Vitamin E—the golden capsule, our most potent fat-soluble antioxidant—has a secret. It turns out to be a many-faceted nutritional gem, with a highly specific form called delta-tocotrienol that offers profound cholesterol-lowering properties, potent cardiovascular benefits, and in laboratory studies, verifiable anticancer effects. In new research, delta-tocotrienol proved 40 to 60-fold more powerful as a free radical scavenger than alpha-tocopherol, the most commonly available Vitamin E in supplements.

Vitamin E in the form of delta-tocotrienol can lower cholesterol by an astonishing 15-22%, and markedly improve LDL/HDL ratios, while preserving and even increasing Coenzyme Q10. Unlike the “blockbuster” statin drugs, which deplete CoQ10 and lead to a host of uncomfortable side effects including muscle deterioration and pain, Vitamin E in the form of delta-tocotrienol is nontoxic, CoQ10 preserving, and serves as a powerful antioxidant that protects lipoproteins. It also has a markedly beneficial effect on cardiovascular function.

In fact, delta- tocotrienol may be one of the most significant, new heart-protective nutrients available today. This is important news, since more than 102 million Americans suffer from high cholesterol (over 200 mg/dL) and cardiovascular disease remains our country’s top killer.

In addition, there is an impressive array of laboratory studies demonstrating that delta-tocotrienol markedly inhibits Chlamydia infection (associated with heart disease); and, that both delta- and gamma-tocotrienol are potentially potent anti-cancer nutrients.

Delta-tocotrienol is present at best in only trace amounts in Vitamin E supplements, while tocopherols dominate. Tocopherols are found in corn, soybean and olive oils—staples of the American diet. In contrast, oils like palm, annatto and rice are rich in the tocotrienols—and rarely used in America. And yet, according to the latest scientific research, the tocotrienols, especially delta, have disease-fighting properties that may herald a new golden age for the golden capsule. In brief:

• Tocotrienols are absorbed better than tocopherols, probably because of their unique shape and tail, which allows them to move throughout the entire cell.
• Tocotrienols are a far stronger class of antioxidants than tocopherols—they can be up to 40 to 60-fold more powerful as a free radical scavenger and up to 70-fold more bio-available. And delta-tocotrienol, in particular, is four times as powerful as the three other tocotrienols.
• Two of the tocotrienols, delta and gamma, can lower cholesterol by 15-22% and improve LDL/HDL ratios.
• Delta- and gamma-tocotrienols lower triglycerides.
• Delta-tocotrienol may be highly protective in atherosclerosis—more so than alpha-tocopherol. It can do a much better job at reducing the fatty streaks that form on artery walls (a first step in atherosclerosis), it helps stop monocytes from sticking to blood vessel lining, and inhibits “platelet aggregation” (sticky platelets that clump together).
• Delta-tocotrienol may fight Chlamydia infection. Chlamydia is implicated in heart disease, and delta-tocotrienol stops Chlamydia from entering cells via “lipid rafts” (yes, literally, little boats of fat).
• Alpha-tocopherol, the “famous” vitamin E, can actually compete with all the other vitamin Es (tocopherols and tocotrienols) and block their health-promoting effects. Worse, alpha-tocopherol accelerates the breakdown of tocotrienols and tocopherols. In fact, alpha-tocopherol can increase cholesterol if given in high doses.
• Delta-tocotrienol functions as a highly protective antioxidant for neurons.
• Laboratory and animal studies on tocotrienols offer promising early results in the treatment of cancer. For instance, delta-tocotrienol can inhibit lung, liver, breast, pancreas, skin, and prostate cancer in laboratory experiments on mice and on human cancer cells.
   

The New Face of Vitamin E

We often think of Vitamin E as alpha-tocopherol, which is by far the most studied form (just as we often focus on beta-carotene when there are over six hundred identifiable, natural carotenoids). In truth, alpha-tocopherol’s main function may be simply as an antioxidant, as the title of a review of alpha-tocopherol by specialist Maret G. Traber of Oregon State University puts it, “”Vitamin E, antioxidant and nothing more.” Traber, who identified the alpha-tocopherol transport protein, writes, “Virtually all of the variation and scope of Vitamin E’s biological activity can be seen and understood in the light of protection of polyunsaturated fatty acids.” In that antioxidant capacity, of course, alpha-tocopherol is important, because it protects the lipid cell membrane. It is the major lipid-soluble antioxidant in the body. 

