What are tocotrienols? Q2 Where do tocotrienols come from? Q3 What are the proven health benefits of tocotrienols?

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Meagan Hensley
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1 What are tocotrienols? Q2 Where do tocotrienols come from? Q3 What are the proven health benefits of tocotrienols? Q4 Q5 Q6 Q7 Q8 Q9 Which of the proven health benefits were carried out clinically on human? Were the studies mentioned above carried out with palm based tocotrienols? This is because of the significant different in ratio of tocotrienols to tocopherol in palm based tocotrienols (3.5:1) compared to rice based tocotrienols (1:1). The above human studies were for therapeutic conditions. Is there a RDA for tocotrienols? What is then the recommended daily dosage for people (normal everyday people) without any therapeutic condition but would like to have the benefits and protection of this new super vitamin E, palm phyto-tocotrienols? Why should anyone take tocotrienols? I'm already taking tocopherol Vitamin E. What can I expect from taking tocotrienols regularly? Q10 How are tocotrienols absorbed in the body? Q11 Being a vitamin E and since vitamin E is extensively used in cosmetics and personal care products, what proven benefits do tocotrienols have on prevention of skin aging and skin damage by ultra-violet rays? Q12 Why is delta-tocotrienol the most potent of all commercially available tocotrienols? Q13 Are there any research papers to show us that delta-tocotrienol is the most potent antioxidant? Q14 Why are there not many research carried out with delta-tocotrienol? Q15 What about gamma-tocotrienol? Q16 Are Tocotrienols safe? Q17 Can I get enough of tocotrienols from my normal diet / food? Q18 Can I get tocotrienols simply from using palm oil in cooking? Q19 Who should take tocotrienols? Q20 What should I look for when purchasing tocotrienols? Q21 What about regulatory approval and registration of tocotrienols? Q22 Will tocotrienols be The Vitamin E for the New Millennium? Q23 Why is tocotrienols much more expensive than tocopherols?

2 Q1: What are tocotrienols? A: Tocotrienols are part of the Vitamin E family. Tocotrienols have similar structure to tocopherols (Alpha-Tocopherol as the most common Vitamin E in the market), but contain three double bonds in the carbon side chain of the molecule. The Vitamin E family is comprised of eight different compounds : alpha, beta, gamma and delta- tocotrienols and tocopherols. Q2: Where do tocotrienols come from? A: Tocotrienols are naturally present in most plants. They are found mostly in palm oil extracted from palm fruits. Other sources are rice, wheat germ, oat and barley. Q3: What are the proven health benefits of tocotrienols? A: The proven additional health benefits (by over 128 research papers in human, animal models and in-vitro) are: 1. Palm based tocotrienols have been shown by the Kenneth Jordan Heart Foundation (US) in a double-blind human study to have the ability to reverse arteriosclerosis. Palm based tocotrienols have the ability to reverse blockage of the carotid artery and hence, reduce the risk of stroke and arteriosclerosis. 2. Tocotrienols have been shown by human and animal studies to have the ability to reduce the production of total serum cholesterols. They inhibit the enzyme HMG-Co A Reductase in the liver that is responsible for the production of cholesterols. Tocopherols have no effect on serum cholesterol. 3. Tocotrienols are very much more potent antioxidant than tocopherols. It has been shown by published research paper that alpha-tocotrienol is times more potent than alpha-tocopherol in the prevention of lipid peroxidation. Delta-tocotrienol is the most potent of all the commercially available tocotrienols. 4. In a recent article published in Clin. Exp. Hypertens. (1999), found that tocotrienol is an effective natural agent to prevent increased in blood pressure in spontaneously hypertensive rats. It also enhanced total antioxidant status in plasma and blood vessels. 5. Tocotrienols especially delta and gamma-tocotrienols have been shown to inhibit certain type of cancers especially human breast cancer cells. Palm based tocotrienols have been shown by four different research centers in the world to have the ability to inhibit both the estrogen positive and estrogen negative breast cancer cells. In those studies, alpha tocopherol has no effect at all on human breast cancer cells. 6. Palm based tocotrienols have been proven to inhibit platelet aggregation. Alpha tocopherol does not. 7. Tocotrienols, with their unsaturated side chain, allow them to pass through the membrane bi-layer (mainly made up of unsaturated fatty acid) in a more efficient manner and faster rate compared to the all saturated tocopherol. Hence facilitating the absorption of tocotrienols. 8. Palm based tocotrienols have also been shown by the University of California, Berkeley to be effective in preventing protein oxidation and lipid

