Research: Which Vitamin D trial is Correct?

Epub: Stewart et al. Interferon-β and serum 25-hydroxyvitamin D interact to modulate relapse risk in MS. Neurology. 2012 Jun 13.

OBJECTIVE: To determine whether interferon-β (IFN-β) medication use is associated with vitamin D levels and whether the two interact in exerting effects on relapse risk.

METHODS: In a prospective cohort of 178 MSers living in southern Tasmania in 2002-2005, serum 25-hydroxyvitamin D [25(OH)D] was measured biannually, with assessment by questionnaire for relevant factors, including IFN-β treatment.

RESULTS: Subjects reporting IFN-β use had significantly higher mean 25(OH)D than persons who did not (p < 0.001). This was mediated by an interaction between personal sun exposure and IFN-β, with treated persons realizing nearly three times 25(OH)D per hour of sun exposure of persons not on therapy. The association between 25(OH)D and 1,25-dihydroxyvitamin D did not differ by IFN-β therapy (p = 0.82). 25(OH)D was associated with a reduced relapse risk only among persons on IFN-β (p < 0.001). Importantly, IFN-β was only protective against relapse among persons with higher 25(OH)D (hazard ratio [HR] 0.58 [95% confidence interval (CI) 0.35-0.98]), while among 25(OH)D-insufficient persons, IFN-β increased relapse risk (HR 2.01 [95% CI 1.22-3.32]).

CONCLUSION: In this study, IFN-β therapy is associated with greater production of vitamin D from sun exposure, suggesting part of the therapeutic effects of IFN-β on relapse in MS may be through modulation of vitamin D metabolism. These findings suggest persons being treated with IFN-β should have vitamin D status monitored and maintained in the sufficiency range. 

Epub: Løken-Amsrud KI et al. Vitamin D and disease activity in multiple sclerosis before and during interferon-β treatment. Neurology. 2012 Jun 13.

OBJECTIVE: Studies based on deseasonalized vitamin D levels suggest that vitamin D may influence the disease activity in MS, and high doses are suggested as add-on treatment to interferon-β (IFN-β). Seasonal fluctuation of vitamin D varies between individuals, thus the relationship to disease activity should preferentially be studied by repeated and simultaneous vitamin D and MRI measurements from each patient.
METHODS: This was a cohort study comprising 88 MSers with relapsing-remitting MS who were followed for 6 months with 7 MRI and 4 25-hydroxyvitamin D measurements before initiation of IFN-β, and for 18 months with 5 MRI and 5 25-hydroxyvitamin D measurements during IFN-β treatment.

RESULTS: Prior to IFN-β treatment, each 10 nmol/L increase in 25-hydroxyvitamin D was associated with 12.7% (p = 0.037) reduced odds for new T1 gadolinium-enhancing lesions, 11.7% (p = 0.044) for new T2 lesions, and 14.1% (p = 0.024) for combined unique activity. Patients with the most pronounced fluctuation in 25-hydroxyvitamin D displayed larger proportion of MRI scans with new T1 gadolinium-enhancing lesions (51% vs 23%, p = 0.004), combined unique activity (60% vs 32%, p = 0.003), and a trend for new T2 lesions (49% vs 28%, p = 0.052) at the lowest compared to the highest 25-hydroxyvitamin D level. No association between 25-hydroxyvitamin D and disease activity was detected after initiation of IFN-β. HLA-DRB1*15 status did not affect the results.

CONCLUSION: In untreated MSers, increasing levels of 25-hydroxyvitamin D are inversely associated with radiologic disease activity irrespective of their HLA-DRB1*15 status

"These two studies have highlighted a possible interaction between 25(OH)D levels and treatment with interferon-β (IFN-β), reaching opposite conclusions. How strong is this evidence and how should it affect clinical practice? Not strong enough to be definitive, but clearly it needs to be looked at in more detail. Hopefully this will tempt the Pharma companies who have done IFNbeta trials to take samples out of the freezer to address this question. Should it affect clinical practice? Yes, it should! I already encourage all MSers under my care to make themselves vD replete; I recommend 5,000IU of vD3 per day."

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