Disposition and metabolism of topically administered alpha-tocopherol acetate: a common ingredient of commercially available sunscreens and cosmetics.
Skin cancers are a serious health problem in the United States. One common method of skin cancer primary prevention is use of sunscreens. Research has been conducted to ascertain the role of active ingredients of sunscreen products in photoprotection and possible carcinogenesis. In contrast, little is known about the "other ingredients", listed or unlisted, on sunscreen product labels. One such ingredient is vitamin E. usually in the form of alpha-tocopherol acetate. Results of recent studies of skin carcinogenesis in an ultraviolet (UV) B mouse carcinogenesis model suggest that topically applied alpha-tocopherol acetate does not prevent and, under some conditions, enhances skin cancer development and growth, whereas the free unesterified from of alpha-tocopherol significantly reduces experimental UVB carcinogenesis. We have performed a Phase II cancer prevention study to evaluate whether topically applied alpha-tocopherol acetate is absorbed in human skin and metabolizes to the free or other forms. In this double-blind study, 19 men and women > 30 years of age who had at least three actinic keratoses on their forearms were randomly assigned to apply alpha-tocopherol acetate (125 mg/g) or difluoromethylornithine cream to their arms twice daily for three months. Blood samples and photographs and punch biopsies of actinic keratoses were obtained before and at the end of the study (Month 4). Plasma and skin concentrations of free alpha-tocopherol, alpha-tocopherol acetate, and gamma-tocopherol were analyzed by high-performance liquid chromatography at Month 4. The results of this report focus only on data obtained from the 11 participants randomized to the alpha-tocopherol acetate arm of the study. Topically applied alpha-tocopherol acetate was substantially absorbed in skin, with no evidence of conversion within skin to its unesterified form (i.e., free alpha-tocopherol). There was no evidence of systemic availability or biotransformation of topically applied alpha-tocopherol acetate. In summary, we have determined that alpha-tocopherol acetate is not metabolized to the free form of alpha-tocopherol in plasma or skin.
Alberts
D S
DS
Arizona Cancer Center, College of Medicine, University of Arizona, Tucson 85724, USA.
Goldman
R
R
Xu
M J
MJ
Dorr
R T
RT
Quinn
J
J
Welch
K
K
Guillen-Rodriguez
J
J
Aickin
M
M
Peng
Y M
YM
Loescher
L
L
Gensler
H
H
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D001706:Biopsy; D003358:Cosmetics / Q000737:chemistry*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007642:Keratosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000378:metabolism; D013473:Sunscreening Agents / Q000737:chemistry*; D024505:Tocopherols; D014810:Vitamin E / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D024502:alpha-Tocopherol / Q000031:analogs & derivatives*
D003358:Cosmetics; D013473:Sunscreening Agents; D014810:Vitamin E; D024502:alpha-Tocopherol; D024505:Tocopherols