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Review paper

Combination of vitamin A and D supplementation for ischemic stroke: effects on interleukin-1ß and clinical outcome

By
Alfansuri Kadri Orcid logo ,
Alfansuri Kadri
Contact Alfansuri Kadri

Department of Neurology, Faculty of Medicine, Universitas Sumatera Utara, Indonesia

Hasan Sjahrir ,
Hasan Sjahrir

Department of Neurology, Faculty of Medicine, Universitas Sumatera Utara, Indonesia

Rosita Juwita Sembiring ,
Rosita Juwita Sembiring

Department of Clinical Pathology, Faculty of Medicine, Universitas Sumatera Utara, Indonesia

Muhammad Ichwan
Muhammad Ichwan

Department of Pharmacology, Universitas Sumatera Utara, Indonesia

Abstract

Aim
Accumulated evidence suggests that vitamin A and D agonists can alleviate the development of atherosclerosis. Therefore, the aim of this study was to determine the effect of vitamin A and D combination supplement on interleukin-1β (IL-1β) and clinical outcome in ischemic stroke.
Methods
A single-blind, randomized controlled trial was conducted on ischemic stroke patients at Adam Malik Hospital between March 2018 to February 2019. The patients were randomized into 4 groups of the treatment consisting of supplementation using vitamin A or D only, combination of vitamin A and D, and placebo group, all given for 12 weeks. Clinical outcome was determined using the National Institute of Health Stroke Scale (NIHSS). At the time of admission and after the treatment was completed, all patients were measured for vitamin A, vitamin D, and IL-1β serum level, and NIHSS score.
Results
From the total of 120 patients, in the combination group there were significant increments on both vitamin A (p=0.04) and vitamin D (p=0.01) serum level after 12 weeks of the treatment, compared to the other groups. In conjunction, IL-1β serum level showed a significant decrement in the combination group (p<0.001). Lastly, the biggest improvement of NIHSS could be seen in the combination group, which was marked by the highest decrement of NIHSS score (p<0.001).
Conclusion
Administration of combination of vitamin A and D supplementation can significantly increase vitamin A and D serum level, decrease IL-1β serum level, and ultimately improve clinical outcome in ischemic stroke patients.

