What Are Tocotrienols?

Overview

• Research on tocotrienols is promising
• The entire family of tocopherols and tocotrienols do not naturally occur together in any significant amounts
• Tocopherols hinder the assimilation of tocotrienols in the human body
• Tocotrienols are not a replacement for tocopherol
• Optimal Supplementation includes the entire Vitamin E complex – with tocopherols ingested hours apart from tocotrienols

Until recently, there had not been much discussion of the tocotrienol portion of the vitamin E family. This is due to several factors, but the most significant is the emphasis of alpha tocopherol at the expense of the rest of the vitamin E complex. Current research suggests that tocotrienols serve as antioxidants and also have important non-antioxidant functions such as lowering cholesterol levels, preventing cell adhesion in certain cells, and suppressing tumor growth.

All of these promising benefits have caused some to ask whether the tocotrienols are more important than the tocopherols. On the other hand, others have insisted that vitamin E supplements should consist of both the tocopherols and tocotrienols in order to provide vitamin E “as found in nature.” This paper examines the implications of tocotrienol research to date.

Vitamin E is a family of eight molecular structures that consist of a chromanol "head” and side-chain “tail.” Of these eight molecules, there are four tocopherol isomers and four tocotrienol isomers. While the chromanol “heads” of the respective alpha, beta, gamma, and delta tocopherols and tocotrienols are the same, they differ in their hydrocarbon “tails.” Tocopherols have phytyl side chains attached to their chromanol nuclei, whereas the tails of the tocotrienols are unsaturated and form an isoprenoid chain.

So, within the vitamin E family are two distinguished lines of tocols that share common chromanol “heads,” (which is why tocopherols and tocotrienols are both designated by the Greek a, b, g , and d letters) yet have different “tails.” Thus the vitamin E family actually consists of two sub-complexes, one tocopherol and one tocotrienol, both of which have distinct bio-activity and function. ^1,2

Research on Tocotrienols is promising

There is no doubt that tocotrienols have beneficial effects on human health, though perhaps different to those of tocopherols. As a company that specializes in vitamin E, we are very interested in the potential benefits of tocotrienols. Research suggests that the tocotrienols have cholesterol-lowering,³ anticarcinogenic⁴ and neuroprotective⁵ properties that are unique and novel.

As with any “newly” researched substance, it will be some time before substantial claims have a place of authority, especially since much of the research in animal and clinical studies have been mixed.

Tocopherols and tocotrienols do not naturally occur together in any significant amounts

One might expect that in nature we would find the complete vitamin E family of tocopherols and tocotrienols together in various plants, especially since some companies produce vitamin E supplements that contain both the tocopherols and tocotrienols. Nothing could be further from the truth. The fact is, plants widely differ in their vitamin E proportions, and no single plant provides the entire vitamin E family in nutritionally adequate amounts. Annatto beans, for instance, are higher in tocotrienols but contain no tocopherols. Sunflower, peanut, walnut, sesame and olive oils contain significant amounts of the tocopherols, yet are virtually void of the tocotrienols.⁶

Even within the categories of plants that predominate in either tocopherols or tocotrienols, we find large variances in their specific alpha, beta, gamma, and delta proportions. For example, annatto is high in delta tocotrienol with moderate amounts of gamma tocotrienol. In oat and barley, alpha tocotrienol predominates. In hulled and de-hulled wheat, beta-tocotrienol is the predominate isomer.⁷

Thus, while tocopherols and tocotrienols both exist in nature, plants differ widely in their vitamin E proportions. This little-known fact radically changes the way we look at “naturally occurring” vitamin E and has important implications in vitamin E supplementation.

Companies that seek to provide the entire vitamin E family in one product derive the tocopherols and tocotrienols from separate plant sources (a review of the ingredient label should confirm this). Such products are typically developed by processing the tocotrienols (usually from palm or rice bran) into the tocopherols (usually from soy). While there are a few products that do provide the full range of tocopherols and tocotrienols without using separate sources, they provide only trivial amounts of portions of the vitamin E complex and are unable to deliver dose-dependant benefits such as the inhibition of c-reactive protein, a potent bio marker and mediator of Cardiovascular Disease.⁸

Tocopherols hinder the assimilation of tocotrienols in the human body

While we don’t understand why vitamin E isomers are distributed differently in various plants in nature, current research has confirmed several facts about the body’s assimilation of tocopherols and tocotrienols that are significant when determining optimum vitamin E supplementation.

