Tretinoin Explained (30 Studies): Literally EVERYTHING You Need To Know!
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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!
Table of Contents
What is Tretinoin?
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.
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…..
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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.
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. (6, 7, 8) 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. (9, 10, 11) 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). (12, 13) 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)
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Treats Hyperpigmentation
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. (15, 16)
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.
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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. (21, 22) 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.
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:
- A-Ret Gel 0.1% Tretinoin (generic version of tretinoin 0.1% gel)
- Retino A Gel 0.04% (Note: Indian version of Retin-A micro just cheaper. It’s manufactured by Johnson and Johnson, which is the same company that makes Retin-A in the U.S.)
- Retino A Gel 0.1% (same as above just stronger)
- Supatret Gel 0.04% (Indian generic for Retin-A Micro)
- Supatret Gel 0.1% (Indian generic for Retin-A Micro)
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.
Alternatively, you can try getting a prescription from Curology.
Well that does it for tretinoin! Hope you’ve enjoyed this reading.
Very warmly,
—f.c.
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So what ever happened with the liver? After you consumed the 7 pounds of liver did you see any marked differences?
You are doing amazing work! Thanks for sharing your wonderful posts! I feel Tretinoin (Retin-A) was very helpful in keeping my skin clear looking,and i think somewhat tighter, it also gave my face a healthy color and appearance 👍. So happy I found in Google “Get365ret” and got coupon code for Tretinoin reliable source. My skin is clear 😀 and people have complimented me on the appearance of my complexion. Good Luck!
I am 15 and have been using tretinoin 0.1% for about a month. It does make my skin peel, but I have been awarded clearer, softer, smoother skin. It takes a lot of patience, and ALOT of sunscreen, but I want to continue using it. I have been struggling with acne since I was 12, and have gone through antibiotic/retinol mixes, benzoyl peroxide, salicylic acid, and bentonite clay, and this has been the best. Since I am South Indian, I have darker skin, so acne scarring leaves darker spots. I also have scarring on my cheeks and forehead, and I have noticed them lightening and fading. I start my skincare with the coconut oil to remove makeup and/or dry skin, and then I use a clean washcloth with Rose Thayer Witch Hazel. Then I wash my face with Mario Badescu Enzyme cleanser, the green one, and dry my face. I wait about a minute and then apply a pea-sized amount of the tretinoin, and finish with my Neutrogena Oil-Free sensitive skin moisturizer. In the morning, I use coconut oil again for the dry skin, and then just apply the same moisturizer and some SPF 30 sunscreen. I know that tretinoin might now work for everyone, but as someone who has been to multiple derms and tried a lot of different methods, I highly recommend it.
Hello, I went to a new dermatologist today, I have some acne, I even feel ok about my skin compared to how bad it used to be, but I wanted to get some advice to have even better skin. She told me never to moisturize because I have oily skin, and to use duac gel in the morning and tretinoin 0,05 straight away, nothing else (just cetaphil cleanser) and that my skin will be very bad, dry, irritated the first month but that’s what we want. My skin is really sensitive and even when I use moisturizers, toners and HA gets easily irritated by acne treatments. I’m really scared to do what she told me, besides vanity, I’m scared I might do some damage. I have no idea what to believe anymore, this is very frustrating.
It’s not right to compare cohort studies among completely different populations using different assessors as a point to say one drug is better than another, when they’re not studied head to head lol… Also it’s a misconception that retinoids only work through preventing hyperkeratinisation, there’s a lot of data that they actually work better for more severe/inflammatory acne because of their action on downregulating toll-like receptor 2 and modulating MMP’s (Leyden et al., 2005; Dreno et al., 2015), so saying they’re more useful for comedones isn’t accurate. Just saying. I like the post otherwise on the anti-aging benefits and tolerability advice though!
How to apply: Is this the correct way to use Tretinoin? Wash my face, use rose water on a piece of cotton to totally cleanse, wiat 20-30 minutes, then apply the tretinoin and then apply an intense moisturizer and then a face cream? Would appreciate your answer!!!!
‘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.’
This caught my eye, because I was prescribed Epiduo, which is obviously Adapalene and Benzoyl Peroxide. Do you happen to know why/how these two work together? Wondering if Epiduo is really the best way to go… Would it generally be better to use these ingredients in separate products (carefully and with appropriate wait times!) that in one product?
Hello! Fellow fungal acne sufferer here…I use 2% ketoconazole on my face 2x daily which keeps the flare-ups at bay (I have to use oral fluconazole for serious flare-ups following antibiotics, etc, too). It seems to be an ongoing battle! Anyway, my derm also prescribed me tretinoin .025% to help combat early signs of aging (I’m almost 28!). If I’m using the ketoconazole 2x daily, how would you recommend I piece that into my routine with the tretinoin? Also–have you experienced any “purging” effects with tretinoin? I’m worried that I’ll be creating one problem (acne-pimples), to solve another (aging). Mind you, I VERY rarely experience an actual acne pimple/breakout. All of my breakouts are fungal-acne related.
Thank you for all you do here! Your information and sincerity are invaluable and very much appreciated.
