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In this blog I would like to re-introduce a topic that was written for us a few years ago by Dr Barrie Tan , his area of expertise is research into Tocotrienols. Before you read Dr Tan’s very informative piece on Tocotrienols I would like to point that as a result of working Dr Tan we only use Delta-Gold as our source of Vitamin E in Reflex products, I think I’m correct in saying we are the only sports nutrition company in the World to be in this pioneering position.
You’ll understand why once you read this post & watch the video:
“Since the early 20th century, life expectancy has increased at an astonishing rate.
While just a century ago we were faced with pathogenic challenges and high infant mortality, we are now confronted with an entirely different problem – we are growing older than ever before. Ageing brings with it both the joys of an extended lifespan and the difficulty of having to cope with its associated chronic challenges. The move from a pathogenic to a chronic challenge is synonymous with a shift in healthcare focus to a prevention model that anticipates adult onset conditions such as cardiovascular disease, diabetes and metabolic syndrome, loss of vision, cancer, and – a dilemma most discernibly associated with ageing – the wrinkling and damage of the skin.
In theory, ageing is a process linked to the cumulative damage free radicals cause in the body over time. While unsaturated lipids in cell membranes are particularly susceptible to the unstable and highly reactive free radicals, antioxidants such as vitamin E have long been known to counteract such oxidative processes. Surprising as it may be, vitamin E is much more than simply an antioxidant, and addresses a variety of chronic conditions linked to ageing.
What is Vitamin E ?
Vitamin E was first discovered in 1922 by Dr. Herbert Evans, and was dubbed the “birth vitamin” to convey its important task in the prevention of fetal resorption. Although often misconstrued as a single entity, vitamin E is a family of two major subgroups, tocopherols and tocotrienols, with each subgroup containing four similar molecules (alpha-, beta-, gamma-, delta- tocopherols and tocotrienols). At first glance they all look exactly the same, fitting the description of a tadpole with a prominent “head” and a “tail”. While nuances in the head structure destine a vitamin E molecule to be an alpha-, beta-, gamma-, or delta-form, the length of the molecule’s tail determines whether a vitamin E molecule belongs to the tocopherol or tocotrienol subfamily. Tocotrienols have a shorter unsaturated tail with double bonds and are more flexible, while tocopherols have a longer saturated tail without double bonds and are less flexible. With the added flexibility afforded to tocotrienols, this vitamin E subfamily exhibits benefits of cholesterol lowering, improving overall cardiovascular and metabolic health, and more recently, cancer kill.
Tocotrienols Are Superior Antioxidants
The so-called “chromanol” head is the fundamental unit of vitamin E, and is also the location of antioxidant activity. The shape of the head also determines how easily a molecule can access the cell membrane. In general, gamma- and delta- (collectively entitled desmethyl-) heads are smaller, and have greater access to cell membranes, treating damage faster. Hence, they are usually more potent in delivering benefits. Several studies have confirmed the order of potency to be delta- > gamma- > alpha- tocotrienol or tocotrienol mixtures >> alpha-tocopherol [1-5]
. For example, ORAC (oxygen radical absorbance capacity) studies at Brunswick Laboratories/Massachusetts compared the antioxidant value of the tocopherol-free delta- and gamma-tocotrienol (DeltaGold®) to tocopherol and mixed tocotrienols, and found that DeltaGold’s antioxidant potential is much higher than that of the other compounds studied. In addition, the Ohio State University found that delta- and gamma-tocotrienol (as in DeltaGold®) protect lard from oxidation at low levels of just 100ppm (parts per million) [6, 7]
Ordinarily, the popular alpha-tocopherol comes to mind in relation to vitamin E’s antioxidant fame. The fact, however, is that tocotrienol is a 40-60 times more potent antioxidant than tocopherol, which was shown by Dr. Lester Packer of the University of California/Berkeley 
. The superior antioxidant capacity of tocotrienol is attributed to its greater flexibility, which permits added mobility to cover a larger surface area of cell membranes..
