TOCOTRIENOLS: TWENTY YEARS OF DAZZLING CARDIOVASCULAR & CANCER RESEARCH
Byron J. Richards, CCN
February 15, 2011
Numerous studies over the past two decades have clearly proven that the tocotrienol form of vitamin E is a top choice for cardiovascular protection and heart health. A recent review of tocotrienol science points out that they are also being researched for benefits to bone health, blood sugar metabolism, brain health, and cancer. Since tocotrienols offer a safe and effective way to help achieve or maintain healthy cholesterol, while simultaneously protecting your arteries, it is worthwhile to understand more about them and how they can help you with your health.
The vitamin E family consists of 4 tocotrienols and 4 tocopherols. D alpha tocopherol is the commonly understood form of vitamin E and has been extensively researched and has its own value to human health. The difference between tocotrienols and tocopherols is the “tail” on the vitamin E molecule. Tocopherols have a long saturated tail. Tocotrienols have a short unsaturated tail. The unique structure of tocotrienols enables them to do many things that tocopherols cannot do. This includes easier access to cells, better antioxidant function in cells, a better ability to move around in cells, and the activation of a wide variety of gene signals – including the regulation of cholesterol.
The first recognition of tocotrienols as regulators of cholesterol occurred in a 1986 study wherein tocotrienols were isolated from barley and fed to chickens. Tocotrienols reduced the rate of synthesis of cholesterol by the liver, in turn reducing total and LDL cholesterol. In April of 1991 the American Journal of Clinical Nutrition published an animal study and two human studies, triggering an explosion in scientific interest in tocotrienols which continues to this day. The animal study involved pigs with inherited high cholesterol. Tocotrienols reduced their total cholesterol by 44% and LDL by 60%. They also reduced factors in the blood associated with sticky platelets, suggesting an additional cardiovascular protective mechanism was in play.
The same University of Wisconsin research team that did the pig study also conducted a double-blind, crossover, 8-wk study with 15 humans. During the 4 weeks on 50 mg per day of tocotrienols the total cholesterol was lowered 15%, LDL by 8%, and factors affecting platelet stickiness were also improved. Another preliminary human study with 42 mgs of tocotrienols per day found that many participants lowered their cholesterol, in some cases up to 35% for both total and LDL cholesterol. The dose of tocotrienols used in these early studies was relatively small, yet still able to show a beneficial influence on cholesterol levels.
Researchers next documented that it was gamma tocotrienol that was responsible for inhibiting cholesterol synthesis in the liver. As the research progressed scientists showed that gamma tocotrienol was reducing the HMG CoA reductase enzyme which is the starting point in the production line for cholesterol synthesis within your liver. It should be pointed out that statins, especially in high doses, take a sledgehammer to this same enzyme, essentially clogging up its receptors so that no communication can get through. By comparison tocotrienols work more on a consulting basis, gently down-regulating the enzyme as part of a communication strategy. Big Pharma invariably likes sledgehammers, as they produce forced behavior on human systems and can change numbers even if a person continues to pig out on food. Maximizing the benefits of tocotrienols would require a person actually eat better. Of course, tocotrienols have none of the toxic side effects that statins have.
While your liver uses this HMG CoA reductase cholesterol-synthesis pathway (melvalonate pathway) to produce LDL cholesterol for your entire body, every cell in your body also uses the same pathway to produce small pieces of cholesterol that are vital for maintaining the health and survival of any cell. In situations of cancer this pathway is hijacked and used by cancer cells to foster their own survival at the expense of your body. Researchers quickly realized that the “consulting style” of tocotrienols within your liver and healthy cells would be very different inside cancer cells and would not place any brakes on tocotrienols stopping HMG CoA reductase activity. In other words, tocotrienols had a unique ability to differentiate between healthy cells and cancer cells and in the case of cancer they could cripple a primary defense system of the cancer. I should point out that statins can also kill cancer in a test tube but the dose required to kill cancer in humans kills the human first. On the other hand, tocotrienols have demonstrated excellent tumor killing ability, even helping chemo drugs work much better on resistant forms of cancer. Tocotrienols do not injure the human body.
