Vitamin E
Description
Vitamin E is a fat soluble chemical which is found in the diet in varying amounts. This vitamin was discovered in 1922. The term vitamin E is used to refer to all tocol and trienol derivatives. The tocols are alpha-, beta-, gamma- and delta-tocopherols and the trienols are alpha-, beta-, gamma- and delta-tocotrienols. All these substances are found in plants and have vitamin E activity, but alpha-tocopherol is the most active form of vitamin E.
In the human body, vitamin E is present primarily as alpha-tocopherol. Vitamin E can be isolated from natural sources (plants, vegetables and meat) or can be made in the laboratory. Therefore, vitamin E is sold commercially as a natural or synthetic preparation.
Naturally occurring alpha-tocopherol is now referred to as RRR-alpha tocopherol (formerly d-alpha tocopherol), whereas synthetic alpha tocopherol is referred to as all-rac-alpha tocopherol (formerly dl-alpha-tocopherol). The esterified forms of vitamin E such as alpha tocopherol acetate, alpha tocopherol succinate and alpha tocopheryl nicotinate are made in the laboratory and are also sold commercially.
Vitamin E is essential for our growth and survival. However, the human body does not make this vitamin. We depend primarily on diet or supplement for our vitamin E needs. About 20% of ingested vitamin E is absorbed from the intestine.
It is now known that vitamin E undergoes very little degradation in the body. The main degradation products of vitamin E are tocopheryl quinone, tocopheryl hydroquinone, dimers, trimers and some water soluble substances.
The major route of excretion is through the feces. Adipose tissue, liver and muscle are major areas for the deposit of vitamin E. The consumption of higher amounts of vitamin E increases its level in all tissues.
Vitamin E is present within the cells in its free form as well as bound to proteins. These vitamin E binding proteins are present in the membrane, cytosol (soluble protein) and nucleus. The role of these vitamin E binding proteins in the mechanism of action of vitamin E is unknown.
Method of Action
The chemical formula of alpha tocopherol is C29H50O2. At least 8 compounds having vitamin E activity have been isolated from plant sources. All have a 6-chromonal ring structure and a side chain. The tocols have a phytol side chain, whereas the trienols have a similar structure, with double bonds at the 3', 7' and 11' positions of the side chain. Both tocols and trienols occur as a variety of isomers which differ from one another by the number and location of methyl groups on the chromonal ring. Alpha tocopherol is the most active form and the side chain is essential for full biological activity of vitamin E.
Vitamin E has more than one mechanism in the body. One of the most well established mechanisms is its capacity to destroy free radicals generated as a part of the oxidation reaction in the human body or by exogenous agents. This antioxidation mechanism of vitamin E has been demonstrated both in vitro and in vivo. Vitamin E has been shown to tabilize membranes by physiochemical interaction between its phytyl side chain and the fatty acyl chain of polyunsaturated phospholipids. It inhibits the synthesis of prostaglandins and prevents platelet aggregation in vitro and in vivo. There are some data which show vitamin E reduces the synthesis of thromboxane and increases the formation of prostacyclin.
Thromboxane is considered the most potent platelet aggregating factor; therefore, further study on the role of vitamin E in regulating the metabolism of arachidonic acid is needed.
Recent studies show that alpha tocopheryl succinate treatment induces cell differentiation in some cancer (melanoma) cells in vitro; however, it inhibits the growth of other tumor cells (murine neuroblastoma, rat glioma and human prostate) in vitro.
On the other hand, alpha tocopherol, alpha tocopheryl acetate and alpha tocopheryl nicotinate at similar concentrations were ineffective. However butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), which have antioxidant properties similar to those of vitamin E, were only partially effective in producing the above changes. Thus the effects of vitamin E succinate on cancer cells, in part, are mediated by its antioxidant mechanism. Alpha tocopherol also causes differentiation of mouse myeloid leukemia in vitro.
Recent in vitro studies have demonstrated a novel mechanism of action of vitamin E in which its antioxidant role is not involved. Vitamin E succinate treatment of cancer cells (neuroblastoma) and normal fibroblasts (murine L-cells) inhibits prostaglandin (PG)E1- and PGA2- stimulated adenylate cyclase (converts ATP to adenosine 3',5'-cyclic monophosphate) activity. This effect is primarily due to an inhibition of the catalytic protein activity of adenylate cyclase.
