Retinoids are a family of molecules that refer to Vitamin A and its derivatives. Widely used in skincare products, as well as in medicine, retinoids come in various forms. Which ones? And what differentiates them? Learn more in this article.
Library
All Topics
The various forms of retinoids.
Summary
- Retinol, the most well-known retinoid
- Retinal, also known as retinaldehyde
- Retinol esters, well-tolerated retinoids
- Hydroxypinacolone retinoate, a directly active retinoic acid ester
- Retinoids strictly for medical use
- A brief overview of the different forms of retinoids
- Sources
Published June 20, 2022,
updated on April 10, 2025,
by
Maylis, Chemical Engineer
—
11 min read
Retinol, the most well-known retinoid.
A leading active ingredient in skincare, retinol is a form of fat-soluble vitamin A, meaning it dissolves in lipids, the molecules that make up the intercellular cement of the corneal layer. Primarily used to prevent and correct signs of skin aging, it also has the ability to accelerate cell renewal, a useful property in cases of blackheads or pigmentation spots. However, unlike retinoic acid, retinol is not biologically active. After application to the skin, it undergoes a double enzymatic conversion: it is first oxidized into retinal and then transformed into retinoic acid. This gradual conversion limits its potency, but contributes to its better tolerance. Despite this, retinol remains an active ingredient to use with caution. It is often associated with irritations, especially at the beginning of use or at high concentrations. That's why its use in non-rinse cosmetic products is limited to 0.3% by European Regulation No 1223/2009.
Once transformed, retinoic acid binds to the nuclear receptors of retinoic acid (RAR) and the retinoid X receptor (RXR), resulting in the formation of an activated RAR/RXR heterodimeric complex that modulates the expression of numerous genes involved in keratinocyte proliferation, type I and III collagen synthesis, and the activity of matrix metalloproteinases, the enzymes involved in the degradation of the dermis' support fibers. This action of the retinoids explains their relevance in skincare, particularly for enhancing skin elasticity and refining skin texture.
Retinal, also known as retinaldehyde.
A direct intermediary between retinol and retinoic acid, retinal, or retinaldehyde, is an oxidized form of vitamin A. Closer to the active form than retinol, retinal is generally considered more potent than the latter but not necessarily more irritating. Once applied to the skin, retinaldehyde undergoes only one conversion to transform into retinoic acid. The action it exerts is then the same as that described previously. Retinal is generally used at concentrations ranging from 0.015% to 0.1%.
A recent study evaluated the effectiveness of two moisturizing creams containing 0.05% and 0.1% retinaldehyde respectively on 40 women showing visible signs of photoaging. After 3 months of twice-daily application, a significant reduction in the appearance of wrinkles was noted, along with an improvement in skin texture (by 13.7% for the 0.1% cream and 17.9% for the 0.05% cream) and a decrease in transepidermal water loss (by 14.5% for the 0.1% cream and 17.9% for the 0.05% cream).
Retinol esters, well-tolerated retinoids.
Retinol esters are retinoids that exhibit high chemical stability. They are also known for their gentleness on the skin. Retinol esters are derived from the combination of retinol with a fatty acid. The most well-known are retinyl acetate (INCI: Retinyl Acetate), retinyl propionate (INCI: Retinyl Propionate), retinyl palmitate (INCI: Retinyl Palmitate), and retinyl linoleate (INCI: Retinyl Linoleate). In short, retinol esters can be easily identified by their "ate" suffix.
However, while retinol esters are stable and well-tolerated, they are the least active retinoids. Indeed, their transformation into retinoic acid requires several enzymatic steps: hydrolysis into retinol, then oxidation into retinal, and finally conversion into retinoic acid. Retinol esters are nonetheless relevant if one has sensitive skin but still wishes to start incorporating retinoids into their skincare routine.
Hydroxypinacolone retinoate, a directly active retinoic acid ester.
Hydroxypinacolone Retinoate (HPR) is a next-generation retinoid that stands out due to an interesting structural feature: although it is an ester, it can directly bind to the nuclear receptors of retinoic acid, without requiring prior enzymatic transformation. It thus combines the tolerance of retinol esters with the biological efficacy of retinoic acid, making it an increasingly sought-after ingredient in the skincare industry. Looking more closely at its structure, Hydroxypinacolone Retinoate is a lipophilic ester derived from retinoic acid and formed by esterification with a hydroxypinacolone group.
A 2023 clinical study examined the synergy between hydroxypinacolone retinoate (HPR) and retinyl propionate (RP) and their skin tolerance. For this purpose, 42 volunteers were recruited and applied a serum containing hydroxypinacolone retinoate and retinyl propionate daily in a 5:9 ratio. The exact percentage of each active ingredient was not disclosed. After 8 weeks of use, wrinkles, skin smoothness, and transepidermal water loss improved by 8.3%, 11.9%, and 25.7% respectively. In addition, 33 participants underwent patch tests. Different concentrations of retinol were tested, as well as formulations containing hydroxypinacolone retinoate and retinyl propionate, still in a 5:9 ratio. The results show that creams containing HPR and RP were significantly better tolerated than those with retinol.
Results of patch tests for retinol compared to the combination of HPR and RP (ratio 5:9).
Source: YE R. & al. The combined effect of retinyl propionate and hydroxypinacolone retinoate on skin aging. Journal of Cosmetic Dermatology (2023).
Retinoids strictly for medical use.
