Paula's Choice Clinical 0.3% Retinol + 2% Bakuchiol Treatment

It's a well-vetted ingredient for safety and does not penetrate into skin due to its large molecule size.

Because it's a long-chain fatty acid ester, this ingredient may not be fungal acne or Malassezia safe.

Isononyl Isononanoate helps give products a velvet feel and improves spreadability.

Though this ingredient works well with most skin types, some people with sensitive skin may experience a reaction such as allergic rashes, closed comedones, or itchiness.

1) produce more collagen (type I, III, and IV)
2) activate the same genes retinoids do

Unlike retinoids, this ingredient will not increase photosensitivity and is safe to use during pregnancy (but please still check in with your doctor!).

The flagship clinical trial from Dhaliwal et al. 2019 found 0.5% bakuchiol (twice daily) and 0.5% retinol (once daily) reduced wrinkles and hyperpigmentation equally, but bakuchiol had significantly less irritation.

Systematic reviews also back this up:

Bakuchiol is comparable to retinol for photoaging but with better tolerability. It also has mild antibacterial properties against Cutibacterium acnes and antifungal activity in vitro against Candida and dermatophytes.

The reason bakuchiol works well is due to its structure; it is a meroterpene phenol, or a hybrid molecule. The phenol half acts as an antioxidant while the terpene half is fat-loving. This helps the molecule slip through the skin barrier.

This ingredient is usually used between 0.5-2%. Only one case of contact dermatitis has ever been reported for this ingredient.

This ingredient is a multitasker:

Just be sure to patch this ingredient if you have a peanut allergy (though this ingredient is highly processed and the allergenic proteins are typically removed).

As a film former, it creates a light and flexible layer on the skin's surface. This helps lock in moisture without feeling heavy.

It's typically used at concentrations up to 1.9% in leave-on products. CIR has concluded that these ingredients are safe in cosmetics at current use levels.

Due to its large molecule size, it doesn't readily penetrate into skin and mostly just sits on the surface. A large UK-based patch test study of over 1,300 patients found that sensitization to related acrylate copolymers is rare.

Emollients help keep your skin soft and hydrated by creating a film that traps moisture in.

In 2000, Behenyl Alcohol was approved by the US as medicine to reduce the duration of cold sores.

Your skin makes glycerin on its own (mostly from sebaceous oil breakdown) and shuttles it to your outermost layer of skin, or your epidermis, via aquaporin-3.

Aquaporin-3 is a transporter that is essential for normal skin hydration, elasticity, and repair. Interestingly, mice lacking in AQP3 have dry and less elastic skin that can be fully corrected with glycerin.

This ingredient is non-irritating, plays well with almost every ingredient, and works across all skin types. Typical use is anywhere between 3-10% but can go up to 79% in some leave-on products.

Just know very high concentrations (>40%) can feel tacky in low humidity.

Glycerin is the name for this ingredient in American English. British English uses Glycerol/Glycerine.

This ingredient is typically used in concentrations between 1-10%. Studies have found it to be non-sensitizing, non-phototoxic, and non-photoallergenic.

A close cousin of this ingredient is Glyceryl Stearate SE ("self-emulsifying"). This just has a small amount of sodium or potassium stearate added so it can emulsify without a co-emulsifier.

Since this ingredient is an ester of a C18 fatty acid, it may not be fungal acne safe. The Malassezia yeast can potentially metabolize within the C11-C24 range.

Fun fact: The human body also creates Glyceryl Stearate naturally.

The Cosmetic Review Expert Panel has concluded the alkyl benzoate group to be safe as used in cosmetics; it wasn't found to be a skin irritant and unlikely to be absorbed due to its low water solubility.

This report recorded almost 1000 reported uses with concentrations up to 59% in leave-on products but your cosmetics will typically use 0.5-15% depending on the product.

It's often called a "SPF booster": this is because it keeps UV filters properly dissolved and evenly distributed to support a sunscreen's performance. It doesn't actually raise SPF on its own.

Overall, this ingredient is well tolerated.

This ingredient is fungal acne safe because it is an ester of benzoic acid.

Think of this ingredient as two parts stuck together: an oily part and an acid part. Malassezia only gets a meal when it can snip off a fatty acid to eat. With C12-15 Alkyl Benzoate, the acid part is benzoic acid, which isn't a fatty acid and which the yeast can't use as food.

