Retinoid: Everything You Need to Know

Let’s explore everything that you need to know about retinoids.

What are retinoids?

Retinoids are derivatives of Vitamin A. They are found in vegetables such as carrots, egg yolk and liver. The concentrations found in natural sources are usually not sufficient for therapeutic purposes. The synthetic forms of retinoids were first used in dermatology in 1943 for acne treatment. Since then we have discovered many other benefits of retinoids on the skin!

What are retinoids used for?

Retinoids are used for so many dermatological conditions that you’ve probably not heard of!

Common aesthetic uses

• Acne vulgaris
• Photoaging
• Aging
• Superficial hyperpigmentation
• Oily skin, milia

Uncommon uses

• Warts
• Severe psoriasis
• Rosacea
• Slow down progress of certain skin cancers
• Keratosis pilaris (inflammation of hair follicles)
• Callus

Why are some retinoids prescription medications in Singapore while others aren’t?

Topical retinoids creams such as differin and epiduo are available OTC in Singapore in 2016 in limited strengths not exceeding 0.1% retinoids. Many cosmetic brands and overseas sellers may sell ‘higher’ strength retinoids via online sellers.

At this point you may be very confused now when you see that some OTC creams carrying retinol over 0.1%. This is because Retinols are much (~100x) weaker forms of the active retinoids. Retinol requires more steps to be converted to the active form of retinoic acid before it can act on the skin hence less active retinoic acid is available and they tend to take a longer time for results to show.

What are the differences between retinoids?

There have been 3 generations of retinoids since the 1980s. There are many ways that it has been modified to minimise irritation to the skin, and improving its effects by adjusting the chemical properties of each retinoid. However, the first generation retinoid such as Retin-A and retinol are still commonly used today.

First generation include retinol, retinal, tretinoin (retinoic acid), isotretinoin (Roaccutane)

Second generation include etretinate and its metabolite acitretin

Third generation include Differin (adapalene), bexarotene, and tazarotene

The difference in the ‘newer’ generation is the increased stability of the retinoids – this means that they are less affected by external factors like sun exposure, and when used in combination with other creams. Third generation differin has better skin retention and lower absorption translating to more targeted action on the skin.

How do retinoids work?

In general, retinoids increase the skin cell turnover and by doing so new, healthy skin cells are produced.

Antiaging

• Prevents sun-related ageing, celled photoaging.
• In patients who applied retinoids regularly, there is less collagenase (the enzyme that breaks down collagen and causes aging) after UV exposure
• Regular application increases collagen production and thickens the dermis, minimising appearance of wrinkles

Acne

• Prevents a build up of comedones by increased cell renewal
• Regulates sebum/oil production evident in the reduction in sebaceous gland size and secretion, resulting in less blackheads/white heads and minimized pores
• Retinoids display antibacterial properties, which prevents bacterial infection of a comedone turning into a pimple/cystic acne

Hyperpigmentation/Melasma

• Increased cell turnover disrupts the deposition of melanin after they are produced
• Reduce the amount of tyrosinase, an enzyme responsible for pigment production, produced in the skin
• Breakdown melanin
• Increase absorption and efficacy of other skin lightening ingredients when used together

Retinoids work and they really do! Its proven right down to the molecular levels. It is one of the most well researched ingredients over the last six decades and we haven’t quite found any other compound that can replace it. It is unbelievable given how much we science has progressed over this time.

What are the side effects of retinoids?

There are some common side effects that most people will experience. They include

• Skin peeling
• Redness
• Skin irritation
• Skin dryness
• Sun sensitivity
• Dry eyes, lips and mouth

These common side effects are generally very well tolerated and resolve when the medication is stopped.

There are other uncommon, but serious side effects, termed as retinoid toxicity, which are more relevant to oral isotretinoins, where the medication is absorbed into the body system.

• Hair loss
• Liver damage
• Risk of fetal malformation

In general, retinoids are very safe and it is widely used. The risk of serious side effects is very low as they require prescription and regular monitoring by a licensed doctor. 

If you are planning for pregnancy, pregnant or lactating, the general consensus is to avoid ALL forms of retinoids as Vitamin A is a lipid-soluble compound which can be absorbed via the skin into the body, affecting the developing fetus/baby.

When should I start using retinoids?

There really isn’t an age limit. As retinoids treat various skin issues, they can be used to treat teenage acne and all the way to treating deep wrinkles at 100 years old! You can start using it as an anti-aging treatment as a maintenance skincare regime in your 20s. There is no need for a clear indication to start on topical retinoids.

Starting on oral retinoids, on the other hand needs a stronger indication, as the risk and side effects tend to be more severe. It should be reserved for acne that is refractory to topical treatments and oral antibiotics or for cases of severe psoriasis. Oral retinoids are not usually prescribed for softer indications like anti-aging.

I have sensitive skin. Can I still use retinoids?

Yes! However do take extra care. My suggestion is

• Build your skin up by using lower dosages or milder forms of retinoids such as retinols first.
• Be wary of the amount that you apply. Start by applying small, pea-sized amounts for the entire face.
• Apply every other night for 2 weeks, and start to apply every night if no adverse side effects develop. If mild irritation occurs, consult your doctor to discuss if this should be stopped completely or continued in the current regime.
• Ensure that your skin is completely dry before applying as wet skin encourages faster absorption.
• Use a (richer) moisturiser after application to reduce irritation and dryness.
• Apply sunscreen to avoid sun sensitivity.
• Do not combine retinoids with other acidic products or strong exfoliants as they can cause more skin irritation.

Sensitive skin is not a contraindication to starting retinoids. Many of our patients with sensitive skin love Alpha-ret! Choosing the correct formulation is important too!

