FAQs about Retinol
In Part I, we discussed the main pathway of retinol metabolism and learned that in order to allow the skin to OPTIMALLY convert retinol into retinaldehyde, and then into tretinoin, a retinol product should have a pH value of between ~5.0-6.0.
So the obvious question that is asked most often is, “Can I use retinol and hydroxy acid products together?”
Based on research and my interpretation of the literature, they should not be used together. This stance has drawn particular criticism HERE from advocates of Paula Begoun, the creator of Paula’s Choice, who attempted to answer this question HERE. Please note that I too, am an advocate of Paula Begoun and her products. I just don’t always agree with some of her rationalizations and interpretations of scientific data.
Now, before you start drawing conclusions, let us walk through and analyze her post. In critiquing it, perhaps we can come up with an independent and more realized assessment. So that you guys (the readers) don’t have to keep skipping back and forth between pages/tabs, I will simply copy and paste the entire article here and address it section by section.
*Please note that the studies Paula referenced will be denoted as [#X], with “X” being a numerical value, and along with the rest of her post, are italicized and bolded. The studies that I reference will be denoted as [(X)] and are not italicized and not bolded. In addition, there will be parentheses around the number or “X”.
Fan FAQs: Retinol, pH and Daytime Use?
Q: “My dermatologist says that it is well-known that retinol increases your sensitivity to the sun, and that I shouldn’t use it during the daytime because sunlight deactivates it. How do you know if I can use my PC retinol during the day?
Is it true that over-the-counter retinol is 20 times weaker than Retin-A and doesn’t work as well? My derm also says that retinol needs a certain pH to work and it shouldn’t be applied with other acidic ingredients. I am so confused!”
A: All retinoids, particularly prescription retinoids like tretinoin, increase skin’s sensitivity to the sun to an extent. We know that tretinoin (the active ingredient in Retin-A and Renova) is deactivated by sunlight; it becomes unstable with exposure to UV rays. Cosmetic, non-prescription retinol is not as unstable, and research has shown when applying a broad-spectrum sunscreen over cosmetic retinol, there is no loss of effectiveness. This doesn’t necessarily mean a day at the beach, but certainly what hasn’t been shown in research is that retinol is unstable when SPF measures are taken.
Paula uses studies #2 and #3 to substantiate this claim. Study #3 will be ignored because one, it hasn’t been peer-reviewed or published in any known journal (it can’t even be found on PubMed); two, the UV blocker discussed isn’t traditionally used (Ethylhexyl Methoxycrylene) or available in sunscreens; and three, the author of the article has a conflict of interest, being that his organization is affiliated with the supplier of the UV blocker discussed.
Now study #2, which can be found HERE, combines retinol with a formulation of avobenzone (UVA sunscreen), octinoxate (UVB sunscreen), and the antioxidant vitamins C and E. The study tested this formulation (4 experimental groups + 1 control group) under varying degrees of light and air, and measurements of retinol stability were taken at 0.5, 1.0, 2.0, and 4.0 hours. At the end of 4.0 hours, when compared to the control group, retinol stability was at 91.3% (UV & nitrogen gas (N2)), 91.5% (UV & air), 96.9% (N2), and 99.2% (air). Please note that the rates of degradation weren’t strictly linear.
At first glance <10% of retinol degradation after 4.0 hours of UV and air exposure, is quite good. However, there are a few things that need to be kept in mind:
>>> We know that, to any sunscreen formulation, the inclusion of both vitamins C and E, can massively boost the level of UV protection (1), up to 4-fold. Numerous other studies support this concept. Study #2 didn’t test retinol stability with only the protection of sunscreen (avobenzone and octinoxate), which most likely would have yielded significantly different results. And the study didn’t test if there were interactions between the hydroquinone and retinol contents, not to mention the effects of the “moisturizers,” as the latter can have a large effect on UV protection. Basically, because this study wasn’t vehicle-controlled, it has no real value. However, I will still address the rest of this study.
>>> In real life situations, this rate of 10% degradation over 4.0 hours needs to be perceived contextually, meaning that the rate of degradation needs to be calculated from a point of reference, which of course, is how much retinol has already degraded. When we purchase a retinol product, we don’t use all of it up immediately. So despite efforts to stabilize the retinol via formulary and packaging choices, the retinol in any product will degrade over time. So in a month, perhaps 10% of the retinol INSIDE the bottle has already decayed, and with exposure to UV light and air, will degrade even further. Why take that risk? Just use retinol at night-time. As you can see from the study, group 3 (exposed to air), only had a degradation of 0.8% after 4.0 hours. That’s more than 10x less than that which occurs with the addition of UV light!
