Vitamin E

Overview

In 1932, Evans and Bishop discovered that something in vegetable oils was necessary for reproduction in rats and named it vitamin E. They referred to it as the antisterility vitamin, which turned out to be an unfortunate designation since it was subsequently found not to have this activity in humans. The same researchers isolated the pure substance from wheat germ oil in 1936 and elucidated the structure in 1938, giving it the chemical name of tocopherol (after the Greek words tokos, meaning offspring, and Phero, meaning to bring forth).

Vitamin E is actually a group of eight compounds including four tocopherols (alpha, beta, gamma, and delta) and four additional tocotrienol derivatives. Alpha tocopherol is the most common and the most potent form. It is what is usually meant by the term vitamin E. Pure vitamin E compounds are easily oxidized, so they are manufactured as acetate or succinate esters.

Dosage Info

Dosage Range

Dosages that have been used in clinical studies generally range from 30 to 1,000IU daily. Doses as high as 3,000IU have been used in certain health conditions such as Huntington's disease. (1)

Most Common Dosage

200 IU daily.

100 IU = 67 mg of natural vitamin E (RRR-alpha-tocopherol or d-alpha-tocopherol) = 100 mg of synthetic vitamin E (all rac-alpha-tocopherol or d,l-alpha-tocopherol)

Dosage Forms

Capsules, gel capsules, and emulsified liquid drops, and mycelized liquid drops.

Adult RDI

20mg (30 IU)

Adult ODA

50-400 IU

RDA

  • Infants <6 months: 4mg(6 IU)(Adequate Intake, AI)
  • Infants 7-12 months: 5mg(7.5 IU)(AI)
  • Children 1-3 years: 6mg(9 IU)
  • Children 4-8 years: 7mg(10.5 IU)
  • Children 9-13 years: 11mg(16.5 IU)
  • Males >14 years: 15mg(22.5 IU)
  • Females >14 years: 15mg(22.5 IU)
  • Pregnancy: 15mg(22.5 IU)
  • Lactation: 19mg(28.5 IU)

Interactions and Depletions

Interactions

Depletions

Active Forms

Eight stereoisomers are possibly with alpha-tocopherol. Seven of these are only found in the synthetic form. Thus synthetic vitamin E, historically known as d,l-alpha-tocopherol, is more accurately referred to as all rac-alpha-tocopherol. The natural stereoisomer of vitamin E, historically d-alpha-tocopherol, is more accurately RRR-alpha-tocopherol. It has been shown that natural vitamin E has a substantially greater bioavailability than synthetic vitamin E. (2) , (3)

Absorption

As with all fats, the intestinal absorption of vitamin E requires adequate production of bile salts and pancreatic enzymes. It is estimated that normally healthy humans absorb from 50 to 70 percent of dietary vitamin E. However, absorption efficiency falls to less than 10 percent with therapeutic doses above 200mg.

Natural vitamin E has approximately one and a half times the bioavailability of synthetic vitamin E. (4)

Toxicities & Precautions

General

There are no known toxicities associated with vitamin E. Approximately 60 to 70 percent of the daily dose is excreted in the feces. Most individuals studied while taking large doses of vitamin E have not shown toxic effects. A recent meta-analysis found that large doses of vitamin e was associated with an increase of over-all mortality. The dosage associated was greater than 400 IU daily. (5)

Side Effects

Isolated cases of people taking over 1,000 IU daily reported side effects that included headache, fatigue, nausea, double vision, muscular weakness, and GI distress.

Functions in the Body

Antioxidant

Vitamin E is the body’s most important fat-soluble antioxidant. As such, it insures the stability and integrity of cellular tissues and membranes throughout the body by preventing free radical (lipid peroxidation) damage. Vitamin E has demonstrated increases in HDL levels and has prevented the oxidation of LDL cholesterol. (6)

A study involving one hundred and fifty three patients with coronary artery disease evaluated the clinical impact of antioxidant supplementation, including vitamin C, vitamin E, beta-carotene and selenium, on people with low HDL levels in an effort to improve the HDL-C:LDL-C ratio. The participants were followed for 12 months after randomization to one of three groups. They received either placebo, simvastatin and niacin, or simvastatin, niacin plus antioxidants (vitamin C, vitamin E, Beta-carotene and selenium). The treatment groups compared to the placebo group had significant reductions in plasma cholesterol, triglycerides and LDL-C. The desired increases in HDL-C were higher in the simvastatin/niacin group than in the simvastatin/niacin/antioxidant group. The investigators noted that the increases in the HDL2-C, Lp(A-I), and HDL particle size noted in the simvastatin/niacin group were apparently blunted by the additional use of the antioxidants. (7)

