Retinol 101: Debunking Retinol as the Gold Standard

Reference Lab

JUL 07, 2021

If you’ve ever considered using anti-aging skin care products, you have likely come across retinol — the commonly-held gold standard for building collagen and improving skin texture. But if you’ve taken the plunge and used a retinoid before, you might have also noticed other, less desirable effects, including redness, skin irritation, sensitivity, and skin fragility. Turns out, there’s a scientific explanation for these symptoms - one that can be helpful to understand when you’re deciding whether to use retinol products and how to use them safely.

01 What is retinol?

Retinol is another name for Vitamin A, and falls under the broader chemical class of retinoids. Retinoids as a whole can be listed on ingredient labels as retinol, retinal, retinoic acid, tretinoin, retinyl palmitate, or retinyl acetate.
As a natural biological molecule, retinol and its derivatives are essential to healthy development of the nervous system and cardiovascular system. It is also one of the main precursor molecules to the formation of rhodopsin, which is critical for proper vision. More recently, one of the molecular configurations of retinoic acid has also been associated with gene regulation.[1] Therefore, naturally occurring retinoids are biologically significant molecules in our bodies.
Given the fact that skin is the largest organ in the body, there are some important functions that retinoids play in maintaining epidermal integrity as well and over the years, this idea has made its way to the forefront of dermatology research.

02 What do Retinoids Do?

The resulting discoveries have laid the groundwork for retinoids to make their way into skincare products as well. So what does retinol do to your skin? Originally, retinol was added to skincare products as an acne treatment. This is due to its comedolytic properties, which allow it to unclog, and even prevent the buildup of oil and dead skin cells in pores.[2]
More recently, however, retinoids have made a bigger name for themselves in the anti-aging sphere due to their ability to boost collagen production, increase blood flow, and encourage faster skin cell turnover.

OneFact The scientists at OneSkin grow 3D human skin models in the lab (every week!) to test the efficacy of products/molecules using gene expression analysis and microscopic imaging.  So if you were wondering, “How does retinol work on skin?”, scientists have studied the short-term effects of retinol on aging skin. Most notably, retinol can reduce the appearance of wrinkles by causing skin cells to renew faster and produce more collagen. This is due to the selective presence of retinoic acid receptors and retinoid X receptors in the epidermal layer.[3] When retinoids bind, it kickstarts a transduction pathway that results in the increase of collagen precursors.
This effect is further made possible by retinoids' ability to promote cells in deeper skin layers to divide more frequently, allowing new cells to replace older cells at the surface, which in turn restores radiance and a youthful appearance. This accelerated process of skin cell turnover can be very effective at temporarily improving skin appearance, which is why it has gained such a cult following over the years. So what’s the catch?

03 Harsh Side Effects of Retinol

Unfortunately, retinol is not without its pitfalls. If caution is thrown to the wind and retinol is used too frequently or at too high of a concentration, or if you have overly sensitive skin, it could impose harsh side effects, including heightened skin sensitivity, redness, peeling, and flaking — all of which could hamper long-term skin health. And if you happened to experience these symptoms associated with the most common retinol side effects on skin, you wouldn’t be alone. In fact, they’re so common that they have been coined the “retinol uglies” .

04 Retinol as a Threat to Skin Barrier Function

A direct consequence of retinol accelerating the rate of cell turnover in skin is the impaired function of new, rapidly produced cells. The new skin cells that are produced too quickly may fail to go through necessary quality checks, and often cause excessive peeling and inflammation. In fact, studies have demonstrated that using retinol impairs skin cell cohesion, which alters the normal barrier that typically seals moisture in and protects the skin from outside stressors. Ultimately, without this protective surface layer, the skin loses moisture and becomes ultra-sensitive, which could serve as a key indicator for when to stop using retinol on your skin.6

05 Heightened Sun Sensitivity

You may have also noticed that unlike peptide moisturizers and serums, retinol products are suggested for nighttime use only. This leads us to another drawback of retinol - extreme sensitivity to sunlight. Not only does this compound rapidly degrade when exposed to UV rays, it also makes your skin more susceptible to sunburn . Since retinol strips the outermost layer of cells from your skin, you are left with a thinner, weaker skin surface that offers less protection from UV damage, which induces damage to DNA and essential structural fibers in the skin, impairing the skin barrier and increasing your risk of skin cancer and other diseases.

06 The “Retinol Uglies”: In Numbers

Intrigued by this phenomenon, the scientists here at OneSkin conducted a genetic expression analysis to observe how various genes associated with skin aging, inflammation, collagen production, and hyaluronic acid production were impacted by retinol, and the results were fascinating. Although retinol was effective at significantly increasing the activity of genes associated with collagen and hyaluronic acid production, it also led to a 10-fold increase in the activity of P16, a gene with long-term expression linked to aging and cellular senescence. Additionally, retinol significantly increased the presence of inflammatory genetic markers in the skin, IL-6 and IL-8. Therefore, although retinol is effective at boosting collagen and hyaluronic acid production, it is done at the expense of increased inflammation and aging.
Alternatively, OneSkin’s proprietary peptide, OS-01, was able to significantly increase the activity of genes associated with hyaluronic acid and collagen production at similar levels to retinol, while reducing the activity of the same genes associated with inflammation and aging that retinol increased. This renders OS-01 a safe alternative to retinol with similar benefits and fewer drawbacks.

Figure 1. Genetic expression analysis of various aging and inflammatory markers, collagen production, and hyaluronic acid production following treatment with OS-01 topical supplement vs. retinol.
Further intrigued by retinol’s impact on skin, the scientists at OneSkin decided to put retinol and OS-01 under the microscope - literally. By using a microscopic visual analysis tool, called histology, to view skin that was exposed to retinol versus OS-01, our R&D team was able to shed light on the impact that these molecules can have on each layer of the skin at the cellular level. Their observations were consistent with those found in the genetic expression analysis. The skin that was treated with retinol experienced a “peeling effect”, further weakening its top layer. Additionally, the cellular structure and organization were compromised with exposure to retinol, indicating that the skin’s barrier function had also been compromised. Conversely, OS-01 induced the formation of a much thicker epidermal layer (dark purple), with a more defined general structure and cellular organization, indicating that skin became thicker and more resilient with improved barrier function when treated with OS-01.
Ex vivo Skin
Figure 2. Ex vivo skin analysis following treatment with OS-01 topical supplement vs. retinol.
OneSkin’s research demonstrates that although retinol is commonly thought to be the gold standard anti-aging ingredient for its ability to boost collagen and hyaluronic acid production, you may want to consider ditching retinol for an alternative or at least use it sparingly, as retinol can ironically accelerate aging and inflammation in the skin.

Key Takeaways

  • Retinol was long thought to be the gold standard of skin care, but new studies have demonstrated that it could be damaging long-term skin health.
  • Due to its potential for long-term damage, it may be time to find a retinol alternative that will help support skin longevity! At OneSkin, we are committed to promoting healthy skin aging without any short- or long-term damage.
  • If you do use retinoid products in your skincare routine, make sure to stay vigilant about skin protection and counterbalance the potential side effects with products that promote cellular damage repair and hydration. Also, make sure to consult your dermatologist if you experience extreme redness, peeling and sensitivity.


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.