Warmly,
Adrienne
I’m 15, and have been suffering with acne for probably three or four years, I’m not completely sure, but I initially assumed it would subside after my ~raging hormones~ from puberty subsided but it’s safe to say that has not been the case. I tried probably a hundred different over the counter treatments for varying amounts of time, but found nothing effective, and even had an allergic reaction to benzoyl peroxide (which only cleared up with time but left scars). Last October (2019), I began using generic 0.025% tretinoin gel. My skin did not “purge” much, or at all, for the first three-ish months I began using it, and I saw no significant changes in my acne, but I experienced quite a bit of dryness and very slight peeling, which I combated by “buffering” with moisturizer and using a “hydrating facial cleanser”, both with no actives. Around January, I noticed slight improvement, but it was so insignificant that I was not sure there was any real improvement without looking at older photos from around October, before I began treatment. My skin has improved a little since then, but feel it may have “plateaued” in February/March. My doctor also diagnosed the small flesh colored bumps on my forehead as closed comedones, and said that the tretinoin should be very effective on them but I have not found that to be the case at all. I have considered the possibility that she may have misdiagnosed malassezia folliculitus. I have also noticed a lot of texture on my nose and in between my eyebrows, that I have no clue what to make of. Should I discontinue use of tretinoin and try a different treatment? Or is it possible that I need a higher concentration of tretinoin, or a cream instead? Any input would be greatly appreciated. Thank you for sharing your knowledge! Finding digestable and reliable information about skincare online is really difficult but your blog is super informative 🙂
I’m wondering if tretinoin is the culprit that worsened my seb derm . I’ve been on Curology since April . Im not sure if it’s the sweet almond oil in the formula , or the fact that I had my prescription changed to remove the azelaic acid . My derm just sent me the exact prescription you have in the pic above . Im hoping the zinc pyrithione and adding the azelaic acid back in will help . I’m 39 and I’m using the tret for antiaging. Do you use Curology? Is that your script in the photo ? Did it help your seb derm or acne , or make worse ? Thanks so much for all the info ???
I’m sorry it didn’t work for you . I know how annoying that can be . I’m hoping the new formula works for me . I’m wondering if my barrier was compromised now that I’ve read your stuff . I never considered that . I had oily skin in high school with mild acne . But it got worse as I got older . My 30’s is when mine acted up the worst . 3 Yrs ago , I got divorced n moved back to my old neighborhood with better water . My skin started clearing , acne wise . But 2 small patches of “dry skin” slowly spread from my cheeks to my entire face over 3 Yrs . I quit using soap completely and just used a soft microfiber cloth to buff the scales off and they’d return wishing 12-24 hours . Believe it or not , the only derm who will even listen to me is my Curology doc. I love her !!! The one who diagnosed me with seb derm barely glanced at it . Didn’t check for fungus or anything. I’m gonna find one and use my red headed stubborn ways to make me listen ???. I have a strange theory about why my acne went away ! I think the malassezia eats the oils on my face and keeps the zits away ! I know that sounds crazy . Thanks to your interesting info about the barrier repair , it makes me realize that maybe when I used to use all those harsh scrubs and soaps , maybe I compromised my barrier and the malassezia got in and set up shop . But then again , not using soap for 3 years coulda helped repair it . I wish that there were more derms in my area ! I’ve seen 5 and driven 1.5 hours to see some of them , only to be glanced at for a second and shoved out the door with steroid creams . I’m with you ! I want to be able to use the Curology somehow ! Even if I have to let my face rest and repair first . I wanna look as good as the 60 year old when I’m 60 also dammit !!! At least the tretinoin in the formula didn’t irritate my skin too bad . Maybe my new one with the zinc will work . Sorry for the long ass story ! Lol . You look to be 25 or younger , so at least you have some time before ya need the anti aging stuff and you’ll have your barrier sorted out by then ! Thanks so much and have a great day ???
HOLY MOLY that woman’s skin is insanely beautiful. Like– she looks better than me and I am 26! So.. I have been using tretinoin for about 1 week. I got my tretinoin online in cream form at the 0.025% strength. So far I have experienced a ton of peeling. I can’t imagine not using moisturizer like the lady in the video– but all skin is different! I’m hoping that this will really clear up my skin and minimize my fine lines.
Can I use tretinoin acid after microneedles?
Which kind of essential oil should I use to match tretinoin acid?
I am oily skin
Is it okay to use Benzoyl Peroxide during the day and tretinoin at night? My doctor prescribed them to me and seems a bit harsh. What do you think?
Hi thank you so much for all you do and the research and time spent making this website and incredible resource. I just wanted to share my experience with tretinion: I had significant side effects using it after a few weeks that resemble vitamin a toxicity including muscle spasams and twitching, heart palpitations, anxiety, and confusion. I’m curious if other people have experienced this. It is frustrating because it is really improves my pigmentation and pore size. I’ve tried it multiple times and each time this happens. It even happens if I use a lot of differn. Weird.
Hey fc! I’m thinking of adding some type of vitamin a derivative into my routine. Have you heard of A313? It is a french retinol/retinaldehyde? cream that is said to be as potent as prescription retin-a minus the purging and is said to be a lot more gentle. The reviews on amazon are amazeballs! I really wanna get my hands on one as I’m not ready to jump the big retin-a gun. I checked the ingredients and it has polysorbate-80 though. Would love to your your thoughts on this product!
Hello, is tretinoin fungal acne safe ??? thank’s a lot
Hey! Thank you for this. I recently read this article that talks about the “short term effects” of tretinoin and retinols (The doctor in the article also said something to the effect of these products actually kind of weakening the skin over the years) . I was wondering if the same concept would apply to azelaic acid? I’ve been on tretinoin for acne and can CONFIRM that once I stopped using it my skin turned normal to how it was before.
Here’s the link, please let me know your thoughts: https://www.google.com/amp/s/www.businessinsider.com/retinol-risks-according-to-a-doctor-2018-6%3famp
I hope this is okay to comment on, but it might be a good idea to include medical disclaimers / notes as retinoids can’t be used for anyone who’s pregnant, or anyone who is going through cancer treatment or chemo. Sorry, I hope that’s okay to say here!
Do you think mixing retinoids could make them more effective such as mixing 0.1 tretinoin and 0.1 adapelene?