What are Retinoids, its Benefits and Different Types

Retinoids, which are derivatives of vitamin A, can be beneficial for fine lines, wrinkles, hyperpigmentation, and acne. There are different types of retinoids including retinol, retinal, retinyl esters, retinoic acid esters, tretinoin, tazarotene, adapalene, and trifarotene.

Table of Contents

What are retinoids?
Benefits
Retinoic acid receptors
Types
Retinyl esters
Retinol
Retinaldehyde
Retinoic acid esters
Tretinoin
Adapalene
Tazarotene
Trifarotene
Which one to choose?
Charts

What are retinoids?

Retinoid is a big group that includes all the Vitamin A derivatives. It includes both prescription and non-prescription retinoids. These are well-researched and effective ingredients, and it has been proven by evidence in real people.

Skin biopsies were seen under the microscope, and changes were seen. So, that is the reason they are considered the gold standard for anti-aging.

A very common question asked is “What is the difference between retinol and retinoids?“. Retinol falls under the big umbrella term of retinoids. So, they are no different. In other words, retinoid is a big tree and retinol is one of its branches.

Note: We cannot clearly classify the retinoids into prescription and non-prescription groups, since the regulations are different in different countries. While one type of retinoid may be available over the counter in one country, it may or may not be available in another (0.1% adapalene is over the counter in the United States but 0.3% is prescription and in some countries, it’s not available over the counter; tretinoin is a prescription drug in most countries and so on).

Different groups

Based on the structural characteristics and the time when they were first introduced, they are grouped into various generations (including oral and topical, prescription and non-prescription topicals).

First generation – Retinol (vitamin A) and its derivatives, tretinoin (retinoic acid – Retin A), isotretinoin, alitretinoin
Second generation – Etretinate, acitretin
Third generation – Arotinoid, adapalene, tazarotene
Fourth generation – Trifarotene

As you can see, first-generation retinoids are the oldest and are the ones that were studied in the 1960s. Adapalene as in Differin (FDA approved in the 1990s for acne) and tazarotene as in Tazorac, are relatively new. Trifarotene is the most recent addition to the retinoid family.

How do they work and their benefits

Retinoids need to be absorbed into the cells after we apply them on our skin, bind to receptors in the cell, and carried to the nucleus where they bind to different receptors (eg, RARs, RXRs), and produce various effects by acting on the genes involved in the formation of skin cells and their differentiation.

This sounds complex but all this results in the normalization of shedding of skin cells. This eventually results in the improvement of skin barrier function, smoother texture of the skin, refined appearance of pores, and unclogging of pores resulting in decreased formation of acne skin lesions.

Retinoids also increase the formation of collagen and prevent the breakdown of collagen due to UV exposure. So, the results are improvement in fine lines and wrinkles.

Its anti-inflammatory and antioxidant properties are beneficial for the skin as well. It is useful for dark spots as it interferes with the cycle of melanin pigment formation.

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Let’s talk briefly about the receptors to which retinoids bind.

Retinoic acid receptors

The action of the retinoids is mediated by various receptors present inside the nucleus of the cell. There are two types of Retinoid nuclear receptors (RNR):

Retinoic Acid Receptors (RAR)
Retinoid X Receptors (RXR)

Retinoids found in our skincare mainly bind to the retinoic acid receptors (RARs) to produce their effects. Some specifics of Retinoic acid receptors:

RAR-γ is mainly expressed in the top layer of skin/epidermis (accounts for nearly 90% of RARs in the top layer of skin /epidermis).
RAR-α is expressed by both epidermis/keratinocytes and cells present in the deeper layer of skin called dermal fibroblasts.
RAR-β is expressed mainly by dermal fibroblasts.

Binding to retinoic acid receptors

Different retinoids bind to different receptors

Tretinoin can bind to all RAR receptors.

New-generation retinoids like adapalene and tazarotene bind specifically to RAR-beta and RAR-gamma. Since it is more selective for these receptors, it comes with the advantage of being more useful for acne and less irritation.

The newest retinoid, trifarotene, is specific for RAR-gamma. This retinoid has the additional advantage that there will be no irritation due to the involvement of RAR-beta and alpha receptors and hence better tolerated. In addition, it can be effective at a lower concentration.

Now let’s talk about each retinoid briefly and see which might be the right fit for you.

Types

1. Retinyl esters

Starting with the ones that need at least three steps of conversion to the active form. These first get converted to retinol, then to retinal, and finally to the active form, all-trans-retinoic acid. This includes derivatives like retinyl acetate, retinyl propionate, and retinyl palmitate.