References

1.
Gofir A. Pengantar Manajemen Stroke Komprehensif. Pustaka Cendikia Press; 2007.
2.
Lakhan S, Kirchgessner A, Hofer M. Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J Transl Med. 2009. p. 97.
3.
Muscogiuri G, Annweiler C, Duval G, Karras S, Tirabassi G, Salvio G. Vitamin D and cardiovascular disease: From atherosclerosis to myocardial infarction and stroke. Int J Cardiol. 2017. p. 577–84.
4.
Makariou S, Michel P, Tzoupi M, Challa A, Milion H. Vitamin D and stroke: promise for prevention and better outcome. Curr Vasc Pharmacol. 2014. p. 117–24.
5.
Sato Y, Meller R, Yang T, Taki W, Simon R. Stereoselective neuroprotection against stroke with vitamin A derivatives. Brain Res. 2008. p. 188–92.
6.
Vonder Haar C, Peterson T, Martens K, Hoane M. Vitamins and nutrients as primary treatments in experimental brain injury: Clinical implications for nutraceutical therapies. Brain Res. 2016. p. 114–29.
7.
Badimon L, Vilahur G, Padro T. Nutraceuticals and atherosclerosis: human trials. Cardiovasc Ther. 2010. p. 202–15.
8.
Aggarwal A, Aggarwal P, Khatak M, Khatak S. Cerebral ischemic stroke: sequels of cascade. Int J Pharma Bio Sci. 2010. p. 1–24.
9.
Sun Q, Pan A, Hu F, Manson J, Rexrode K. 25-Hydroxyvitamin D levels and the risk of stroke. A prospective study and meta-analysis. Stroke. 2012. p. 1470–7.
10.
Judd S, Morgan C, Panwar B, Virginia J, Wadley V, Jenny N, et al. Vitamin D deficiency and incident stroke risk in community living black and white adults. Int J Stroke. 2017. p. 93–102.
11.
Nargesi A, Heidari B, Esteghamati S, Hafezi-Nejad N, Sheikhbahaei S, Pajouhi A, et al. Contribution of vitamin D deficiency to the risk of coronary heart disease in subjects with essential hypertension. Atherosclerosis. 2016. p. 165–71.
12.
Agbalalah T, Hughes S, Freeborn E, Mushtaq S. Impact of vitamin D supplementation on endothelial and inflammatory markers in adults: A systematic review. J Steroid Biochem Mol Biol. 2017. p. 292–300.
13.
Kato S. The function of vitamin D receptor in vitamin D action. J Biochem. 2000. p. 717–22.
14.
Pike J, Meyer M, Martowicz M. New techniques in transcription research extend our understanding of the molecular actions of the vitamin D hormone. IBMS Bone Key. 2009. p. 169–80.
15.
Germain P, Chambon P, Eichele G, Evans R, Lazar M, Leid M, et al. International Union of Pharmacology. LXIII. Retinoid X receptors. Pharmacol Rev. 2006. p. 760–72.
16.
Lera D, Krezel A, Rühl W, R. An Endogenous mammalian retinoid X receptor ligand, at last. Chem Med Chem. 2016. p. 1–12.
17.
Allenby G, Bocquel M, Saunders M, Kazmer S, Speck J, Rosenberger M, et al. Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acid. Proc Natl Acad Sci. 1993. p. 30–4.
18.
Rühl R, Krzyżosiak A, Niewiadomska-Cimicka A, Rochel N, Szeles L, Vaz B, et al. 9-cis-13,14-Dihydroretinoic acid is an endogenous retinoid acting as RXR ligand in mice. PLOS Genetics. 2015. p. 1005213.
19.
Min K, Min. Relation of serum vitamin A levels to all-cause and cause-specific mortality among older adults in the NHANES III population. Nutr Metab Cardiovasc Dis. 2014. p. 1197–203.
20.
Wei Z, Kuang J. Vitamin D deficiency in relation to the poor functional outcomes in nondiabetic patients with ischemic stroke. Biosci Rep. 2018. p. 1–8.
21.
Kong L, Wang Y, Wang X, Wang X, Zhao Y, Wang L, et al. Retinoic acid ameliorates blood-brain barrier disruption following ischemic stroke in rats. Pharmacol Res. 2015. p. 125–36.
22.
Rist P, Jiménez M, Tworoger S, Hu F, Manson J, Sun Q, et al. Plasma retinol-binding protein 4 levels and the risk of ischemic stroke among women. J Stroke Cerebrovasc Dis. 2018. p. 68–75.
23.
Yu S, Airavaara M, Wu K, Harvey B, Liu H, Yang Y, et al. 9-cis retinoic acid induces neurorepair in stroke brain. Sci Rep. 2017. p. 1–12.
24.
Panickar K, Dawson H. Acute effects of Alltrans-retinoic Acid in ischemic injury. Transl Neurosci. 2012. p. 143–52.
25.
Lin L, Peng F, Liu Y, Chai D, Ning R, Xu C, et al. Co-administration of VDR and RXR agonists synergistically alleviates atherosclerosis through inhibition of oxidative stress: an in vivo and in vitro study. J Atheroscler. 2016. p. 273–81.
26.
Witham M, Crighton L, Gillespie N, Struthers A, Mcmurdo M. The effects of Vitamin D Supplementation on physical function and quality of life in older patients with heart failure. J Am Heart Assoc. 2010. p. 195–201.
27.
Schleithoff S, Zitterman A, Tenderich G, Berthold H, Stehle P, Koerfer R. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2006. p. 754–9.
28.
Zittermann A, Frisch S, Berthold H, Götting C, Kuhn J, Kleesiek K, et al. Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. Am J Clin Nutr. 2009. p. 1321–7.
29.
