Tretinoin Explained (30 Studies): Literally EVERYTHING You Need To Know!

by | Last updated Apr 18, 2020 | 68 comments

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Tretinoin, a.k.a. what Tina Fey says is a great way to ensure large chunks of peeling skin. Besides turning people into lizards, it’s touted as one the best anti-aging ingredients in dermatology.

With continued use, it promises to tighten skin, increase collagen production, reverse the signs of aging, treat acne and hyperpigmentation. Heck, you name it and it probably does it. But is it true? Let’s find out!

Here’s a table of contents with everything we’ll be discussing in case you wanna skip ahead to a section!

What is Tretinoin?

tretinoin cream 0.1

Tretinoin (also known as all-trans retinoic acid) is a pharmaceutical derivative of vitamin A. Retinoic acid is a necessary component of human biology that facilitates growth and development.

It can be found in foods like salmon, egg yolks, grassfed butter and cream, cod liver oil, and my personal favorite — beef liver (sarcasm). If you’ve never tried it, I can’t say I recommend. Quick story about that (feel free to skip ahead).

So….. beef liver is the most nutrient dense food on planet earth. 100 grams of that stuff has 53,400 IU of Vitamin A! To give you some perspective, think about carrots a.k.a. the thing people always harp on about having a ton of vitamin A. Well, 100 grams of carrots only contain 40 IU of Vitamin A.

  • Beef liver (100 g) = 53,400 IU of Vitamin A
  • Carrots (100g) = 40 IU of Vitamin A

Isn’t that NUTS? So of course when impulsive me found out about how nutritious this delicious succulent treat was, I decided to buy 7 POUNDS of it!

Note: at this point, I had never tried beef liver in my life.

Got home, cooked up a nice hefty chunk, set up the dinner table, put on some romantic music, lit some candles  — I did the whole shebang. I took my first bite and nearly vomited. It was awful.

You can only imagine how mortified I was knowing I had 6 more pounds of that stuff in the fridge. Long story short: I froze it for 14 days to kill off pathogens, cut it into little bite sized pieces, and swallowed the whole 6 pounds raw. Oh yeah, that’s a thing.

Anyway… about tretinoin.

It is considered one of the most powerful retinoids available. The most recognized prescription name for it is Retin-A, but there are other brands too: Atralin, Refissa, Tretin-X, Renova, Avita etc. All of these require a doctor’s prescription. However, you can buy it online through Reliable RX Pharmacy.

retino a micro

Weaker retinoids can be found over the counter and will be listed as retinyl palmitate, retinol, or retinaldehyde in a product’s ingredient list.

NOTE: as of 2017, Differin a.k.a. adapalene can be purchased without a doctor’s referral! It’s the first FDA-approved, prescription strength retinoid available over the counter. You can read more about it here.

Tretinoin’s bioavailability isn’t the best, meaning it isn’t easily absorbed by the skin. In fact, upwards of 80% of it remains on the skin’s surface. As an aside, tretinoin cream has been shown to penetrate a little bit better than tretinoin gel (by about 5%). (1)

Fun fact: Accutane, which is the most powerful acne medication in the world, is simply an oral form of retinoic acid (vitamin A). Hence the pharmaceutical name Isotretinoin.

Benefits of Tretinoin.

First and foremost…..

  • It Kicks Aging in the Ass

Tretinoin is considered the gold standard anti-aging ingredient in dermatology. (2)

How effective is it, you ask? Check out what this 61 year old woman looks like after using tretinoin for 28 years! Full video here.

28 years of tretinoin woman

I KNOW RIGHT?! Like, zayum gurl! You looking GOOD.

Given, this is just one person. Maybe she just got lucky or eats kale for dinner. What do we know, right? Well, the scientific literature paints a similar picture!

For example, a very well controlled study involving 360 participants found significant improvements in fine lines and wrinkles after 24 weeks of using tretinoin cream 0.025%. (3) Other studies have been replicated with similar findings. (4) Despite most improvements occurring with fine wrinkling, a reduction in deeper wrinkles and tactile roughness was also observed.

On a side note, 0.025% tretinoin cream is on the lower end of the strengths available. Some people use a full 0.1% daily (that’s 4 times the potency)! However, using this high of a percentage may be unnecessary altogether.

