Deborah Brauser

September 29, 2016

LONDON — Having a vitamin D deficiency and/or being an active smoker may increase disability accumulation in patients with clinically isolated syndrome (CIS), new research suggests.

A cohort study of more than 460 patients with CIS showed that those with severely low levels of serum 25(OH) vitamin D, defined as less than 8.0 ng/mL, had more than twice the risk for increased disability as those with normal vitamin D levels (>20 ng/mL).

In addition, the patients with serum cotinine levels greater than 14 ng/mL, signifying active smoking range, had 2.5 times greater risk for disease severity than did nonsmokers.

"The impact of both of these factors was less consistent, however, when it came to conversion from CIS to MS [multiple sclerosis]," reported Maria Isabel Zuluaga, MD, Centre d'Esclerosi Múltiple de Catalunya (CEMCAT), Hospital Universitario Vall D'Hebron, Barcelona, Spain.

Dr Zuluaga presented her findings at a Late-Breaking News session at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2016.

"Basically, the investigators found that cigarettes and vitamin D deficiency have an effect on disease severity," Michael Hutchinson, MD, St Vincent's University Hospital, Dublin, Ireland, told Medscape Medical News when asked for comment.

So the take-away message "is simple: those with early MS need to supplement their vitamin D and they need to stop smoking," said Dr Hutchinson, who was not involved with this research.

"This is in line with other evidence. For some reason, smoking increases the inflammatory disease in the brain," he added. "But these factors didn't speed up time to clinically definite MS, which was interesting."

"Independent Effects"

The investigators examined data from CEMCAT's Barcelona CIS cohort (n = 1127), which began in 1995. All of the participants were older than 50 years at baseline.

MRIs were conducted at baseline and at follow-up visits (mean follow-up, 8 years), and blood samples were collected within 6 months of a CIS diagnosis and stored. The current researchers prospectively assessed these samples for both 25(OH) vitamin D and cotinine levels.

The main study outcomes were clinically definite MS, MS identified by using McDonald MS criteria, and disability accumulation, defined as a score of 3.0 on the Expanded Disability Status Scale (EDSS).

The mean value of 25(OH) vitamin D in 503 patients with CIS was 17.6 ng/mL. Low levels, defined as less than 20 ng/mL, were found in 72% of the participants. Of these, 9% had severe deficiency.

Compared with those who had normal levels of 25(OH) vitamin D, those with severely low levels had a hazard ratio (HR) of 2.3 for increased risk for disability accumulation, as shown on the EDSS (95% confidence interval [CI], 1.1 - 5.0; P = .03).

After adjustment for multiple factors, including sex, age at CIS diagnosis, and number of T2 lesions, the HR was still 2.3 (95% CI, 1.0 - 5.5; P < .05).

However, the association was not significant between severely low 25(OH) vitamin D levels and risk for clinically definite MS (HR, 1.4) or between severely low levels and risk for McDonald MS (HR, 1.3; both comparisons, P = .3).

Among the 464 participants who had their cotinine levels tested, the mean value was 0.54 ng/mL. Forty-three percent were active smokers (>14 ng/mL) and, compared with the nonsmokers, had an HR of 2.5 for "accrual disability" (95% CI, 1.5 -  4.1; P = .001).

Even after multiple adjustments, the HR was a significant 2.4 (P = .002). But, as with the vitamin D levels, cotinine levels were not significantly associated with conversion to MS.

"The conclusion of our study is that severe vitamin D deficiency and smoking at the time of the CIS have an independent effect on disability accumulation in CIS patients," said Dr Zuluaga.

She noted that limitations included performance of the study at one highly specialized center and collection of samples during different seasons.

A More Severe Trajectory

Dr Hutchinson commented that although there wasn't an association between the two factors and conversion to MS, they made the trajectory of disease "much more severe."

He added that past research has shown that smoking isn't good for any form of MS. And as for second risk factor, "evidence has said you should take about 4000 units of vitamin D per week."

"I don't know what it's like in the States, but I can't prescribe that. You just need to get them to go to the health food shop and buy the cheapest form possible."

During a "Clinical Highlights" session at the end of the meeting, Dr Hutchinson reiterated the importance of defining and correcting environmental factors in disease pathogenesis and severity.

"My personal take-home message to the MS clinic from ECTRIMS 2016 is that for each MS patient, address environmental factors, including obesity, smoking, vitamin D deficiency, and probably exercise," he told attendees at his session.

The study was supported by the Ministry of Economy and Competitiveness of Spain, by a research grant from Fundación Genzyme, and by an ECTRIMS clinical fellowship to Dr Zuluaga. She and Dr Hutchinson have disclosed no relevant financial relationships.

Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2016. Oral presentation 252; oral presentation 258. Both presented September 17, 2016.

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