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The 21st Century Vitamin E?

Dr. Michael Murray
Michael T. Murray, ND


The vitamin E family consists of four tocopherols and four tocotrienols each designated as alpha, beta, gamma, or delta based upon slight differences in attached molecules. Of these naturally occurring vitamin E compounds, alpha-tocopherol (alpha T) has emerged has the most potent of these compounds in terms of vitamin E activity. However, newer information indicates that for other activities including antioxidant, cholesterol lowering, and anti-cancer effects that the tocotrienols (T3s), especially delta-tocotrienol (delta T3) exert more profound effects.1 So, while in terms of vitamin E activity the order of potency would be:

alpha T > beta T > gamma T > alpha T3 > delta T > gamma T3 > delta T3

The order of potency for acting as an antioxidant, cholesterol-lowering agent, and in cancer prevention may be just the opposite:

delta T3 > gamma T3 > delta T > gamma T > alpha T3 > beta T > alpha T

What is the difference between a tocopherol and a tocotrienol?

The difference is that the tocotrienol has 3 double bonds within the main body of the molecule. Just like as in polyunsaturated oils, the presence of these double bonds give the tocotrienols greater fluidity and make it much easier for the body to incorporate them into cell membranes, especially delta-tocotrienol.2 Differences between the various individual members of the tocopherol and tocotrienol family are due to different molecules found at the R1, R2, and R3 positions.

Compound R1 R2 R3



What are the health benefits of tocotrienols?

In comparing the health benefits of the tocopherols vs. the tocotrienols I will limit the discussion to the following areas: antioxidant effects, anticancer effects, cholesterol lowering effects, and effects on other aspects of cardiovascular disease. Do not misunderstand me. I am NOT saying that vitamin E (alpha-tocopherol) is not important. It possesses the greatest physiological vitamin E activity and is an important component of any nutritional supplementation plan. However, when some specific or additional support is needed then the tocotrienols, especially delta-tocotrienol, appears to offer even greater benefit.

Antioxidant activity

While vitamin E is generally regarded as the most important fat-soluble antioxidant, alpha-tocotrienol has been shown to be 40 to 60 times more potent than alpha-tocopherol in the prevention of lipid peroxidation. Even more potent is delta-tocotrienol - by far the most powerful antioxidant of the entire vitamin E family. Tocotrienols may prove more valuable in protecting the interior cell membranes, such as those that surround the cell nucleus and mitochondria, because of their greater ease in being incorporated into cellular membranes.1,2

Cholesterol reduction

Tocopherols have virtually no cholesterol-lowering activity, but numerous clinical studies have shown tocotrienols, specifically gamma-tocotrienol and delta-tocotrienol, to inhibit the manufacture of cholesterol within the liver.3 Specifically, these tocotrienols inhibit the liver enzyme HMG-CoA reductase - the same enzyme inhibited by the statin drugs and red yeast rice. Although clinical studies have yielded inconsistent results with tocotrienol preparations in lowering cholesterol, that is easily explained by taking a closer look at the types of tocotrienols used in the study and their dosage.

Commercial sources of tocotrienols

There are three commercial sources of tocotrienols - rice bran oil, palm oil, and annatto bean (DeltaGOLD™). It is important to understand the shortcomings of the first two to truly appreciate the differences in the results achieved in the clinical trials on lowering cholesterol.

Ratios of tocopherols and tocotrienols in commercial sources

  Rice Palm DeltaGOLD™
Alpha-tocopherol 41.7% 21.8% 0%
Other tocopherols 6.7% 0% 0%
Alpha-tocotrienol < 2% 22.1% 0%
Gamma-tocotrienol 51.6% 45.7% 10%
Delta-tocotrienol 0% 10.4% 90%

There are a couple of very important points to make when looking at the results:

  1. The higher the level of tocopherols in a tocotrienol preparation, the less effective the product is at lowering cholesterol levels. Tocopherols block the ability of delta- and gamma-tocotrienol to inhibit HMG-CoA reductase.4
  2. Proper dosage is also important. Since tocotrienols can be converted to alpha-tocopherol in the body, taking too high a dosage of tocotrienols actually reduces their ability to lower cholesterol levels.5 Dosages of 25 to 100 mg may prove more effective than dosages of 200 mg or more daily.

When these factors are taken into consideration it is easy to explain why certain studies were positive and others were negative.1,5-9 Tocotrienol concentrates with higher amounts of gamma- and delta-tocotrienols, and lower alpha-tocopherol have produced reductions of total cholesterol of 15% and an 8% reduction in LDL levels within the first four weeks of use.

Additional cardiovascular benefits

Tocotrienols have been shown to exert additional benefits to the cardiovascular system including an ability to decrease in the amount of cholesterol plaque in arteries, lower the level of the extremely damaging lipoprotein (a), prevent the aggregation of platelets, and inhibit the expression of cellular adhesion molecules.1,10 All of these factors are extremely important in the development and progression of atherosclerotic plaque. Delta-tocotrienol has been shown to be the most active of the tocotrienols.

Summary of benefits of delta-tocotrienol

  • Most powerful antioxidant of the vitamin E family.
  • The most potent tocotrienol to activate anticancer effects.
  • More effective at accumulating in cells compared to other tocotrienols.
  • Most effective member of the vitamin E for reducing endothelial expression of adhesion molecules, thereby preventing the accumulation of inflammatory cells within the arterial wall.
  • Most potent tocotrienol in inducing apoptosis (cell deaths) of human breast cancer cells. Delta-tocotrienol was twice as potent as of gamma-tocotrienol.
  • Inhibits the excessive aggregation of blood platelets much more effectively than vitamin E or other tocotrienols.

