Overview Stroke and vitamin D

Summary - as with many other diseases,

• 2000+ IU of vitamin D will provide some stroke prevention
• 10,000+ IU of vitamin D will provide some treatment and prevention
• need more if in a high risk group
  • examples include elderly, dark skin, live far from equator, obese, avoid the sun, ...

---

Google Scholar had 160,000 hits for Stroke and Vitamin D as of Feb 2024

Google Scholar

• The relationship of vitamin D deficiency with severity and outcome of acute stroke - Dec 2021 https://doi.org/10.2478/rjim-2021-0013 FREE PDF
• Low vitamin D levels and the long-term functional outcome of stroke up to 5 years - Sept 2021 PDF
• Does vitamin D administration play a role in outcome of patients with acute ischemic stroke? A randomized controlled trial - Jan 2021PDF
• The Evaluation of the Neuroprotective Effect of a Single High-Dose Vitamin D3 in Patients with Moderate Ischemic Stroke - PDF
  • 600,000 IU injection
• Vitamin D supplementation, cardiac events and stroke: A systematic review and meta-regression analysis - June 2020PDF
• Vitamin D Supplementation and Post-Stroke Rehabilitation: A Randomized, Double-Blind, Placebo-Controlled Trial - June 2019 PDF

---

Stroke mortality 3X worse among seniors with less than 26 ng of vitamin D – June 2014

---

See also at Vitamin D Life

• Strokes result in many years of disability (Vitamin D can help) GBD – March 2019
• Vitamin D levels drop after ischemic stroke – Dec 2017
• Intracranial arterial calcification in 85 percent of ischemic strokes (Vitamin K and Vitamin D should help) – Oct 2017
• Ischemic stroke and low vitamin D – 3X higher risk of poor outcome, 6 X higher risk of a second stroke, Oct 2017
• Ischemic Stroke risk best predicted by Vitamin D, including PTH improves the prediction – Feb 2017
• Ischemic stroke 5 times more likely to recur if very low vitamin D – June 2016
• Second stroke 2X more likely if low vitamin D – Feb 2015
• Following a stroke, 10 ng less vitamin D associated with 2X more white matter hyperintensities – Nov 2014
• All items in Stroke and vitamin D 122 items
• Twice as many fatal strokes among whites who were low on vitamin D – Jan 2012
• Stroke 50 % more likely if low vitamin D – meta-analysis March 2012
• Vitamin D associated with 50 percent less ischemic stroke – meta-analysis Aug 2012
• Cardiology diseases highly associated with low vitamin D – Oct 2010 less than 30 ng/ml
• Question - Does more vitamin D make veins less stiff Nov 2007
• Heart disease, stroke, ...all linked to insufficient vitamin D levels LEF 2009 75% more likely to have a stroke
• Too much and too little Calcium both increase death after strokes – Jan 2011
• Calcium without vitamin D INCREASED heart risk by 30 percent - Jan 2011 and stroke by 20%
• 0.4 year of the 5 year life penalty for having black skin = fatal stroke

---

9 Stroke Meta-analyses

This count and list are automatically updated

---

7 Stroke Interventions

This count and list are automatically updated

---

Reasons for better hemorrhagic stroke outcome if higher Vitamin D - Aug 2021

Nutritional Supplementation of Naturally Occurring Vitamin D to Improve Hemorrhagic Stroke Outcomes
Front Neurol. 2021 Jul 30;12:670245. doi: 10.3389/fneur.2021.670245
Rani Ashouri 1, Madison Fangman 1, Jordan Brielmaier 1, Zoe A Fields 1, Natalie Campo 1, Sylvain Doré 1 2
 Download the PDF from Vitamin D Life

Vitamin D deficiency, if left untreated, is associated with bone disorders, cardiovascular damage, and an increased risk of ischemic stroke. While there are various nutritional options for the natural intake of vitamin D, we hope to elucidate the potential mechanisms dietary vitamin D may play in hemorrhagic stroke pathology. This scoping review outlines findings from studies relevant to the biochemical activity of vitamin D, the impact of vitamin D deficiency on hemorrhagic stroke outcomes, and the potential benefit of nutritional vitamin D on hemorrhagic stroke outcomes. Here, we analyze the relevant factors that can lead to vitamin D deficiency, and subsequently, a higher risk of hemorrhagic stroke incidence with worsened subsequent outcomes.
The neuroprotective mechanisms through which vitamin D works to attenuate hemorrhagic stroke onset and post-stroke outcomes have not yet been thoroughly examined.

