Saturday, August 4, 2012

Beyond Vitamin E by Jerry Brainum

New Findings On the Controversial Nutrient

     Recent reports in the popular media have suggested that those who take vitamin E and other antioxidants may be harming themselves. In fact, the most recent quoted studies conclude that vitamin E may cause premature death. As a result of such reports, many wonder about the wisdom of using not only vitamin E supplements but vitamins and minerals in general. Bodybuilders may find this particularly troubling, since many of their supplements contain extra vitamins.

     How can something as natural as a vitamin be so toxic? The truth is, it isn’t. A closer scrutiny of all these vitamin E studies shows that they had major flaws, rendering their findings completely wrong. For example, many of the studies were meta-analyses of previously published studies. You can easily prove anything you want by using the negative studies about a subject and ignoring the studies that show benefits. And that’s precisely what was done with the recent negative vitamin E studies. In addition, some of the studies used subjects who were near death, then gave the moribund patients vitamin E. Since many were past the point of no return in a health sense, the vitamins not only didn’t work but appeared to hasten their deaths—hence the misleading headlines.

     Still another problem with the recent studies about vitamin E is that in most cases only one form of vitamin E—alpha tocopherol—was used. Alpha tocopherol is considered the most potent form of vitamin E, but it is only one of eight forms. All forms exist in nature, and like other nutrients they work best together. In fact, some members of the vitamin E family that aren’t included in most food supplements go well beyond the health benefits offered by alpha tocopherol alone.

Man Does Not Live by Alpha Alone

     In 1922, researchers found that without vitamin E rats couldn’t reproduce. That link to reproduction branded vitamin E a “sex vitamin,” despite the connection between the nutrient and sex being tenuous at best. Other scientists isolated vitamin E from wheat germ in 1936 and figured out its chemical structure. The word tocopherol is from the Greek words tokos and pherein, and the two words combined translate into “to bear and bring forth offspring,” a reference to the initial discovery that rats deprived of tocopherol suffer spontaneous abortion.

     The vitamin E complex consists of four tocopherol forms: alpha, beta, gamma and delta, with the differences being minor structural changes. Also included in the complex are tocotrienols, which have four members as well: alpha, beta, gamma and delta. The tocotrienols have a slightly different structure in the tail sequence that gives them some highly beneficial properties.

      As noted earlier, some recent studies showed that alpha tocopherol, which is what most people think of when they consider vitamin E, provides surprisingly little cardiovascular protection. Yet other studies show that when consumed in food, vitamin E appears to offer potent cardiovascular protection. Why would getting the same nutrient in food prove superior to taking it in supplemental form? The answer is that foods contain the entire vitamin E complex.

That touches on an ongoing controversy: whether the natural or synthetic form is superior. While many scientists suggest that the synthetic version is just as potent as the natural, other research shows that natural vitamin E is clearly more potent and that it takes twice as much of the synthetic version to equal the effects of the natural version.

      Vitamin E’s history is similar to that of whey protein. For years whey was considered a waste product of dairy production and was discarded. Eventually, the great nutritional properties of whey became evident, and the picture changed dramatically. After the discovery of vitamin E, it became known that soybean oil was a rich source of alpha tocopherol. The biggest producer of soybean oil was the Eastman Kodak company, which used it in photo processing. Someone at the company realized that they could extract alpha tocopherol from the soybean oil waste products and then sell it in bulk to vitamin companies. To this day a division of Eastman Kodak is still the largest supplier of natural vitamin E.

       But that form of vitamin E isn’t as natural as many think. The soybean oil is processed by a chemical methylation technique, extracting only the alpha tocopherol form. The other vitamin E forms are discarded, even though they are found naturally in the soy oil. So even “natural” alpha tocopherol isn’t truly natural, since it doesn’t exist in an isolated form in nature.1

       The two most common forms of vitamin E found in food are alpha tocopherol and gamma tocopherol. The predominant of the two is gamma tocopherol, since the best sources of natural vitamin E are various vegetable oils, all of which contain larger amounts of gamma tocopherol than alpha tocopherol. The tocopherols are there for a good reason. Vegetable oils are polyunsaturated fats, which means they are highly prone to oxidation and rancidity. Tocopherols prevent that. Note that natural oils contain the entire vitamin E complex. If they only contained alpha tocopherol, they would turn rancid because, when found alone in oils, alpha tocopherol becomes a pro-oxidant.

     Those who take fish oil supplements should consider that effect. Most commercial fish oil supplements, whether liquid or capsules, contain only alpha tocopherol. To prevent fat oxidation in the oil, however, would require the presence of other tocopherols besides just alpha tocopherol, such as gamma and delta tocopherols. Indeed, some studies have tested fish oil supplements and found them to be oxidized. Now you know why.