Because of the involvement of prostaglandins in the carcinogenic events, it has been proposed one of the mechanisms of cancer prevention by vitamin E may involve a reduction in adenylate cyclase response to prostaglandins. Since the production of excess of prostaglandins is associated with suppression of the immune system and platelet aggregation, the above mechanism of vitamin E may be involved in vitamin E-induced stimulation immunity and inhibition of platelet aggregation.
In a recent study, it has been observed vitamin E treatment of neuroblastoma cells increases the expression of c-mye gene (normal cellular gene) by about five-fold (Sharma & Prasad, unpublished observation).
This is the first demonstration that vitamin E can enhance the transcription of a particular sequence of DNA. The significance of this observation in the control of growth, differentiation and malignancy is unknown at this time.
The relative efficacy of natural and synthetic forms of vitamin E has not been adequately studied. In vitro experimental systems, the natural and synthetic forms of vitamin E were equally effective in causing growth inhibition of neuroblastoma and melanoma cells. However, d-form of vitamin E was more potent than dl-form in inhibiting the growth of glioma cells.
The studies discussed in this chapter show that vitamin E has a direct role in the regulation of gene expression both at the levels of transcription and translation.
The maximal potential of vitamin E for maintaining an optimal health and for disease prevention remains to be determined. The above goal cannot be realized until we know how vitamin E works on cellular and molecular levels.
Future vitamin E research will focus on this issue and at the same time will continue to emphasize the evaluation of the role of vitamin E in human health and disease prevention and treatment.
Properties & Uses
In recent years, consumers have been advised to use polyunsaturated fats instead of saturated fats in order to reduce the risk of heart disease. Some preliminary data suggest this advice is having a favorable impact in reducing the risk of heart disease. It has been reported in animals, the dietary need for vitamin E increases when the intake of polyunsaturated fatty acid becomes greater.
Nutrition scientists have established cellular membranes containing polyunsaturated fats are more easily damaged by free radicals than those which contain saturated fats. In order to protect membranes which contain high levels of polyunsaturated fats, the increased consumption of vitamin E is not only justified but essential.
In chickens, selenium deficiency causes poor absorption of vitamin E from the digestive tract. Vitamin E enhances the cancer preventive effect of selenium on chemical-induced breast cancer in rats. The relevance of this observation in humans has not been evaluated as yet. Both vitamin E and zinc act as a stabilizer of cellular membranes. Red blood cells from zinc- or vitamin E-deficient animals are easily broken by free radicals. Supplementation of diets with either vitamin E or zinc makes these membranes more resistant to free radical attack. Zinc-deficient diets cause skin and joint damage in the chicken. Dietary supplementation with high vitamin E doses prevents the above harmful effects of zinc deficiency. These studies suggest some effects of vitamin E and zinc on cells are similar.
The exposure of vitamin E to iron and copper enhances the destruction of vitamin E. It has been reported in low birth weight infants, administration of iron may cause the development of vitamin E deficiency anemia, particularly in those infants who were fed formula containing higher levels of polyunsaturated fatty acids.
Vitamin C protects vitamin E from the harmful effects of iron and copper as well as helps to regenerate vitamin E immediately after it has been destroyed by free radicals. During vitamin E deficiency, the levels of vitamin A (retinol and retinyl esters) in liver and retinol in plasma decrease.
These levels are increased during alpha tocopherol supplementation. The consumption of higher levels of dietary vitamin A increase the need for vitamin E in the body. Most human studies suggest that the consumption of vitamin E is essential for efficient vitamin A utilization and liver storage. Vitamin E deficiency may also cause deficiency of vitamin B-12. Thus the alterations in the level of vitamin E may effect the levels of other vitamins such as vitamins A, C and B-12.
Vitamin E has been shown to interact with some pollutants which are present in the environment and diet. The primary atmospheric pollutants are ozone and nitric oxide which are capable of generating free radicals in the body. Vitamin E has been shown to protect against the harmful effects of ozone and nitric oxide. The major food pollutants are nitrites which are present in fresh fruits and vegetables as well as in bacon, sausage and cured meat. Nitrites by themselves are not harmful to adults, but they can combine with amines in the stomach to form nitrosamine.
