This is Part 3 of our Deep Guide to Retinoids. If you haven't read the earlier parts, start with Part 1 here. Today we grapple with the conundrum: Retinol, Retinal, or Tretinoin — which retinoid reigns supreme?
Retinal (retinaldehyde) emerges as the champion. It boasts a potency comparable to Tretinoin (aka Retinoic Acid), and its tolerance profile rivals — if not surpasses — that of Retinol. Let's demystify these skincare heroes, one molecule at a time.
Which retinoid is the most potent?
The body of scientific literature we've compiled suggests that tretinoin may be, not just marginally, but potentially 10 to 20 times more potent than retinol. And, standing shoulder to shoulder with tretinoin in terms of potency, we find retinaldehyde, or retinal.
To translate this into a practical scenario — if one were to seek the same level of results from retinol as those experienced with retinal or tretinoin, they would require a concentration of retinol that's 10 to 20 times higher.
Now, one might wonder why such a stark disparity in potency exists between retinol and tretinoin, while retinal and tretinoin are near equals. The answer is found in the fascinating world of enzymes.
Two conversions versus one
Remember from the Deep Guide to Retinoids Part 1 that retinol undergoes a transformation to become retinal, which subsequently is converted into retinoic acid. In essence, retinol has to undergo two stages of conversion. In contrast, retinal only needs a single transformation. Retinoic acid, on the other hand, is all set and ready to go, requiring no conversion whatsoever.
The crux of the matter lies in understanding that all these conversions are not created equal.
The rate-limiting step in going from retinol to retinal
The reason behind retinol's significantly lower potency compared to retinal or retinoic acid lies in its conversion process to retinal, which is notably ineffective — a situation we call "rate-limiting". Think of it as attempting to FaceTime over spotty cell reception — the connection is patchy, and not much gets through.
In biochemistry, an enzymatic reaction is said to be "rate-limiting" when it is the slowest step in a metabolic pathway. This step essentially determines the overall rate at which the pathway proceeds. For retinol, the enzyme that mediates its conversion to retinal is often the rate-limiting step — meaning it happens relatively slowly, limiting how efficiently retinol can reach its active form (retinoic acid). This inefficiency is precisely why retinol is less potent than retinal or retinoic acid.
On the other hand, the process that transforms Retinal into Retinoic Acid is impressively efficient — like video-calling on a fast Wi-Fi connection or a 5G network. Data goes right through.
As Retinal requires one fewer stage of conversion, and given that this remaining conversion is so effective, Retinal stands out as considerably more potent than Retinol, and its effectiveness nearly matches that of prescription-grade Tretinoin.
Which retinoid is the most irritating?
Now, let's address the other side of this equation. Retinoids have earned a reputation for sometimes causing skin irritation, which, despite their demonstrated effectiveness, might deter you from using them in high concentrations.
Broadly speaking, tretinoin tends to be the most irritating, while retinal usually causes the least discomfort. Nonetheless, potent retinoids like tretinoin and retinal can lead to skin peeling and dryness in the initial few weeks of application.
If you're a newcomer to the world of retinoids, you might prefer starting with retinol, as it is milder and thus less likely to cause peeling and dryness. Remember, its gentleness is a result of its weaker potency.
Before we go further, let's get to know the 3 types of irritation you can get from retinoids.
Fluhr and colleagues study (1999): How different retinoids cause different irritations
Let's understand irritation profiles better by diving deep into a scientific paper that explores the various types of irritation caused by different types of topical retinoids. This paper, published by Fluhr and colleagues in 1999, comprises two separate studies.
Study 1: Two weeks, three retinoids
The first study involved a daily regimen over a span of two weeks, where 0.07% Retinol, 0.05% Retinal, and 0.05% Retinoic Acid were applied to the forearm skin of six male participants. A dermatologist rated each of the three types of irritation using a scale of 0 (absent) to 3 (severe). In Figure 1, the Y-axis is the sum of those scores — higher bars mean more irritation. Erythema is shown in white bars, scaling in grey bars, and burning in black bars.
You can see that 0.05% retinoic acid is the most irritating overall, with the greatest amount of erythema and peeling.
But in terms of burning and itching, retinol was the worst — despite the low concentration of 0.07%.
It's noteworthy that 0.05% Retinal resulted in less redness and burning sensation compared to both 0.07% Retinol and 0.05% Retinoic Acid. Impressively, the application of Retinal in this study didn't report any instances of burning sensation at all. In terms of causing redness and sensations of burning or itching, Retinal proved to be the gentlest among the tested retinoids.
We can see that retinal and retinoic acid are about the same in terms of scaling and peeling of the skin. The reason is simple — generally speaking, the stronger the retinoid, the more scaling there is during the early days.
Think of retinoids as your skin's personal trainer — a tough-love coach that pushes your skin to shed its old, worn-out surface and grow fresh, new layers. This can make your skin feel flaky and dry, like how a tough workout leaves you sore. The stronger the retinoid, the more intense the "workout." But just like exercise, it's all part of the process of building healthier, better-looking skin. And just like your body adapts to regular workouts, your skin adapts to retinoid use — and the dryness and flaking start to fade.
Study 2: How irritations fade over time (44 weeks)
In the second study, Fluhr and his team took a longer-term view and tracked changes in skin irritation over 44 weeks. During this nearly year-long period, they tested 355 patients with both 0.05% retinal and 0.05% retinoic acid, as well as a control vehicle. Note: retinol wasn't part of this particular study, so it's a straight-up comparison between retinal and tretinoin.
Let's focus on Chart A, which illustrates the outcomes after the first month of treatment.
