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r/Tretinoin wiki
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Welcome to the /r/tretinoin wiki!

Quickstart

I was just prescribed tretinoin, what should I know?

Routine Suggestions

PM Step 1) - Cleanse

PM Step 2) - Apply tret and moisturizers

Buffering option 1 (The Sandwich method):

Buffering option 2 (The Moisture Blanket method):

No buffering option (The Rogue method):

AM Step 3) - Apply Moisturizer and SPF

General routine tips

Required: Sunscreen

Common Questions and Discussion Topics

All about purging

What is purging?

Does everyone purge?

How long does the purge last?

If I stop using tret will I purge again if I restart it?

All about flaking / peeling

How do I avoid flaking and peeling?

All about buffering

Which formulation should I use?

What percentage should I use?

Troubleshooting

Still lots of irritation after 2-5 months?

What is tretinoin?

Tretinoin vs Adapalene vs Tazarotene vs Retinol vs ...

Tretinoin vs Retinol

What is tretinoin good for?

What is tretinoin NOT as good for?

Does tretinoin thin the skin or thicken it?

Is Adapalene good for anti-aging?

Where can I get tretinoin?

Is tret photostable?

Long-term use

Logistics

Before and Afters

Research Summaries

Sun sensitivity

[1] There is no evidence that sun sensitivity returns to normal after continual usage of tretinoin.

Acne

[2] There is some evidence that higher strengths of tretinoin is more effective for acne.

[3] Aloe vera topical gel enhances tretinoin efficacy compared to a placebo in a randomized, double-blind, prospective trial.

[4] Using a moisturizer improves tolerability for tretinoin.

[5] Moisturizer improves tolerability for tazarotene and does not negatively impact efficacy.

[7] Gentle cleansers and moisturizers are key to treating acne.

[8] Tretinoin + niacinamide is better for improving wrinkles, pigmentation, and texture than tretinoin alone.

[9] Using a moisturizer with ceramides makes tretinoin hurt less.

Aging

[6] The increased cell turnover triggered by tretinoin does not “use up” your cells early.

Retinol vs Retinoic acid

Studies that need summarizing

Research Summary Template

Quickstart

I was just prescribed tretinoin, what should I know?

Further reading:

Routine Suggestions

PM Step 1) - Cleanse

PM Step 2) - Apply tret and moisturizers

Short contact therapy (the most gentle method):

Buffering option 1 (The Sandwich method):

Buffering option 2 (The Moisture Blanket method):

No buffering option (The Rogue method):

AM Step 3) - Apply Moisturizer and SPF

General routine tips

Wear sunscreen. Sunscreen is an absolute must while using tretinoin. If you cannot commit to daily use, find another ingredient to use. Azelaic acid is excellent.

Always apply retinoids to dry skin. That means either 1) pat-dry your skin after cleansing and wait a few minutes for it to dry completely, or 2) wait for your moisturizer to dry completely. It has long been known that hydration of the stratum corneum increases its permeability[11, 12, 13, 14]. Hydration increases skin permeability overall [11, 12, 14], and also increases the absorption of topically-applied molecules [13]. Additionally, manufacturers advise using topical drugs on clean and dry skin, so that’s what you should do. If your skin is wet at all when you apply tretinoin, you will likely see an increase in flaking, peeling, and irritation.

Apply a pea-sized amount of tretinoin for your entire face. Apply a small dot in the center of forehead, on cheeks, nose, and chin. Sweep out to outer parts of the face to spread it. Do not put directly under eyes, around the mouth or in the nose folds. It may feel as if it is not enough, but it is. The reason for this is because tretinoin being a fat soluble molecule is immediately absorbed by our cells and bound to its receptors. When all of the receptors become saturated, the excess is stored in the cell, and the amount of unused tret in our skin is exactly what has the strongest link to irritation and side effects. So if you’re using more than it’s necessary every time, the amount of free tretinoin in your skin will quickly skyrocket. The best way to check if you’re using more than you should is to gently apply a thin tissue to your face when you finish spreading your tret. The tissue should fall off. If it sticks, you’ve used too much.

Only apply tretinoin at night. It degrades in the sunlight, so there is no point in wearing it during the day.

Apply tretinoin evenly to your entire face. Tret is NOT a spot treatment. Uneven application can mean weird patches of irritation and discoloration, especially on darker skin tones.

Buffering does not decrease effectiveness. For acne treatment, studies show buffering does not cause problems with tazarotene, a relative of tret. We haven't seen any studies of buffering with tretinoin (Message the moderators if you have research you’d like to share!). Some people in the sub say buffering doesn't work as well, especially with the micro-gel forms. Redness and flaking are not desirable side-effects, minimizing them will not decrease effectiveness. If you don’t have irritation, it doesn’t mean tretinoin isn’t working. It can take 1-3 weeks to feel the effects.

Use moisturizer! Keeping skin healthy and happy is key to treating acne. Research shows that using moisturizer actually ENHANCES the effects of retinoids[4], [5], [7], [9], especially a moisturizer containing niacinamide [8]. An occlusive like Vaseline or Aquaphor applied on top of moisturizer at night can minimize Trans-Epidermal Water Loss and keep skin moisturized and healthy without clogging pores.

