Vitamin "E" for Everybody © VR By Bill Sardi Most consumers know vitamin E as vitamin E. But it is a family of vitamins that includes tocopherols and tocotrienols, with four varieties of each identified by their Greek prefix: alpha, beta, delta and gamma. Though vitamin E was discovered in 1922, researchers are just now gaining an understanding of the role of all the tocopherols and tocotrienols in human health. First, vitamin E is important because it is the major fat-soluble antoxidant in the human body that can pass through fatty membranes and enter cells. Fat-soluble antioxidants protect fatty tissues from spoiling or turning rancid, what scientists call lipid peroxidation. Fatty organs of the body (e.g. brain, prostate, breast, liver) may require more vitamin E than other tissues. For example, one study showed that 2000 IU a day of vitamin E slows the rate of progression of Alzheimer's disease. There are many difficulties in ascertaining the health benefits of vitamin E. The initial health benefit observed for vitamin E was its ability in states of deficiency to bring a rat fetus to full term. (The word tocopherol emanates from the Greek, which means "to bear offspring.") But in humans, significant vitamin E deficiency is considered to be rare, so do healthy humans need to take vitamin E supplements? Do We Need Supplemental E? The Reference Daily Intake (RDI) for vitamin E for older adults is 15 IU, and the American diet provides 9 to11 IU, so most adults end up a bit short. But the RDA and new Reference Daily Intake (RDI) were developed to prevent deficiencies in the population at large and may not be a good measure of the individual need for vitamin E. The Third National Health and Nutrition Examination Survey published in 1999 found 30 percent of the U.S. population exhibit low concentrations of vitamin E in blood serum, which would put them at increased risk for heart disease, cancer and other maladies. Need for Vitamin E Many factors affect vitamin E levels in the human body. Thyroid hormones, cholesterol-lowering drugs and consumption of unsaturated fats reduce blood serum levels of tocopherols. Another problem in assessing the need for vitamin E is its relationship with cholesterol. Vitamin E is carried from the liver to tissues on cholesterol particles. There is an over-reliance upon measurements of blood serum vitamin E levels rather than tissue levels. In 1972, MK Horwitt and colleagues noted that the blood carries only about 1 percent of the tocopherols in the body. Furthermore, as cholesterol levels drop in the blood circulation, so do circulating levels of the tocopherols. It's no coincidence that as total cholesterol drops below 160 mg per deciliter that the risk of cancer more than doubles. There is simply less vitamin E reaching tissues as cholesterol concentrations decline. Even though there is evidence that dietary and supplemental vitamin E is helpful in reducing the risk of cataracts and certain forms of cancer and vitamin E is beneficial for diabetes, the primary focus for this vitamin has been in reducing cholesterol and the overall risk of heart disease. In the 1960s the Shute brothers of London, Ontario, Canada utilized mega-dose vitamin E to remedy cases of angina and heart disease with reported success. But this only proves that vitamin E is helpful for people with heart and blood vessel disease. Again, what about healthy individuals? Since vitamin E travels on cholesterol particles produced in the liver for transport to tissues, it also protects circulating blood fats from oxidizing and hardening in blood vessel walls. So vitamin E should produce cardiovascular health benefits. Demand for Vitamin E Soars In 1992-93 it was widely reported that the consumption of 100 IU of vitamin E from supplements reduced the relative risk of coronary heart disease in males and females by 26 and 46 percent respectively over a two-year period. No benefit was observed from lower doses. This widely heralded report was followed by numerous other studies on the potential benefits of taking vitamin E supplements. In a study of healthy individuals it was found that it takes 400 IU or more of vitaminE, either natural source of synthetic, to protect LDL cholesterol from oxidizing. In 1996 it was found that vitamin E supplements did more than lower the risk of heart disease, they reduced overall mortality rates. Further proof of the health benefits provided by vitamin E supplements came from a study of middle-aged males taking 100 IU or more of vitamin E per day which reduced progression of coronary artery disease as evidenced by arterial imaging. The news media carried reports of these and other studies to the public and the demand for vitamin E soared. Manufacturers were in short supply for a time, said a 1996 report in The Wall Street Journal. The Los Angeles Times published a