Anticancer effects of tocotrienols

The anticancer effects of tocotrienols have garnered a lot of attention. In addition to their important antioxidant effects, several other mechanisms have been proposed. For example, one of the innate protectors against cancer is a process known as "apoptosis." Basically, apoptosis is an encoded suicide program designed to protect cells from becoming cancerous. When this process does not work cancer develops. Tocotrienols are effective promoters of apoptosis with delta-tocotrienol being twice as potent as gamma-tocotrienol.11 Another anticancer mechanism involves inhibiting enzymes within cancer cells that stimulate them to replicate. Gamma-tocotrienols was shown to be three times more potent in inhibiting growth of human breast cancer cultured cells than chemotherapy drug tamoxifen.12

What are the dosage, drug interactions, and safety information for tocotrienols?
The effectiveness of tocotrienols for some specific indications requires using tocopherol-free, high delta-tocotrienol products at a proper dosage. For example, for lowering cholesterol, utilize the 90% delta-tocotrienol preparation and begin with a dosage of 50 mg tocotrienols. Recheck cholesterol levels in four to six weeks and alter dosage accordingly. If cholesterol levels drop into the normal range, the dosage can be reduced. If cholesterol levels do not change enough, the dosage can be increased to 100 mg per day. For best results take the tocotrienols with food and at least one hour away from any vitamin E.

Tocotrienols are extremely safe and no side effects have been reported.13 Given the effects on platelet aggregation, you will need to inform your physician of their use if you are going in for surgery, or taking the blood thinning drug Coumadin® (warfarin) or anti-platelet drugs like Ticlid® (ticlopidine).

Tocotrienols enhance the cholesterol-lowering effects of statin drugs and, presumably, red yeast rice extract.7



  1. Theriault A, Chao JT, Wang Q, Gapor A, Adeli K. Tocotrienol: a review of its therapeutic potential. Clin Biochem 1999;32:309-19.
  2. Yap SP, Yuen KH, Wong JW. Pharmacokinetics and bioavailability of alpha-, gamma- and delta-tocotrienols under different food status. J Pharm Pharmacol 2001;53:67-71.
  3. Pearce BC, Parker RA, Deason ME, Qureshi AA, Wright JJ. Hypocholesterolemic activity of synthetic and natural tocotrienols. J Med Chem 1992;35: 526-541 and 3595-606.
  4. Qureshi AA, Pearce BC, Nor RM, et al. Dietary alpha-tocopherol attenuates the impact of gamma-tocotrienol on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in chickens. J Nutr 1996;126:389-94.
  5. Qureshi AA, Sami SA, Salser WA, Khan FA. Dose-dependent suppression of serum cholesterol by tocotrienol-rich fraction (TRF25) of rice bran in hypercholesterolemic humans. Atherosclerosis 2002;161:199-207.
  6. Mustad VA, Smith CA, Ruey PP, Edens NK, DeMichele SJ. Supplementation with 3 compositionally different tocotrienol supplements does not improve cardiovascular disease risk factors in men and women with hypercholesterolemia. Am J Clin Nutr 2002;76:1237-43.
  7. Qureshi AA, Sami SA, Salser WA, Khan FA. Synergistic effect of tocotrienol-rich fraction (TRF(25)) of rice bran and lovastatin on lipid parameters in hypercholesterolemic humans. J Nutr Biochem 2001;12:318-329.
  8. Mensink RP, van Houwelingen AC, Kromhout D, Hornstra G. A vitamin E concentrate rich in tocotrienols had no effect on serum lipids, lipoproteins, or platelet function in men with mildly elevated serum lipid concentrations. Am J Clin Nutr 1999;69:213-9.
  9. Qureshi AA, Bradlow BA, Brace L, et al. Response of hypercholesterolemic subjects to administration of tocotrienols. Lipids 1995;30:1171-7.
  10. Theriault A, Chao JT, Gapor A, et al. Tocotrienol is the most effective vitamin E for reducing endothelial expression of adhesion molecules and adhesion to monocytes. Atherosclerosis 2002:160:21-30.
  11. Yu W, Simmons-Menchaca M, Gapor A, et al. Induction of apoptosis in human breast cancer cells by tocopherols and tocotrienols. Nutr Cancer 1999;33:26-32.
  12. Guthrie N, Gapor A, Chambers AF, Carroll KK. Inhibition of proliferation of estrogen receptor-negative MDA-MB-435 and -positive MCF-7 human breast cancer cells by palm oil tocotrienols and tamoxifen, alone and in combination. J Nutr 1997;127:544S-548S
  13. Nakamura H, Furukawa F, Nishikawa A, et al. Oral toxicity of a tocotrienol preparation in rats. Food Chem Toxicol 2001;39:799-805.

Michael T. Murray, N.D., is widely regarded as one of world's leading authorities on natural medicine. A prolific author, Dr. Murray has written over 20 books on health and nutrition including the best-selling Encyclopedia of Natural Medicine and his latest book The Encyclopedia of Healing Foods. Dr. Murray is also Director of Product Development and Education for Natural Factors one of the leading manufacturers of natural products.

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