>>> Overall, while this claim certainly has value and merit (I have read other articles that support this), it’s just better and smarter to use retinol at night time. At the right concentration and formulation, using retinol every night will be sufficient and potent enough for most people. In fact, it may even be TOO potent. There are no benefits (only potential drawbacks) to using retinol during the day.
In terms of retinol’s strength vs. that of prescription retinoids, we’ve seen various figures as to how they compare. However, the “20 times weaker” number comes up most often—but the question is whether that is relevant to you, as all this means is that cosmetic retinol takes longer to show the same results as tretinoin, which is why tretinoin requires a prescription.
The often cited “20 times” reference refers to a 1988 study on mice, of which references a 1987 study on mice, which really isn’t that impressive when you consider the depth of research since showing the anti-aging benefit of cosmetic retinol in skin care, especially when combined with a well-formulated skin care routine.
Paula doesn’t actually cite the 1987/1988 studies, but I can tell you that “20 times weaker” is quite an accurate measurement of the strength of retinol vs that of tretinoin.
>>> Like I’ve said many times in the past, keep in mind that the word “strength” only refers to how much tretinoin accumulates in the skin. Therefore, if you apply 1 unit of tretinoin, 1 unit of tretinoin will be in contact with the skin. However, if you apply 1 unit of retinol, only about 1/20th of a unit of tretinoin will come into existence due to the average rate of conversion. It doesn’t necessarily mean that you need 20 units of retinol to achieve the same visible effects that 1 unit of tretinoin can do, as several studies have demonstrated that low levels of tretinoin can have similar effects on the skin as higher levels (2). It just varies from person to person.
>>> Also, Paula’s assertion that it just takes retinol longer to achieve the same results as tretinoin (basically that it takes something like 20 days of retinol use to achieve the safe effects as 1 day of tretinoin use), is untrue. Why do you think there are varying degrees of tretinoin available at the pharmacy? Because different people and disorders respond to different strengths of tretinoin. In terms of retinol, different people can have different physiological capabilities to convert/metabolize it to tretinoin. Not to mention, the existence of varying and unregulated degrees of efficacy when it comes to retinol products, which have different delivery systems, stabilizers (if any), etc… To make a blanket statement that retinol will do the same thing as tretinoin, with just more time, is lazy, inaccurate, and unsupported by evidence. This topic will be explored further in Part III, which will explain why retinol can never replace tretinoin.
>>> Now, to show evidence of my own, several studies including this one (3) have established that the skin converts retinol to tretinoin at a rate of about 5%, on average. The cited study measured the rates at which expression of the enzyme, type I epidermal transglutaminase (TET-1), were reduced when retinol or tretinoin was applied to the skin. (Reduction of TET-1 expression is a well-known indicator of tretinoin activity). The study discovered that approximately half-maximal (EC50) reduction was observed at 10 nM retinol and 1 nM of tretinoin, indicating that tretinoin is about 10 times more potent than retinol. Before you tell me that “10” is not the same as “20,” keep this in mind. The study also showed that most of the retinol converted to retinyl esters, and that as retinol concentration increased, only marginally more tretinoin appeared in the skin, indicating the same concept I stated in Part I: that the metabolism of retinol to tretinoin is strictly regulated by the skin. But because tretinoin cannot be reduced back to retinaldehyde, how much tretinoin is applied to the skin, is what the skin has to deal with. Therefore, because it was demonstrated that 10 units of retinol was required to achieve the same results seen with 1 unit of tretinoin for HALF-maximal response, FULL “maximal” response would be twice that number. Hence, 10 x 2 = 20. Keep in mind that this was done to test the capacity of response. It was not referring to the threshold of response, meaning that there is no “baseline” concentration that can be applied to everyone.
>>> Therefore, the modified conclusion that: tretinoin is UP TO and ABOUT 20 times stronger than retinol, is quite true!
The upside of retinol versus prescription tretinoin? There is a significantly reduced likelihood your skin will experience negative side effects (redness, flaking, sensitivity) from retinol than from tretinoin. So if you’re willing to be patient, you’ll find results from retinol will, over time, equate to those from prescription tretinoin.
Paula has no citation for this claim, but fortunately it’s true. Retinol is comparatively much less irritating than tretinoin (4). However, like I discussed above, retinol won’t necessarily have the same effects as tretinoin when used over time.
