BACKGROUND

Since its discovery in the 1920s, vitamin E has been the subject of controversy and extensive research. At first it was labeled the "fertility" vitamin and as such was named "tocopherol" after the Greek "tocos" (childbirth), because of the ability of alpha-tocopherol to restore fertility to experimental animals subjected to vitamin E-deficient diets. This early association has tended to obscure the many important physiological and biochemical processes in which it is involved.
Over the past decades, a large number of studies have been conducted, which leave little room for doubt over the need for vitamin E in the maintenance of normal body metabolism and there is increasing acceptance of its role in the prevention of chronic diseases, such as cardiovascular disorders. There is also growing evidence that it plays a crucial role in protecting the body tissues and skin from damage caused by natural body processes, certain lifestyle choices and environmental stresses, such as chemical pollutants, UV radiation, ozone, severe climatic conditions, etc. This work relating to topical application of vitamin E has revealed very interesting effects which are of importance in developing functional high performance skin care, sun care, hair care, make-up, and other cosmetic products.

CHEMISTRY

Several tocopherols have been isolated from natural sources. All have a 6-chromanol ring and a side chain and they differ only in number of methyl groups.

Tocopherol, the free alcohol form, both synthetic and natural, is a strong antioxidant and as such, oxidizes, particularly in the presence of oxygen, light, heat, alkali, and heavy metals. Its most popular commercial form is tocopheryl acetate, which is very stable but does not have any antioxidant activity in vitro, unless conditions of its application bring about hydrolysis of the ester. Both alpha-tocopherol and alpha tocopheryl acetate are viscous, oily substances that are insoluble in water, but quite soluble in oils, fats, alcohol, acetone and most solvents.

ABSORPTION & TISSUE DEPOSITION

The absorption of oral intake of vitamin E is similar to that of other fat soluble vitamins. In the presence of normal amounts of bile salts and pancreatic juice, about 20 to 40 percent of the orally ingested tocopherol and/or its esters is absorbed. Vitamin E undergoes very little metabolic change and almost all of it is present in the body as alpha-tocopherol rather than as a metabolite. Major route of excretion is fecal elimination, with less than I percent being excreted in the urine.

Absorption through the skin occurs readily, either as the alcohol or the acetate form. Quantitative penetration studies with C-14 labeled vitamin E acetate reported this vitamin form to be well absorbed through the stratum corneum.(1)

There are two routes of absorption from the skin’s surface to the dermis.

The first leads through the horny layer, the epidermis, and the area between epidermis and dermis. Linear increase of vitamin E in the tissues was observed. After 4 hours, the epidermis and the upper portion of the dermis showed the highest levels. After 24 hours, the highest levels were detected in the lower dermis.(2)

The second route goes through the pilosebaceous canal and the interior of the hair follicles. There is no absorption through sebaceous glands and sweat ducts.(3) It was also shown that the vitamin is absorbed directly into the cortex of the hair.

BIOCHEMICAL FUNCTION & PROTECTIVE EFFECTS

One of the most important biochemical functions of vitamin E is as an in vivo antioxidant protecting cell membranes against the damaging effects of free radicals. A free radical is a substance which has one unpaired electron and as a result, is a highly reactive compound (RO•; HO•; ROO•). Free radicals are generated as part of normal biochemical processes, and also are taken into the body or formed internally as a result of environmental factors such as chemical pollutants (e.g. nitrogen dioxide, ozone, cigarette smoke), certain drugs, alcohol and UV radiation. Vitamin E plays a major role in providing protection against these internal and external free radical generators.

Cell Membrane Protection
The chain reaction of free radical formation in the cell membrane is a complex phenomenon, the steps of which are shown in Figure 1. It involves removal of a hydrogen atom from a polyunsaturated fatty acid, resulting in formation of a radical.

The peroxy radical is formed from the addition of oxygen. The peroxy radical in turn can attack other polyunsaturated molecules so that unless interrupted, an accelerated "chain reaction" can occur. In addition, fatty acid peroxide molecules can break down to aldehydes and other smaller molecules that can be toxic or damaging by themselves.

Vitamin E might react with a peroxy radical and convert it to a more stable peroxide, which in turn can be safely reduced to a fatty alcohol by glutathione peroxidase. The tocopherol radical that is formed can be converted back to tocopherol by vitamin C or glutathione (regeneration step).(4) Vitamin E, which appears to function in the cell membrane, is not the only antioxidant in the body but it acts in concert with antioxidant enzymes such as glutathione peroxidase, catalase and superoxide dismutase as well as some smaller molecules with antioxidant properties such as ascorbic acid, glutathione, and uric acid. It is the most important lipid-soluble, membrane-bound antioxidant in the body.

