Tocotrienols Introduction

Tocotrienols consist of four natural compounds, alpha-, beta-, gamma-, and delta-tocotrienol; all belong to the vitamin E family. Other members of the vitamin E family include the four natural tocopherols, alpha-, beta-, gamma-, and delta-tocopherol, that differ from tocotrienols by the chemical structure of their side chains (tocotrienols have an unsaturated side-chain, rather than the saturated side-chain of the tocopherols).

Tocotrienols are fat-soluble, water-insoluble oils that occur naturally in plant oils and cereal grains. The tocotrienols, as well as the tocopherols, are potent antioxidants and may have various health benefits including; immunomodulatory, hypocholesterolemic, anti-atherogenic, antithrombotic, and anticarcinogenic effects. [1-5]

As mandated by the Food and Nutrition Board of the National Academy of Sciences, the Recommended Dietary Allowance (RDA) of vitamin E includes only alpha-tocopherol, since it’s considered the most active vitamin E form. The other natural vitamin E compounds, beta-, gamma-, and delta-tocopherol and tocotrienols, do not meet the RDA vitamin E requirement since they are not converted to alpha-tocopherol in humans. However, some experts question the current RDA for vitamin E (defined as only alpha-tocopherol), believing that tocotrienols may be superior to alpha-tocopherol in various clinical situations. Commercially, natural vitamin E supplements often contain a mixture of tocopherols and tocotrienols to confer the greatest benefits. [1-5]

Tocotrienols are free-radical scavengers that protect polyunsaturated fatty acids (PUFAs), such as low density lipoproteins (LDLs), from damage induced by toxic free radical molecules. Research suggests that tocotrienols may be more potent antioxidants and inhibitors of lipid peroxidation (including LDL cholesterol oxidation) and protein oxidation than tocopherols. [3-7] However, since alpha-tocopherol is the most active form in the human body, it may be the more dominant antioxidant. More research needs to be done to determine in which conditions tocotrienols are more potent that tocopherols.

Unlike the tocopherols, the tocotrienols may lower serum lipids by blocking the production of HMG-CoA reductase (beta-hydroxy-beta-methlyglutaryl-coenzyme A), a rate-limiting enzyme of the cholesterol biosynthetic pathway. [8-13] Research has found that the tocotrienols’ inhibition of HMG-CoA reductase may also suppress the oncogene ras protein and the growth of tumor cells, including human breast cancer cells. [16-22]

It is theorized that tocotrienols may have antithrombotic effects due to their inhibition of thromboxane B2 and platelet factor 4 production. [3-10]

Tocotrienols Food Sources

The best dietary sources include plant oils such as palm oil, rice bran oil, and coconut oil. Other food sources include cereal grains, like barley, oat, and rye. [2-3]

Tocotrienols Uses

Tocotrienols may be used to support cardiovascular health by helping to reduce serum lipids, cholesterol oxidation, and atherosclerotic plaque. Animal and human studies have found that treatment with tocotrienols lowered cholesterol levels and in some cases, platelet aggregation, in hypercholesterolemic animals and humans. [8-13] However, some study results did not completely support these claims. [14-15] One study showed that supplementation with tocotrienols did not have lipid-lowering effects in men with carotid stenosis and hyperlipidemia, but did inhibit progression of the carotid stenosis. [14] More human studies are needed to determine tocotrienols’ hypocholesterolemic and cardiovascular effects.

Tocotrienols may have anticancerous properties. In vitro studies have indicated that tocotrienols (particularly gamma- and delta-tocotrienols) may help prevent the growth of human breast cancer cells. [16-22] Some studies suggest that tocotrienol supplementation may be beneficial when combined with the prescription drug tamoxifen as a breast cancer treatment. [21-22] Experimental animal and in vitro studies suggest that tocotrienol may also have anti-tumor effects for other cancers such as liver cancer and melanoma. [23-24] More studies are needed to determine tocotrienols’ anticarcinogenic effects.

Tocotrienols may be useful for healing gastric ulcers, although more studies are needed to determine its benefits. [3]

Tocotrienols Dosages

Dosage: Ranges from 35 to 300 mg daily; the most common dosage is 40 - 50 mg of mixed tocotrienols daily. [2-3]

Delivery Forms: Tablets, softgel capsules, and emulsified liquid.

Tocotrienols Toxicities and Deficiencies

Tocotrienol Toxicities

Tocotrienols should not be taken by those individuals with vitamin K deficiencies (such as those with liver failure) or a history of bleeding problems (such as peptic ulcers, hemorrhagic stroke, or hemophilia). Pregnant, lactating women, and children should not take supplemental tocotrienols, unless recommended by a health care provider. High doses of tocotrienols (greater than 100 milligrams daily) should not be taken one month prior to any type of surgery or dental work. [1-3]

No adverse side effects or overdosage have been reported. Due to its potential interactions, individuals should avoid combining tocotrienols with the following drugs and nutritional supplements:

  • Warfarin
  • Bile acid sequestrants (i.e. cholestyramine, colestipol)
  • Isoniazid
  • Neomycin
  • Statins (i.e. atorvastatin, cerivastatin, fluvastatin)
  • Sucralfate
  • Orlistat
  • Medium-chain triglycerides
  • Phytosterols and phytostanols (i.e. beta-sitosterol and beta-sitostanol)
  • Dessicated ox bile
  • Olestra containing products
  • Mineral oil

Always inform your health care provider about the dietary supplements you are taking, as there is potential for side effects, interactions, or allergy.

