VITAMIN E

VITAMIN E (tocopherol)

Introduction

The recognition in 1920 that rats, given a semi-purified diet containing all the then known vitamins, failed to support reproduction was followed two years later by the demonstration of an unknown dietary factor, then called X, the inadequacy of which in the diet resulted in fetal resorption (Evans and Bishop, 1922). Wheat germ oil and lettuce were identified as good sources of factor X, which was shortly afterwards recognized as a vitamin and called vitamin E.

Vitamin E is a fat-soluble essential nutrient that stabilizes cell membranes. Naturally occurring tocopherols are a mixture of closely related compounds (isomers) designated alpha-tocopherol, beta-tocopherol, gamma-tocopherol and delta-tocopherol. Alpha-tocopherol has the greatest vitamin E activity in the body. Synthetic vitamin E, designated as dl-tocopherol or vac-tocopherol, is less active. Supplements usually incorporate vitamin E bound to simple acids to prevent its oxidation. Alpha tocopherol acetate and succinate are common forms; the acetate and succinate are forms broken down by intestinal enzymes to release vitamin E.

Free radicals: Vitamin E is the major lipid antioxidant in the body, the property for which it is best known. It squelches free radicals, highly reactive molecules that can attack neighboring molecules and damage polyunsaturated fatty acids in membrane lipids, proteins and DNA, damaging cells and leading to disease. Free radical damage is linked to CANCER, HEART DISEASE, CATARACTS and aging. This vitamin plays important roles in the immune system, the nervous system and the endocrine (hormonal) system.

Possible Roles in Maintaining Health

Cancer Population studies suggest that low blood levels of vitamin E and BETA-CAROTENE correlate with an increased risk of lung cancer. Mammary dysplasia, a precancerous condition of breast tissue, has been treated with vitamin E.

Cardiovascular disease: Supplementation with vitamin E has been effective in treating pain in the lower leg due to narrowed leg arteries (intermittent claudication). In research with experimental animals vitamin E was found to slow plaque build-up in arteries and seems to inhibit blood clot formation. Men with higher levels of vitamin E were found to have a decreased risk of angina, a type of chest pain that often occurs before a heart attack. The World Health Organization found that a low blood level of vitamin E was the highest risk factor in predicting heart disease and death.

Healthy men and women who supplemented with at least 100 IU of vitamin E daily had less heart disease. They may have experienced less oxidative damage to LDL (LOW-DENSITY LIPOPROTEIN, the undesirable form of blood cholesterol). In the test tube vitamin E is a potent inhibitor of LDL oxidation. Oxidation of LDL by free radicals and its uptake by cells in arterial walls may initiate the development of ATHEROSCLEROSIS. Patients with severe heart disease enrolled in the Cambridge Heart Antioxidant Study were treated with either 400 or 800 IU of vitamin E daily. After 17 months they had a significantly lower risk of developing heart attacks than those who received a placebo (blank) pill. A longer study may be needed to reveal an overall decline in death rate with supplementation. Other research suggests that the accumulation of plaque in arteries slows down with supplementation of 100 IU of vitamin E or more daily.

Neurologic disorders: Vitamin E plays an important role in maintaining normal nerve function. Vitamin E deficiency is usually associated with symptoms of peripheral NEUROPATHY. Recent results suggest that low vitamin E content in nerves precedes nerve degeneration. Vitamin E has been found to be beneficial in reducing the severity of symptoms Of TARDIVE DYSKINESIA, a side effect of long-term use of tranquilizers (phenothiazines) that produces involuntary movements.

Eye diseases: Population studies indicate that cataract free people consume more vitamin E and vitamin C than those with cataracts do. Premature infants can develop vitamin E deficiencies because they possess almost no FAT; hence fat-soluble vitamin stores are marginal. Premature infants receive vitamin E to prevent anemia and retinopathy (retrolental fibroplasia).

