Touted by dermatologists as the gold standard for anti-aging, retinol is beloved for its ability to reduce fine lines, improve skin texture, and create brighter-looking skin. But for all its advantages, retinol also comes with some potentially serious downsides: redness, irritation, sensitivity and peeling. Also called skin retinization, these side effects could be enough to deter even the most committed users from sticking with a retinol routine. So is there any alternative out there? Let’s dig into the science behind retinol to understand more about its cons.

The first question to address is, what do retinoids do? Retinol is a form of vitamin A that falls under a class of topical ingredients called retinoids. Retinoids come in a variety of different forms including retinol, retinal, retinaldehyde, retinoic acid, tretinoin, retinyl palmitate, and retinyl acetate.

Naturally occurring retinoids are critical to many of our body’s essential processes including the healthy development of the nervous system, cardiovascular system and proper vision. Most of us get plenty of retinol in our diets through meat and eggs or by eating veggies rich in yellow, orange and dark green plant pigments called carotenoids, which the body then converts into retinol in the liver.

As the body’s largest organ, skin also benefits from a diet with enough vitamin A. Studies have shown that retinoic acid helps manage the production of sebum and indirectly regulates the skin microbiome.¹ This effect on oil production is one of the primary reasons why topical retinol was first introduced as a treatment for acne.First studied in the 1960s and 70s as an acne treatment, topical retinoids are still prescribed today as comedolytics – ingredients that unclog pores and prevent the buildup of oil and dead skin cells.² While studying retinoids for acne, scientists noticed that participants experienced not only a reduction in blemishes, but also smoother skin texture and an overall decrease in wrinkles. So how do they work? When applied topically, retinoids cause skin cells to renew faster and produce more collagen,which can result in an increase in epidermal thickness.³This collagen-boosting effect is thanks to the selective presence of retinoic acid receptors and retinoid X receptors in the epidermal layer.⁴ When retinoids bind to these receptors, they kickstart a transduction pathway that increases collagen precursors. Additionally, retinoids promote cells in deeper skin layers to divide more frequently, allowing new cells to replace older cells at the surface. This accelerated skin cell turnover can address skin concerns and reduce the appearance of wrinkles, smooth out uneven skin texture and give skin tone a noticeably brighter appearance. While topical retinoids have plenty of perks, they are not without their pitfalls. After starting a retinol routine, many people experience redness, sensitivity, peeling and flaking–an adjustment called skin retinization. Some people with acne also notice that their breakouts actually get worse rather than better in the first few weeks. While you can mitigate retinization by using retinol less frequently and slowly adding it to your routine, many people still experience these common retinol side effects. In fact, they’re so common that they have been coined the “retinol uglies”.Part of the reason why retinol is so popular among the aesthetic medical community is that it improves epidermal thickness – an effect that’s well-documented in scientific literature.⁵ However, while thickening the epidermis, retinol thins another vital skin structure: the stratum corneum, the outermost layer that performs a majority of the skin’s protective functions and gives skin its dewy, glowing appearance.

By weakening the stratum corneum, retinol may compromise the skin’s barrier function, exposing the body to increased threats from external exposures. Part of this unwanted effect may actually be a result of retinoic acid’s impact on cellular turnover; rapidly-produced skin cells may generate quicker at the expense of adhesion and lipid properties essential to a healthy skin barrier.⁶

Ultimately, with a potentially compromised protective surface layer, the skin can lose moisture and become ultra-sensitive, which means your skin could stay reactive, dry, and flaky for much longer than just the initial adjustment period that dermatologists say is normal. So how do you know if retinol is doing more harm than good? Prolonged sensitivity, redness and dryness could serve as a key indicator for when to stop using retinol on your skin.While ubiquitous in night creams, retinol rarely shows up in sunscreens or other daytime products. The reason is simple: unlike peptides which can be used both morning and night, retinol degrades when exposed to UV rays and has been shown to make your skin more susceptible to sunburn. This means that if you apply retinol during the day, you’re not only getting fewer benefits from your treatment but also risking sun damage to DNA and structural skin fibers⁷, impairing the skin’s structural integrity and increasing your risk of skin cancer and other diseases.Retinol’s long list of side effects leave many of us wondering whether the pros are worth the cons of retinol. To get to the bottom of that question, we took it to the lab. Our scientists here at OneSkin conducted an expression analysis on ex vivo human skin samples that were exposed to retinol versus OS-01 FACE in order to observe how they each impact biomarkers associated with skin aging, cellular proliferation, and collagen production. The results were fascinating.


Figure 1. Expression of biomarkers associated with aging (CDKN2A), collagen production (COL1A1), and cell proliferation (MKi67) following treatment with nothing (No Treatment), OS-01 FACE, or 1% retinol on the dermis of ex vivo human skin samples (Zonari, et al).