Required: Sunscreen

Sunscreen is *required* when on any retinoid. Not using sunscreen leaves your skin extremely vulnerable to sun damage and does more long-term damage than short-term good.

Dark-skinned folks also need to wear sunscreen.

**If you cannot commit to using sunscreen daily, do not start tretinoin.** Tretinoin makes you sun sensitive for up to 2 weeks [citation needed] so wear sunscreen for up to 2 weeks after stopping tret. There is no evidence that sun sensitivity returns to normal with long-term use of tretinoin.[1]

Further reading:

Common Questions and Discussion Topics

All about purging

What is purging?

(Thanks to /u/caffeinatedlackey and /u/condescending-fork for their great contributions to this section!)

To understand purging you need to first understand the skin cycle. The ELI5 version is that the organ generates new cells from the inside out to replace older cells that slough off. This is called turnover. For adults the cycle is roughly 6 weeks.

When you're a child, your skin generates new cells more quickly, which is one major reason why kids are blessed with great skin and heal more quickly from injuries.

Retinoids accelerate the skin cycle, meaning that you generate new cells more quickly and your skin has an enhanced ability to heal. However, this also means that the acne cycle (impurities and bacteria underneath your skin coming to the surface as acne) accelerates as well. Typically, it may take a few weeks for the acne lesion that is formed in your skin to make its way to the surface and show up to your skin. So, purging is actually a phenomenon by which acne lesions that were already formed in your skin make their way to the top of your skin faster than they usually would, giving the impression that you’re getting new acne, when you’re actually just getting rid of ‘old’ ones faster. If purging is bound to happen to you, it cannot be avoided, nor should you want to avoid it, because you’re basically just dealing with your existing problems faster.

By the nature of its physiology, purging will usually last only for 6-8 weeks and will usually appear only on your usual breakout locations. If you’re getting new waves of acne in places you usually didn’t have them, or if those acne linger, or just keep coming again and again, that is likely not a purge. A purge is, by its definition, a one time thing. There is no ‘purging for 6 months’ or ‘second, third, sixth etc wave of purging’. That would likely be a consequence of irritation.

This does not mean that tretinoin will bear its full effects in 6-8 weeks, you can still get acne after that period like you used to, but it would most likely not be considered a purge. However, once tret shows its full effects after about 6 months, and your skin’s structure gets in order, it is important to keep maintenance of those effects and continue using tret. After that some people never have any acne again, and others have a reduced amount. It's all individual.

Does everyone purge?

Purging is also actually not that common, people are just usually misinterpreting it. Here is a link to one study to support that, and the study defined purging as a 10 to 20% increase in inflammatory lesions, which is a significant but not an enormous difference[10].

Remember, irritation also causes breakouts. Retinoids are very irritating. THE SLOWER YOU GO, THE LESS LIKELY YOU ARE TO HAVE IRRITATION. Go as slowly as possible and focus on hydration and gentleness.

If you don't have regular acne you are less likely to purge. Closed comedones may purge by becoming pimples.

What does a purge look like?

A purge should not be more than a 20% increase in breakouts. Closed comedones often come to the surface, so it can feel like your skin is getting much worse.

How long does the purge last?

It can last anywhere from a few days to 6-8 weeks. The purge should only be a 10-12% increase in your existing acne [10]. If your purge is worse than that, or lasts longer than 6-8 weeks, it is probably not a purge and is irritation instead.  You may be sensitive to an ingredient in your tretinoin formula, but far more likely - you’re using it too much, too often. You can check up with your dermatologist to discuss what’s your best plan, changing the formulation or changing the regimen.

If I stop using tret will I purge again if I discontinue, and then restart it?

Maybe! This is difficult to predict.

All about flaking / peeling

How do I avoid flaking and peeling?

All about buffering

Which formulation should I use?

Tretinoin is available in 3 primary vehicles: cream, gel, and gel microsphere. The cream is often preferred by those who have drier skin. The gel is good, although it does have alcohol but a solid routine can make up for it. The microsphere formulation really helps with irritation and the texture is gel-cream like, but it may be less effective when buffering for some, so if you have extremely dry skin it may not work as well. (Thanks to /u/rose_valley for contributing to this section!). The micro form may also be much more photostable than the other two options. The “vehicle” in either formulation can trigger breakouts - so if you’re still breaking out after 4-6 months, consider switching types (gel → cream, cream → gel).

What percentage should I use?

Troubleshooting

Still lots of irritation after 5 months?

If you're still getting tons of irritation, there are a few common issues we've seen. As with all skincare, your mileage may vary! Some have success doing everything "wrong". This is just a troubleshooting guide, not rules set in stone. Contact your doctor if you're very concerned! Here are some ideas:

Do you have other troubleshooting tips? Message the moderators about contributing to the wiki!

What is tretinoin?

Tretinoin vs Adapalene vs Tazarotene vs Retinol vs ...

Look here for a chart comparing the different types of retinoids.

(Thanks to /u/jdm71384 for this succinct write-up!)

