Everything you need to know about topical retinoids,
in one place, reviewed and edited by dermatologists.
Mother, Wife, Hairstylist
“Skincare is a confusing place, and retinoids even more confusing. If you’ve wondered which
anti-wrinkle cream is best; if you’ve tried typical anti-aging serums or acne treatments and
haven’t seen results; or if you’re just trying to figure out where to get started – this guide is for
you.” - Dr. Lilliana Ramirez, M.D.
If you’ve paid even a smidge of attention to skincare in the last two decades, you likely know that topical retinoids can do some heavy lifting.
They’re useful in treating acne breakouts, melasma, scarring, as well as smoothing fine lines and wrinkles, among other skin concerns.
But with a variety of retinoids in use and a multitude of formulations, it’s hard to know where to begin.
What are the best anti-aging creams for wrinkles?
The buck stops here, with Nava MD’s Definitive Guide to Retinoids for Wrinkles.
The term “retinoid” refers to synthetic and natural forms of Vitamin A. Retinoids are a class of compounds either derived from Vitamin A or showing structural and/or functional similarities to Vitamin A.
Simply put, retinoids are some form of Vitamin A.
Vitamin A is crucial to a variety of physiological functions, including during embryogenesis and development of the nervous system, liver, intestine, eyes, and limbs. It also plays a pivotal role in vision function, and it’s used to treat a variety of skin conditions such as rosacea, acne, and psoriasis.
But because humans don’t produce Vitamin A endogenously (naturally in our bodies), we must get Vitamin A from our diets!
Foods of an animal origin, including milk, meat, dairy, eggs, and fish, are the most important sources of Vitamin A for most Americans, but Vitamin A is also found in many fruits and vegetables.
Due to the prevalence of Vitamin A deficiencies in much of the developing world, many staple foods have even been fortified with Vitamin A too.
The use of retinoids in skincare and for medical purposes dates all the way back to Ancient Egypt. At the time, Egyptians used animal livers to combat endemic night blindness (yuck).
The liver contains high concentrations of Vitamin A, and though these ancient people didn’t know exactly why their concoctions worked… they did! The Egyptians had stumbled onto a use for Vitamin A that persists all the way to current times.
Retinoids gained the attention of the medical community in the early 1900s for a few reasons.
Scientists isolated Vitamin A from an egg yolk for the first time and launched an improved ability to replicate and attain Vitamin A at any meaningful scale.
In the following decades, scientists also began to recognize that low levels of Vitamin A were associated with skin and eye conditions.
Around the same time, researchers made a connection to certain cancers when rats that were fed a diet deficient in Vitamin A developed carcinomas of the stomach.
Modern Vitamin A usage really took off in the 1970s, when doctors first began prescribing retinoids for acne treatment.
During this time doctors and their patients noticed additional benefits, such as the reduced appearance of fine lines and wrinkles, and Vitamin A became the first Vitamin approved by the U.S. Food and Drug Administration as an anti-wrinkle agent.
As practitioners learned more about Vitamin A’s capabilities in reducing the appearance of wrinkles and its ability to tighten pores, combating aging quickly became one of its primary uses.
Today, accessing retinoids is easier than ever, with both over-the-counter (OTC) options and prescription retinoids (Rx) for wrinkles in plentiful supply and variety. More retinoid options exist today than most people realize or care to know.
But not all prescription retinoids are created equal. Thankfully, dermatologists know which retinoids to use for wrinkles and skin care treatments—and why stronger isn’t always better.
The skin constantly produces new cells to replace old ones and repair surface damage. This is how wounds heal and scars fade over time.
Epidermis: The thin uppermost “crust” of the skin contains cells that produce pigment (melanocytes) and protect the immune system (Langerhans cells).
Dermis: The dermis is the thickest skin layer, making up 90% of the skin’s thickness, and contains connective tissue, blood vessels, nerve endings, and oil and sweat glands. This is where hair follicles reside.
Subcutaneous Tissue: Made up mostly of fat and connective tissue, this is also home to larger blood vessels and nerves. This is the cushioned layer of the skin that also serves to regulate body temperature.
By way of example, tattoos (which are permanent) penetrate the epidermis and dermis, but third-degree burns damage all three layers of the skin and may not heal on their own, requiring skin grafts.
Known as the skin cell turnover process, your epidermis (which is only 1-2 pieces of paper thick) is replaced completely every 28-30 days.
