FREQUENTLY ASKED QUESTIONS
- What are tocotrienols?
Although Herbert McLean Evans discovered vitamin E in 1922  as a vital nutrient to prevent birth defects, it was not until the late 1950s that the scientific community became aware that the vitamin E family consists of two major subgroups, namely tocopherols and tocotrienols. Each subgroup also contains four structurally and chemically diverse molecules (alpha-, beta-, gamma-, delta-): four tocopherols and four tocotrienols.
- How are tocopherols and tocotrienols alike, and how do they differ?
At first glance, the vitamin E particles appear the same, but nuances in their molecular framework set them apart. Figuratively speaking, all vitamin E molecules consist of a “head” and a “tail”. In both vitamin E subfamilies, the chromanol head is the location of antioxidant activity. Since all vitamin E molecules have a chromanol head, all of them are antioxidants, albeit to varying effectiveness. The shape of the head also determines whether a vitamin E molecule is an alpha-, beta-, gamma-, or delta-isoform. In general, gamma- and delta- (collectively entitled desmethyl-) heads are smaller, and have greater access to cell membranes, treating damage faster. Hence, they are usually more potent in delivering benefits.
The length of the molecule’s tail, on the other hand, determines whether a vitamin E molecule belongs to the tocopherol or tocotrienol subfamily of vitamin E. Tocotrienols have a shorter tail with double bonds (farnesyl) that renders them more flexible and better equipped to cover a large surface area of cell membrane. Tocopherols have a longer tail without double bonds (phytyl), causing them to be stationary and consequently protect a more confined surface area of the cell membrane. With the added flexibility afforded to tocotrienols, this vitamin E subfamily exhibits benefits of cholesterol lowering, overall cardiovascular and metabolic health, and more recently, cancer kill. Tocotrienols also display up to 50x greater antioxidant potential than tocopherols.
- What is so special about DeltaGold annatto tocotrienol?
The discovery of annatto as major source of tocotrienols baffled scientists: The plant naturally provides only the most potent delta- and gamma-tocotrienol while being tocopherol-free, a composition never before seen.
- Why is tocopherol-free important?
Tocopherol interferes with tocotrienol benefits. In 1996, the cholesterol-lowering properties of tocotrienol were found to be compromised by one of its very own vitamin E siblings, alpha-tocopherol . The researchers concluded that effective tocotrienol preparations should contain less than 15% of alpha-tocopherol and more than 60% of desmethyl tocotrienols (gamma- and delta-tocotrienol). The only natural source of tocotrienols that fits this prerequisite is annatto, which is essentially tocopherol free and contains only the most potent delta- and gamma-tocotrienols (90% and 10%, respectively).
- Why is delta-tocotrienol the most active tocotrienol compound?
The substitution of methyl groups on the chromanol head of the tocotrienol molecule plays an important role in its efficiency. Tocotrienol isomers (as well as tocopherol isomers) are designated by the substitution of methyl groups on the chromanol head. If the chromanol head contains three methyl substitutes (trimethylated) at position C-5, -7, and -8, we have alpha-tocotrienol. Substitution with two methyl groups (dimethylated) is either beta-tocotrienol (substitution at position C-5 and -8) or gamma-tocotrienol (substitution at position C-7 and -8). Delta-tocotrienol has only one methyl group (monomethylated) at position C-8. In general, less methylated tocotrienols are more active than fully methylated tocotrienols, especially when C-5 is left vacant or unsubstituted.
Most recent studies show that delta- and gamma-tocotrienol, which are collectively named “desmethyl tocotrienols” (Des T3) , are the most potent in their effects. This is most likely due to the lack of stearic hindrance with less methylated tocotrienols, which allows them to penetrate deeper into damaged membrane, and at the same time regenerate (or recharge) the spent (or oxidized) tocotrienol faster (or efficiently) . Translated, desmethyl tocotrienols, and delta-tocotrienol in particular, can have easier access to action, and treat damaged membranes faster.
- How does annatto tocotrienol compare to other tocotrienol sources?
Until 2003, only two major commercial sources of natural tocotrienol existed, namely palm and rice. Hence, early studies utilized tocotrienol derived from these two sources. Both sources, however, contain significant amounts of alpha-tocopherol, which was established to interfere with tocotrienol benefits. “Palm tocotrienol” and “rice tocotrienol”, also sometimes called tocotrienol-rich fraction (TRF), are actually mixtures of tocopherol and tocotrienol, typically containing 25-50% tocopherol (mostly as alpha-tocopherol).
