Author(s)

Hanlin Cao ¹, Junting Yang ¹, Furong Zheng ², Gongwei Jia ¹

Affiliation(s)

¹ Department of Rehabilitation, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
² Hubei Maternal and Child Health Hospital, Wuhan, Hubei, 430070, China

Corresponding Author

Gongwei Jia

ABSTRACT

Oxidative stress may contribute to post-stroke injury, but whether circulating diet-derived antioxidants influence functional recovery remains uncertain. We used two-sample Mendelian randomization to examine associations of genetically predicted absolute or metabolite concentrations of ascorbate, retinol, β-carotene, lycopene, α-tocopherol, and γ-tocopherol with poor functional outcome after ischemic stroke. Outcome summary statistics were obtained from the GISCOME genome-wide association study. Inverse-variance weighted analysis was the primary method; weighted median, MR-Egger, heterogeneity, and pleiotropy analyses were performed where instrument numbers permitted. Most estimates showed no clear association. Higher genetically predicted absolute retinol was nominally associated with lower odds of poor outcome (OR 0.094, 95% CI 0.012–0.710; P=0.022), although this estimate was based on only two variants. No clear associations were observed for the other antioxidants or metabolite measures. These findings do not support a general protective association; the retinol signal requires replication with stronger instruments and independent outcome data.

KEYWORDS

Ischemic Stroke; Functional outcome; Circulating antioxidants; Retinol; Mendelian randomization; Rehabilitation

CITE THIS PAPER

Hanlin Cao, Junting Yang, Furong Zheng, Gongwei Jia. Diet-Derived Circulating Antioxidants and Functional Outcome after Ischemic Stroke: A Two-Sample Mendelian Randomization Study. MEDS Basic Medicine (2026). Vol. 4, No. 1, 140-149. DOI: http://dx.doi.org/10.23977/medbm.2026.040118.

