The Ultimate Guide to Retinols—
And Next Gen Retinoids Worth a Try

Woman with glowing skin

When it comes to the skin, topical retinoids (along with sunscreen!) are the gold standard for anti-aging skincare products. These vitamin A derivatives help slow down formation of wrinkles and improve skin texture by smoothing out fine lines with regular use. They also help lighten dark spots and even out skin tone. So why wouldn’t everyone be using this ingredient with such amazing properties? Unfortunately, retinoids can cause irritation, redness, and peeling, and those with sensitive skin can also develop itching and burning. These side effects cause many to look for other forms of vitamin A, or reduce or even stop use. But we firmly believe that with careful product selection and appropriate moisturization, most people should be able to work this hero ingredient into their routines. In this post we’ll review the multitude of options for retinoids - over the last 10 years, there has been a veritable explosion of options, both over the counter and prescription - and go over how best to incorporate retinoids into your skincare routine. 

How do retinoids work? 

Topical retinoids accelerate skin turnover and help skin cells “mature”, or differentiate, properly, When applied to the skin, these molecules bind to retinoic acid receptors in the skin and “turn on” different pathways for skin cell growth and maturation. Skin has several layers, each with differing structures and functions. The various layers also have different  receptor subtypes (RAR in the epidermis, or first layer of skin, RARbeta in the dermis, or second layer, and RXRa in all layers of skin). Each type of retinoid has varying affinities for these receptors and thus affects the skin differently. 

So what does this mean for skincare? These superpower topicals can remove dead skin cells, unclog pores, and prevent new acne from forming. They block several inflammatory pathways. Retinoids also block pigment transfer between skin cells and thus can lighten dark spots. And for anti-aging, retinoids have been shown to slow down the process of collagen breakdown—which is how it’s effective for that all-important anti-wrinkling effect—and even induce formation of new collagen in the skin.

If they’re so great, why isn’t everyone using them?

If retinoids are anti-aging, brightening, and fight acne, you would think that everyone would be using them every day! The reason that retinoids may get a bad rap can be summed up in one word: irritation. As they affect how the cells in your skin develop and interact, they can cause peeling, flaking, excess dryness, itching, and redness. Most can build some tolerance over time, but some people are unable to tolerate most retinoids and so end up using them so rarely they don’t see any benefit, or set them aside entirely. 

Ok, so what are the different types and how do I choose one?

There are over 2,000 retinoids in existence! But just a few are used widely in skin care. Some are biologically active right out of the gate, like retinoic acid, and some require conversion of the vitamin A molecule into retinoic acid by the skin. It’s easiest to think about these as prescription, available only through your doctor or dermatologist, and over-the-counter (OTC) options, which do not require a prescription. 

As you can see in the above diagram, “retinoid” is an umbrella term that refers to a group of vitamin A derivatives. Retinoic Acid is the format that is most bioavailable for your skin but it is also the most irritating and available only with a prescription. The next most bioavailable is retinaldehyde (being one step away from Retinoic Acid), then retinol (two steps), then retinyl palmitate and retinyl acetate (3 steps). Each has its pros and cons so read on to see which is most suitable for you. 

Over-the-Counter Retinoids 

OTC retinoids are the ones you’ll find on retail store shelves. There are dozens of products, so we hope this guide will help demystify this ingredient a bit. In our diagram above, these encompass all the retinoids except for Retinoic Acid.

Retinyl Esters 
This is a group of retinols that have an extra molecular “tail” attached, usually to help slow their absorption and reduce irritation. There are a bunch: retinyl acetate, retinyl palmitate, even retinyl sunflowerate. These retinols require hydroxylation to retinol, which is then oxidized to retinaldehyde, which is then changed into retinoic acid, the active form, which goes on to bind those receptors in the skin and work its magic. So if you’re counting, that means that retinyl esters require 3 steps of conversion before it reaches the active form of retinoic acid. Because of this long conversion process, retinyl esters are weaker than the other topical OTC options and generally take a very long time to work. 
Retinols are one step closer to the active form than retinyl esters. There are some studies showing that retinol induces the same skin changes as tretinoin with regular use, including reduced appearance of fine wrinkles, and increased production of collagen. Compared to prescription tretinoin, retinols are not as strong - but they are also less irritating, and are widely accessible at many price points. 
These are another OTC form of vitamin A used in skincare. It is only one step removed from the active retinoic acid form, so it’s considered stronger, but also carries increased potential for irritation, peeling, and dryness, like with tretinoin. It can also be difficult to stabilize in skincare formulations. 

Prescription Retinoids 

Now that we’ve covered the OTC retinoids, let’s look at the prescription options. There are four generations of prescription retinoids. These are super-strong with some studies showing good long-term effectiveness, but can often be irritating. Prescription topicals can be the right solution for many folks, but may carry higher price tags and require a doctor’s evaluation. 