Immune system: Moderate amounts of vitamin E seem to increase the ability of macrophages to destroy bacteria and to boost activity of T lymphocytes, the foot soldiers and generals of the IMMUNE SYSTEM. Vitamin E may alter production of certain PROSTAGLANDINS; hormone-like substances derived from essential fatty acids that promote INFLAMMATION. It has been used to manage autoimmune conditions like LUPUS ERYTHEMATOSUS. Healthy elderly men and women supplemented with moderate amounts of vitamin E can show greater immune responsiveness than those who do not supplement with this vitamin. On the other hand, very high levels of vitamin E may inhibit immune function.

Other conditions: Case studies support claims that vitamin E promotes wound healing and minimizes scar tissue formation. Vitamin E supplementation has been suggested to reduce symptoms of PREMENSTRUAL SYNDROME. Most careful studies on the effects of vitamin E supplementation on muscular strength, maximum oxygen consumption or endurance have failed to demonstrate benefits. It is possible vitamin E can reduce oxygen debt and increase maximum oxygen consumption in adapting to high elevations.

Diabetes: Sometimes supplementation with vitamin E can improve glucose tolerance and insulin sensitivity in diabetic patients, and reduce the level of secondary damage due to the buildup of glucose-bound proteins.

Osteoarthritis: Vitamin E possesses mild and inflammatory activity, which may explain why it can help lessen pain associated with osteoarthritis.

Skin conditions: A variety of skin conditions such as Raynaud’s phenomenon and polymitosis have been treated with vitamin E.

Eye conditions: Oxidative damage probably promotes CATARACTS and macular degeneration associated with aging. Animals fed vitamin E-deficient diets develop macular degeneration. People with low-levels of antioxidants in blood have a higher risk of cataracts.

Sources

The highest levels of vitamin E occur in VEGETABLE OILS (safflower, soybean and sunflower Oils), BUTTER and MARGARINE, NUTS, wheat germ, whole-grain CEREALS, EGGS and green leafy vegetables. Most fruits and white bread contain negligible vitamin E. To obtain 100 IU of vitamin E, a level found to reduce the risk of heart disease, a person would have to eat six cups of kale, or 4.5 cups of sweet potatoes. Therefore, you can see we all need to supplement our diet with Vitamin E.

Requirements

The RECOMMENDED DIETARY ALLOWANCE (RDA) for vitamin E is 10 mg (10 IU) of alpha tocopherol per day for men and 8 mg (8 IU) per day for women over 25 years of age. Typical intakes in the United States range from 5 to 10 mg daily. It is generally believed that few individuals are frankly vitamin E deficient. However, surveys have revealed that 45% of affluent, elderly Americans may consume less than the RDA, and even susceptible but healthy persons eating a BALANCED DIET may benefit from vitamin E supplements, with less free radical damage and less risk of cancer and heart disease. Premature infants, individuals on very-low-calorie/low-fat diets or who do not absorb fat very well (including some elderly people) may be deficient. Chronic malabsorption of fat and fat-soluble vitamins, including vitamin E, can accompany cystic fibrosis, SPRUE and non-tropical sprue, chronic PANCREATITIS, CELIAC DISEASE and bile duct inflammation or blockage, among other conditions. SEE NOTE BELOW.

Symptoms of severe vitamin E deficiency include ANEMIA and neurologic disorders. Newborn infants, especially premature infants with vitamin E deficiency, experience EDEMA and blood abnormalities. The requirement for vitamin E increases with increased consumption of polyunsaturated oils due to the increased susceptibility to peroxidation. However, the optimal ratio is unclear. In extreme situations the requirement may exceed the RDA.

Safety

Vitamin E is one of the least toxic fat-soluble vitamins when administered orally, and most healthy adults can tolerate 400 to 2000 mg (IU) daily. Excessive vitamin E may cause fatigue, muscle weakness, stomach upset, headache, nausea and skin disorders. In certain patients with high blood pressure, vitamin E may elevate blood pressure. Those with HYPERTENSION, rheumatic heart disease or diabetes should seek medical advice before supplementing with vitamin E. People taking anticoagulant medications or who are deficient in VITAMIN K, or who have blood clots, should follow their physician’s advice regarding vitamin E supplements to avoid the potential problem with increased bleeding.

Meydani, Mohsen, “Vitamin E,” Lancet, 345 (January 21, 1995), pp. 170-75.