Benzoic acid is actually used as a preservative to stop yeast from growing.

The oily part is a blend of C12-15 fatty alcohols but fatty alcohols in this size range can support only a little Malassezia growth (mostly for one species of Malassezia as well).

In the ingredient, those alcohols stay locked inside the molecule. The yeast can only reach them by snipping the benzoate bond, and that type of bond is harder for it to cut than a normal fatty bond.

So not much gets released. And whatever does get snipped comes packaged with benzoic acid, which discourages yeast growth.

The common safety discussion around this ingredient involves a manufacturing byproduct called 1,4-dioxane.

Trace amounts can form during production but the EU's Scientific Committee on Consumer Safety has concluded that levels at/below 10 ppm in finished products are safe (commercial products consistently fall within acceptable margins).

True allergic reactions are uncommon and the CIR Expert Panel has confirmed this ingredient to be safe as used in cosmetics.

Because it is derived from lauric acid, it may not be fungal acne safe.

Because it’s oil-soluble, THD dives deep into your skin’s fatty layers (think ceramides and cholesterol) to fight off the kind of free radicals that mess with your skin barrier. This makes it a great pair with water-based vitamin C (ascorbic acid) that mainly works on the surface.

Even at just 0.1%, THD is already showing great antioxidant activity. When used up to 2%, it helps keep your skin happy and calm, especially when it’s stressed from pollution or sun.

Want to fade dark spots or tackle hyperpigmentation? You’ll want 5% or more. Pairing it with brightening buddies like niacinamide or licorice root gives even better results. One study even used 30% THD with other brighteners and saw real results on stubborn discoloration, even in melasma-prone skin.

A note on THD: It’s has a slightly silky, oily texture and usually shows up colorless or pale yellow (though the exact shade can vary by supplier).

While you can sneak it into water-based formulas, it really shines when paired with silicones or oils, which help your skin soak it up better.

THD is pretty stable, but it’s still vulnerable to degradation like ascorbic acid. Too much light or heat (above 113°F / 45°C) can break it down over time. Go for dark and opaque packaging that keeps it safe and shady!

Read more about other types of Vitamin C:

It has the most scientific studies backing up its skin benefits out of all the non-prescription ingredients.

Retinol is proven to:

This is why retinol is effective at removing wrinkles, fading dark spots, treating acne, and reducing the appearance of pores.

Studies show retinol is less effective when exposed to UV. Be sure to look for appropriate packaging to keep your retinol potent (similar to Vitamin C).

Using retinol or any retinoids will increase sun-sensitivity in the first few months. Though studies show retinoids increase your skin's natural SPF with continuous use, it is best to always wear sunscreen and sun-protection.

We recommend speaking with a medical professional about using this ingredient during pregnancy.

Retinol may cause irritation in some people, so be sure to patch test. Experts recommend 'ramping up' retinol use: start using this ingredient once a week and work up to using it daily.

Read about Tretinoin

Ceramides are an important building block for our skin barrier. A stronger barrier helps the skin look more firm and hydrated. By bolstering the skin ceramides act as a barrier against irritating ingredients. This can help with inflammation as well.

If you would like to eat ceramides, sweet potatoes contain a small amount.

Read more about other common types of ceramides here:
Ceramide AP
Ceramide EOP
Ceramide NP

This ingredient calms down a specific inflammation signal in your skin cells (called IL-6). When left unchecked, this signal triggers enzymes that break down collagen and elastin.

Clinical testing showed statistically significant improvements in:

Studies also found the more of this ingredient used, the more your skin produces Collagen I, fibronectin, and hyaluronic acid.

You'll likely see this ingredient paired with Palmitoyl Tripeptide-1 in the well-known Matrixyl 3000 complex for enhanced anti-aging effects.

A 3% concentration applied twice daily for two months showed meaningful skin rejuvenation results in clinical panels.

Fungal acne note:
Usually a palmitic acid component can feed Malassezia in unbound form, but here is is covalently bonded to the peptide. This means it is very difficult for Malassezia to access, and therefore very unlikely to cause fungal acne.