The problem with these is that they don’t have great evidence of their effectiveness. There are mixed studies in the literature. Some consider retinyl propionate better than the other esters. But even this ester doesn’t have convincing data.

Studies showing the effects of retinyl esters

In one study (1998), 0.15% retinyl propionate cream and the plain vehicle had no significant difference in any of the parameters of skin photoaging.
In another study done by Procter & Gamble, an anti-aging regimen with multiple actives niacinamide, peptides, and 0.3% retinyl propionate (Olay products) was compared to 0.02% tretinoin. It was found that these ingredients worked better and were tolerated well as compared to tretinoin. However, we cannot be sure if all the positive effects were due to retinyl propionate, since it has niacinamide which can have many benefits for aging skin, and peptides which can enhance the skin’s appearance by hydrating it.

Still, more studies are needed to compare these molecules and how the results vary among different people.

Who should use retinyl esters?

If you have a lot of photodamage of skin, these might not give you the desired results. However, if your skin is sensitive and you are new to retinoids, these might be useful. Personally, I would look for retinyl propionate.

Confusing marketing: Sometimes these are referred to as pro-retinol which is often confused with retinol. Pro retinol is just a name for precursors of retinol. So, make sure to take a look at the ingredient list.

Retinyl ester products

Vivant Skin Care Derm-A-Gel [Vivant] [Amazon] – retinyl propionate along with kojic acid, niacinamide, and urea.
A313 Vitamin A Pommade [French pharmacy] [Walmart] – It has retinyl palmitate. The texture is that of a thick ointment and you may not need a moisturizer.

2. Retinol

Retinol is the buzz over-the-counter retinoid since this is what is seen in the majority of skincare products. It is the alcohol form of Vitamin A.

This needs two steps for conversion to the active form. Also, it not only gets converted to retinoic acid but several other derivatives. It is considered around 20 times less potent than retinoic acid or tretinoin.

Studies showing the effects of retinol

Multiple studies have shown it to be effective for aging, acne, hyperpigmentation, and improving skin texture just like retinoic acid but with a better tolerance profile.
One study used retinoic acid (0.1%) and retinol (0.1%) for comparison and found that they both led to similar changes in the skin, gene expression, and collagen synthesis. However, the effects produced by retinol were of a smaller magnitude.
In another study, retinol 0.2%/LR2412 2% and tretinoin 0.025% cream led to similar clinical results. However, LR2412: tetra-hydro-jasmonic acid is a potent plant derivative and is beneficial for skin aging. So, this is a confounding factor, which means we cannot attribute all the positive effects to retinol alone.

In simple words, retinol is not as strong as tretinoin. However, retinol is stronger than its derivatives. So, start slow if you are new to retinoids.

Products with retinol

Cerave Resurfacing Retinol serum [Target] [Ulta] Encapsulated retinol, Niacinamide, Licorice extract
Cerave Skin Renewing Retinol Serum [Amazon] [Ulta] Encapsulated retinol, Niacinamide
Paula’s Choice CLINICAL 0.3% Retinol + 2% Bakuchiol Treatment [Amazon] [Paula’s Choice]
Paula’s Choice RESIST Intensive Repair Cream [Amazon] [Paula’s Choice] 0.01% Retinol, Magnesium Ascorbyl Phosphate, Niacinamide, Vitamin F, Licorice extract, Soy extract. This is a petrolatum-based product so it can be used as an effective moisturizer.

3. Retinaldehyde

If you are looking for the most potent over-the-counter retinoid, probably this is the one. Retinaldehyde (aka retinal) needs just one step of conversion. It can be metabolized to both retinol and its derivatives, and the active form, retinoic acid (RA). Also, it is 11 times more potent than retinol.

It can increase the thickness of the epidermis, increase skin elasticity, improve skin texture, and reduce skin roughness. In addition, its antibacterial properties make it very useful for acne.

Studies showing the effects of retinaldehyde

Retinaldehyde 0.05 % and retinoic acid 0.05% in a cream vehicle led to a similar outcome as seen in one study. They both significantly reduced wrinkles and skin roughness (measured by an imaging system). Retinoic acid, however, caused more irritation.

Products with retinaldehyde

Avene retrinal 0.1 Intensive cream [Amazon] [Avene]
Geek and gorgeous A-game 5 [Geek & gorgeous]

Related: Best retinaldehyde products

4. Retinoic acid esters

These are the new addition to the family, with limited research and data. However, they do look promising, and hopefully, in the future, we will see more studies. These are considered more potent than retinol but without or lesser side effects.

