Protocol Enzyme-Active Retinol Serum

You might have heard of "niacin flush", or the reddening of skin that causes itchiness. Niacinamide has not been found to cause this.

In very rare cases, some individuals may not be able to tolerate niacinamide at all or experience an allergic reaction to it.

If you are experiencing flaking, irritation, and dryness with this ingredient, be sure to double check all your products as this ingredient can be found in all categories of skincare.

When incorporating niacinamide into your routine, look out for concentration amounts. Typically, 5% niacinamide provides benefits such as fading dark spots. However, if you have sensitive skin, it is better to begin with a smaller concentration.

When you apply niacinamide to your skin, your body converts it into nicotinamide adenine dinucleotide (NAD). NAD is an essential coenzyme that is already found in your cells as "fuel" and powers countless biological processes.

In your skin, NAD helps repair cell damage, produce new healthy cells, support collagen production, strengthen the skin barrier, and fight environmental stressors (like UV and pollution).

Our natural NAD levels start to decline with age, leading to slower skin repair, visible aging, and a weaker skin barrier. By providing your skin niacinamide, you're recharging your skin's NAD levels. This leads to stronger, healthier, and younger looking skin.

Another name for vitamin B3 is nicotinamide. This vitamin is water-soluble and our bodies don't store it. We obtain Vitamin B3 from either food or skincare. Meat, fish, wheat, yeast, and leafy greens contain vitamin B3.

The type of niacinamide used in skincare is synthetically created.

Once applied to your skin, enzymes gradually break down the cyclodextrin "ring"; this releases the active ingredient in a controlled way.

In practice, that translates to a long shelf life and a consistently elegant skin feel.

While there is an assumption Caprylic Triglyceride can clog pores due to it being derived from coconut oil, there is no research supporting this. Just patch test if you have concerns.

Fractionated coconut oil and MCT Oil are both listed as Caprylic/Capric Triglyceride according to INCI. This is because INCI names are based on the ingredient’s final chemical composition and not its marketing name or source.

This ingredient is treated as the gold standard fungal acne safe oil. Even though it is coconut derived, the problematic lauric acid is stripped out.

This leaves just caprylic (C8) and capric (C10) acid. These chain lengths actually trend antifungal; a 2020 study found caprylic acid was enough to disrupt Malassezia furfur cell membrane, with a caprylic acid derivative damaging membrane structures at concentrations as low as 0.2%.

PHAs are more gentle than AHAs due to their larger structure. They do not penetrate as deeply as AHAs and take a longer time to dissolve dead cells. Studies show PHAs do not cause as much irritation.

Gluconolactone has some interesting properties:

In a 2004 study, Gluconolactone was found to prevent UV damage in mouse skin cells and has not been found to increase sun sensitivity. However, we still recommend wearing SPF daily.

This ingredient is is an created by reacting gluconic acid with an alcohol.

In skincare, this process helps regulate sebum production. One study found topical L-carnitine can help reduce excess oil and improve skin oil balance. This makes it a great addition for oily or acne-prone skin.

Besides oil control, carnitine supports healthy skin metabolism by boosting lipid breakdown. Research has shown it can improve skin’s resilience against aging and external stressors like UV exposure.

There are no downsides to using this ingredient and it is a great multifunctional ingredient for both sebum regulation and anti-aging care.

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.

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.

That conversion happens in two steps: your skin first turns Retinol into Retinaldehyde (also called Retinal), then turns Retinaldehyde into Retinoic Acid.

Retinol is converted to biologically active retinoic acid via retinaldehyde by dehydrogenases in a two-step oxidation process.

Each step is a little "upgrade" toward the active form which is part of why Retinol is gentler than prescription Retinoic Acid; your skin does the work gradually. This also explains where Retinol sits in the retinoid family.

Here is the retinoid family ranked roughly by strength: Retinyl Esters (like Retinyl Palmitate) < Retinol < Retinaldehyde < Retinoic Acid.

Retinoid activity increases in that order, while tolerance runs in reverse; retinyl esters are the gentlest and retinoic acid the most irritating.

The more conversion steps an ingredient needs, the gentler (and slower) it tends to be, so Retinol lands in a nice middle spot. It's more effective than the esters, gentler than prescription options.

Once it becomes Retinoic Acid, it binds to receptors inside your cells' nuclei (called RARs and RXRs). These receptor pairs bind to specific DNA motifs called retinoic acid response elements and act like switches that turn certain genes on or off.

In practice, this means a few things happen in a formula. It:

That last two are worth a closer look.

