<SPAN class=byline><SPAN class=articletitle>Very good read on illiciting all the benefits of vitamin E other than the common kind you buy of the shelf. WW7&nbsp;</SPAN></SPAN>

<SPAN class=byline><SPAN class=articletitle>The therapeutic effects</SPAN><SPAN class=articletitle>
of natural tocotrienols

<SPAN class=byline>By Dr. Phil Maffetone</SPAN> Vitamin E was discovered at the University of California at Berkeley in 1922. Subsequently, scientists isolated and identified at least eight biologically active vitamin E isomers from plant sources -- four tocopherols and four tocotrienols. Since this discovery, antioxidant effects, and to a lesser degree cell-signaling&nbsp; aspects, of tocopherols and tocotrienols have been studied. Today, vitamin E is a generic name referring to alpha tocopherol. This definition was implemented because alpha tocopherol is the only vitamin E isomer the body retains in its tissues, and is therefore the only isomer defined as a human requirement.<SUP><B>1</B></SUP> <SPAN class=text>Clinically, however, vitamin E is best thought of as a vitamin complex, consisting of two therapeutic groups of compounds with vitamin E activity -- tocopherols and tocotrienols. Each group comprises four different isomers, alpha, beta, gamma and delta, which all have different biological activities and potential therapeutic benefits. Tocopherols are present in most vegetable oils and are more common in the diet than tocotrienols, which are found at relatively high concentrations in oil extracted from the fruit of the palm tree. Tocotrienols are shown to be more potent, therapeutically, than tocopherols. For example, the antioxidant capabilities of tocotrienols are 40-50 times that of tocopherols.<SUP><B>2</B></SUP> In addition, other isomers are more potent than alpha tocopherol. Both gamma tocopherol and alpha tocotrienol may be more potent antioxidants than alpha tocopherol.<SUP><B>3</B></SUP></SPAN> Tocotrienols have an unsaturated isoprenoid side-chain rather than the saturated side-chain of tocopherols. This allows tocotrienols to function in a uniquely different manner than tocopherols. One example, discussed below, is the ability of tocotrienols to suppress HMG-CoA reductase in the liver, thereby reducing cholesterol production. <SPAN class=text><B>Sources of tocotrienols</B></SPAN> <SPAN class=text>
Plants and their oils are the best sources of both tocopherols and tocotrienols, with meat and eggs containing some of the latter. However, since there are eight different isomers of the vitamin E complex, it's important to consume all eight in the diet. Palm-fruit oil is the only complete source of all four tocotrienols.<SUP><B>2</B></SUP> Other sources include rice bran, wheat germ and barley, although they are not complete sources. Palm-kernel oil, in addition to raising LDL cholesterol<SUP><B>4</B></SUP> is a poor source of tocotrienols.</SPAN>&nbsp;
<SPAN class=text><B>Therapeutic effects</B></SPAN> <SPAN class=text>
In the last few years, tocotrienols have been extensively studied, with the main areas of interest surrounding their antioxidant effects, with particular interest in breast cancer, cardiovascular disease, skin health, and aging, and their cholesterol-lowering capabilities.</SPAN>
<SPAN class=text><B>Antioxidant effects</B></SPAN> <SPAN class=text>
Both tocopherols and tocotrienols have antioxidant effects. However, as previously mentioned, tocotrienols are 40-50 times more effective in their antioxidant capabilities.<SUP><B>2</B></SUP> In protecting for chromosome damage, they are also significantly more effective than tocopherols. There may be several reasons for this, including more effective uptake by cells and better distribution throughout cell membranes.<SUP><B>6</B></SUP></SPAN>