Annatto, on the other hand, naturally provides only the most potent delta- and gamma-tocotrienol while being tocopherol-free, a composition never before seen.
- How was annatto tocotrienol discovered?
Dr. Barrie Tan, founder of American River Nutrition, stumbled upon the annatto plant on a “medicine man” exploratory trip to South America in the late 90s, and was stunned by the eye-catching red color (carotenoid) of the plant’s pods and seeds. The plant was named Bixa orellana after the Spanish discoverer Francisco de Orellana in the 1500s, and was first introduced to the United States as a food colorant about 150 years ago. The annatto pods are phototrophic, following the sun. Since carotenoids in general are very labile, researchers of American River Nutrition, LLC were curious as to what was protecting the carotenoid from oxidation, and especially accelerated photo-oxidation. After analyzing a sample, they found that the carotenoid’s protector was tocotrienol.
In addition, it was (and still is) the only known source of tocotrienol that is free of tocopherols. Interestingly, only two dominant peaks were found: delta-tocotrienol at about 90% and gamma-tocotrienol at about 10%. Dr. Tan remarks: “Right then, I knew we had stumbled onto the best-in-class tocotrienol that nature makes. To this day, I have never seen a similar composition in any other plant.”
- Is annatto tocotrienol all-natural?
Annatto naturally contains only the most potent delta- and gamma-tocotrienol while being naturally tocopherol-free.
- What are the benefits of tocotrienol?
- Heart Health: Consumption of tocotrienols is associated with reduced risk of coronary heart disease, reduced susceptibility to ischemia-induced arrhythmia, and reduced heart rate accompanied by improved myocardial efficiency [5-7].
- Free Radical Damage Control: Tocotrienol protects the body’s estimated 75 trillion cells from oxidative damage [8, 9], improving the oxygen-carbon dioxide (O2-CO2) and nutrient-waste (N-W) exchanges efficiently in the body’s estimated 10 trillion red blood cells. These O2-CO2 and N-W exchanges are essential, immediate, and systemic to simply living. Tocotrienol is involved in the “exchanges of life”.
- Lipid Management: Numerous studies demonstrate that tocotrienols lower LDL cholesterol and triglyceride levels. Elevation of these lipid levels is associated with heart disease, diabetes, and metabolic syndrome .
- Cancer Prevention: Tocotrienols have been shown to reduce the risk of certain types of cancer, including pancreatic [11, 12], prostate , skin , and breast cancer . In the context of cancer, angiogenesis is the aberrant production of new blood vessels that feed tumors. Tocotrienols have been shown to curb angiogenesis [16, 17], essentially starving the tumors.
- Anti-Inflammation: There are 30,000 miles of arteries that need to be protected for proper functions. Tocotrienols control inflammatory processes and markers, including reduction of atherogenic lipoprotein(a)[Lp(a)]  and NFkB [18, 19] , as well as inhibition of the sticky adhesion molecules  present in early stages of atherosclerosis. Bacterial infections contribute to the body’s inflammatory response, and tocotrienols have been shown to reduce infection by Chlamydia , a bacterium that has been found in atherosclerotic tissue and exacerbates inflammation .
- Skin Health: Tocotrienols have been shown to reduce UVB-induced skin damage [23, 24] and produce tumor retardation in mice with metastatic melanoma . Tocotrienols also reduce skin pigmentation . The skin is exposed to many elements of the environment, both inside (endothelium) and outside (epithelium). Tocotrienols are preferentially deposited in these tissues for their protection .
- What are some clinical studies on tocotrienol?
The first clinical study on tocotrienol was performed in 1992 at the University of Wisconsin . In this study, patients initially received 200mg/day tocotrienol-rich fraction (TRF). Total cholesterol and LDL cholesterol dropped 15-22% and 10-20%, respectively. However, 15% of the patients did not show improvement, and because of the greater effectiveness of delta- and gamma-tocotrienol, these patients were continued on a high delta- and gamma-tocotrienol supplement (100mg/day). Following 4 weeks of supplementation, the total cholesterol in these initially non-responsive patients dropped 35-40%.
A 1993 internal study by Bristol Meyers Squibb, in consideration of tocotrienol as drug candidate, found that 100mg of delta- and gamma-tocotrienol per day reduced total and LDL cholesterol by 20-25% and triglycerides by 15-20%. In this study, delta-tocotrienol was more effective than gamma-tocotrienol.