Nitrosamines are among the most potent cancer causing agents for both animals and human beings. The presence of vitamin C or vitamin E in the stomach may prevent the formation of or reduce the levels of nitrosamines. Taking vitamin C or E before eating fresh fruits and vegetables containing high levels of nitrites is not needed, because they contain another group of chemicals called phenolics, which, like vitamin E, act as an antioxidant and can prevent the formation of nitrosamines. However, it is important to take vitamin E just before eating bacon, sausage, or cured meat in order to prevent the formation of nitrosamines.
In addition to nitrosamines, many other mutagenic substances (agents which cause genetic changes) are formed in the digestive tract. All mutations do not cause cancer, but all cancers are preceded by mutations. It has been shown that the levels of mutagenic substances in the feces are higher for persons who are meat eaters than for those who are vegetarians. The presence of higher levels of fecal mutagenic substances may increase the risk of some cancers. It has been reported that taking vitamin E or vitamin C reduces the mutagenic substances in the feces. Furthermore, reports indicate that taking both vitamin E and C is more effective than taking either individually.
Many chemicals are not carcinogenic until they are converted to an active form in the body. In some cases vitamin E can prevent the conversion of inactive forms of such cancer causing substances to active forms. Vitamin E also prevents the action of tumor promoting and tumor initiating agents which are present in the environment and diet.
Vitamin E influences the effectiveness of many drugs which are currently used in cancer treatment. The above concept has been demonstrated on cancer cells in vitro. For example, vitamin E acetate in combination with vincristine, 5-fluorouracil, adriamycin, or chlorozotocin produced a synergistic effect, whereas vitamin E in combination with bleomycin, 1-(2-cholrethyl)-3-cyclohexyl-1-triazeno-imidazole-4-carboxamie (DTIC), mutamycin or cis-diamine) dichloro-platinum II (cis-platinum II) produced an additive effect on the inhibition of growth of neuroblastoma cells in vitro.
In glioma cell cultures, vitamin E acetate in combination with vincristine or CCNU produced a synergistic effect, whereas vitamin E in combination with bleomycin, 5-fluorouracil, adriamycin, DTIC, mutamycin and cis-platinum produced an additive effect on the inhibition of growth.
These studies suggest the effectiveness of the interaction of vitamin E with cancer chemotherapeutic drugs depends upon tumor form and type of drug. Vitamin E succinate also enhances the effect of some naturally occurring substances such as prostaglandins and sodium butyrate on neuroblastoma cells in vitro. The relevance of the above results in humans is not known at this time.
Several experimental studies have reported vitamin E protects normal tissue against radiation damage; however, higher doses of vitamin E succinate enhance the effect of radiation on cancer cells in vitro.
In addition, vitamin E succinate markedly reduces the occurrence of radiation-induced cancer in vitro. High doses of vitamin E succinate also enhance the effect of heat on cancer cells in vitro. The above effects of vitamins have not been tested on humans as yet.
Vitamin E protects cells from the toxicity of certain heavy metals. For example, organic mercury is known to cause neurological diseases because of damage to the brain cells. The administration of vitamin E immediately before treatment of animals with organic mercury markedly reduces the symptoms of brain damage in rats, mice and quail. Vitamin E succinate also protects glia cells, one of the cell types present in brain, in vitro against organic mercury-induced toxicity. Only selenium appears to enhance the effect of vitamin E on the prevention of chemical-induced cancer in vitro.
Vitamin E administration has been useful in the treatment of those diseases in humans which are due to vitamin E deficiency. Vitamin E acetate (400 I.U.) has been shown to be useful in the treatment of cystic mastitis, the most common noncancerous growth of the breast in females.
Vitamin E acetate (1600 I.U./day) before the administration of adriamycin reduces its toxic effect in patients with cancer. This is consistent with the animal studies in which vitamin E has been shown to reduce the toxic effects of adriamycin on heart and skin. Vitamin E also protects against lung damage in animals produced by bleomycin, a commonly used drug in the treatment of cancer. One study reports vitamin E therapy reduces some of the symptoms of premenstrual syndrome. Several animal and a few human studies have suggested vitamin E may be useful in the prevention of some human cancer. Currently, the effect of oral intake of vitamin E (400-800 I.U./day) in the form of alpha tocopherol, alpha tocopheryl acetate or alpha tocopheryl succinate on the risk of developing some forms of cancer among the high risk human population is being studied.