During this process, new cells emerge from the deeper skin layers to replace surface cells, which are sloughing off all day, every day (this is where much of the dust in your house comes from—dead skin cells!)
As we age, the turnover process happens less frequently and more slowly. In older individuals, turnover can take up to 50 days. This increases the likelihood of wrinkles and fine lines as you move into your 30s and 40s.
As we age, the skin also begins to produce less collagen, elastin, and sebum, all of which are crucial to resilient, glowing, moisturized skin. Your skin becomes thinner and drier, particularly around the neck and on the face.
Lifestyle factors can make the skin aging process faster and more apparent as well. For example, people who smoke tend to have deeper and more noticeable wrinkles.
Similarly, constant exposure to UV rays from the sun can damage the skin and make signs of aging more apparent.
Retinoids hasten the regeneration of your uppermost skin cells. They also cause the skin to:
Retinoids work by binding to particular receptors called Retinoic Acid Receptors (RAR) and Retinoid X Receptors (RXR).
These in turn affect the way genes are expressed and cells behave and manifest physically through the skin: faster turnover, more of them, collagen production, etc.
Not all retinoids work the same way on these receptors, and these receptors can be further subdivided by specific types, which is key to differentiating some of the many retinoids.
Some retinoids work on certain RAR subtypes only (Gamma or Beta, for example), while others trigger all of them at once.
One drawback to the amazing benefits of retinoids is that they don’t produce results overnight. It can take 8 weeks of regular use before people begin to see results, and they generally need to continue use to maintain those results.
Best results with retinoids are typically visible after 3 months to a year of use. But retinoids are an incredibly powerful active ingredient to introduce into your skincare routine.
“Retinoids are probably the single most important tool that the field of cosmetic dermatology has in its toolbelt,” says Dr. Lilliana Ramirez Garcia, “They work for a variety of conditions, and I think just about everyone will find that regular use of a retinoid will improve the look and feel of their skin.”
Here’s the most confusing part about retinoids: there are lots of options, they’re not all the same, and providers and manufacturers sometimes use retinoid-related terms interchangeably and as catch-alls.
Retinoid is a general term to describe the many Vitamin A derivatives that are similar in structure and work toward similar skincare goals.
The most common is retinol, and it’s the retinoid you’ll see in most OTC skin care products.
But OTC retinol products do not work the same way as retinoic acid, retinyl, or retinaldehyde, which are all terms you may have come across.
Retinoic acid is the only natural form that the skin can put to use.
Retinoic Acid receptors, you may recall, are the biological mechanism on which retinoids work. They require retinoic acid for signaling.
All of the other retinoids, like retinol and retinaldehyde, are precursors to retinoic acid. These must be converted to retinoic acid to affect your skin.
Tretinoin vs Retinol
That’s part of the reason that retinol, which is in many over-the-counter products, is less potent than medication tretinoin. It goes through a two-step conversion process first. Compared to retinol, tretinoin (retinoic acid) is about 20x more powerful.
From Beauty Cream to Signaling Molecule
Retinyl Esters (retinyl acetate, retinyl oleate, retinyl palmitate, retinyl stearate, etc.) -> Retinol -> Retinaldehyde -> Retinoic Acid
Retinoids differ meaningfully in potency and selectivity. Here’s a rundown of the many retinoids you may run into, in general order of their potency from lowest to highest.Retinyl Esters (Retinyl Acetate, Propionate, Retinyl Palmitate, etc.)
Retinyl esters are considered the most stable of the retinoids, which means that they may be the most gentle for some people—but also generally the least effective.
Retinyl esters must be converted to retinol and then retinaldehyde before finally moving to the active form of retinoic acid. You may experience fewer side effects with retinyl esters, but that comes with reduced efficacy or longer wait times for effectiveness.
As it’s so mild, retinyl esters may be ideal for super sensitive skin types, but don’t have high expectations if you’re just starting on your skincare journey.
Typical Application: 0.05% to 0.3% cream concentrationsRetinol (In many OTC beauty products)
Most consumers and patients first turn to a retinol product when using retinoids for wrinkles. It’s most commonly recommended for anti-aging purposes and is generally considered one of the most effective options.
Remember, retinol must be converted to retinaldehyde and then retinoic acid before it becomes functional as a healing and anti-aging serum.
People generally begin to see results with an over-the-counter retinol within three months. These manifest as fewer wrinkles and lightening of fine lines. Retinol users may experience less irritation than with prescription or more potent retinoids.
