Tocotrienol: The Biologically Effective Vitamin E
Tocopherol was first identified by Evans in 1922 when he found that without tocopherol, female rats could not reproduce and resorbed its fetus. For the longest time, the vitamin E family is thought to be comprised of a single molecule – alpha-tocopherol. More than 40 years after the discovery of tocopherols, tocotrienols were first isolated by R.A. Morton in 1965.
Tocotrienols are the other half of the vitamin E family. Like tocopherols, tocotrienols support fertility  and provide antioxidant protection for all living cells.  These common attributes between tocotrienols and tocopherols reflect the similarity in their chemical structures. Both tocotrienols and tocopherols each have four homologues with four different chromonal heads: alpha (a), beta (b), gamma (g), and delta (d) ─ making up the eight members of the vitamin E family and each is associated with distinct health benefits.
Each tocopherol homologue has a tocotrienol counterpart with the same chromonal head, but with the difference being in the three unsaturated bonds in the tocotrienol side chain as compared to fully saturared side chain of the tocopherols.
Behind the tail
Tocopherol’s fully saturated hydrocarbon tail is straight throughout its length and allows the tocopherol molecule to be bound tightly by covalence bonding to the other phospholipids in the cell membrane bilayer and to stay within the membrane bilayer. Each of tocotrienol’s unsaturated bonds on the other hand causes a 30° kink in the tail. Because of the kinks in the tails where double bonds are located, unsaturated hydrocarbon tails cannot pack together as closely as saturated hydrocarbon tails, and this makes the membrane bi-layer more fluid and allows tocotrienols to penetrate the membrane bi-layer.
There is substantial evidence that tocotrienols may be more efficient free radical scavengers in cell membranes than the corresponding tocopherols. Tocotrienols were found by scientists from the University of California Berkely to have 40 to 60 times more powerful antioxidation properties in cells or biological systems than tocopherol.  Lester Packer, one of the foremost antioxidant researchers from the University of California Berkely, explained that the greater antioxidant activity of alpha-tocotrienol than alpha-tocopherol results from the following :
· More uniform distribution in membrane bilayer
· Stronger disordering of membrane lipids
· More effective collision with radicals
· Greater recycling activity of chromanoxyl radical
· Recycling activity correlates with inhibition of lipid peroxidation
Antioxidants that show high antioxidation power in in vitro chemical reactivity tests do not necessarily perform well in the body due to low bioavailability and/or absorption or uptake by the cells. In cell membranes, the mobility of the molecule becomes important, and this depends on the structure of the hydrophobic side chain. Other scientists from the National Institute of Advanced Industrial Science and Technology in Japan have also found that there is much higher initial uptake of tocotrienol by cells of up to 70 times more than alpha tocopherol, as tocotrienol’s unsaturated tail structure allows rapid cellular incorporation for higher antioxidation activity. 
Tocotrienol is a natural form of vitamin E derived from certain plant seeds. Being an essential vitamin, tocotrienols and tocopherols are not synthesized by the body; thus, it has to be obtained from the diet. Lack of vitamin E can cause nerve damage, blood disorders and infertility.
Common sources of tocotrienol. Image from Aggarwal, et al. Tocotrienols, the vitamin E of the 21st century: its potential against cancer and other chronic diseases. Biochem Pharmacol, 2010. Click on image for full view.
Tocopherols and tocotrienols are found naturally in various types of plant seeds, ranging from wheat, rice, soybean, palm and grape seed to peanut, walnut and pecan. Most of these seeds contain only tocopherols; only a few contain both forms. Tocotrienols are found mainly in palm fruit and wheat and rice bran in the hard outer layer beneath the husk. Research has shown that tocotrienol possesses unique biophysical properties that provide greater antioxidation and health benefits than the alpha-tocopherol form of vitamin E. Palm fruit has one of the richest sources of tocotrienols and red palm oil is recommended by Dr. Oz for its tocotrienols.
Identified health benefits
Increasingly, scientific research has shown that the tocotrienol form of vitamin E possesses biophysical properties and health benefits beyond its antioxidation activity and the alpha-tocopherol form of vitamin E. Over 900 research studies on tocotrienols (as listed on PubMed) have been published that show tocotrienols provide health benefits for anti-cancer wellness, cardiovascular, metabolic and skin health, neuroprotection, radiation protection and anti-inflammation.
It is well established that chronic inflammation is one of the underlying causes for many modern day human diseases, including cardiovascular disease, inflammatory bowel disease and cancer. Some of the causes for the chronic inflammation include obesity, diet, environmental triggers, viruses, bacteria and autoimmune/genetic reasons.