Cardiovascular Benefits
There is strong evidence for the value of vitamin E supplements in reducing the risk or slowing the progression of coronary heart diseases. Vitamin E prevents oxidation of the LDL (low density lipoproteins), and thus the formation of artery clogging plaque of arteriosclerosis.
A study conducted at the University of Texas Southwestern Medical Center in Dallas found that a minimum dose of 400 IU of vitamin E a day is needed to counter LDL oxidation.(5) Unfortunately, more than 40% of elderly Americans fall dangerously below it.
Among patients with poor circulation in their legs due to arteriosclerosis, those who took 300 IU a day, there was improved blood flow and greater improvement in walking ability.(6)
Vitamin E also inhibits clotting and in one small but well-controlled study of patients with vascular disease, vitamin E plus daily aspirin was more effective than aspirin alone in countering heart attacks and strokes.(7)

Aging and Immune System
Damage to body cells by free radicals is thought to be the major factor of aging and the decline in the immune system.(8)

By inhibiting the oxidation of fats, vitamin E could assist in protecting the cell membranes. Studies in elderly people have shown that supplements of vitamin E could improve the immunological response.

Lifestyles/Exercise
It has been said that oxygen is a dangerous friend: you can't live without it but you can't live indefinitely in its presence. More than 40 years ago, physiologists showed an inverse correlation between basal metabolic activity and the life span of about 70 mammalian species (animals with more active metabolism had shorter lives). Since oxygen consumption or metabolism activity is much increased during physical exercise, this could pose interesting questions about the long-term effect of oxygen and the defense against its toxicity via vitamin E.
Studies with rats and guinea pigs conducted by Dr. Lester Packer have shown that strenuous exercise causes increased tissue oxidative damage (even more damage occurs when animals are fed insufficient amounts of vitamin E). Furthermore, more vitamin E was destroyed in the tissues of animals made to exercise heavily.(9) Similar findings extended to humans are shedding light on vitamin E's role in oxygen toxicity. A study conducted by Dr. William J. Evans at Pennsylvania State University found that vitamin E supplements helped protect against muscle damage.(10)

ROLE IN TOPICAL APPLICATIONS

Perhaps no other vitamin has greater anecdotal background than vitamin E. A Roche marketing study conducted among users of vitamin E supplements revealed that a high percentage of those who take single vitamin E capsules also use it in creams, lotions, and even directly from soft gelatin capsules. They believe it to be good for cuts, burns, age spots, dryness, and many other symptoms. But the cosmetic industry's main claim for vitamin E has been as a "natural moisturizer" to relieve dry skin and indirectly to aid in concealment of wrinkles and facial lines perceived as characteristics of aging and dry skin.
However, extensive studies conducted over the last 10 years with topically applied vitamin E, and especially recent ones, have revealed significant benefits beyond moisturization of dry skin, most important of which are:

Experimental Therapeutics
Treatment of chronic skin diseases?Either alone or in combination with other materials or vitamins, especially vitamin A.
Wound healing?Although it was claimed, when applied topically, to have such effects, studies suggest it has value only in reducing scarring, not in healing (probably by inhibiting excessive collagen formation at the wound site). (11)
Anti-inflammatory action?First suggested in a study done in the early 1970's in which it was found that vitamin E reduced both erythema and swelling, probably by suppression of histamine release.(12) A 1982 study assessed the ability of vitamin E (at 100% vitamin E acetate USP) to act as an anti-inflammatory, by measuring reduction of thermal conductivity in human skin. These studies confirmed the anti- inflammatory effects of vitamin E acetate.(13)

Cosmetics & Toiletries
Skin moisturizationSkin moisturization was studied using three levels of vitamin E acetate in an emulsion (1%, 2.5% and 5%). Measurement of Transepidermal Water Loss (TEWL) showed the 1.0 and 2.5% levels to be ineffective, though the 5.0% concentration was effective in reducing TEWL by 19%, 30 minutes after application and by 24% after four days of twice daily applications. This is an indication that vitamin E's efficacy is increased with repeated use and as such it is an ideal dry skin moisturizer. Unlike petrolatum, which has an occlusive effect, vitamin E moisturizes from within because of its known penetration. (14)

Skin smoothness
Studying the skin’s surface topography has been used as an indication of the degree of hydration as well as interpretation of smoothness and softness. Dry, rough, or damaged skin manifests a "scruffy" appearance, with discontinuities in the lines, decreased distance between lines, and an irregular appearance. Hydrated skin has comparatively wider lines with a more regular appearance and is less sharply demarcated. Using a modification of the Goldschmidt-Kligman technique, a 5% vitamin E acetate emulsion showed a 30% improvement over the control emulsion, which contained no vitamin E. (15)