Once inside, it helps with keeping skin springy and firm. It works by mimicking the skin repair signals your skin naturally sends out when it's damaged and telling it to kick into rebuild mode.

Studies have shown it can help strengthen the skin barrier as well so it's useful beyond just anti-aging.

In vitro studies suggest it can switch on genes that help skin cells grow, move around, and rebuild skin structure. Just keep in mind most of the strong evidence is from lab studies rather than large-scale clinical trials.

Lab studies suggest it can switch on genes that help skin cells grow, move around, and rebuild skin structure.

This ingredient is usually used at very low concentrations (0.002% in leave-on products).

Fungal acne note:
Usually a palmitic acid component can feed Malassezia in unbound form, but here is is covalently bonded to the peptide. This means it is very difficult for Malassezia to access, and therefore very unlikely to cause fungal acne.

Interestingly, the size of the molecule affects its behavior:

Some clinical evidence links low molecular weight versions to improved wrinkle depth, elasticity, anti-inflammatory effects, and barrier repair.

Many serums use a blend of both weights so you can get surface hydration plus longer-lasting and deeper effects.

You'll typically see concentrations between 0.1-2% for this ingredient.

One component, glabridin, has extra potent antioxidant and soothing properties. It has also been found to block pigmentation from UVB rays in guinea pigs.

Licorice Root also contains a flavonoid. Flavonoids are a natural substance from in plants. Flavonoids also have antioxidant properties.

Another component, glycyrrhizin, has been found to have anti-inflammatory and antimicrobial benefits. This may make licorice root extract effective at treating acne. However, more research is needed to support this.

Liquiritin is one of the flavone compounds found in licorice. It has been found to help lighten skin by preventing tyrosinase from reacting with tyrosine. When the two react, protein is converted to melanin. Melanin is the substance in your body that gives your features pigmentation.

Licorice root is native to Southern Europe and Asia. It has been used in traditional Chinese medicine to help with respiratory issues.

Licorice Root also contains a flavonoid. Flavonoids are a natural substance from in plants. Flavonoids also have antioxidant properties.

Another component, glycyrrhizin, has been found to have anti-inflammatory and antimicrobial benefits. This may make licorice root extract effective at treating acne. However, more research is needed to support this.

Liquiritin is one of the flavone compounds found in licorice. It has been found to help lighten skin by preventing tyrosinase from reacting with tyrosine. When the two react, protein is converted to melanin. Melanin is the substance in your body that gives your features pigmentation.

The cellulose and fiber in colloidal oatmeal help reduce inflammation. This can also help the skin feel softer.

Colloidal Oatmeal is also an antioxidant. Antioxidants protect our skin from free-radical damage.

Oatmeal also contains beneficial compounds:

This ingredient is created by mixing grounded oatmeal and a liquid base.

Evidence in humans is limited to the non-root parts of this plant; topical arctium fruit extract showed improvements in dermal extracellular matrix metabolism and visible wrinkles.

Your skin can't convert salicin to salicylic acid because it needs specific enzymes that aren't present on the skin's surface. It won't behave like true salicylic acid, especially at the concentrations used in cosmetics.

However, this ingredient has its own perks. It contains flavonoids, polyphenols, and tannins that give it proven antioxidant and soothing properties.

An 8-week clinical study found a cream with 2% of this extract improved skin microcirculation, elasticity, and dark circles. This is most likely due to its role in increasing hyaluronic acid synthesis in fibroblasts and improved vascular integrity.

Another study found a topical serum with 0.5% salicin showed improvements in visible signs of aging, hyperpigmentation, and texture.

Just be careful if you have a known aspirin/salicylate allergy and be sure to consult with a medical professional about using this ingredient if you do.

Fun fact: Willow Bark extract has been used for thousands of years and ancient civilizations used white willow to help treat pain and fevers.

Phytosterols aid skin barrier recovery by traveling deeper into the skin rather than just sitting on top of it. Once inside, they reduce transepidermal water loss (TEWL) and keep skin feeling soft / supple.

Research on phytosterols in keratinocyte and macrophase models has shown meaningful inhibition of pro-inflammatory mediators. This supports their reputation as a calming ingredient for reactive or sensitive skin.