Tocopherols, mainly alpha tocopherol, hinder the assimilation of tocotrienols in the human body.⁹ This is due to the preferential uptake of tocopherol via the tocopherol-transfer protein,¹⁰ which discriminates between tocopherols and tocotrienols.¹¹ Thus, combining tocotrienols and tocopherols together does not appear to be efficacious.

Tocotrienols are not a replacement for tocopherols

Long ago, it was established that alpha tocopherol was the only active factor in vitamin E, thus the other portions of the vitamin E complex were rendered worthless. Today, we know more about the functioning of vitamin E, and we know that all isomers of the vitamin E complex play important roles in the body that are both distinct and synergistic.

Yet, it is easy to see why some researchers mistakenly thought alpha tocopherol was the only active factor in vitamin E. Out of all vitamin E isomers, the human body preferentially incorporates alpha tocopherol into the plasma due to the function of the hepatic tocopherol-transfer protein in the liver.¹² The specificity of this protein (inherent in the body) is why alpha tocopherol is always found to be the most bio-active in humans. In addition, recent research has shown that alpha tocopherol plays a role in the modulation of specific gene expressions¹³ and the regulation of five different groups of genes (including proteins involved in cell-signaling).^14,15 The importance and implications of this discovery are unprecedented, yet it has been largely unnoticed.

Furthermore, tocotrienols are not maintained in the blood at the same level as tocopherols (especially alpha tocopherol and gamma tocopherol).¹⁶

Stated simply, the body prefers alpha tocopherol over any other tocopherol or tocotrienol isomer. This preference seems to be based on a specific need for alpha tocopherol in various functions that are part of the constitutional homeostasis of human health. This special role of alpha tocopherol is unlike that of any other antioxidant or vitamin E isomer. This fact is interesting when you consider the current tendency to dismiss the significance of alpha tocopherol.

The body’s preference for alpha tocopherol does not mean that the rest of the vitamin E complex isn't needed. Scientific evidence has shown that while alpha tocopherol is maintained at higher levels in the body, the other isomers are maintained too, only in different tissues. Several studies suggest that the various vitamin E molecules work together in the body, and that humans have a selective mechanism for maintaining specific levels of the tocopherols and tocotrienols in various tissues.¹⁷ Plus, different vitamin E isomers provide distinct activities that are not shared with alpha tocopherol.^1819,20

For instance, gamma tocopherol has been shown to reduce TNF-alpha (65%;P=0.069), total nitrate/nitrite (40%;P=0.1), and lactate dehydrogenase activity (30%;P=0.067) – all bio-markers for disease. Gamma tocopherol also attenuates inflammation-mediated damage and inhibits prostaglandin E2 and leukotriene B4, both of which were not inhibited by alpha tocopherol in the same study.²¹ These findings strongly suggest that gamma tocopherol has anti-inflammatory activities in vivo that are not shared with alpha tocopherol, and that may be important for human disease-prevention and therapy. We have already mentioned emerging research showing the cholesterol lowering activity of tocotrienols, an activity apparently also not shared with tocopherols.

Optimal supplementation includes the entire Vitamin E complex – with tocopherols ingested hours apart from tocotrienols

Since the pathways that determine the concentration and metabolism of vitamin E are tightly regulated by the human body,^22,23,24 creating vitamin E supplements that produce optimum benefits is possible only by taking into account all of the scientific evidence.

We strongly believe in the benefit of taking the entire tocopherol complex, and separately taking tocotrienol. The synergistic benefits are not completely understood, but research has shown, for instance, that when the entire tocopherol complex was ingested as a whole, its effectiveness was greater in protecting against lipid peroxidation²⁵ and inhibiting platelet aggregation²⁶ than when alpha tocopherol was ingested alone.

In addition, the importance of supplementing with the complete tocopherol complex can be seen clearly by the fact that taking alpha tocopherol alone actually depletes the body’s levels of gamma tocopherol.²⁷ This does not occur when the entire complex is ingested together.

