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What are retinoids?

What are retinoids? What’s the difference between the different retinoids? Should I be using retinoids?

There’s a lot of confusion and inaccurate information about retinoids, so it’s not surprising that I get a lot of questions about them.

If you stick around to read this lengthy blog article, I promise to answer all these questions about retinoids and a whole lot more.

If you’re interested in skin care and anti-ageing, then you’ve already heard about retinoids, and they’re probably in your bathroom cabinet, although you won’t see them listed on the ingredient label as retinoids. Let me explain.

What are retinoids?

Retinoids is the general term used to refer to a class of molecules that bind to retinoic acid and retinoid receptors in the body. They’re derivatives of Vitamin A, an antioxidant, and can be natural or synthetic. Retinoids can be found in prescription oral form and prescription topical form, but are also found in over-the-counter skin care products.

Isotretinoin is found in Roaccutane and is used as a prescription oral medication to treat severe acne. Tretinoin is also a prescription medication used to treat acne, however it comes in a topical form and is better recognised by many under its brand names Retin A, Renova, ReTrieve or Stieva-A. The other two prescription topical retinoids used to treat acne are Adapalene, more commonly recognised as Differin, and Tazarotene, more commonly recognised as Tazorac.

History of retinoids

Tretinoin was first used in 1969. It was found to be astoundingly effective in treating acne vulgaris. Dermatologists using Tretinoin on patients with acne also noticed that it did a lot more than that – the Tretinoin significantly improved other skin conditions too!

In 1988, Dr John Voorhees and colleagues at Michigan University Medical School published the first double-blind study of Tretinoin’s effect on photo-aged skin and found that all 30 participants showed significant improvement in their skin. Their findings were published in the Journal of the American Academy of Dermatology and made headlines around the world. This was the first time a topical product had been found to remodel skin at the cellular level.

Today retinoids are still used to treat acne, however they’re also used to tackle many common skin concerns, including skin ageing, psoriasis, melasma and sun damage, including actinic keratoses. From a skin ageing perspective, retinoids can improve the appearance of wrinkles, hyperpigmentation, visible pores, rough texture and lax or sagging skin.

As well as prescription retinoids, there are less potent retinoids that can be found in various skin care products, including serums, treatments and moisturisers.

Benefits of retinoids

Vitamin A in the diet is essential for healthy skin and eyes. It can be found in liver, butter and eggs and can be converted in our bodies from beta carotene – think carrots, spinach, sweet potatoes and more. Vitamin A in the body becomes Retinoic Acid.

Vitamin A in skin care products is a skin rejuvenating ingredient that improves the skin’s surface and its underlying structure. It stimulates the healthy division of skin cells and the production of collagen and elastin. Vitamin A also inhibits the enzymes that break down collagen and elastin and may increase the lifespan of dermal fibroblasts, which are marvellous little factories in the skin that make connective tissue and enable repair.

Our skin comprises three layers: epidermis, dermis and hypodermis. The dermis is made up of connective tissues and is responsible for temperature regulation and supply of nutrients to the epidermis. Fibroblasts secrete collagen and elastin, which are what provide the skin with support, density and elasticity.

Tretinoin is a Retinoic Acid that delivers on a long list of benefits, and this is why it’s so popular. What’s more, it’s been extensively researched and widely used since 1969.

Dermatologists recognise the effectiveness of Tretinoin, and other prescription retinoids, and use them in their practices. Research has shown that they can benefit a wide range of skin conditions. These include:

Retinoids are hero ingredients because of their established pedigree in improving skin. There’s a significant body of quality research that has been collected over decades to back up their standing, however most of the research done on retinoids has involved prescription retinoids and Retinol, rather than the newer forms that have come onto the market. Despite manufacturer claims for these newer retinoids, they don’t as yet have robust scientific evidence behind them.

How do retinoids work?