One study found there was “no clinical or statistically significant difference” between 0.025% and 0.1% tretinoin after 48 weeks, besides the severity of irritation (0.1% tretinoin obviously being more irritating). (5) So if you decide to use Tretinoin for anti-aging purposes, know that you will still be getting the benefits with smaller dose prescriptions.

The assumption is that tretinoin works by tightening the skin and increasing collagen production, which leads to epidermal thickness. (678) Collagen being a structural protein that provides strength, flexibility, and resilience to the skin.

Unfortunately this lovely protein decreases overtime and becomes a main culprit in aging. For some perspective, collagen production slows down by about 1% every year after a person turns 20. As a result, skin becomes less elastic and thinner with age, making it more prone to sagging and wrinkling.

Point being, the more collagen we can produce the more we slow down the aging process. Hence, why tretinoin is awesome — it increases collagen production!

Tretinoin also reverses photodamage (the adverse effects of sun exposure), and increases hyaluronic acid production in the epidermis. (91011) Hyaluronic acid is another necessary component of human skin. It speeds up wound healing and is a potent humectant that hydrates the skin by drawing water from the environment and dermis (deeper layer of skin). (1213) This in turn gives a “plumping” effect that reduces fine lines and wrinkles.

Related reading: Hyaluronic Acid for Skin Explained (25 Studies): EVERYTHING You Need to Know!

Perhaps you noticed how long the studies I listed above were (24 to 48 weeks respectively). This is because tretinoin works gradually over time. Don’t expect to see results quickly; this medication requires patience, time, and persistence!

On the upside, improvements never seem to slow down. In fact, one study found that there was still improvements being made in collagen organization and production after 2 years of continued use! (14)

tretinoin gel 0.1

Tretinoin is somewhat effective against PIH (post inflammatory hyperpigmentation), though not terribly impressive in this department. It works by inhibiting tyrosinase (an enzyme that produces melanin), interfering with pigment transfer, and speeding up cell turnover rate. (1516)

One study assessed its efficacy in treating liver spots (a.k.a age spots), or the brown and black spots commonly seen on elderly folks. The study was 10 months long, involved 58 patients, 24 of which used tretinoin cream 0.1% daily. At the end of it, 83% of the tretinoin users saw a reduction in age spots. (17) Another similar study found improvement in 68% of patients after 10 months of daily tretinoin cream 0.1%. (18)

In my opinion, 10 months and only slight or no improvement in nearly 20% to 30% of patients isn’t groundbreaking. Especially considering these participants were using the strongest prescription tretinoin available.

Tretinoin’s ability to treat melasma has also been assessed. One study found a 32% improvement across all patients after 10 months of daily tretinoin cream 0.1%. (19) Again, I don’t know about you, but 10 months for a 32% improvement — ain’t nobody got time for that.

Sorry if I sound overly critical here, :p but in my humble opinion tretinoin is a bit overrated in its ability to reduce hyperpigmentation. And if used excessively, it can actually cause or make erythema like PIE worse! One study found “moderate side-effects of erythema” in 88% of patients treated with tretinoin! (20) The researches ended up ruling that tretinoin helps, but improvement is slow.

This is why it’s particularly important to buffer tretinoin if you want to reduce its side effects, and have better treatment outcomes! More about this in the “How to Use” section below.

  • Treats Acne (Meh)

Tretinoin is a well established acne treatment. In the U.S. alone, it’s prescribed in 12.5% of all acne cases. Benzoyl peroxide and adapalene being the most prescribed at 12.8% and 14.4% respectively. (2122) As an aside, don’t ever use tretinoin and benzoyl peroxide together. Tretinoin is an unstable molecule and oxdizes in the presence of benzoyl peroxide.

Research shows that tretinoin reduces both inflammatory and noninflammatory acne. (23) However, its efficacy largely depends on its local tolerability, in other words, how irritating it is on the skin. Let’s review some of the data!

In a very well controlled study with 178  patients, 0.04% tretinoin gel reduced acne by about 36% after 3 months. (24) You might be thinking that a 36% reduction after three months isn’t very impressive. I hear you! Compare that to something like azelaic acid, which in one study reduced acne on average by 60% after only 45 days. (25) It makes tretinoin look rather lackluster.

To put that into perspective, azelaic acid did double the work in half the time.

