Paolo Giacomoni, PhD, Insight Analysis Consulting08.02.22
Tocopherol. This possibly unfamiliar and certainly bewildering word is the chemical name of the molecule that, in layman’s terms, is called vitamin E. It was discovered a century ago by Herbert Evans and Katherine Bishop. They studied the effect of nutrition on the reproduction of rats and observed that rats did not procreate when they were fed rancid lard, whereas they happily reproduced when lettuce or whole wheat were added to the diet. They identified the wheat component responsible for the happy outcome of rat mating, and called it tocopherol, from the Greek words tokos that means childbirth, and pherein that means bring forth. They added the “-ol” suffix to indicate that the molecule is in the alcohol form. In the following decades much was discovered about the physiological properties of the molecules belonging to the chemical family of tocopherols (a-tocopherol, a-tocopheryl acetate, a-tocopheryl succinate, etc.) We now know that vitamin E is essential for both animal and human health.
Firstly, it has to be said that, for vitamin E to be beneficial to skin, topical application is mandatory. As a consequence of its lipidic nature, ingested vitamin E does not reach the epidermis because it is trapped in the fat of the adipose tissue underneath the dermis. When topically applied in appropriate galenic forms, it reaches the epidermis and can exert its antioxidant activity on the membrane and the cytoskeleton of the epidermal keratinocytes. This action is very important because several undesired skin conditions stem from excessive oxidative stress and peroxidative cascades.
As a matter of fact, clinical phenomena such as solar erythema, skin aging, skin inflammation and the like share, as a common feature, the formation or the release of pro-oxidant molecules that affect the morphology of epidermal cells by attacking membrane lipids and cytoskeletal proteins.
When the skin is exposed to excess ultraviolet radiation, erythema develops within 16 to 24 hours. During the same time frame, epidermal keratinocytes in vivo have been shown by histological analysis to lose contact from one another and to display a phenomenon called “spongiosis” because of the appearance of unidentified foreign bodies in the intercellular space. Electron microscopy analysis of spongiotic epidermis has been able to show that these foreign bodies do originate from the blebs provoked by the oxidative action of UV-generated Reactive Oxygen Species on cellular membranes and cytoskeletons.1 Blebs appear as bubbles on cellular surfaces and are indicators of cellular damage. Needless to say, when the epidermis is exposed to ultraviolet radiation in the presence of a-tocopherol, neither erythema nor spongiosis occur.
Even more interesting, the presence of vitamin E totally abolished the damage provoked by UVA and reduced by 75% the damage provoked by UVB, as if the protective effect were indeed exerted on membranes and cytoskeleton, and only partially on nuclear DNA. Furthermore, in a remarkable experiment, it was observed that the addition of vitamin E up to seven hours after UV irradiation resulted in a 75% protection against the damage provoked by UVA and in a 75% protection against the damage provoked by UVB.
Needless to say, vitamin E does not absorb UV so that a “sunscreen” effect to explain these phenomena is ruled out.
That should not be a reason to worry, though, or to add mega amounts of vitamin E in one’s formula. Oxidized, and therefore useless, vitamin E can be reduced; that is, regenerated and become useful again, by powerful reductants.
One reductant is ascorbic acid; aka, vitamin C, which provides an electron to oxidized tocopherol. Vitamin C is abundant in the skin and in the body of healthy human beings. It can also be added to the formula containing vitamin E in stabilized forms such as magnesium ascorbyl phosphate or similar moieties.
The experiments described in this column were performed years ago to illustrate the beneficial effects on skin by vitamin E nano-capsules that were formulated in Lancôme’s Primordial. The results relative to the protective action of vitamin E against cellular blebbing provoked enthusiasm and standing ovations by marketing executives of the brand who wanted to use these results to advertise the product. This enthusiasm was quickly quenched by the CEO of the company who feared that the FDA, confronted with such results, could consider vitamin E to be a drug.
References
Paolo Giacomoni, PhD
Insight Analysis Consulting
paologiac@gmail.com
516-769-6904
Paolo Giacomoni acts as an independent consultant to the skin care industry. He served as executive director of research at Estée Lauder and was head of the department of biology with L’Oréal. He has built a record of achievements through research on DNA damage and metabolic impairment induced by UV radiation as well as on the positive effects of vitamins and antioxidants. He has authored more than 100 peer-reviewed publications and has more than 20 patents.
Tocopherol in Skin Care
As of today, vitamin E is one of the molecules whose beneficial action to the skin is best documented. In this column, I will summarize some of the results obtained when I was working on the effects of vitamin E topically applied to human epidermis and its mechanism of action.Firstly, it has to be said that, for vitamin E to be beneficial to skin, topical application is mandatory. As a consequence of its lipidic nature, ingested vitamin E does not reach the epidermis because it is trapped in the fat of the adipose tissue underneath the dermis. When topically applied in appropriate galenic forms, it reaches the epidermis and can exert its antioxidant activity on the membrane and the cytoskeleton of the epidermal keratinocytes. This action is very important because several undesired skin conditions stem from excessive oxidative stress and peroxidative cascades.