3 peroxidation after a strenuous bout of exercise. Athletes especially body builders and sprinters generate tremendous amount of free radicals in their body. Hence, tocotrienols being a very potent antioxidant and vitamin E, protects athletes and body builders against protein and lipid peroxidation. Q4: Which of the proven health benefits were carried out clinically on human? A: The various human studies and dosage used in these studies specifically for a therapeutic condition are: 1. Since the early 1990s, there were hints that antioxidants could have some effect in showing regression of arteriosclerosis (improvement of artery health and blood flow). Dr Anthony Verlangieri of the Atherosclerosis Laboratory at the University of Mississippi published his research in reversing atherosclerosis in monkeys with antioxidant nutrients. A report in JAMA in 1995 showed that antioxidant vitamins slowed progression of coronary atherosclerosis. In a three-year, double-blind clinical study at the Kenneth Jordan Heart Foundation, New Jersey, on 50 patients with Carotid Stenosis (blockage of the carotid artery, the main artery that supplies blood to the brain), patients were given a supplementation of 240mg palm based tocotrienols per day. Within 6 months, 92% of the patients had an improvement in their blood flow through the carotid artery, indicating the ability of palm based tocotrienols to reverse artery blockage and improve artery health. 2. Palm based tocotrienols have been proven by numerous human and animal studies to have the ability to inhibit cholesterol production in the liver. Tocotrienols especially the delta-tocotrienol are potent and effective natural antioxidant nutrients to have the ability to inhibit the key enzyme that is responsible for cholesterol production in the body: HMG Co A Reductase. In human cholesterol lowering human studies, mild hypercholesterolemia patients were given a supplementation of 200mg palm based tocotrienols per day. Significant reduction of total serum cholesterol was observed within 6 to 8 weeks. The reduction of total serum cholesterol was between 15-33% whereas the HDL level was no affected. In another cross-over human study carried out at the Science University of Malaysia, randomly picked subjects with uncontrolled diet was given supplementation of 100mg palm tocotrienols per day. Within 8 to 10 weeks, there was a significant reduction of 10-12% of total cholesterol level in the group that received tocotrienols. 3. There are four reputable research centers that are currently furthering their research on the ability of palm tocotrienols to inhibit both the estrogen positive and negative human breast cancer cells. The research centers are University of Reading, UK, University of Louisiana, University of Western Ontario, and Palm Oil Research Institute of Malaysia (PORIM). At the moment, research is focused on elucidating the mechanism of inhibition of breast cancer cells by tocotrienols, In addition, the University of Wisconsin is currently carrying out studies on the inhibitory effect of tocotrienols on hepatocarcinogenesis.