How do retinoids improve so many different skin conditions, ranging from acne to acne scarring, wrinkles to skin tone, sun damage to visible pores, rough texture to sagging skin?

One, there are retinoic acid and retinoid receptors in the skin, and so retinoids can communicate with cells, signalling to them how to behave ‘correctly’. Through this remarkable messaging, they’re able to tell skin cells in the lower levels of the skin to develop normally rather than in an abnormal or damaged way.

Two, retinoids speed up the process of skin cells regenerating and replicating. This process slows down as we get older and our skin doesn’t produce fresher, healthier skin cells in the way it did when we were young. The stimulation of epidermal growth factor leads to increased shedding of skin cells at the surface and eventually a thickening of the epidermis. This improved turnover of skin cells helps to exfoliate and disperse skin cells with melanin at the surface, but it doesn’t affect melanin or the cells that produce this pigment, melanocytes, which are found in the lower level of the skin.

Three, retinoids are able to inhibit several inflammatory pathways that are activated in the case of acne, and the reason why they’re prescribed by dermatologists. The American Academy of Dermatology considers retinoids a core therapy for acne for the reasons already described, namely  they help clear blocked pores, prevent new baby blemishes (microcomedones) forming and reduce associated inflammation. They’re also useful in maintaining clear skin following a successful acne treatment program.

What are the main retinoids?

There are four generations of retinoids. The first generation includes the well-known Retinol, Retinaldehyde, Tretinoin and Isotretinoin. The second generation includes Etretinate and its metabolite Acitretin, which are used to treat severe psoriasis. Adapalene and Tazarotene are third generation and are most commonly used for acne. Fourth generation is Trifarotene, which has shown promise in trials in reducing inflammation and hyperpigmentation.

Prescription retinoids

Non-prescription retinoids

Prescription retinoids

Prescription retinoids come in five different forms: Isotretinoin, Tretinoin, Adapalene, Tazarotene and Trifarotene. Tretinoin is also known as Retinoic Acid, the biologically active ingredient. Retinoic Acid does not need to undergo conversion in the body and so is immediately available to the skin. Because of this, it is also more potent than over-the-counter retinoids.

Isotretinoin: Isotretinoin (Roaccutane) is a prescription oral Vitamin A derivative that has the greatest activity due to it being ingested. Its use is reserved for severe forms of acne, cystic acne and acne scarring.

Isotretinoin is the only acne medication that targets all four causes of acne: excess sebum, clogged pores, high levels of P. acnes bacteria and inflammation.

Due to its side effects, patients taking this daily medication need to be closely monitored by their doctor or dermatologist. These side effects may include dry lips, increased photosensitivity, muscle aches and pains, headaches and possibly depression.

Patients who successfully complete this course of treatment, which lasts 4-5 months, find they’re free of acne for a prolonged period or even for life.

Tretinoin: Tretinoin is also a prescription retinoid, but unlike Isotretinoin it’s a topical product. Tretinoin is used to treat acne and sun-damaged skin. As already mentioned, Tretinoin is a high-strength retinoid because it comes as Retinoic Acid, which means it doesn’t need to be converted in the skin. The retinoic acid receptors in the skin can therefore readily take up Retinoic Acid.

Retinoic Acid plays a role in cell growth, stimulates collagen and elastin production, and improves hyperpigmentation and discoloration. Most over-the-counter retinoids, however need to be converted to Retinoic Acid through a biological process in the skin before they can deliver their benefits.

Tretinoin is typically used by dermatologists to treat acne, ageing skin, sun-damaged skin and stretch marks, and ranges in strength from 0.025% to 0.1%. At the lowest strengths, Tretinoin is used for its anti-ageing properties, while at the highest strengths it’s used for acne.

Given its proven ability to also improve fine wrinkling, hyperpigmentation, pores and sagging skin, many people use Tretinoin as part of an anti-ageing skin care routine.

A study  in the Journal of Cosmetic Dermatology in 2015 showed that Tretinoin is remarkable for being able to block the production of collagenase, an enzyme that breaks down collagen in our skin.

