Retinoid for fighting pigmentation, acne and ageing skin.

As part of the series for active ingredients for pigmentation and as a continuation to my blog post on “vitamins and skin”, let’s dive in the details of another vitamin, that is – Vitamin A, also known as Retinoid.

Retinoid was a term first used to describe the active form of vitamin A. It comes in two forms: trans retinoic acid (tretinoin) and cis retinoic acid (isotretinoin), depending on the molecule groups orientation. The prefixes “cis” and “trans” are Latin for: “this side of” and “the other side of”.

fig. molecule’s bonding and geometry for Tretinoin (left) and Isotretinoin (right).

Today retinoid is used as an umbrella term to encompass all derivatives of viatmin A such as retinoic acid, retinol, retinal esters, retinaldehyde.

Vitamin A and its derivative

The order of activity of a topical retinoid

The order of activity of a topical retinoid is as follows:

In others words retinoic acid is highly effective while retinol esters are least reactive. The irritant potential however is reverse, retinol esters causes the minimum irritation while retinoic acid causes maximum irritation.

How Vitamin A works on the skin?

Vitamin A derivative found in our skin are retinol and retinyl esters. These are then converted to retinoic acid, the biologically active form, by certain enzymes. Retinoic acid binds to receptors present inside the nucleus (center) of our skin cells to mediate various biological effects.

It regulates the cell turnover: As the cells in our skin divide and move from the basal layer to the uppermost layer as dead cells (the stratum corneum) and are shed off, there are various changes that can take place, such as changes in the shape and composition of the cells. This entire process is call “keratinisation” or in simple words “cell turn over” which takes approximately 28-30 days. Retinoids help regulates and makes sure this process is occurring normally. This is particularly useful for acne, where the follicular keratinisation (the cell lining inside of a hair follicle) is abnormal. Check out my previous blog post on to see how acne develops: “How to deal with truncal acne?”.

fig. Layers of the epidermis (superficial most layer of skin)

It also affects the growth and differentiation of cells: it increases the activity of cells responsible for production of collagen, and causes an increase in the thickness of the epidermis.

Retinoids also increase production of extracellular matrix and prevent its degradation by UV rays. Extracellular matrix are carbohydrate molecules present in the dermis which act as a cushion in which blood vessels, collagen and elastin are embedded and is responsible for the suppleness of our skin.

Anti-inflammatory: Thus helps prevent the development of inflammatory (red, painful) acne.

Reduction in pigmentation: Retinoid inhibits tyrosinase – an enzyme required for melanin production (pigment responsible for our skin colour) and due to the increase cell turnover it reduces the transfer of melanin to the keratinocytes. †

The expected results with retnoid

The overall clinical effects of topical retinoid are:

  • It prevents formation of comedones (white heads, black heads), reduces the number of breakouts. Retinoids are the topical medication for choice for non inflammatory comedonal acne.
  • Helps reduce fine lines, and can reverse changes seen with chronic unprotected sun exposure (photoaging).
  • Retinoids can help improve the appearance of pores, and provides a smooth texture with a youthful appearance to the skin.
  • Retinoid in the form of retinoic acid (tretinoin) is used in combination with hydroquinone (depigmenting agent) and mild steroid called “triple combination” to decrease pigmentation and evens out skin tone. This combination has been the standard first line treatment by dermatologists for pigmentary disorders such as melasma, post inflammatory pigmentation (dark spots following conditions such as acne, or various forms of dermatitis). Another combination using 10% retinol + 7% lactic acid has shown to be equally effective to reduce pigmentation.
  • Therefore, retinoids in various forms are used for the management of acne and as an anti ageing ingredient.

Commercially available retinoids

1. Retinoic acid

The biologically active retinoid, retinoic acid is available as tretinion. It comes in three strengths : 0.025%, 0.05% and 0.1% formulated in a cream base. There is also a microsphere gel base in the strength 0.04% and 0.1%.

Image credit: dr viggiano.

2. Adapalene

Adapalene is a synthetic retinoid similar to all trans retinoic acid tretinoin. It is available as a 0.1% gel, cream or solution and as a 0.3% gel for the treatment of acne. Adapalene (Differein) can be bought at the pharmacy without a prescription. It is now available as a combination with benzoyl peroxide (Deriva BPO gel, Epiduo gel) or with clindamycin (ClearApgel, Deriva CMS gel) as well.