One problem with retinol and OTC retinoid formulations is that their concentration is imprecise for two reasons. Firstly, they are notoriously unstable. They don’t sit well on a shelf, and light (like what filters through their packaging) can degrade these retinoids quickly.
By the time your OTC retinoid goes home with you, it may not work nearly as well as it was intended to from the factory.
Second, because OTC retinoids are not FDA-approved, they attract less scrutiny and monitoring from regulators: concentrations are not always precisely checked, making their effectiveness questionable if the manufacturer is unscrupulous.
Typical Application: 0.0015% - 1% cream and gel concentrationsRetinaldehyde or Retinal (In many OTC beauty products)
This retinoid has become a strong rival to retinol in the cosmeceutical space and is often used by those with sensitive or easily irritated skin.
Like retinol, it must be converted to its functional form retinoic acid, but unlike retinol, it’s one step closer to the final product. Retinaldehyde is typically considered less effective than retinol.
Typical Application: 0.05% to 0.1% cream concentrationsAdapalene (Common brand names: Differin®, Epiduo®)
This retinoid is technically a naphthalenecarboxylic acid derivative with retinoid-like activity.
It was prescription-grade after its 1996 approval but received FDA approval for OTC use without a prescription in 2016.
Patients more commonly use it to treat acne than wrinkles, and it can resolve skincare issues related to blackheads, whiteheads, spots, and clogged pores.
People with sensitive skin sometimes prefer adapalene gel because it has a lower risk of causing irritation.
There’s a reason adapalene is OTC: it tends to be less effective than other prescription retinoids.
Typical Application: 0.1% gelRetinoic Acid or Tretinoin (Common brand names: Retin-A®)
This is where things get interesting. Retinoic acid (also called all-trans-retinoic acid) is the active molecule that your body puts to work.
At full strength doctors prescribe it for acne, and in lower strengths it can be used for anti-aging purposes.
It can be found in both cream and gel forms, and patients taking tretinoin should follow professional medical advice closely.
Tretinoin requires a prescription. That’s because this substance is up to 20 times more powerful than retinol and other options you might find without a prescription.
Not surprisingly, tons of studies have supported its effectiveness, and it’s a workhorse of the dermatology field.
Tretinoin is also known for its ability to irritate skin.
The mechanism that makes tretinoin effective for fighting fine lines and wrinkles also leads to a temporary condition called retinoid dermatitis—redness, irritation, peeling, and dryness. It’s so common, in fact, that it has its own colloquialism: the retinoid purge.
Niacinamide is an anti-inflammatory often used in conjunction with tretinoin and other prescription retinoids to ease that process and improve tolerability.
Typical Application: 0.01% to 0.1% gels, creams, microspheres, and emollients.Isotretinoin (Common brand names: Accutane®, Accutin®)
This retinoid is taken orally. It requires a prescription and is considered one of the strongest forms of retinoid.
Doctors generally do not prescribe isotretinoin for wrinkles. Instead, patients use it to treat cystic acne, aggressive acne, or scarring acne. It is also not safe for pregnant women.
Typical Application: Oral Capsule 0.5-1 mg/kg of body weightTazarotene (Common brand names: Tazorac®)
This is one of the strongest retinoids and is prescription-grade for a reason. It’s so effective that it’s more frequently used to treat psoriasis than acne or wrinkles.
Yet of all the many retinoids, this remains one of the least studied, especially as it applies to treating wrinkles.
Tazarotene is known for being harsh on the skin, and it’s often reserved for the most hard-to-treat skincare conditions.
Typical Application: 0.05% to 0.1% creams.Trifarotene (Common brand names: Aklief®)
Trifarotene is the first retinoid to receive approval from the U.S. FDA to treat acne in some time. Approved for acne in 2019, it’s indicated for use on the face, chest, back and shoulders.
What makes this topical retinoid unique is its specificity for the gamma Retinoic Acid receptor, one of three RAR isotypes, meaning that it is potentially gentler on and less irritating to the skin.
While trifarotene is still fairly new, it may be a compelling option for those with sensitive skin. Because trifarotene is new to the market, it’s also typically the most expensive of the retinoids.
Typical Application: 0.005% cream.Alternative Plant-Based Anti-Aging Creams: Bakuchiol
For people who prefer vegan anti-aging creams, there are plant-based options. Bakuchiol, which is a jelly-textured serum extracted from the babchi plant, is considered one of the most potent.
