Let’s talk about Retinyl Palmitate
When a client I was talking to questioned me about the efficacy of Retinyl Palmitate as in ‘does it even do anything at all?’ I was perplexed. I’ve been dealing with vitamin A and its derivatives in skin care for a long time and had adopted a mindset of quietly accepting that the palmitate derivative of this vitamin was a useful compromise for most skin care brands – sure it’s less effective and slower acting but it’s also safer, more stable and when all is said and done it does get the job done eventually (and at a reasonable price point). For me retinyl palmitate is something that works, albeit to a lesser degree than pure retinol but without the stability headache.
Apparently I was wrong.
Apparently top scientists around the world have dismissed retinol esters as being ‘of no value in photo protection’.
The more I talked to the client the more curious I became. I’m always fascinated at how we (humans) form and hold opinions that are, once tested, based on very little solid ‘truth’ as far as what we can actually bring to mind. This, for me was one such occasion. I resolved to delve in deep as soon as I could, collected the clients email address and could think of nothing else for the next 48 hours. Yes, I’m a science research tragic, especially when it comes to good old chemistry, and that, my friends, is where I started.
Retinyl Palmitate. Stands accused of doing nothing, being no good and faking its own identity as a decent source of vitamin A for the skin.
Really?
Here are the two articles that got this thing started.
- How much do we really now about our favourite cosmeceutical ingredients?
- Workingwithretinoidsforanti-agingandskinrepairformulations
The first thing to note is that these papers are both ‘scientific’ and written by people with authority, typically a higher level of authority than most (if not all) of my customers and even me maybe. However, we should never let that stop us digging in and around what they have said, not because we suspect they are wrong but mostly because not everyone has the motivation to dig like you do, in the same spot or for as long. I am one of those annoying people who has more ‘why’s’ in them than almost anyone else I know and the stamina to boot so I’ll be using that here.
So what do these two papers say?
So the earlier paper from 2010 (how much do we really know, written by dermatologists) sets the scene really well, identifying a problem (it’s likely there isn’t much evidence behind our favourite cosmeceuticals) then proceeding to break down the ‘evidence’ based on good scientific rigour and protocol. The paper has all of the right words in all the right order but it does make one glaring mistake to my mind and that’s when it dismisses retinyl palmitate early in the piece. This article dismisses retinyl esters based on this article here and this one here. If you have a subscription to the scientific paper database DEEPDYVVE you can download the whole papers.
One of the papers that is used to dismiss Retinyl Palmitate (Antioxidants and vitamins in cosmetics) is quite odd in that the paper doesn’t its self dismiss the ingredient at all. It merely points out the obvious that, for Retinyl Palmitate to work it has to be relieved of its palmitate tail and then has to undergo other chemical conversions in the skin to release the dragon (so to speak). The paper acknowledges this and acknowledges that retinol (which also needs further converting) needs to be present in concentrations of 0.25% or more to illicit a positive response. With Retinyl Palmitate being only somewhere around 1/2 as effective as Retinol that would mean adding 0.5% of it to a formula to guarantee an effect. That’s very do-able. This paper found retinyl palmitate to increase epidermal thickness and collagen levels which confirm its ability to act as a skin normaliser which is what it is supposed to do.
The other paper is largely irrelevant to my mind as for a start it focuses on Retinyl Propionate and not Retinyl Palmitate and for second it only used 0.15% of the molecule. Chemically Retinyl Propionate has a molecular weight of 342.51g/ mol whereas Retinyl Palmitate has a MW of 524.86g/mol so you could be forgiven for thinking that Retinyl Propionate should be much stronger and better than the palmitate as the retinol part accounts for a higher percentage of the overall molecule. However, weight isn’t the most important thing when it comes to dermal penetration – I’ve said this before but it does seem to me that lots of people love to cling to the notion that size is super important. Anyway, with these molecules what matters is how easy it is for the body to rip the tail off these things. The main reason I quickly began to suspect that the first two papers had missed the point is because Retinyl Palmitate is naturally found in the body, indeed, it is the molecule that the body converts retinol to and from in order to transport it around and store it. The article ‘working with retinoids for anti ageing skin formulations’ mentions this but emphasises a conversion reaction of retinyl palmitate that happens in the liver, this may lead the reader to think that all conversion happens there but that isn’t true. Retinyl Palmitate can be cleaved in the skin (epidermis) and it can also be created there too depending on the needs of the cells at the time. Surely a molecule that the body can make and convert is going to be better than a molecule that came out of nowhere (un-natural)? I think so. Weight or size isn’t relevant here.
So basically, with that I started to build up a picture that Retinyl Palmitate had been more mis-judged, the victim of an unfair trial if you will. Rather than it being guilty of being useless, it was just guilty of being slow (compared to retinol or retinoic acid) and more clunky.
While it looks like Retinyl Palmitate is useful for the skin in general, is it fair to say that it is useless in photo protection, another key claim against it?
That may well be somewhat true, signs that something protects against photo ageing are:
- A reduction in fine lines and wrinkles.
- Decreased hyper pigmentation.
- Decreased skin roughness.
Cosmetic trials can last for any length of time but it is most likely that a trial of significance run for at least one skin cycle – 28 days. They may go on for up to two before becoming too expensive. During this time any active should have soaked into the active layers of the skin to influence whatever it is supposed to influence, with retinol its the growing of new cells – keratinocytes.