      While alpha tocopherol is considered the most potent antioxidant of the tocopherols, it’s ineffective against some types of free radicals, which are by-products of oxygen metabolism that attack fatty structures in the body, such as cellular membranes. Gamma tocopherol, unlike the alpha version, defuses one of the most potent free radicals, peroxynitrate, and other nitrogen species that are linked to disease. Peroxynitrate is simply a combination of nitric oxide and the hydrogen peroxide that’s produced during normal metabolism.

      Nitric oxide precursor supplements, usually based on the amino acid arginine, are popular among bodybuilders. On the other hand, NO itself is a free radical, which is harmless unless it meets up with hydrogen peroxide in the body. Thus, those who take NO-producing supplements would be well advised to also use a supplement containing either mixed tocopherols or gamma tocopherol.

     Many free radicals are produced as a result of the metabolism of certain minerals, such as copper and iron. They are highly destructive, and are linked to various neurodegenerative diseases, such as Parkinson’s and Alzheimer’s. While alpha tocopherol has little effect on those mineral-associated free radicals, gamma and delta tocopherols attach to them and thus render them harmless.

     The other tocopherols also have an anti-inflammatory effect.2 Inflammation is now known to be the cornerstone of most serious diseases, such as cardiovascular disease and cancer. In addition, while some initial inflammation is required for muscular growth, extended inflammation blunts muscular recovery after training. That’s why antioxidants are often suggested for bodybuilders.

     While the anti-inflammatory power of alpha tocopherol is zilch, gamma tocopherol shows potent effects in that regard.3 It inhibits inflammatory eicosanoids made from dietary fat and also inhibits the same enzyme, COX-2, that is blocked by popular analgesic drugs used to treat arthritis and other types of chronic pain. Unlike the drugs, however, using gamma tocopherol won’t also increase the risk of dying from cardiovascular side effects. Since high levels of COX-2 are linked to various types of cancer, such as colon cancer, gamma tocopherol may offer preventive effects. Alpha tocopherol is useless in that area.

Diabetics experience low-level inflammation in the pancreas, which can destroy the beta cells that produce insulin, thus worsening the disease. Studies show that gamma and delta tocopherols block that inflammatory effect. 

     An increase in the density of vascular smooth muscle cells is linked to cardiovascular disease. While alpha tocopherol does inhibit that, taking the other tocopherols increases the potency significantly and thus offers more protection. In addition, mixed tocopherols are far more potent than the alpha variety alone in preventing platelets from sticking to each other in the blood.4 The clot that forms when this happens is often the immediate cause of most heart attacks and strokes.

     One of the most exciting findings about gamma tocopherol occurred in a study of 20,000 men. It found a protective effect of gamma tocopherol against prostate cancer, an effect not offered by alpha tocopherol. Men with the highest level of gamma tocopherol were 80 percent less likely to develop prostate cancer than men with the lowest levels. Gamma tocopherol inhibits the growth of prostate cancer cells far more than does alpha tocopherol. In addition, gamma tocopherol seems to prevent the cells from turning into cancer in the first place.

     Reactive nitrogen species, a form of free radicals, are implicated in the onset of Alzheimer’s disease. The brains of those who suffer from that dreaded disease show higher levels of nitrates, which are linked to brain destruction.5 Only gamma tocopherol protects against that internal onslaught in the brain, not alpha tocopherol.

     Bodybuilders would also be interested in another effect of gamma tocopherol. The primary breakdown product of the gamma form acts as a natural diuretic that promotes the excretion of sodium, thus alleviating water retention. From a health standpoint, that means less risk of high blood pressure. From a bodybuilding vantage, it means more muscular definition. Gamma tocopherol helps prevent high blood pressure thanks to its ability to protect nitric oxide in the blood from oxidation. NO dilates blood vessels, leading to a greater muscular pump, along with the notable “side effect” of lower resting blood pressure.

     The primary tocopherol blood carrier protein produced in the liver has a preference for alpha tocopherol over the other tocopherols (only 9 percent of gamma tocopherol is carried in that manner). That leads the other forms of vitamin E to be broken down much more quickly than alpha tocopherol. On the other hand, more recent investigations show that gamma tocopherol tends to concentrate in tissues such as fat, muscle and skin.