Tretinoin vs Adapalene vs Tazarotene vs Retinol

(Thanks to /u/rose_valley and u/healingfemme for contributing to this section!)

While all of them are derivatives of Vitamin A, Tazarotene is the strongest form of topical vitamin A [30].  Retinoids are fat soluble compounds, and as such, they are freely and immediately absorbed into our cells upon application, where their receptors, Retinoic Acid Receptors (RAR) alpha, beta, and gamma, can be found. Tretinoin and adapalene, being a form of retinoic acid, can instantly bind to those receptors, but retinol and retinal can not and they need to be converted to retinoic acid first. Retinol converts to retinal, and retinal converts to retinoic acid. For that reason, retinol is much better tolerated, but its effects are also more limited. Because those receptors work by modifying gene expression, all positive effects of tretinoin and adapalene can not be immediate and take time, which is even longer for retinol due to the extra steps necessary [30].

What is tretinoin good for?

What is tretinoin NOT as good for?

Does tretinoin thin the skin or thicken it?

One study found that the stratum corneum (outermost layer of skin) "became compact in the first 3 to 6 months whereas it returned to normal (basket weave pattern) in 12–24 months and remained normal until the end of the therapy" (source, arg I had it then lost it, once I find it again I’ll add it here.), which sounds like the thinning of the stratum corneum goes back to normal with continued use. This does NOT mean sun sensitivity goes back to normal [1].

Is Adapalene good for anti-aging?

Inconclusive! Read more here. 

Where can I get tretinoin?

Is tret photostable?

Long-term use

Use while pregnant or trying to conceive

For more information about using Tretinoin during pregnancy or while breastfeeding see: https://mothertobaby.org/fact-sheets/tretinoin-retin-a-pregnancy/

Before and Afters

This gallery contains some inspiring before and after pictures from /r/tretinoin members

From /u/LongJourneySadly


From /u/ewhelann

 


From /u/alex0332:


From /u/zScourgez:

(We got permission to post all of these pictures, but if any of these pictures are yours and you have changed your mind and you would now like us to remove them, please message the moderators with proof they’re you so we can take them down!)


Research Summaries

Have you read other research papers you’d like to add here? Message the moderators so we can add them to the wiki :)

Sun sensitivity

[1] There is no evidence that sun sensitivity returns to normal after continual usage of tretinoin (while using tretinoin).

Wear sunscreen daily, and reapply after 2 hours of cumulative sun exposure. So if you walk to your car in the morning and you're in the sun for 15 minutes, then sit in your office away from a window for 3 hours, that counts as 15 minutes of direct sun exposure and there's technically no need to reapply. HOWEVER, sweat and friction like rubbing your face also removes sunscreen. How much? There’s really no way to know, so this is why dermatologists just recommend the general rule of “every 2 hours”. If you sit near windows indoors, you also still need to use sunscreen since windows don't block UVA light.

If you discontinue tretinoin, your skin will eventually return to normal levels of sun sensitivity. The exact timeline is unknown - probably safe to assume that your skin will be normal a month after quitting. If you are concerned about aging, you need to wear sunscreen every day no matter what.

Acne

[2] There is some evidence that higher strengths of tretinoin is more effective for acne.

Title and authors: Safety and Efficacy of Tretin‐X Compared With Retin‐A in Patients With Mild‐to‐Severe Acne Vulgaris (2007). Webster Guy F. MD, PhD.

Variables: 3 concentrations of tretinoin from 2 brands (Tretin-X and Retin-A) and 2 formulations (gel vs cream)

Participants: 1642 adolescents and adults, 12–40 years of age, with mild‐to‐severe acne vulgaris

Methods: Four double‐blind, three‐treatment, parallel‐group studies randomly assigned 1642 adolescents and adults, 12–40 years of age, with mild‐to‐severe acne vulgaris to receive topical tretinoin therapy with Tretin‐X, Retin‐A, or placebo (drug vehicle) as 0.1% cream (study 1), 0.025% cream (study 2), 0.025% gel (study 3), and 0.01% gel (study 4) once daily for 84 days. The primary efficacy measures were overall acne severity and the number of inflammatory lesions. The secondary efficacy measure was the total number of lesions.

Results: In each trial, Tretin‐X and Retin‐A were clinically equivalent according to all primary and secondary end points at Weeks 2, 4, 8, and 12, a finding also demonstrated by the averaged scores from Weeks 2 through 12. Moreover, each active treatment was significantly more efficacious than placebo at the conclusion of the study ( p≤0.05). Both of the Tretin‐X and Retin‐A formulations compared in each study were well tolerated. The severity of erythema and peeling did not differ significantly among the three groups studied. Conclusions. The four bioequivalence studies demonstrated that Tretin‐X and Retin‐A tretinoin products behaved similarly in patients with mild‐to‐severe acne vulgaris and were thus clinically bioequivalent. Both treatments were well tolerated, and their associated adverse events were similar to those with placebo.