Collagen is what gives skin its firmness and elastin is what gives skin its elasticity and rebound. Glycosaminoglycans are another component of youthful skin and they keep our skin hydrated. All of these get depleted as we get older. Interestingly, or rather sadly, our production of collagen reduces at a rate of about 1% a year from the age of 20.

The abundant collagen we have when we’re young is what makes our skin look nicely plump and firm.

Tretinoin can cause redness, burning, dryness, itching and peeling until the skin adjusts and becomes acclimatised. For some people, the side effects are too great and they’re unable to use it.

Adapalene: Adapalene is a topical synthetic retinoid that works similarly to Tretinoin. It selectively binds to retinoic acid receptors and is primarily used to treat acne.

Adapalene is more chemically stable than Tretinoin and can be used at a higher concentration with fewer side effects. A 0.1% concentration of Adapalene has been found to be as effective as a 0.025% concentration of Tretinoin.

Adapalene causes less irritation or dermatitis  than its cousins Tretinoin and Tazarotene. This is largely due to its direct anti-inflammatory properties, and therefore it may be tolerated by those with more sensitive skin. However its absorption through the skin is lower.

Due to Adapalene’s high effectiveness in treating acne and lower levels of reactions, Adapalene 0.1% is now available over the counter in a number of countries as Differin. Adapalene is also available at higher strengths, up to 0.3%, by prescription to treat mild to moderate acne.

Adapalene, however, does not increase the number of skin cells in the epidermis and therefore it’s not used to treat sun-damaged skin.

Tazarotene: Tazarotene is synthetic retinoid used to treat acne, psoriasis and sun-damaged skin, and works in a similar way to Tretinoin. Tazarotene also improves fine wrinkles, skin texture, hyperpigmentation and dilated pores.

Tazarotene has been shown to be more effective than Tretinoin for acne, although more irritating. When compared with Adapalene, it appears to be at least comparable, if not more effective, however it causes more burning, itching, dryness and peeling than Adapalene.

Tazarotene comes in concentrations of 0.05% or 0.1%. This potent retinoid is used in lower strengths  for acne and higher treat for psoriasis. In effectiveness, it’s compared with Tretinoin 0.5% cream.

Non-prescription retinoids

When it comes to over-the-counter retinoids, you’ll find the following retinoids used in skin care products:

Hydroxypinacolone Retinoate: Hydroxypinacolone Retinoate is a mild retinoid. One of the newest forms of Vitamin A, it can attach itself directly to the retinoid receptors in the skin, just like Tretinoin. It’s directly related to Retinoic Acid and so doesn’t need to be converted in the skin, which in theory means it can pack a punch.

Remarkably, Hydroxypinacolone Retinoate’s molecular structure makes it much less irritating and more stable than Retinol, or at least according to the manufacturer.

There’s no solid independent research to verify that it’s similarly effective to Retinoic Acid, or that it can equally stimulate collagen, prevent the breaking down of elastin and collagen, or improve sun damage.

A lab study by a global skin care brand found Hydroxypinacolone to be more effective than Retinol, but not as effective as Tretinoin.

In its favour is that Hydroxypinacolone Retinoate is more stable than Retinol, and it’s claimed you can use it at higher concentrations without the usual side effects, but again this needs to be verified.

You may be more familiar with its brand name, Granactive Retinoid.

Retinyl Retinoate: Retinyl Retinoate is another new retinoid. This synthetic retinoid is created by attaching Retinol to Retinoic Acid to make it more active and more stable.

Retinyl Retinoate has to be converted in the skin, but interestingly this happens in two distinct steps. It gets broken down to become Retinoic Acid and Retinol, which slows down the conversion.

The Korean company that invented this ingredient undertook respectable studies showing that Retinyl Retinoate has better anti-ageing effects than Retinol. However it‘s not up there with Tretinoin when it comes to stimulating collagen production and preventing its degradation. Despite having higher activity than Retinol, Retinyl Retinoate is no more irritating.

