Retinol or Vitamin A?

Chemically speaking Retinol is a monocyclic (one ring structure) unsaturated (containing double bonds) primary diterpene alcohol. Its structure is responsible for its biological function and reactivity as well as for some of the challenges that formulators working with Retinol have to face. Retinol is sometimes referred to as Vitamin A, however confusingly, Vitamin A is not one distinct substance, rather than a number of individual molecules. Other chemical compounds belonging to the Vitamin A group are Retinal (the oxidation product of Retinol) Retinoic acid (the oxidation product of Retinal) and several Retinyl esters such as Retinyl acetate or Retinyl palmitate.

Retinol, Retinoic acid and the skin

Retinol and its natural derivatives are involved in multiple biological functions including vision, inflammation and the generation and development of different tissues.

In the skin not Retinol itself but Retinoic acid is mainly involved in the processes that control a.o. the development of the epidermis and its thickness, the stratum corneum as well as the production and storage of dermal structures like Hyaluronic acid.

These mechanisms are governed by complex cascades of cellular interactions including multiple receptors and the activation of transcription factors. Many of these have also been found to be affected during the intrinsic aging process as well as in photoaged skin. This makes these pathways as well as substances that show activity in them interesting targets for cosmetic ingredients and products.

Retinoic acid can be formed from free Retinol in the skin or by release of Retinol from a Retinyl ester (e.g. Retinyl palmitate) and by subsequent two step oxidation via the Retinal intermediate. These required chemical transformation steps are considered one of the reasons that Retinol or its esters topically applied are viewed not as potent as Retinoic acid in respect to their clinical effects.

Retinoids from the Vitamin A group


The suffix -oid (as in Retinoid) can be used to describe a resemblance between chemical structures. Starting from the alcohol Retinol the oxidation to the aldehyde Retinal leads to a molecule that is similar to Retinol, but not identical. Retinal is hence not the same as Retinol, but can be described as a Retinoid as they share the same structural origin. The same principle applies for Retinoic acid and Retinyl esters, which can also be classed as Retinoids. The naturally occurring Retinoids (including the ones above) are also sometimes called “First Generation Retinoids” or “non-aromatic Retinoids” in respect to their ring structure.

The application of Retinoic acid to the skin can come with unpleasant irritation side-effects such as redness, dryness and discomfort, which are considerably milder under the use of Retinol. These side effects gave the impetus to further develop chemical structure modifications of the Retinol molecule scaffold which lead to two more generations of Retinoids, the “Second” and “Third” Generation Retinoids according to their ring structure also referred to as “mono-aromatic” and “poly-aromatic” Retinoids.

First generation Retinoids differ in their chemical stability as well as their activity depending on the necessary steps to convert them into their active form Retinoic acid.  They can be ranked in their activity as Retinoic acid > Retinal > Retinol >> Retinyl esters. This order corresponds to the number of transformation steps that are necessary to derive Retinoic acid through biotransformation in the skin and it also mirrors the reverse order of side effect severity when these substances are applied.

Newer generations of Retinoids differ in their selectivity for individual receptors that are involved in the cellular signaling cascades and can be used for different clinical purposes. Retinoids are powerful remedies that are often used in prescription formulations of drugs in order to treat severe clinical conditions including acne and psoriasis.

Retinol, Vitamin A, Retinoids

Retinoids in cosmetics and personal care products

Multiple Retinoids are available for use in cosmetic products including Retinol, Retinal, various Retinyl esters including Retinyl Acetate, Retinyl linoleate or Retinyl palmitate. Further modifications of Retinoic acid such as Hydroxypinacolone retinoate are listed. Their safe usage in cosmetics is restricted to a maximum level depending on the product type, taking the surface area and amount a product would be applied with, into account. Different regions and countries also take different approaches in respect to concentration guidelines for Retinoids in cosmetics:

Example Europe SCCS opinion:

  •   Body Lotion 0.05%
  •   Hand/face cream, leave-on (other than body lotions) and rinse-off products up to 0.3%
  •   The use of Retinoic acid is banned in cosmetic products in the EU (Annex 2, entry 375 EU regulation)

Example according to US CIR:

  •   Retinol and Retinyl palmitate are described as safe for use up to 1% however there are reports of products on the market that exceed these concentrations.

An important limiting factor for the use of Retinol is the skin irritation potential that can be experienced with higher concentrations. The use of another type of Retinoid for example an ester can mitigate these side effects. Pre-formulation of Retinol may also have a positive impact. Modifications that allow a time-controlled release of the ingredient from the formula can further contribute to a better skin-tolerance. Multiple preformulated technologies have found their way to the market over the past years.