As expected, retinoic acid didn't pull any punches when it came to skin irritation. Close to half the subjects (44%) experienced redness, over a third (35%) had skin peeling and scaling, and about 29% reported feelings of burning and itching.
On the flip side, retinal adjusted very quickly, causing irritation in less than 10% of participants across all categories after just four weeks.
And after 18 weeks, irritations had subsided for most subjects for both retinal and retinoic acid — suggesting that retinoid-induced irritation naturally resolves over time for most patients.
Going even further out, by 44 weeks even fewer test subjects experienced any irritation compared to the 4-week and 18-week marks.
Retinoic acid takes the crown for being the most irritating — no wonder it's only available via prescription. Even a very low concentration of retinol (0.07%) has a high tendency to cause irritation, particularly in the form of uncomfortable burning sensations. But retinal, despite being highly potent, is surprisingly gentle on the skin. This is precisely why we stand by retinal as the preferred choice over retinol or retinoic acid.
However, if you're new to retinoids, you might still want to start with retinol. As you can see again in this chart, during the initial couple of weeks you might experience considerably more peeling and dryness with retinal and retinoic acid that could be pretty uncomfortable.
Well-formulated products containing retinal and retinoic acid should be able to offset these effects with moisturizing ingredients. If you are new to retinoids, it could make sense to begin with a weaker retinol product with around 0.1% to 0.25% concentration for several weeks until the peeling and dryness disappears, and then switch to the more potent retinal or retinoic acid product.
Why does retinoic acid (tretinoin) cause more erythema (skin reddening)?
You get more redness from topical tretinoin compared to retinol and retinal. That's because tretinoin has something called carboxylic acid attached at its tail end. Carboxylic acid seems to cause skin irritation and redness when applied on the skin's surface.
Retinol and retinal do not have carboxylic acid in their composition. So when retinol or retinal is applied on the skin, there is no irritation on the skin's surface caused by carboxylic acid.
We had mentioned earlier — in Part 1 of the Deep Guide to Retinoids — that retinol and retinal undergo conversion to retinoic acid. But this conversion happens inside the skin cells, where carboxylic acid does not cause irritation problems.
What causes the burning sensation?
Ever wondered why you feel a burning sensation when using retinoids? It's because retinoids stimulate TRP receptors in your skin, tricking your brain into feeling a "burn." TRP receptors are essentially nerve endings — if you've ever felt that cooling rush when applying menthol to your skin, that's your TRP receptors being triggered.
When you apply retinol and tretinoin at the same dosage, they stimulate the TRP receptors to a similar extent. However, retinal is a bit of a game changer — it's softer on the TRP receptors than both retinol and tretinoin. Let's look at the evidence from a study conducted by Luo and his team.
In the chart, retinol is represented by the green bars while tretinoin (denoted as ATRA or all-trans retinoic acid) is indicated by the dark blue bars. As you'll observe, both retinol and tretinoin are equally potent when it comes to stimulating TRP receptors, thus causing irritation.
On the other hand, retinal (the bright pink bars) is much less likely to stimulate TRP receptors, leading to less irritation.
In the majority of skincare products, retinol concentrations tend to be considerably higher than those of tretinoin — often by a factor of five to ten times. As such, it's not difficult to envision how retinol could potentially cause a significantly greater sensation of burning compared to both retinal and tretinoin.
What causes peeling and flaking?
Retinoids essentially push a reboot button on your skin's cell renewal cycle, leading to some initial surface disruption. When you apply retinoids to your skin, they disrupt the organization of corneocytes — the dead cells that form the outermost layer of your skin.
Think of your skin's renewal cycle as a sort of conveyor belt. The formation of corneocytes happens through a process known as keratinization. Fresh skin cells are born in the lowest layer of the epidermis (the basal epidermis). As newer cells are formed underneath, the older cells are pushed outward toward the skin's surface. As they approach the surface, they go through a transformation — they lose their nuclei, flatten out, and fill up with keratin. These transformed, dead cells are what we call corneocytes.
In younger skin, corneocytes shed off naturally, renewing the entire epidermis layer roughly every 30 days. This natural shedding process is known as desquamation — and retinoids assist and regulate it.
But there's a catch. When you first begin using retinoids, this initial phase of rebooting desquamation can cause irritation. You might notice your skin peeling and flaking in the early weeks — it's the old surface cells peeling away before the new skin renewal process has had the chance to stabilize. Your skin might also feel drier and more irritated during this phase, and it becomes more vulnerable to the sun.
This phase of skin peeling is typically short-lived as your skin adjusts to its new rhythm of regeneration. Niacinamide will help lessen the dryness felt during this process, which is why we recommend using retinoids with niacinamide. Similarly, while your skin will be extra sensitive to the sun at the beginning, it will normalize over a period of a few months.
That's it for Part 3 of the Deep Guide to Retinoids. In Part 4, we're going to answer the question: how fast do retinoids work, and how long would it take for you to notice changes in your skin? See you again soon and have a wonderful day!
- Fluhr JW, Vienne MP, Lauze C, Dupuy P, Gehring W, Gloor M (1999). "Tolerance Profile of Retinol, Retinaldehyde and Retinoic Acid under Maximized and Long-term Clinical Conditions." Dermatology 199(suppl 1): 57–60.
- Luo J, Clark R, Yang Q, Du G, Zhou S, Yu W, Qian A, Walters E, Carlton S, Hu H (2013). "Retinoids activate the irritant receptor TRPV1 and produce sensory hypersensitivity." The Journal of Clinical Investigation. DOI: 10.1172/JCI66413.