Retinoic acid is the biologically active form of retinoids and is the primary retinoid used in the medical field. Unlike retinol, retinal, or retinol esters, it acts directly by binding to nuclear retinoic acid receptors (RAR) and retinoid X receptors (RXR), thus modulating the expression of genes involved in cell differentiation, keratinization, sebum production, and collagen synthesis. Its use is reserved for the medical field, due to its powerful effectiveness... but also its notable side effects. Retinoic acid can be divided into several sub-families.
Tretinoin.
Used in dermatology since the 1970s, tretinoin is primarily prescribed for treating acne. It regulates the proliferation of keratinocytes, normalizes desquamation, and reduces the formation of comedones. It also stimulates collagen production and increases the thickness of the dermis. However, tretinoin is often irritating and its application frequently leads to erythema, burning sensations, and desquamation. This sometimes limits its tolerance, especially in thin or sensitive skin.
Isotretinoin.
Primarily known in its oral form under its former trade name Roaccutane, isotretinoin is used in cases of severe acne or acne resistant to traditional treatments. It works by reducing the size of the sebaceous glands, decreasing sebum production, inhibiting the proliferation of Cutibacterium acnes, the bacteria involved in the pathogenesis of acne, and normalizing keratinization. It is one of the most effective medications against acne but requires strict medical supervision due to its systemic side effects (intense dryness, liver disorders, high teratogenic risk). In topical use, isotretinoin is better tolerated but is less frequently prescribed because it is less effective.
Alitretinoin.
Less known, the alitretinoin stands out for its ability to bind to all known subtypes of retinoic acid receptors, namely RAR-α, RAR-β, RAR-ɣ, RXR-α, RXR-β, and RXR-ɣ, unlike other retinoids that are specific agonists of RAR or RXR receptors. This gives it a broader biological action. It is primarily used orally in the treatment of severe chronic hand eczema resistant to corticosteroids. Alitretinoin modulates inflammation, reduces hyperkeratinization, and improves healing. Again, its use is regulated, particularly due to teratogenic risks and the systemic side effects that surround it.
Lastly, tazarotene is a synthetic retinoid used topically to treat psoriasis and occasionally acne. It belongs to the class of acetylenic retinoids. Tazarotene is a pro-drug that is rapidly converted into tazarotenic acid after application on the skin. This compound preferentially binds to RAR-β and RAR-ɣ receptors and exerts anti-proliferative effects on keratinocytes, anti-inflammatory effects, and stimulates cell regeneration. Like other retinoids, tazarotene can cause local irritation, which sometimes limits its continuous prescription.
All forms of retinoids are strictly contraindicated for pregnant women as they are teratogenic, meaning they increase the risk of fetal malformations.
A brief overview of the different forms of retinoids.
| Retinoids | Mechanism of Action | Usage |
|---|---|---|
| Retinol | Inhibits collagenase and the expression of MMPs, stimulates the synthesis of type I collagen and glycosaminoglycans | Prevention of skin aging, reduction of fine lines, improvement of skin texture, antioxidant |
| Retinal | Oxidized into retinoic acid by retinaldehyde dehydrogenases (RALDH2) or certain enzymes from the CYP family, it stimulates the proliferation of epidermal cells | Prevention of skin aging, reduction of fine lines, improvement of skin texture, antioxidant |
| Retinol Esters | Converted into retinol through ester bond cleavage, and then into retinoic acid, they stimulate the proliferation of epidermal cells. | Prevention of skin aging, improvement of skin texture, antioxidant |
| Hydroxypinacolone Retinoate | Acts directly on RAR receptors, stimulates collagen production, regulates keratinization | Prevention of skin aging, reduction of fine lines, improvement of skin texture, antioxidant |
| Tretinoin | Stimulates the proliferation of epidermal cells, accelerates the elimination of sebum in the channels, thereby reducing inflammation of the sebaceous glands, inhibits keratinization | Acne, psoriasis, chronic inflammation of hair follicles and sebaceous glands |
| Isotretinoin | Reduces the size and activity of sebaceous glands, decreases sebum production, inhibits the proliferation of keratinocytes and inflammation, and regulates pro-inflammatory mediators | Severe or persistent acne, rosacea |
| Alitretinoin | Activates RAR and RXR receptors, regulates cell differentiation, reduces inflammation, exhibits anti-proliferative action | Chronic and Resistant Hand Eczema |
| Tazarotene | Reduces the markers of differentiation and proliferation of keratinocytes as well as inflammation | Acne, psoriasis |
The various retinoids used in cosmetics and dermatology.
Adapted from: ZASADA M. & al. Retinoids: active compounds impacting skin structure development in cosmetic and dermatological treatments. Advances in Dermatology and Allergology (2019).
Sources
MUKHERJEE S. & al. Retinoids in the treatment of skin aging: An overview of clinical efficacy and safety. Clinical interventions in aging (2006).
Règlement (CE) No 1223/2009 du Parlement Européen et du Conseil.
BAE J. M. & al. Efficacy and safety of retinaldehyde 0.1% and 0.05% creams used to treat photoaged skin: A randomized double-blind controlled trial. Journal of Cosmetic Dermatology (2018).
ZASADA M. & al. Retinoids: active molecules influencing skin structure formation in cosmetic and dermatological treatments. Advances in Dermatology and Allergology (2019).
YE R. & al. The synergistic effect of retinyl propionate and hydroxypinacolone retinoate on skin aging. Journal of Cosmetic Dermatology (2023).
Diagnostic
Understand your skin
and its complex needs.