3. Retinaldehyde

Retinaldehyde is the immediate precursor of the active form of Vitamin A-retinoic acid. Retinaldehyde in 0.05% and 0.1% concentration used twice daily for 12 weeks have been shown to be effective in treating photodamaged skin (rough, dry skin with fine or coarse wrinkling) and pigmentation. After application, retinaldehyde needs to be converted in the skin to retinoic acid by certain enzymes. This prevents the over saturation of our skin with retinoic acid and thus is better tolerated with fewer side effects. However the expected results can be slower than with retinoic acid.

3. Retinols

Many over the counter anti ageing, and pigmentation cream contain various concetration of retinols (0.3%, 0.5%, 0.1%) as the active ingredient. As you can see from the above image on vitamin A & its derivative, retinol needs to be converted to retinaldehyde which is in turn converted to retinoic acid. Retinol is 20 times less potent than retinoic acid (tretinoin) but the bears the advantage of less side effects. But retinol is highly unstable and gets degraded easily to inactive forms therefore the choice of the vehicle is of utmost importance for this ingredient. This neutrogena does not mention the concentration of retinol but from what I found online, its probably a lower concentration of 0.025%, which is great if you’re just starting with a retiniod.

Side effects of topical retinoids and how to combat it

Over saturation of our skin with retinoic acid can irritate our skin. Therefore the side effects are mostly seen with topical retinoic acid such as tretinoin. For this reason and because retinoic acid has biological effect when applied on the skin, it is considered a drug and requires a doctor’s prescription. Such regulations are not followed in India, and one can buy almost anything over the counter here, but I strongly discourage using retinoic acid as part of your skin care regimen without a prior dermatological evaluation or without supervision from your prescribing doctor.

During the first few weeks of topical application of a retinoid, redness, flaking of the skin, acne flare, photosensitivity are expected. This can be minimised by starting with the lowest concentration of retinoid, or by limiting the amount and the frequency of application.

It is advised to start with either twice in a week application, or alternate days application once at night for the entire face and never in the morning. The frequency and strength can be increase according to our skin’s tolerance to the product. Moisturisers and sunscreens are a must while using a retinoid.

Retinaldehyde and retinols have fewer chances of causing this irritation and are the best bet if one wants to start using a retinoid in their skin care and for someone with sensitive skin.

Retinoic acid such as tretinoin being more irritant should be avoided for someone with dry, sensitive skin or someone with skin conditions such as Rosacea.

Retinoids should not be used during pregnancy.

Interested in a vegan option?

Retinol, retinaldeyde and retinoic acid are animal derived forms of vitamin A while beta carotene is derived from plant and fruits. Beta carotene can be converted to retinal esters and retinaldehyde in our body which are then converted to the active form retinoic acid.

A study done to assess the effectiveness of beta carotene based cream with a sunscreen for melasma patients showed that beta carotene helped to gradually reduce the pigmentation in patients over a 16-24 weeks time. Beta carotene is also an anti oxidant that can help as an anti ageing ingredient by reducing oxidative stress.

Ecco bella natural age antidote day cream contains beta carotene along with titanium dioxide (physical sunscreen), vitamin C and vitamin E as active ingredients.

Is oral supplementation even better?

I’ve highlighted in my previous blog posts on oral vitamin supplementation and its indication. Studies have shown that oral supplementation with 30mg/day of beta carotene for 90 days can improve the appearance of wrinkles and elasticity of the skin. Thus stemmed the phrase:

A carrot a day keeps the wrinkles away

However a carrot can only provide a maximum of 6 mg of beta carotene. So if you want to duplicate the results of this study, you’ll need at least 6 large carrots a day.

Since long term study on the effect of vitamin A supplementation on our body as a whole has not been carried out, the potentials dangers that may result from toxicity of vitamin A has not been ruled out yet. Till we know more about the the benefits and risks of oral intake of vitamin A (beta carotene supplements), its best to avoid oral supplementation and stick to what we know, which is topical sunscreens and topical retinoids to fight signs of ageing and pigmentation.

It is important to note that, scientific research on the role of an active ingredient for pigmentation or ageing are performed over weeks with a minimum of 12 weeks before any conclusion can be drawn from the studies.

Therefore, always use a product for at least 12 weeks before you decide to conclude that the product is not working and move on to the next best thing.