Tocotrienol’s Cardiovascular Benefits
Currently, tocotrienol is most well-known for its cholesterol-lowering properties, its claim to fame when discovered in the 1980’s 
. Numerous studies since have demonstrated that tocotrienols lower LDL cholesterol and triglyceride levels.
The first clinical study on tocotrienol was performed in 1991 at the University of Wisconsin/Madison. In this study, patients initially received 200mg/day tocotrienol-tocopherol mixture. Total cholesterol and LDL cholesterol dropped 15-22% and 10-20%, respectively. However, 15% of the patients did not show improvement, and because of the greater effectiveness of delta- and gamma-tocotrienol, these patients were continued on a high delta- and gamma-tocotrienol supplement (100mg/day). Following 4 weeks of supplementation, the total cholesterol in these initially non-responsive patients dropped 35-40% 
In 1993, Bristol Myers Squibb found in an internal study that 100mg of delta- and gamma-tocotrienol per day reduced total and LDL cholesterol by 20-25% and triglycerides by 15-20%. In this study, delta-tocotrienol was the most effective of the tocotrienols.
Clinical studies also determined the optimal dose of tocotrienol for cholesterol and triglyceride reduction to be 75-100mg/day 
. Tocotrienol reduces cholesterol by down-regulating the enzyme responsible for its production in the liver [3, 12]
. This is a safe route of addressing cholesterol as compared to statin with its damaging side effects.Although cholesterol management is important for heart health, there are 30,000 miles of arteries that need protection for proper functions. Tocotrienols control inflammatory mechanisms and markers, including reduction of atherogenic lipoprotein(a)[Lp(a)]
and inhibition of the sticky adhesion molecules 
present in early stages of atherosclerosis. Bacterial infections contribute to the body’s inflammatory response, and tocotrienols have been shown to reduce infection by Chlamydia 
, a bacterium that has been found in atherosclerotic tissue and exacerbates inflammation 
. In short, tocotrienols promote arterial health.
Consumption of tocotrienols has been associated with reduced risk of coronary heart disease, regression of carotid artery stenosis in humans in a 4-year study 
, reduced susceptibility to ischemia-induced arrhythmia, and reduced heart rate accompanied by improved myocardial efficiency [17, 18]
Tocotrienol in Diabetes and Metabolic Syndrome
The statistics on obesity are shocking: globally, there are more than 1 billion overweight adults, and at least 300 million of them are obese 
. Obesity gives way to a cluster of dangerous cardiovascular risk factors including elevated blood pressure, triglycerides, blood sugar, and insulin resistance, all hallmarks of a condition referred to as metabolic syndrome or pre-diabetes. Drawing from clinical studies, tocotrienols are regarded as excellent candidates in a prevention model for metabolic syndrome. Tocotrienols safely address the three areas of atherogenic dyslipidemia: reduction of triglyceride levels, moderate increase of HDL cholesterol, and reduction of LDL cholesterol. In addition, there is evidence in animal studies that tocotrienol reduces blood pressure 
, arterial plaques 
, adhesion molecules 
, and blood sugar 
, all signs of metabolic syndrome.