Conflicts of Interest: None

Notes: The real important results here are the comparison between the brands, comparison between gel vs cream, and the comparison between the strengths. The article is paywalled so I'll have to summarize, but the two brands were basically equivalent and so was the gel vs the cream. As for the concentrations, the metric they use in this study is the "percentage reduction in mean total number of acne lesions from baseline to week 12" and the numbers are around (not exact due to copyright) 44% for 0.01%, 55% for 0.025%, and 71% for 0.1%. So yes, there is likely evidence that higher strength of tret = better effectiveness for acne!

Major thanks to /u/CarlFriedrichGauss for this summary!

[3] Aloe vera topical gel enhances tretinoin efficacy compared to a placebo in a randomized, double-blind, prospective trial.

Title (Year). Authors: Effect of Aloe vera topical gel combined with tretinoin in treatment of mild and moderate acne vulgaris: a randomized, double-blind, prospective trial.  (2014) Hajheydari, Zohreh; Saeedi, Majid; Morteza-Semnani, Katayoun; Soltani, Aida

Variables: Compare the efficacy and safety of the combination of tretinoin (TR) cream (0.05%) and Aloe vera topical gel (50%) with TR and vehicle.

Participants: 60 subjects with mild to moderate acne vulgaris

Methods: Randomized, double-blind, prospective 8-week trial evaluated inflammatory and non-inflammatory lesion scores and tolerability.

Results: The combination therapy showed superior efficacy to TR and placebo. TR/Aloe vera gel (AVG) was significantly more effective in reducing non-inflammatory (p = 0.001), inflammatory (p = 0.011) and total (p = 0.003) lesion scores than control group. The highest percentage of adverse cutaneous effect was reported for scaling. At the end of study, erythema in the TR/AVG-treated group was significantly less severe (p = 0.046).

Conflicts of Interest: None listed...

Notes: This is now the 3rd paper I've seen showing that using moisturizer actually *enhances* tretinoin effectiveness.

[4] Using a moisturizer improves tolerability for tretinoin.

Title (Year). Authors: Adjunctive use of a facial moisturizer SPF 30 containing ceramide precursor improves tolerability of topical tretinoin 0.05%: a randomized, investigator-blinded, split-face study. Schorr et al., 2012

Variables: This was a randomized, investigator/evaluator-blinded, split-face comparison in subjects with healthy skin.

Participants:

Methods: Subjects applied tretinoin cream 0.05% once daily to the whole face and Cetaphil Moisturizer (CM) once daily to one side of the face based on randomization. Tolerability, preference and skin hydration were evaluated at each week, and a cosmetic acceptability questionnaire regarding CM was completed at the end of the study.

Results: The majority (about 83% to 86%) of subjects experienced skin irritations on both sides of their face, though predominantly mild for the CDM + tretinoin treated side. Tolerability preferences favored the CDM+tretinoin sides.

Conflicts of Interest: None listed...

Notes: This was a great study. Love the evaluator-blinded study. Doesn't seem to say anything about efficacy, only tolerability.

[5] Moisturizer improves tolerability for tazarotene and does not negatively impact efficacy.

Major thanks to /u/scumteam14 for this writeup!

Title (Year). Authors: Moisturizer use enhances facial tolerability of tazarotene 0.1% cream without compromising efficacy in patients with acne vulgaris Tanghetti, Emil, et al.  Poster presented at 32nd Annual Hawaii Dermatology Seminar. 2008.

Variables: once daily 0.1% tazarotene cream vs once daily 0.1% tazarotene cream + twice daily moisturizing cream (with the PM moisturizer being applied 20 minutes prior to tazarotene)

Participants: 96 participants with mild to moderate facial acne completed the study (originally 119); originally 39 in the tazarotene alone group and 80 in the tazarotene + moisturizer group

Methods: Multicenter, investigator-blind, randomized, parallel-group, 16-week study

Washout periods:

Routines:

All participants cleansed twice daily with a gentle cleanser

Both groups applied tazarotene in the PM. The tazarotene + moisturizer group applied moisturizer in the AM and PM, with the PM moisturizer being applied 20 minutes prior to tazarotene. The tazarotene-only group was allowed to use moisturizers, but only if absolutely necessary.

Both groups were encouraged to avoid UV exposure, and to use sunscreen if necessary.

Investigator ratings:

Patient ratings:

Results: Baseline mean inflammatory lesion count for both groups was 22; mean noninflammatory lesion count was 36 (taz) and 38 (taz+moisturizer). Reduction in lesion count was similar between the tazarotene + moisturizer group and tazarotene-only group: 57% vs 46% for inflammatory lesions, and 50% vs 46% for non-inflammatory lesions. Reduction in overall severity score was also comparable between groups.

Compliance was "mostly" or "very compliant" in both groups; moisturizer use was significantly greater in the taz+moisturizer group (....that's good); taz-only group used moisturizer "a little" and "occasionally".

Side effects:

Conflicts of Interest: Supported by Allergan

Notes: Sorry for choosing the poster option, it's basically already in summary format! It's awesome that buffering didn't significantly mess with efficacy, although I'd like to see the full study.

[7] Gentle cleansers and moisturizers are key to treating acne.