But Vitamin E is far more than alpha-tocopherol. Vitamin E is really a generic term for eight common but different vitamin variations—four tocopherols and four tocotrienols (alpha, beta, gamma and delta). In this special report, we introduce new research demonstrating the unique benefits of delta-tocotrienol, an unusually potent antioxidant. As researchers at the Laboratory of Molecular Medicine at Ohio State Medical University put it in a 2007 research article: “The abundance of alpha-tocopherol in the human body and the comparable efficiency of all vitamin E molecules as antioxidants led biologists to neglect the non-tocopherol vitamin E molecules as topics for basic and clinical research. Recent developments warrant a serious reconsideration of this conventional wisdom. The tocotrienol subfamily of natural vitamin E possesses powerful neuroprotective, anticancer, and cholesterol-lowering properties that are often not exhibited by tocopherols... A rapidly expanding body of evidence supports that members of the vitamin E family are functionally unique.”

One reason the benefits of delta-tocotrienol have remained a bit of a secret is that they were expensive to source. That is no longer true. Biochemist Barrie Tan, Ph.D., formerly of the University of Massachusetts, and a world expert on tocotrienols, recently discovered that South American annatto is abundant in easily sourced tocotrienol that is already tocopherol-free. (See interview below.)

“Carotene is my love but tocotrienol is my fate,” confesses Dr. Tan. “I went to Malaysia and discovered that natural palm oil is a rich orange color. That orange is carotene—and the signature is almost analogous to that of a carrot! But lo and behold, when I extracted the carotene, I found that the fraction of palm oil without the color had potent antioxidant properties. It looked like Vitamin E, and it turned out to be tocotrienol. Years later I stumbled onto annatto, a South American and true Amazon Rainforest plant with a red pod rich in carotenoids. Once again it was the beautiful carotene that attracted me, and once again when I tried to find out what was protecting that carotene from decomposing, it turned out to be tocotrienols, and nearly exclusively delta-tocotrienol. I became very interested in this potent antioxidant. What’s even better is, in annatto we have discovered a natural source of tocotrienol that is tocopherol-free and needs no chemical manipulation.”

The timing was perfect, as tocotrienols have been gaining increasing recognition for their cardiovascular benefits in general, and their unique cholesterol-lowering properties in particular.

Powerful And Safe Cholesterol Buster

Delta-tocotrienol has proved effective at lowering cholesterol in laboratory, animal and human studies. In vitro, in liver cells, delta-tocotrienol showed a 30-fold greater inhibition of cholesterol than alpha-tocotrienol. When animals’ diets were supplemented with delta- and gamma-tocotrienol, their cholesterol decreased by a total of 32%, and their LDL cholesterol decreased 66%. The ratio of HDL to LDL improved by up to 150%.

In the first human study by researchers at the University of Wisconsin, published in 1992 and mentioned above, four weeks of supplementation with delta- and gamma-tocotrienol at 100 milligrams a day reduced cholesterol by 15-22% and decreased LDL cholesterol by 10-20%. According to Dr. Tan, there was some hope at that time among researchers that tocotrienol might be a drug candidate for cholesterol reduction. Instead, today, we have the statins, all of which reliably lower cholesterol, but also produce myopathy and raise liver enzymes, among other side effects. Delta-tocotrienol has no such side effects.

In open trials in humans, fasting blood lipids were measured before and two months after daily supplementation with tocotrienols from annatto (67 milligrams of delta-tocotrienol and about 8 milligrams of gamma-tocotrienol). In both studies, total cholesterol levels dropped 13%, LDL dropped between 9-15%, and HDL increased by 4-7%. The LDL/HDL ratio improved by up to 21%.

Can delta-tocotrienol be used on its own, or in conjunction with statins to potentiate their effect? Yes, according to molecular geneticists at Texas Southwestern Medical Center. Delta-tocotrienol is unique, compared to all other forms of vitamin E, in its ability to reduce cholesterol, according to their 2006 study. Thus it might “potentiate the therapeutic effectiveness of statins or, in some cases, provide an alternative therapy.” (In fact, as will be explained later in this article, other research suggests that statins and tocotrienol together could offer a novel approach to cancer.)

Finally, tocotrienol from annatto appears to preserve or increase Coenzyme Q10, which is depleted by statins. Patients given a daily dose of 75 milligrams of tocotrienols had their fasting CoQ10 measured after two months of supplementation. CoQ10 rose about 19% overall. “Further research will shed more light on the tocotrienol-CoQ10 connection,” says Tan.

Delta Benefits Diabetes and the Heart

Nearly 47 million American adults suffer from “metabolic syndrome”--a constellation of high triglycerides, high blood pressure, high blood sugar, and insulin resistance. These individuals are at increased risk for heart disease and diabetes. Delta- and gamma-tocotrienol are able to help protect against metabolic syndrome in a number of remarkable ways. First, they increase the heart’s vascular integrity by preventing cross-linking of proteins and sugars; cross-linking stiffens tissues and decreases their function. Second, they decrease blood glucose and help control blood sugar. Third, they reduce triglycerides in the blood and the liver. In clinical studies with both Type 1 and Type 2 diabetics and metabolic-syndrome patients, even small amounts of tocotrienol (from rice bran) were beneficial in all three ways. In a 2005 study of Type 2 diabetics, (80% of deaths in type 2 diabetics are related to cardiovascular complication) delta-tocotrienol decreased serum total lipids by 23 percent, total cholesterol by 30 percent and LDL cholesterol by 42 percent (plummeting from 179 mg/dL to 104 mg/dL) within a mere 60 days.

