# Vitamin D and Rehabilitation after Stroke: Status of Art
## 4 Vitamin D and Stroke  
A study from [PERSON] et al. [59] concluded that reduced 25(OH) D (<20 ng/mL) was found in 77% of 44 patients analyzed within 30 days of their first-ever stroke. They hypothesized that the vitamin D deficiency was probably present before the stroke, given that the biological half-life of 25(OH)D is about 3 weeks and an acute reduction in 25(OH)D due to a decline in hormone synthesis or existing storesseemed impossible for the time between stroke event and 25(OH)D sampling. In a successive review, [PERSON] et al. sustained that, among the new strategies to prevent stroke, there was administration of vitamin D [57]. Supplementation of this vitamin aimed to preserve a serum concentration of 25(OH)D above 30 ng/mL in the patient after a stroke insult, as well as in subjects at high risk of stroke, and was suggested to be a promising and protective therapy [57].  
A review from [PERSON] et al. [16] outlined the possible pathways that match the vitamin D deficiency with increased stroke risk. Arterial hypertension is the principal risk factor for stroke and was associated with low vitamin levels; the mechanism seems related to the renin-angiotensin-aldosterone system, but also to the prevention of hyperparathyroidismism, re neuroprotective and anti-inflammatory effects and to vasculoprotective properties.  
Moreover, vitamin D deficiency is related to an augmented risk for type 2 diabetes mellitus [66]. Other risk factors for ischemic cerebrovascular events are atherosclerosis, prothrombotic states, secondary hyperparathyroidismism, and inflammation.  
More recently, [PERSON] et al. deepened the role of Vitamin D deficiency in atherosclerosis, myocardial infarction and stroke, explaining the mechanism hypothesis together with a detailed description of all animal model studies [60].  
In a large study cohort, in the Copenaghen City heart study and meta-analysis, [PERSON] et al. [61] evaluated 10,170 individuals and, during a 21 years follow-up, observed that a total of 1256 developed ischemic stroke. When comparing subjects with severe vitamin D deficiency (10 ng/mL) to individuals with optimal vitamin D status (30.0 ng/mL), the multivariate adjusted hazard ratio of ischemic stroke was 1.36 (1.09-1.70). The vitamin D concentrations were not associated with the risk of hemorrhagic stroke. This result was confirmed by a meta-analysis that compared the lowest vs. highest quartile of 25(OH)D; the multivariate-adjusted odds ratio of ischemic stroke was 1.54 (1.43-1.65) with a corresponding hazard ratio of 1.46 (1.35-1.58) in prospective studies [61].  
[PERSON] et al. published an interesting systematic review and meta-analysis, including 19 studies exploring the possible association of vitamin D with risk of stroke [64]. The meta-analysis sustained the hypothesis that lower vitamin D status is associated with an increased risk of ischemic, but not hemorrhagic, stroke (relative risk = 2.45, 95% CI:1.56-3.86).  
In particular, one study presented in this meta-analyses showed an association of Vitamin D deficiency with stroke risk, without differences by race [62].  
Two studies not included in this metanalysis deserve to be cited. One is the Ludwigshafen Risk and Cardiovascular Health (LURIC) study [63], which analyzed more than 3000 patients followed-up for 8 years. In this study, low levels of 25(OH)D and 1,25(OH)2D were shown to be predictive of fatal stroke [63]. The second is a study on vitamins as stroke predictors in elderly; this study showed that low vitamin D intake and low 1,25(OH)2D serum levels implied a major stroke risk [65].  
Observational studies suggest that vitamin D may protect against stroke, but a recent important randomized, double-blind, placebo-controlled study (VITAL Study) on 25,871 subjects revealed that vitamin D3 (200 IU/days) supplementation does not reduce cardiovascular events, including stroke [58] (Table 1).