However, researchers have proposed several potential protective mechanisms, including

• reduction of blood brain barrier disturbance by inhibiting the production of reactive oxygen species,
• mitigation of inflammation through a reduction of levels of proinflammatory cytokines, and
• prevention of cerebral vasospasm and
• delayed cerebral ischemia following subarachnoid hemorrhage and intracerebral hemorrhage.

While more research is needed and there are limitations to vitamin D supplementation, vitamin D as a whole may play a significant role in the dynamics of hemorrhagic stroke. Further research should focus on expanding our understanding of the neuroprotective capacity and mechanisms of vitamin D, as well as how vitamin D supplementation could serve as an effective course of treatment of hemorrhagic strokes.

---

Ischemic Stroke while asleep is associated with <9 ng Vitamin D - June 2022

Surrogate biomarkers of outcome for wake-up ischemic stroke
BMC Neurol . 2022 Jun 9;22(1):215. doi: 10.1186/s12883-022-02740-z.
Pablo Hervella 1 2, María Luz Alonso-Alonso 3, María Pérez-Mato 4, Manuel Rodríguez-Yáñez 5, Susana Arias-Rivas 5, Iria López-Dequidt 5, José M Pumar 3 6, Tomás Sobrino 7, Francisco Campos 8, José Castillo 3, Ramón Iglesias-Rey 9 10

Background: Wake-up ischemic stroke (IS) has been usually excluded from acute stroke therapy options for being outside of the safe treatment window. We identified risk factors, and clinical or molecular biomarkers that could be therapeutic targets for wake-up stroke prevention, thus hopefully leading to a decrease in its mortality and disability in medium to long-term outcome.

Methods: 4251 ischemic stroke (IS) patients from a prospectively registered database were recruited; 3838 (90.3%) had known onset-symptom time, and 413 (9.7%) were wake-up strokes. The main endpoint was to analyze the association between different serum biomarkers with wake-up IS episodes and their progression. Leukocytes count, serum levels of C-reactive protein, fibrinogen, interleukin 6 (IL-6), and vitamin D were analyzed as inflammation biomarkers; N-terminal pro-B-type Natriuretic-Peptide and microalbuminuria, used as atrial/endothelial dysfunction biomarkers; finally, glutamate levels as excitotoxicity biomarker. In addition, demographic, clinical and neuroimaging variables associated with the time-evolution of wake-up IS patients and functional outcome at 3 months were evaluated. Good and poor functional outcome were defined as mRS ≤2 and mRS > 2 at 3 months, respectively.

Results: Wake-up IS showed a poorer outcome at 3-months than in patients with known on-set-symptom time (59.1% vs. 48.1%; p < 0.0001). Patients with wake-up IS had higher levels of inflammation biomarkers; IL-6 levels at admission (51.5 ± 15.1 vs. 27.8 ± 18.6 pg/ml; p < 0.0001), and low vitamin D levels at 24 h (5.6 ± 5.8 vs. 19.2 ± 9.4 ng/ml; p < 0.0001) are worthy of attention. In a logistic regression model adjusted for vitamin D, OR was 15.1; CI 95%: 8.6-26.3, p < 0.0001. However, we found no difference in vitamin D levels between patients with or without clinical-DWI mismatch (no: 18.95 ± 9.66; yes: 17.84 ± 11.77 ng/mL, p = 0.394). No difference in DWI volume at admission was found (49.3 ± 96.9 ml in wake-up IS patients vs. 51.7 ± 98.2 ml in awake IS patients; p = 0.895).

