Research in the past decade shows that the commonly used non-desmethyl vitamin Es (e.g., alpha-tocopherol and alpha-tocotrienol) do not share the beneficial effects of desmethyl vitamin Es (e.g., gamma and delta isomers of tocopherols and tocotrienols). Research also shows that high levels of alpha-tocopherol may attenuate the bioavailability and functional activity of other vitamin E isomers. In general, desmethyl tocotrienols are much more bioactive than desmethyl tocopherols, especially in cancer inhibition. This paper delineates the role of desmethyl tocopherols and desmethyl tocotrienols in biological studies and in human health. A new perspective is presented for applications of delta-tocotrienol, gamma-tocotrienol, delta-tocopherol and gamma-tocopherol that are consistent with the emerging science of vitamin E. The paper concludes that formulated vitamin E should be “appropriate spectrum” and not merely “full spectrum” based on 35-40 mg of daily consumption (DC) of vitamin E in foods. Formulated “appropriate spectrum” vitamin E should more closely reflect the composition of our diet, and is therefore well suited for maintenance; (1X DC); prevention (10X DC) and treatment (50-200 mg/day desmethyl tocotrienols) formulations may require higher doses. Diversity brings out the best in unique cultures. This diversity can be appreciated not only in human societies but also in the plant kingdom. For example, there are in excess of 600 naturally occurring carotenoids in plants yet only a handful, namely beta-carotene, lycopene and lutein, are actively being researched. Similarly, there are more than twelve vitamin Es found in nature but only alpha-tocopherol is primarily being studied. This paper calls into question the suitability of unqualified use of large doses of alpha-tocopherol as well as the unqualified use of the “full spectrum” vitamin E. The advent of “appropriate spectrum” vitamin E for human health is a derivative concept1 from punctuated research development. This review addresses recent research developments to delineate the functional roles of desmethyl tocotrienols and desmethyl tocopherols apart from common alpha-tocopherol.
The effects of tocotrienols on murine liver cell viability and their apoptotic events were studied over a dose range of 0-32 microg mL(-1). Normal murine liver cells (BNL CL.2) and murine liver cancer cells (BNL 1ME A.7R.1) were treated with tocotrienols (T(3)), alpha tocopherol (alpha-T) and the chemo drug, Doxorubicin (Doxo, as a positive control). Cell viability assay showed that T(3) significantly (P < or = 0.05) lowered the percentage of BNL 1ME A.7R.1 cell viability in a dose-responsive manner (8-16 microg mL(-1)), whereas T did not show any significant (P>0.05) inhibition in cell viability with increasing treatment doses of 0-16 microg mL(-1). The IC(50) for tocotrienols were 9.8, 8.9, 8.1, 9.7, 8.1 and 9.3 microg mL(-1) at 12, 24, 36, 48, 60 and 72 hours respectively. Early apoptosis was detected 6 hours following T(3) treatment of BNL 1ME A.7R.1 liver cancer cells, using Annexin V-FITC fluorescence microscopy assay for apoptosis, but none were observed for the non-treated liver cancer cells at the average IC(50) of 8.98 microg mL(-1) tocotrienols for liver cancer cells. Several apoptotic bodies were detected in BNL 1ME A.7R.1 liver cancer cells at 6 hours post-treatment with tocotrienols (8.98 microg mL(-1)) using Acridine Orange/Propidium Iodide fluorescence assay. However, only a couple of apoptotic bodies were seen in the non-treated liver cancer cells and the BNL CL.2 normal liver cells. Some mitotic bodies were also observed in the T(3)-treated BNL 1ME A.7R.1 liver cancer cells but were not seen in the untreated BNL 1ME A.7R.1 cells and the BNL CL.2 liver cells. Following T(3)-treatment (8.98 microg mL(-1)) of the BNL 1ME A.7R.1 liver cancer cells, 24.62%, 25.53% and 44.90% of the cells showed elevated active caspase 3 activity at 9, 12 and 24 hours treatment period, respectively. DNA laddering studies indicated DNA fragmentation occurred in the T(3)-treated liver cancer cells, BNL 1ME A.7R.1 but not in non-treated liver cancer cells and the T(3)-treated and non-treated normal liver cells. These results suggest that tocotrienols were able to reduce the cell viability in the murine liver cancer cells at a dose of 8-32 microg mL(-1) and that this decrease in percentage cell viability may be due to apoptosis.