report entitled, "The Rags To Riches Story of E." Consumer Reports on Health said it was the first time a vitamin taken at dosages many times greater than the RDA might provide protection against an array of diseases including cataracts, nervous disorders and heart disease. For the first time there was firm evidence that vitamin E supplements defied the traditional advice to rely on foods rather than pills. Natural-Source E Superior At that time producers of vitamin E did a good job of educating the public about the superior qualities of natural-source vitamin E (d-alpha tocopherol) derived from soy over synthetically produced vitamin E (dl-alpha tocopherol). Synthetic vitamin E doesn't fit as well into the receptors designed for d-alpha tocopherol on the LDL cholesterol particles. The often cited figure is that natural source vitamin E is 36 percent more bioavailable than synthetic vitamin E, but this data was obtained from animal studies, not humans. Robert Acuff, reporting in the American Journal of Natural Medicine, cites studies that show d-alpha tocopherol is twice as bioavailable as the synthetic form and the placenta prefers d-alpha tocopherol versus synthetic vitamin E by a 4-to-1 ratio. In animal studies, Graham Burton has shown striking differences in the way natural source vitamin E accumulates in tissues versus synthetic vitamin E. Natural source vitamin E is retained by brain tissue 5.3 times more than synthetic vitamin E. Red blood cells prefer d-alpha tocopherol over dl-alpha tocopherol by a ratio of 3.6 to 1. Burton's work has recently been corroborated by Japanese researchers who found d-alpha tocopherol to be three times more bioavailable than synthetic vitamin E. Natural-source vitamin E, obtained from soy, was found to be so superior that some companies that manufactured synthetic forms had to abandon production. But don't inform your customers that synthetically produced vitamin E is not beneficial. It was synthetic vitamin E that was used to slow down the rate of progression of Alzheimer's disease. Synthetic vitamin E, if taken in high doses (1600 IU per day), is comparable to natural-source vitamin E in protecting LDL cholesterol from oxidation. Another example is a study where 800 IU of dl-alpha tocopherol was found to be beneficial in reducing oxidative damage following physical exercise. Subsequent Studies Lose Shine Most doctors were surprised by these unexpected reports and slowly physicians began attending to their patients' inquiries about vitamin E. But then more studies began to be published, and they were perplexing. Up to 2000 IU of vitamin E taken over an eight-week period by healthy adults produced no reduced markers of lipid peroxidation. A 300 mg dose of vitamin E taken for 3.5 years did not reduce the risk of stroke or heart attack among adults who had survived a previous heart attack. A 300 mg dose of vitamin E among adults with a variety of health problems taken for 3.6 years did not result in a drop in adverse cardiovascular events. A 400 IU daily dose of natural-source vitamin E taken by senior adults for a period of 4.5 years also resulted in no reduced risk of stroke or heart attack. These reports began filtering into the news media and the public began to ask questions. While physicians began to dismiss reasons for taking vitamin E supplements based upon these studies, there were other health benefits that were being overlooked. For example, just 50 mg of vitamin E significantly reduces the risk of prostate cancer. A Tufts University study showed that 200 IU taken daily by senior adults increased the activity of immune cells by 65 percent. Why the quick dismissal of supplemental vitamin E? Which Form of E? Defenders of vitamin E supplements have called attention to the type of vitamin E being employed in these studies. The Shute brothers in Canada indicated early on that it was the alpha form of vitamin E that produced cardiovascular benefits. It's no wonder since alpha tocopherol has a higher concentration in blood serum compared to beta, delta or gamma tocopherols. The biological activity of vitamin E is partly determined by the time it remains in the blood and tissues where it exerts its effect. Alpha tocopherol is found in significant amounts 24 hours after ingestion, not the other forms of tocopherols. Only d-alpha tocopherol exhibits prolonged retention in tissues compared to other forms of vitamin E. Non-Alpha Tocopherols Yet there is a growing body of evidence that non-alpha tocopherols and the tocotrienols may yield health benefits even in small doses and even when not retained in the body for long. In 1949 the ratio of alpha to gamma tocopherol in the daily diet was about equal. But largely due to the widespread use of soybean oil this ratio has changed and Americans consume about 2.5 times more gamma than alpha tocopherol from the