Vitamin E may reduce lung damage produced by cigarette smoke. There is increasing evidence free radicals are generated in the lung by the substances which are present in the cigarette smoke. These free radicals are responsible for increasing the risk of lung cancer as well as of emphysema (a chronic lung disease in which breathing becomes difficult).
The level of vitamin E in the fluid surrounding lung tissue is six times less among smokers in comparison to those who do not smoke. The presence of higher levels of vitamin E in these fluids or in lung tissue may protect lungs from the attack of free radicals. Vitamin E may have a role in the management of some neurological diseases. A group of neurologists are initiating a new clinical study using vitamin E in combination with deprenyl in order to slow down the progression of disease in patients with Parkinsonism. It is believed free radicals are generated by degradation products of dopamine (a chemical which is essential for brain function) and by drugs used in the treatment of Parkinsonism.
There are very limited animal studies regarding the use of vitamin E in the management of cancer. One clinical study has utilized high intravenous doses (up to 2 grams per day) of alpha tocopherol in the treatment of IV Stage metastatic neuroblastomas. The objective regression was observed in 50% of treated patients. Preliminary data suggest vitamin E can help in the management of cancer in more than one way. It can kill tumor cells, enhance the effect of tumor therapeutic agents (drug, radiation and heat), reduce their toxic effect and enhance the immune functions. Numerous animal and one human study suggest high doses of vitamin E may enhance the body's immune defense system. More human studies are needed to evaluate the rate of vitamin E in the treatment of cancer.
Free radicals have been implicated in accelerating the aging processes of organisms as well as individual organs in the body. Therefore, the supplemental use of vitamins on a regular basis should slow down aging processes. This hypothesis has not been adequately tested in humans or animals. In vitro data show the addition of vitamin E increases the survival of nerve cells.
Consequence of Deficiency
Vitamin E deficiency can result from a low intake of fresh fruit and vegetables and other foods not rich in vitamin E. Deficiency can also occur in those individuals who cannot absorb fat. In addition, damage to the pancreas, bile duct, liver, and surgical removal of the major portion of the digestive tract can cause vitamin E deficiency. The plasma level of vitamin E in normal adults is about 10 mcg/ml; a plasma level of 5 mcg/ml or less is considered an indication of vitamin E deficiency.
Several human diseases are associated with vitamin E deficiency. Premature infants are born with a deficiency of vitamin E. The smaller the infant, the greater the degree of deficiency. The lack of adequate tissue storage and poor absorption due to immature digestive systems are responsible for this deficiency.
Premature infants can suffer lung and brain damage. The above symptoms appear to be related to vitamin E deficiency because when vitamin E is injected into the muscle these symptoms do not develop. Children with the disease of poor absorption from the intestine develop brain damage as well as muscle damage. When vitamin E is injected into the muscle, the symptoms resulting from brain damage improve. In children with cystic fibrosis symptoms of nerve damage are commonly seen and are considered due to vitamin E deficiency due to poor absorption from the digestive tract.
Hemolytic anemia results from the deficiency of the enzyme glucose-6-phosphate dehydrogenase or of glutathione synthetase. Red blood cells become more sensitive to attack by free radicals, because they cannot form lipids in which vitamins can be stored. Increasing the blood level of vitamin E has been found to be useful in this disease.
In animals, vitamin E deficiency leads to severe damage to muscles. In addition, vitamin E deficiency has been associated with aggregation of platelets. This chemical change in the blood increases the risk of heart disease. Lower blood levels of vitamin E appear to be related to higher risks of subsequent development of breast cancer. Animal studies suggest vitamin E deficiency may decrease the immune competency of the host.
Toxicity Factors
In a large human trial involving 9,000 adults, a daily oral intake of 3,000 I.U. per day of vitamin E acetate for 11 years did not produce any detectable major side effects; however, isolated cases of fatigue, skin reactions and upset stomach have been reported after ingestion of high doses (above 1000 I.U.) of vitamin E for a prolonged period of time. Local complications such as soft tissue calcification at the site of injection were reported in two cases of infants who received vitamin E acetate through muscle.
It should be emphasized some of the solvents used in vitamin E preparations have been found to be extremely toxic in vitro. Therefore, any clinical report on humans which does not use solvent as a control cannot be considered conclusive.