Note: These are different from the retinyl/retinol derivatives mentioned above.

There are two types: Hydroxypinacolone retinoate and retinyl retinoate (in a few countries, these have some restrictions and may come under prescription topicals)

Hydroxypinacolone retinoate (HPR) – Part of granactive retinoid

The good thing about this retinoid is that it can bind directly to retinoic acid receptors, so it does not need conversion to retinoic acid. Most of the data about this comes from the manufacturer, which showed it to be beneficial for wrinkles, photodamage, and age spots.

Granactive retinoid is a mixture of HPR at 10% concentration with a solvent (dimethyl isosorbide). So, if you see a product with it and are curious about its concentration, divide it by 10 to get the concentration of active HPR.

Studies showing the effects of Hydroxypinacolone retinoate

A study sponsored by Estee Lauder found that it can lead to greater gene transcription (using retinoid acid responsive elements assay) than retinol and retinyl palmitate. However, the levels were less than all-trans-retinoic acid. So, it should be more effective than retinol and its derivatives.
In a few studies (like the first, second, and third study), it was found to be useful for acne but it was used with several other ingredients like retinol, niacinamide, salicylic acid, etc. So, we don’t know if it as a stand-alone ingredient can be beneficial for acne or not.

Products with Hydroxypinacolone retinoate (HPR)

When buying a retinoic acid ester, make sure to check the ingredient list since some products have both esters and retinol.

The Ordinary Granactive Retinoid 2% in Squalane [Deciem]
The Ordinary Granactive Retinoid 5% in Squalane [Deciem]
Garden of Wisdom Granactive Retinoid 5% Serum [Victoria Health]

Retinyl retinoate

This is formed by combining retinoic acid and retinol, making it more stable and active (less sensitive to heat and light). Our skin cells break down this into retinoic acid, which is the active form, and retinol which can be later converted to the active form.

It is considered superior to retinol in benefits. We don’t have a lot of data but there are few convincing studies.

Studies showing the effects of Retinyl retinoate

One study was done on 46 women with wrinkles around their eyes, and compared 0.06% retinyl retinoate to 0.075% retinol and plain vehicle (used twice daily). Retinyl retinoate was significantly more effective than plain vehicle and retinol.
In another study done with a smaller sample (11 females), 0.06% retinyl retinoate showed improvement in facial wrinkles.
It can also be beneficial for acne as seen in one study. Retinyl retinoate 0.05% decreased acne lesions and sebum or oil production. It also had some antibacterial activity against Cutibacterium acnes (a new name for Propionibacterium acnes, linked to acne).

Products with Retinyl retinoate (not many)

Medik8 R-Retinoate Youth Awakening Cream [Medik8]
VERSO Super Facial Serum (has fragrance) [Verso] [Amazon]

5. Tretinoin

Tretinoin (commonly known by the brand name Retin-A) is the gold standard when it comes to anti-aging (it’s prescription topical in most countries). This is the active all-trans retinoic acid, so it doesn’t need any conversion step.

It reduces wrinkles and hyperpigmentation (like melasma or post-inflammatory hyperpigmentation), hydrates skin by increasing glycosaminoglycans, and smoothens the skin surface. It is photoprotective, meaning when skin is treated with tretinoin, it prevents the degradation of collagen due to UV light.

It is also beneficial for acne as it normalizes the cell turnover of the lining epithelium of the hair follicle, preventing its plugging, and creates a more aerobic/oxygen-rich environment for Cutibacterium acnes, preventing its growth. Its anti-inflammatory properties are also beneficial for the skin.

Studies showing the effects of tretinoin

There are multiple studies that show that tretinoin is an effective ingredient for acne, wrinkles, and dark spots. Another important point is that you don’t need to jump to the highest percentage to get the best results.

In one study, daily use of 0.1% and 0.025% tretinoin cream for 48 weeks resulted in significant improvement in photodamaged skin. In addition, there was no significant difference in the results between 0.1 % and 0.025% concentration.
Also, using retinoids just a few times a week can be beneficial for the skin.

However, this is the most irritating of the retinoids as well. So, it should be used carefully and introduced slowly into the routine. Since it is a prescription topical, using it under the guidance of a professional is the best.

The newer formulations like Atralin gel, Altreno lotion (micronized), and tretinoin with microspheres, are considered gentler as compared to the traditional forms.

6. Adapalene

Adapalene, well known by the brand name Differin, is a third-generation retinoid. It is FDA-approved for the treatment of acne.

It is now available over the counter at a concentration of 0.1% in the US. It doesn’t need any step of conversion and is also more photostable as compared to tretinoin.