Subjects with soy allergies did not show a reaction to phytosterols in safety tests, but it wouldn't hurt to patch test if you do have a soy allergy.

Fungal acne:
Malassezia uses sterols to build its own cell walls so there's a theoretical concern that it could also make use of sterol ingredients in skincare.

Though no study has actually proven this happens with topical products, we err on the side of caution and list this ingredient as not safe for fungal acne. However, it may not be a trigger for everyone.

It plays well with most ingredients and is typically used at 0.1-1%. However, concentrations up to 50% have been reported in moisturizers.

Research shows it can encourage your skin cells to turn over and renew by stimulating keratinocyte and fibroblast proliferation.

It also has mild keratolytic properties to help loosen and shed dead skin cells without being harsh.

Studies also suggest allantoin can help calm inflammation by dialing down some of the chemical signals your skin sends out when it is irritated.

This ingredient is typically used in the 0.1-0.5% range, and the FDA recognizes it as a skin protectant in OTC products up to 2%.

Overall, allantoin is a wonderful addition to most routines; it is stable across a wide pH range (~4-8), works well with other ingredients, and is considered non-sensitizing/non-irritating.

Fun fact: Allantoin is naturally occurring in comfrey root, beets, chamomile, and wheat sprouts. Our bodies even produce it as a byproduct of uric acid metabolism.

Tocopheryl Acetate is commonly found in both skincare and dietary supplements.

The smaller fragments are water-loving so it forms a thin, moisture-retentive film on skin that helps reduce water loss and leaves things feeling softer and smoother.

You'll often see it credited with "firming" or "anti-aging" benefits as well; this claim traces back to lab research like Tokudome et al. (2012). This study added low-molecular-weight soybean peptides to cultured human skin fibroblasts and saw increased type I collagen gene expression + collagen content.

The caveat is that this is in-vitro and oral-peptide research so the only solid, well-established role for the topical ingredient is skin conditioning.

Typical use concentrations go up to 3.5% in mascara but this ingredient is typically used at low levels well under 1%.

It has a reassuring safety profile as well; it's not a skin irritant in testing up to 20% and has limited skin penetration due to its large size and water-loving nature.

Anyone with a known soy allergy should definitely patch test or skip this ingredient. There's also a single case of a soy-containing product aggravating rosacea via protein contact dermatitis, but this is very rare.

Once there, it acts as a matrikine, a signaling peptide that prompts fibroblasts to produce more collagen, fibronectin, and hyaluronic acid.

In vitro studies show it can boost collagen production in skin cells even when UV-damaged skin samples were treated with it at a tiny concentration (it almost fully restored dermal collagen at 5ppm). It achieved this at 100x lower concentration than retinoic acid, which needed 500 ppm to do the same thing.

Human clinical data is promising, but modest:

A study of 23 female volunteers found a small but statistically significant increase (~4%) in skin thickness after treatment at 4 ppm.

A separate small trial of 15 women showed statistically significant reductions in wrinkle length, depth, and skin roughness after applying it twice daily for four weeks.

You'll likely see Pal-GHK paired with Palmitoyl Tetrapeptide-7 as part of the Matrixyl 3000 complex.

Fungal acne note:
Usually a palmitic acid component can feed Malassezia in unbound form, but here is is covalently bonded to the peptide. This means it is very difficult for Malassezia to access, and therefore very unlikely to cause fungal acne.

Your skin has a natural pH and acid mantle. This acid mantle helps prevent harmful bacteria from breaking through. The acid mantle also helps keep your skin hydrated.

"Alkaline" refers to a high pH level. A low pH level would be considered acidic.

This ingredient may not be fungal acne safe because behenic acid falls into the chain-length range that Malassezia yeasts can feed on.

Because it is not a free-fatty acid, this ingredient is fungal acne safe (there's nothing for Malassezia to feed on).

The root of the plant has been used in traditional folk medicine throughout Asia.

It is soluble in water. The number '8' stands for the molecular weight of the ingredient.

Like other types of silica, this ingredient can be used to thicken a product. As an absorbent, it may be used to absorb extra water or help prevent clumping.

Although “aluminum” in an ingredient name can raise red flags for some consumers, the form and usage context matter significantly. For typical topical applications, there is no substantial evidence of health risks - such as cancer, neurotoxicity, or systemic “aluminum overload.”

