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Building health by building cell membranes

More than eight decades after its discovery, vitamin E is still identified primarily with the four tocopherol nutrients, particularly alpha-tocopherol. Yet the tocotrienols do everything the tocopherols do, and much more. totalhealth’s Science Adviser Dr. Parris Kidd (PK ) interviewed Dr. Barrie Tan (BT ), the pioneering tocotrienol expert.

PK: Dr. Tan—Barrie, please explain briefly to our readers, what are the tocotrienols?

BT: The tocotrienols are four nutrients that are vitamin Es AND have other, unique nutritional properties. Vitamin E is a group of eight nutrients with two major subgroups, four tocopherols and four tocotrienols. Each tocopherol or tocotrienol molecule has a “head” section and a “tail” section. The heads are of four types, alpha-, beta-, gamma-, or delta-, with the tocopherols and tocotrienols having the same set of heads. It is the tail that determines whether the molecule is a tocopherol or a tocotrienol. The tocotrienols have shorter tails with high electron density (from double bonds), whereas the tocopherols have longer tails with lower electron density (single bonds). Their differing tail sections make the tocotrienols the more versatile cell membrane molecules.

PK: Since our cell membranes manage most life processes, is this why the tocotrienols work better than the tocopherols?

BT: The tocotrienols’ shorter and thicker tails render them more flexible to influence cell membrane dynamics, versus the tocopherols’ longer and thinner tails.

The shape of the head also helps determine their access into the cell membrane molecular sheet. The gamma- and delta-heads work best for this purpose, and the gamma- and delta-tocotrienols have the most impressive health benefits of all eight vitamin Es. The annatto plant is a great source of gamma and delta tocotrienols.

PK: I remember seeing beautiful annatto plants while growing up in Jamaica. So, just how good are the tocotrienols versus the tocopherol vitamin Es?

BT: The tocotrienols have shown benefits far superior to the tocopherols, in lowering total and LDL cholesterol, supporting overall cardiovascular and metabolic health, and recently even in cancer cell suppression. When we hear “vitamin E” we immediately think “cell membrane antioxidant.” Dr. Lester Packer of the University of California at Berkeley found that tocotrienols are 40–60 times more potent than tocopherols as antioxidants. Other studies confirm his observation.

PK: So Barrie, which of the tocotrienols’ health benefits are most clinically established?

BT: The first clinical study on tocotrienols was in 1991 at the University of Wisconsin. Patients initially received 200 milligrams per day of a mix of tocotrienols and tocopherols. Total cholesterol and LDL cholesterol dropped 15–22 percent and 10–20 percent, respectively. However, 15 percent of the patients did not show improvement. The researchers decided to continue these patients on a purely delta- and gamma-tocotrienol supplement (at 100 milligrams per day). After four weeks on these tocotrienols, total cholesterol in these initially non-responsive patients had dropped 35–40 percent!

PK: Wow! So that’s why you prefer the annatto tocotrienols?

BT: Yes. The annatto preparation contains exclusively tocotrienols, with no tocopherols to interfere. And it is almost 100 percent gamma- and delta-, the forms that work best of all. In 1993, a Bristol Meyers Squibb internal study found that 100 milligrams per day of delta- and gamma-tocotrienol reduced total and LDL cholesterol by 20 –25 percent and triglycerides by 15–20 percent. The delta-tocotrienol was the most effective of the tocotrienols.

PK: What about other clinical applications?

BT: The tocotrienols’ biological activities extend beyond cholesterol- and triglyceride- lowering, as important as those benefits are. They help reduce atherosclerotic plaque in the arteries, help keep platelet aggregation normal, and reduce “adhesion molecules” that can promote atherosclerosis. They help suppress inflammatory atherosclerosis while helping prevent high cholesterol and triglycerides from pushing the atherosclerosis into clinical cardiovascular disease. High dietary tocotrienol intakes are associated with reduced risk of coronary heart disease, lowered susceptibility to ischemic heart arrhythmia, and a healthy lowering of the resting heart rate accompanied by improved myocardial efficiency. In one four-year study the tocotrienols achieved regression of carotid artery stenosis in humans.

PK: How do the tocotrienols promote healthy cholesterol management?

BT: Like statins, tocotrienols down-regulate the liver pathway from HMGR (3-hydroxy-3-methyl-glutaryl-CoA reductase). Statins not only block cholesterol synthesis, they (unfortunately) block other products of this pathway important for health, such as coenzyme Q10. Unlike statins, the tocotrienols “dial down” cholesterol production without side effects. The delta- and gamma-tocotrienols subtly affect the genes that program HMGR. Delta-tocotrienol also uniquely down-regulates “SREBPs” (sterol regulatory element-binding proteins), cell membrane factors that naturally regulate other genes linked to low-density lipoprotein (LDL). This effect also may down-regulate harmful triglyceride synthesis—very important to help prediabetic and diabetic conditions. Other than delta-tocotrienol, none of the other seven vitamin Es substantially regulate the SREBPs. In short, delta-tocotrienol and gamma-tocotrienol exclusively fine-tune cholesterol synthesis as well as triglyceride synthesis—a positive double-whammy for human health.