Clinical studies also determined that the optimal dose of tocotrienol for cholesterol and triglyceride reduction is 75-100mg/day .
To confirm this, patients in an open label study were given 75mg of delta- and gamma-tocotrienol each day. After a two-month study period, patient’s total and LDL cholesterol levels dropped 15%, and triglyceride levels dropped 20-25%, reducing cardiovascular risk by 15-20%. Patients did not experience side effects as are observed with statin cholesterol-lowering drugs (many of which are due to statin’s inhibition of CoQ10 synthesis). Instead, tocotrienols in this study increased CoQ10 levels by 20% .
- Is tocotrienol an effective antioxidant?
In studies at Brunswick Laboratories, Dr. Boxin Ou has compared the ORAC value of our tocopherol-free tocotrienol product (DeltaGold®) to tocopherol and mixed tocotrienols, and he found that DeltaGold’s antioxidant potential is much higher than that of the other compounds studied . In addition, the Ohio State University found that delta- and gamma-tocotrienol (as in DeltaGold) protect lard from oxidation at low levels of just 100ppm. Dr. Lester Packer of the university of California/Berkley showed that tocotrienol is a 40-60 times more potent antioxidant than tocopherol [29, 30].
- How are tocotrienols absorbed, and are they bioavailable?
As part of the vitamin E family, tocotrienols are fat-soluble, and are hence absorbed in a similar fashion as fats from food in the gut. Tocotrienols are bioavailable, and have been shown to deposit in lipid-rich organs, including the liver, brain, spleen, lung, kidney, and heart. They peak in the blood at approximately 4 hours following ingestion, and are known to absorb more readily when taken along with fatty foods .
- What is the daily recommended dosage?
Clinical studies determined that the optimal dose of tocotrienol for cholesterol and triglyceride reduction is 75-100mg/day . The supplement is best taken at dinner with a fatty meal to increase absorption in the gut . When used for maintenance of lipid levels and as an antioxidant, smaller doses of 25-50mg may be taken.
- Why is it that until now few studies on annatto-based tocotrienol have been carried out?
It is reasonable to say that many of the human studies were done with palm, not because it was the most potent, but because it was the first commercial source containing tocotrienols to become available. Some significant human studies with palm tocotrienol did not work [32, 33]. The reason they did not work was because of the high alpha-tocopherol content. Simply put, alpha-tocopherol is a liability to tocotrienol functions when composed together. Annatto provides 90% delta-tocotrienol, which has been repeatedly shown to be the most potent. This is followed in potency by gamma-tocotrienol as close second, of which annatto contains 10%. Wherever tocotrienol isomers may be purified from (e.g., palm, rice, and annatto), the chemical identity of the isomers is still the same, and delta was repeatedly shown to work best. This is the science of delta and gamma. The source (e.g., palm, rice, annatto) must be subservient to this fact, not the other way around.
- How safe are annatto tocotrienols?
Annatto seed and its extracted colors have been used throughout South America since its discovery by Spanish Francisco De Orellana in 1543, more than 450 years. Palm oil has been in use in Southeast Asia for about 45 years. Therefore, annatto usage is 10x longer than palm usage. People in Brazil use huge amounts of annatto coloring, and have done so more than a century without side effects. The recommended JECFA ADI for annatto is approximately 4mg/d for a 60kg individual. However, annatto is considered essentially non-toxic, and the natural colorant is “exempt from certification”. Safety of annatto is based on traditional use for many centuries as a food colorant by millions of people in South America , and several studies conclude that the ADI should be increased [35, 36]. Brazilians may have used 10-20x more than the JEFCA, and throughout the history of its usage for more than 100 years no related disease was identified among consumers of annatto coloring .
Carotenoids such as lutein, astaxanthin, alpha- and beta- carotene have been taken with food in high amounts, typically 5-30mg without known toxic effect. Annatto color (also a carotenoid) has the longest history of use of all the carotenoids.
Studies estimated the safe dose of tocotrienols for human use may be as high as 1,000mg/day.
High levels of tocotrienols were also used in several clinical studies.
- Should I take tocotrienols if I am already taking a multivitamin or tocopherol product?
Most multivitamins contain alpha-tocopherol, which has been shown to interfere with tocotrienol benefits. However, a tocotrienol supplement can be taken at least 6 hours apart from a multivitamin or tocopherol product to prevent alpha-tocopherol interference.
