Although they’ve been around for decades, the vitamin A derivatives known as retinoids remain the gold standard for treating acne and wrinkles, with the skin-care and pharmaceutical industries continuing to develop and manufacture new products featuring them. Retinoids — including the most commonly known, retinol — are found in both prescription medications and over-the-counter formulations in a variety of strengths and product types.

But despite their longevity and proven results, these compounds retain the potential for undesirable side effects, such as peeling skin and sun sensitivity. It’s important, therefore, to understand the various types of retinoids and the safest ways to incorporate them into a skin-care regimen.

Attempts to use retinoids to tame acne date to the mid-20th century, when tretinoin, a derivative of vitamin A also known as retinoic acid, was studied in Europe for treating skin disorders including acne and skin cancer. Although it was deemed too irritating for practical use, American dermatologist  Albert Kligman became determined to find the optimal dosage for acne treatment. In the 1960s, he notoriously tested tretinoin on inmates at Holmesburg Prison in Philadelphia until he found a dosage that could be tolerated. This led to tretinoin’s approval by the Food and Drug Administration in 1971, subsequently marketed under the brand name Retin-A

In 1986, after adult patients using tretinoin to treat acne reported that the product was also reducing their wrinkles and improving their complexion, Kligman and his associates conducted a study on 400 adult women, concluding that topical tretinoin is capable of at least “partly reversing the structural damages of excessive sunlight exposure and may be useful in decelerating the photoaging process.”

Since Kligman’s 1986 work, there have been thousands of studies on tretinoin, making it one of the most researched anti-aging ingredients in dermatology. “Tretinoin is considered the gold standard in skin care, because of the extensive body of research that supports how well it works at increasing cell turnover,” said Ranella Hirsch, a dermatologist based in Cambridge, Mass. This boost in cell turnover helps increase collagen production, unclog pores (one way it helps to treat acne), smooth fine lines, reduce the appearance of sun damage and manage dark spots, Hirsch added.

The ability of retinoids to vanquish acne and wrinkles, however, has been accompanied by their reputation for painful side effects, such as peeling, flaking, redness, sun sensitivity, irritation and, for some skin types, hyperpigmentation. Evan Rieder, a New York-based dermatologist and psychiatrist at NYU Langone, thinks education about retinoids is as vital as the products themselves. “I have a picture from my sophomore dance in high school where my skin is literally falling off my face from using too much Retin-A to treat my acne,” because he wasn’t given the right information, he said. “So, part of this is the fault of dermatologists. We need to give people the right information about how to safely and tolerably introduce a retinoid.” That means knowing what strength retinoid to start with and how often to apply.

Retinoids are usually categorized by where they fall in the conversion pathway to retinoic acid, which is the strongest and the most likely to cause irritation. “For example, tretinoin is retinoic acid, so it’s much more potent than over-the-counter versions, because there is no conversion necessary before it has a biological effect on the skin,” said Joshua Zeichner, a New York-based dermatologist and director of cosmetic and clinical research in dermatology at Mount Sinai Hospital. The packaging on over-the-counter items should clearly state which kind of retinoid is in the product; one of the most commonly seen is retinol.  

 When Hirsch is explaining the difference in retinoid strengths to her patients, she likes to borrow a royal family analogy from author and skin-care expert Caroline Hirons: Think of prescription-strength retinoic acid (tretinoin, Retin-A) as Queen Elizabeth; it’s the strongest, because no conversion is necessary. Retinaldehyde (retinal) is Prince Charles, because it’s only one conversion away from retinoic acid; retinol is Prince William, because it’s two conversions away; and retinoid esters (retinyl palmitate, retinyl acetate and retinyl linoleate) are Prince George, the weakest of the retinoids and usually best tolerated.

“And not everyone needs to get to the queen. Some people will never need more than Prince William or Prince George,” Hirsch said.

The key to safely and tolerably introducing a retinoid is not only to start with a low strength but also to only apply a pea size of the retinoid two to three times per week, depending on your skin’s tolerability, Rieder said. “I love to start my patients on retinol or retinaldehyde [retinal] for a month or two, and then transition them to prescription-strength tretinoin,” said Sarvenaz Zand, a dermatologist based in Marin County, Calif. “This regimen helps to avoid all the irritation, peeling and redness that you can get with starting a prescription-strength retinoid right off the bat.”

Retinoids can treat acne and hyperpigmentation in people with darker skin tones. But if overused, they can cause further hyperpigmentation and dark marks from the peeling and inflammation, said Susan Taylor, a Philadelphia-based dermatologist and founder of the Skin of Color Society. “Light skin can get red, dry and flaky, but retinoids don’t necessarily cause darkness on light skin tones,” she said. With patients of color, she said, “I tend to select the lowest concentration, and then slowly titrate up.” She often starts by treating these patients with adapalene, which can be found over the counter as Differin, because it is perceived to be a bit milder.

Skin-care brands have developed a new generation of high-strength retinoids in the past few years that are intended to be more easily tolerated by the skin because of the addition of hydrating ingredients to the formulas, such as RoC Retinol, a line that includes creams and serums; Medik8 Crystal Retinal, sold in four different strengths, so users can slowly titrate up; and Altreno, a prescription medicine from the makers of Retin-A. Though these new formulas are meant to make retinoids more tolerable, you should still expect some irritation, Zeichner said.

“The first two to four weeks of usage, the skin goes through a process called retinization, where your skin adjusts to the application of the product,” he said. “And this can lead to redness, dryness, burning, stinging, peeling.” If you develop irritation, you need to put your foot on the brakes, use the retinoid less frequently and combine it with a moisturizer to help your skin tolerate it, Zeichner said.

Another reported side effect, particularly in people with active acne, is new outbreaks known as skin purging. “Purging is typically a sign that there was acne underneath the surface of the skin, and that the rapid skin-cell turnover from the retinoid is forcing the acne to the surface, making the acne appear worse before it gets better,” said Chicago-based dermatologist Caroline Robinson. But dermatologists say the purge usually resolves within weeks if patients stay the course.

When considering incorporating a retinoid into your skin-care routine, be mindful that retinoids are contraindicated for pregnant women and women planning a pregnancy. Also, you should avoid other products that exfoliate, Robinson said. “This means chemical exfoliants like hydroxy acids and physical exfoliation with any brushes, towels, pads.”

 She also emphasized that if you have a retinoid in your routine, you should always wear proper sunscreen and moisturizer to prevent irritation. “The biggest issue I see with darker skin tones and retinoids is if the patient doesn’t use adequate sun protection or moisturizer, it can lead to irritation and place the skin at some risk of hyperpigmentation,” she said.

Hirsch tells patients to hold off on starting other active skin-care ingredients, such as benzoyl peroxide, hydroxy acids or vitamin C, when incorporating a retinoid. “What I tell patients is that the retinoid needs to be the star of the show. She’s a bit of a diva, and you really have to let her have her time to set the stage just the way she wants it before allowing the supporting cast onstage.”

Rieder emphasized patience when it comes to seeing results from retinoids, whether using them for the treatment of acne or wrinkles. “I always tell my patients that in the beginning, you’re going to ask yourself, ‘Why the hell am I doing this to my skin?’ after having irritated, flaky skin for weeks and not seeing any difference at all. It’s like that six-month point, that one-year point that you really start seeing results. But it’s a journey, a long journey.”

Zeichner tells his patients that it will be worth it in the end. “It’s like going to Hawaii from New York,” he said. “It takes you a really long time to get there, but once you get there, you’re in paradise.” 

Mandell is a journalist based in the San Francisco area covering the beauty industry. Follow her on Instagram and Twitter.