Infusing New Life into an Old Reliable Skin Treatment: Retinaldehyde


Retinaldehyde, in conjunction with complementary treatments that include chemical peels, dermabrasion and lasers, can provide a wide-spectrum skin care arsenal to estheticians, dermatologists and consumers, offering multifaceted attributes (see Applications sidebar).1 These benefits are reviewed here, along with mechanisms to deliver such effects.

Retinoids and Retinaldehyde: From Anti-aging to Zits

Retinoids are compounds that affect the body in ways similar to vitamin A.13 In broader terms, they are any of a group of compounds providing the same biological benefits as vitamin A. The chemical structures of select retinoids and compounds having the biological activity of retinoids are illustrated in Figure 1. In fact, β-carotene is converted into retinaldehyde by the body, which is further processed to form vitamin A (see Figure 2).26

Retinoids have found application in the treatment of both chronological and photo-aging.2 Additionally, they are potent therapeutic agents used topically and systemically as anti-acne agents.3

Repair and defend: In relation, retinaldehyde effectively treats dermatoporosis—a chronic, cutaneous insufficiency/fragility syndrome characterized by extreme skin atrophy.4 Furthermore, topical retinaldehyde has been found to induce β-defensin-3 expression, which is implicated in the resistance of epithelial surfaces to microbial colonization; thus, it acts as an antibacterial agent.5

Retinaldehyde and retinol have also been reported as regulators of gene expression in keratinocytes. Keratinocyte proliferation and hyaluronan synthesis are believed to be partly mediated through the heparin-binding EGF-like growth factor (HB-EGF) activated EGFR pathway.6 Retinaldehyde has been shown to increase the expression of HB-EGF and involucrin (IVL) greater than retinol, reducing the appearance of aged skin.7

Another application for retinaldehyde is the topical treatment of Lichen sclerosus,8 an uncommon chronic dermatosis that can occur on the anogenital area in perimenopausal women.

Skin depigmenting: Retinoids have been reported to exert skin-depigmenting activity as well, but unlike most depigmenting agents that target tyrosinase, retinoids are not phenolic and may act via different mechanisms.9 Although retinoids show promise in the treatment of skin aging, irritant reactions such as burning, scaling or dermatitis have been associated with some of these therapies, thus limiting their acceptance by patients.2

Rosacea: Topical retinoids have also been used to treat rosacea. Retinoic acid, for example, has beneficial effects on the vascular component of rosacea but treatment has drawbacks, including the delayed onset of efficacy and development of skin dryness, erythema, burning and stinging. A higher tolerance in photo-damaged skin was shown with retinaldehyde versus retinoic acid, with similar efficacy, which makes retinaldehyde more suited for sensitive, irritated skin in conditions such as rosacea and red face syndrome.10 As such, a combination of retinaldehyde with the anti-inflammatory agents dextran sulfate and hesperidin methyl chalcone has thus been reported.10

Irritation Potential

To evaluate the skin metabolism of retinoids employed in the treatment of skin disorders and predict their potential irritation, MetaSite was developed. This tool is based on a computational approach to assess metabolic transformations related to cytochrome and flavin-containing monooxygenase mediated reactions. It therefore can project retinol behavior.11

In general, topical retinoic acid precursors such as retinaldehyde or retinol are less irritating than acidic retinoids.12 All-trans retinaldehyde is the most commonly used, although retinaldehyde is increasingly gaining favor, possibly due to consumer concerns over the perceived retinoid-related skin irritation.

New topical delivery systems also are being developed to circumvent skin irritation-related issues. Recent discoveries bring new life into this age-old ingredient for alleviating select topical disorders.

Nanoparticles to Trojan Horses: Delivering Retinoids

Nanoparticles have shown good potential in improving the stability, tolerability and efficacy of retinoids.14 However, they have recently become less favorable due to concerns over potential safety issues.

Additional approaches to retinoid delivery include certain Schiff’s bases with polylysine, and retinaldehyde-hyaluronic acid fragments.15 Liposomes of retinaldehyde and other retinoids also have been reported;16 indeed, one system to deliver retinaldehyde for treating obesity has been patented.17

Various emulsion-based delivery systems for retinaldehyde and other retinoids have been reported, too,18 as well as encapsulated retinaldehyde formulated in a gel-based system.19

In addition, a Trojan horse delivery system, known as a retinaldehyde γ-cyclodextrin complex (RCC), was developed to expand retinaldehyde’s application in cosmetics by releasing it in a controlled manner. RCC is developed from the reaction of a polyene aldehyde such as retinaldehyde, with a cyclodextrin; in this case, γ-cyclodextrin.21

Gene expression data confirmed that retinaldehyde delivery via this approach effectively treated many of the skin symptoms for which retinaldehyde was noted above, in addition to: oxidative damage; inflammation; the loss of cell adhesion, desquamation, keratinization and skin barrier function; cellular senescence; and topical wounds.20

Combinatorial Therapies

Combinations of retinoids with other agents to provide greater efficacy and reduced skin irritation are receiving renewed interest for dermatological applications.

Skin whitening, acne and anti-aging: For example, the combination of retinaldehyde or tretinoin with other skin depigmenting agents has been shown to significantly improve the depigmentation of solar lentigines.22 Retinaldehyde in combination with glycolic acid also has been reported to treat mild to moderate acne during sun exposure and with good skin tolerability.23 Also, glycylglycine oleamide, a peptide derivative reported to protect connective tissue from glycation and elastosis, has been combined with retinaldehyde to treat skin aging.24

Psoriasis: Furthermore, elevated levels of Epidermal Retinol Dehydrogenase 2 (RDH2) have been found in psoriatic skin, and the potential role of RDH2 in the oxidation of retinol to retinaldehyde for retinoic acid biosynthesis in human keratinocytes has been acknowledged. In fact, 11-cis-retinoic acid in particular, an oxidation product of 11-cis-retinaldehyde, has found applications in the treatment of psoriasis.25


As this review indicates, retinaldehyde offers a less irritating alternative to retinoids for a wide array of skin care products. In relation, a new delivery system based on a γ-cyclodextrin provides multifunctional benefits to cosmetics using stabilized retinaldehyde.


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