As for its effects on acne, Retinyl Retinoate also holds promise. It appears to reduce sebum, lessen inflammatory and non-inflammatory blemishes and have some activity against P. acnes bacteria.

One study also found Retinyl Retinoate to be better at stimulating Hyaluronic Acid production than other retinoids.

Unfortunately, there really isn’t enough research yet to confirm that this retinoid is a better alternative to Retinol.

Retinaldehyde: Retinaldehyde, or Retinal, has the advantage of being able to be directly converted to Retinoic Acid in the skin, making it more active than Retinol or retinol esters. Like other newer forms of retinoids, this ingredient hasn’t been around long enough to have a body of research behind it.

The manufacturer claims that Retinaldehyde can deliver its anti-ageing benefits up to 11 times faster than Retinol, while at the same time being less irritating.

Two studies on people found that 0.5% Retinaldehyde was comparable to 0.05% Tretinoin, but with less side effects. Interestingly, though, Retinaldehyde was found to be more effective when Glycolic Acid was also part of one’s skin care routine.

And while Retinaldehyde is more stable than Retinol, it’s still subject to oxidisation.

Retinaldehyde may be helpful for those with acne who find the side effects of prescription retinoids too much.

You won’t find Retinaldehyde in a lot of skin care products due to its higher cost and limited research. And of the brands that do use it, they typically don’t declare what percentage they’re using either, so it’s hard to directly compare it with a product with a declared percentage of Retinol.

Retinol: Retinol is a tried and true retinoid that has been friend to many.

Retinol is the purest form of Vitamin A and is widely found in skin care formulations. It has a long record of use in improving the most common signs of skin ageing. Retinol is far less potent than prescription retinoids as it requires two conversion steps, but it can still accelerate cell turnover, boost collagen production, smooth wrinkles and even out skin tone.

Research confirming Retinol’s anti-ageing effects involved using concentrations of 0.4-1%, higher than is found in many skin care products.

A study published in the Journal of Cosmetic Dermatology found a 0.1% retinol formulation reduced the appearance of wrinkles by 63.74% on the cheeks and 38.74% on the eye area after 12 weeks of use. And a  study on actual people published in The Journal of Investigative Dermatology observed a thickening of the epidermis and minimal signs of redness and irritation with the use of Retinol.

Studies by Fisher and colleagues in 1996 and 1997 demonstrated that Retinol inhibits damage caused by UV rays and stimulates collagen production in photo-aged skin.

Retinol is 20 times more potent than Retinyl Palmitate but 20 times less potent than Tretinoin.

Skin care manufacturers have extensive experience and expertise in formulating with this ingredient. Better brands will use Retinol that releases slowly and combine it with soothing ingredients so as to minimise irritation. You can find it in many serums, targeted treatments and moisturisers.

Retinol is affected by air, heat and light, and these degrade its effectiveness. Retinol also can oxidise and become pro-ageing. Look for a quality brand that uses microencapsulated technology and airless packaging.

As with other retinoids, only apply it at night.

Retinol is one of our Hero Ingredients and you can read more about it on our Skin Intelligence pages.

Retinyl esters: Retinyl esters are most stable over-the-counter retinoids, but also the weakest. They need to undergo three conversion steps to become Retinoic Acid in the skin.
First, they need to convert to Retinol, second to Retinaldehyde and third to Retinoic Acid. It’s not known how effectively this process occurs in the body and how much of the original concentration actually gets converted. We do know that each conversion steps weakens the concentration.

Despite this, retinyl esters have the advantage of being less irritating and easier to combine with other active ingredients.

A little more about each of the retinyl esters:

Retinyl Propionate: Retinyl Propionate is a retinol ester that combines Retinol and Propionic Acid molecules.
Like other retinol esters, it needs to be converted three times for it to be available for use by the skin. This very much weakens its effectiveness.