Retinoids in prescription and over the counter (OTC) medication

Retinoids of the Retinoic acid type including Retinoic acid itself and the Retinoic acid derivatives of the second, third and newer generation are not permitted for use in cosmetics and personal care products. They generally require a prescription as they are formulated and distributed in drug products.

The difference between drugs and cosmetics lies in their intended use. Individual countries have different specific definitions for drugs and cosmetics, however the main distinguishing factors are for a drug to treat or prevent a medical condition, without limitation to the location of the physiological structure that is targeted, and for a cosmetic product to improve an appearance and/or keep in good condition the external parts of the body (i.e. the skin and its appendages).

In 2016 the US FDA approved the use of Adapalene 0.1% (3rd generation Retinoid) as an OTC drug with the intended use to treat acne (which is a medical condition). The drug had been a prescription- only drug since 1996. Despite its availability without a prescription, the product remains a drug and falls under the relevant regulations. As such and should not be used for cosmetic intentions.

Cosmetic benefits

Several Retinoids are listed in the CosIng (The Cosmetic Ingredient Database of the European Union) with the “Skin Conditioning” function. In the US, Retinyl palmitate is according to CIR  also added to sun-care and hair care products. The key reason that most Retinoids are used (mainly in skincare formulations) is their intended effect on the appearance of wrinkles, dark spots, hyperpigmentation as well as multiple aspects associated with the signs of ageing. Due to their structure, they can act as antioxidants in addition to their proclaimed receptor-mediated effects.

The majority of data on wrinkles and pigmentation is available for the use of Retinoic acid, which is not permitted for use in cosmetic products in the EU and US. However, multiple studies are available for cosmetic-use permitted Retinoids as well. In a double-blind, split face, placebo-controlled study on facial skin both Retinol and a Retinyl ester (Retinyl propionate) showed significant effects on the reduction of pigmentation and crows- feet wrinkles after 12-weeks of use (Draelos, Cosmetic Dermatology, Wiley-Blackwell, 2010 Chapter 39: Topical vitamins, pp. 320) . It should be mentioned that the efficacy and tolerability of a Retinoid are both tightly linked to their formulation.

Challenges for formulating Retinoids

The safety and tolerability of a formulation depends a.o. on the used concentration, the type of Retinoid, its pre-formulation and the overall composition of the formula.

Retinoids show sensitivity towards oxidation, temperature and light, which makes them considerably unstable and requires their stabilization via pre-formulation (combination with antioxidants, encapsulation etc.) as well as in many cases the use of specialized packaging i.e. airless and opaque packaging material. Both Retinol and some of its esters can bind to PVC in plastics. The manufacturing setup also plays a key role as oxygen and light exposure during the process itself can impact the shelf-life of a Retinoid formula. When produced under inert conditions and stored in aluminum tubes at 20° C for example Retinol has been shown to be stable for at least 6 months. Retinol itself is unstable to acids and to high pH. Retinyl palmitate and other esters are generally more stable, not only in an alkaline environment. 

Retinol “alternatives”

Due to their efficacy but also the challenges associated with their use (regulatory limitations, side effects, stability), the search for alternatives to Retinoids could maybe be considered the quest for the “holy grail” of active ingredient development for the skincare market. Multiple ingredients and products have entered the market making statements of comparison to either the efficacy or the mode of action that Retinol and other Retinoids demonstrate.

Brands and consumers should be aware of the distinct difference in this space. An ingredient that shows similar efficacy in clinical trials where a direct head-to-head comparison to Retinol or another Retinoid can be demonstrated may be considered as an ingredient which can potentially produce similar effects to a Retinoid in the distinct efficacy space that is looked at (e.g individual signs of aging, pigmentation etc.). This does not necessarily mean that the ingredient follows the same mechanism of action compared to a Retinoid; The appearance of wrinkles and pigmentation may be affected by other cellular mechanisms than the ones affected by Retinoids.

Equally, an ingredient influencing similar cellular mechanisms as a Retinoid, may not necessarily provide the same efficacy in respect to its cosmetic benefits despite the potential absence of side effects or instability.


Ten examples for Retinoid-containing products that are available on the market: 

    1. Peter Thomas Roth -  Retinol Fusion PM Night Serum
    2. Avène - RetrinAL 0.1 Intensive Cream
    3. Murad - Retinol Youth Renewal Night Cream
    4. La Roche-Posay - REDERMIC Retinol Concentrate
    6. Vichy - LIFTACTIV RETINOL TREATMENT Anti-Wrinkle Cream
    8. Estée Lauder - Perfectionist Pro Rapid Renewal Retinol Treatment
    9. Neutrogena - Rapid Wrinkle Repair®
    10. Elizabeth Arden - Advanced Ceramide Capsules Daily Youth Restoring Serum