4 Q5: Were the studies mentioned above carried out with palm based tocotrienols? This is because of the significant different in ratio of tocotrienols to tocopherol in palm based tocotrienols (3.5:1) compared to rice based tocotrienols (1:1). A: Almost all of the in-vitro, animal, human studies published so far, on the health benefits of tocotrienols was carried out with palm based tocotrienols. Palm based tocotrienols have very different chemistry and contents from rice based tocotrienols. The ratio of tocotrienols to tocopherol in palm based tocotrienols is very much higher at 3.5 to 1.0. In rice base tocotrienols, it is approximately 1.0 to 1.0. In addition, palm based tocotrienols contains additional phytonutrients such as phytosterols (which have been shown to prevent absorption of cholesterol in the intestine) and plant squalene (strong antioxidant) that are naturally extracted together with tocotrienols from the fruits of oil palm. Q6: The above human studies were for therapeutic conditions. Is there a RDA for tocotrienols? A: At the moment, there is no RDA for tocotrienols. It was only in the early 1980s that research scientist all over the world, started to look seriously into this new vitamin E. As the scientific evidence of tocotrienols is relatively new, the US FDA and US Pharmacopeia have not assigned vitamin E activity to tocotrienols. All the human and animal studies have been based on milligram of pure tocotrienols per day basis. Q7: What is then the recommended daily dosage for people (normal everyday people) without any therapeutic condition but would like to have the benefits and protection of this new super vitamin E, palm phytotocotrienols? A: So far, dosages of palm tocotrienols in human studies were for a specific therapeutic condition hypercholesterolemia, carotid stenosis and breast cancer at high dosages of tocotrienols. Individual who are interested in enhancing their antioxidant status as part of a long term nutritional plan should consider a moderate use levels. For these people who want to maintain a healthy level of cholesterol, a healthy heart and cardio vascular condition and breast health, the consensus among tocotrienol research scientists was a dosage of 30-50mg/day. Commercial dietary supplements currently offer daily supplementation of tocotrienols from 20-60mg for healthy adults. Dr Asaf Qureshi (University of Wisconsin the first research scientist to show that tocotrienols found in barley have the ability to lower total serum cholesterol), in his article titled The Mutitherapeutic Properties of Palm Oil and its Novel Vitamin E quoted that daily intake of mg of pure tocotrienols obtained from palm oil will provide enough tocotrienols for all the health benefits associated with them. Q8: Why should anyone take tocotrienols? I'm already taking tocopherol Vitamin E.

5 A: Individuals interested in enhancing their antioxidant status should take tocotrienols. Most Vitamin E supplements contain only alpha-tocopherol whereas palm based tocotrienols contain tocotrienols, phytosterols (proven to prevent absorption of cholesterol), squalene (a powerful antioxidant) and carotenoids. A combination of all these phytonutrients in which recent research have suggested may be highly effective in the overall maintenance of health. Q9: What can I expect from taking tocotrienols regularly? A: The effect of antioxidants, and likewise tocotrienols, only become apparent in the long term. Supplementing daily with tocotrienols will result in the reduction in cholesterol level and reduce the risk of free-radical degenerative diseases. Q10: How are tocotrienols absorbed in the body? A: Tocotrienols are fat soluble. It is absorbed in the same manner as fat, just like other fat-soluble vitamins (A,D and K) and phytonutrients like carotenoids. The absorption of these compounds is dependent on the physiological processes in the stomach and small intestines, induced by food, especially fat intake. Only when sufficient pancreatic juice and bile are secreted to emulsify the fat and fat soluble vitamins do we get satisfactory absorption. Since factors such as foods and fat intake tend to be variable, the absorption of fat-soluble nutrients will also be variable. Q11: Being a vitamin E and since vitamin E is extensively used in cosmetics and personal care products, what proven benefits do tocotrienols have on prevention of skin aging and skin damage by ultra-violet rays? A: The idea of using tocotrienols in cosmetic and personal care products is fairly new and recent. Being a more potent vitamin E, research scientists especially at the University of California, Berkeley, have started to investigate the additional benefits of tocotrienols over the alpha tocopherol vitamin E in the prevention of skin aging and skin damage. A study conducted at the University of California, Berkeley showed that dietderived or topically applied tocotrienols preferentially accumulate at the strata corneum of defense against free radicals generated by exposure to environment agents such as sun ray (UV), ozone, chemicals, etc. Q12: Why is delta-tocotrienol the most potent of all commercially available tocotrienol?

