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Aklief (Trifarotene) vs Tretinoin for Wrinkles and Acne

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Aklief (trifarotene) is a new retinoid that is selective for the RAR-gamma receptor, while tretinoin binds to all RAR receptors. So, Aklief is less likely to cause side effects compared to tretinoin.

Tretinoin is effective for wrinkles and has many research studies supporting its efficacy. While Aklief may also be effective, we don’t have any studies comparing Aklief and tretinoin yet.

Bottle and a tube.

If you are into skincare, you probably know about retinol or retinoids. They are one of the ingredients with a lot of research and data behind them which prove their effectiveness. Over the years we have seen a lot of advancements in their formulations.

Recently a new retinoid was approved for the treatment of acne – Trifarotene (Brand name – Aklief). It was first approved in the USA (October 2019), then Canada (November 2019), and Europe (December 2019).

So, how does Aklief differ from tretinoin or other retinoids, and what about anti-aging? Is it as effective as tretinoin for anti-aging?

Let’s dive deep into all this.

What are retinoids?

Retinoid is a big group that includes all the Vitamin A derivatives. Depending on when they were introduced and their structure, they can be grouped as follows: 

  • First generation: oldest and first studied in the 1960s, includes retinol and its derivatives, tretinoin (retinoic acid – Retin A), isotretinoin, alitretinoin
  • Second generation – Etretinate, acitretin
  • Third generation – Arotinoid, adapalene (approved for acne in the 1990s), tazarotene
  • Fourth generation – Trifarotene

Trifarotene is the most recent addition to the family.

You can read about all these different retinoids in detail in this post.

How do retinoids work?

Retinoids need to get absorbed into the cells after we apply them to our skin. Once inside the cell, retinoids need to be converted to the active form – All-Trans-Retinoic Acid (ATRA). This is carried to the nucleus of the cell with the help of cellular retinoic acid-binding proteins (CRABP). 

Inside the nucleus, they bind to different receptors (retinoid nuclear receptors), and produce various effects by acting on the genes involved in the formation of skin cells and their differentiation.

Retinoid nuclear receptors

There are two types of Retinoid nuclear receptors (RNR) 

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

Our skincare retinoids mainly bind to retinoic acid receptors (RARs). It has 3 subtypes:

  • RAR-γ: mainly found in the top layer of skin/epidermis (most abundant – 90%).
  • RAR-α: found in the upper (expressed by keratinocytes) and deeper layer (dermal fibroblasts) of skin. 
  • RAR-β is found in the deeper layer of skin (expressed mainly by dermal fibroblasts).

Receptor binding

  • Tretinoin can bind to all retinoic acid receptors (RAR). 
  • New-generation retinoids like adapalene and tazarotene bind specifically to RAR-beta and RAR-gamma. 
  • The newest retinoid, trifarotene, is specific for RAR-gamma. This retinoid has the additional advantage that there will be minimal irritation due to the involvement of RAR-beta and RAR-alpha receptors and hence better tolerated. 
Tretinoin and retinoic acid receptors.
Tretinoin binds to all retinoic acid receptors.
Trifarotene and retinoic acid receptors.
Trifarotene specifically binds to the gamma subtype of retinoic acid receptors.

Comparison chart

The chart below summarizes the differences between Aklief and tretinoin. More detailed explanations can be found below.

Aklief (trifarotene) vs tretinoin comparison chart.

Acne

Tretinoin for acne

There are multiple studies documenting the benefits of tretinoin for acne as it normalizes the exfoliation process of the skin, prevents plugging of pores, lets in more oxygen, and prevents the growth of Cutibacterium acnes (which causes acne). Tretinoin acts on all the RARs in the skin.

Aklief for acne

Trifarotene was recently approved by the FDA for the topical treatment of facial and truncal acne for ages 9 and older. It is sold under the brand name Aklief and is available only by prescription (just like tretinoin). This is the first retinoid that is approved for use on truncal acne.

