Tocotrienols, the vitamin E of the 21st century: its potential against cancer and other chronic diseases

Abstract

Initially discovered in 1938 as a "fertility factor," vitamin E now refers to eight different isoforms that belong to two categories, four saturated analogues (α, β, γ, and δ) called tocopherols and four unsaturated analogues referred to as tocotrienols. While the tocopherols have been investigated extensively, little is known about the tocotrienols. Very limited studies suggest that both the molecular and therapeutic targets of the tocotrienols are distinct from those of the tocopherols. For instance, suppression of inflammatory transcription factor NF-κB, which is closely linked to tumorigenesis and inhibition of HMG-CoA reductase, mammalian DNA polymerases and certain protein tyrosine kinases, is unique to the tocotrienols. This review examines in detail the molecular targets of the tocotrienols and their roles in cancer, bone resorption, diabetes, and cardiovascular and neurological diseases at both preclinical and clinical levels. As disappointment with the therapeutic value of the tocopherols grows, the potential of these novel vitamin E analogues awaits further investigation.

Figure 1

Chemical structure of tocotrienols and tocopherols

Figure 2

Figure 2a: Natural sources of tocotrienols. For reference see red annatto [10]; palm oil [198]; rice bran oil [199]; grape seed oil, maize, wheat germ oil [200]; hazel nut [201]; olive oil [202]; buckthorn berry [203]; rye [204]; oat and barley [205]; flax seed oil, poppy seed oil, safflower oil [206] Figure 2b: Content of tocotrienol and tocopherol isomers from various sources. For reference see http://www.tocotrienol.org/

Figure 2

Figure 2a: Natural sources of tocotrienols. For reference see red annatto [10]; palm oil [198]; rice bran oil [199]; grape seed oil, maize, wheat germ oil [200]; hazel nut [201]; olive oil [202]; buckthorn berry [203]; rye [204]; oat and barley [205]; flax seed oil, poppy seed oil, safflower oil [206] Figure 2b: Content of tocotrienol and tocopherol isomers from various sources. For reference see http://www.tocotrienol.org/

Figure 3

Figure 3a: Molecular targets of tocotrienols Figure 3b: Proteins that directly interact with tocotrienols

Figure 3

Figure 3a: Molecular targets of tocotrienols Figure 3b: Proteins that directly interact with tocotrienols

Figure 4

Physiological functions of tocotrienols