurologist or if there was a history of 2 or more attacks and a magnetic resonance imaging (MRI) study consistent with MS and a neurologist diagnosis.
  • Probable MS was diagnosed if the diagnosis was made by a neurologist or laboratory confirmation, or if at least 2 of the following were present: 2 or more clinical attacks, MRI consistent with MS, or neurologist diagnosis of probable MS.
  • 515 MS cases were reviewed, and 315 were determined to be definite and 78 probable.
  • Two control subjects without MS diagnosis, matched for each MS case, were randomly selected from the same population and matched by age, sex, ethnicity, dates of collection, and Army vs Navy.
  • Information was collected on place of residence by latitude.
  • Vitamin D (25-hydroxyvitamin D) level was extracted and measured using radioimmunoassay. The laboratory was blinded to case/control status.
  • MS cases were, on average, 28.5 years old at symptom onset.
  • Disease course was relapsing-remitting in 73%, primary progressive in 7%, and uncertain in the remaining 20%.
  • Average time between collection of first and last serum samples and onset of first MS symptoms was 4.4 years. Between first sample collection and symptom onset, the average time was 5.3 years.
  • The average serum 25-hydroxyvitamin D level was 29.7 nmol/L higher among whites (75.2 nmo/L) than blacks and 8.6 nmol/L higher among whites than Hispanics. This was consistent with known levels in the US general population.
  • Among whites there was a 41% decrease in MS risk for every 50 nmol/L increase in 25-hydroxyvitamin D (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.36 - 0.97; P = .04).
  • There was no significant difference by sex, with an OR of 0.60 for men and 0.53 for women, P = .90.
  • MS risk was highest among those in the bottom quintile of 25-hydroxyvitamin D level, with an OR of 0.38 for the top vs the bottom quintile ( P = .006).
  • There was a significant 51% reduction in risk among those with 25-hydroxyvitamin D levels of 100 nmol/L of higher (17 cases and 58 controls: OR, 0.49; P = .02).
  • Serum levels of hydroxyvitamin D in adolescence (available for 39 cases) significantly predicted MS risk with an OR of 0.09 for those whose 25-hydroxyvitamin D levels were more than 100 nmol/L compared with less than 100 nmol/L.
  • Among blacks (77 cases and 154 controls), the overall association between 25-hydroxyvitamin D levels and MS was not significant.
  • Among Hispanics (32 cases and 64 controls), the OR for every 0.50 nmol/L increase in 25-hydroxyvitamin D level was 0.97 (not significant).

Pearls for Practice


  • Higher levels of 25-hydroxyvitamin D levels are associated with lower risk of MS among whites, independent of sex.
  • The protective effect of higher 25-hydroxyvitamin D level for MS is greatest among those with serum levels higher than 100 nmol/L and greater if levels are higher than 100 nmo/L in adolescence.

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