PK: But Barrie, do the tocotrienols block the body’s coenzyme Q10 production, like statins do?

BT: Coenzyme Q10 (CoQ10) is a really important cell membrane nutrient. In the various tocotrienol clinical studies, patients did not show any bad effects related to statin inhibition of CoQ10 synthesis. We found that gamma- plus delta-tocotrienols actually increased CoQ10 levels, by up to 20 percent. This CoQ10 increase has been confirmed in other studies.

PK: What about brain benefits?

BT: The tocotrienols can benefit familial dysautonomia (FD), a genetic disease that causes dysfunction of the autonomic and sensory nervous system. The gamma- and delta-tocotrienols showed the greatest benefits, and some specialists now recommend children with FD take daily tocotrienol supplements.

PK: What about diabetes? And so-called metabolic syndrome?

BT: With obesity soaring to its highest point yet, metabolic syndrome is also on the rise. An astonishing 20 –25 percent of the world’s adult population is affected by a cluster of the most dangerous cardiovascular risk factors, which includes high triglycerides, high blood pressure, high blood sugar, and insulin resistance. Tocotrienols safely reduce triglycerides, and there is evidence from animal studies that they can reduce blood pressure and normalize blood sugar, both hallmarks of metabolic syndrome.

PK: And how do the tocotrienols offer promise against cancer?

BT: Long-term tocotrienol consumption is linked to reduced risk of prostate, skin, and breast cancer. Delta-tocotrienol is now in Phase I clinical trials at the Moffitt Cancer Center in Florida for the treatment of pancreatic cancer, one of the deadliest of all cancers. Angiogenesis—the aberrant production of new blood vessels that feed cancerous tumors—is a major target for tocotrienol research. Other studies, especially from Tohoku University in Japan, suggest that tocotrienols can curb angiogenesis, essentially starving the tumors to death. Delta-tocotrienol is the most potent in cancer application.

PK: This seems further reason for annatto with its high delta-tocotrienol to be the best tocotrienol supplement.

BT: Delta-tocotrienol is the vitamin E molecule with the smallest molecular size, and this has overriding importance to its potency. Delta-tocotrienol has the best molecular characteristics to access and optimize cell membranes.

Until 2003, only two major commercial sources of natural tocotrienol existed, namely “palm tocotrienol” and “rice tocotrienol” (sometimes called “tocotrienol-rich fraction,” TRF). Hence, early studies utilized tocotrienol derived from these two sources. However, both these sources typically contain very little of the most potent delta-tocotrienol, and carry 25–50 percent of tocopherols which interfere with the tocotrienol benefits. Annatto provides only the most potent delta- and gamma-tocotrienol while being tocopherol-free, a composition never before seen. The discovery of this potent tocotrienol material comes right out of the Amazonian rainforest.

PK: And you deserve a great deal of credit for this discovery. How much of the annatto tocotrienols should we supplement each day?

BT: At least 50, preferably 100 milligrams per day. From the peer-reviewed clinical studies and my studies, the optimal dose of the annatto tocotrienols for cholesterol and triglyceride reduction seems to be 75–100 milligrams per day. The supplement is best taken with a meal, preferably dinner, to maximize absorption in the intestinal tract.

PK: Are there any conflicts between supplementing with the tocotrienols and taking a multivitamin with vitamin E as tocopherol?

BT: Since most multivitamins contain a significant amount of alpha-tocopherol that could interfere with tocotrienol benefits, I always recommend taking the multivitamin in the morning, and the tocotrienols in the evening or at least six hours apart from the tocopherol supplement. Taking tocotrienols in the evening with dinner has an additional benefit: The body’s cholesterol production peaks after midnight, so tocotrienol levels would peak in the blood when they are needed most.

PK: Great. I gather you and your colleagues are continuing to explore new applications for the annatto tocotrienols. As a parting gift to our readers, please share with us your most exciting findings for new applications of the tocotrienols.

BT: A comprehensive tocotrienol book was published last year, called Tocotrienols: Vitamin E Beyond Tocopherols. In this book my colleague Anne Trias (formerly Mueller) and I contributed chapters on tocotrienol in heart disease and tocotrienol benefits against Chlamydia pneumonia, which is believed to aggravate the progression of atherosclerosis. In 2010, public TV will air our tocotrienol discovery from the rainforest annatto plant in a segment entitled “Merger of Modern Innovation and Nature.”

PK: Barrie, thanks so much for thisinterview. I’ve enjoyed discussing with you the considerable science behind the tocotrienols.

Doctor Parris Kidd

Dr. Kidd has been a contributing editor and science advisor to Total Health magazine since 1996. His columns include interviews with Dr. Andrew Weil, cancer treatment pioneers Drs. Nick Gonzalez and Linda Isaacs, Dr. Dharma Khalsa, Dr. Barrie Tan, and environmentalist Erin Brockovich. Other columns such as Why You Should Take Vitamins became instant classics. Dr. Parris Kidd’s website provides detailed information on his professional reviews, seminars, books and other career accomplishments.