And this wasn’t the only study that showed tretinoin’s mediocre effect on acne. For example, a 3 month long study found tretinoin gel 0.05% reduced acne on average by about 34.9%, with a whopping success rate of only 19%! (Sarcasm.) Whereas another 12 week study found that tretinoin gel 0.05% reduced acne by about 46%. (26)

An 11.1% difference is quite the discrepancy! What gives?

As mentioned earlier, tretinoin’s effectiveness largely depends on its local tolerability. The more irritating it is, the less effective it will be. This is why it’s especially important to use it correctly and reduce irritation wherever possible. I give tips and discuss how to do this in the section below.

Additionally, use micronized versions of tretinoin if possible! These have been formulated to be gentler on the skin. My personal favorite is Retino A Gel 0.04%.

In terms of treating acne, I think tretinoin is better served for it’s comedolytic properties more than anything else — that is, it’s ability to prevent clogged pores rather than treat inflammatory acne. (27)

Overall, I wouldn’t really recommend tretinoin for treating inflamed acne per se. In my opinion, something like benzoyl peroxide or azelaic acid are better suited for this. However, if blackheads, clogged pores, or congestion are your main issues than tretinoin or salicylic acid are good options!

Lastly, if you decide to stick with tretinoin remember that the results are cumulative and get better with time! For example, the suppression of comedogenesis rises from approximately 30% after 2 months to about 60% at 4 months and so on. (32)

Side Effects.

Unfortunately Tretinoin is pretty irritating. Tina Fey didn’t say you’ll see wafting chunks of peeling skin for no reason.

retin a micro gel

The most frequent side effects are erythema (redness), peeling, and dryness. This occurs in approximately 60% of patients. (28) So be warned, you might become a lizard.

If you start using it daily, the irritation and dryness becomes especially bothersome during weeks 3 and 4. (29)

How to Use Tretinoin and Reduce Irritation.

Don’t go all out with this stuff! Less is more here. Using too much could lead to inflammation, cause redness, and make hyperpigmentation worse!

Make sure that your skin is absolutely dry before applying it. Ideally, you should wait 20 minutes after washing your face to use it. Damp skin increases its topical permeability, which will make it more irritating.

Use it before or after your moisturizer. Applying it over moisturizer doesn’t reduce its efficacy and makes it less irritating. (30) You only need to apply a pea-sized amount for the whole face. Yes, that is enough! It may not seem like it, but trust me: IT IS!

To reduce the side effects, simply begin incorporating it into your skincare routine more slowly. You can start using it once or twice a week and work your way up. For example, on week one use it Monday and Thursday. Week two on Monday, Thursday, and Saturday. Week three Monday, Wednesday, Friday, Sunday. So on and so forth.

Using products containing Niacinamide (e.g. CeraVe PM or EltaMD AM Therapy) have been shown to minimize its irritating effects. (31)

Because tretinoin will increase your sensitivity to the sun, it’s important that you wear sunscreen! And last but not least, make sure to apply it at night! Tretinoin degrades in sunlight.

To summarize: start slowly, use a pea-sized amount at night on dry skin before or after moisturizing, and wear sunscreen during the day. Use products with niacinamide to counteract irritation.

UPDATE 10/21/19: one study found that using short contact therapy is still effective and far less irritating versus leave-on treatment. This is what I’ve been doing very successfully with 0.1% tretinoin gel the past month. Do do this, simply apply tretinoin for 30 minutes on dry skin before thoroughly rinsing with water.

With this method, only 20% of participants in the above study experienced irritation, whereas it’s normally 80%! And if that wasn’t cool enough already, none of them were using moisturizer either! 🙂

Where Can I Buy Tretinoin?

Tretinoin is a prescription drug, which means you’ll need a doctor’s referral to get it in the U.S…. but uh, you can always get it online through Reliable RX Pharmacy. I’ve used them many times, and their service is great! Here are the ones I’ve tried and recommend:

reliable rx tretinoin

If you don’t feel comfortable buying prescription drugs online, Differin is another option! It’s a comparable prescription strength retinoid that’s available over the counter! I used it for 3 months and documented my experience here.

See Differin on Amazon!

Alternatively, you can try getting a prescription from Curology.

curology prescription

Well that does it for tretinoin! Hope you’ve enjoyed this reading.

Very warmly,


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