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Physiology of the Skin: A New Look at Vitamin A

By Peter T. Pugliese, MD
Posted: April 23, 2008, from the May 2008 issue of Skin Inc. magazine.

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     Treatment. There is no need to ever to get a wrinkle and wrinkles are mainly sun induced. The second cause of wrinkles is smoking. The first goal in the treatment of skin aging is prevention. 
     Photograph the client sitting up—get a good high-resolution camera that will allow for great definition close up. Photograph front and both side views. Next, have client lie flat for 20 minutes. Photograph the client with the camera perpendicular to her face; that is, immediately above her face, and then photograph both sides again with the camera at a right angle to her face. See Figure 8. Compare the lines in the face, around the eye, the cheek areas, the nasolabial fold and the labiomental fold. If the wrinkles are effaced by 50% or more, you can get a good result. If there is no change, the wrinkles are deep and refractory to treatment, and it will take no less than a very deep peel plus a face lift to improve this condition. See Guidelines for Treating Aging Skin.
     Keep in mind that the amount of product placed on the skin will not all penetrate into the skin. In fact, only a small amount will penetrate and that will need to be converted to retinoic acid, which is further reduced. Although there is no hard and fast rule and little data to back it up, I use the rule of one-tenth. That is, about one-tenth of the amount of vitamin A, as retinol or retinyl acetate placed on the skin will become retinoic acid. It may be even less than this, but my studies have shown that a 1% vitamin A will give about the same hyperproliferative effect on the epidermis as 0.1% retinoic acid. It is possible to use 1% and 2% vitamin A product on the skin after you have had training in the use of lower doses, but do not use these higher levels without additional training. Remember that vitamin A is a hormone and, at high levels, can be systemically toxic, even when used topically.7

     Hyperpigmentation. Hyperpigmentation disorders of the skin are quite common. The most frequent forms include melasma, lentigines and postinflammatory hyperpigmentation. Pigmention problems are often difficult and require a lengthy treatment program. Melasma, for example, is not fully understood—although it is associated with hormones and UV exposure—but there appear to be more factors associated with this condition.
     When retinol is used in high concentrations, that is above 0.5%, irritation will occur, manifested by flaking and erythema. Retinol does not seem to be effective at low concentrations for pigmented lesion. See Guidelines for Treating Hyperpigmentation.

Getting familiar with retinoids
     Vitamin A is one of the best therapeutic agents available to a skin care professional. Knowing the chemistry and the physiology of retinoids is extremely helpful when applying them for the treatment of acne, aging skin and hyperpigmentation. Vitamin A comes in several forms lumped under the term retinoids. This includes retinol, the natural alcohol form; retinal, the aldehyde form used in the biochemistry of vision; and retinoic acid, the acid form that binds to the nuclear receptor and programs the biological effects via DNA. The alcohol can be units with fatty acid to make both an acetate ester, known as retinyl acetate and palmitate ester—retinyl palmitate. The most irritating form is retinoic acid and the least irritating form is retinyl palmitate.
     All the retinoids have essentially the same effect, which includes cellular differentiation, proliferation, morphogenesis and immune stimulation. In addition, retinal is germicidal, as well as being essential for vision. In the treatment of aging skin, retinyl acetate is very effective and less irritating than retinoic acid. The retinoids are both powerful and effective in treating acne and hyperpigmentation. The skin care professional needs to be familiar with the chemistry and biological actions to use retinoids both effectively and safely.

FOOTNOTES
a. The term retinoids is a general chemical classification that refers to all forms of vitamin A: retinol; retinal; retinoic acid; all the esters, such as retinyl palmitate; and all the synthetic prescription forms.

b. Isomerization is a chemical process in which a molecule changes its shape, but has the same number of atoms. In other words, the molecule weight and number of atoms is exactly the same.

c. The designation -cis and -trans in the formula denotes the presence of chemical entities on the long chain that are on the same side of the chain, that is -cis. When they occur on the opposite side, the designation -trans is used, which means across.

d. Teratogenic, from the Greek teras, meaning “monster.” Teratogenic substances cause great malformation in an embryo or fetus.

REFERENCES
1. PA Lehmann and AM Malany AM, Evidence for percutaneous absorption of isotretinoin from the photoisomerization of topical tretinoin. J Invest Dermatol (93), 595–599 (1999)
2. EH Harrisson, WS Blaner, DS Goodman and AC Ross, Subcellular localization of retinoids, retinoid binding proteins, and acyl-CoA retinol acyltransferase in rat liver. J Lipid Res (28), 973–981 (1987)
3. CE Orfanos, CC Zouboulis, B Almond-Roesler and CC Geilen, Current use and future potential role of retinoids in dermatology. Drugs (53),
358–388 (1997)
4. JP Ortonne, Retinoic acid and pigment cells: a review of in-vitro and in-vivo studies. Br J Dermatol. (127 Suppl 41) 43–47 (September 1992)
5. F Ballanger, P Baudry, JM N’Guyen, A Khammari and B Dréno, Heredity:
a prognostic factor for acne. Dermatology 212(2), 145–149 (2006)
6. AR Shalita, JG Smith, LC Parish, et al., Topical nicotinamide compared
with clindamycin gel in the treatment of inflammatory acne vulgaris.
Int J Dermatol (34), 434–437 (1995)
7.  A Meyer-Heim, K Landau and E Boltshauser, Treatment of acne with consequences—pseudotumor cerebri due to hypervitaminosis A. Schweiz Rundsch Med Prax. 91(1–2), 23–6 (Jan 9, 2002) (article in German)
8. K Yoshimura et al., Clinical trial of bleaching treatment with 10% all-trans retinol gel. Dermatol Surg. 29(2), 155–156 (Feb 2003)