Knowledge Popularization | Clinical Study on the Anti Aging Effect of Retinol
In the field of skin anti-aging, as an important member of the retinoid family, the efficacy and safety of retinal have always been the focus of clinical research. A review article published in Advances in Therapy, titled "Use of Retinoids in Topical Antiaging Treatments: A Focused Review of Clinical Evidence for Conventional and Nanoformulations," systematically reviewed multiple clinical studies on retinal, providing solid evidence-based support for its application in topical anti-aging[1].
The most effective anti-aging ingredient among retinoids: mild and non-irritating
The article points out that as a natural precursor of retinoic acid, retinaldehyde has a good activity/tolerance ratio when applied topically and is therefore considered one of the most effective vitamin A derivatives in cosmetics. Retinoic acid is the active ingredient, but it is too irritating. Retinol and retinal are both sustained-release drugs for retinoic acid. The one-step oxidation process from retinal to retinoic acid is faster and more effective, allowing differentiated keratinocytes to form new cells more efficiently. Under the same concentration, the efficacy of retinal is stronger, with a conversion efficiency 11 times that of retinol. It can quickly activate anti-aging pathways and shorten the skin rejuvenation cycle. Only a small amount of retinal is needed in formulations to achieve effects comparable to retinol, and it has antibacterial advantages. It achieves the dual value of "anti-aging + anti-inflammatory" and is more suitable for acne-prone and sensitive skin[2,3]. Retinal has low irritability. The reason is that the formation of new cells in keratin requires a time process: locally applied retinal does not directly bind to retinoid receptors, but is mainly converted into retinol esters, which are divided into many small parts and metabolized into biologically active retinoic acid. Research suggests that skin irritation is partly caused by the receptor being "overloaded" with non-physiological doses of exogenous retinoic acid, and the use of retinal can effectively avoid this process.
A study comparing the skincare effects of retinol, retinal, and retinoic acid through a 12-week non-invasive evaluation[4]. It was found that the skin penetration rate of retinal is about 25% higher than that of retinol, and it performs better in anti-aging effects. Its wrinkle depth reduction is 35% higher than retinol, and the skin elasticity improvement is 22% higher than retinol. At the same time, the effect of reducing pores is more significant (31.8% vs 24.6%), and its tolerance is better. Only 12.5% of users reported mild skin irritation, which is lower than the 17.5% of the retinol group. It also performs better in maintaining skin barrier function, demonstrating a good balance between efficacy and tolerance. It is a better topical anti-aging retinoid derivative than retinol (see Figure 1).
Figure 1: Comparison of the efficacy of retinol and retinal within 12 weeks (based on retinol), data sourced from reference [4].
Multi-dimensional improvement of photoaging skin
A 3-month randomized double-blind controlled clinical trial was conducted to evaluate the efficacy of 0.1% retinal cream and 0.05% retinal cream in four dimensions: skin moisture retention, wrinkle depth/number, skin roughness, and transepidermal water loss (TEWL, a core indicator reflecting skin barrier function)[5]. After a 3-month intervention period, both groups of subjects showed significant improvement in their skin condition: significant improvement in skin moisture retention, reduction in wrinkle depth and number, reduced surface roughness of the skin, and significant decrease in transepidermal water loss (indicating that the skin barrier function has been repaired). This study confirms that both 0.1% and 0.05% concentrations of retinal cream can improve the problem of photoaging skin from multiple dimensions of "moisturizing anti-wrinkle skin rejuvenation barrier repair", providing a concentration reference for different tolerance groups to choose retinal products (see Figure 2).
The 3D image in Figure 2 shows that after topical retinal treatment, the roughness and fine wrinkles of the skin have improved. (A) and (B): Comparison of patients 3 and 6 before and after 12 weeks of using 0.05% local RAL medication. (C) and (D): Comparison of patients 34 and 28 before and after 12 weeks of using 0.1% local retinal treatment.
Nanoformulations: Controlled release technology enhances efficacy and reduces side effects
To further optimize the topical efficacy and safety of retinal, researchers have explored the application of nano-formulation technology. Compared with 0.025% tretinoin hydrogel, the anti-aging effect and safety of nano preparation were evaluated[6]. The core advantage of this formulation lies in its controlled-release characteristics. Through the design of nanoparticle carriers, a slow and sustained release of retinal is achieved. This significantly enhances the stimulation of epidermal cell proliferation — a key process for skin renewal and repair of aging damage — thereby improving anti-aging efficacy. On the other hand, it avoids the irritant reactions caused by large amounts of active ingredients contacting the skin in a short period, minimizes side effects such as dryness and redness, and achieves a dual breakthrough in both efficacy enhancement and safety improvement (see Figure 3).
Figure 3 shows representative images of H&E stained tissue sections after 28 days of treatment: (a) 0.1% (w/v) or 0.0033 mmol/mL retinoic acid, (b) 0.0033 mmol/mL retinal, (c) PrN (equivalent to 0.0033 mmol/mL retinal concentration), and (d) representative images of H&E-stained tissue sections after distilled water treatment.
From the three dimensions of efficacy comparison, concentration selection, and formulation optimization, the evidence fully confirms the outstanding value of retinal in skin anti-aging. It not only exhibits the same anti-wrinkle, skin-softening, and repair effects as the classic anti-aging ingredient (retinoic acid) but also offers better skin tolerance. Furthermore, the application of nanoformulation technology has further expanded its potential in the development of effective, low-irritation anti-aging products.
References
[1]Milosheska D, Roškar R. Use of Retinoids in Topical Antiaging Treatments: A Focused Review of Clinical Evidence for Conventional and Nanoformulations. Adv Ther, 2022, 39(12):5351-5375.
[2] https://thesummerstudy.com/retinal-vs-retinol/
[3] https://www.omorovicza.co.uk/blogs/news/what-is-retinol
[4]Mathad V, Bhaskaran H, Shivprasad S. Retinol, retinal and retinoic: making sense of skincare with vitamin A derivatives. International Journal of Research in Dermatology, 2025; 11(6):511-517.
[5]Kwon HS, Lee JH, Kim GM, Bae JM. Efficacy and safety of retinaldehyde 0.1% and 0.05% creams used to treat photoaged skin: a randomized double blind controlled trial. J Cosmet Dermatol. 2018; 17(3):471-6.
[6]Pisetpackdeekul P, Supmuang P, Pan-In P, et al. Proretinal nanoparticles: stability, release, efficacy, and irritation. Int J Nanomed. 2016; 11:3277-86.