We have not seen any research indicating that retinol needs a certain pH to work—this is one of the strangest misunderstandings in skin care recently. The research cited when you hear the claim of retinol needing a pH of 5.5-6 is from 1990, and this demonstrates why it is important to understand the study before using it to back your claims. The 1990 research discussed the formation of skin cells in response to all-trans retinol (tretinoin), and no surprise, your skin’s cell production is optimal at the skin’s natural pH, which is 5.5-6. Surprisingly, the study’s authors did not use cosmetic retinol (all-trans retinol is the prescription version) and in the end, the pH discussion is all about the optimal level for skin, not retinol!
One more point: retinol is naturally acidic (the prescription form is also known as retinoic acid) which is why some people find they’re sensitive to it.
Paula says that study #1, which can be found HERE, is the basis for the (in her opinion) false claim that retinol needs a certain pH in order to function. She is correct in the sense that retinol does NOT need a certain pH to function. But as I stated in Part I, she is incorrect in the sense that a retinol product doesn’t need a certain pH range in order to allow the skin to OPTIMALLY CONVERT retinol into tretinoin. But let’s get into the study and point out the fallacies made.
>>> Paula discusses study #1, as if it were correctly used to substantiate the fact that retinol products need a pH of 5.5-6.0. She goes on to explain why that study doesn’t apply. But the problem is that, study #1 shouldn’t even be used to explain this idea! As I explained in Part I, the 5.5-6.0 pH range is the optimal range necessary for the enzyme, acyl CoA:retinol acyltransferase (ARAT), to optimally convert retinol to retinyl esters, which is going in the complete OPPOSITE direction on the retinol metabolic pathway! The enzymes responsible for the conversion of retinol to tretinoin are completely different, and have different (higher and more basic) optimal pH ranges! Once again, see Part I for more information. By not addressing this issue, Paula shows a serious lack in judgment.
>>> Not to mention that she also equates all-trans-retinol to tretinoin, which are definitely not the same. The “all-trans” prefix only denotes directional configuration, not compound identification. Jack, one of my readers, claimed in the silicone entrapment discussion, that as a “professional” talking to laypersons, Paula was flexibly interchanging scientific terms to not confuse us. But she supposedly knows the difference between the two. Well, I don’t know what she THOUGHT, but all of us can see what she WROTE. And since she erred on one of the most critical terms (since the focal point of our ENTIRE debate hinges on whether or not the skin needs a certain pH range to optimally convert retinol into tretinoin), her logical conclusion and authority (on this topic) only diminish in validity and strength.
What is stranger still about the claim of retinol working best at any pH level is that it actually works best in formulas that have no pH at all (this is true of many antioxidants and cell-communicating ingredients,) such as silicone-based serums.
Again, no citation was used to substantiate this claim. While it may be true, I’d imagine that a water- and oil-based emulsion (liposomes) with chemical penetration enhancers like ethoxydiglycol, limonene, or even ethanol, while being not as stable and more drying, will be more effective than silicone-based serums due to a better delivery system.
We’ve heard the claim (as have many) that retinol can’t be combined with acidic products like AHA or vitamin C because of the pH concern, but there is no research supporting this (and we’ve looked on numerous occasions) aside from the study mentioned above, which really wasn’t talking about this issue to begin with!
As I mentioned above, the pH concern isn’t about allowing retinol to function, but allowing the skin to optimally convert it to tretinoin. When a correctly formulated hydroxy acid or L-ascorbic acid (vitamin C) product is applied to the skin, the skin is saturated with the product, and the pH (of the skin) is temporarily lowered to something close to that of the product. Glycolic acid, an alpha hydroxy acid, requires an approximate pH of <4.0 to exfoliate and penetrate the skin, while L-ascorbic acid requires a pH of <3.5. Therefore, because the pH necessary for the skin to optimally convert retinol into tretinoin is far more neutral than that, they shouldn’t be used together. Not to mention that, while pH doesn’t affect retinol all that much, it does affect hydroxy acids and vitamin-C. So if used together, the retinol won’t be optimally converted to tretinoin, and the hydroxy acid or vitamin C may not even work much at all! Talk about a “lose-lose” scenario!
Now, it’s important to note (like I said in Part I), that the pH range of 5.0-6.0 was estimated and is only required for the enzymes to convert OPTIMALLY. Since no studies have been done to compare how well the skin converts retinol to tretinoin across various pH values, right now it’s really just a “better-safe-than-sorry” attitude that I make this recommendation.