6 A: If you look at the molecular structure of tocotrienol, it has a chromanol ring as the head and an unsaturated phytyl side chain as the tail. The number of methyl groups attached to the carbon position 5, 7 and 8 on the head denotes the four isomers of tocotrienols alpha, beta, gamma and delta. Alpha-tocotrienol has three methyl groups attached to the chromanol ring, beta and gamma-tocotrienols have two methyl groups and last but not least deltatocotrienol with only one methyl group attached to the carbon position 8. The antioxidant activity of tocotrienols depends on the ease and availability of the hydroxyl group (attached to carbon position 6 on the chromanol ring) to donate its electron to neutralize the highly reactive free radicals. Tocotrienols exert its antioxidant capability by donating the electron from the hydroxyl group on carbon position 6. As such, the efficiency and effectiveness of a particular tocotrienol in neutralizing free radicals (antioxidant activity) depends on the relative ease of the hydroxyl group to donate its electron. Now, if you look at alpha-tocotrienol, it has three methyl groups which are located very near to the hydroxyl group. The crowding effect of these three methyl groups creates steric hindrance for the hydroxyl group to donate its electron to neutralize the free radicals. Crowding raises energy of the transition state and slows down the reaction. In comparison, beta and gamma-tocotrienol have two methyl groups, hence the effect of the steric hindrance is lower compared to alphatocotrienol meaning a higher antioxidant activity than alpha-tocotrienol. Delta-tocotrienol with only one methyl group attached to the chromanol ring has the least steric hindrance for its hydroxyl group to donate electron to neutralize free radicals. As such, delta-tocotrienol has the highest antioxidant potency compared to alpha, beta and gamma-tocotrienols. Due to the least crowding effect, the hydroxyl group on the delta-tocotrienol readily donates its electron to neutralize free radicals, making it the most potent antioxidant of all commercially available tocotrienols. Q13: Are there any research papers to show us that delta-tocotrienol is the most potent antioxidant? A: Published research studies which showed delta-tocotrienol is the most potent of the tocotrienol isomers: i. University of Reading, UK (Lipids, 1998(33)) found that delta-tocotrienol is the most potent tocotrienol in inhibiting estrogen negative MDA-MB-231 human breast cancer cells. ii. Dr Charles Elson (Patent WO 98/38993), found the anti-carcinogenic activity of tocotrienols increase in the order alpha-tocopeherol < alphatocotrienol < gamma tocotrienol < delta-tocotrienol. iii. University of Texas (Nutrition and Cancer, (1)), found that deltatocotrienol is the most potent in inducing apoptosis (cell deaths) of estrogen-responsive MCF7 and estrogen-nonresponsive MDA-MB-435 human breast cancer cells. In fact the potency of delta-tocotrienol is twice that of gamma-tocotrienol. iv. University of Hawaii (in a yet to be published research paper / will be presented at the American Association for Clinical Chemistry, July 2000),