As of now, it comes at a concentration of 0.005%, which is a much smaller dose as compared to tretinoin (since it specifically binds to RAR-gamma receptors, we are able to use a smaller dose). Due to this, it can be used on a large surface area like the chest, shoulders, and back for the treatment of acne. 

It is rapidly metabolized by human hepatic microsomes and has low absorption into the systemic circulation as suggested by this study. So, overall Aklief has a better safety profile.

Data/studies on Trifarotene and Acne

For trifarotene, we have 2 large randomized 12-week trials, where it was compared to a plain vehicle. These studies clearly show that trifarotene is effective for face and truncal acne – both inflammatory and noninflammatory lesions.

This was followed by a long – 52-week study to evaluate its effectiveness. In this study, patients reported improvement in facial acne: 41.4% of all patients at week 12, 54.8% at week 26, and 66.6% at week 52. So basically longer it was used, the better the results were.

There is also a recent case series of 3 patients who used trifarotene 50 μg/g cream on both the face and trunk for 12 weeks. All three patients showed a reduction in acne, especially the inflammatory lesions.

Is Aklief better than Tretinoin for acne?

Unfortunately, so far, we don’t have any study that directly compares Aklief to tretinoin, so we can’t definitively say which is better.

However, theoretically speaking, trifarotene might have fewer side effects as we can use a lower concentration, and it primarily affects RAR gamma receptors. Additionally, since RAR gamma is the main subtype in the epidermis, the effects should be similar.

A unique advantage of trifarotene is that it can be used on larger areas due to its lower dosage and safety profile. It’s the only retinoid currently approved for treating trunk acne.

Wrinkles/Anti-aging

Tretinoin is well-studied for its anti-aging benefits. It can reduce wrinkles, hydrate the skin, and help with pigmentation.

So far, there is no data to show whether Aklief has anti-aging benefits.

However, speaking theoretically, trifarotene, the active ingredient in Aklief, binds specifically to RAR gamma receptors, which make up 90% of the receptors in the epidermis. So, it’s likely that Aklief may also provide some anti-aging benefits, even if they are not as significant as those of tretinoin.

Nevertheless, more research is required to give us a definitive answer on this topic.

Irritation/side effects

Now just like tretinoin, trifarotene can also cause irritation. The most common adverse effects seen in the studies with trifarotene were pruritus (itching), irritation, and sunburn. They mostly occurred in the first few weeks of treatment. 

Trifarotene is 20 times more specific for RAR-gamma. So, there should be minimal irritation due to the involvement of RAR-beta and RAR-alpha receptors. In addition, we are able to use a very low concentration.

But again ~90% of retinoic acid receptors in the epidermis are of gamma-subtype, so it probably can still cause irritation, and the studies above show that it can have some side effects.

So just like every other retinoid, you have to be careful when starting it. Some tips are:

  • Start slow
  • Gentle cleansing routine
  • Use over-moisturized skin
  • Consider the moisturizing sandwich method
  • Use a few times a week when starting
  • Avoid exfoliants 
  • Avoid Ascorbic acid (Vitamin C) serums
  • Use along with niacinamide
  • Make sure to use sunscreen

You can also read this post which has 18 tips (with details) on preventing retinoid peeling.

Summary

To summarize, we don’t have data to directly compare tretinoin and Aklief (trifarotene). However, these two retinoids have different specificities for retinoic acid receptors. As a result, we can use a lower concentration of trifarotene, which may reduce the likelihood of side effects.

Furthermore, trifarotene can be applied to larger areas compared to tretinoin.

Since RAR gamma is the most abundant receptor in the epidermis, Aklief could potentially benefit our skin just like tretinoin. More studies that directly compare trifarotene to other retinoids will provide more answers.

Read more articles on retinoids

References

Disclaimer: This blog post is for information purposes only and does not replace medical advice.

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