Vitamin D3 and Ischemic Stroke: A Narrative Review

Abstract

Ischemic stroke is one of the major causes of death and permanent disability worldwide. The only efficient treatment to date is anticoagulant therapy and thrombectomy, which enable restitution of blood flow to ischemic tissues. Numerous promising neuroprotectants have failed in clinical trials. Given the complex pathomechanism of stroke, a multitarget pharmacotherapy seems a more rational approach in stroke prevention and treatment than drugs acting on single molecular targets. Recently, vitamin D3 has emerged as a potential treatment adjunct for ischemic stroke, as it interferes with the key prosurvival pathways and shows neuroprotective, anti-inflammatory, regenerative and anti-aging properties in both neuronal and vascular tissue. Moreover, the stimulatory effect of vitamin D3 on brain-derived neurotrophic factor (BDNF) signaling and neuroplasticity may play a role not only in the recovery of neurological functions, but also in ameliorating post-stroke depression and anxiety. This narrative review presents advances in research on the biochemical mechanisms of stroke-related brain damage, and the genomic and non-genomic effects of vitamin D3 which may interfere with diverse cell death signaling pathways. Next, we discuss the results of in vitro and in vivo experimental studies on the neuroprotective potential of 1alpha,25-dihydroxyvitamin D3 (calcitriol) in brain ischemia models. Finally, the outcomes of clinical trials on vitamin D3 efficiency in ischemic stroke patients are briefly reviewed. Despite the mixed results of the clinical trials, it appears that vitamin D3 still holds promise in preventing or ameliorating neurological and psychiatric consequences of ischemic stroke and certainly deserves further study.

Association between Vitamin D and Short-Term Functional Outcomes in Acute Ischemic Stroke

“…In addition, multivariate regression analysis based on these cut-offs revealed significant associations with lower serum Vit D levels. These results are consistent with those of previous studies that demonstrated an association between Vit D deficiency and poor short-term post-stroke functional outcomes [11,14].…”

“…Infectious complications such as post-stroke pneumonia have been associated with Vit D deficiency [13]. Vit D levels affect stroke recurrence and functional outcomes [14].…”

Vitamin D supplementation in later life: a systematic review of efficacy and safety in movement disorders

“…However, the extensive literature on this topic does not seem to link neither Vitamin D nor the higher dosage regime to cerebral infarction as in this instance. While researchers consider vitamin D deficiency to be associated with ischemic stroke risk, severity, and prognosis (Alharbi et al, 2022), vitamin D3 supplementation, on the other hand, appears to prevent and improve the neurological and psychiatric effects of ischemic stroke (Lasoń et al, 2022).…”

Role of Calcitriol and Vitamin D Receptor (VDR) Gene Polymorphisms in Alzheimer’s Disease

“…The non-genomic pathways are rapid compared to the genomic response and are mediated through specific membrane receptors like VDR and PDIA3 (protein disulfide isomerase family A member 3) (Figure 2). VDR interacts with various target proteins such as β-catenin, c-Jun, STAT1, inhibitor of nuclear factor-κB (IκB) kinase (IKK), cAMP response element-binding protein, and Runt-related transcription factor 1 (RunX 1) in the non-genomic response in vitro [76,77].…”