Animal studies on toxicity of vitamin E appear contradictory. For example, a high dose of vitamin E acetate (500 mg/kg of body weight) was not toxic in mice; whereas in another study a dose of 400 mg/kg of body weight of dl-alpha tocopheryl acetate was lethal to mice. Unfortunately, the effect of the solvent in which vitamin E was dissolved, was not studied. This may, in part, explain the above opposing results.
One study reports the chronic intake of supplemental vitamin E with food causes an increased deposit of fat in the rat liver. A very high dose of vitamin E (4% of diet) enhances the incidence of chemically-induced tumor.
If one considers the average adult human consumes about 1 kg of food daily, the above dose of vitamin E would be the equivalent of 40 g/day. Such high doses of vitamin E are not consumed by humans and are not relevant to human health or to disease prevention.
Based on many studies, it can be estimated that doses up to 400 I.U. of vitamin taken orally, divided into two doses per day, are unlikely to produce any major toxic effects in an average normal adult. Vitamin E is sold commercially as the esterified form (alpha tocopheryl acetate, alpha tocopheryl succinate and alpha tocopheryl nicotinate) or as the non-esterified form alpha tocopherol). They are sold in tablets, capsules, gelatin or in liquid. It should be emphasized the solutions in which vitamin E is dissolved markedly vary from one preparation to another, and many of them have been found to be very toxic in vitro.
The efficacy of various forms of vitamin E appears to be different. Recent experimental studies suggest alpha tocopheryl succinate is more effective than the other forms of vitamin E; however, this has not been tested in humans as yet.
The unesterified form of vitamin E is absorbed from the digestive tract, whereas the esterified forms are first converted to alpha tocopherol by an enzyme and then they are absorbed. The juices from the pancreas and bile help to solubilize vitamin E and thus aid in its absorption. A small protein in the blood acts as a carrier for vitamin E and takes it to all the organs in the body. Since the maximum level of alpha tocopherol in the blood appears 4 to 6 hours after vitamin E is ingested and drops to a basal level in about 12 hours, the maintenance of higher blood levels of vitamin E requires taking it twice a day (morning and evening).
Vitamin E should be consumed both as alpha tocopherol and in the form of an ester (alpha tocopheryl acetate or alpha tocopheryl succinate). The ester form of vitamin E is not degraded in the presence of light and oxygen as rapidly as alpha tocopherol; therefore, its potency in the bottle can be maintained for a longer time. However, they cannot act as antioxidants until they are converted to alpha tocopherol. The presence of alpha tocopherol in the stomach in necessary in order to block carcinogenic events such as the formation of nitrosamines.
Recommended Dietary Allowance
| age | RDA (mg) | I.U. | |
| infants/children | |||
| 0-6 months | 3 | 4.5 | |
| 6-12 months | 4 | 6 | |
| 1-3 years | 6 | 9 | |
| 4-10 years | 10 | 15 | |
| males | |||
| 11-14 years | 10 | 15 | |
| 15+ years | 10 | 15 | |
| females | |||
| 11-14 years | 8 | 12 | |
| 15+ years | 8 | 12 | |
| pregnancy | 10 | 15 | |
| lactation(1st 6 month) | 12 | 18 | |
| (2nd 6 month) | 11 | 16.5 |
1 mg d-alpha tocopherol = 1 alpha tocopherol.
1 alpha tocopherol equivalent = 1.5 international units.
1 international unit (iu, IU) = 1 USP (United States Pharmacopoeia)
An average U.S. diet contains about 7.4 - 9.0 mg of alpha tocopherol. This represents only about half of the amount of RDA. RDA of a vitamin is defined as the amount which is needed for growth and survival. This amount is sufficient to prevent vitamin deficiency. At this time the doses of vitamin E necessary for the greatest benefit to human health or for disease prevention are unknown.
For over thirty years, Recommended Daily Amounts has existed in the United Kingdom. It has been used to measure the adequacy of an individual's diet. However, in 1991 the Committee on Medical Aspects of Food Policy (COMA) gave forth a whole new set of figures upon the request of the Department of Health's Chief Medical Officer. Reference Nutrient Intake (RNI) is one of these sets collectively known as "Dietary Reference Values." RNI is an amount of a nutrient that is enough for almost every individuals, even someone who has high needs for the nutrient. This level of intake is, therefore, considerably higher than what most people would need. If individuals are consuming the RNI of a nutrient they are most unlikely to be deficient in that nutrient.