Although retinol significantly increased a key biomarker associated with collagen production, COL1A1, it also created a tenfold activity increase in a biomarker linked to aging, CDKN2A. Alternatively, treatment with OS-01 FACE was able to significantly increase the collagen production biomarker, COL1A1, at similar levels to retinol, without affecting the same biomarker associated with aging, CDKN2A, that retinol increased. OS-01 FACE also significantly increased a key biomarker associated with cell proliferation, MKi67, while retinol did not, indicating that OS-01 FACE could be more effective at promoting cell proliferation in the skin (Zonari, et al).To take a closer look at retinol’s impact on skin, our scientists put retinol under the microscope– literally. Using a microscopic visual analysis tool called histology, our R&D team examined ex vivo human skin samples that had been treated with OS-01 FACE versus retinol to observe the impact of both treatments on each layer of the skin.


Figure 2. Histology images of ex vivo human skin samples from a 35 year old donor exposed to OS-01 FACE vs. 1% retinol (Zonari, et al).

Our observations were consistent with those found in the expression analysis. Skin that was treated with retinol experienced a peeling effect in the stratum corneum (top layer), which has potential to lead to a thinner and weaker skin barrier. Additionally, the skin that was exposed to retinol appeared to be compromised with less cellular structure and organization. Conversely, treatment with OS-01 FACE promoted a more cohesive stratum corneum, with a more defined general structure and enhanced cellular organization, indicating that the skin’s barrier was likely strengthened and cellular function was likely improved when treated with OS-01 FACE (Zonari, et al).Finally, to validate OS-01 as an effective retinol alternative, our scientists tested whether OS-01 could match one of retinol’s primary benefits–increased epidermal thickness. To do this, our scientists measured the epidermal thickness of ex vivo human skin samples from a 35-year-old donor, a 55-year-old donor, and a 79-year-old donor before and after treatment with OS-01 FACE. The results were positive, as skin treated with OS-01 FACE displayed a significant increase in epidermal thickness of 23.15% on average (Zonari, et al).


Figure 3. Epidermal thickness analysis of ex vivo human skin samples topically exposed to nothing (NT) or OS-01 FACE. Treatment with OS-01 FACE induced a significant increase in epidermal thickness of 23.15%, taken from the average of three measurements from each skin sample (35, 55, and 79 yr). *p<0.05 (Zonari, et al)

This data confirms that OS-01 FACE can help promote epidermal thickness, one of the main drivers of retinol’s anti-aging benefits.

Overall, our research shows that while retinol is commonly considered the gold standard anti-aging ingredient, it also has significant downsides, like the potential to compromise barrier function*, which could ultimately degrade long-term skin health. Alternatively, OS-01 FACE offers comparable benefits, including increase in a key collagen production biomarker and epidermal thickness*, without the observed drawbacks of retinol (Zonari, et al).

*Shown in lab studies on ex vivo human skin samples (Zonari, et al)If you aren’t ready to give up on retinol just yet, you can safely use OS-01 FACE with a topical retinoid to counteract its harsh effects.

You can incorporate OS-01 FACE with retinol in one of two ways:

1. Alternate OS-01 FACE and retinol: Alternating allows your skin to reap the benefits of both products without either of them interfering with the absorption of the other. Since retinol should only be applied at night, you can alternate the two by using OS-01 FACE in the mornings.
2. Combine OS-01 FACE and retinol: When combining retinol with OS-01 FACE in the same skin care routine, it’s up to you to decide which skin care product to apply first. Just keep in mind that the OS-01 peptide will achieve maximum penetration if it’s applied as the first step after cleansing.
Sensitive to retinol? Skip it! OS-01 FACE is an excellent alternative and could be better for preserving your barrier function and long-term skin health.

• Retinol is considered the gold standard in anti-aging, but it can be difficult to tolerate, as it commonly causes sensitizing side effects, especially for those with sensitive skin
• Studies show that one of the cons of retinol is that it could potentially damage skin’s barrier function if used excessively or in too high of concentration
• OS-01 FACE could help counterbalance the side effects of retinol, presenting many of the same benefits with none of the drawbacks.
• If you use a retinoid, it's crucial to pair it with the daily use of sunscreen. Also, make sure to consult your dermatologist if you experience extreme redness, peeling and sensitivity.

References:

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678709/
2. https://www.aocd.org/page/Retinoidstopical
3. https://pubmed.ncbi.nlm.nih.gov/26578346/
4. https://pubmed.ncbi.nlm.nih.gov/15773538/
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699641/
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764495/
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229936/