We believe the current influx of products that combine tocotrienols with tocopherols is not ideal, since tocopherol negatively affects the assimilation of the tocotrienols, and has also been shown to reduce beneficial effects of alpha tocotrienol.²⁸

We recommend that tocotrienol supplements be separated from tocopherol supplements by a good length of time for best assimilation of the tocotrienols – for instance, taking tocopherols earlier in the day with a meal, and taking tocotrienols in the evening with a meal. This allows not only for better tocotrienol assimilation, but also effective utilization of any potential cholesterol-lowing properties of the tocotrienols by synchronizing cholesterol synthesis in the liver with peak tocotrienol levels.*

In Summary

The growing research on tocotrienols is promising; however research demonstrates the importance of the tocopherols over the tocotrienols. The human body prefers alpha tocopherol over any other vitamin E form; however the entire family plays synergistic roles in human health.

While both tocopherols and tocotrienols do occur in nature, there is no plant that provides the entire family of tocopherols and tocotrienols in adequate amounts. Thus supplements that provide both tocopherols and tocotrienols are derived from separate plant sources. Such products are not optimal since the tocopherols actually hinder the assimilation of the tocotrienols when taken together.

We believe that a good tocotrienol supplement is one that has little to no tocopherol, and contains the most potent delta and gamma tocotrienol. It is also important that the concentration of tocotrienols — or tocopherols for that matter — be as high as possible to ensure the greatest purity and effectiveness. Unfortunately, the current standard for tocotrienol products is a 50 percent concentration, with 50 percent or more of oil diluents.

The only thing stopping this extra oil from turning rancid is the antioxidant function of the tocotrienols themselves. Most people take vitamin E with the intention that their bodies, not the oil carrier, should benefit from the antioxidant properties.

* We, along with many holistic practitioners, question the validity of this cholesterol-lowering paradigm.

References

¹ J . Nutr. 2001 Feb; 131(2):369S-73S. Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling.

² Free Radic Biol Med. 1991;10(5):263-75. Free radical recycling and intramembrane mobility in the antioxidant properties of alpha-tocopherol and alpha-tocotrienol.

³ Parker RA, Pearce BC, Clark RW, Gordon DA, Wright JJK. J. Biol Chem1993;268:11230–8. Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methyl glutaryl-coenzyme A reductase.

⁴ Shah SJ, Sylvester PW. Exp Biol Med (Maywood ). 2005 Apr; 230(4):235-41.Gamma tocotrienol inhibits neoplastic mammary epithelial cell proliferation by decreasing Akt and nuclear factor kappaB activity.

⁵ Sen C. K., Khanna S., Roy S., Packer L. J. Biol. Chem 2000; 275:13049-13055. Molecular basis of vitamin E action. Tocotrienols potently inhibit glutamate-induced pp60c-scr kinase activation of HT4 neuronal cells.

⁶ Heinonen M., Piironen V. Int. J. Vitam. Nutr. Res. 1991;61:27-32. The tocotrienol and vitamin-E content of the average Finnish diet.

⁷ Panfili G, Fratianni A, Irano M. J Agric Food Chem. 2003 Jul 2; 51(14):3940-4. Normal phase high-performance liquid chromatography method for the determination of tocopherols and tocotrienols in cereals.

⁸ Singh U, Jialal I. Laboratory for Atherosclerosis and Metabolic Research, University of California Davis Medical Center , 4635 Second Avenue , Res 1 Building, Room 3000, Sacramento , CA 95817 . Anti-inflammatory Effects of {alpha}-Tocopherol.

⁹ Packer L, Weber SU, Rimbach G. J Nutr. 2001 Feb; 131(2):369S-73S. Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling.

¹⁰ Arita M., Sato Y., Miyata A., Tanabe T., Takahashi E., Kayden H. J., Arai H., Inoue K. Biochem. J. 1995;306:437-443. Human alpha-tocopherol transfer protein: cDNA cloning, expression and chromosomal localization.

¹¹ Packer L, Weber SU, Rimbach G. J Nutr. 2001 Feb;131(2):369S-73S. Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling.

¹² Traber MG. Vitamin E. In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. Baltimore : Williams & Wilkins, 1999:347–62.