The requirement for Vitamin E is determined to a large extent by the polyunsaturated fatty acid (PUFA) content of the diet. The COMA 1991 panel on Dietary Reference Values felt PUFA intakes in Britain varied so widely it was impossible to set RNI's. Also, people's individual requirements for Vitamin E vary dramatically.
Food Sources
Vitamin E occurs in plants, fruits and vegetables primarily as the unesterified form; however, vitamin E is added to many food preparations primarily as an esterified form (alpha tocopheryl acetate). This is due to the fact that the ester form of vitamin E is more stable than the non-ester form.
Among vegetables, spinach, parsley, mustard, sweet potato and turnip leaves are very rich sources of vitamin E, whereas broccoli and cauliflower are poor sources. Other rich sources of vitamin E include fruits (apple skins and cucumbers), egg yolk, meat and fish (fish is much richer than meat), milk (human milk is much richer than cow milk), oil and fats (vegetable oils are generally much richer than animal fats), and nuts (almonds have high amounts, peanuts have medium and pecans and coconuts have lowest contents of vitamin E). Vegetables are the richest source of vitamin E. The level of vitamin E in vegetable oil ranges from 100 (olive oil) to 1194 mcg/g of oil (wheat germ oil) whereas fish and meat contain in the range of 4 - 33 mcg/g of fish or meat. Alpha tocopherol is destroyed rapidly when exposed to oxygen and light, however, the ester form of vitamin E is not. During food processing the vitamin E content is reduced. Natural drying is done by exposing the dietary materials directly to the sun. This process destroys 100 percent of vitamin E content of food. The artificial drying process causes only 36 - 45% loss of vitamin E.
Canning of food results in a loss of 40 - 65% of vitamin E content. Vitamin E is not degraded during the freezing process; however, frozen foods are generally stored at higher temperatures than those used for freezing and this causes a reduction in the vitamin E content of frozen food. Commercial packaging also produces significant vitamin E loss. Refining and bleaching food products reduces the content of vitamin E. Frying readily degrades alpha tocopherol; however, the esterified form of vitamin E is not destroyed under this condition. Ordinary methods of cooking do not cause appreciable loss of vitamin E.
References
Azuma-E et al: Acute hemolysis during cyclosporine therapy successfully treated with vitamin E. Bone-Marrow-Transplant. 1995 Aug; 16(2): 321-2.
Bendich, A., Machlin, L.J. Am J Clin Nutr., 1988; 48: 612-619.
Borek, Ong, Mason, Donahue, and Biaglow, J.E. eds. Selenium and Vitamin E Inhibit Radiogenic and Chemically-Induced Transformation In Vitro Via Different Mechanism. Proc. Natl. Acad. Sci. Usa 83:1490-1494, 1986.
Bourantas-KL et al: Treatment of 34 patients with myelodysplastic syndromes with 13-CIS retinoic acid. Eur-J-Haematol. 1995 Oct; 55(4): 235-9.
Chai-J et al: [Protective effects of vitamin E on impaired neutrophil phagocytic function in patients with severe burn] Chung-Hua-Cheng-Hsing-Shao-Shang-Wai-Ko-Tsa-Chih. 1995 Jan; 11(1): 32-5.
Chalmers-TC: Antioxidants and cardiovascular disease: why do we still not have the answers? [editorial; comment] Ann-Intern-Med. 1995 Dec 1; 123(11): 887.
Chavance, M., et al. In: Nutrition, Immunity, and Illness in the Elderly. Pergamon Press: New York, 1985, pp. 137-142.
Cheraskin, E., Ringsdorf, W.M., Jr. Nutr Rep Int., 1970; 2: 107-117.
De Duve, C. and Hayaishi, O. eds. Tocopherol, Oxygen and Biomembranes. Elsevier North Holland Biomedical Press, N Y, 1978.
de-la-Maza-MP et al: Effects of long-term vitamin E supplementation in alcoholic cirrhotics. dJ-Am-Coll-Nutr. 1995 Apr; 14(2): 192-6.
DiMascio, P., Murphy, M., Sies, H. Am J Clin Nutr., 1991; 53: S194- S200.
Dimitrov, N.V., et al. Am J Clin Nutr., 1991; 53: 723-729.
