###### Abstract  
Although the current treatments for stroke and myocardial infarction contribute to an improvement in mortality rates, the consequences of reperfusion therapy have remained a challenge. Tocotrienols have been shown to exert beneficial effects on the brain and heart. This review aimed to determine the effects of tootrienols in cerebral and myocardial ischemia-reperfusion (I/R) injury. We retrieved articles from Scopus, MEDLINE and PubMed from inception to June 2021, and included any studies usingtoctrienols as a treatment for cerebral or myocardial I/R injury therapy. Observational studies and review articles were excluded, and the risk of bias was conducted using a specific tool for animal study (SYRCLE). The data were analyzed qualitatively. Twelve articles met the eligibility for animal study (SYRCLE). Tocotrienols significantly improved the structural, functional, and biochemical parameters in both cerebral and myocardial I/R injury models. In contrast, oxidative stress, inflammation, and apoptosis were markedly attenuated by locotrienol treatment. Limitations to the analysis included marked differences in animal models, disease inductions, forms of tocotrienols, and an unclear risk of bias in certain types of bias. However, tocotrienols have the potential to serve as a supplement for reducing the impact of reperfusion injury.  
myocardial infarction; stroke; locotrienols +
Footnote †: journal: Medical  
fromtocopherol in that it contains an isoprenoid side chain, making it polyunsaturated in nature [6]. Both isomers can be further classified, based on the amount and position of the methyl group in the chemical structures, into alpha, beta, gamma, and delta groups [7].  
A recent meta-analysis reported that vitamin E significantly reduced the risk of ischemic stroke but not hemorrhagic stroke [8]. However, this meta-analysis was limited to \(\alpha\)-tocopherol treatment, as the authors retrieved no studies on tocotrienols. Another meta-analysis reported the remarkable effects of vitamin E in reducing myocardial infarction when used alone at a high dose concentration [9]. Again, no clinical data is available concerning locotrienol supplementation for risk reduction.  
Results in pre-clinical studies have reported various beneficial effects of tocotrienols as a cardioprotective agent [10; 11; 12; 13; 14; 15; 16] and neuroprotective agent [17; 18; 19; 20; 21]. The effects vary across different types of tocotrienols, and the gamma-type has been observed to produce remarkable effects compared to other types as a cardioprotective agent [10; 11]. In contrast, a study using the cerebral ischemia-reperfusion (I/R) injury model reported that \(\alpha\)- and \(\gamma\)-tocopherol and \(\alpha\)-tocotrienol are neuroprotective. The latter two were found to be more potent than \(\alpha\)-tocopherol [18]. The mechanisms of the protective effects of tocotrienols in cerebral and myocardial I/R injuries are attributable to their antioxidative, anti-inflammatory, and anti-apoptotic activities, making the brain and heart more resistant toward I/R injury [10; 11; 13; 14; 15; 17; 19; 20; 21].  
Given their significant positive impact on the brain and heart, tocotrienols have a huge potential to be used as a supplement or incorporated into a diet as part of cerebral and coronary ischemic disease prevention and management. To our knowledge, no systematic review has been conducted that focuses on the effects of tocotrienol on both cerebral and myocardial I/R injury. Therefore, a systematic approach to analyzing the current state of evidence, drawing conclusions on the significance of tocotrienol use and addressing the current limitations for future research, is indispensable. This review aimed to determine the effects of tocotrienols on the structural, functional, biochemical, and other possible signaling mechanisms of tocotrienol-induced neuroprotection and cardioprotection, in cerebral and myocardial I/R injury models.