It’s not actually a retinoid, but studies have shown that it works similarly to OTC retinol.
It brightens, exfoliates, and smooths skin texture and combats the appearance of aging. A 2014 study found that participants had similar results to retinol after 12 weeks with none of the usual side effects.
If you want to include retinoids in your skincare routine, you don’t actually need to visit a doctor’s office to get a prescription.
In fact, your doctor may even recommend an over-the-counter retinol-containing formulation to begin.
This can be the case for mild acne treatment because lower-strength retinoids can reduce discoloration of the skin and keep pores from becoming clogged. A less potent retinoid can also lead to lower chances of skin dryness, peeling, and irritation.
Because of this, people with sensitive skin tend to start with over-the-counter options. However, they’re often not nearly as effective as prescription medications that can kick the cell turnover process into overdrive.
Even though tretinoin and prescription retinoids are considered more potent than OTC retinoids like retinol, sensitivities can be ameliorated with the help of a professional.
On top of that, because OTC retinoids are not approved by the FDA, they face less scrutiny and regulation. Concentrations (and effectiveness) can vary far more than most professionals would like.
Prescription-grade formulas avoid this issue.
Where should you begin? That’s a personal question, but dermatologists generally prefer prescription-grade retinoids for wrinkles and more serious acne treatment.
Newer formulas have also managed to achieve effectiveness with a lower likelihood of skin irritation, and for more serious skin conditions, dermatologists might even prescribe oral retinoids.
When using retinoids for wrinkles and more, there are some side effects to be aware of and precautions to take. Adhering to recommendations from your doctor can ensure you reap the rewards of your retinoid treatment with few problems.Skin Irritation
When using retinoids for wrinkles and more, there are some side effects to be aware of and precautions to take in your skincare routine.
Adhering to recommendations from your doctor can ensure you reap the rewards of your prescription retinoid treatment with few problems.Your Skin Type
If you have sensitive skin—and sometimes even when you don’t—it’s prudent to start slowly with retinoid treatment. This might mean applying a topical treatment less frequently until your skin becomes accustomed to it.
Using only a small amount can also help ease your skin into the new skincare products. Dermatologists generally recommend applying a gentle moisturizer before applying your retinoid to help with any sensitivity.Your Skin Type
All skin types can use retinoids. Even so, people with fair, sensitive or oily skin should take stronger precautions.
Those who’ve recently over-exfoliated or experienced sun damage should hold off on using retinoids until their skin recovers.Mixing with Other Skin Care Treatments
If you use other skincare products, be mindful of how they might react. It’s not a good idea to mix retinoid products, and using a scentless moisturizer and a basic cleanser while starting a new retinoid is often recommended.
Because retinoid-related dermatitis is so common, go easy with makeup during the first few weeks of your new skincare routine.Minimizing Sunlight Exposure
Retinoids are notoriously unstable. Sunlight can negatively impact the stability of retinoids, which is why your physician will likely recommend applying them before bed rather than in the morning.
Retinoids are known for teratogenicity, meaning they can cause birth defects in a developing fetus.
Even if you have the most resilient skin in the world, introduce a retinoid product slowly. Almost every patient will deal with some dryness or irritation while their body acclimates.
This is normal and to be expected, and Dr. Lilliana M. Ramirez Garcia recommends these steps to train your skin for active ingredients like retinoids:
Most retinoids are approved for use as early as the teenage years for acne treatment, and there are no major restrictions on their use aside from avoiding retinoids during pregnancy.
Dermatologists often recommend that people begin using retinoids in their 30s and 40s because this is when the body begins to slow down that generous skin regeneration process and collagen growth and sebum slows.
In reality, a gentle retinoid under the guidance of professional medical advice can do wonders for people at almost any age.
Because over-the-counter retinol for wrinkles don’t all require prescriptions, you may be tempted to pick one up at the grocery store.
For those with super finicky, sensitive skin, that may be a good starting place. Otherwise, connect with a skincare specialist to get the real deal and great advice. It’s no longer the hassle or expense it once was.
At Nava MD, our licensed clinicians can determine the strength and retinoid to serve your needs best, all while considering your skin type, condition, and known sensitivities. Then they can provide you with professional medical advice throughout the treatment process.
Nava MD’s custom prescription creams contain both tretinoin and niacinamide, a combo that can help to cut down on irritation while smoothing fine lines and wrinkles.
It begins with an online questionnaire that gives your assigned clinician the background and details that they need to make a quality assessment of your situation.