Diplock, A.T., et al [eds.]. Vitamin E: Biochemistry and Health Implications. Vol 570. Ann NY Acad Sci: New York, 1989, pp. 1-535.
Esterbauser, H., et al. Am J Clin Nutr., 1991: 53; S314S-321S.
Evans-DJ et al: Symptomatic vitamin E deficiency diagnosed after histological recognition of myometrial lipofuscinosis. Lancet. 1995 Aug 26; 346(8974): 545-6.
Fong, J.S.C. Experientia, 1976; 32: 639-641.
Gaby, W.K., Machlin, L.J. In: Vitamin Intake and Health: A Scientific Review. Marcel Dekker: New York, 1991, pp. 71-101.
Gattaz-WF: Does vitamin E prevent tardive dyskinesia? [letter]. Biol-Psychiatry. 1995 Jun 15; 37(12): 896-7.
Giani, E., Masi, I., Galli, C. Lipids, 1985; 20: 439-448.
Godukhin-OV et al: [The effect of antioxidants on functional brain disorders caused by low-intensity ionizing radiation] Radiats-Biol-Radioecol. 1995 Jul-Aug; 35(4): 500-6.
Gorozhanskaia-EG et al: [The role of alpha-tocopherol and retinol in correcting disorders of lipid peroxidation in patients with malignant liver neoplasms] Vopr-Onkol. 1995; 41(1): 47-51.
Guarnieri-C et al: Vitamin E can protect myocardium against oxidative damage. Cardiovasc-Res. 1995 Jul; 30(1): 153-5; discussion 156-7.
Haenszel, W., et al. Int J Cancer, 1985; 36: 43-48.
Horwitt, M.K. Am J Clin Nutr., 1988: 47; 1088-1089.
Inder-TE et al: Vitamin A and E status in very low birth weight infants: development of an improved parenteral delivery system. J-Pediatr. 1995 Jan; 126(1): 128-31.
Inglod, K.U., et al. Arch Biochem Biophys, 1978; 259: 224-225.
Jacques, P.F. Arch Opthalmol., 1988; 106: 337-340.
Johnson-L et al: Severe retinopathy of prematurity in infants with birth weights less than 1250 grams: incidence and outcome of treatment with pharmacologic serum levels of vitamin E in addition to cryotherapy from 1985 to 1991. J-Pediatr. 1995 Oct; 127(4): 632-9.
Kessopoulou-E et al: A double-blind randomized placebo cross-over controlled trial using the antioxidant vitamin E to treat reactive oxygen species associated male infertility. Fertil-Steril. 1995 Oct; 64(4): 825-31.
Kirschmann, J.D. Nutrition Almanac: Nutrition Search. McGrew-Hill: New York. 1990.
Kleijnen-J: Vitamin E [letter; comment] Lancet. 1995 Mar 18; 345(8951): 737.
Knekt, P. et al. Am J Clin Nutr., 1991; 53: 283S-286S.
Kneckt, P. Int J Epidem., 1988; 17: 281-286.
Kok, F.J. et al. N Eng J Med., 1987; 316: 1416.
Knekt, P., et al. Am J Epidemiol., 1988; 127: 28-41.
Machlin, L.J. ed. Handbook of Vitamins; Nutritional, Biochemical, and Clinical Aspects. Marcell Dekker, Inc., New York, 1984.
Machlin, L.J. ed. Vitamin E. Marcel Dekker, Inc., New York, 1980.
Mandal-AK et al: Is quinine effective and safe in leg cramps? J-Clin-Pharmacol. 1995 Jun; 35(6): 588-93.
Menkes, M.S., et al. N Eng J Med, 1986; 315: 1250-1254.
Meydanin, S.N., et al. FASEB J., 1989; 3: A1057.
Meyskens, F.L. & Prasad, K.N. eds. Modulation and Mediation of Cancer by Vitamins. Karger Press, Basel, 1982.
Meyskens, F.L. & Prasad, K.N. eds. Vitamins and Cancer. Humana Press, New Jersey, 1986.
Miyamota, H. et al. Cancer, 1987; 60- 1159-1162.
Murray, M.T. & Pizzorno, J.E. Encyclopedia of Natural Medicine. Rocklin, CA: Prima Publishing,1991.
Nachbar-F & Korting-HC: The role of vitamin E in normal and damaged skin. J-Mol-Med. 1995 Jan; 73(1): 7-17.