Moreover, vitamin E works as a complex in its antioxidant activity, rather than in isolation. This has been referred to as the antioxidant network.<SUP><B>2</B></SUP> This network includes tocopherols, tocotrienols, vitamin C, thiols (glutathione, lipoic acid and cysteine) and other natural substances. Specific studies demonstrate that tocotrienols can reduce the oxidative stress associated with aging, and can penetrate the skin and efficiently combat oxidative stress induced by UV or ozone.<SUP><B>7</B></SUP> <SPAN class=text><B>Cardiovascular effects</B></SPAN> <SPAN class=text>
While vitamin E is often associated with cardiac benefits, tocotrienols offer more advantages than tocopherols.<SUP><B>2</B></SUP> Tocotrienols can lower plasma concentrations of atherogenic LDL cholesterol by suppression of the key enzyme in cholesterol synthesis, HMG-CoA reductase.<SUP><B>8</B></SUP> It appears that both gamma and delta tocotrienols are most active in these cholesterol-lowering effects. In addition, tocotrienols also prevent LDL cholesterol oxidation through their actions as antioxidants.</SPAN>
<SPAN class=text>A study of dietary tocotrienols from natural palm oil demonstrated reductions in the concentrations of plasma cholesterol and apolipoprotein B, thromboxane B2, and platelet factor <B>4</B>. This indicated a protective effect on the endothelium and platelet aggregation, which suggests an anti-thrombotic effect from tocotrienols.<SUP><B>9</B></SUP></SPAN> In humans, both an eight-week study<SUP><B>10</B></SUP> and a four-week study<SUP><B>11</B> </SUP>demonstrated a significant lowering of cholesterol using palm oil tocotrienols. Reductions in cholesterol occurred predominantly in the LDL fraction. It was also shown that high doses of alpha tocopherol, such as 50 IU or greater, prevented the cholesterol-lowering effects of tocotrienols.<SUP><B>5</B></SUP> <SPAN class=text><B>Anticancer effects</B></SPAN> <SPAN class=text>
Tocotrienols have been shown to display anticancer activity.<SUP><B>12</B></SUP> In particular, Guthrie, et al.<SUP><B>13</B></SUP> demonstrated that tocotrienols can inhibit proliferation of human breast-cancer cells, and Yu, et al.<SUP><B>14</B></SUP> demonstrated that naturally occurring tocotrienols are effective apoptotic inducers for human breast-cancer cells. These anticarcinogenic activities may be related to mechanisms other than the antioxidant effects.</SPAN>&nbsp;
<SPAN class=text><B>Neuroprotective effects</B></SPAN> <SPAN class=text>
Elevated levels of glutamate in the brain have been implicated in many neurological</SPAN>
<SPAN class=text>diseases, including epilepsy, Alzheimer's and Parkinson's. Induction of oxidative stress by glutamate has been demonstrated to be the primary cytotoxic mechanism.<SUP><B>15</B></SUP> High glutamate levels result in depletion of glutathione levels in the brain, signficantly reducing antioxidant activity. In the pathogenesis of these diseases, oxidative damage may accumulate over a period of years leading to significant brain damage. Tocotrienols can protect against this oxidative damage to the brain.<SUP><B>6</B></SUP> Tocotrienols also perform this antioxidant activity more effectively than tocopherols. Interestingly, lower doses of tocotrienols can successfully prevent neuronal cell death early in the process, whereas larger doses can help "rescue" cells in later stages. In these situations, the protection by tocotrienols may also go beyond its effect as an antioxidant. </SPAN><SPAN class=text><B>Anti-inflammatory effects</B></SPAN> <SPAN class=text>
Tocotrienols may inhibit the release of arachidonic acid from cell membranes.<SUP><B>3</B></SUP> The clinical importance of this can be significant since this can reduce the production of inflammatory eicosanoids which are associated with a number of chronic disease state such as cancer, heart disease, Alzheimer's, and others (see "A review of anti-inflammatory actions of select foods").</SPAN>
<SPAN class=text><B>Conclusion</B></SPAN> <SPAN class=text>