Chemotherapy stresses the antioxidant defense system and may lead to lower antioxidant levels which could cause an increase in the adverse side effects of the therapy. A study was conducted involving children with acute lymphoblastic leukemia who were undergoing chemotherapy were administered greater intakes of antioxidants. The increased consumption of vitamin E at 3 months decreased the risk of infection. (8)

Blood

Decreases platelet adhesion, protects blood vessels against developing atherosclerotic lesions, and prevents LDL-cholesterol from being oxidized.

Immune System

Vitamin E supplementation has been shown to enhance the immune system and support resistance to infection.

Exercise

During heavy exercise, vitamin E markedly reduces the amount of exercise-induced free radical damage to the blood and tissues, and also helps the body reduce the incidence of exercise-induced muscle injury.

Eyes

Helps the body protect the eyes against cataracts and macular degeneration.

Clinical Applications

Heart Attack Prevention

Patients with a previous myocardial infarction who took 400 or 800 IU of vitamin E daily had a 47 percent reduction in secondary heart attacks. (9)

Atherosclerosis.

Vitamin E retards LDL oxidation, inhibits the proliferation of smooth muscle cells, and reduces the damage to vascular endothelial cells. (10)

Cataracts

Vitamin E supplements result in a 50 percent decrease in risk of cataracts. (11) In fact, 158 patients were followed for three years and daily use of beta-carotene, vitamin C and vitamin E demonstrated a small deceleration in the progression of age-related cataracts. (12)

Cervical Dysplasia

Women with cervical dysplasia have significantly lower plasma vitamin E levels. (13)

Alzheimer's Disease

Over a period of 2 years, vitamin E 2,000 IU/day was shown to slow the progression of the disease. (14)

Cancer

Vitamin E protects against carcinogenesis and tumor growth and also reduces the toxicity of several anticancer therapies. (15)

Diabetes

Low vitamin E levels increase the risk of non-insulin dependant diabetes (16) and supplementation with vitamin E 900IU/day improves insulin action. (17)

Osteoarthritis

At 400 IU daily, vitamin E produced significant reduction in pain scores, equal to the benefits other patients obtained from using Diclofenac. (18)

PMS

A dose of 400 IU daily produced significant improvement in certain affective symptoms and physical symptoms in some women with PMS. (19)

Rheumatoid Arthritis

Vitamin E 1,200 IU daily exerts a small but significant analgesic in patients with RA. (20)

Respiratory Tract Infections

Researchers investigated the role of vitamin E supplementation and the occurrence of colds in the elderly.This group received a multi-vitamin and either 200 IU of vitamin E or placebo. Researchers collected data on the incidence and the number of days with upper and lower respiratory tract infections. The results showed that vitamin E showed no improvement in the number of infections or the number of days being sick. However, it was shown that vitamin E supplementation did reduce the occurrence of the common cold when compared to those taking the placebo. (21)

Symptoms and Causes of Deficiency

Vitamin E is destroyed by heat and oxidation during cooking or food processing. Therefore, reliance on processed foods and/or fast foods can contribute to depletion. Low levels of selenium and high intake of polyunsaturated fatty acids both contribute to vitamin E depletion. Symptoms of vitamin E deficiency include: dry skin, dull dry hair, rupturing of red blood cells resulting in anemia, easy bruising, PMS, fibrocystic breasts, hot flashes, eczema, psoriasis, cataracts, benign prostatic hyperplasia, poor wound healing, muscle weakness, and sterility.

Dietary Sources

Good sources of vitamin E include vegetable oils, wheat germ oil, seeds, nuts, and soy beans. Other adequate sources are leafy greens, brussels sprouts, whole wheat products, whole grain breads and cereals, avocados, spinach, and asparagus.