Even so, it’s more effective than Retinyl Palmitate because it can penetrate the skin more easily, likely due to its molecular size.

For people with sensitive skin, or those who find more potent retinoids too aggressive, retinyl esters such as Retinyl Propionate may be a good choice.

There is little research on this ingredient. An independent human study (1998!) did not find it made a noticeable difference to wrinkles, but did help with acne.

The scientist who came up with Retinyl Propionate claimed in the patent application that it has the advantage over Retinyl Palmitate because its “molecular weight and configuration” allow it to remain in a stable solution and be delivered transdermally to a site where it’s active.

An independent study in 2007 found Retinyl Propionate to be as effective as Retinol in reducing the appearance of wrinkles and hyperpigmentation, while one in 1998 did not uncover any differences between it and the placebo, other than on actinic keratoses – but that was after 48 weeks.

Retinyl Acetate: Retinyl Acetate is another ester of Retinol, a preformed source of vitamin A. Like other retinol esters, it is a milder form of Vitamin A. It’s better tolerated by the skin than retinol.

Retinyl Acetate is more stable and more bioavailable than other forms, but Retinyl Acetate is still sensitive to air, heat and light. It’s a form of Vitamin A that gets stored in the liver.

Retinyl Acetate supports collagen synthesis and reduces in the appearance of fine lines and wrinkles. Additionally, it can help clear sebum and reduce pore congestion.

It’s not seen often in skin care products, but it does make an appearance now and then.

Retinyl Linoleate: Retinyl Linoleate is an ester of Retinol combined with Linoleic Acid – an unsaturated omega-6 fatty acid found in corn, safflower and sunflower oils. Again there is little research on it and you won’t see it too often on skin care ingredient lists, unlike its super popular cousin Retinyl Palmitate.

Retinyl Palmitate: Retinyl Palmitate is one of the weakest and therefore gentlest retinoids. It’s an ester of Retinol that is combined with Palmitic Acid, a saturated fatty acid derived from the ubiquitous but  environmentally unfriendly palm oil.

Even though Retinyl Palmitate is an earlier form of Retinol, it doesn’t deliver the same effects. It has a high molecular weight so it doesn’t penetrate easily. But despite this, there’s some weak evidence to indicate that Retinyl Palmitate boosts collagen production in the skin. A study in 2014 found that the application of Retinyl Palmitate to the skin of rats for 14 days resulted in increased protein and collagen, and a thickening of the epidermis.

Retinol is the purest form of Vitamin A and about 20% more potent than Retinyl Palmitate. Retinyl Palmitate must be converted three times to be available to the skin. First into Retinol, second into Retinaldehyde and third into Retinoic Acid.

Sunlight rapidly reduces the efficacy of Retinyl Palmitate, and it may cause damaging free radicals in the skin. Retinyl Palmitate used to be added to many sunscreens and SPF moisturisers. However there are ongoing health concerns in the US, Germany and Norway about the use of Retinyl Palmitate and other retinoids in skin care products used during the day. The US Environmental Working Group recommends “consumers avoid sunscreens and other skin and lip products containing vitamin A, retinyl palmitate, retinol, retinyl acetate, retinyl linoleate and retinoic acid”.

Nonetheless Retinyl Palmitate is more stable and resistant to heat than Retinol, and one of the reasons it’s widely used. But it too has a limited ‘fresh’ shelf life.

Remember to only apply products with Retinyl Palmitate at night.

Plant alternatives: Some plant ingredients are making it into skin care products as phyto-retinoids. They’re claimed to mimic the effects of over-the-counter retinoids. Bakuchiol, an extract of the babchi plant, is one that is increasingly being used, and with good reason. It’s the only plant ingredient that has some research behind it showing that it has a retinoid-like effect when it comes to wrinkles and hyperpigmentation. What’s more, Bakuchiol is less irritating than traditional retinoids.