Title (Year). Authors: Del Rosso, James Q. “The role of skin care as an integral component in the management of acne vulgaris: part 1: the importance of cleanser and moisturizer ingredients, design, and product selection” Journal of clinical and aesthetic dermatology vol. 6,12 (2013): 19-27.

Title (Year). Authors: Del Rosso, James Q and Staci Brandt. “The Role of Skin Care as an Integral Component in the Management of Acne Vulgaris: Part 2: Tolerability and Performance of a Designated Skin Care Regimen Using a Foam Wash and Moisturizer SPF 30 in Patients with Acne Vulgaris Undergoing Active Treatment” Journal of clinical and aesthetic dermatology vol. 6,12 (2013): 28-36.

Summary: This wasn’t a study so much as a summary of existing literature and the author’s own clinical experience treating patients with acne. It can be summed up in the following way: fancy treatments are important, but skin health also matters and cleansers and moisturizers are super important too. Hilariously the author also described doing a web search on “Ask Jeeves” for ““What are the best treatments for acne?”. The author goes on to critique the page and the recommendations there, and basically advises doctors that this is where patients are getting their information from. “Dermatologists need to be keenly aware that the internet and many other sources of information that do not evaluate the patient with [acne] and other conditions are commonly consulted and trusted by the public.”

Conflicts of interest: Author has worked with a bunch of pharmaceutical companies (Allergen, Bayer, etc. etc. etc.) but none of them were involved in this write-up.

[8] Tretinoin + niacinamide is better for improving wrinkles, pigmentation, and texture than tretinoin alone.

Title (Year). Authors: Draelos, Zoe Diana. "Clinical situations conducive to proactive skin health and anti-aging improvement." Journal of Investigative Dermatology Symposium Proceedings. Vol. 13. No. 1. Elsevier, 2008.

Summary: “barrier-enhancing skin cleansers and moisturizers can both maintain and aid in the restoration of skin health”

Study 1: 41 adult female subjects (n=41) were treated with control versus 2% niacinamide for their forearm skin for 24 days, and TEWL was determined at day 1, day 12, day 19 and day 24. The 2% niacinamide treatment had statistically significantly less trans-epidermal water loss (they were less dry).

Study 2: 50 people used tretinoin plus a basic moisturizer, or tretinoin plus a niacinamide-enhanced moisturizer for 8 weeks. The researchers assessed them for photodamage at baseline and after the 8-week treatment. The moisturizer with niacinamide showed more improvement for every measure: fine lines/wrinkles, mottled pigmentation, blotchiness, and texture.

Conflicts of interest: Author was paid an honorarium by Proctor and Gamble for writing up this paper. The studies themselves were done independently and this was just a review of all the related work.

Notes: Holy cow I am surprised at what a difference niacinamide makes!! Definitely add some niacinamide to your routine if you don’t already have some.

[9] Using a moisturizer with ceramides makes tretinoin hurt less.

Title (Year). Authors: Schorr, Ethlynn S., Farzi Sidou, and Nabil Kerrouche. "Adjunctive use of a facial moisturizer SPF 30 containing ceramide precursor improves tolerability of topical tretinoin 0.05%: a randomized, investigator-blinded, split-face study." Journal of drugs in dermatology: JDD 11.9 (2012): 1104-1107.

Study: No idea how many participants, their age/gender/etc, or how long it was run for. Investigator/evaluator-blinded, split-face comparison in subjects with healthy skin. Participants applied tretinoin to their entire face, then moisturizer to half their face. Majority of participants (~84%-86%) experienced only mild irritation on the side that got moisturized.

[10] Retinoid-Induced Flaring in Patients with Acne Vulgaris: Does It Really Exist?

Title (Year). Authors: Del Rosso, James Q., and F. A. O. C. D. Tretinoin. "Retinoid-induced flaring in patients with acne vulgaris: does it really exist." J Clin Aesthet Dermatol 1.1 (2008): 41-43

[14] Acne lesion count decreases over 12 weeks.

Thiboutot, D., Pariser, D., Egan, N., Flores, J., Herndon, J., & Kanof, N. et al. (2006). Adapalene gel 0.3% for the treatment of acne vulgaris: A multicenter, randomized, double-blind, controlled, phase III trial. Journal Of The American Academy Of Dermatology, 54(2), 242-250. doi:10.1016/j.jaad.2004.10.879

[15] Short-contact therapy shows ~50% decrease in acne lesions over 12 weeks (tazarotene).

Bershad, S., Singer, G., Parente, J., Tan, M., Sherer, D., Persaud, A., & Lebwohl, M. (2002). Successful Treatment of Acne Vulgaris Using a New Method. Archives Of Dermatology, 138(4). doi:10.1001/archderm.138.4.481

[16] Expect to see lesion decrease after 8 weeks (0.05% tretinoin gel).