References

  1. View Abstract: Peyser CE, Folstein M, Chase GA, Starkstein S, Brandt J, Cockrell JR, et al. Trial of d-alpha-tocopherol in Huntington's disease. Am J Psychiatry. 1995;152:1771-1775.
  2. View Abstract: Ferslew KE, et al. Pharmacokinetics and Bioavailability of the RRR and All Racemic Stereoisomers of Alpha-tocopherol in Humans after Single Oral Administration. J Clin Pharmacol. Jan1993;33(1):84-88.
  3. Panel on Micronutrients, Subcommittees on Upper Reference Levels of Nutrients and of Interpretation and Use of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press; 2000:190.
  4. View Abstract: Burton BW, et al. Human plasma and tissue alpha-tocopherol concentrations in response to supplementation with deuterated natural and synthetic vitamin E. Am J Clin Nutr. Apr1998;67(4):669-84.
  5. View Abstract: Miller ER 3rd, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality.Ann Intern Med. 2005 Jan 4;142(1):37-46.
  6. View Abstract: Rezaian GR, Taheri M, Mozaffari BE, Mosleh AA, Ghalambor MA. The salutary effects of antioxidant vitamins on the plasma lipids of healthy middle aged-to-elderly individuals: a randomized, double-blind, placebo-controlled study. J Med Liban. Jan2002;50(1-2):10-3.
  7. View Abstract: Cheung MC, Zhao XQ, Chait A, Albers JJ, Brown BG. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol. Aug2001;21(8):1320-6.
  8. View Abstract: Kennedy DD, Tucker KL, Ladas ED, Rheingold SR, Blumberg J, Kelly KM. Low antioxidant vitamin intakes are associated with increases in adverse effects of chemotherapy in children with acute lymphoblastic leukemia. Am J Clin Nutr. Jun2004;79(6):1029-36.
  9. View Abstract: Stephens NG, et al. Randomised Controlled Trial of Vitamin E in Patients with Coronary Disease: Cambridge Heart Antioxidant Study. Lancet. Mar1996;347(9004):781-86.
  10. View Abstract: Chan AC. Vitamin E and Atherosclerosis. J Nutr. Oct1998;128(10):1593-96.
  11. View Abstract: Robertson JM, et al. Vitamin E Intake and Risk of Cataracts in Humans. Ann NY Acad Sci. 1989;570: 372-82.
  12. View Abstract: Chylack LT Jr, Brown NP, Bron A, Hurst M, Kopcke W, Thien U, Schalch W. The Roche European American Cataract Trial (REACT): a randomized clinical trial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow progression of age-related cataract. Ophthalmic Epidemiol. Feb2002;9(1):49-80.
  13. View Abstract: Palan PR, et al. Plasma Levels of Antioxidant Beta-carotene and Alpha-tocopherol in Uterine Cervix Dysplasias and Cancer. Nutr Cancer. 1991;15(1):13-20.
  14. View Abstract: Sano M, et al. A Controlled Trial of Selegiline, Alpha-tocopherol, or Both as Treatment for Alzheimer’s Disease. The Alzheimer’s Disease Cooperative Study. N Engl J Med. Apr1997;336(17):1216-22.
  15. View Abstract: Das S. Vitamin E in the Genesis and Prevention of Cancer. A Review. Acta Oncol. 1994;33(6):615-19.
  16. View Abstract: Salonen JT, et al. Increased Risk of Non-insulin Dependent Diabetes Mellitus at Low Plasma Vitamin E Concentrations: A Four-year Follow-up Study in Men. BMJ. Oct1995;311(7013):1124-27.
  17. View Abstract: Paolisso G, et al. Pharmacologic Doses of Vitamin E Improve Insulin Action in Healthy Subjects and Non-insulin-dependent Diabetic Patients. Am J Clin Nutr. May1993;57(5):650-56.
  18. View Abstract: Scherak O, et al. High Dosage Vitamin E Therapy in Patients with Activated Arthrosis. Z Rheumatol. Dec1990;49(6):369-73.
  19. View Abstract: London RS, et al. Efficacy of Alpha-tocopherol in the Treatment of the Premenstrual Syndrome. J Reprod Med. Jun1987;32(6):400-04.
  20. View Abstract: Edmonds SE, et al. Putative Analgesic Activity of Repeated Oral Doses of Vitamin E in the Treatment of Rheumatoid Arthritis. Results of a Prospective Placebo Controlled Double-blind Trial. Ann Rheum Dis. Nov1997;56(11):649-55.
  21. View Abstract: Meydani SN, et al. Vitamin E and Respiratory Tract Infections in Elderly Nursing Home Residents. JAMA. Aug 2004;292(7):828-836.