MORE VITAMIN E INFO

Vitamin E is an Antioxidant that Protects Nerve Cells

Vitamin E is an antioxidant and can prevent or reverse the effects of free-radicals — toxic oxygen compounds such as peroxide, superoxide, hydroxyl radical, singlet oxygen, peroxynitrite, and hypochlorite (1,2). Vitamin E is essential for the proper functioning of all tissue cells, but is especially crucial to the proper functioning of nerve cells. This is because toxic oxygen is produced at an increased rate in nerves, and because nerves are rich in lipids (3).

Vitamin E May Protect Against Cardiovascular Disease

Lipoproteins are also prone to damage from toxic oxygen. Lipoproteins are particles which continuously circulate in the bloodstream, serving to distribute food energy to muscle, heart, and other tissues of the body. They are made in the liver and contain fat, cholesterol, and significantly, small amounts of vitamin E that are used for self-maintenance. When lipoproteins are seriously damaged by free-radicals, they are devoured and removed by white blood cells, or phagocytes. When this occurs over time and in sufficient numbers within the walls of our arteries, atherosclerotic lesions result. Over the course of decades buildup of lesions result in artery narrowing.

Basic scientific research supports such a fundamental model: studies have revealed that dietary supplements can be used to raise the level of vitamin E in the lipoprotein particles (4,5,6). Useful dosages appear to be 800-1600 IU/day (7,8). Other studies show that such supplementation leads to the protection of the lipoproteins from toxic oxygen damage (7,9). Furthermore, studies suggest that vitamin E may protect directly against cardiovascular disease (10). A 17-month study of 2,002 patients, all with atherosclerosis, demonstrated a significant decrease in nonfatal myocardial infarctions with supplementation (11). Large-scale epidemiological surveys involving 87,245 females (12) and 39,910 males (13,14) revealed that daily supplements of vitamin E resulted in a striking decrease in risk for cardiovascular disease. The risk was about 40% less than in persons not taking vitamin E supplements. The effect of vitamin E supplements appeared to require at least two years of daily doses in order to take effect (15,16).

Vitamin E May Protect Against Cataracts

Cataracts are a condition of increased opacity of the lens of the eyes. The eyes are especially vulnerable to the free-radical damage that vitamin E counters, as this tissue is exposed to ultraviolet rays from the sunshine. A 3-year Finnish study of 410 men (17) has demonstrated an association between risk for early-state lens opacity and plasma vitamin E levels. It was shown that men with low levels of plasma vitamin E were 3.7 times greater at risk for acquiring lens opacity than men with high levels of plasma vitamin E.

Vitamin E, Free-Radicals, and Cancer

When free-radical oxygen compounds damage nucleic DNA, cancer may result. Studies have shown that vitamin E protects guanosine amino acid, a component of DNA, from damage by hydroxyl and superoxide radicals (18, 19). It destroys two other free-radicals, singlet oxygen and peroxynitrite (a substance similar to the nitrogen dioxide compounds present in cigarette smoke), that react with DNA, causing damage (20, 21, 22). In detoxifying singlet oxygen and peroxy radicals, it also protects cell membranes, including those adjacent to nucleic material (23).

Vitamin E and Lung Cancer

One epidemiological study of 3,968 men and 6,100 women in the United States (24) found that lightsmokers who consumed over 5.1 mg vitamin E/day had reduced risk for lung cancer while those who consumed under 3.69 mg vitamin E/day had an increased risk.

Vitamin E and Prostate Cancer

Studies in Finland and Switzerland suggest a connection between vitamin E and lowered risk for prostate cancer. A large epidemiological study of male smokers in Finland revealed a clear association between vitamin E supplementation and protection from prostate cancer (25). Of the 29,133 males who were studied, 151 of the non-supplemented males acquired prostate cancer, but fewer (99 males) of the supplemented males acquired prostate cancer. The Swiss study revealed that low levels of vitamin E in plasma (in smokers) was associated with an 8-fold increase for fatal prostate cancer (26).