This property also makes Pentylene Glycol a great texture enhancer. It can also help thicken or stabilize a product.

Pentylene Glycol also acts as a mild preservative and helps to keep a product microbe-free.

Some people may experience mild eye and skin irritation from Pentylene Glycol. We always recommend speaking with a professional about using this ingredient in your routine.

Pentylene Glycol has a low molecular weight and is part of the 1,2-glycol family.

The CIR Expert Panel assessed the safety of 126 acrylates copolymers and concluded they are safe in cosmetics at current use levels when formulated to be non-irritating. They also noted the levels present in finished cosmetic products are not considered a safety risk and Genotoxicity testing (Ames tests, chromosomal aberration assays) has come back negative across the board.

Though the raw building blocks (like acrylic acid) can be irritating on their own, cosmetic-grade versions go through purification to keep levels extremely low.

Sodium Acrylates Copolymer is a large molecule that doesn't penetrate skin barrier in any meaningful way.

You'll likely find this ingredient with steareth-2 (it's oil-loving sister) where the two work together to give products a cushiony feel.

Typical use levels sit at around 1-5% and this ingredient has been found to be non-irritating by the CIR Expert Panel.

It plays several roles in a formula:

Typical use levels for this ingredient sit around 1-10% and the Cosmetic Ingredient Review Expert Panel has affirmed safety at concentrations up to 25% in leave-on products.

Multiple assessments have found it to be non-irritating and non-sensitizing to most people.

However, there have been some cases of allergic contact dermatitis in patients with chronically compromised skin barriers.

Cetearyl alcohol has a comedogenic rating of 2 and irritancy rating of 1. Both of these numbers come from the 1989 study that used rabbit ears; a "2" means mildly comedogenic and a "1" means low irritancy.

Here's the catch: rabbit skin is more sensitive than human skin and throws a lot of false positives. A 1996 reappraisal found that ingredients rated 1-2 in the rabbit ear tests are generally safe for humans.

Remember comedogenic ratings are unable to assess the entire formula of a product or how it will react on your skin. Just be sure to patch test if you are unsure about certain ingredients.

This ingredient is not fungal acne safe. Cetearyl alcohol is a fatty alcohol with chain lengths that fall within the range that Malassezia can metabolize.

A 2019 study has also observed Malassezia growth in the presence of this ingredient, confirming it to be not-fungal acne safe.

This ingredient is considered gentle and non-comedogenic. However, it may still be irritating for some.

Overall, HMC is a gentle and supportive ingredient. Further research is needed on the claims that this ingredient can "erase dark circles".

On top of that, this ingredient can counteract the effects of hard water by binding to the minerals in it.

One thing worth knowing is that Disodium EDTA has been shown to be a mild penetration enhancer. It can help other ingredients absorb into skin more effectively which can be a double-edged sword (great for actives, but can also make the active too strong if you have sensitive skin).

Clinical patch testing showed no significant skin irritation at typical use concentrations and minimal dermal absorption.

You'll most likely see this ingredient near the end of an ingredient list. It's typically found in concentrations less than 1%.

The way it works is worth understanding; benzoic acid works when the formula is acidic. It is able to sneak into a microbe's cell and mess up how it functions to stop it from growing in an acidic product.

However, the acid switches to an inactive form and stops working if a product isn't acidic enough (above ~5 pH). This is why you'll often see it in low pH products or teamed up with other preservatives to cover the gap.

Safety wise, it's one of the better studied preservatives out there.

The Cosmetic Ingredient Review Expert Panel has concluded this ingredient to be safe for use in cosmetic formulations at concentrations up to 5%.

A large international review found this ingredient had no effects on the human body and had low irritation potential.

Just so you know, real world use is usually much lower than the 5% ceiling (usually 1% of less).

The EU caps it at 2.5% in rinse-off products, 1.7% in oral care, and 0.5% in leave-on products.

One thing worth mentioning (it's nothing to worry about): some people get a little stinging or flushing where they apply it. This isn't a true allergy; it's a temporary and harmless reaction. This is the same kind of mild tingle you might notice from sorbic acid.

Industry-reported use ranges from 8% in rinse-off products and 2% in leave-on formulations.