Do Anti-Aging Creams Work? Part 1

If you think the claim of “younger looking skin overnight” sounds too good to be true, you may be right. Today is the first in our two-part series on the efficacy of anti-aging creams.

What is the truth about over-the-counter “anti-aging” products, which constitute a billion-dollar industry? There is a “psychological effect from spending more,” wrote a team of dermatologists, but “don’t be seduced by fancy packaging and high prices.” Many products advertise dramatic results that are frequently exaggerated and misleading, and are rarely scientifically supported.  An independent product-testing institute questioned the efficacy of anti-aging creams generally, finding that beneficial effects could only be picked up using sensitive instruments without becoming clinically or noticeably detectable. They suggest these products may not work any better than typical moisturizers.

Cross-sectional studies of Chinese and British women found that those who regularly used facial moisturizers were guessed to be about two years younger than those the same age who didn’t. However, a third, larger Dutch study did not, and regardless, snapshot-in-time studies can never establish cause and effect. Studies on moisturizers are limited. But they can improve the appearance of dry skin, which can otherwise look discolored, flaky, and rough. Moisturizers can hydrate the skin, and may reduce the appearance of fine lines by 15 to 20 percent––called “the oldest trick [in] the cosmetic industry,” but may not do anything to treat the underlying cause.

Whether facial foundation, or night cream, or anti-aging serum, the formulations of most skin products are basically a moisturizer combined with purported active ingredients for marketing appeal. Which ingredients are actually active anti-aging agents? I’ll give you a hint: up to 90 percent of the visible aging of someone’s face is due to sun exposure. From an anti-aging standpoint, the most biologically active ingredient in skin products is sunscreen.

Considered the most important thing to maintaining youthful skin is the daily application of sunscreen and other protective measures like wearing a hat. All other things you can do for your skin pale in comparison, especially for those with pale skin. To prevent skin cancer, the American Academy of Dermatology recommends sunscreen with an SPF of 30 or higher. But an SPF of 15 can prevent skin aging. How do we know? Because it’s been put to the test.

Nine hundred adults were randomized to years of daily sunscreen use, or to continue with their own discretionary use. (It was considered unethical to withhold protection by giving people placebo sunscreen.) In the end, 77 percent in the recommended daily sunscreen group were applying sunscreen at least three to four days per week, compared with 33 percent in the discretionary use group. Would that be enough of a difference to make a difference? Yes, there was significantly less skin aging in the instructed daily-use group. In fact, they suffered no detectable increase in skin aging over the 4.5-year study. The researchers concluded, “Daily sunscreen use protects against skin aging.”

Although sunscreens are primarily intended to prevent further facial aging, rather than reverse photodamage already done, some in the daily sunscreen use group did show an improvement in skin texture. The results are all the more striking given the control group was told to continue to use sunscreen and hats whenever they thought necessary––suggesting people are poor judges or planners for excess UV exposure when left to their own devices. So, a daily facial moisturizer with an SPF 15 in it is recommended, even if it’s cloudy or raining outside. Considered the “gold standard” for anti-aging skin care: “daily use of sunscreens in the daytime and retinoids at night.”

Retinoids? I’ll cover them next.

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 signs of aging. Also known as all-trans retinoic acid, tretinoin (sold under a variety of brands including Retin-A) is a prescription-only topical form of vitamin A that can visibly improve mild to moderate photodamage, including fine and coarse wrinkles, freckles, other pigmentation, and 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 tretinoin versus placebo found that while skin collagen formation dropped 14 percent in the control group, it rose 80 percent 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 .025 percent instead of 0.1 percent) 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, isotretinoin (sold formerly as the acne drug Accutane).

There are gentler, less potent, over-the-counter topical retinoids: retinyl, retinol, and retinal. There’s retinyl acetate, retinyl palmitate, retinyl propionate, retinol, and retinaldehyde. Once absorbed into your skin, your body can convert them into small amounts of retinoic acid. However, data is limited on these nonprescription retinoids. The results of clinical trials on the retinyl esters have been routinely disappointing. Even 48 weeks of daily use was found to be ineffective for reducing wrinkles compared to placebo. Retinaldehyde and retinol, however, hold some promise.

There was a 48-week head-to-head trial of retinaldehyde vs. retinoic acid vs. 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 they analyzed scans of the molds using high-resolution digital image processing. The retinaldehyde group showed a similar reduction in fine lines and wrinkles as the retinoic acid group, with less irritation. Only 23 percent of the retinaldehyde group experienced skin irritation, compared to 71 percent in the retinoic acid group, versus 4 percent in the placebo cream group.

Of all the nonprescription retinoid options, retinol may be the preferred choice, though. It causes even less irritation than retinaldehyde (insignificantly different than placebo), and a randomized double-blind, placebo-controlled trial found that 52 weeks of use improved crow’s feet fine lines by 44 percent, and mottled pigmentation by 84 percent. But tretinoin—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 tretinoin use may increase your risk of an even more stinging side effect: death.

“Topical Tretinoin Therapy and All-Cause Mortality: The Veterans Affairs Topical Tretinoin 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 in the placebo-cream group. At the time the study was halted, 19 percent of the subjects in the tretinoin group had died, compared to 14 percent in the placebo group. Between 1 to 8 percent 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. Tretinoin continues to be banned in Europe for cosmetic purposes.