First Generation Retinoids

Tretinoin, the “original” topical retinoid, is a synthetic form of retinoic acid (the biologically active form) that has an official FDA approval for anti-aging as well as acne treatment. It binds to all three retinoic acid receptors so is incredibly effective. It comes in cream, gel, and lotion forms, and also has a microsphere/encapsulated form, which helps with irritation as the medication is slowly released onto the skin. It is fairly unstable in the sun, so it’s recommended to use this at night. Unfortunately, while it’s the most studied for anti-aging purposes, it is also widely known for being irritating: many patients may not be able to get past the first few weeks where redness and peeling is an issue. Many will give up or rarely use it, meaning its potential benefits aren’t fully realized, in which case other options like the OTC options may be better. 

Second Generation Retinoids

There are only a few drugs in this generation - acitretin and etretinate - which are prescribed for medical conditions like severe psoriasis. There are no topical versions of retinoids in the second generation so we won’t discuss them here.  

Third Generation Retinoids

The two in 3rd gen retinoids in wide use are tazarotene and adapalene. Tazarotene is a prescription medication, found in cream and gel form, as well as a combination lotion with a steroid, which is primarily used for psoriasis. Considered the strongest of the topical retinoids, it’s also used for acne, especially more severe types, and for those lucky folks with skin tolerant of strong retinoids, it can be an effective medication for anti-aging as well. 
Adapalene is available as cream and gel, and comes in two strengths- one over the counter, and one prescription. Considered the weakest prescription retinoid (but also the least irritating) it can be used in the daytime as well as nighttime as it doesn’t break down with sun exposure like tretinoin does. There are ongoing studies on whether adapalene has the same anti-aging effects as tretinoin. 

Fourth generation Retinoids

These retinoids are the new kids on the block. Trifarotene, or “Aklief”, is the first new FDA-approved retinoid in nearly 20 years! Because it binds to the RARgamma receptor that is most abundant in skin, making it more selective than the other retinoids, it can be more effective at a lower dose - which means fewer side effects. Since a little goes a long way, it can be helpful for acne on the back and chest in addition to the face. Studies are ongoing to see whether this can help with anti-aging as well.  

How to use topical retinoids 

Once you’ve selected the right retinoid product for your skin, whether that’s a low concentration encapsulated retinol designed for daily use, or a higher strength tretinoin prescription cream - you’ll want to work it into your regular skincare rotation. The key to starting a retinoid is patience! Slow and steady wins the race. Dermatologists counsel patients to start using this slowly - every 3-4 nights initially, and just a small, pea-sized amount to clean, dry skin - and gradually increase use as tolerated. Applying your favorite moisturizer after the retinoid will help keep your skin moist while the retinoid goes to work. For the especially sensitive, applying moisturizer to the skin first and then the retinoid may also help build tolerance. During the first few weeks of use, skin turnover is accelerated and the skin cells aren’t quite as cohesive or “stuck together” as they usually are - which can show up as irritation, redness, and peeling. If you can get through this stage, you may well end up on the other side, where the irritation decreases and skin is smoother and brighter. If you find you can’t get past the irritation or it’s severe, talk to your dermatologist about other options. 

Other Considerations: Encapsulation and Packaging

Scientists have been working on retinoids for years, trying to develop one that is effective as well as easy to use without the unpleasant side effects. One of the most useful developments is that of encapsulation, where the retinol is wrapped in a protective blanket. When applied to the skin, this blanket helps slow the absorption down until the molecule reaches deeper into the skin before it is activated. This helps make the product more tolerable with less skin dryness, flaking, and irritation. And, importantly, it helps stabilize the retinol in the product to ensure it remains active on store shelves, in your bathroom cabinet, and ultimately on your skin. Unfortunately, like vitamin C, retinol products vary widely in stability and some studies have shown that many products show significant decreases in concentration over a short period, which means your pricey product may be nothing more than a fancy moisturizer after just a few months. Using an encapsulated retinoid product that is designed to slowly release active retinol means it can stay in your regular rotation with less irritation and maximum benefit. You should also only use formulas that are packaged in opaque airless containers since air and light can quickly degrade the effectiveness of retinoids. Selecting a product specifically formulated and tested for stability is important to ensure this mainstay of your skincare routine remains effective and can deliver all its anti-aging benefits. 

Disclaimer: As with all of the information on this site, this post is meant to be for informational and educational purposes only, and is not medical advice. When in doubt, please ask your physician. 

Teresa Fu, M.D.

Dr. Teresa Fu is a board certified dermatologist and mother of two. She graduated from Stanford Medical School and practices in the San Francisco Bay Area.