From there, your clinician selects the right ingredients and concentrations that will work well for you and writes a prescription for them, if approved.
Our partner compounding pharmacy mixes your blend, and your custom formula is sent to your door. Don’t worry about running out! Refills are sent monthly, and you can access your clinician any time through the Nava MD Patient Portal.
1. Zasada M, Budzisz E. Retinoids: active molecules influencing skin structure formation in cosmetic and dermatological treatments. Postepy Dermatol Alergol. 2019;36(4):392-397. doi:10.5114/ada.2019.87443
2. Pawson, Beverla A. History of retinoids. Journal of the American Academy of Dermatology, 6(4), 577-582. Doi: https://doi.org/10.1016/S0190-9622(82)70050-7
3. Urbańska M, Nowak G, Florek E. Wpływ palenia tytoniu na starzenie sie skóry [Cigarette smoking and its influence on skin aging]. Przegl Lek. 2012;69(10):1111-1114.
4. Ghyselinck NB, Duester G. Retinoic acid signaling pathways. Development. 2019;146(13):dev167502. Published 2019 Jul 4. doi:10.1242/dev.167502
5. Szymański Ł, Skopek R, Palusińska M, et al. Retinoic Acid and Its Derivatives in Skin. Cells. 2020;9(12):2660. Published 2020 Dec 11. doi:10.3390/cells9122660
6. O'Byrne SM, Blaner WS. Retinol and retinyl esters: biochemistry and physiology. J Lipid Res. 2013;54(7):1731-1743. doi:10.1194/jlr.R037648
7. Kwon HS, Lee JH, Kim GM, Bae JM. Efficacy and safety of retinaldehyde 0.1% and 0.05% creams used to treat photoaged skin: A randomized double-blind controlled trial. J Cosmet Dermatol. 2018;17(3):471-476. doi:10.1111/jocd.12551
8. Kong R, Cui Y, Fisher GJ, et al. A comparative study of the effects of retinol and retinoic acid on histological, molecular, and clinical properties of human skin. J Cosmet Dermatol. 2016;15(1):49-57. doi:10.1111/jocd.12193
9. Bhawan J, Gonzalez-Serva A, Nehal K, et al. Effects of tretinoin on photodamaged skin. A histologic study [published correction appears in Arch Dermatol 1991 Sep;127(9):1382]. Arch Dermatol. 1991;127(5):666-672.
10. Weinstein GD, Nigra TP, Pochi PE, et al. Topical tretinoin for treatment of photodamaged skin. A multicenter study. Arch Dermatol. 1991;127(5):659-665.
11. Bagatin E, Gonçalves HS, Sato M, Almeida LMC, Miot HA. Comparable efficacy of adapalene 0.3% gel and tretinoin 0.05% cream as treatment for cutaneous photoaging. Eur J Dermatol. 2018;28(3):343-350. doi:10.1684/ejd.2018.3320
12. Hernandez-Perez E, Khawaja HA, Alvarez TY. Oral isotretinoin as part of the treatment of cutaneous aging. Dermatol Surg. 2000;26(7):649-652. doi:10.1046/j.1524-4725.2000.99210.x
13. Rouvrais C, Baspeyras M, Mengeaud V, Rossi AB. Antiaging efficacy of a retinaldehyde-based cream compared with glycolic acid peel sessions: A randomized controlled study. J Cosmet Dermatol. 2018;17(6):1136-1143. doi:10.1111/jocd.12511
14. Urbańska M, Nowak G, Florek E. Wpływ palenia tytoniu na starzenie sie skóry [Cigarette smoking and its influence on skin aging]. Przegl Lek. 2012;69(10):1111-1114.
15. Zasada M, Budzisz E. Retinoids: active molecules influencing skin structure formation in cosmetic and dermatological treatments. Postepy Dermatol Alergol. 2019;36(4):392-397. doi:10.5114/ada.2019.87443
16. Chaudhuri RK, Bojanowski K. Bakuchiol: a retinol-like functional compound revealed by gene expression profiling and clinically proven to have anti-aging effects. Int J Cosmet Sci. 2014;36(3):221-230. doi:10.1111/ics.12117
17. Dhaliwal S, Rybak I, Ellis SR, et al. Prospective, randomized, double-blind assessment of topical bakuchiol and retinol for facial photoageing. Br J Dermatol. 2019;180(2):289-296. doi:10.1111/bjd.16918