Retinol 101: Debunking Retinol as the Gold Standard

Reference Lab

JUL 07, 2021

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.

01 What is retinol?

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.

02 What Do Topical Retinoids Do?

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, resulting in an increase in epidermal thickness.[3] This 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 reduces the appearance of wrinkles, smooths out uneven skin texture and gives skin tone a noticeably brighter appearance.

03 Retinization & The Harsh Side Effects of Retinol

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”.

04 Retinol’s Impact on Epidermal Thickness & Barrier Function

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 thinning the stratum corneum, retinol compromises 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 retinol’s impact on cellular turnover; rapidly-produced skin cells lack adhesion and lipid properties essential to a healthy skin barrier. In fact, studies have shown that using retinol impairs skin cell cohesion, which alters the normal barrier that seals in moisture and protects the skin from outside stressors.[6]

Ultimately, without this protective surface layer, the skin loses moisture and becomes 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.

05 Heightened Sun Sensitivity

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 damage to DNA and structural skin fibers [7], impairing the skin barrier and increasing your risk of skin cancer and other diseases.

06 The “Retinol Uglies” In Numbers: Retinol vs the OS-01 Peptide

Retinol’s long list of side effects leave many of us wondering whether its pros are really worth its cons. To get to the bottom of that question, our scientists here at OneSkin conducted a genetic expression analysis to observe how retinol impacts genes associated with skin aging, inflammation, collagen production, and hyaluronic acid production. The results were fascinating. Although retinol significantly increased the activity of genes associated with collagen and hyaluronic acid production, it also created a tenfold activity increase in a gene linked to aging and cellular senescence. Additionally, retinol significantly increased the presence of inflammatory genetic markers, IL-6 and IL-8. So while retinol does effectively boost collagen and hyaluronic acid production, it comes at a cost: increased inflammation and aging.

When compared to retinol at the molecular level, our proprietary peptide, OS-01, provided similar benefits with none of the drawbacks. Like retinol, OS-01 significantly increased gene activity associated with hyaluronic acid and collagen production. However, OS-01 actually reduced activity of the same inflammation and aging genes that retinol increased. This comparison shows that OS-01 works to hydrate and boost collagen without any of the aging and inflammatory downsides associated with retinol.

Figure 1. Genetic expression analysis of various aging and inflammatory markers, collagen production, and hyaluronic acid production following treatment with the OS-01 peptide vs. retinol.

Impact on skin morphology & structure

To take a closer look at retinol’s impact, our scientists put retinol under the microscope– literally. Using a microscopic visual analysis tool called histology, our R&D team examined the impact of both retinol and OS-01 on each layer of the skin. Our observations were consistent with those found in the genetic expression analysis. Skin that was treated with retinol experienced a peeling effect in the stratum corneum, creating a thinner and weaker skin barrier. Additionally, the skin that was exposed to retinol showed compromised cellular structure and organization, likely due to the increased rate in cellular turnover. Conversely, the OS-01 sample showed a thicker epidermal layer (dark purple), a cohesive stratum corneum (top layer), and more defined structure and cellular organization, indicating that OS-01 strengthened the skin barrier and improved cellular function.

Figure 2. Ex vivo skin analysis following treatment with OS-01 topical supplement vs. retinol.

Impact of the OS-01 peptide on epidermal thickness

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 skin from a 35-year-old donor, a 55-year-old donor, and a 79-year-old donor before and after treatment with OS-01. The results were positive, with epidermal thickness increasing by 16% in the 35-year-old skin, 28% in the 55-year-old skin, and 11% in the 79-year-old skin.

Figure 3. Histology analysis of ex vivo skin from a 55-year-old donor

This data confirms that OS-01 promotes epidermal thickness, one of the main drivers of retinol’s anti-aging benefits, particularly its anti-wrinkle and elasticity-boosting effects.

Overall, our research shows that while retinol is commonly considered the gold standard anti-aging ingredient, it also has significant downsides, like compromised barrier function and accelerated irritation, that may ultimately degrade long-term skin health. Alternatively, OneSkin’s OS-01 Topical Supplements, powered by our OS-01 peptide, offer comparable benefits, including an increase in collagen production and epidermal thickness, without the drawbacks.

07 How to use OS-01 with Retinol

If you aren’t ready to give up on retinol just yet, you can safely use your OS-01 Topical Supplements with a topical retinoid to counteract its harsh effects. However, to ensure that your skin fully absorbs OS-01, you should apply your OS-01 Topical Supplement as the first product in your routine directly after cleansing and follow with retinol if desired.

Sensitive to retinol? Skip it! Our OS-01 Topical Supplements are an excellent alternative and actually better for preserving your barrier function and long-term skin health.

Key Takeaways

  • Retinol is still considered the gold standard in anti-aging, but new studies have shown that it could be damaging to skin’s barrier function.
  • Due to retinol’s sensitizing side effects and inflammatory properties, it may be time to find a new alternative
  • At OneSkin, we are committed to promoting healthy skin aging without any short- or long-term damage.
  • If you do use retinoids in your skincare routine, counterbalance the side effects with products that promote cellular repair, barrier function, and hydration. Also, make sure to consult your dermatologist if you experience extreme redness, peeling and sensitivity.
  • If you use a retinoid, it's crucial to pair it with the daily use of sunscreen. Opt for a sunscreen with mineral protectants which are gentler on sensitized skin.


Reviewed by Alessandra Zonari, PhD, Chief Scientific Officer (CSO) and Co-Founder of OneSkin

Alessandra earned her Master’s degree in stem cell biology, and her PhD in skin regeneration and tissue engineering at the Federal University of Minas Gerais in Brazil in collaboration with the 3B’s Research Group in Portugal. Alessandra did a second post-doctoral at the University of Coimbra in Portugal. She is a co-inventor of three patents and has published 20 peer-reviewed papers in scientific journals.

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