7 found that delta-tocotrienol is the most effective vitamin E for reducing the endothelial expression of adhesion modecules, hence as a means to reduce the risk of developing cardiovascular disease. Q14: Why are there not many research carried out with delta-tocotrienol? A: The reason why not many research was carried out with delta-tocotrienol is due to the simple fact that delta-tocotrienol is scarce and only available in limited level and sources. Rice based tocotrienol does not or have negligible level of delta-tocotrienol. Q15: What about gamma-tocotrienol? A: As far as cholesterol reduction is concerned (not antioxidant activity), both the gamma-tocotrienol and delta-tocotrienol are as effective (Dr A. Qureshi European Patent No A3). Both of these tocotrienols are as potent in reducing total serum cholesterol level. Q16: Are Tocotrienols safe? A: Toxicological and pharmacological studies showed that supplementation with palm based tocotrienols up to 2500mg per day per kilogram of body did not produce any significant side effects. Tocotrienols are natural compound found in various food and oils such as palm olein, rice bran oil, wheat germ, barley, etc. They are vitamin E and one may be taking tocotrienols through these normal foods without even realizing it. Q17: Can I get enough of tocotrienols from my normal diet / food? A: Most of the oils and food contain tocopherols but virtually no tocotrienols. Tocotrienols only occur at very low level (below 800ppm) in nature with the highest concentration found in palm oil. Other sources are rice bran, barley, wheat germ, saw palmetto and certain types of nuts and grains. Due to their low level, it is practically impossible to attain the amount of tocotrienols studies suggest may have a beneficial effect, from diet alone. For example, one has to take a cup of palm oil per day to attain this level. Q18: Can I get tocotrienols simply from using palm oil in cooking? A: Refined palm olein (palm cooking oil) have some tocotrienols as well as tocopherols but the levels found are very low, approximately 0.08%. In order to get the amount of tocotrienols (50 mg mg per day) that medical studies suggest may have a beneficial effect, one would have to consume about 80g - 160g (about one to two tea cup) of palm olein a day. Other cooking oils from corn, soy-bean and sunflower contain virtually no tocotrienols. Q19: Who should take tocotrienols?

8 A: Everyone. Research has shown tocotrienols to actively lower cholesterol levels, prevent blood from clotting, having anti-cancer activity and anti-tumour qualities. People looking for an effective antioxidant should take tocotrienols. It is wise to begin tocotrienols supplementation in young adulthood and continue throughout one's life. Q20: What should I look for when purchasing tocotrienols? A: Look for a natural, palm-oil derived tocotrienol product. If minimally processed, it should also contain the other phyto-nutrients found naturally in palm oil. These include phytosterols, squalene and mixed carotenoids, thus offering a "platter" of a natural and wholesome phyto-nutrient complex. Other rice-derived tocotrienols are also available in the market. Some formulas include additional phyto-nutrients, such as soy isoflavones, Ginkgo biloba, or beta sitosterol. You can also look for a natural palm tocotrienol product combined with a phyto-carotenoid complex. In addition to the full range of tocotrienols, such a product may contain carotene, lycopene, natural palm squalene, and phytosterols commonly found in fruits and vegetables. This type of supplement contains a ratio of carotenes that mirror the carotenoid content found in carrots. A good mix! Q21: What about regulatory approval and registration of tocotrienols? A: Tocotrienols have been approved as a food additive in Japan. In France, finished products with palm based tocotrienols have been approved in the dietary supplement market. In Malaysia, the Health Ministry has approved palm based tocotrienols as a dietary supplement. Due to the recent nature of research work with tocotrienols and that scientific evidence supporting the benefits of tocotrienols is relatively new, the FDA has not assigned vitamin E activity to tocotrienols. Q22: Will tocotrienols be The Vitamin E for the New Millennium? A: Yes! Many research scientists and nutritionists, backed by extensive published research papers, agree that tocotrienols, being a natural more potent vitamin E and have many additional biological benefits over the normal tocopherols, will be the vitamin E for the 21st century. There are researchers who remarked that instead of focusing on tocopherols, people should start taking tocotrienols as the better vitamin E. Q23: Why is tocotrienols much more expensive than tocopherols? A: In nature, the level of tocotrienols is at such a low level (part per million level) that is it takes a huge amount of the raw material to extract out 1kg of tocotrienols. For example, for every 1000kg of soy fatty acid distillate, one can extract out about 70kg of the tocopherols. In comparison, every 1000kg of palm oil, one can only theoretically extract out 0.5kg of tocotrienols. In addition, the process to extract tocotrienols by molecular distillation is an expensive process compared to the convention distillation processes.

HEALTH BENEFITS OF TOCOTRIENOLS (SUPER VITAMIN E)

HEALTH BENEFITS OF TOCOTRIENOLS (SUPER VITAMIN E) Western medicine is desperately searching for compounds that can help trigger the death signal in cancer cells, and the tocotrienol form of natural Vitamin