Also, keep in mind that when I say “used together” I mean like both products (retinol + acidic) are applied one after the other, with no significant wait time in between, or if they’re in the same formulation. I don’t mean that they can’t be used in the same routine. And once again, because no study has been done to see how quickly the skin homeostatically returns to its normal pH when a topical product of a different pH is applied (probably because there are too many factors that are difficult to control and can drastically alter results such as: vehicle occlusion, amount of product applied, and every individuals’ skin pH, etc…), it’s still a “better-safe-than-sorry” approach and recommendation: to apply them on different days. However, if you feel like you MUST use acid products with retinol ones at the same time, wait at least one hour between applications, just to allow for the adequate re-alignment of the skin’s natural pH, and the optimal conversion of retinol to tretinoin.
In contrast, there is research supporting concurrent use of an alpha hydroxy acid (AHA) product with retinoids. The final decision is up to you, but as long as you’re being good about wearing an SPF 15+ every day without exception, there is no research-supported legitimate reason why you can’t use your cosmetic retinol product during the daytime!
Paula uses citations #4, #5, and #6 to substantiate this claim. Studies #5 and #6 will be ignored because they both test a hydroxy acid with tretinoin… As this entire series so far has emphasized, RETINOL products need a certain pH range to allow the skin to optimally convert retinol to tretinoin!!! Of course the skin doesn’t need a pH range to convert tretinoin… it’s already TRETINOIN! Again, the fact that Paula would use citations #5 and #6 displays either a cunning attempt to fool readers (on this topic), or a serious lack of knowledge (on this topic). Both instances are quite alarming.
>>> Now study #4, as the title suggests, was done to test tolerance and acceptability, not drug interactions. So maybe they were used together, but it doesn’t tell me if retinaldehye worked better in the presence or absence of glycolic acid.
>>> Furthermore, as I can’t see the entire article (I’d have to ask a university friend to download it for me, which I can if you guys want me to), I don’t know if the two products were actually “used together” (see above for definition), or that there was a significant wait time between the two, if there were even two separate products. This is important because glycolic acid functions by thinning the top dead layer of skin. So if they weren’t “used together,” glycolic acid would naturally amplify the effects of retinaldehyde by allowing more of the latter to penetrate into the skin and penetrate more deeply, since there’s fewer layers of dead cells that the latter must first traverse.
Vitamin A esterification in human epidermis: a relation to keratinocyte differentiation. Journal Investigative Dermatology. 1990; 94(1):132-8. (#1)
Assessing Retinol Stability in a Hydroquinone 4%/Retinol 0.3% Cream in the Presence of Antioxidants and Sunscreen Under Simulated-Use Conditions: A Pilot Study. Clinical Therapeutics. 2008; 30(3). (#2)
Photostabilization of Retinol and Retinyl Palmitate by Ethylhexyl Methoxycrylene. Cosmetics & Toiletries. 2011; 126(1). (#3)
Topical Retinaldehyde with Glycolic Acid: Study of Tolerance and Acceptability in Association with Anti-Acne Treatments in 1,709 Patients. Dermatology. 2005; 210(1):22-29. (#4)
Compatability of a glycolic acid cream with topical tretinoin for the treatment of photo damaged face of older women. Journal Geriatric Dermatology. 1993; 1:179–181. (#5)
An evaluation of the compatibility of tretinoin cream 0.05% and a glycolic acid 8% solution for acne-prone skin. Cosmetic Dermatology. 1996; 9:26–38. (#6)
Ultimately, what you decide to do is your choice. My main goal is to tell you guys that in most cases, to get the best out of your routine, you shouldn’t use retinol products with acidic ones. With the right concentration and formulation (and routine of course), retinol used once per day at night time should be more than enough to satisfy most people. And if after reading through all of this, you still feel compelled to use acidic products and retinol together, please wait at least one hour between applications! Until more conclusive and specific studies are done to elucidate the various mysteries present above, this is the best that we can hope for!
I’d like to quickly point out that while I evaluated Paula’s assessment of this topic quite harshly, please keep in mind that I absolutely LOVE most of Paula’s Choice products, in addition to Paula’s own crusade to enlighten the general public with (mostly) accurate and refreshing advice. So what if I strongly disagree with a few things that she claims? It doesn’t make her any LESS awesome! But keep in mind that “everyone makes mistakes,” myself included. Besides, the WORDS being said are more important than the PERSON saying the words. Please note that, like I said in my Disclaimer, I am self-educated in the literature and am in no way a professional. But does that make my correct assessments more correct? Or my faults more wrong? No. Therefore, always seek multiple opinions on a topic, so you can make a more informed decision. And in the end, if you disagree with me, that’s perfectly fine!
What do you guys think of this article/topic/viewpoint? I’d love to hear your opinions!