Nattakom-TV et al: Use of vitamin E and glutamine in the successful treatment of severe veno-occlusive disease following bone marrow transplantation. Nutr-Clin-Pract. 1995 Feb; 10(1): 16-8.
Nicki, E., et al. Am J Clin Nutr., 1991; 53: S201-S205.
Pacht, E.R., et al. J Clin Invest., 1986; 77: 789-798.
Palmieri-B et al: Vitamin E added silicone gel sheets for treatment of hypertrophic scars and keloids. Int-J-Dermatol. 1995 Jul; 34(7): 506-9.
Paolisso-G et al: Chronic intake of pharmacological doses of vitamin E might be useful in the therapy of elderly patients with coronary heart disease. Am-J-Clin-Nutr. 1995 Apr; 61(4): 848-52.
Pascoe, G.A., et al. Eur J Biochem., 1987; 166: 241-247.
Prasad, J.S. Am J Clin Nutr., 1980; 33: 606-608.
Prasad, K.N. ed. Vitamins, Nutrition and Cancer, Karger Press, Basel, 1984.
Pryor, W.A. Am J Clin Nutr., 1991; 53: 702-722.
Reaven-PD et al: 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. 1995 Jun; 18(6): 807-16.
Recommended Dietary Allowances. 1989. National Academy of Science, National Academy Press, Washington, D.C.
Riemersma, R.A., et al. In: Vitamin E: Biochemistry and Health Implications. Vol 570. Ann NY Acad Sci: New York, 1989, pp. 291-295.
Riley-JD; & Antony-SJ: Leg cramps: differential diagnosis and management. Am-Fam-Physician. 1995 Nov 1; 52(6): 1794-8.
Robertson, J., Donner, A.P., Trevithick, J.R. In: Vitamin E: Biochemistry and Health Implications. Vol 570. Ann NY Acad Sci: New York, 1989, pp. 372-382.
Rodrigues-CI et al: Results of radiotherapy and vitamin E in the treatment of Peyronie's disease. Int-J-Radiat-Oncol-Biol-Phys. 1995 Feb 1; 31(3): 571-6.
Sahu, S.N., Prasad, J.E. & Prasad, K.N. eds. Vitamin E Succinate-Induced Inhibition of Prostaglandin-Stimulated Adenylate Cyclase Activity in Neuroblastoma Cells. Inter J. Cancer, in press.
Salonen, J.T., et al. Br Med J., 1985; 290: 417-420.
Steiner, M. Thromb Haemostas., 1983; 49: 73-77.
Sword, J., Pope, A., Hoekstra, W. J Nutr., 1991: 121; 258-264.
Sword, J., Pope, A., Hoekstra, W. J Nutr., 1991: 121; 251-257.
Taylor, A. Nutr Rev., 1989; 47: 225-234.
Taylor, A. Nutr Rev., 1989; 47: 225-234.
Tolonen, M., Markku, H., Sarna, S. Biol Trace Elem Res., 1985; 7: 161- 168.
Van Den Berg, J.J., et al. In: Vitamin E: Biochemistry and Health Implications. Vol 570. Ann NY Acad Sci: New York, 1989, pp. 527-529.
Volkert-D; Schlierf-G: [Vitamin E] Dtsch-Med-Wochenschr. 1995 Oct 27; 120(43): 1486-7.
Wagdi-P et al: [Cardioprotection in chemo- and radiotherapy for malignant diseases--an echocardiographic pilot study] Schweiz-Rundsch-Med-Prax. 1995 Oct 24; 84(43): 1220-3.
Wald, N.J., et al. Br J Cancer, 1984; 49: 321-324.
Walji, H., Vitamin Guide: Essential nutrients for healthy living., Element: Dorset, U.K. 1992.
Walji, H., Vitamin Minerals & Dietary Supplements., Hodder Headline Plc.: London, U.K. 1994.
Weisburger, J. Am J Clin Nutr., 1991; 53: S226-S237.
Young-EG & Frazier-JL: Vitamin E and the risk of coronary artery disease. Ann-Pharmacother. 1995 May; 29(5): 531-3.
| Signup Free Applied Health Journal |
||||
|
FREE Sample Issue Your email address is all we need to start you on a better path to health. We respect your privacy.
|