As a matter of fact, clinical phenomena such as solar erythema, skin aging, skin inflammation and the like share, as a common feature, the formation or the release of pro-oxidant molecules that affect the morphology of epidermal cells by attacking membrane lipids and cytoskeletal proteins.
When the skin is exposed to excess ultraviolet radiation, erythema develops within 16 to 24 hours. During the same time frame, epidermal keratinocytes in vivo have been shown by histological analysis to lose contact from one another and to display a phenomenon called “spongiosis” because of the appearance of unidentified foreign bodies in the intercellular space. Electron microscopy analysis of spongiotic epidermis has been able to show that these foreign bodies do originate from the blebs provoked by the oxidative action of UV-generated Reactive Oxygen Species on cellular membranes and cytoskeletons.1 Blebs appear as bubbles on cellular surfaces and are indicators of cellular damage. Needless to say, when the epidermis is exposed to ultraviolet radiation in the presence of a-tocopherol, neither erythema nor spongiosis occur.
Mechanisms of Action
Cultured normal human keratinocytes were exposed to either UVA or UVB and 30 micromolar a-tocopherol (0.0013%) was added before or after the irradiation. The endpoints of the analysis were the photon-microscopy analysis of actin and tubulin filaments as well as of the structure of cellular chromatin, and the scanning electron microscopy analysis of cell morphology.2 Chromatin fragmentation was used as an indicator of apoptosis and cell blebbing was taken as an indicator of cell damage. In addition to a remarkable protective effect on the structure and assembly of actin and tubulin filaments, the presence of vitamin E resulted in the reduction by 50% of the number of apoptotic cells provoked by UVA and by 30% of the number of apoptotic cells provoked by UVB.Even more interesting, the presence of vitamin E totally abolished the damage provoked by UVA and reduced by 75% the damage provoked by UVB, as if the protective effect were indeed exerted on membranes and cytoskeleton, and only partially on nuclear DNA. Furthermore, in a remarkable experiment, it was observed that the addition of vitamin E up to seven hours after UV irradiation resulted in a 75% protection against the damage provoked by UVA and in a 75% protection against the damage provoked by UVB.
Needless to say, vitamin E does not absorb UV so that a “sunscreen” effect to explain these phenomena is ruled out.
Conclusions for Skin Care
Vitamin E is safe and is effective at very low concentrations. That is the good news! The bad news is that it can be used up by all the peroxide radicals that are generated during inflammation and exposure to solar radiation. To decide the concentration at which it should be applied, we do not know how to estimate the stoichiometry of the redox phenomena going on between reactive oxygen species, lipid peroxidation, protein carbonylation and vitamin E.That should not be a reason to worry, though, or to add mega amounts of vitamin E in one’s formula. Oxidized, and therefore useless, vitamin E can be reduced; that is, regenerated and become useful again, by powerful reductants.
One reductant is ascorbic acid; aka, vitamin C, which provides an electron to oxidized tocopherol. Vitamin C is abundant in the skin and in the body of healthy human beings. It can also be added to the formula containing vitamin E in stabilized forms such as magnesium ascorbyl phosphate or similar moieties.
The experiments described in this column were performed years ago to illustrate the beneficial effects on skin by vitamin E nano-capsules that were formulated in Lancôme’s Primordial. The results relative to the protective action of vitamin E against cellular blebbing provoked enthusiasm and standing ovations by marketing executives of the brand who wanted to use these results to advertise the product. This enthusiasm was quickly quenched by the CEO of the company who feared that the FDA, confronted with such results, could consider vitamin E to be a drug.
References
- Straface E, Falchi M, Giacomoni PU and Malorni W (2001) Cytotoxicity and morphological endpoints of exposure to UV: cultured cells as a model system, in (PU Giacomoni ed) Sun Protection in Man, Elsevier (Amsterdam, London, New York) pages 321-336
- Malorni W, Straface E, Donelli G and Giacomoni PU (1996) UV-induced cytoskeletal damage, surface blebbing and apoptosis are hindered by a-tocopherol in cultured human keratinocytes (1996) Eur J Dermatol 6 ; 414-420
Paolo Giacomoni, PhD
Insight Analysis Consulting
paologiac@gmail.com
516-769-6904
Paolo Giacomoni acts as an independent consultant to the skin care industry. He served as executive director of research at Estée Lauder and was head of the department of biology with L’Oréal. He has built a record of achievements through research on DNA damage and metabolic impairment induced by UV radiation as well as on the positive effects of vitamins and antioxidants. He has authored more than 100 peer-reviewed publications and has more than 20 patents.