A study that tested Retinol directly (not just prescription Retinoic Acid) found that four weeks of retinol thickened the epidermis and switched on the genes for Collagen I and Collagen III, with more procollagen I and III showing up in the skin. And after twelve weeks, facial wrinkles were visibly reduced.

Retinoids more broadly stimulate the skin's synthesis of hyaluronan and other glycosaminoglycans, part of what gives skin a plumper, more hydrated look over time.

So even the gentler OTC form is doing real structural work (not just sitting on the surface).

It's also worth knowing Retinol isn't only a wrinkle ingredient; it can help with uneven tone, dark spots, rough texture, and the look of pores as well because it speeds up turnover and influences pigment.

The research backs this up as well.

A pooled analysis of six clinical studies found that 0.1% stabilized retinol improved all signs of photoaging versus vehicle as early as week 4 and through 12 weeks, with only a few mild cases of irritation.

Another study comparing concentrations found that 0.3% and 1% Retinol were similarly effective at remodeling photodamaged skin, but 0.3% caused fewer adverse reactions when used daily (a useful reminder that more isn't always better).

Retinol is about tenfold less potent than Retinoic Acid. This is why it works as a gentler, non-prescription option that builds results over time.

Typical concentrations range from 0.1-1%, with 0.1% to 0.3% being a well-supported sweet spot for visible benefits with good tolerability.

One quirk worth mentioning: Retinol is famously unstable.

It's highly sensitive to light and oxygen, and UV exposure breaks it down into a range of degradation products.

Real-world testing bears this out, with retinoid content in some products dropping anywhere from 0% to 80% after six months at room temperature, and even more at higher temperatures.

This is why good formulations lean on opaque, air-tight packaging (think tubes and pumps, not clear jars) and often "encapsulate" the Retinol to shield it.

Signs of oxidation include your product turning yellow or smelling "off". Keeping it somewhere cool and dark, and using it up within a few months of opening helps it stay effective.

The most common side effects are mild and temporary: usually some dryness, redness, or light peeling as your skin adjusts. These tend to settle with consistent and lower-frequency use.

Like all retinoids, Retinol works best with nightly use, a good moisturizer, and daytime sunscreen.

The "ramp up" method works well: start with Retinol once a week to give your skin time to adjust, which keeps irritation low. Slowly add more nights until you reach your goal frequency once your skin feels comfortable.

Retinoids also make your skin more sensitive to the sun in the first few weeks, so wear sunscreen every morning and protect your skin from direct sun while you build up tolerance.

One safety note: topical Retinoids aren't recommended during pregnancy or breastfeeding. Systemic absorption from creams is low but because high oral vitamin A is a known teratogen and topical safety data are limited, most clinicians recommend stopping retinoids when pregnant or trying to conceive.

Because retinal only requires 1 conversion step to become retinoic acid, it's the strongest over-the-counter retinoid. It also works at lower concentrations than retinol, since retinal is about 10x more bioavailable.

Studies back up its efficacy in skin:

A foundational trial showed that applying 0.05-0.5% retinal for 1-3 months produced a dose-dependent and significant increase in epidermal thickness + cell turnover markers.

And a head-to-head comparison of 0.05% retinal against a 0.05% retinoid acid found both formulations were effective for the basis of wrinkle/skin roughness features, but retinoic acid caused more local irritation.

More recent controlled trials confirm it improves wrinkles, dermal density, and firmness over 12-24 weeks, with significant improvements in skin texture and firmness (particularly with the higher 0.1% concentration).

Retinal also has one trick the other retinoids do not: it directly fights against acne bacteria since a clinical study showed retinaldehyde-treated areas displayed a significant decrease in counts of viable P. acnes.

This makes it a great pick for people who want to treat aging and breakouts.

Typical cosmetic use sits in the 0.05-0.1% range with 0.05% being the gentle starting point and 0.1% giving stronger results.

Like all retinoids, retinal works best with nightly use, a good moisturizer, and daytime sunscreen. It can cause some irritation so ease into it slowly rather than going all in.

The "ramp up" method works well: start with Retinal once a week to give your skin time to adjust, which keeps irritation low.

Slowly add more nights until you reach your goal frequency once your skin feels comfortable.

Retinoids also make your skin more sensitive to the sun in the first few weeks, so wear sunscreen every morning and protect your skin from direct sun while you build up tolerance.

Tyrosinase is an enzyme that plays a key role in melanin production, which leads to skin darkening when exposed to UV light. By inhibiting this enzyme, PR can help with skin brightening and lifting dark spots.