Tocotrienol Deficiencies

A deficiency concerning the natural forms of vitamin E (including tocotrienols) may increase the susceptibility of cellular damage, which can cause various problems such as nerve damage, red blood cell damage, muscle weakness, and poor coordination. Vitamin E deficiency has been associated with fat malabsorption syndromes, premature infants, hereditary red blood cell disorders, and hemodialysis patients. [1]


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2. Tocotrienols, Dietary Supplement Information Bureau:

3. Tocotrienols, PDR Health:

4. Vitamin E, PDR Health:

5. Theriault A et al. Tocotrienol: a review of its therapeutic potential. Clin Biochem. 1999 Jul;32(5):309-19.

6. Kamat JP, Devasagayam TP. Tocotrienols from palm oil as inhibitors of lipid peroxidation and protein oxidation in rat brain mitochondria. Neurosci Lett. 1995; 195:179-182.

7. Kamat JP. Sarma HD, Devasagayam TPA, et al. Tocotrienols from palm oil as effective inhibitors of protein oxidation and lipid peroxidation in rat liver microsomes. Mol Cell Biochem. 1997; 170:131-137.

8. Qureshi AA, Pearce BC, Nor RM, et al. Dietary alpha-tocopherol attenuates the impact of gamma-tocotrienol on hepatic 3-hydroxy-3-methlyglutaryl coenzyme A reductase activity in chickens. J Nutr. 1996; 126:389-394.

9. Parker RA, Pearce BC, Clark RW, et al. Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. J Biol Chem. 1993; 268:11230-11238.

10. Qureshi AA, Quereshi N, Hasler-Rapacz JO, et al. Dietary tocotrienols reduce concentrations of plasma cholesterol, apolipoprotein B, thromboxane B2 and platelet factor 4 in pigs with inherited hyperlipidemica. Am J Clin Nutr. 1991; 53(Suppl):1042S-1046S.

11. Pearce BC, Parker RA, Deason ME, et al. Inhibitors of cholesterol biosynthesis. 2. Hypocholesterolemic and antioxidant activities of benzopyran and tertrahydronaphthalene analogues of the tocotrienols. J Med Chem. 1994; 37:526-541.

12. Watkins T, Lenz P, Gapor A, et al. gamma-Tocotrienol as a hypocholesterolemic and antioxidant agent in rats fed atherogenic diets. Lipids. 1993; 28:1113-1118

13. Qureshi A, et al. Response of Hypercholesterolemic Subjects to Administration of Tocotrienols. Lipids. 1995;30(12):1171-1177.

14. Tomeo A, et al. Antioxidant Effects of Tocotrienols in Patients With Hyperlipidemia and Carotid Stenosis. Lipids. 1995;30(12):1179-1183.

15. 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; 69:213-219.

16. McIntyre BS, Briski KP, Tirmenstein MA, et al. Antiproliferative and apoptotic effects of tocopherols and tocotrienols on normal mouse mammary epithelial cells. Lipids. 2000; 35:171-180.

17. McIntyre BS, Briski KP, et al. Antiproliferative and apoptotic effects of tocopherols and tocotrienols on preneoplastic and neoplastic mouse mammary epithelial cells. Proc Soc Exp Biol Med. 2000 Sep;224(4):292-301.

18. Nesaretnam K, Guthrie N, Chambers AF, Carroll KK. Effects of tocotrienols on the growth of a human breast cancer cell line in culture. Lipids. 1995; 30:1139-1143.

19. Nesaretnam K, et al. Tocotrienol-rich fraction from palm oil and gene expression in human breast cancer cells. Ann N Y Acad Sci. 2004 Dec;1031:143-57.

20. Nesaretnam K, Stephen R, Dils R, Dabre P. Tocotrienols inhibit the growth of human breast cancer cells irrespective of estrogen receptor status. Lipids. 1998; 33:461-469.

21. Nesaretnam K, Dorasamy S, Darbre PD. Tocotrienols inhibit growth of ZR-75-1 breast cancer cells. Int J Food Sci Nutr. 2000;51(Suppl):S95-103.

22. 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.

23. Rahmat A, et al. Long-term administration of tocotrienols and tumor-marker enzyme activities during hepatocarcinogenesis in rats. Nutrition. May1993;9(3):229-32.

24. He L, et al. Isoprenoids suppress the growth of murine B16 melanomas in vitro and in vivo. J Nutr. May1997;127(5):668-74.


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