As the benefits of tocotrienols became apparent so did the commercial interests in potentially different sources of them. Palm oil was high in gamma tocotrienol but not as high in alpha tocotrienol, which was turning out to be highly relevant to antioxidant protection of the arteries and brain, as I will explain shortly. Palm oil is more difficult to work with in terms of putting it into capsules and requires the addition of other oils to make it flow easily. rice bran oil is a rich source of both gamma and alpha tocotrienol and with some additional attention to quality can be produced without any filler oils, enabling the production of a highly purified end product with no additive oils should a manufacturer chose to go the extra mile.
rice bran oil was known for some time to help cholesterol reduction. The recognition that tocotrienols were a main component of the oil in combination with all the emerging tocotrienol research soon led scientists to study tocotrienols isolated from rice bran oil. Leading the pack was the University of Wisconsin research team that a decade earlier had done the pioneering work with palm tocotrienols, hypercholesterolemic pigs, and the first human studies. They tested 50 mgs per day of rice bran oil tocotrienols in the genetically high-cholesterol pigs. After 6 weeks total cholesterol was reduced 32-38%, LDL cholesterol was reduced 35-43%, glucose was reduced 22-25%, triglycerides were reduced 15-19%, and various factors influencing sticky platelets were also reduced.
Next the Wisconsin researchers placed 28 people with high cholesterol on a restricted diet for a month and then gave them either 50 mg of rice bran oil tocotrienols, 10 mg of the statin drug Mevacor (a relatively low dose which is generally not toxic), or 50 mg tocotrienols, or a combination of 50 mg tocotrienols and 10 mg Mevacor. In the 50 mg tocotrienol group total cholesterol was lowered by 14% and LDL by 18%. In the Mevacor group total cholesterol was lowered by 13% and LDL by 15%. And in the combination group total cholesterol was lowered by 20% and LDL by 25%. Several months later the researchers tested various doses of rice bran oil tocotrienols (25 mg, 50 mg, 100 mg, 200 mg). After being put on a restricted diet for a month 90 people were then broken up into various groups. The 100 mg per day dose worked best, lowering total cholesterol by 20%, LDL by 25%, and triglycerides by 12%. This is excellent human data to support the use of tocotrienols from rice bran oil in combination with eating well in the management of cholesterol.
In addition to the cholesterol-lowering properties of tocotrienols scientists were becoming interested in the ability of tocotrienols to positively benefit the health of arteries. In this case the focus turned primarily to alpha tocotrienol, which demonstrated a high level of antioxidant function. It was first recognized that alpha tocotrienol could prevent free radical damage to LDL cholesterol in humans with high cholesterol. Only damaged (oxidized LDL) can form plaque in the arteries.
Scientists then tested tocotrienols in mice who are genetically programmed to develop high cholesterol and hardening of the arteries when they eat a high fat diet. When given tocotrienols and a high fat diet these mice did not develop high cholesterol and the hardening of their arteries was almost completely stopped (98% reduction). Other researchers found similar results when they placed rabbits on a diet designed to produce hardening of the arteries. Free radical damage in the blood was significantly reduced and the rabbits fed tocotrienols along with the bad diet had much less thickening of their arteries as well as retaining more elastic properties in their arteries.
In order for damaged cholesterol to stick to the lining of your arteries it is engulfed by macrophages (immune cells) that then stick to the endothelial cells that line your arteries. When endothelial cells become inflamed they project a Velcro-like piece of fly paper on the surface of their cells (adhesion molecules) which then enable the cholesterol-laden macrophages to lock on and start the plaque-forming process. A study with inflamed human endothelial cells shows that alpha tocotrienol powerfully inhibits this sticking process, turning off the sticky adhesion molecules by turning down the inflammatory gene regulator within the endothelial cell (NF-kappaB).
The ability of alpha tocotrienol to regulate the core inflammatory gene signal is highly relevant to many aspects of human health since it is now recognized that chronic low-grade activation of NF-kappaB is involved with just about every disease of aging as a primary feature. Indeed, researchers soon discovered that alpha tocotrienol, but not d alpha tocopherol, could completely inhibit excitotoxic injury to brain cells (a key feature to most aspects of cognitive decline and memory loss).
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This article highlights some of the key tocotrienol cardiovascular and cancer research going on around the world – which continues in full swing today. Human studies continue to show cholesterol-lowering benefits, even in difficult problems like type 2 diabetes. Numerous review articles tout the broad range of benefits, including the prevention of disease, offered by the unique form of vitamin E known as tocotrienols – which truly is the vitamin E for the 21st Century.
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