Retinoic acid, the form of retinol that is immediately active can jump into action at the site of application straight away and put 100% of its effort into righting the wrongs that it finds. Retinyl Palmitate has to shape shift and then stay where it was rubbed to work. I am not totally sure about this but I would hypothesise that sometimes retinyl palmitate might end up either being transported away by the body to other places or might be rubbed off with normal wear-and-tear of the day if it doesn’t penetrate relatively quickly. Retinoic acid has to be built-up to retinyl palmitate in order to be transported anywhere – a biological cost or effort. Further, photo ageing is caused by free radicals that are released due to the sun’s energy, retinoic acid has its hands free to act as an antioxidant and PREVENT the free radicals causing trouble whereas Retinyl Palmitate has baggage and can’t do that until it is cleaved and it won’t get cleaved on the surface, where the free radicals are. A similar situation exists with vitamin E, vitamin E acetate can be cleaved in the skin and act as an antioxidant but will not act as an antioxidant in your cosmetic pot. So vitamin E acetate is useless at holding back oxidation of oils for example but it would be foolish to say it is of no value.
I would surmise from this that Retinyl Palmitate is not an antioxidant (or not a good one anyway) so it can’t prevent photo ageing or mop up the inflammation that comes from irradiation. I would surmise that Retinyl Palmitate is likely to be very slow to act compared with retinoic acid and that some of it may well end up somewhere other than the skin when applied, especially if the body needs it elsewhere (because of its mobile form). Lastly I would surmise that neither of these points really matter as we have already shown that this ingredient can and does have some benefits for the skin, can be used safely at a level that will elicit those positive responses, is stable enough, affordable enough and cosmetically acceptable enough to be of value in daily (or nightly) long-term skin ‘normalising’ or ‘optimising’ formulations including anti-ageing products.
My final conclusion therefore is as follows:
That rather than their being no evidence to support Retinyl Palmitate as a good skincare active, there is evidence of its benefits, backed up by scientific logic (its chemistry and biochemistry) and in-vivo results. The main issue being that the studies are small and the dose rate used is not always fair. Pair that with the fact that a number of experts have discounted this molecule and you have the situation we have today.
I would be comfortable in saying that it probably isn’t fair to expect Retinyl Palmitate to be a good photo protective molecule based on its lack of antioxidant capacity as supplied, but it is fair and beneficial to see it as a valuable input into a well-balanced anti-ageing formula for long-term use. It is proven to boost collagen production and to thicken the epidermis which is a desirable.
Overall I see no reason to not include retinyl palmitate into a cosmetic formula, it might be slower and less dramatic than retinoic acid or even retinol but it does work and like the hair and the tortoise race taught us, as long as it gets there in the end it succeeds.
Realize Beauty 
I completely agree that people brush off retinyl palmitate too easily, the issue is that one of the main claims against it is true, there is not enough reliable evidence in the published peer-reviewed literature.
There are ex vivo studies indicative of the transformation of retinyl palmitate to retinol in the skin for instance: Duell, E. A. et al. Invest. Dermatol. 1997, 109 (3), 301. So if penetration is allowed effect is to be expected.
And retinyl palmitate does indeed penetrate the skin (at least ex vivo) which has been proved by, amongst others, L’Oreal (Cited here: https://ec.europa.eu/health/sites/health/files/scientific_committees/consumer_safety/docs/sccs_o_199.pdf).
However, I disagree with the notion, indicated while not explicitly mentioned, that retinyl propionate should be any less effective. It is, just as with retinyl palmitate a matter of penetration. Granted Green C et al. Clin Exp Dermatol 1998: 23: 162- 7 showed no improvement, however, a more recent study indicates improvement with a different formulation: Hawkins, S. et al. Int. J. Cosmet. Sci. 2017, 39 (6), 589.
As for the “smaller is better” Lipinski’s rule of fives is easily understood and (mis)used by people because it is simple and logical. That is also why it is taught to organic chemists and pharmacology students. It is simply a great guideline, but only a guideline.
Great post by the way!
Thanks Simon, very interesting. With regards to the Retinyl Propionate I was pondering on how that could be more effective than a structure that’s found in the body. That said they would both be cleaved at the same spot and the structures only differ in the chain length after the functional group so maybe I was too harsh in my judgement. The propionate has a lower molecular weight too so there would be more moles per gram added so maybe on balance it is a good option. It’s always interesting to think on these things 🙂
Do you know wether Hydroxipinacolone Retinoate is effective and stable enough the be used in cosmetics? A cosmetic dermatologist from The Netherlands told me, that although there’s not a lot of evidence yet, HPR does bind directly to the receptors, doesn’t need conversion and looks promising to give results like retinol and retinoic acid without irritation. However she says it still is very unstable so it needs airless packaging and needs to be fresh, preferably stored in fridges in the warehouse. So in short, no product on the market will be any good, because airless packaging is rare, but it is impossible to find out how old a product is. And then the question is, how quickly does it degrade? I find it difficult to find any additional information. What do you think?
Hi Peter, I have no idea to be honest. I haven’t done any pro-active research on this form of vitamin A yet. Often the problem is with stability with some forms of vitamin A being so unstable that even though they are super fast acting, they can’t really give reliable enough results. Sometimes this can be overcome by encapsulation but compounds have to be stable enough to encapsulate and then have to release appropriately when applied. Encapsulation is not always a fool-proof answer. I do agree broadly speaking with what is said above based on what I know and have tested with retinol. Some brands can stabilise the ingredient better than others and you can still get a 6-12 month shelf life in some cases. Testing stability of retinol is easy so this is definitely one situation where I would say ‘show me the evidence’ or ‘bring me the data’ and if there isn’t any, let’s generate it!