REFERENCES

[1] Feigin VL, Stark BA, Johnson CO, et al. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021;20(10):795-820. doi:10.1016/S1474-4422(21)00252-0.
[2] Ren JX, Li C, Yan XL, Qu Y, Yang Y, Guo ZN. Crosstalk between oxidative stress and ferroptosis/oxytosis in ischemic stroke: possible targets and molecular mechanisms. Oxid Med Cell Longev. 2021;2021:6643382. doi:10.1155/2021/6643382.
[3] Kahles T, Brandes RP. NADPH oxidases as therapeutic targets in ischemic stroke. Cell Mol Life Sci. 2012;69(14):2345-2363. doi:10.1007/s00018-012-1010-8.
[4] Kamal FZ, Lefter R, Jaber H, et al. The role of potential oxidative biomarkers in the prognosis of acute ischemic stroke and the exploration of antioxidants as possible preventive and treatment options. Int J Mol Sci. 2023;24(8):7136. doi:10.3390/ijms24087136.
[5] Lawlor DA, Harbord RM, Sterne JAC, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27(8):1133-1163. doi:10.1002/sim.3034.
[6] Loh HC, Lim R, Lee KW, et al. Effects of vitamin E on stroke: a systematic review with meta-analysis and trial sequential analysis. Stroke Vasc Neurol. 2021;6(1):109-120. doi:10.1136/svn-2020-000519.
[7] Rabadi MH, Kristal BS. Effect of vitamin C supplementation on stroke recovery: a case-control study. Clin Interv Aging. 2007;2(1):147-151. doi:10.2147/ciia.2007.2.1.147.
[8] Polidori MC, Cherubini A, Stahl W, et al. Plasma carotenoid and malondialdehyde levels in ischemic stroke patients: relationship to early outcome. Free Radic Res. 2002;36(3):265-268. doi:10.1080/10715760290019273.
[9] Ozkul A, Akyol A, Yenisey C, et al. Oxidative stress in acute ischemic stroke. J Clin Neurosci. 2007;14(11):1062-1066. doi:10.1016/j.jocn.2006.11.008.
[10] Cherubini A, Ruggiero C, Polidori MC, Mecocci P. Potential markers of oxidative stress in stroke. Free Radic Biol Med. 2005;39(7):841-852. doi:10.1016/j.freeradbiomed.2005.06.025.
[11] Daga MK, Madhuchhanda, Mishra TK, Mohan A. Lipid peroxide, beta-carotene and alpha-tocopherol in ischaemic stroke and effect of exogenous vitamin E supplementation on outcome. J Assoc Physicians India. 1997;45(11):843-846. PMID:11229181.
[12] Kadri A, Sjahrir H, Sembiring RJ, Ichwan M. Combination of vitamin A and D supplementation for ischemic stroke: effects on interleukin-1ß and clinical outcome. Med Glas (Zenica). 2020;17(2):425-432. doi:10.17392/1137-20.
[13] Soderholm M, Pedersen A, Lorentzen E, et al. Genome-wide association meta-analysis of functional outcome after ischemic stroke. Neurology. 2019;92(12):e1271-e1283. doi:10.1212/WNL.0000000000007138.
[14] Major JM, Yu K, Wheeler W, et al. Genome-wide association study identifies common variants associated with circulating vitamin E levels. Hum Mol Genet. 2011;20(19):3876-3883. doi:10.1093/hmg/ddr296.
[15] Zheng JS, Luan J, Sofianopoulou E, et al. Plasma vitamin C and type 2 diabetes: genome-wide association study and Mendelian randomization analysis in European populations. Diabetes Care. 2021;44(1):98-106. doi:10.2337/dc20-1328.
[16] Mondul AM, Yu K, Wheeler W, et al. Genome-wide association study of circulating retinol levels. Hum Mol Genet. 2011;20(23):4724-4731. doi:10.1093/hmg/ddr387.
[17] Hendrickson SJ, Hazra A, Chen C, et al. beta-Carotene 15,15'-monooxygenase 1 single nucleotide polymorphisms in relation to plasma carotenoid and retinol concentrations in women of European descent. Am J Clin Nutr. 2012;96(6):1379-1389. doi:10.3945/ajcn.112.034934.
[18] D'Adamo CR, D'Urso A, Ryan KA, et al. A common variant in the SETD7 gene predicts serum lycopene concentrations. Nutrients. 2016;8(2):82. doi:10.3390/nu8020082.
[19] Shin SY, Fauman EB, Petersen AK, et al. An atlas of genetic influences on human blood metabolites. Nat Genet. 2014;46(6):543-550. doi:10.1038/ng.2982.
[20] Long T, Hicks M, Yu HC, et al. Whole-genome sequencing identifies common-to-rare variants associated with human blood metabolites. Nat Genet. 2017;49(4):568-578. doi:10.1038/ng.3809.
[21] Bowden J, Davey Smith G, Haycock PC, Burgess S. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol. 2016;40(4):304-314. doi:10.1002/gepi.21965.
[22] Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512-525. doi:10.1093/ije/dyv080.
[23] Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013;37(7):658-665. doi:10.1002/gepi.21758.
[24] Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50(5):693-698. doi:10.1038/s41588-018-0099-7.
[25] Kamat MA, Blackshaw JA, Young R, et al. PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations. Bioinformatics. 2019;35(22):4851-4853. doi:10.1093/bioinformatics/btz469.
[26] Tu WJ, Qiu HC, Zhang Y, et al. Lower serum retinoic acid level for prediction of higher risk of mortality in ischemic stroke. Neurology. 2019;92(15):e1678-e1687. doi:10.1212/WNL.0000000000007250.
[27] De Keyser J, De Klippel N, Merkx H, Vervaeck M, Herroelen L. Serum concentrations of vitamins A and E and early outcome after ischaemic stroke. Lancet. 1992;339(8809):1562-1565. doi:10.1016/0140-6736(92)91828-4.

Sponsors, Associates, and Links

---

• MEDS Clinical Medicine
  
  
• Journal of Neurobiology and Genetics
  
  
• Medical Imaging and Nuclear Medicine
  
  
• Bacterial Genetics and Ecology
  
  
• Transactions on Cancer
  
  
• Journal of Biophysics and Ecology
  
  
• Journal of Animal Science and Veterinary
  
  
• Academic Journal of Biochemistry and Molecular Biology
  
  
• Transactions on Cell and Developmental Biology
  
  
• Rehabilitation Engineering & Assistive Technology
  
  
• Orthopaedics and Sports Medicine
  
  
• Hematology and Stem Cell
  
  
• Journal of Intelligent Informatics and Biomedical Engineering
  
  
• MEDS Stomatology
  
  
• MEDS Public Health and Preventive Medicine
  
  
• MEDS Chinese Medicine
  
  
• Journal of Enzyme Engineering
  
  
• Advances in Industrial Pharmacy and Pharmaceutical Sciences
  
  
• Bacteriology and Microbiology
  
  
• Advances in Physiology and Pathophysiology
  
  
• Journal of Vision and Ophthalmology
  
  
• Frontiers of Obstetrics and Gynecology
  
  
• Digestive Disease and Diabetes
  
  
• Advances in Immunology and Vaccines
  
  
• Nanomedicine and Drug Delivery
  
  
• Cardiology and Vascular System
  
  
• Pediatrics and Child Health
  
  
• Journal of Reproductive Medicine and Contraception
  
  
• Journal of Respiratory and Lung Disease
  
  
• Journal of Bioinformatics and Biomedicine