Shifting Perspectives on the Role of Tocotrienol vs. Tocopherol in Brain Health: A Scoping Review.

Vitamin E has been extensively studied for its neuroprotective properties, with increasing evidence supporting its broader roles in brain health. This scoping review aims to systematically identify, analyze, and synthesize evidence of the existing literature over the last 10 years on tocotrienol and tocopherol supplementation in humans. A systematic search was conducted across PubMed, Scopus, and EBSCOhost yielding 42 eligible articles. Findings suggest that tocopherols, especially α- and γ-forms, are associated with improved cognitive performance, reduced neuroinflammation, and preservation of synaptic proteins. Despite tocotrienol's lower plasma bioavailability, tocotrienol availability in selective brain regions has been associated with structural protection, particularly in white matter. Both compounds exhibit complementary effects, suggesting a potential advantage of combined supplementation. However, heterogeneity in study designs, subject characteristics, dosage, duration, and assessment methods limit direct comparisons and generalizability of findings. Based on our review's findings, further research such as dose-optimization, long-term exposures, and delivery methods on human studies should be performed. This review highlights the multifaceted roles of vitamin E in brain health and underscores the urgent need for well-designed studies to clarify the distinct and synergistic effects of tocopherols and tocotrienols, particularly in human populations.