If you don’t like to use harsh ingredients on your skin, or prefer to go the natural route, this may be worth a try … just don’t expect anything dramatic!

Retinoid conversion steps

Conversion Steps
Hydroxypinacolone RetinoateMedium0
Retinyl RetinoateMedium1
Retinyl ProprionateLowest3
Retinyl LinoleateLowest3
Retinyl PalmitateLowest3

Are retinoids better than Retinol?

Well, not necessarily. Prescription retinoids are certainly stronger than over-the-counter retinoids, but they also have more side effects. All retinoids are derivatives of Vitamin A, however they are differences in strength and the conversion steps required to become Retinoic Acid.

Retinol works more slowly and in some cases that’s preferred. For example, it may work better for someone with sensitive skin or someone who is young and really doesn’t need to be using potent  retinoids.

There’s some debate currently around starting prescription retinoids too early and whether this can be harmful to the skin over the longer term. Indeed, there are cases of people who’ve developed highly sensitised and intolerant skin are being on prescription retinoids for a long period.

Leading UK dermatologist Dr Mervyn Patterson has sounded the alarm on retinoids saying they’re being overused. He’s quoted in a prominent article saying that skin care companies have lost sight of what’s good for the skin and are leading consumers down the path of massive experimentation.

Dr Patterson says that, when retinoids are overused, skin cells cannot function properly because they’ve been rapidly produced and lack the necessary adhesion and lipid production to protect the skin properly. And this affects the skin’s ability to perform its barrier function.

So, too much of a good thing may be a bad thing for your skin and health.

What’s the best product?

How often do I hear this question!

So many factors come into play: your age, skin type, skin concerns and, of course, the strength, type and formulation.

Your can find off-the-shelf products in different strengths, such as 0.1, 0.25, 0.3, 0.5 and 1%. The better brands will tell you the strength It’s always best to start with the lowest concentration and introduce it gradually, until your skin can tolerate the product more frequently.

But that alone isn’t enough. You need to look beyond just the percentage. The formulation and the delivery system are just as important. And that’s why we follow the research and extensively test the products we choose for their results. We also look for encapsulation of Retinal and Retinol and for as few other irritants in the product as possible. Retinoids are irritating enough on their own, so you don’t want other ingredients that are going to mess with your skin. There are also other important factors to consider, such as stabilisation and packaging. You can read How to Use Retinoids … Like a Pro to find out more about why these matter and how to get the most out of them.

Personal preferences also come into play, however here is a starting point for you to make selection easier:

Medik8 Crystal Retinal 3 and Medik8 Crystal Retinal 6

Pestle & Mortar Superstar Retinoid Night Oil

BioBare Skin Revivify Encapsulated 0.5% Retinol Cream

Medik8 Bakuchiol Peptides

Who can benefit from retinoids?

Retinoids are used for many skin conditions, including in medical practice. They have a wide range of uses, but that doesn’t mean they should be used by everyone. If you want to use retinoids, ensure you understand the benefits and risks.

Anyone with a skin condition or medical condition that could be affected by the use of a Vitamin A derivative should consult a health professional first.

Retinoids have been found to be potentially helpful for those with:

Who shouldn’t use them?

There’s little clinical data on the safety of retinoids during pregnancy. Some studies indicate that high concentrations of Vitamin A can harm the foetus and cause birth defects, especially when taken orally. As a precaution, it’s recommended that no retinoids are used during pregnancy or breast-feeding, or when trying to conceive. Look for safer alternatives, such as Bakuchiol, Glycolic Acid, Latic Acid, Peptides and Vitamin C.

If you have a skin condition such as acne, psoriasis or rosacea, don’t jump straight in! Talk to a professional to make sure retinoids are right for you.

Now that you’re the full bottle on What are Retinoids? you can find out How to Use Retinoids … Like a Pro and get our top tips in part 2 of our blog article.

Yours truly in better skin

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