A New Angle: Eye Health
Tocotrienols may have application in improving eye conditions, especially those of angiogenic nature. In macular degeneration, central vision loss occurs due to neovascularization in the retina beneath the macula, and leaking blood vessels push up the retina. Similarly, diabetic retinopathy is caused by damage to blood vessels of the retina, and is the leading cause of adult blindness. In both cases, angiogenesis – the aberrant growth of new blood vessels – is to blame. Recent studies found tocotrienol to be a superb anti-angiogenic agent, with delta-tocotrienol being the most potent and reducing angiogenesis in a dose-dependent manner [22, 23]
Breakthroughs in Cancer Research
In the context of cancer, angiogenesis is also the fundamental culprit in malignant tumor formation. A variety of studies, especially from the Tohoku University in Japan, show that tocotrienols curb angiogenesis, essentially starving the tumors to death [22, 23]
. Of the tocotrienol isomers, delta is the most potent in cancer application, since it is the most potent cholesterol-producing enzyme inhibitor, the most potent anti-inflammatory and anti-angiogenic agent, and has recently been found to have an elegant key-lock structure for breast cancer 
. Delta-tocotrienol is now also in Phase I clinical trials for the treatment of pancreatic cancer, the deadliest type of cancers [25, 26]
Tocotrienols and Skin Health
One of the obvious signs of ageing is skin wrinkling due to prolonged oxidative damage. Aside from being an excellent antioxidant, tocotrienol has been shown to reduce UVB-induced skin damage [27, 28]
, inhibit melanoma cell growth, and produce tumor retardation in mice with highly metastatic melanoma 
. Tocotrienols also reduce skin pigmentation 
. The skin is exposed to many elements of the environment, both inside (endothelium) and outside (epithelium). Tocotrienols are preferentially deposited in these skin tissues for their protection 
About DeltaGold® Annatto Tocotrienol
DeltaGold® contains the wholesome rainforest annatto-derived tocotrienols that have a high concentration of the most effective component of tocotrienols, delta-tocotrienol, using a patented solvent-free extraction method. Annatto tocotrienol contains 90% delta-tocotrienol and 10% gamma-tocotrienol, and better yet, it is tocopherol-free. The composition of tocopherol-free tocotrienol in annatto is unique among the plant kingdom. This uniqueness is preserved in DeltaGold®.
Alpha-tocopherol, which is a popular ingredient in most supplements and is also present in palm- and rice-derived tocotrienol supplements, interferes with the function of tocotrienol. Due to this conflict, tocotrienols should be taken at least six hours apart from a tocopherol product, and preferably in the evening with dinner. Researchers concluded that effective tocotrienol preparations should contain less than 15% of alpha-tocopherol and more than 60% of desmethyl tocotrienols (referring only to gamma- and delta-tocotrienol). Absence of alpha-tocopherol such as in DeltaGold® is unmatched.
DeltaGold® owes its superior functions to a unique composition, one that earns it star power in the field of anti-ageing medicine. Indeed, it is the 21st century vitamin E!”
Thank you Barrie for a great article on an ingredient that features heavily throughout the Reflex Nutrition range, especially in Sports Anti Oxidants. I’m sure our readers now have a much greater understanding of why it’s important to look for Tocotrienols in preference to Tocopherols.