Tocotrienol has anti-inflammatory properties not only because it is a powerful antioxidant, but also because of its ability to down-regulate many of the cytokines that control the body’s inflammation. Tocotrienol especially its gamma form is found to have anti-cancer and anti-inflammatory properties. Pre-clinial studies by scientists at the MD Anderson Centre have shown that gamma-tocotrienol can regulate key inflammatory pathway transcrition factors such as TNF-a , NFкβ  and the STAT3  which are elevated in certain inflammatory diseases.
Read more about tocotrienol’s anti-inflammation properties
According to the WHO, 40% of cancers are preventable.  Results of pre-clinical studies show that tocotrienol possesses apoptotic, anti-angiogenic and anti-proliferative effects on certain cancer cell types including breast, colon, pancreatic and prostate cancer cells. 
For example, in a study by Davos Life Science published in the International Journal of Cancer (July 2010), gamma-tocotrienol prevented prostate cancer from forming in 75% of the mice implanted with prostate cancer cells, as compared to 100% cancer tumour formation in the control group. The study showed that gamma tocotrienol targeted not only normal prostate cancer cells but also a small group of cancer stem cell unaffected by docetaxel, a chemotherapy drug.  Cancer stem cells are believed to be involved in the initiation and recurrence of cancer. Phase I/II trials using tocotrienol are currently being conducted in castration resistant prostate cancer (gamma rich tocotrienol), stage IV breast cancer (gamma rich tocotrienol) and resectable pancreatic cancer subjects (delta tocotrienol from palm).
Read more about tocotrienol’s anti-cancer effects
Cholesterol and Triglyceride Lowering
Unlike tocopherol, tocotrienol can down-regulate 3-hydroxyl-3-methylglutaryl-coenzyme A (HMG CoA) reductase, a key enzyme of the mevalonate pathway for the production of cholesterol in the body and the same protein targeted by anti-cholesterol drugs. A clinical study also showed that it could reduce the level of triglycerides by 28%. 
Read more about tocotrienol’s cholesterol-lowering properties
Studies in in-vivo animal studies show that alpha tocotrienol could substantially reduce the size of induced ischemic strokes. A clinical study showed reduction of white matter lesions (WML) in subjects taking palm tocotrienols which has alpha tocotrienol as compared to an increase in WML in the placebo control group. 
Apart from its anti-inflammation, anti-cancer and cholesterol-lowering properties, studies have shown that tocotrienols provide radiation protection and overall skin wellness.
Read Top Articles
1. Khanna, S., et al., Delivery of orally supplemented alpha-tocotrienol to vital organs of rats and tocopherol-transport protein deficient mice. Free Radic Biol Med, 2005. 39(10): p. 1310-9.
2. Tomeo, A.C., et al., Antioxidant effects of tocotrienols in patients with hyperlipidemia and carotid stenosis. Lipids, 1995. 30(12):1179-83.
3. Serbinova E, K.V., Han D and Packer L, Free radical recycling and intramembrane mobility in the antioxidant properties of alpha-tocopherol and alpha-tocotrienol. . Free Radic Biol Med 1991. 10(5): p. 263-75. .
4. Packer, L., S.U. Weber, and G. Rimbach, Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling. J Nutr, 2001. 131(2): 369S-73S.
5. Aggarwal BB, A.K., Sundaram C, Prasad S, Kannappan R., Tocotrienols, the vitamin E of the 21st century: its potential against cancer and other chronic diseases. Biochem Pharmacol, 2010. 80(11):1613-31.
6. Ahn, K.S., et al., Gamma-tocotrienol inhibits nuclear factor-kappaB signaling pathway through inhibition of receptor-interacting protein and TAK1 leading to suppression of antiapoptotic gene products and potentiation of apoptosis. J Biol Chem, 2007. 282(1): 809-20.
7. Kannappan, R., V.R. Yadav, and B.B. Aggarwal, gamma-Tocotrienol but not gamma-tocopherol blocks STAT3 cell signaling pathway through induction of protein-tyrosine phosphatase SHP-1 and sensitizes tumor cells to chemotherapeutic agents. J Biol Chem, 2010. 285(43):33520-8.
8. WHO., The World Health Organization’s Fight Against Cancer Strategies that Prevent Cure and Care. 2007.
9. Yap, W.N., et al., Id1, inhibitor of differentiation, is a key protein mediating anti-tumor responses of gamma-tocotrienol in breast cancer cells. Cancer Lett, 2010. 291(2):187-99.
10. Luk, S.U., et al., Gamma-tocotrienol as an effective agent in targeting prostate cancer stem cell-like population. Int J Cancer, 2011. 128(9):2182-91.
11. Zaiden N, Y.W., Ong S, Xu C, Teo V, Chang C, Zhang X, Nesaretnam K, Shiba S and Yap Y: , Gamma Delta Tocotrienols Reduce Hepatic Triglyceride Synthesis and VLDL Secretion. . J Atheroscler Thromb. , 2010.
12. Rink, C., et al., Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis. J Cereb Blood Flow Metab, 2011. 31(11):2218-30.