Conclusions: Inflammatory biomarkers are the main factors that are strongly associated with wake-up IS episodes. Wake-up IS is associated with lower vitamin D levels. These data indicate that vitamin D deficiency could become a therapeutic target to reduce wake-up IS events.
 Download the PDF from Vitamin D Life

---

Depression lead to Strokes (Vitamin D Life notes that both are related to low vitamin D)

Article about Brigham Women's Hospital Study which was published in Stroke
"women with a history of depression had a 29 percent higher risk of stroke, even after considering other stroke risk factors."
"The study included more than 80,000 female nurses between the ages of 54 to 79 years old from 2000-06 without a prior history of stroke. "
"More than 1000 cases of stroke were documented among the women during the six years."
CLICK HERE for abstract Aug 2011
(Vitamin D Life notices that the principal author has published many other papers on cardiovascular problems and low vitamin D levels. Kathryn M. Rexrode krexrode at partners.org)

See in Vitamin D Life No longer depressed, but risk of stroke is still 1.7X higher (did not consider low vitamin D) – May 2015

---

Stroke is more severe and disabling if vitamin D is lower - April 2021

The Relationship of Vitamin D Deficiency with Severity and Outcome of Acute Stroke
Rom J Intern Med. 2021 Apr 13. doi: 10.2478/rjim-2021-0013
Reza Ebrahimi Rad 1, Mohammadreza Zarbakhsh 2, Samira Sarabi 3

Background: There are currently conflicting results regarding the link between vitamin D deficiency and increased risk for stroke and its poor prognosis. The present study aimed to assess the relationship between vitamin D deficiency and prognosis of acute stroke.Methods: This bi-center cross-sectional study was performed on 140 consecutive patients who referred to two general hospitals in Iran with the diagnosis of acute stroke. The levels of 25-hydroxy vitamin D were evaluated by Electrochemiluminescence (ECL) technique. Clinical severity of stroke on admission as well as on discharge time were evaluated using the National Institutes of Health Stroke Scale (NIHSS) or Modified Rankin (mRS) tools.Results: Mean serum level of vitamin D was 25.51 ± 18.87 ng/mL, ranging from 3.0 to 98.6 ng/ml. There was a significant difference between the two groups (with and without vitamin D deficiency) in terms of stroke severity and disability, as reflected by mRS (P=0.003) and NIHSS evaluation (14.24 ± 9.23 versus 9.73 ± 7.36, P=0.003). Also, regarding patients' clinical condition, the mean NIHSS score in those with deficient and normal levels of vitamin D was 14.24 ± 9.23 and 9.73 ± 7.36, respectively with NIHSS score > 5 in 76.1% and 61.5%, respectively (P = 0.003).
Conclusion: According to the results of study, vitamin D status can be related to the severity of stroke. However, considering the cross-sectional design of our study, it could not point out the causality between vitamin D deficiency and acute stroke and further studies are warranted. It is not possible to draw any conclusions in terms of causality. Further studies are required in order to assess the relationship between the serum vitamin D levels and stroke severity.

---

Hypertension (blood pressure) increases incidence of strokes

• Overview Hypertension and vitamin D at VitaminDWki
• About.com
  70% of strokes related to high blood pressure
  "high blood pressure the single most important controllable stroke risk factor, especially in the elderly."

---

Stroke patients with low vitamin D were 10X more likely to become depressed – Aug 2014

Stroke patients with low vitamin D were 10X more likely to become depressed – Aug 2014

---

Strokes occur 25% more often in the Spring - when the vitamin D blood levels are the lowest

Incidence of Stroke and Season of the Year: Evidence of an Association
Am J Epidemiol 2000;152:558–64.

Evidence of seasonal variation in the incidence of stroke is inconsistent. This may be a likely consequence of one or more methodological shortcomings of the studies investigating this issue, including inappropriate analytic models, insufficient length of time, small sample size, and a regional (vs. national) focus. The authors' objective was to ascertain whether an association exists between season of the year and the incidence of stroke by using a methodological approach designed to overcome these limitations.
The authors used a longitudinal study design involving 72,779 veterans hospitalized for stroke at any Veterans Affairs hospital nationally during the years 1986–1995.
These data were analyzed by using time series methods.
There was clear evidence of a seasonal occurrence for stroke in general.
This seasonal effect was found for ischemic stroke, but not for hemorrhagic stroke.
The peak occurrence was in mid-May.
Neither the region (i.e., climate) nor the race of the patient substantially modified the seasonal trend. An explanation for this pattern remains to be determined.

