REPORT FROM THE AMERICAN ACADEMY OF NEUROLOGY (AAN) ANNUAL MEETING, PHILADELPHIA PA, APRIL 26-MAY 3, 2014 – For over 50 years, solar radiation and vitamin D have been implicated in the pathogenesis of MS (Acheson et al. Acta Psychiatr Scand Suppl 1960;35:132-147), in large part due to the latitude effect. However, the relevance of serum 25(OH)D levels and the virtues of vitamin D supplementation remain controversial.
Some studies have reported that lower vitamin D status is associated with greater MS disease activity on MRI (Mowry et al. Ann Neurol 2012;72:234-240). However, most randomized trials to date have reported that high-dose vitamin D supplementation produces little benefit on clinical or MRI endpoints (Stein et al. Neurology 2011;77:1611-1618; Kampman et al. Mult Scler 2012;18:1144-1151; Mosayebi et al. Immunol Invest 2011;40:627-639). Some have observed that the effects of vitamin D on CNS demyelination are distinct from those seen with sun exposure (Lucas et al. Neurology 2011;76:540-548). A more recent suggestion is that there is a limited window of opportunity for achieving a benefit with vitamin D supplementation: vitamin D has been shown to produce a marked reduction in CNS inflammation in juvenile EAE rats but not in adult EAE rats (Adzemovic et al. Exp Neurol 2013;249:39-48).
More favourable results have been seen with vitamin D as an add-on therapy to interferon-beta. A study in 66 MS patients reported fewer new T2 lesions and Gd-enhancing T1 lesions with the combination versus IFNbeta alone, although there was no significant difference in annualized relapse rates (Soilu-Hanninen et al. J Neurol Neurosurg Psychiatry 2012;83:565-571). A subsequent analysis of data from the BENEFIT trial of IFNbeta-1b found that higher serum 25(OH)D levels were associated with significantly lower rates of new active lesions, relapses, and brain atrophy (Ascherio et al. JAMA Neurol 2014;71:306-314).
At AAN 2014, a study examined whether the benefits of adjunctive vitamin D also apply to patients treated with glatiramer acetate (Rotstein et al. AAN 2014; abstract S24.005 and I7-1.004). Serum
25(OH)D levels were measured in 247 adults with MS and compared to time to first relapse or Gd-enhancing lesion. Higher 25(OH)D levels were significantly associated with a longer time to first event for the full cohort and for the IFNb subgroup on multivariate analysis. However, there was no significant association in patients treated with glatiramer acetate, suggesting that the effects of vitamin D may be influenced by the type of disease-modifying therapy.
Also noteworthy was the finding in a separate study that higher EDSS scores were significantly associated with lower serum vitamin D levels and markers of obesity – but only in females (Bove et al. AAN 2014; abstract S24.003). In males, EDSS was correlated with testosterone levels, indicating a complex interaction of vitamin D, sex hormones and obesity in the pathogenesis of neurodegeneration.
A preliminary double-blind study in 158 MS patients (mean age 41 years) reported an improvement in MS fatigue with alfacalcidol, a vitamin D analogue (Barak et al. AAN 2014; abstract S23.004). Subjects received alfacalcidol 1 mcg/day or placebo for six months. Greater improvements in Fatigue Impact Scale scores from baseline were seen with alfacalcidol compared to placebo (-41.6 vs. -27.4%), and a treatment benefit was also seen in QOL psychological and social subscale measures.
A small study has reported that MS patients with higher dietary sodium intake have a greater risk of relapses and MRI activity (Farez et al. AAN 2014; abstract P6.150). These results were previously presented at ECTRIMS 2013 and reported on Neurosens (see Dietary sodium linked to increased disease activity in MS).
Guest Reviewer: Dr. Daniel Selchen, Head of Neurology, St. Michael’s Hospital, Toronto, Canada