The 2020s are shaping up to be the decade of cosmeceuticals. No longer is skin care a niche hobby: clinical grade preparations are taking over luxury brands and high street cosmetics alike. Retinoic Acid, or vitamin A, is an especially confusing example of this takeover. With so many different forms, different doses and talk of EU bans it can be hard to choose products.
These days online skincare mavens are more likely to have a chemistry degree than a background in cosmetology, but don’t let that put you off.
With a little bit of context, you’ll be navigating the ingredients lists like a pro, and we’re here to help.
History of Vitamin A
If you haven’t heard of retinol, you must have heard of vitamin A. Many people associate vitamin A with carrots and improving vision, but its topical form, namely retinoid, is the most effective skincare ingredient known to date.
The first use of vitamin A for skin goes all the way back to the mid-20th century. The foremost article on retinoic acid was in 1943 in Northwestern Medicine, authored by J. V. Straumfjord. His article, titled ‘Vitamin A: its effect on acne’ demonstrated the efficacy that vitamin A had on patients with acne vulgaris. In his experiment, Straumfjord treated 100 patients with 100,000 IU of vitamin A daily for six months – a whopping 79 patients showed considerable improvement in their acne.
Retinoic Acid and Anti-ageing
Seeing the results of retinoic acid on acne, dermatologists quickly recognized its potential for skin rejuvenation. Retinoids promote skin turnover, collagen synthesis, skin smoothing and the amelioration and prevention of fine lines and wrinkles. These effects make it an exceptionally effective ingredient in anti-ageing formulations.
Its mechanism of action is multifaceted. Retinoids are able to have an effect on skin cells – their death, growth, and differentiation. For example, a type of skin cell is ‘keratinocyte’ which retinoids cause to grow. Since the function of a keratinocyte is to protect the skin, more keratinocytes means more protection from environmental factors such as UV rays, water loss, and microbes. They also inhibit a type of enzyme which degrades collagen. Collagen is what keeps skin plump and bouncy – and also the what adults start losing year by year in their mid-twenties.
Types of Retinoic Acid Preparations
Today, there are many options of topical vitamin A for consumers. Topical Vitamin A can come in different forms – retinol and tretinoin are just two of them! What differentiates these different retinoids is how many steps it takes for them to become chemically bioavailable in the skin once it is applied.
The fewer steps there are, the stronger the retinoid is.
What they all have in common is the vitamin A structure, consisting of 20 carbons – or, for those more familiar with biochemistry, ‘four isoprene units with a head-to-tail structure’.
Retinyl esters
This is the mildest form of retinoid acid, found in everyday use products such as
Derma E Anti-Wrinkle Renewal Cream, Paula’s choice triple Active Total Repair Serum, Shani Darden Retinol reform.
Retinyl esters are the least potent form of retinoic acid. They need multiple steps to convert into bioavailable retinoic acid in your skin. Once you apply the preparation, the retinyl ester is turned into retinol by an esterase, which is then turned into retinal by alcohol dehydrogenase, which is then turned into retinoic acid by retinal dehydrogenase. (Fun fact: one type of retinyl ester can be made by chemically unifying vitamin F and vitamin A.)
Retinol
Retinol is the next level, a slightly stronger form of retinoid. The Ordinary markets a line of products containing various retinol concentrations suspended in squalene. A little more potent than retinyl esters, retinol only needs processing by alcohol dehydrogenase and then retinal dehydrogenase to reach its active form.
Retinaldehyde or Retinal
Retinaldehydes are fast acting and often found in serums marketed as ‘clinical’ grade. Said to be as close to prescription strength as possible this ingredient shows up in products for occasional use such as Paula’s Choice PRO Retinaldehyde Dual-Retinoid Treatment, Naturium’s Retinaldehyde Cream Serum 0.10% and Maelove’s Moonlight Retinal Super Serum. This very powerful form of Vitamin A is often used as an exfoliator in addition to its anti-ageing properties.
Retinaldehyde, or retinal, needs only one level of processing. In this step, an enzyme found in the body called retinal dehydrogenase removes hydrogen from the backbone structure of the molecule activating its skin resurfacing properties.
Tretinoin
Tretinoin is the unmodified version of the molecule. A heavy weight contender, this is the Lennox Lewis to retinyl’s Manny Paquito.
Tretinoin is immediately bioavailable, which should be a cause for celebration… unfortunately this immediacy comes with a price. Tretinoin has unpleasant side effects causing dryness, irritation and skin peeling. Available only with a prescription, this form of Vitamin A is a potent exfoliant prescribed for acne alongside cosmetic applications and should be used under the supervision of a doctor
How Do I Choose My Retinoid?
For those who are just starting their retinoic journey, there are many things to consider before making a decision. It is important to remember that stronger does not always mean better. Those with dry skin cannot start out with 0.1% tretinoin! Retinoic acid comes with many side effects, some of which include redness and irritation, not to mention the initial purging that occurs when skin turnover is accelerated by the actions of RAR and RXR. It would be advisable to start off with the most gentle formulations of retinyl esters once or twice a week, and work your way to every day. If you do not notice enough of a change, move on to low percentages of retinol formulations – as low as 1%. Anything stronger than retinols is usually prescription – and the next steps should be discussed with your doctor.
How Does Retinoic Acid Work?
It might be surprising to some that to this day, scientists don’t exactly know the therapeutic mechanism of retinoic acid. What we do know, though, is that retinoic acid binds to RAR (Retinoic Acid Receptor) and RXR (Retinoid X Receptor) bind to nuclear receptors in the skin cell. Retnoic Acid is fat-soluble, that’s why you often see it in oily or alcohol based solutions. It’s also why chemists can’t manipulate retinoids to become water soluble! If a molecule is fat-soluble, it can slip through our fatty cell membrane. Retinoids must penetrate your skin and get into the individual skin cells to activate skin renewing gene expression. For chemistry enthusiasts, it might be interesting to note that retinoic acid exists in two isomers: fully-trans form and 9-cis form. The latter of which affects proliferation and differentiation of cells through gene binding.
Nuclear receptors can be thought of as the keyholes on your nucleus for which RAR and RXR are the keys. Once the keys go into the keyhole, a cascade of events starts and the end result is certain genes being activated that cause skin turnover, reduction in collagen degradation, and cell proliferation. Zoomed out, this means smoothing out of wrinkles, skin evenness and facial plumpness!
Chemical Evolution of Retinoids
Scientists are not yet done with this hero ingredient. New ways of optimizing this ingredient are put to the test every day. For example, the company Sederma is testing out retinol delivered in liposomes which may enhance their bioavailability. A new retinoid by the name of hydroxypinacolone retinoate, or HPR, might be just as effective as tretinoin but without the side effects, we are waiting to see how it pans out.
With so many new ingredients in the skincare products of today, it can be overwhelming to keep up with all the names and their functions. Retinoids such as retinol and tretinoin continue to be the most research backed and reliable staples in anyone interested in minimizing visible signs of ageing on their skin.
Antiaging effects of retinoid hydroxypinacolone retinoate on skin models. Journal of the American Academy of Dermatology. 2018;79(3):AB44. doi:10.1016/j.jaad.2018.05.215
Zasada M, Budzisz E. Retinoids: active molecules influencing skin structure formation in cosmetic and dermatological treatments. Postepy Dermatol Alergol. 2019;36(4):392-397. doi:10.5114/ada.2019.87443
If you are a vintage science enthusiast like us, we have linked the original 1943 article linking retinoids to skin care for your enjoyment!