Due to its stability, it can be safely combined with benzoyl peroxide (as in Epiduo). This can be very useful for treating acne. It selectively targets retinoic acid receptors (RAR β/γ), which makes it less irritating.

Studies showing the effects of Adapalene

Adapalene 0.1% gel is considered similar in efficacy to 0.1% tretinoin microsphere gel and 0.025% tretinoin gel in treating acne.
Adapalene 0.3% is considered superior to 0.1% gel in treating acne.
In regard to its anti-aging effects, we don’t have a lot of studies. However, there are some convincing studies that show its beneficial role in anti-aging. In one study, 0.3% gel was compared to 0.05% tretinoin cream. They both led to comparable results in improving photodamaged skin at 24 weeks of daily treatment.

Products with Adapalene

Differin Adapalene gel 0.1% [Amazon] [Target]
La Roche-Posay Effaclar Adapalene Gel 0.1% [Amazon] [Ulta]

7. Tazarotene

Tazarotene is a third-generation retinoid (prescription in most countries) and is receptor-selective just like adapalene. It specifically binds to RAR-β and RAR-γ receptors. It is FDA-approved for the treatment of acne and psoriasis. It needs to be converted to the active metabolite, tazarotenic acid.

Just like other retinoids, it targets cell proliferation, differentiation, and inflammation. It also affects some genes involved in hyper proliferation of skin cells. It is available at 0.05% and 0.1% concentrations.

Studies showing the effects of Tazarotene

One study compared tazarotene 0.1% cream versus adapalene 0.3% gel (both used once daily) and found tazarotene to be more effective in treating acne and post-inflammatory hyperpigmentation.
Tazarotene 0.1% gel was more effective than tretinoin 0.025% gel in treating closed comedones and equally efficacious in treating papules, pustules, and open comedones as seen in one study. The same study showed that tazarotene 0.1% gel when used every other day gives similar results as adapalene 0.1% in treating acne.
Multiple studies have shown its benefits for photodamaged skin. It can increase the thickness of the epidermis/the top layer of skin, improve wrinkles, hyperpigmentation, surface roughness, and improve pore size.

8. Trifarotene

Trifarotene is the newest addition to the retinoid family (first approved in 2019 for the treatment of acne) and is available in the US by prescription (sold under the brand name Aklief – 0.005%). As compared to other retinoids, it specifically targets the retinoic acid gamma receptors.

This avoids any skin irritation due to other RAR receptor subtypes. Due to this, it is considered to have fewer side effects and is better tolerated as compared to other retinoids.

Studies showing the effects of Trifarotene

It has less data behind it. However, the studies (first study and second study) show that it is an effective treatment for facial and trunk acne.

Will it have anti-aging benefits just like tretinoin? That is unknown as for now, more studies are needed to show its additional benefits. However, if you are someone with acne and other prescription topicals that are too irritating, this might be useful.

Read more: Tretinoin Vs Trifarotene

Which one should you use?

When it comes to prescription topicals, your treating physician will decide which is better for your skin type and condition. It is important to use these under the supervision of a professional.

If your condition doesn’t get better or the side effects are getting worse, it is better to check with your doctor. They can adjust and make changes to your prescription accordingly.

Moving on to over-the-counter retinoids:

If your skin is very sensitive, go for a retinoic acid ester or retinyl ester.
If your skin is sensitive, go for a retinoic acid ester, lower-strength retinol, or retinal.
If your skin is more tolerant, go for a medium-strength retinoid and build your tolerance.
If acne is your main concern, adapalene is a better choice over other retinoids.

Charts

Below are the charts that display the specific features associated with each retinoid.

Adapalene and retinoic acid esters for skin.

Summary

The beauty industry has some amazing skin-loving ingredients. Among these, retinoids are the ones that have a lot of data and research behind them. They are considered the gold standard for anti-aging. In addition, they can be beneficial for acne, hyperpigmentation, and some inflammatory skin conditions.

Retinol and retinoids are no different. In fact, retinoids are a big group and retinol is a member of it and so are some others. If you are unsure, check the ingredient list of your product and you will know what type of retinoid it contains.

Retinoids can be drying and irritating, however taking baby steps and using the right formula for your skin can minimize the chances of getting the side effects. Don’t be afraid of starting a retinoid. Every skin type can benefit from it.

There is no right age to start a retinoid. So, don’t think you are late to the party and it won’t be effective. Consistency is the key to getting the most from the retinoids. So, join the retinoid party, and don’t forget your sunscreen!!