      One problem with taking large doses of alpha tocopherol (more than 100 units a day) is that the more alpha tocopherol you take in, the more gamma tocopherol is rapidly excreted. Conversely, taking in larger amounts of gamma tocopherol does the same thing to alpha tocopherol—more rapid excretion.6 The answer may be to use either a mixed, balanced blend of tocopherols or to take gamma tocopherol and alpha tocopherol supplements at different times. Sesamin, a lignan from sesame seeds, prevents the premature breakdown of gamma tocopherol, and some specific gamma-E, or mixed-tocopherol, supplements contain sesamin for that reason. On the other hand, rat studies show that combining sesamin with gamma E also blocks the production of the beneficial diuretic breakdown product of gamma tocopherol.

     Not all scientists think that consuming a lot of gamma tocopherol is a good idea. For example, Jiyan Ma, an assistant professor of molecular and cellular biochemistry at Ohio State University, published a study that involved exposing isolated brain cells taken from mice to high levels of end products of the metabolism of alpha and gamma tocopherols called quinones. The gamma tocopherol quinone led to cellular destruction by preventing an essential process called protein folding while alpha tocopherol quinones did not have that toxic effect. The experiment was also repeated with kidney cells from monkeys and on skin cells from mice, with similar results.

     Commenting on the results of the study, Ma said, “We think that gamma tocopherol may have this kind of damaging effect on nearly every cell in the body.” But once again, this study involved isolated cells taken from animals, not humans. In addition, the researchers looked at the activity of only alpha and gamma tocopherol by-products—not the actual nutrients. There is no human evidence that the toxic metabolite in question—gamma tocopherol quinone—accumulates or even exists in human cells. In fact, in the human body, half of ingested gamma tocopherol is converted into gamma-CEHC, the metabolite of gamma tocopherol that offers diuretic effects, and is excreted. In nature antioxidants work as a team, preventing toxic reactions that may develop from the normal metabolism. 

      The tocotrienols are even rarer than gamma tocopherol, though specific supplements, usually based on a palm or rice bran oil, are available. The tocotrienols have properties not offered by other members of the vitamin E complex.7 For example, only tocotrienols inhibit the enzyme in the liver that synthesizes cholesterol.8 Inhibiting that enzyme would lower blood cholesterol levels, and the most popular drugs prescribed to treat cardiovascular disease, statins, work in that manner. Tocotrienols may more effectively block the oxidation of low-density-lipoprotein cholesterol in the blood.9

Tocotrienols are distributed more evenly through the fatty membranes of cells, thus offering more protection than other members of the vitamin E family. Animal and cell studies show that tocotrienols alone may help prevent breast cancer.             

    They also prevent the destruction of neurons from overexcitation caused by large releases of glutamate in the brain.10 That happens during most strokes and accounts for the brain damage that often ensues. Tocotrienols reduce lipoprotein(a), which acts like low-density lipoprotein in accelerating cardiovascular disease, by an impressive 17 percent. Alpha tocopherol doesn’t affect lipo (a); in fact, most nutrients—other than niacin in large doses—don’t help in that regard.

     It’s clear that man does not live by alpha tocopherol alone, indicating once again that you cannot improve on the inherent wisdom of nature. Those wanting the complete health benefits offered by vitamin E need to take the entire complex, not just alpha tocopherol.


1 Saldeen, K. ,et al. (2005). Importance of tocopherols beyond a-tocopherol: evidence from animal and human studies. Nut Res. 25:877-889.

2 Jiang, Q., et al. (2001). Gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention. Am J Clin Nutr. 74:714-22.

3 Jiang, Q., et al. (2000). Gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. Proc Natl Acad Sci USA. 97:11494-9

4 Liu, M. , et al. (2003). Mixed tocopherols inhibit platelet aggregation in humans: potential mechanisms. Am J Clin Nutr. 77:700-6.

5 Williamson, K.S., et al. (2002). The nitration product 5-nitro-gamma tocopherol is increased in the Alzheimer brain. Nitric Oxide. 6:221-227.

6  Yoshikawa, S., et al. (2005). The effect of gamma tocopherol administration on alpha tocopherol levels and metabolism in humans. Eur J Clin Nutr. In press.

7 Theriault, A., et al. (1999). Tocotrienol: a review of therapeutic effects. Clin Biochem. 32:309-19.

8 Black, T.M., et al. (2000). Palm tocotrienols protect apo+E mice from diet-induced atheroma formulation. J Nutr. 130:2420-26.

9 Qureshi, A.A., et al. (1997). Novel tocotrienols of rice bran modulate cardiovascular disease risk parameters of hypercholesterolemic humans. Nutr Biochem. 8:290-98.

10 Packer, L., et al. (2001). Molecular aspects of a-tocotrienol antioxidant and cell signaling. J Nutr. 131:369S-373S.

©,2013 Jerry Brainum. Any reprinting in any type of media, including electronic and foreign is expressly prohibited.   

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