Kasner S. Clinical interpretation and use of stroke scales. Lancet Neurol. 2006. p. 603–12.
30.
Kennel K, Drake M, Hurley D. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clin Proc. 2010. p. 752–7.
31.
Gibson R, Ed. Principles of nutritional assessment. Oxford University Press; 2005.
32.
Sommer A. Vitamin A deficiency and its consequences: a field guide to detection and control. World Health Organization; 1995.
33.
Quantikine ®, Hs. ELISA Human IL-1β/IL-1F2 Immunoassay. 20AD.
34.
Sari D, Zaimah Z, Lestari S, Hutagalung S. Ganie RA. Vitamin D supplementation in women with vitamin d receptor gene polymorphisms: a randomized controlled trial. Asian J Clin Nutr. 2017. p. 89–96.
35.
Sari D, Alrasyid H, Nurindrawaty L, Zulkifli L. Occurrence of vitamin D deficiency among women in North Sumatera, Indonesia. Mal J Nutr. 2014. p. 63–70.
36.
Tanumihardjo S, Muherdiyantiningsih, Permaesih D, Komala, Muhilal, Karyadi D. Daily supplements of vitamin A (8.4 μmol, 8000 IU) improve the vitamin A status of lactating Indonesian women. Am J Clin Nutr. 1996. p. 32–5.
37.
Golzarand M, Shab-Bidar S, Koochakpoor G, Speakman J, Djafarian K. Effect of vitamin D 3 supplementation on blood pressure in adults: An updated meta-analysis. Nutr Metab Cardiovasc Dis. 2016. p. 663–73.
38.
Hsia J, Heiss G, Ren H, Allison M, Dolan N, Greenland P, et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation. 2007. p. 846–54.
39.
Daraghmeh A, Bertoia M, Al-Qadi M, Abdulbaki A, Roberts M, Eaton C. Evidence for the vitamin D hypothesis: The NHANES III extended mortality follow-up. Atherosclerosis. 2016. p. 96–101.
40.
Christakos S, Ajibade D, Dhawan P, Fechner A, Vitamin M, D. metabolism. Endocrin Metab Clin. 2010. p. 243–53.
41.
Challoumas D. Vitamin D supplementation and lipid profile: What does the best available evidence show? Atherosclerosis. 2014. p. 130–9.
42.
Brough D, Galea J. The role of inflammation and interleukin-1 in acute cerebrovascular disease. J Inflamm Res. 2013. p. 121–8.
43.
Denes A, Pinteaux E, Rothwell N, Allan S. Interleukin-1 and Stroke: Biomarker, harbinger of damage, and therapeutic target. Cerebrovasc Dis. 2011. p. 517–27.
44.
Jain S, Buttar H, Chintameneni M, Kaur G. Prevention of cardiovascular diseases with anti-inflammatory and antioxidant nutraceuticals and herbal products: an overview of pre-clinical and clinical studies. Recent Pat Inflamm Allergy Drug Discov. 2018. p. 145–57.
45.
Kamal K, Majeed F, Naqvi I. Vitamin D supplementation for preventing recurrent stroke and vascular events in patients with stroke or transient ischemic attack (Protocol). Cochrane Database Syst Rev. 2012. p. 41–8.
46.
Lips P, Eekhoff M, Van Schoor N, Oosterwerff M, De Jongh R, Krul-Poel Y, et al. Vitamin D and type 2 diabetes. Steroid Biochem Mol Biol. 2017. p. 280–5.
47.
Michos E, Carson K, Schneider A, Lutsey P, Xing L, Sharrett A, et al. Vitamin D and subclinical cerebrovascular disease. JAMA Neurol. 2014. p. 863.
48.
Ren W, Gu Y, Zhu L, Wang L, Chang Y, Yan M, et al. The effect of cigarette smoking on vitamin D level and depression in male patients with acute ischemic stroke. Compr Psychiatry. 2015. p. 9–14.
49.
Chehaibi K, Trabelsi I, Mahdouani K, Slimane M. Correlation of oxidative stress parameters and inflammatory markers in ischemic stroke patients. J Stroke Cerebrovasc Dis. 2016. p. 2585–93.
50.
Poole K, Loveridge N, Barker P, Halsall D, Rose C, Reeve J, et al. Reduced Vitamin D in Acute Stroke. Stroke. 2006. p. 243–5.
51.
Penkert R, Jones B, Häcker H, Partridge J, Hurwitz J. Vitamin A differentially regulates cytokine expression in respiratory epithelial and macrophage cell lines. Cytokine. 2017. p. 1–5.
52.
Jimenez-Lara A, Aranda J. Interaction of vitamin D and retinoid receptors on regulation of gene expression. Horm Res. 2001. p. 301–5.
53.
Røsjø E, Myhr K, Løken-Amsrud K, Bakke S, Beiske A, Bjerve K, et al. Increasing serum levels of vitamin A, D and E are associated with alterations of different inflammation markers in patients with multiple sclerosis. J Neuroimmunol. 2014. p. 60–5.
54.
Barker T, Martins T, Hill H, Kjeldsberg C, Dixon B, Schneider E, et al. Vitamin D sufficiency associates with an increase in anti-inflammatory cytokines after intense exercise in humans. Cytokine. 2014. p. 134–7.
55.
Anand P, Kaul D, Sharma M. Synergistic action of vitamin D and retinoic acid restricts invasion of macrophages by pathogenic mycobacteria. J Microbiol Immunol Infect. 2008. p. 17–25.
56.
Park S, Lee I. The influence of age, lesion side and location on rehabilitation outcome after stroke. J Phys Ther Sci. 2011. p. 817–9.
57.
Belanger H. Recovery from stroke: factors affecting prognosis. Clin Neuropsychol. 2019. p. 813–6.

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