Tretinoin - Is it Bad for Skin Long Term?

First Posted on January 20, 2024 in:acneanti-aginghyperpigmentationretinolscience deep dive

Tretinoin is by far the most famous retinoid of the Vitamin A category and for good reason. It has a prevalent history of use plus a long long history of validation for multiple benefits including acne, anti-aging, and hyperpigmentation. 

However, much like any other popular skincare ingredient, with its fame comes a few areas of confusion. Tretinoin beginners may find themselves asking questions like, is using tretinoin long term actually bad for me?. Am I still purging? Or is this concentration too much?  Well not to worry! In this guide, we go through tretinoin’s purpose, some of its clinical testing, address your burning questions, and go over some best practices to capitalize on this gold standard retinoid in your skincare routine. Let’s make sure your tretinoin journey is just one long, smooth ride!

What is Tretinoin?

Tretinoin is retinoic acid. In the US, tretinoin is a prescription-only ingredient that can be prescribed at concentrations between 0.01% - 0.1%. These concentrations sound significantly lower than the concentrations you’re used to hearing about with retinol for good reason! Retinoic acid is the direct molecule that interacts with your retinoic acid receptors in skin. So you don’t need a lot. On the other hand, retinol has to convert a couple times into retinoic acid to interact with these receptors to yield those lovely retinoid benefits. This is why retinol concentrations are between 0.1-1%.

In literature, we’ve found that most of the supported benefits come from studies that tested concentrations of 0.05% and higher for 6 months. This doesn’t necessarily mean everyone should start with this concentration, but it does give us a frame of reference of the kind of concentrations and length of time needed to use tretinoin to see results.

Is Tretinoin Bad for My Skin Long Term?

Something Something… Skin Has a Limited Amount of Cells?

With tretinoin use dating back to the 60s, there’s definitely a cohort that has probably had a few decades of tretinoin experience under their belts. It’s really only natural to wonder if we really should be using tretinoin for that long. In fact, one of the most common questions we get is, “Does tretinoin use long-term thin my skin out?.” Well, let’s look at the science.

*Full disclosure: We get this question with all the retinol too. We decided to tackle this question with tretinoin because it has the most historical data so there’s actual testing we can look at and use as a guideline. 

When you start going down the google rabbit hole on long term tretinoin use, you’ll run into a line that roughly sounds like this: “Our skin cells can only divide a limited number of times.” This sounds pretty scary, because isn’t the purpose of exfoliants and retinoids supposed to help speed up cell turnover? Have we just been using up our limited supply of skin cells at an accelerated pace?

This train of thought comes from the Hayflick Limit. The Hayflick Limit is a theory that predicts that some cells have a finite ability (~50 times) to regenerate before they stop replicating and die. And the fear is that tretinoin accelerates this cell regeneration process, therefore causing your skin to “reach its limit” faster with long term use. But the keyword here is…some cells!

This limit only applies to “differentiated” cells, cells that have already divided into functional cells. So in our skin’s case, this pertains to coreneocytes and keratinocytes and not our skin’s stem cells. This is a key difference since stems cells also self-renew and differentiate into different cell lineages. If we have confused you, think “unlimited regeneration of stem cells”can differentiate into all sorts of skin cells with different functions. Once cells have their function, then do they fall under the Hayflick Limit.

Also if you’re worried about skin thinning, keratinocytes (the cells that make up the outer layer of your skin) don’t regenerate per se. They’re meant to die off every skin cycle and shed. So our skin is naturally producing new keratinocytes constantly! If we were truly limited in the number of times our skin cells regenerated we would have a much bigger problem with things like wound healing.

TLDR: The Hayflick Limit does not apply to our skin stem cells. Keratinocytes don’t regenerate. They are supposed to die off every skin cycle and shed. We are not using up all our good skin cells too early or thinning the skin out by having tretinoin in our lives.

But let’s go one step further because the clinical testing side is also helpful to know!

What Does the Tretinoin Research Say?

Because tretinoin has been used since the 1960s, that means there’s a lot of time and opportunity to test tretinoin the right way. This ingredient is probably one of the few you’ll find that has been studied for periods of longer than a year. 

