Tocotrienol research: past into present Rebecca SY Wong and Ammu K Radhakrishnan The vitamin E family consists of eight isomers known as alpha-, beta-, gamma-, and delta-tocopherols and alpha-, beta-, gamma-, and delta-tocotrienols. Numerous studies focused on the health benefits of these isomers have been performed since the discovery of vitamin E in 1922. Recent discoveries on the potential therapeutic applications of tocotrienols have revolutionized vitamin E research. Nevertheless, despite the abundance of literature, only 1% of vitamin E research has been conducted on tocotrienols. Many new advances suggest that the use of tocotrienols for health improvement or therapeutic purposes is promising. Although the mechanisms of action of tocotrienols in certain disease conditions have been explored, more detailed investigations into the fundamentals of the health- promoting effects of these molecules must be elucidated before they can be recommended for health improvement or for the treatment or prevention of disease. Furthermore, many of the studies on the effects of tocotrienols have been carried out using cell lines and animal models. The effects in humans must be well established before tocotrienols are used as therapeutic agents in various disease conditions, hence the need for more evidence-based human clinical trials. © 2012 International Life Sciences Institute INTRODUCTION Vitamin E is an important nutrient in the human diet and is a well-known antioxidant that is readily available in lipid-rich plant products. Historically, drug discovery research has focused on natural products, some of which are huge reservoirs of biological com- pounds with pharmacologic properties. 1 Since the discovery of vitamin E in 1922, many studies have focused on the potential health benefits and therapeutic use of the two main forms of vitamin E, namely, tocopherols and tocotrienols. Tocotrienols represent a very important part of the vitamin E family. How- ever, most of the vitamin E research has focused on alpha-tocopherols, and only 1% of vitamin E studies have investigated tocotrienols. 2 Several studies have reported that tocotrienols may have more potent antioxidation 3 and anticancer effects 4,5 than tocopherols. Studies have also reported that tocotrienols possess lipid-lowering, 6–10 antiatherogenic, 11,12 blood-pressure- lowering, 13,14 antidiabetic, 15–17 neuroprotective, 18–20 and anti-inflammatory 21 effects. The abundance of literature suggests that the use of tocotrienols for therapeutic pur- poses is very promising. The health benefits of toco- trienols have been reviewed previously, 2,22 but the rapid expansion of the literature on tocotrienol research and the more recent discoveries pertaining to the benefits of tocotrienols necessitate frequent updates on this topic. This review, therefore, aims to provide an overview that includes the major discoveries of the past as well as the more recent advances in tocotrienol-related health benefits. Affiliations: RSY Wong is with the Division of Human Biology, School of Medical and Health Sciences, International Medical University, Kuala Lumpur, Malaysia, and the School of Biosciences, Division of Medicine, Pharmacy and Health Sciences, Taylor’s University, Selangor, Malaysia. AK Radhakrishnan is with the Department of Pathology, School of Medical and Health Sciences, International Medical University, Kuala Lumpur, Malaysia. Correspondence: RSY Wong, Division of Human Biology, School of Medical and Health Sciences, International Medical University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia; E-mail: rebeccawongsy@gmail.com; RebeccaShinYee.Wong@taylors.edu. my. Phone: +603-2731-7281. Fax: +603-8656-7229. Key words: health-promoting benefits, therapeutic applications, tocotrienols, vitamin E Lead Article doi:10.1111/j.1753-4887.2012.00512.x Nutrition Reviews® Vol. 70(9):483–490 483