References 1. McIntyre, B.S., et al., Antiproliferative and apoptotic effects of tocopherols and tocotrienols on preneoplastic and neoplastic mouse mammary epithelial cells. Proc Soc Exp Biol Med, 2000. 224(4): p. 292-301. 2. Naito, Y., et al., Tocotrienols reduce 25-hydroxycholesterol-induced monocyte-endothelial cell interaction by inhibiting the surface expression of adhesion molecules. Atherosclerosis, 2005. 180(1): p. 19-25. 3. Pearce, B.C., et al., Hypocholesterolemic activity of synthetic and natural tocotrienols. J Med Chem, 1992. 35(20): p. 3595-606. 4. Sylvester, P.W. and S.J. Shah, Mechanisms mediating the antiproliferative and apoptotic effects of vitamin E in mammary cancer cells. Front Biosci, 2005. 10: p. 699-709. 5. Yu, S.G., et al., Dose-response impact of various tocotrienols on serum lipid parameters in 5-week-old female chickens. Lipids, 2006. 41(5): p. 453-61. 6. Kim, H.J., Oxidation mechanism of riboflavin destruction and antioxidant mechanism of tocotrienols., in PhD Dissertation. 2007: Food Science and Nutrition. Columbus, The Ohio State University. 7. Kim, H.J. and D.B. Min, Effects, quenching mechanisms, and kinetics of alpha-, beta-, gamma-, and delta-tocotrienol on chlorophyll photosynthesized oxidation of lard., in IFT. 2007. 8. Serbinova, E., et al., 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. 9. Qureshi, A.A., et al., The structure of an inhibitor of cholesterol biosynthesis isolated from barley. J Biol Chem, 1986. 261(23): p. 10544-50. 10. Qureshi, A.A., et al., Lowering of serum cholesterol in hypercholesterolemic humans by tocotrienols (palmvitee). Am J Clin Nutr, 1991. 53(4 Suppl): p. 1021S-1026S. 11. Tan, B. and A.M. Mueller, Tocotrienols in Cardiometabolic Diseases., in Tocotrienols: Vitamin E beyond Tocopherol, R. Watson and V. Preedy, Editors. 2008, AOCS/CRC Press. p. 257-273. 12. Song, B.L. and R.A. DeBose-Boyd, Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase stimulated by delta- and gamma-tocotrienols. J Biol Chem, 2006. 281(35): p. 25054-61. 13. Qureshi, A.A., et al., Dietary tocotrienols reduce concentrations of plasma cholesterol, apolipoprotein B, thromboxane B2, and platelet factor 4 in pigs with inherited hyperlipidemias. Am J Clin Nutr, 1991. 53(4 Suppl): p. 1042S-1046S. 14. Mueller, A.M., B. Tan, and E.S. Stuart, Tocotrienol in the potential treatment of infectious disease., in Tocotrienol: Vitamin E beyond Tocopherol., R. Watson and V. Preedy, Editors. 2008, CRC Press. p. 343-359. 15. Campbell, L.A. and C.C. Kuo, Chlamydia pneumoniae--an infectious risk factor for atherosclerosis? Nat Rev Microbiol, 2004. 2(1): p. 23-32. 16. Kooyenga, D.K., et al., Antioxidants modulate the course of carotid atherosclerosis: A four-year report., in Micronutrients and Health, K. Nesaretnam and L. Packer, Editors. 2001, AOCS Press: Illinois. p. 366-375. 17. Rasool, A.H., et al., Arterial compliance and vitamin E blood levels with a self emulsifying preparation of tocotrienol rich vitamin E. Arch Pharm Res, 2008. 31(9): p. 1212-7. 18. Rasool, A.H., et al., Dose dependent elevation of plasma tocotrienol levels and its effect on arterial compliance, plasma total antioxidant status, and lipid profile in healthy humans supplemented with tocotrienol rich vitamin E. J Nutr Sci Vitaminol (Tokyo), 2006. 52(6): p. 473-8. 19. WHO. Obesity and overweight. 2010[cited 2010 2/1/10]
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22. Miyazawa, T., et al., Antiangiogenic and anticancer potential of unsaturated vitamin E (tocotrienol). J Nutr Biochem, 2009. 20(2): p. 79-86.
23. Shibata, A., et al., delta-Tocotrienol suppresses VEGF induced angiogenesis whereas alpha-tocopherol does not. J Agric Food Chem, 2009. 57(18): p. 8696-704.
24. Comitato, R., et al., A novel mechanism of natural vitamin E tocotrienol activity: involvement of ERbeta signal transduction. Am J Physiol Endocrinol Metab, 2009. 297(2): p. E427-37.
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27. Traber, M.G., et al., Diet-derived and topically applied tocotrienols accumulate in skin and protect the tissue against ultraviolet light-induced oxidative stress. Asia Pac J Clin Nutr, 1997. 6(1): p. 63-67.
28. Yamada, Y., et al., Dietary tocotrienol reduces UVB-induced skin damage and sesamin enhances tocotrienol effects in hairless mice. J Nutr Sci Vitaminol (Tokyo), 2008. 54(2): p. 117-23.
29. McAnally, J.A., et al., Tocotrienols potentiate lovastatin-mediated growth suppression in vitro and in vivo. Exp Biol Med (Maywood), 2007. 232(4): p. 523-31.
30. Michihara, A., et al., Delta-tocotrienol causes decrease of melanin content in mouse melanoma cells. J Health Sci, 2009. 55(2): p. 314-318