I’d recommend alpha-ret to our ‘sensitive skin’ patients as it is designed for sensitive skin. The two gold standard ingredients AHA (alpha hydroxy acid) and retinoid are bonded together, which is only activated when they are hydrolysed in the skin. This enzymatic reaction limits the rate of release of the active retinoic acid, thereby reducing risks of irritation. Retinoids increase cell turnover and work on the deeper layers of the skin, while AHA exfoliates from the top layers of the skin to allow better penetration.

Why do some retinoid products recommend night time application, while others don’t?

Retinoic acids are damaged by sunlight. I.e. They will be less effective. Therefore most retinoid containing products are kept in opaque and preferably air tight containers to preserve the integrity of the active components. Generally, nighttime application is preferred.

With the exception of third generation retinoids, Differin, which are designed to be highly stable, it is recommended for a day and night application.

‘Encapsulated’ retinol is also a technique to house the ‘unstable’ first generation retinol in a carrier system to protect the integrity of the retinoic acid and improve the penetration into the skin. They are less affected by sunlight.

What should I do if I experience side effects with retinoids?

It is common to experience some peeling and mild redness, in most cases, you can continue to use the retinoids. If the irritation gets increasingly unbearable, stop the retinoids immediately. Applying moisturizer and sunblock, the skin should ‘calm down’ in a week. Use only hypoallergenic moisturisers and avoid chemical sunblock. This is usually sufficient.

For any other complications, e.g. worsening of acne, extreme itchiness, or unusual side effects, please seek medical attention.

What are some skincare products that you should avoid when you are using retinoids?

Do not use different types of retinoid containing products i.e applying differin on top of retinol. This increases the risk of skin irritation. It is also not advisable to be using exfoliating agents like Benzoyl peroxide and peels as they can cause excessive irritation and deactivate certain retinoids such as tretinoin by altering the pH. Vitamin C and retinols seems like the perfect combination but they do not work as well together as the optimal pH is not the same for each ingredient.

Why are retinoids not safe for pregnancy?

Although we have mentioned this before, it is important that you FULLY understand this if you are a woman of child-bearing age using this product or if you are THINKING of passing your unfinished stocks to your friend. When we say you CANNOT get pregnant while you are on oral retinoids, that doesn’t mean that it doubles up as a contraceptive. What we mean is you really cannot afford to be pregnant.

Oral retinoids e.g. Roaccutane is classified as Category D drugs with definite evidence of causing harm to a developing fetus. These potential malformations are usually severe and can be fetal. Despite best efforts, pregnancy still occurs and patients often find it difficult to decide if they should pursue a termination of pregnancy. Even doctors find it difficult to give the ‘correct’ advice. Termination of pregnancy is often regarded as the ‘safer’ option and a study showed that up to 84% of women exposed to oral retinoid chose to undergo a termination of pregnancy.

Topical Retin-A is classified by the FDA as a Category C drug – i.e. the use by a pregnant woman has not been extensively studied to be proven safe. For this reason, it is not generally not recommended. Realistically, the absorption of retinoic acid into the body is rather minimal and if you have been using it before you discover that you are pregnant, there is a high chance that your baby will be ok.   

This dilemma is totally avoidable and unnecessary. It has been suggested that the safe levels of retinoic acid are achieved as early as 2 weeks and it has been suggested by RCOG that effective contraception should be continued for at least one month after cessation of retinoid. The risk of congenital malformations returns to normal after retinoids are intentionally stopped before conception.

Do retinoids thin my skin?

In contrary to popular belief, retinoids DO NOT actually thin the skin. It actually does the reverse. Some people have the misconception that the peeling of the skin leads to thinning of the skin. However, the peeling is a result of increased skin cell turnover and production, increasing collagen and thickening the dermis, which plumps up the skin! However, retinoids can in certain circumstances thin out the skin if it is overused at the strengths too strong for skin, or noncompliance to the use of sunblock resulting in sunburns.

Should I go for the strongest retinoid available so that I can get the best results?

It is true that prescription products and stronger products can potentially achieve better results. However, a more aggressive treatment usually comes with increased risk of developing irritation to the skin. It is best that you start at a lower strength retinoid and slowly build up to the higher recommended strengths for your skin concerns. Jumping straight into the strongest strength products usually leads to discontinuation of use due unbearable skin irritation and the misconception that ‘my skin is not suitable for retinoids’. You may also cause more harm than good to your skin. You should discuss with your doctor your skin care regime and your lifestyle so that he can prescribe you the dose that you require in a preparation that suits your skin best.

Will retinoids worsen my acne?

There is a small risk of “purging”.

First, let us look at how a pimple usually forms and you will understand why things have gone in the wrong direction.

First a pore becomes clogged by dead skin or excessive sebum. These clogged pores, comedones can present as a whitehead and blackhead and eventually go away on their own without any issues. However, bacteria infection can trigger an inflammation response to this clogged pore, and manifests as a pimple or even a cystic acne!

What retinoids did is called ‘purging’. You should be warned before you start on topical retinoids that this could happen and this is the intended purpose of retinoids. Retinoids increase the skin turn over, hence the entire cycle is expedited. For example, if you would normally develop 10 pimples in a month at different times, using retinoids may cause them to surface all at once resulting in a worsened appearance! But fret not, purging a common process before your skin clears out. If you’ve persisted with the product for more than six weeks and you are still not back on track, you should definitely return to the doctor! Your progress should be monitored as retinoids come in different preparations and occasionally retinoids can cause irritation and more inflammation.     

Are retinoids suitable for people with darker skin tone?

People with darker skin tone are at higher risk of developing post-inflammatory hyperpigmentation. The risk of having PIH from the use of retinoids is minimal. In fact, retinoids are the first line agents that should be considered to treat PIH and sun spots and proven to be safe and effective for dark skinned individuals.