Vitamin E and Stomach and Colon Cancer

Studies of 34,691 post-menopausal women at the University of Minnesota revealed reduced rates of stomach cancer among those who took more than 2.0 mg or more vitamin E/day (27). Another study at the same university, this of 35,215 women (55-69 years old at the start of the study) demonstrated a correlation between vitamin E intake and colon cancer (28). During the course of the 5-year study, the 212 cases of colon cancer were associated with lower (36 IU/day) vitamin E intake while those cancer-free had an average vitamin E intake of about 66 IU/day. The increased intake of vitamin E among the non-cancerous subjects was due to vitamin E supplements and not diet.

REFERENCES

1. Sies , H. and Stahl, W. (1995) Vitamins E and C, ?-carotene, and other carotenoids as antioxidants. Am. J. Clin. Nutr. 62, 1315-1321
2. Heinecke, J.W. (1997) Pathways for oxidation of low density lipoprotein by myeloperoxidase: tyrosyl radical, reactive aldehydes, hypochlorous acid and
molecular chlorine. Biofactors 6, 145-155
3. Traber, M.G. (1997) Regulation of human plasma vitamin E. Adv.Pharmacol. 38, 49-63
4. Kayden, H. and Traber, M. (1993) Absorption, lipoprotein transport, and regulation of plasma concentrations of vitamin E in humans. J. Lipid Res. 343-358.
5. Jialal, 1. and Grundy, S. (1992) Effect of dietary supplementation with alpha-tocopherol on the oxidative modification of low density lipoprotein. J. Lipid Res. 33,899-906
6. Thomas ‘ S., Neuzil, J., Mohr, D., and Stocker, R. (1995) Coantioxidants make ?-tocopherol an efficient antioxidant for low-density lipoprotein. Am. J. Ctin. Nutr.62 , 1357-1364
7. Fuller, C., Chandalia, M., Garg, A., Grundy, S.M., and Jialal, 1. (1996) RRR-7-toxopheryl acetate supplementation at pharmacologic doses decreases low-
density lipoprotein oxidative susceptibility but not protein glycation in patients with diabetes mellitus. Am. J. Clin. Nutr. 63, 53!759
8. Dimitrov, N., Meyer-Leece, C., McMillan, J., Gillilang, , Per off, M., and Malone, W. (1996) Plasma a-tocopherol concentrations after supplementation with water- and fat-soluble vitamin E. Am. J. Clin. Nutr. 64, 329-335
9. Reaven, P.D., Herold, D., Barnett, J., and Edelman, S. (1995) Effects of vitamin E on susceptibility of low-density lipoprotein and low-density lipoprotein
subfractions to oxidation and on protein glycation in NIDDM. Diabetes Care 18, 807-816
10. Steinberg, D. (1997) Oxidative modification of LDL and atherogenesis. Circulation 95, 1062-1071
11. Stephens, N., Parsons, Schofield, P., Kelly, F., Choeseman, K., Mitchinson, M., and Brown, M. (1996) Randomised controlled trial of vitamin E in patients with coronary disease. Lancet. 347, 781-785.
12. Stampfer, M., Hennekens, C., Manson, J., Colditz, G., Rosner, B., and Willet, W. (1993) Vitamin E consumption and the risk for coronary disease in women. NewEngl. J. Mod. 328,1444-1449
13. Rimm, E., Stampfer, M., Ascherio, A., Giovannucci, E., Colditz, G., and Willett, W. (1993) Vitamin E consumption and the risk for coronary heart disease in men. New E21. J. Med. 328,1450-1456
14. Willet, W.C. (1997) Potential benefits of preventive nutrition strategies in Preventive Nutrition (Ed.by A.Bendich and R.Deckelbaum) Humana Press, Totowa, NJ
15. Bonithon-Kopp, C., Coudray, C., Berr, C., Touboul, P., Feve, A., Favier, J, and Ducimetiere, P. (1997) Combined effects of lipid peroxidation and antioxidant status on carotid atherosclerosis in a population aged 59-71: The EVA study. Am. J. Clin. Nutr. 65, 121-127
16. Kritchevsky, S., Shimakawa, T., Tell, G., Dennis, B., Carpenter, J., Eckfeldt, J., Peacher-Ryan, G., and Heiss, G. (1995) Dietary antioxidants and carotid artery wall thickness. Circulation 92, 2142-2150
17. Rouhianinen, P., Rouhiainen, H., and Salonen, J. (1996) Association between low plasma vitamin E concentration and progression of early cortical lens
opacities. Am. J. Epidemiol. 144, 496-500
18. Zhang, D., Okada, S.,Yu,Y.,Zheng, P. Yama uchi,R Kasai, H. (1997) Vitamin E inhibits apoptosis, DNA modification, and cancer incidence induced by iron–mediated peroxidation in Wistar rat kidney. Cancer Res,57, 2410-2414
19. Moneghini, R. (1997) Iron homeostasis, oxidative stress, and DNA damage. Free Radical Biol. Med. 23, 783-792
20. Christen, S., Gee, P., and Ames, B.N. (1996) Methods Enzymol. 269, 267-278
21. Christen, S., Woodall, A., Shigenaga, M., Southwell-Keely, P., Duncan, M., and Ames, B.N. (1997) Proc. Nat. Acad. Sci. 94, 3217-3222
22. Kamal-Eldin, A. and Appelqvist, L.-A. (1996) The chemistry and antioxidant properties of tocopherols and tocotrionols. Lipds 31, 671-701
23. Liebler, D.C. and Burr, J.A. (1992) Oxidation of vitamin E during iron-catalyzed lipid peroxidation. Biochemistry 31, 8278-8284
24.Yong, L.-C., Brown, C.C., Schatzkin, A., Dresser, C.M., Slesinski, M., Cox, C.S., and Taylor, P.R. (1997) Intake ofvitamins E, C, and A and risk of lung cancer. Am. J. Epidemiology 146, 231-243
25. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group (1994) The effect ofvitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. New Engl. J. Med. 330,1029-1035
26. Eichholzer, M., Stahelin, H., Gey, K., Ludin, E., and Bernasconi, F. (1995) Int. J. Cancer 66, 145-150
27. Zheng, W., Sellers, T., Doyle, T., Kushi, L., Potter, J.D., and Folsom, A.R. (1995) Retinol, antioxidant vitamins, and cancers of the upper digestive track in a prospective cohort study of postmenopausal women. Am. J. Epidemiology 142, 955-960
28. Bostick, R Potter J , McKenzie, D., Sellers, T., Kushi, L., Steinmetz, K., and Folsom, A. (1993) Reduced risk of colon cancer with high intake of vitamin E: The Iowa Women’s H*~alth St~d`y. Cancer Res. 53, 4230-4237