Chalker, D., Lesher, J., Smith, J., Klauda, H., Pochi, P., & Jacoby, W. et al. (1987). Efficacy of topical isotretinoin 0.05% gel in acne vulgaris: Results of a multicenter, double-blind investigation. Journal Of The American Academy Of Dermatology, 17(2), 251-254. doi:10.1016/s0190-9622(87)70200-x

[29] Oiliness decreases after 3 months for both 0.1% adapalene and 0.025% tretinoin

Ellis, Millikan, Smith, Chalker, Swinyer, & Katz et al. (1998). Comparison of adapalene 0 ·1% solution and tretinoin 0 ·025% gel in the topical treatment of acne vulgaris. British Journal Of Dermatology, 139, 41-47. doi:10.1046/j.1365-2133.1998.1390s2041.x

Hyperpigmentation

[17] Time frame for hyperpigmentation improvement is 9 months (0.1% tretinoin)

Bulengo-Ransby, S., Griffiths, C., Kimbrough-Green, C., Finkel, L., Hamilton, T., Ellis, C., & Voorhees, J. (1993). Topical Tretinoin (Retinoic Acid) Therapy for Hyperpigmented Lesions Caused by Inflammation of the Skin in Black Patients. New England Journal Of Medicine, 328(20), 1438-1443. doi:10.1056/nejm199305203282002

[18] 0.1% Tazarotene is approximately as effective as 0.05% tretinoin for hyperpigmentation and fine wrinkles after 6 months.

Kang, S., Leyden, J., Lowe, N., Ortonne, J., Phillips, T., & Weinstein, G. et al. (2001). Tazarotene Cream for the Treatment of Facial Photodamage. Archives Of Dermatology, 137(12). doi:10.1001/archderm.137.12.1597

[19] Both 0.05% and 0.1% tretinoin improve hyperpigmentation and fine lines over 6 months.

Olsen, E., Irving Katz, H., Levine, N., Shupack, J., Billys, M., & Prawer, S. et al. (1992). Tretinoin emollient cream: A new therapy for photodamaged skin. Journal Of The American Academy Of Dermatology, 26(2), 215-224. doi:10.1016/0190-9622(92)70030-j

[20] 0.5% tretinoin improved hyperpigmentation and fine lines over 6 months

Leyden, J., Grove, G., Grove, M., Thorne, E., & Lufrano, L. (1989). Treatment of photodamaged facial skin with topical tretinoin. Journal Of The American Academy Of Dermatology, 21(3), 638-644. doi:10.1016/s0190-9622(89)70231-0

[21] 0.1% tretinoin improves hyperpigmentation and fine lines over 9 months.

Also, topically-applied tretinoin can be detected in the blood, but doesn’t build up over time.

Maddin, S., Lauharanta, J., Agache, P., Burrows, L., Zultak, M., & Bulger, L. (2000). Isotretinoin improves the appearance of photodamaged skin: Results of a 36-week, multicenter, double-blind, placebo-controlled trial. Journal Of The American Academy Of Dermatology, 42(1), 56-63. doi:10.1016/s0190-9622(00)90009-4

Indented scars

[22] 0.3% adapalene improves indented scarring after 6 months.

Loss, M., Leung, S., Chien, A., Kerrouche, N., Fischer, A., & Kang, S. (2018). Adapalene 0.3% Gel Shows Efficacy for the Treatment of Atrophic Acne Scars. Dermatology And Therapy, 8(2), 245-257. doi:10.1007/s13555-018-0231-8

Aging

[6] The increased cell turnover triggered by tretinoin does not “use up” your cells early.

Discussion on Senescence (Long-term aging). This phenomenal write-up is by the wonderful /u/Feather-Light!

I've spent the last few hours reading the research on this topic, which was largely going through the studies of interest cited in this review of Hayflick limit research.

Terms to understand:

Basic concepts for the reader to understand:

So you have to understand that Hayflick limit research is done in vitro. You also have to understand that RS was observed after a period of months. So do you see the disconnect here? Clearly we know our skin cells divide for far longer than a period of months that the in vitro Hayflick limit research has found. This is to say to not take in vitro research so literally. This is why our gold standard with anti aging studies are in vivo, so we know what actually happens in living humans, which is what we are, because again, we're not cell culture petri dishes.

A main takeaway here is that RS is often reached by many other means other than cellular division. Cytotoxic factors such as alcohol and radiation cause stress-induced premature senescence (SIPS). And of note here is that Hayflick's research used cell cultures with 20% oxygen to come up with that 250 figure. Actual physiological conditions in the human body are ~3% oxygen, which in vitro research using this parameter has reported a limit of 2^70. This demonstrates oxidative stress induces RS.

When we have RS due to cellular division, we see telomere shortening. But our gold standard of in vivo research on human subjects has shown that "studies in centenarians have raised doubts on whether telomere shortening occurs in vivo and whether senescence-associated genes in vitro are also differentially expressed in vivo." So basically, we see RS occurring not because of cellular division limits but because of stress inducers, such as oxidative stress. And oxidative stress is the whole concept of why UVA rays are bad: UVA rays generate reactive oxygen species (i.e. free radicals) and cause a negative chain reaction of cellular and DNA damage, thus the signs of premature aging which we call photoaging or sun damage.