- Is annatto tocotrienol better than full spectrum tocotrienols?
Annatto tocotrienol is better in the sense that it is tocopherol-free, and hence there is no risk for interference with benefits by alpha-tocopherol. In addition, annatto tocotrienol provides only the most potent delta- and gamma-tocotrienol isomers.
- Isn’t alpha-tocotrienol most effective for neuron protection?
Studies at the Ohio State University showed that alpha-tocotrienol is undoubtedly a brain protectant [38, 39]. These studies, however, focused on glutamate-induce (that is, trauma-induced) stroke injury, a very severe and specific condition. Data on delta-tocotrienol appear to be absent in this area of research. With this said, one has to remember that neurotoxicity goes far beyond trauma-induced stroke injuries. There is an array of chronic neurodegenerative disorders, including Alzheimer’s, Huntington’s, and Parkinson’s disease, as well as familial dysautonomia (FD – a genetic disease that causes dysfunction of the autonomic and sensory nervous system). The latter has been extensively studied with tocotrienols, and gamma- and delta-tocotrienol had the greatest effect on improving the condition by raising cellular levels of IKAP [40, 41]. IKAP is a protein that is largely non-functional in this neurodegenerative disease, resulting in autonomic crises characterized by hypertension, abnormally accelerated heart beat, excessive sweating, and vomiting. Following this original study, children with FD now take daily tocotrienol supplements to reduce symptoms of the disease.
In short, the jury is still out as to which tocotrienol isomer is best for neuroprotection. It may be that tocotrienol isomers all work to varying degrees in neuroprotection.
- How does tocotrienol inhibit cholesterol?
It is believed that tocotrienols, which contain a unique farnesyl moiety, disphosphorate the farnesyl pyrophosphate; the thus-freed farnesol down-regulates 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), the enzyme responsible for the body’s cholesterol production . Tocotrienols also degrade the protein HMGR, a mechanism of action that was elucidated in the early 1990s [43, 44]. Fifteen years later, this original study carried out by Bristol-Myers Squibb was recently revalidated, where researchers elucidate the biochemical mechanism for the hypocholesterolemic effect of tocotrienols on HMGR . In both earlier and recent studies, only desmethyl tocotrienols (namely, delta- and gamma- isomers) had this effect on HMGR. Tocotrienol was found to act like a sterol, creating a feedback mechanism that causes a decrease of HMGR activity by increase of sterol-sensing, including inhibition of gene transcription, blocking translation of mRNA and accelerating degradation of HMGR protein. However, in the more recent study, tocotrienol’s mechanism of action goes further. Tocotrienol was found to block processing of sterol regulatory element-binding proteins (SREBPs), membrane-bound transcription factors that modulate transcription of genes encoding cholesterol biosynthetic enzymes and low-density lipoprotein (LDL) receptor. With increased sterol-sensing, the configuration of HMGR changes, which in turn promotes binding of Insig (an insulin-induced protein found in the ER) to the sterol-sensing domain of SREBP cleavage-activating protein (SCAP). Binding of Insig to SCAP prevents SCAP from binding SREBP and escorting the complex to the Golgi, where SREBP is proteolitically processed to generate transcription factors that activate lipid synthesis. Only gamma-tocotrienol and delta-tocotrienol stimulate the ubiquitination and degradation of the HMGR and delta-tocotrienol uniquely blocks processing of sterol SREBPs . Blocking SREBP processing may specifically reduce triglyceride synthesis with importance in prediabetic and diabetic conditions. Other forms of vitamin E (all four tocopherols and alpha-tocotrienol and beta-tocotrienol) do not degrade, down-regulate, or block SREBP processing .
In short, delta-tocotrienol and gamma-tocotrienol inhibit the cholesterol synthesis via down-regulation and ubiquitination of HMGR and inhibit triglyceride synthesis via the sterol-mimic blocking of SREBP processing.
Tocotrienol’s biological activity expands beyond cholesterol- and triglyceride-lowering, and studies have shown its activity in plaque reduction [5, 46, 47], prevention of platelet aggregation , reduction of adhesion molecules, where delta- and gamma-tocotrienol were the most active .
- In what forms is DeltaGold® available?
DeltaGold® is available in oil form at a 50% tocotrienol concentration (DeltaGold® 50), and in powder form at a 35% tocotrienol concentration (DeltaGold® 35).
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