Anti-Tumor Proliferation Properties of Vitamin EKimberly Kline and Bob G. Sanders
Vitamins and Minerals in the Prevention and Treatment of Cancer
Maryce M. Jacobs, PhD., Ed.
Nutritional modulation of antitumor mechanisms leading to the destruction of tumor cells with no effect on normal cells and minimal toxic side effects to the patient is the ultimate goal of nutrition-immunology-cancer research. The studies reviewed here show that vitamin E succinate is a potent, and potentially important, antitumor agent in that it prevents the growth of a wide range of tumor cells of hematopoietic origin. Vitamin E succinate also has the unique property of enhancing the proliferation of resting splenic and thymic lymphocytes but inhibiting the proliferation of mitogen stimulated T lymphocytes. Understanding how vitamin E succinate enhances the proliferation of normal resting lymphocytes, inhibits tumor cell growth, and inhibits the proliferation of mitogen stimulated T lymphocytes may be fundamental to our understanding of the role vitamin E plays as a modulator of retrovirus-induced immune dysfunctions and malignant cell growth.


NOTE: Like the other oil-soluble vitamins, vitamin E can be difficult to absorb from the intestine. Research has shown that as much as 90% of the vitamin E ingested is lost in the stool, that is, only 10% of vitamin E is absorbed.

Therefore, the vitamin E products we use in our office, from Biotics Research Corp, are emulsified so that the body absorbs almost 100% of the vitamin.

NOTE: There is an excellent BOOK on this vitamin at Amazon books.