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Observational studies have suggested that vitamin D may reduce inflammation in relapsing-remitting multiple sclerosis (RRMS), but this has not been clearly confirmed in randomized controlled trials. To further explore the possible anti-inflammatory effects of vitamin D in RRMS, we examined the effect of high-dose oral vitamin D on eleven markers of systemic inflammation in 68 RRMS patients enrolled in a double-blinded randomized placebo-controlled trial of vitamin D supplementation (20,000 IU/week) (NCT00785473). Serum inflammation markers and 25-hydroxyvitamin D (25(OH)D) were measured at baseline and week 96, and no restrictions were set on additional standard immunomodulatory treatment for RRMS. The mean 25(OH)D level rose from 56 ± 29 to 123 ± 34 nmol/L among patients receiving vitamin D supplementation, whereas only a minor increase from 57 ± 22 to 63 ± 24 nmol/L was seen in the placebo group. However, no significant differences appeared between the vitamin D group and the placebo group for any of the inflammation markers. Patients on immunomodulatory therapy had significantly higher levels of interleukin-1 receptor antagonist and chemokine (C-X-C motif) ligand 16 than patients without immunomodulatory treatment, but there were no clear synergistic effects between immunomodulatory therapy and vitamin D supplementation on any of the inflammation markers. The rise in 25(OH)D levels after vitamin D supplementation was unaffected by immunomodulatory treatment. We conclude that in this study of RRMS patients, high-dose oral vitamin D supplementation prominently increased serum 25(OH)D levels without affecting markers of systemic inflammation, while a more anti-inflammatory phenotype was found among patients on immunomodulatory treatment. [ABSTRACT FROM AUTHOR]

A remarkable increase in female to male ratio of multiple sclerosis (MS) is recognised in high incidence areas. Norway is a high-risk area for MS, spanning latitudes 58-71°N. We studied whether the sex ratio has changed over time and whether it differs by clinical phenotype or by latitude. Population-based epidemiological data and data from the Norwegian MS Registry on patients born from 1930 to 1979 were combined in this study. Place of birth was retrieved from the Norwegian Population Registry and information on clinical subtypes was obtained from the Norwegian MS Registry. The female to male ratio ranged from 1.7 to 2.7 (median 2.0) in 5,469 patients born in Norway, and increased slightly by 5-year blocks of year of birth ( p = 0.043). The sex ratio was 2.6:1 in 825 patients born 1970-1979, which is significantly higher than in those born 1930-1969 ( p < 0.001). In patients with relapsing remitting onset, the sex ratio was 2.4:1, while it was 1.1:1 in those with primary progressive disease. The sex ratio did not differ between the south, the middle and the north of the country. The overall sex ratio of MS is strongly determined by cases with relapsing remitting onset. We did not observe the remarkable increase in sex ratios of MS reported from other high-risk areas. The high sex ratio in the youngest birth cohorts may change as an increasing proportion of cases in this age group is being diagnosed. Sex ratio was not associated with latitude. [ABSTRACT FROM AUTHOR]