---

Chart from a 2010 Vitamin D book edited by Dr. Holick

---

Magnesium in water also associated with reduction in stroke - 2012

100 mg more Magnesium in water associated with 8 percent reduction in stroke – Feb 2012
Independent evidence shows that Vitamin D and Magnesium both reduce strokes.
Expect that they would do well together - perhaps more than 2X the benefit

---

Stroke 50 % more likely if low vitamin D - Meta-analysis May 2012

25-Hydroxyvitamin D Levels and the Risk of Stroke. A Prospective Study and Meta-analysis
Qi Sun, MD, ScD qisun at hsph.harvard.edu ; An Pan, PhD; Frank B. Hu, MD, PhD; JoAnn E. Manson, MD, DrPH; Kathryn M. Rexrode, MD, MPH
From the Departments of Nutrition (Q.S., A.P., F.B.H.) and Epidemiology (F.B.H., J.E.M.), Harvard School of Public Health, Boston, MA; and the Channing Laboratory (Q.S., F.B.H., J.E.M.) and the Division of Preventive Medicine (J.E.M., K.M.R.), the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Background and Purpose—Despite evidence suggesting that vitamin D deficiency may lead to elevated cardiovascular disease risk, results regarding the association of 25-hydroxyvitamin D (25OHD) levels with stroke risk are inconclusive. We aimed to examine this association in a prospective study in women and to summarize all existing data in a meta-analysis.

Methods—We measured 25(OH)D levels among 464 women who developed ischemic stroke and an equal number of control subjects who were free of stroke through 2006 in the Nurses' Health Study (NHS). We searched MEDLINE and EMBASE for articles published through March 2011 that prospectively evaluated 25(OH)D levels in relation to stroke.

Results—After multivariable adjustment for lifestyle and dietary covariates, lower 25(OH)D levels were associated with an elevated risk of ischemic stroke in the NHS: the OR (95% CI) comparing women in the lowest versus highest tertiles was 1.49 (1.01–2.18; Ptrend=0.04). We found 6 other prospective studies that examined 25(OH)D in relation to stroke outcomes. After pooling our results with these prospective studies that included 1214 stroke cases in total, low 25(OH)D levels were associated with increased risk of developing stroke outcomes in comparison to high levels: the pooled relative risk (95% CI) was 1.52 (1.20–1.85; I2=0.0%, Pheterogeneity=0.63). In 2 studies that explicitly examined ischemic stroke, this association was 1.59 (1.07–2.12; I2=0.0%, Pheterogeneity=0.80).

Conclusions—These data provide evidence that low vitamin D levels are modestly associated with risk of stroke.
Maintaining adequate vitamin D status may lower the risk of stroke in women.

---

4X more likely to have good function after a stroke if have high vitamin D level - May 2014

Prognostic Value of Serum 25-Hydroxyvitamin D in Patients with Stroke.
Neurochem Res. 2014 May 1.
Wang Y1, Ji H, Tong Y, Zhang ZB.

We aimed to evaluate the association between 25-hydroxyvitamin D [25(OH) D] levels and both clinical severity at admission and outcome at discharge in patients with acute ischemic stroke (AIS). From June 2012 to October 2013, consecutive first-ever AIS patients admitted to the Department of Emergency of The Fourth Affiliated Hospital of Harbin Medical University, China were identified. Clinical information was collected. Serum 25(OH) D levels were measured at baseline. Stroke severity was assessed at admission using the National Institutes of Health Stroke Scale (NIHSS) score. Functional outcome was evaluated at discharge using the modified Rankin scale (m-Rankin). Multivariate analyses were performed using logistic regression models. During the study period, 326 patients were diagnosed as AIS and were included in the analysis. Serum 25(OH) D levels reduced with increasing severity of stroke as defined by the NIHSS score. There was a negative correlation between levels of 25(OH) D and the NIHSS (r = - 0.389, P = 0.000). In multivariate analyses, serum 25(OH) D level was an independent prognostic marker of discharge favorable functional outcome and survival [odds ratio 3.96 (2.85-7.87) and 3.36 (2.12-7.08), respectively, P = 0.000 for both, adjusted for NHISS, other predictors and vascular risk factors] in patients with AIS. Serum 25(OH) D levels are a predictor of both severity at admission and favorable functional outcome in patients with AIS. Additional research is needed on vitamin D supplementation to improve the outcome of post-stroke patients.
 Download the PDF from sci-hub via Vitamin D Life

