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Table of Contents
Year : 2021  |  Volume : 24  |  Issue : 2  |  Page : 130-131

Vitamin D and cerebrovascular disease

1 Department of Neurochemistry, NIMHANS, Bengaluru, India
2 S-VYASA, NIMHANS, Bengaluru, India
3 Department of Neurology, NIMHANS, Bengaluru, India

Date of Submission28-Nov-2020
Date of Acceptance28-Nov-2020
Date of Web Publication06-Apr-2021

Correspondence Address:
Prof. Rita Christopher
MD Professor of Neurochemistry, NIMHANS, Bengaluru 560 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aian.AIAN_1207_20

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How to cite this article:
Christopher R, Majumdar V, Nagaraja D. Vitamin D and cerebrovascular disease. Ann Indian Acad Neurol 2021;24:130-1

How to cite this URL:
Christopher R, Majumdar V, Nagaraja D. Vitamin D and cerebrovascular disease. Ann Indian Acad Neurol [serial online] 2021 [cited 2021 Jun 19];24:130-1. Available from:

   Editorial Commentary Top

Vitamin D (25-Hydroxyvitamin D (25(OH) D)), is a secosteroid provitamin obtained by dermal synthesis following exposure to sun and through oral consumption from food and supplements. Though initially related to bone and mineral homeostasis, a diversified range of physiological roles of 25(OH) D has been documented over the years. Concurrently, a vast array of >100 human diseases have been linked to low circulating concentrations of 25(OH) D.[1] The intriguing but worrisome estimates of more than a half of global population with inadequate vitamin D status, suggest a vast potential for vitamin D-based interventions targeted at the prevention, and management of these diseases.[2]

In the present point-of-view article, the authors have presented an epidemiological as well as clinical perspective on the incidence, severity, and rehabilitation of stroke caused by vitamin D deficiency.[3] Although a decline in stroke mortality has been documented recently in developed nations because of the implementation of strict guidelines on risk factor management like hypertension,[4],[5] the global burden of stroke continues to rise due to an increase in the developing countries.[4] The authors have presented an overall view on the association of vitamin D status with stroke risk; most of the evidence discussed is derived from reported observational prospective studies.[3] The authors have also given a run-through over the status of intervention studies; however, a few important reports could be included. To this end, we would like to refer to the recently published, randomized, placebo-controlled, VITAL trial, that reported no decrease in the incidence of cardiovascular events including stroke in the elderly, when the use of vitamin D supplements and marine omega-3 fatty acids were compared with placebo, during a mean follow-up of 5.3 years.[6] The trial concluded that the beneficial influences of vitamin D supplementation on stroke risk could only be limited to severely vitamin D deficient individuals. The finding raises concerns on the implementation of vitamin D supplementation for the prevention of stroke. Similarly, the recent findings from a prospective, population-based study (n = 9680) from Rotterdam[7] showed low circulating vitamin D in prevalent stroke but only severe vitamin D deficiency was linked to incident stroke. The study concluded with a view that lower vitamin D levels might not lead to higher stroke risk, but rather could be an outcome of stroke.[7]

Given the inconsistent findings with a lack of reports on large sample sizes, the authors have indicated the limitations in inferring the causal association of vitamin D deficiency with stroke and have advocated that this should be explored in further studies.[3] Authors have also opined that a plausible causal relationship between vitamin D deficiency and risk of stroke cannot be excluded based on a recently published Mendelian randomized study.[3],[8] In the referred study on 116,655 individuals, observational but not genetic low 25(OH)D concentration was linked to ischemic stroke; however, a causal relationship could be established between vitamin D deficiency and hypertension through the Mendelian randomization approach.[8] An interesting mechanistic and epidemiological intersection lies between vitamin D levels, risk of stroke, and hypertension, one of the most prevalent pathophysiological risk factors for stroke.[9] In a case–control study from China, the joint occurrence of vitamin D deficiency with hypertension was found to increase the probability of developing small vessel stroke by 5.6-fold [OR = 5.609 (95% CI 2.006–15.683)].[10] Similarly, in our cross-sectional evaluation in an Asian Indian population, the presence of hypertension was found to aggravate the risk of ischemic stroke associated with low vitamin D levels. We observed a distinct association between reduced circulating 25(OH)D and risk of ischemic stroke in hypertensives (OR = 13.54, 95% CI = 1.94–94.43) when compared to lack of association in non-hypertensives, (Pinteraction = 0.04).[11] The synergistic influence of severely deficient vitamin D status along with hypertension on an aggravated stroke risk needs meticulous assessment in a prospective and interventional manner to answer the issue of combined treatment of low vitamin D levels and/or hypertension to prevent stroke and reduce the severity of its outcomes.

   References Top

Manousaki D, Richards JB. Commentary: Role of vitamin D in disease through the lens of Mendelian randomization-Evidence from Mendelian randomization challenges the benefits of vitamin D supplementation for disease prevention. Int J Epidemiol 2019;48:1435-7.  Back to cited text no. 1
Lutsey PL, Michos ED. Vitamin D, calcium, and atherosclerotic risk: Evidence from serum levels and supplementation studies. Curr Atheroscler Rep 2013;15:293.  Back to cited text no. 2
Kaul S, Manikinda J. Role of vitamin D in cerebrovascular disease. Ann Indian Acad Neurol 0;0:0.  Back to cited text no. 3
Donkor ES. Stroke in the 21st century: A snapshot of the burden, epidemiology, and quality of life. Stroke Res Treat 2018;2018:3238165.  Back to cited text no. 4
Johnson W, Onuma O, Owolabi M, Sachdev S. Stroke: A global response is needed. Bull World Health Organ 2016;94:634.  Back to cited text no. 5
Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med 2019;380:33-44.  Back to cited text no. 6
Berghout BP, Fani L, Heshmatollah A, Koudstaal PJ, Ikram MA, Zillikens MC, et al. Vitamin D status and risk of stroke: The rotterdam study. Stroke 2019 50:2293-8.  Back to cited text no. 7
Afzal S, Nordestgaard BG. Vitamin D, hypertension, and ischemic stroke in 116 655 individuals from the general population: A genetic study. Hypertension 2017. doi: 10.1161/HYPERTENSIONAHA.117.09411.  Back to cited text no. 8
Furie KL, Kasner SE, Adams RJ, Albers GW, Bush RL, Fagan SC, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:227-76.  Back to cited text no. 9
Si J, Li K, Shan P, Yuan J. The combined presence of hypertension and vitamin D deficiency increased the probability of the occurrence of small vessel disease in China. BMC Neurol 2019;19:164.  Back to cited text no. 10
Majumdar V, Prabhakar P, Kulkarni GB, Christopher R. Vitamin D status, hypertension and ischemic stroke: A clinical perspective. J Hum Hypertens 2015;29:669-74.  Back to cited text no. 11


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