The fact is that we're finding environmental stressors to be the cause of RS, not cellular division rates. So as a layperson who is merely a skincare research hobbyist and who constantly seeks out the knowledge to curate an optimized anti aging routine for fun, I'll absolutely keep on using retinoids and chemical exfoliants which we know increases the rate of skin cell turnover. And I'll certainly keep using an SPF 50+ PA++++ sunscreen to prevent the deleterious effects of UVA damage and its key role in oxidative stress.

I'll end this writeup quoting the review: "while there is little evidence to suggest that cells running out of divisions are a major factor in aging, it is possible that stress and various insults trigger cell senescence in vivo."

[23] 0.1% tretinoin decreases wrinkles after 3 months

Tretinoin increases epidermal thickness, and stimulates collagen.

Kong, R., Cui, Y., Fisher, G., Wang, X., Chen, Y., Schneider, L., & Majmudar, G. (2015). A comparative study of the effects of retinol and retinoic acid on histological, molecular, and clinical properties of human skin. Journal Of Cosmetic Dermatology, 15(1), 49-57. doi:10.1111/jocd.12193

[24] 0.4% retinol improves already-aged skin (doesn’t just prevent aging) after 6 months.

Kafi, R., Kwak, H., Schumacher, W., Cho, S., Hanft, V., & Hamilton, T. et al. (2007). Improvement of Naturally Aged Skin With Vitamin A (Retinol). Archives Of Dermatology, 143(5). doi:10.1001/archderm.143.5.606

[25] 0.05% tretinoin improves hyperpigmentation and fine wrinkles after 6 months.

Weinstein, G., Nigra, T., Pochi, P., Savin, R., Allan, A., Benik, K., Jeffes, E., Lufrano, L., & Thorne, E. (1991). Topical Tretinoin for Treatment of Photodamaged Skin. Archives Of Dermatology, 127(5), 659. doi:10.1001/archderm.1991.01680040067005

[26] 0.05% tretinoin improves wrinkles and hyperpigmentation after 3 months

Lever, L., Kumar, P., & Marks, R. (1990). Topical retinoic acid for treatment of solar damage. British Journal Of Dermatology, 122(1), 91-98. doi:10.1111/j.1365-2133.1990.tb08244.x

[27] Tretinoin improves photodamage after 4 months (unknown percentage)

Weiss, J. , Ellis, C. , Headington, J. , Tincoff, T. , Hamilton, T. , & Voorhees, J. (1988). Topical Tretinoin Improves Photoaged Skin. JAMA, 259(4), 527. doi:10.1001/jama.1988.03720040019020

[28] 0.05% tretinoin and 0.02% tretinoin both improves wrinkles and hyperpigmentation over 6 months

Nyirady, J., Bergfeld, W., Ellis, C., Levine, N., Savin, R., & Shavin, J. et al. (2001). Tretinoin cream 0.02% for the treatment of photodamaged facial skin: a review of 2 double-blind clinical studies. Cutis, 68(2), 135-142.

General

[11] Water increases skin permeability.

Barai, Namrata D. Effect of hydration on skin permeability. Diss. University of Cincinnati, 2002.

Summarizes current (as of 2002) knowledge around the role that hydration plays in skin permeability.

[14] Water increases absorption

Mojumdar, Enamul Haque, et al. "Skin hydration: interplay between molecular dynamics, structure and water uptake in the stratum corneum." Scientific reports 7.1 (2017): 1-13.

[12] Excessive hydration increases skin irritation

This is because excessive hydration causes changes in the skin structure of the stratum corneum.

Ogawa‐Fuse, Chie, et al. "Impact of water exposure on skin barrier permeability and ultrastructure." Contact Dermatitis 80.4 (2019): 228-233.

[13] Hydration helps molecules be absorbed by the skin

“​​Water is the most natural and biocompatible penetration enhancer known to improve the permeability of skin…we use cryo-scanning electron microscopy…” to study how changes in the stratum corneum (SC) affect the absorption of other molecules. “We clearly show that the SC is a dynamic structure, where extended hydration (>8 h) swells corneocytes, creates intercorneocyte ruptures, and causes microstructural changes in lipid self-assembly. The implications to biomacromolecule penetration are significant, since these disruptions allow penetration through the barrier of the SC.”

[30] Retinoids vary in strength

“Tazarotene is the strongest retinoid, while retinol is the weakest (retinyl palmitate is even weaker than retinol - more on that below*). The strength of a retinoid depends on the type of retinoid. Your skin is only able to use a retinoid when it's in retinoic acid form. Therefore, all types of retinoids are converted to this state by your skin before it can even be used. How does this have anything to do with a retinoid's strength? Allow me to explain.

When you apply a retinoid product that is retinoic acid (ex. Retin-A), your skin is able to use it immediately because it's already in the proper form. However, if you use a product with retinol, the retinol first has to be converted into retinaldehyde and then the retinaldehyde has to be converted to retinoic acid before your skin can use it. Therefore, retinol is weaker than retinaldehyde and retinaldehyde is weaker than retinoic acid. Retinol is the weakest of those three because it takes your skin two extra steps for it to be converted to retinoic acid before it can be utilized. For each conversion step, there is also some uncertainty as to how much of the retinoid was actually converted in the oxidation process (i.e. the retinol may not be 100% converted into retinoic acid). Therefore, the fewer the conversions it takes to get to retinoic acid, the stronger the retinoid.” skinacea.com

Tan, Grace, et al. "Hydration effects on skin microstructure as probed by high-resolution cryo-scanning electron microscopy and mechanistic implications to enhanced transcutaneous delivery of biomacromolecules." Journal of pharmaceutical sciences 99.2 (2010): 730-740.