---

Stem cells reverse stroke for many months, even if more than 1 year since stroke (nothing about vitamin D)

Chronic stroke patients safely recover after injection of human stem cells June 2016

• "Proved safe and effective in restoring motor (muscle) function in a small clinical trial led by Stanford University School of Medicine investigators. "
• "The procedure involved injecting SB623 mesenchymal stem cells, derived from the bone marrow of two donors and then modified to beneficially alter the cells’ ability to restore neurologic function."
• “We know these cells don’t survive for more than a month or so in the brain,” he added. “Yet we see that patients’ recovery is sustained for greater than one year and, in some cases now, more than two years.”

---

More likely to have stroke if < 20 ng of vitamin D - Community living seniors

Vitamin D deficiency and incident stroke risk in community-living black and white adults Jan 2016
8.5 X more likely if black, 1.6X more likely if white - but racial difference was not statistically significant

---

Vitamin D and Stroke: Promise for Prevention and Better Outcome - 2015

Current Vascular Pharmacology, Jan 2014 free PDF online
Table 1. Association of Vitamin D Deficiency with Risk Factors for Cerebrovascular Events
Indirect
Hypertension
Diabetes mellitus
Metabolic syndrome
Atherosclerosis
Direct
Limitation of Antithrombotic Effects
Enhancement of platelet aggregation
Up-regulation of tissue factor gene
Down-regulation of antithrombin gene
Down-regulation of thrombomodulin gene
Limitation of Neuroprotective Effects
Biosynthesis of neurotrophic factors:
- Nerve growth factor
- Glial cell line derived neurotrophic factor (GDNF)
Biosynthesis of neurotransmitters
Brain detoxification pathways:
- Expression of inducible nitric oxide synthase (iNOS)
- Intracellular glutathione levels
- Gamma-GT levels
Modulation of neuronal death:
- Regulation of L-Type calcium channels (L-VSCC) in hippocampal neurons

---

Association between Vitamin- D Deficiency and Stroke - A Comparative Study - 2017

Charts of Vitamin D levels for the two types of strokes
 Download the PDF from Vitamin D Life

---

Quick review of Hemorrhagic Stroke - June 2017

Vitamin D - maybe, Vitamin C - maybe, Cholesterol - maybe, Omega-3 - YES

• There has been some Hemorrhagic Stroke research: https://academic.oup.com/aje/article-lookup/doi/10.1093/aje/kwp227
  There was not enough data to show that vitamin D was significant - but the trend indicated a 40% reduction
• https://www.ncbi.nlm.nih.gov/pubmed/22627988 PDF online
  "We found no significant associations between dietary vitamin D and hemorrhagic stroke."
• How LOW Cholesterol Can Harm Your Health Green Medical Information, Sept 2012
  Cholesterol Is Needed To Prevent Hemorrhagic Stroke:
• The Role of Omega-3 Polyunsaturated Fatty Acids in Stroke - 2016
   Download the PDF from Vitamin D Life
• Omega-3 and vitamin C both PREVENT Hemorrhagic Stroke- Life Extension 2015
• Omega-3 Good After Heart Attacks And For Hemorrhagic Stroke Prevention 2015

Vitamin D and Ischemic Stroke -need more data - April 2019

What is the current role for vitamin D and the risk of stroke ?
Curr Neurovasc Res. 2019 Apr 12. doi: 10.2174/1567202616666190412152948.
Siniscalchi A1, Lochner P2, Anticoli S3, Chirchiglia D4, De Sarro G4, Gallelli L5.

Increasing evidence support the relationship between vitamin D and stroke. Vitamin D have now been proposed as a prognostic biomarker for also functional outcome in stroke patients. A revision of the data suggests that low vitamin D is associated more with ischemic than with haemorrhagic stroke, even if the role of optimal vitamin D levels for vascular wall is still unclear. Vitamin D deficiency induces with different mechanisms an alteration of vascular wall. However, to date, the research supporting the effectiveness of vitamin D supplementation in stroke and in post-stroke recovery is still inadequate and conclusive evidences have not been published. In this review, we provide a better understanding of the role of vitamin D in stroke.

Most other mammals never suffer strokes. Bill Bryson, The Body, 2019