Delta-tocotrienol helps stop the fatty streaks that form on artery walls—the first step in atherosclerosis. These fatty streaks form when white blood cells (monocytes) stick to an inflamed blood vessel lining. The monocytes are trying to fight inflammation, but by sticking to the artery walls they reduce blood flow. Tocotrienol stops the monocytes from being so sticky. Compared to other forms of vitamin E, delta-tocotrienol has the most profound inhibitory effect on monocyte “stickiness”, according to a 2005 study from the Kyoto Prefectural University of Medicine. Delta-tocotrienol accumulates in heart endothelial cells up to 95-fold more than alpha-tocopherol. The researchers suggest that tocotrienol’s power comes from its ability to accumulate inside the heart cells.

Delta-tocotrienol also helps prevent platelets from clumping, another step in atherosclerosis. Plaques form when platelets clump on the inner, inflamed blood vessel walls, form clots and then reduce blood flow. In a double-blind crossover study, delta-tocotrienol proved a potent inhibitor of such clumping—as much as 71% percent (compared to between 5 and 37 percent with other tocotrienols.) When mice were fed a diet designed to create atherosclerosis, those mice receiving tocotrienols had a 60% lower cholesterol level than a control group. Atherosclerotic lesion size was reduced ten-fold. Alpha-tocopherol, in contrast, had no such effect. In another mouse study, atherosclerotic lesions diminished by 92-98% with tocotrienol compared to alpha-tocopherol or control mice.

Tocotrienol even reverses carotid artery arteriosclerosis. In a four year clinical study, patients received tocotrienol supplements derived from palm (for the first three years) and rice bran (for the fourth year). The rice bran oil also contained other useful sterols. Arteriosclerosis stabilized or even regressed in an astonishing 88% in the tocotrienol/tocopherol group arteriosclerosis. Yet in a placebo group, 60% deteriorated, and only 8% improved. In that last year, the rice bran oil group also saw a 14% decrease in total cholesterol and a decrease in triglycerides as well. This drop in cholesterol and triglycerides was most likely due to other micronutrients such as rice plant sterols and oryzanol, the latter of which is only available from rice. As the researchers note, “Tocotrienols and tocopherols…represent a promising adjunct therapy in cardiovascular patients, especially the post stroke patient.”

A Highly Potent Bioavailable Antioxidant

Tocotrienol from annatto has a far greater L-ORAC (Oxygen radical absorption capacity) value than alpha-tocopherol, and is more potent than resveratrol and green tea catechins. It is up to 60-fold more potent and 70-fold more bioavailable than alpha-tocopherol.

Tocotrienol has proven its antioxidant power in several studies. A 2006 study found that delta-tocotrienol had the most potent antioxidant properties of all the tocotrienols, and all the tocotrienols were more efficient antioxidants than tocopherols. Tocotrienol-rich Vitamin E protects against oxidation from ultraviolet radiation of the skin, and is more potent than alpha-tocopherol alone. In a 2003 study, tocotrienol was more potent than tocopherol at preventing cellular death from selenium deficiency. Another year-long study of 50 patients with high cholesterol found that tocotrienol (from rice bran) not only lowered total cholesterol levels but was able to reduce a sign of lipid peroxidation called TBARS (thiobarbituric acid-reactive substances). And a six month double-blind study of tocotrienol-rich Vitamin E found that 118 mg/day of tocotrienols (80 mg of delta- and gamma-tocotrienol) and 42 mg/day of alpha-tocopherol was able to prevent oxidative damage to DNA in older adults. In a study in rats, tocotrienols protected the brain against stroke- and glutamate-induced damage.    

Delta Wags Its Handsome Tail

Tocopherols have a long tail and tocotrienols a short one. And therein lies a major difference between the two, with significant consequences for health. First, a shorter tail allows delta to move freely throughout the cell, rendering it more bioavailable to tissue—as much as 70-fold.

Second, of course, is delta-tocotrienol’s impact on cholesterol. The pathway that leads to cholesterol also leads to Coenzyme Q10, heme (in blood), and other very important molecules. Statin drugs inhibit an enzyme at the center of this pathway, HMG CoA reductase (HMG-CoAR). Statins inhibit HMG-CoAR directly by blocking it through “competitive inhibition.” When they do this, they also block other products dependent on HMG-CoAR, and this includes Coenzyme Q10 and other important molecules. This can lead to statin side effects including myopathy, iron-unrelated anemia, fatigue, and heart problems.