diet. Even though gamma tocopherol is only rated to have 10 percent of the biological activity of alpha tocopherol, its presence in the diet is not insignificant. A recent report suggests re-evaluation of gamma tocopherol's importance given it raises both gamma and alpha forms of tocopherol in plasma, whereas alpha tocopherol only raises concentrations of itself. Furthermore, gamma tocopherol has unique anti-inflammatory qualities over alpha tocopherol. Alpha tocopherol is considered to be a more potent antioxidant than gamma tocopherol, particularly in preventing lipid peroxidation. But gamma tocopherol is active against nitrogen-induced radicals that are associated with chronic inflammation. While alpha tocopherol is still the most important form of vitamin E, gamma tocopherol makes a significant contribution towards health promotion. More Gamma Tocopherol Gamma tocopherol has been found to be superior to alpha tocopherol in inhibiting prostate cancer in laboratory studies. Males who consume the highest amounts of gamma tocopherol from dietary sources appear to have a five-fold reduction in their risk of developing prostate cancer compared to men who consume the lowest amounts. Recent reviews suggest more attention be given to gamma tocopherol. Misleading News Reports Somehow medical reports about vitamin E get twisted around into negative news stories. For example, a recent Associated Press story entitled, "Vitamin E Dangers" mistakenly claimed that mega-doses of alpha tocopherol may be a mistake because they reduce levels of gamma tocopherol. Supplementation with alpha tocopherol does significantly reduce (50-70 percent) plasma concentrations of beta and gamma tocopherol. But again science confounds such presumptions. While scientists suggest the absence of mixed forms of tocopherols, in particular gamma tocopherol, from food supplements may be responsible for the lack of efficacy in recent clinical trials, this has only been shown in animal studies. Another human study showed there was no protection against nonfatal heart attacks among adults who consume the highest dietary amounts of gamma tocopherol. However, this does not rule out supplemental gamma tocopherol as being beneficial since even the highest dietary consumption may still be relatively low. In a laboratory dish, mixed tocopherols were recently found to be superior to alpha tocopherol alone in protecting red blood cells from oxidation. Tocotrienols Furthermore, let's not forget the tocotrienols either, the other vitamin E-like family of antioxidant molecules. Tocotrienols from rice bran employed with a cholesterol-lowering drug (lovastatin) reduced blood fats in an animal study better than the statin drug alone. Whereas alpha tocopherol induces the activity of the coenzyme A liver enzyme, tocotrienols have an opposite effect and thus may be more effective at lowering cholesterol levels than tocopherols. Since tocotrienols convert to tocopherols when given at high doses, the optimal dose needs to be determined. In a group of adults with high cholesterol on the American Heart Association Step-1 diet, varying amounts of rice bran tocotrienols reduced serum total cholesterol and triglycerides by 14 percent which was considered the optimal dose. In another study 42 mg of palm oil tocotrienols (200 mg per day) reduced by 15 percent the total serum cholesterol levels compared to subjects taking corn oil. The gamma form of tocotrienol was identified as the most potent cholesterol inhibitor in the palm oil. Tocotrienols aren't limited to cardiovascular health benefits alone. Whereas there is little or no evidence that alpha tocopherol supplementation in animals reduces the risk of breast cancer, in laboratory studies alpha, gamma and delta tocotrienols, and to a lesser extent delta tocopherol, exhibit significant anti-breast cancer properties. Conclusions The family of molecules that fall under the umbrella of vitamin E exhibit significant and profound health benefits, some which are just now being realized. A sufficient portion of Americans exhibit low circulating levels of vitamin E to warrant supplementation. The failings of vitamin E in recent cardiovascular disease trials may signify a flaw in the idea that cholesterol is the governing factor in preventing heart attacks and strokes rather than any failing of vitamin E itself. Expect the demand for mixed tocopherols and tocotrienols to increase as the public learns more about them. Soybeans provide the most abundant and economical raw material from which to produce natural-source vitamin E, though soy solely provides the family of tocopherols. Only palm kernal oil and rice bran provide a significant amount of both tocopherols and tocotrienols, but are not yet in as abundant supply as soy to meet world demand for vitamin E. VR
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