The manufacturer states 0.5% of PR is more effective than 1% kojic acid. In 2013, a study of 80 participants found combining PR with other skin-brightening ingredients found 57% showed moderate improvement and 17% saw no change. Another study with 20 women reported a 43% reduction in uneven skin tone.

While more research is needed to fully confirm PR's efficacy, there’s no harm in trying it - especially when combined with other proven skin-brightening ingredients.

A clinical study found that applying 0.5% bisabolol daily for 8 weeks produced an average 9% decrease in skin pigmentation. Researchers found it can also suppress the process that leads to excess melanin production in skin.

In vitro studies found that bisabolol combined with propylene glycol significantly increased skin permeability by increasing lipid fluidity in the stratum corneum.

You'll likely see use concentrations quite low, usually 0.1-0.2%.

Overall, this is a well-tolerated ingredient that works well in formulas designed for sensitive, reactive, or post-procedure skin.

It's actually inactive on its own and works like a slow-release "storage" form; the enzymes in your skin called esterases gradually convert it into active vitamin E over time.

One in vivo study showed 5% of the acetate in the living layer of the epidermis converted to vitamin E after 5 days of application. This study also found the skin gained protection against UV damage even though the conversion was slow and small.

Once converted, vitamin E acts as a skin's main fat-soluble antioxidant that fights free radicals to protect skin from damage.

Topical vitamin E generally boosts the skin's photoprotection, and it reduced UV-damage in animal models.

This ingredient has some brightening potential but it's more of a prevention ingredient than spot-fader. Cell studies show it can slow down melanin production but it's worth noting that it's not the most powerful brightener out there.

Overall, it has a pretty solid safety profile and has been found to be non-irritating and non-comedogenic. Allergic reactions may happen but stay rare due to how widely the ingredient gets used.

The concentration will vary depending on the formula; industry data shows 0.1% in baby lotions, 3% in lipsticks, and 5% in foot powders. You can also find this ingredient at 100% in a pure vitamin E oil.

Most leave-on skincare keeps it at the lower end, often between 0.5-1%.

This honeysuckle is native to East Asia and used in traditional Chinese medicine to treat fever and inflammation.

Honeysuckle contains flavonoids and saponins. Both of these components are natural antioxidants that can help soothe the skin.

As most flowers do, honeysuckle has a natural fragrance.

High percentages of Sodium Lactate can have an exfoliating effect.

Fun fact: Sodium Lactate is produced from fermented sugar.

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

Is it bad for your skin?

The answer comes down to concentration. Patch and wash studies have found highly concentrated alcohol-based hand rubs (60-100%) cause less barrier disruption than washing with a basic detergent like SLS. The only measurable effect in these studies was a temporary dip in skin hydration.

Concentrations below 12-15% in leave-on cosmetics is generally well-tolerated. Concentrations above start to see increased transepidermal water loss (TEWL) and reduced hydration.

In concentrations about 58%, it creates temporary channels in your skin's lipid layers to become more permeable and allow other ingredients to slip through easily.

This ingredient can be up to 80% of the formula in alcohol-based perfumes.

Overall, this ingredient is probably harmless if found lower down an ingredients list but worth side-eyeing if it's high up (especially if your barrier is already struggling).

Alcohol can worsen dry skin, eczema, and oily skin, especially at higher concentrations. This is because it can increase transepidermal water loss and decrease hydration to disrupt the skin barrier.

According to the National Rosacea Society based in the US, you should be mindful of products with these alcohols in the top half of ingredients.

True allergic contact dermatitis to ethanol is uncommon, but be sure to patch test if you have dry or sensitive skin.

On the safety side, the Cosmetic Ingredient Review Expert Panel has concluded this ingredient to be safe as used in current cosmetic practices + concentrations.

Typical use levels in a formula run about 1-5%.

Safety-wise, this ingredient is pretty solid; it's even recognized as a food additive. Both animal and clinical studies found no adverse effects at the levels used in cosmetics.

Industry data shows this ingredient is used up to 45.7% in spray products and up to 33% in powder products.

Xanthan gum is a pretty common and great ingredient. It is a natural, non-toxic, non-irritating ingredient that is also commonly used in food products.

Sodium benzoate works as a preservative by inhibiting the growth of bacteria inside of cells. It prevents the cell from fermenting a type of sugar using an enzyme called phosphofructokinase.

It is the salt of benzoic acid. Foods containing sodium benzoate include soda, salad dressings, condiments, fruit juices, wines, and snack foods.

Studies for using ascorbic acid and sodium benzoate in cosmetics are lacking, especially in skincare routines with multiple steps.

We always recommend speaking with a professional, such as a dermatologist, if you have any concerns.