Delta-tocotrienol, on the other hand, downregulates HMG-CoAR in an entirely different way that actually preserves CoQ10. It does so through its unique, short tail, which is “farnesylated” (contains a farnesyl group). In general, its small tail allows it to move easily through the cell and thus be far more bioavailable and potent than the tocopherols. This tail also helps regulate HMG-CoAR in a healthy fashion, by releasing farnesol (alcohol form of farnesyl). As farnesol increases, HMG-CoAR automatically decreases in response in a feedback manner. This “dial down” feedback effect is gentler than a simple “shut down” effect, and does not deplete CoQ10.

This short farnesyl tail of tocotrienol causes it to be less anchored in the cell membrane, allowing it to move faster and cover a greater area over a shorter period of time. It also has a unique “head”. Its head has fewer methyl groups attached, and so is smaller, and also has greater access to repair damaged membranes in tissue. All this may explain why delta-tocotrienol is a potent and highly bioavailable antioxidant.

Fighting Infection: A New Weapon Against Chlamydia

Intracellular Chlamydia bacteria have been implicated in atherosclerotic plaques as well as Alzheimer’s disease, asthma and respiratory tract infections. According to research by Dr. Elizabeth Stuart at the University of Massachusetts, tocotrienols inhibit Chlamydia. They do so by interfering with Chlamydia’s use of cell membrane cholesterol, so that it can’t infect cells as easily. Chlamydia may enter the cell through a “lipid raft”, taking cholesterol and using it to survive and replicate. Tocotrienols from annatto, which contain high amounts of delta and gamma, may help prevent this. In vitro, when cells were incubated with delta-tocotrienol before being infected with Chlamydia, their infection levels were 50% less than untreated cells. There were also changes in the Chlamydia bacteria that rendered it less infectious overall in delta-tocotrienol cells.

What Lies Ahead: Tocotrienols and Cancer

Tocotrienols have repeatedly been shown to inhibit proliferation and induce cell death in cancer cells. They may be doing so in multiple ways: by inhibiting angiogenesis, through free-radical quenching, by interfering with tumor pathways (through HMG-CoAR suppression), and more. In laboratory experiments with breast cancer cell lines, tocotrienols inhibited growth irrespective of estrogen receptor status. Delta- and gamma-tocotrienol were the most potent. In mouse studies from Kyoto Prefectural University of Medicine, delta-tocotrienol “resulted in significant suppression of liver and lung carcinogenesis.” In cancer cell lines, delta-tocotrienol was found particularly effective against prostate cancer cells. According to the researchers at East Tennessee State University, delta-tocotrienol “may prove very useful as chemotherapeutic or chemopreventive agent for treating prostate cancer.” In a  nother study from Case Western Reserve University, tocotrienol-rich extracts of palm oil inhibited human prostate cancer cell growth and even encouraged cell death. Other in vitro laboratory studies have found that both delta- and gamma-tocotrienol inhibit pancreatic tumor growth and reduce cervical cancer growth.

In fact, a 2007 study from Texas Woman’s University suggests that tocotrienols may potentiate the anticancer effect of statins. The problem until now has been that the high dose of statins required to inhibit cancer is toxic. The doses required lead to myalgia, muscle weakness, anorexia, lesions, nausea, diarrhea, fatigue and elevated creatine phosphokinase activity. However, using statins and tocotrienols “may lead to synergistic impact on tumor HMG-CoA reductase activity and consequently tumor growth,” they speculate. This may allow medicine to use lower doses of statins that are better tolerated, and “offer a novel approach to cancer chemoprevention and/or therapy.” Melanoma cell lines were markedly inhibited by a combination of lovastatin and tocotrienol 48 hours after treatment. Cells shrunk and died. In follow-up research, melanoma tumors were implanted into mice that were either supplemented with nothing (control), lovastatin alone, tocotrienol alone, or a blend of lovastatin and delta-tocotrienol for 22 days. Tumors in the “blend” group were smaller than the other groups. “Our study has shown for the first time that lovastatin and delta-tocotrienol, two suppressors of HMG-CoA reductase, synergistically suppress tumor growth in vivo,” they conclude.

In fact, according to a 1990 review article in Nature, regulating the pathway involving HMG-CoA reductase may have major implications for both heart disease and cancer. This review was written by the Nobel laureates of 1985, Dr. Joseph Goldstein and Dr. Michael Brown, for their discovery of the LDL receptor. With all this good news, delta-tocotrienol may turn out to be our 21st century vitamin E.

Flower and Fruit of the Annatto tree (Bixa orellana)

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