¹³ Azzi, A., Boscoboinik, D., Fazzio, A., Marilley, D., Maroni , P., Ozer, N. K., Spycher, S. & Tasinato, A. Z. Ernaehrwiss. 37: 21–28. (1998) RRR -a-Tocopherol regulation of gene transcription in response to the cell oxidant status.

¹⁴ Azzi A, Gysin R, Kempna P, Munteanu A, Negis Y, Villacorta L, Visarius T, Zingg JM. Ann N Y Acad Sci. 2004 Dec ;1031:86-95. Vitamin E mediates cell signaling and regulation of gene expression.

¹⁵ Angelo Azzi, Isabel Breyer, Maria Feher, Roberta Ricciarelli, Achim Stocker, Sabine Zimmer and Jean-Marc Zingg. Nonantioxidant Functions of a-Tocopherol in Smooth Muscle Cells. Presented as part of the symposium, Molecular Mechanisms of Protective Effects of Vitamin E in Atherosclerosis, given at Experimental Biology 2000, April 16, 2000 in San Diego , CA .

¹⁶ Chow, CK. Am. J. Clin Nutr . 1975 Jul; 28(7):756-60. Distribution of tocopherols in human plasma and red blood cells.

¹⁷ Podda M, Weber C, Traber MG, Packer L. J. Lipid Res. 1996 Apr; 37(4):893-901. Simultaneous determination of tissue tocopherols, tocotrienols, ubiquinols, and ubiquinones.

¹⁸ Saito H, Kiyose C, Yoshimura H, Ueda T, Kondo K, Igarashi O. Gamma-tocotrienol, a vitamin E homolog, is a natriuretic hormone precursor. PMID: 12730299 [PubMed - indexed for MEDLINE].

¹⁹ Jiang Q, Ames BN. FASEB J. 2003 May; 17(8):816-22. Gamma-tocopherol but not alphatocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats.

²⁰ AA Qureshi, N Qureshi, JJ Wright, Z Shen, G Kramer, A Gapor, YH Chong, G DeWitt, A Ong and DM Peterson. American Journal of Clinical Nutrition, Vol 53, 1021S-1026S. Lowering of serum cholesterol in hypercholesterolemic humans by tocotrienols (palmvitee).

²¹ Jiang Q, Ames BN. FASEB J. 2003 May; 17(8):816-22. Gamma-tocopherol but not alphatocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats.

²² Galli F, Lee R, Atkinson J, Floridi A, Kelly FJ. Gamma-Tocopherol biokinetics and transformation in humans. Lung Biology, School of Health and Life Sciences, King's College, London , UK .

²³ Podda M, Weber C, Traber MG, Packer L. J. Lipid Res. 1996 Apr; 37(4):893-901. Simultaneous determination of tissue tocopherols, tocotrienols, ubiquinols, and ubiquinones.

²⁴ Hosomi A, Arita M, Sato Y, Kiyose C, Ueda T, Igarashi O, Arai H, Inoue K. FEBS Lett. 1997 Jun 2; 409(1):105-8. Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs.

²⁵ Liu M, Wallin R, Wallmon A, Saldeen T. J. Cardiovasc Pharmacol. 2002 May; 39(5):714-21. Mixed tocopherols have a stronger inhibitory effect on lipid peroxidation than alpha-tocopherol alone.

²⁶ Liu M, Wallmon A, Olsson-Mortlock C, Wallin R, Saldeen T. Am. J. Clin. Nutr. 2003 Mar; 77(3):700-6. Mixed tocopherols inhibit platelet aggregation in humans: potential mechanisms.

²⁷ Handelman GJ, Machlin LJ, Fitch K, Weiter JJ, Dratz EA. J. Nutr. 1985 Jun; 115(6):807-13. Oral alpha-tocopherol supplements decrease plasma gamma-tocopherol levels in humans.

²⁸ Qureshi A. A., Bradlow B. A., Brace L., Manganello J., Peterson D. M., Pearce B. C., Wright J. J., Gapor A., Elson C. E. Lipids 1995; 30:1171-1177. Response of hypercholesterolemic subjects to administration of tocotrienols.