Consumption of the whole vitamin E complex from foods ensures the intake of both tocopherols and tocotrienols in their natural state. Intake of high doses of alpha tocopherol may pose problems for tocotrienol activity. Tocotrienols have been shown to have a significant impact on cancer, heart disease, aging and other common conditions, and most often are more effective than alpha tocopherol.</SPAN>

<B><SPAN class=subheads>References</SPAN></B> <B><SUP><SPAN class=text>1</SPAN></SUP><SPAN class=text>&nbsp; International Institute of Medicine (2000).</SPAN></B><SPAN class=text> Standing Committee on the Scientific Evaluation of Dietary Reference Intake of Vitamin C, Vitamin E, Selenium, and Carotonoids, pp. 58-72, National Academy Press, Washington, DC.</SPAN> <B><SUP><SPAN class=text>2</SPAN></SUP><SPAN class=text>&nbsp; Packer L, Weber S, Rimbach G (2001).</SPAN></B><SPAN class=text> Molecular Aspects of alpha Tocotrienol Antioxidant Action and Cell Signaling. J Nutr 131:369S-373S.</SPAN> <B><SUP><SPAN class=text>3</SPAN></SUP><SPAN class=text>&nbsp; Theriault A, Chao J, et al. (1999).</SPAN></B><SPAN class=text> Tocotrienol: A Review of Its Therapeutic Potential. Clin Biochem 32(5):309-319.</SPAN> <B><SUP><SPAN class=text>4&nbsp;</SPAN></SUP><SPAN class=text> Grundy SM. (1996).</SPAN></B><SPAN class=text> Dietary Fat. In: Present knowledge in nutrition, ed. EE Ziegler and LJ Filer Jr., p 44-57. Washington DC: International Life Sciences Institute.</SPAN> <B><SUP><SPAN class=text>5</SPAN></SUP><SPAN class=text>&nbsp; Qureshi A, Pearce C, et al. (1996).</SPAN></B><SPAN class=text> Dietary alpha tocopherol attenuates the impact of gamma tocotrienol on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in chickens. J Nutr 126:389-394.</SPAN> <B><SPAN class=text>6&nbsp; Sen C, Khanna S, et al.</SPAN></B><SPAN class=text> (2000). Molecular Basis of Vitamin E Action. J Biol Chem 275(17):13049-13055.</SPAN> <B><SUP><SPAN class=text>7</SPAN></SUP><SPAN class=text>&nbsp; Adachi H, Ishii N (2000).</SPAN></B><SPAN class=text> Effects of Tocotrienols on Life Span and Protein Carbonylation in Caenorhabditis elegans. J Gerontol 55A (6):B280-B285.</SPAN> <B><SUP><SPAN class=text>8&nbsp;</SPAN></SUP><SPAN class=text> Qureshi A, Salser S, et al. (2001).</SPAN></B><SPAN class=text> Novel Tocotrienols of Rice Bran Inhibit Atherosclerotic Lesions in C57BL/6 ApoE-Deficient Mice. J Nutr 131:2606-2618.</SPAN> <B><SUP><SPAN class=text>9</SPAN></SUP><SPAN class=text>&nbsp; Qureshi A, Qureshi N, et al. (1991).</SPAN></B><SPAN class=text> Dietary tocotrienols reduce concentrations of plasma cholesterol, apolipoprotein B, thromboxane B2, and platelet factor 4 in pigs with inherited hyperlipidemias. Am J Clin Nutr 53:1042S-1046S.</SPAN> <B><SUP><SPAN class=text>10</SPAN></SUP><SPAN class=text>&nbsp; Qureshi A, Qureshi N, et al. (1991b).</SPAN></B><SPAN class=text> Lowering of serum cholesterol in hypercholesterolemic humans by tocotrienols (palmvitee). Am J Clin Nutr 53:1021S-1026S.</SPAN> <B><SUP><SPAN class=text>11</SPAN></SUP><SPAN class=text>&nbsp; Qureshi A, Bradlow B, et al.</SPAN></B><SPAN class=text> (1995) Response of hypercholesterolemic subjects to administration of tocotrienols. Lipids 30:1171-1177.</SPAN> <B><SUP><SPAN class=text>12</SPAN></SUP><SPAN class=text>&nbsp; He L, Mo H, et al. (1997).</SPAN></B><SPAN class=text> Isoprenoids Suppress the growth of Murine B16 Melanomas In Vitro and In Vivo. J Nutr 127:668-674.</SPAN> <B><SUP><SPAN class=text>13&nbsp;</SPAN></SUP><SPAN class=text> Guthrie N, Gapor A, et al. (1997).</SPAN></B><SPAN class=text> 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 127:544S-548S.&nbsp;</SPAN> <B><SUP><SPAN class=text>14 </SPAN></SUP><SPAN class=text>Yu W, Simmons-Menchaca M, et al.</SPAN></B><SPAN class=text> (1997). Induction of apoptosis in human breast cancer cells by tocopherols and tocotrienols. Nutr Cancer 33(1):26-32.</SPAN> <B><SUP><SPAN class=text>15&nbsp;</SPAN></SUP><SPAN class=text> Han D, Sen C, et al. (1997).</SPAN></B><SPAN class=text> Protection against glutamate-induced cytotoxicity in C6 glial cells by thiol antioxidants. Am J Physiol 273:R1771-R1778.</SPAN>