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You are here: Anti-Aging Skin Treatments > Topical Actives >

Retinoids in skin care. Advancing beyond tretinoin.

Tretinoin a.k.a. trans-retinoic acid (the active ingredient in such popular products as Retin A and Renova) is one of the very few agents whose skin rejuvenation effects have been documented in many well-designed studies. Tretinoin works by triggering molecular switches in skin cells called retinoid receptors. These switches affect many intracellular processes including cell growth and differentiation, synthesis and breakdown of proteins (including collagen and elastin), sebum production, and possibly even the cell's lifespan clock (telomeres).

However, tretinoin is not the only substance capable of activating retinoid receptors. In fact, a number of related but distinct agents (collectively called retinoids) can do that. The success of tretinoin in dermatology and skin care prompted researchers to study other retinoids as a potential treatment for problems ranging from wrinkles, to acne, to age spots.

Why spend time and money looking for other retinoids if we already have tretinoin? Isn't this just another case of the questionable "me-too" drug strategy when pharmaceutical companies try to patent similar drugs with no significant additional benefit? Well, not quite. The "me-too" drugs are redundant when the original drug highly selectively hits a single target, such as a receptor or enzyme, and is very safe. In such a case, creating more drugs that hit the same target is more beneficial to the patent holder than the consumer. For instance, omeprazole (Prilosec), a very successful stomach acid suppressor, has been followed by half a dozen copy cats (Prevacid, Aciphex, Nexium and others) doing exactly the same thing in exactly the same way.

The situation with tretinoin is different for two reasons. First, there are several kinds of retinoid receptors, each affecting different cellular processes. Some retinoids hit a particular type(s) of the receptors harder than the other types. As a result, the net effect of different retinoids on the cells may vary significantly from one retinoid to the next. Second, tretinoin sometimes causes significant side effects, such as skin dryness and irritation, so it does make sense to look for its gentler cousins. To that end, the goal of retinoid research in dermatology has been to find retinoids that are safer than tretinoin and/or are more effective in skin rejuvenation or treatment of acne and other conditions.

So far the there has been some progress, albeit not as dramatic as anticipated. Only two new retinoids, tazarotene (Tazorac) and adapalene (Differin), have gained a broad clinical acceptance. Based on several studies, tazarotene appears to be at least as effective as tretinoin against wrinkles. Furthermore, in one study 0.1% tazarotene reduced wrinkles faster and more significantly then 0.05% tretinoin over a 24-week period. Side-effect were similar for both agents, except tazarotene was more likely to cause a burning sensation during the first week (but not thereafter). The study would have been more useful if it lasted longer and also included 0.1% tretinoin for comparison. Further research is needed to determine if tazarotene may be a better wrinkle fighter than tretinoin over the long term. Adapalene (Differin) is a new retinoid that has become a widely used alternative to tretinoin as an acne treatment - mainly because it is somewhat less irritating. While adapalene clearly has some anti-wrinkle properties, it remains to be determined whether it is as good a wrinkle-fighter as tretinoin or tazarotene.

Another notable retinoid is isotretinoin, which is structurally close but distinct from tretinoin. Oral isotretinoin (Accutane) has been used to treat acne for decades. It is very effective but may cause serious side effects and, therefore, is typically reserved only for severe cystic acne. Recent research indicates that topical isotretinoin may be useful for both acne and skin rejuvenation. Topical isotretinoin has far less side effects than its oral form and may be even less irritating than topical tretinoin. In one small human study, topical isotretinoin was as effective as tretinoin for acne but caused less skin irritation (each agent was applied as 0.05% gel). Another study showed that 0.05% topical isotretinoin (with sunscreen) improved fine lines and wrinkles after 6 month. More research is needed to investigate the benefits and risks of topical isotretinoin vs other retinoids. In particular, it would be useful to compare topical isotretinoin and tretinoin in regard to skin rejuvenation.

A word about vitamin A. Some experts (usually non-scientists) include various forms of vitamin A (such as retinol, retinaldehyde and retinyl palmitate) among retinoids. Physiologically speaking, vitamin A is not a retinoid because it does not interact directly with retinoid receptors. Cells have to first convert vitamin A to retinoic acid (i.e. to tretinoin or other retinoid). The rate of such conversion is low and varies significantly among individuals. What does this mean in practice? Low strength topical vitamin A formulations are usually ineffective - not enough of vitamin A is converted into a retinoid. Stabilized, high strength topical vitamin A may be effective, but due to variability in conversion rates the results are far less consistent than with true retinoids and the side effects may be almost as significant. New vitamin A derivatives combining reliably high effectiveness, stability and good side effect profile, such as retinyl retinoate, are being developed but remain relatively untested. For people who cannot tolerate or cannot afford retinoids, a well-selected vitamin A formulation may be worth a try (see our articles on retinaldehyde, retinol and retinyl retinoate). Otherwise, a retinoid is likely to deliver a better performance.

Bottom line

As of the time of this writing, tretinoin remains the primary wrinkle-fighting retinoid. However, due to individual variability some people may have better overall results with other retinoids. It is also worthwhile to keep an eye on the further advances in the retinoid research.

Do not forget that retinoids have a flip side. Overuse or misuse can lead to chronic skin irritation, dryness and other problems, leaving you skin in the worse condition than before the treatment. For practical details on the optimal use of retinoids, including the ways to avoid skin-damaging irritation, see Skin Rejuvenation Infopack.


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