One clinical study run by J&J, looked at using 0.05% tretinoin for two years and performed both a clinical evaluation and histological biopsies. This placebo-controlled clinical tested on 204 subjects and had subjects apply the treatment once a day. Test subjects were also given an SPF 30 to apply daily as well. After two years of use, they found that the tretinoin group resulted in a significantly greater improvement in wrinkles, mottled hyperpigmentation, and sallowness. Additionally, they did not find any indication of cell abnormality, dermal elastosis (aka. degradation), or negative effects on the stratum corneum. They also found that there was a significant increase in one of the procollagen synthesis markers after 1 year.

Worried about even longer term tretinoin use? We should also mention a four-year clinical with histological biopsies that we found. Although this clinical test was significantly smaller with just 27 subjects, and the protocol was much less consistent where some patients used varying concentrations throughout the 4 years, this study still does help demonstrate the safety of long-term use of topical tretinoin. Through computerized image analysis, they found an increase in epidermal mucin (glycoproteins involved in many important biological processes that suggest good skin health) and decreased dermal elastosis (degeneration of tissue). Biopsies also showed nothing abnormal in keratinocytes and melanocytes after 4 years. 

Finally, we’d like to remind you that there is a clinical test (n=34) that found using 0.05% tretinoin after 6 months doesn’t thin the skin but thickens the collagen band and increases collagen matrix deposition. Hopefully, we all can now put this question to rest!  

How do I use Tretinoin in my Skincare Routine?

Ready to start your tretinoin journey? Let’s review some general guidelines!

Where does it go in my skincare routine?

Tretinoin typically comes in cream/emulsion form. We recommend using it after your watery serum products and before your face oils and balms.

Can tretinoin be used with “X” active? 

Tretinoin can be layered with most actives. We recommend exercising some caution when using it with low pH actives like AHAs and ascorbic acid vitamin C, which can cause additional irritation. Consider using these in a separate routine from your tretinoin step. You also might hear how using BPO and tretinoin together will cause tretinoin to degrade. There’s been a couple of studies in the 2010s that have debunked this claim, so if you do need to combine these actives, go right on ahead! 

Checkout our retinol actives pairing guide for more details. Generally speaking, you can approach any retinoid with the same guidelines.

Anything else to keep in mind while I’m on tretinoin?

 It’s important to remember that tretinoin does have an initial retinization period (aka. The purgeeee). Studies have found that this period of adjustment takes up to 2 months. Flaking, dryness, and breakouts are pretty common side effects during this period. We recommend finding a great soothing serum to pair with your retinol to help keep these side effects to a minimum. Also, did we mention to sunscreen?!



  • What is tretinoin?Tretinoin is retinoic acid and is common topical retinoid that’s prescribed between the concentrations of 0.01% and 0.1%
  • Does using tretinoin long-term cause skin thinning?
  • There is no evidence that tretinoin causes skin thinning or depletes skin cells. Tretinoin actually has been found to do the opposite and thicken skin’s collagen band. There is also clinical evidence of up to 4 years of tretinoin use, showing that long-term tretinoin use does not harm skin. 

    • Where does tretinoin go in my routine? Tretinoin typically comes in an emulsion, cream form, which means you’ll use it after your serum step but before any face oils or skin balms.
    • Can I combine tretinoin with other skincare actives? You can combine tretinoin with all other actives. However, we recommend using caution layering with low pH actives such as ascorbic acid and AHAs due to potential skin irritation

    tretinoin review - concentration, how to use


    Jin K. Modern Biological Theories of Aging. Aging Dis. 2010 Oct 1;1(2):72-74. PMID: 21132086; PMCID: PMC2995895.

    Petersen T, Niklason L. Cellular lifespan and regenerative medicine. Biomaterials. 2007 Sep;28(26):3751-6. doi: 10.1016/j.biomaterials.2007.05.012. Epub 2007 May 25. PMID: 17574669; PMCID: PMC2706083.

    Bhawan, Elise Olsen, L. Lufrano, E.G. Thorne, B. Schwab, B.A. Gilchrest, Histologic evaluation of the long term effects of tretinoin on photodamaged skin,

    Journal of Dermatological Science, Volume 11, Issue 3, 1996, Pages 177-182, ISSN 0923-1811,

    Cho, S., Lowe, L., Hamilton, T. A., Fisher, G. J., Voorhees, J. J., & Kang, S. (2005). Long-term treatment of photoaged human skin with topical retinoic acid improves epidermal cell atypia and thickens the collagen band in papillary dermis. Journal of the American Academy of Dermatology, 53(5), 769–774. doi:10.1016/j.jaad.2005.06.052 


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