Retinol vs Retinoic acid

Antiaging Action of Retinol: From Molecular to Clinical

Molecular basis of retinol anti‐ageing properties in naturally aged human skin in vivo.

Application of Retinol to Human Skin In Vivo Induces Epidermal Hyperplasia and Cellular Retinoid Binding Proteins Characteristic of Retinoic Acid but Without Measurable Retinoic Acid Levels or Irritation.

Improvement of Naturally Aged Skin With Vitamin A (Retinol).

A comparative study of the effects of retinol and retinoic acid on histological, molecular, and clinical properties of human skin

A Stabilized 0.1% Retinol Facial Moisturizer Improves the Appearance of Photodamaged Skin in an Eight-Week, Double-Blind, Vehicle-Controlled Study

Studies that need summarizing

Message the moderators if you’d like to summarize one of these studies, or another one you’ve found!

- Rosso, James Del et al. “Tretinoin photostability: comparison of micronized tretinoin gel 0.05% and tretinoin gel 0.025% following exposure to fluorescent and solar light” Journal of clinical and aesthetic dermatology vol. 6,2 (2013): 25-8.

- Elbaum, David J. "Comparison of the stability of topical isotretinoin and topical tretinoin and their efficacy in acne." Journal of the American Academy of Dermatology 19.3 (1988): 486-491.

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- Rocha, M. A., and E. Bagatin. "Skin barrier and microbiome in acne." Archives of dermatological research 310.3 (2018): 181-185.

- Bartlett, Kyle B., Scott A. Davis, and Steven R. Feldman. "Topical antimicrobial acne treatment tolerability: A meaningful factor in treatment adherence?" Journal of the American Academy of Dermatology 71.3 (2014): 581-582.

- Griffiths, Christopher EM, et al. "Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation: a double-blind, vehicle-controlled comparison of 0.1% and 0.025% tretinoin creams." Archives of dermatology 131.9 (1995): 1037-1044.

- Del Rosso, James Q et al. “Absence of Degradation of Tretinoin When Benzoyl Peroxide is Combined with an Optimized Formulation of Tretinoin Gel (0.05%)” Journal of clinical and aesthetic dermatology vol. 3,10 (2010): 26-8.

-  Tretinoin Photostability. Comparison of Micronized Tretinoin Gel 0.05% and Tretinoin Gel 0.025% Following Exposure to Fluorescent and Solar Light https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579485/ 

Research Summary Template

    **Title (Year). Authors.**

    **Variables:**

    **Participants:**

    **Methods:**

    **Results:**

    **Conflicts of Interest:**

    **Notes:**

Make sure there are two spaces at the end of each line!

- Variable(s) of interest: what's the study looking at, exactly?

- Brief procedural run down: how was the study conducted?

- Participant type;

- Number of participants;

- Methods: how the variables were investigated

- Summary of the results - what did the study find?

- Conflicts of interest - generally found at the end of the paper in a disclosure statement

- Notes - your own thoughts about the study, including any potential methodological strengths/weaknesses

Excerpts from Leslie Baumann's Cosmetic Dermatology retinoids/tretinoin.

Generously shared by the kind and generous /u/S3mirmis

On indications:

Not surprisingly, she recommend tret for acne (p.122 and following) and to heal photoaging (p. 257 among others). On the preventation of aging you can read the following:

"[E]vidence suggests that it [tretinoin] also plays a role in the prevention of aging. This can be linked to inhibitory effects of retinoids on damaging metalloproteinases. UVB exposure dramatically upregulates the production of several collagen degrading enzymes known as matrix metalloproteinases (MMPs) (see Chapter 6). Activation of MMP genes results in production of collagenase, gelatinase, and stromelysin, which have been shown to fully degrade skin collagen17(Box 30-1). Fisher et al. demonstrated that application of tretinoin inhibits the induction of all three of these harmful MMPs.1 In addition to increasing levels of destructive enzymes such as collagenase, UV exposure has also been shown to decrease collagen production. Fisher et al. demonstrated that expression of collagen types I and III is substantially reduced within 24 hours after a single UV exposure. Pretreatment of the skin with all-trans-retinoic acid (tretinoin) was shown to inhibit this loss of procollagen synthesis. Therefore, pretreatment of the skin with topical retinoids, when used consistently, is likely to be beneficial in prevent-ing as well as treating photodamage." (p. 257)

On introducing tret and other misc:

On frequency of usage

In the 1990s a study found that the benefits gained by using 0,05% tret daily for four years could be kept by using it 3 times a week for the next two years. using it only once a week was not enough to maintain the good results. The same study showed that the benefits would reverse themselves if one stops using tret altogether. Dr. Baumann follows that tret should be used at least three times a week. (p. 258, 259).

On side effects:


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