Skin softening
A 15 day cumulative study with soaps containing 0.5% and 1.0% vitamin E acetate showed substantial skin softening effect as compared to conventional soaps without vitamin E acetate.
The effect is dose dependent, with 1.0% providing better skin softening than 0.5%.
The skin softening effect is cumulative, with the benefits increasing over time (tests were conducted at 5, 10 and 15 days). (16)

Furthermore, certain commercial soaps without vitamin E increased the skin stiffness.
Reduction of Lipid Peroxidation?Cell membranes are composed of phospholipids, many of which are highly unsaturated and therefore susceptible to forming lipid peroxides. The latter have been implicated in the aging process of animals, especially where they can be indicated by age pigments or lipofuscin. The latter has been observed to accumulate almost linearly with advancing age. It is believed that this pigment is formed from the reaction of lipid peroxides and protein.

A known breakdown product of lipid peroxides is malondialdehyde (MDA). It has been shown to cross-link collagen, a possible explanation of the decreased elasticity of skin with age. Topically applied 5% vitamin E acetate was found to reduce MDA in the skin as compared to the control hairless mice. (17)

Protection against UV damageIt has been recognized for many years that UV light induces the production of free radicals in skin of test animals. In vitro studies of tocopherol and other antioxidants point to the free radical scavenging mechanism as protecting unsaturated materials found in vegetable oils as well as in the lipid components of animal cell membranes.
Studies conducted at the University of California indicate that exposure to UVA and UVB sharply reduces the level of tocopherol (vitamin E alcohol) in the skin. Topical application of 5% vitamin E acetate cream increases the levels of tocopherol by 15-fold, thus providing increased protection to the skin. (18)

Studies carried out with hairless mice showed that the vitamin is useful in reducing UV light damage as determined by activity of the enzyme ornithine decarboxylase (ODC). (17)
Human studies showed a small but nevertheless significant increase in the Sun Protection Factor (SPF) rating with UVB sunscreen formulations. The tentative conclusion to be drawn here is that, though vitamin E acetate has essentially no SPF value, it nevertheless (after absorption by the skin) scavenges free radicals generated in the skin by UVB irradiation.

If free radical trapping is a major role for the vitamin E in topical applications, one may be able to attribute the above applications to vitamin E's anti-inflammatory, anti-scarring, and ODC reduction effects in animals to the absorption of E acetate by the stratum corneum and its subsequent conversion to tocopherol. Otherwise vitamin E by itself would not be expected to lead to such phenomena. Overall, this reduction in ODC suggests a strong rationale for incorporating the vitamin in sun care preparations.

Protection Against OzoneStudies conducted by the Department of Molecular and Cell Biology at the University of California in Berkeley indicate that exposure of skin to ozone reduces the levels of lipophilic antioxidants in the skin. In mice, there was a decrease of 38% tocopherol and 26% of Ubiquinol 9, indicating oxidative stress.

A single application of a 5% vitamin E acetate cream increased the levels of vitamin E alcohol 6-10 fold. Daily applications for 15 days with 5% vitamin E acetate cream increased the levels of vitamin E alcohol by 15-fold.

After exposure to ozone (1 day), the vitamin E treated group had a greater vitamin E alcohol level than the non-treated group which was not exposed to ozone, indicating enhanced protection against environmental stress. (19)

Antioxidant in Cosmetic Products?Alpha-tocopherol has been used as an antioxidant for many years. It is classified among the "natural antioxidants" which function as electron donors and as such, react directly with free radicals. Through this action it can prevent or delay rancidity of fats and oils, particularly unsaturated fatty acids and their derivatives. When used in combination with ascorbyl palmitate, which acts as an oxygen scavenger, it provides a powerful antioxidant system useful in extending shelf-life of cosmetics & toiletries, especially of products formulated with natural ingredients (including natural perfume extracts), vitamins, and herbal extracts. (20)

Blockage of Nitrosamine Formation?Use of amines or amides as cosmetic ingredients and the presence of nitrite as a contaminant can lead to formation of nitrosamines or nitrosamides, many of which are known carcinogens. Prevention of the formation of nitrosamines can be achieved by removing the nitrosating species and by adding blocking agents. Studies conducted by Roche indicate that combination of an oil-soluble blocking agent such as free tocopherol, and/or ascorbyl palmitate, are highly effective in preventing nitrosamine formation in emulsion type creams and lotions. (21)

