 Sunscreens are intended to prevent further facial photoaging, but can't dramatically reverse damage presently visible, whereas topical retinoids are the most important drug class to reverse the size of aging. Also known as all-trans retinoic acid, tritinoin, sold under a variety of brands including Retin-A, is a prescriptionally topical form of I-M-N-A that can visibly improve mild to moderate photo damage, including fine and coarse wrinkles, freckles, other pigmentation, improve overall skin texture after months of daily use. This is accompanied by a restoration of collagen formation, skin biopsies taken before and after 10 to 12 months of tritinoin versus placebo found that while skin collagen formation dropped 14% in the control group, it rose 80% in the retinoic acid group. The downsides are the side effects. So common they have their own name, retinoid reaction, plaguing a high proportion of patients including redness, stinging, burning, itching, and peeling. Ironically, the constant irritation may be a causal mechanism, constantly forcing the skin to renew. The adverse effects do tend to improve over time, after a peak after about two weeks of daily use, and you can minimize the irritation by starting at a lower concentration, for example 0.025% instead of 0.1%, and slowly ramping up from applying at first twice a week for a few weeks then to every other night for a few more weeks before finally advancing to nightly application as tolerated. Given that a small amount is systemically absorbed out of an abundance of caution, women of child-bearing capacity may want to steer clear, given the severe birth defects caused by a similar drug, isotritinoin, sold formally as the Acne Drug Accutane. There are gentler, less potent over-the-counter topical retinoids, retinol, retinol, and retinol. There's retinol acetate, retinol palmitate, propionate, retinol, retinaldehyde. Once absorbed into your skin, your body can convert them into small amounts of retinoic acid. However, data is limited on these non-prescription retinoids. The results of clinical trials on the retinol esters have been routinely disappointing. Even 48 weeks of daily use was found to be ineffective for reducing wrinkles compared to placebo. Retinoldehyde and retinol, however, hold some promise. There was a 48-week head-to-head trial of retinoldehyde versus retinoic acid versus placebo. Now retinoids can be so irritating that it's hard to blind participants as to whether or not they're in the control group. So objective measures that may be less susceptible to placebo effects are especially important. So what they did is make silicone molds of the crow's feet wrinkles around the eyes of the participants before and after being randomized to one of those three groups, and then analyze scans of the molds using high-resolution digital image processing. The retinoldehyde group showed a similar reduction fine lines and wrinkles as the retinoic acid group with less irritation. Only 23% of the retinoldehyde group experienced skin irritation compared to 71% in the retinoic acid group versus 4% in the placebo cream group. Of all the non-professional retinoid options, retinol may be the preferred choice, though. It causes even less irritation than retinoldehyde, in significantly different than placebo, and a randomized double-blown placebo-controlled trial found that 52 weeks of use improved crow's feet fine lines by 44% and modelled pigmentation by 84%. But tritinoldehyde retinoic acid has by far the most robust track record of efficacy, so why not just ask your doctor for a prescription? Because long-term topical tritinoldehyde use may increase your risk of an even more stinging side effect? Death. Topical tritinoldehyde therapy in all-cause mortality. The Veterans Affairs Topical Tritinoldehyde Chemoprevention Trial was to be a six-year randomized controlled trial to see if it could help prevent skin cancer. But the trial had to be stopped early because significantly more people were dying in the retinoic acid group than the placebo cream group. At the time the study was halted, 19% of the subjects in the tritinoldehyde group had died, compared to 14% in the placebo group. Between 1% to 8% of topically applied retinoic acid is absorbed into the bloodstream. Could it be killing people? We don't know if the increase in deaths was a statistical fluke that happened by chance or a real biological effect. The probability that we'd see such a discrepancy just by chance is about 1 in 100. Tritinoin continues to be banned in Europe for cosmetic purposes.