RECOMMENDED LEVELS

Oral Supplementation
• Daily Intake – up to 400 IU

Topical Application
Vitamin E Acetate (Tocopheryl Acetate)
• 0.5-5%

Vitamin E Alcohol (Tocopherol)
• 0.05-0.2%

SUMMARY

The central role of vitamin E is that of an in vivo antioxidant, protecting the cell membrane against the damaging effects of free radicals. Natural body processes, lifestyle choices, environmental pollutants, UV radiation and ozone, all are potential sources of free radicals. In addition to systemic protection by vitamin E, topical application also is very important since the storage levels in the skin (and particularly the epidermis) are not very high.
Although the main claim for vitamin E in cosmetics has been as a "natural moisturizer", extensive studies conducted over the last 10 years point to significant benefits beyond moisturization.
In its esterified form, vitamin E may have anti-inflammatory effects and it also could provide protection from UV damage to the skin, suggesting a strong rationale for incorporating it into suncare preparations. There is also considerable evidence that alpha-tocopherol has antioxidant effects against lipid peroxidation in living tissues, and as such might play a role against aging, particularly of the skin.
The vast data available on vitamin E points to its importance as one of the key ingredients in formulating functional, high performance cosmetics, particularly skin care and sun care products.

REFERENCES

1. Klecak, G., Percutaneous Absorption of alpha tocopherol and alpha-tocopheryl acetate through rat skin. F. Hoffmann-La Roche, Switzerland, 1986.
2. Klain, J. G., Dermal Penetration of 14 C labeled Vitamin E into Human Skin Grafted on Nude Mice. Internat. J. Vit. Nutr. Res. 59; 333-337, 1989.
3. Kamimura M., Matsuzawa T., Percutaneous Absorption of Alpha-Tocopheryl Acetate. The Journal of Vitaminology, 14, 150-159, 1968.
4. McCay P, King M. Vitamin E - Its Role as a Biologic Free Radical Scavenger and its Relationship to the Microsomal Mixed Function Oxidase System ‘Vitamin E, Comprehensive Treatise’ Vol. 1, L. Machlin, 1980.
5. Jialal I., Fuller CJ, Huet B. A., The Effect of Alpha-Tocopherol Supplementation on LDL Oxidation; a Dose-Response Study. Arterioscler Thromb Vase. Biol. 15:190, 1995.
6. Haeger K. Long Term Study of Alpha Tocopherol in Intermittent Claudication. Annals of the New York Academy of Sciences. Vol. 393; 369-375; 1982.
7. Steiner M., Glantz M., Lekos A., Vitamin E plus Aspirin Compared with Aspirin Alone in Patients with Transient Ischemic Attacks. Am. J. Clin. Nutr. 62 (Suppl): 1381s, 1995.
8. Miller R., Aging and Immune Function: Cellular and Biochemical Analysis. Exp. Gerontol: 29:21, 1994.
9. Packer L., Vitamin E, Physical Exercise and Tissue Oxidative Damage, Biology of Vitamin E, Ciba Foundation Symposium 101: 56-59, 1983.
10. Evans W., Exercise Nutrition and Aging J. Nutr. 122: 796-801, 1992.
11. Ehrlich H.P., Traver H., Hunt T., Inhibitor Effects of Vitamin E on Collagen Synthesis and Wound Repair. Annals of Surgery Vol. 175, No. 2, 1972.
12. Kamimura M., Anti-Inflammatory Activity of Vitamin E. The Journal of Vitaminology, 201-209; 1972.
13. Puglise P., Anti-Inflammatory Activity of Vitamin E. Conducted for Hoffmann-La Roche Inc., 1982.
14. Puglise P., Vitamin E - Skin Moisturization Study. Conducted for Hoffmann-La Roche Inc., 1982.
15. Puglise P., Vitamin E - Skin Smoothness Study. Conducted for Hoffmann-La Roche Inc., 1982.
16. Yeung D., Vitamin E - Skin Softening Effect. Conducted for Hoffmann-La Roche Inc., 1994
17. Puglise P., Alpha-Tocopheryl AcetateModulation of Ornithine Decarboxylase Activity. Conducted for Hoffinann-La Roche Inc. – 1985.
18. Packer L., Effect of UV Radiation on Vitamin E Levels in Tissues. Conducted for Hoffmann-La Roche Inc. 1991.
19. Packer L., Effects of Acute Ozone Exposure on Cutaneous Lipopholic Antioxidants in Hairless Mice and Protection by Tocopheryl Acetate. Journal of Investigative Dermatology Vol. 98. No. 4, April 1992.
20. Cort W., Antioxidant Activity of Tocopherols, Ascorbyl Palmitate, Ascorbic Acid and Their Mode of Action. Journal of the American Oil Chemists Society, Vol. 51, No. 7, 321-325; 1974.
21. Mergens W., DeRitter E., Nitrosamines in Cosmetics. Cosmetic Technology. January 1980.