Numbuzin No.5 Vitamin Glutathione Dark Spot Cream

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.

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.

You'll likely see this in many BHA products because this is the go-to solvent for salicylic acid.

This ingredient is typically used at levels between 2-20%.

Regarding fungal acne:
In 2019, this ingredient was tested against multiple Malassezia species (the yeast that causes fungal acne) and showed no growth.

The reason this ingredient is so effective is because it forms a thin film on the skin that reduces transepidermal water loss (TEWL) while supplying linoleic acid to the stratum corneum to improve barrier strength.

The high linoleic acid content is particularly noteworthy for acne-prone skin.

Research suggests that acne-prone skin tends to be deficient in linoleic acid in sebum. Topical application may help replenish this to support a healthier follicular environment and less comedone-promoting sebum.

One randomized study found sunflower seed oil preserved skin barrier integrity in adult volunteers with and without atopic dermatitis (outperforming olive oil).

This ingredient is well-studied, gentle, and an effective emollient suitable for most skin types.

On fungal acne: This ingredient may not be Fungal acne (Malassezia folliculitis) safe. This is because it contains fatty acids with carbon chain lengths in the C11-C24 range.

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.

Due to its antioxidant properties, trehalose may help with signs of aging. Antioxidants help fight free-radical molecules, unstable molecules that may damage your skin.

In medicine, trehalose and hyaluronic acid are used to help treat dry eyes.

Some animals, plants, and bacteria create trehalose as a source of energy to survive freeze or lack of water.

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%.

Some studies suggest this ingredient may inhibit pigment production in the skin to help even out skin tone.

This makes it a promising ingredient for slimming and anti-cellulite products!

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.

Studies show these polyphenols help improve skin health.

The more famous ingredient from cocoa tree is cocoa butter.

Research shows centella asiatica can help increase Type I collagen production by increasing fibroblast production. Fibroblast helps form connective tissue.

The combination of all these properties makes centella asiatica leaf extract effective at soothing the skin.

Other components of centella asiatica leaf extract include Vitamin A, vitamin C, several B vitamins, and Asiatic Acid.

Recent studies found madecassoside may help prevent damage from UV rays by preventing UV-induced inflammation. Further research is needed.

This plant has been used as a medicine and in food for many centuries. As a medicine, it is used to treat burns, scratches, and wounds.

Two clinical studies in postmenopausal women found that applying argan oil for 60 days significantly improved skin elasticity and moisturization (reduced transepidermal water loss and increased epidermal water content).

Since it is high in oleic and linoleic acid, this ingredient may not be fungal acne safe. Both of these fall in the C11-C24 range that Malassezia yeast can metabolize.

This pairing gives it barrier-supporting and moisturizing properties. Linoleic acid, an essential omega-6 fatty acid, can be incorporated into complex skin lipids. Topical application has shown barrier repair, anti-inflammatory, and wound-healing effects in cell and animal studies.

Beyond fatty acids, sesame oil brings something more distinctive to the table:

It contains natural antioxidants sesamol, sesamolin, and gamma-tocopherol. These also give the oil notably high oxidative stability.

One of the oil's key lignans, sesamin, has also demonstrated anti-inflammatory activity in preclinical models.

A 2023 clinical study found that a single application of sesame seed oil to the forearms of 35 healthy women improved stratum corneum hydration (though it didn't outperform raspberry seed oil).

The comedogenic rating of 1-3 depends on the type of sesame oil; unrefined carries a rating of 3 while refined sesame oil drops to a 1.

This ingredient may not be safe for fungal acne as it contains fatty acids that can feed Malassezia.

You can also find carbohydrates, lipids, proteins, minerals, vitamin A, and Vitamin C in these berries.

This ingredient is volatile which means it will mostly evaporate (but it evaporates slower than older cyclomethicones, like Cyclotetrasiloxane).

Typical concentration ranges from 1-30% depending on if it's being used to tweak the feel of a product or acting as the main emollient.

D-panthenol is also known as dexpanthenol. Most cosmetics use dexpanthenol or a mixture of D and L-panthenol.

Panthenol is famous due to its ability to go deeper into the skin's layers. Using this ingredient has numerous pros (and no cons):

Like hyaluronic acid, panthenol is a humectant. Humectants are able to bind and hold large amounts of water to keep skin hydrated.

This ingredient works well for wound healing. It works by increasing tissue in the wound and helps close open wounds.

Once oxidized, panthenol converts to pantothenic acid. Panthothenic acid is found in all living cells.

This ingredient is also referred to as pro-vitamin B5.

Polymethylsilsesquioxane has not been shown to clog pores. It has been deemed safe to use up to 55%, but most cosmetics use much less.

If you have concerns about using this ingredient, we recommend speaking with a professional.

Propanediol is not likely to cause sensitivity and considered safe to use. It is derived from corn or petroleum with a clear color and no scent.

These "skin-like" liquid crystals improve skin barrier integrity and promote the delivery of actives into the skin.

This ingredient is well-tolerated and has no significant sensitization data.

Because it is derived from the fatty acids in olive oil, this ingredient may not be fungal acne safe.

The Cosmetic Ingredient Review (CIR) Expert Panel evaluated it (along with 22 other acryloyldimethyltaurate polymers) and concluded it's:

Due to its large molecular size, it sits on the surface of skin rather than penetrating it.

This ingredient is also known as part of Olivem 1000, with Cetearyl Olivate being the other part.

According to a manufacturer, this ingredient helps preserve the natural microbiome of skin. Having a healthy microbiome helps keep our skin healthy and protects against harmful bacteria.

Please note, having a healthy microbiome is different from fungal acne; a healthy microbiome includes small amounts of yeast that normally live on your skin without causing problems.

Fungal acne happens when one type of yeast (Malassezia) grows out of control. This is usually because it's feeding on certain oils or fatty acids. Due to the olive oil base, this ingredient may not be fungal acne safe.

It can also form a thin protective film on skin. One study found that a formula using this polymer helped slow down how quickly other ingredients (like DEET) were absorbed through skin.

A 2024 study of over 1,300 patients confirmed that sensitization to this ingredient is rare. It is also non-mutagenic and has a clean track record.

This matters a lot because a lot of actives (like vitamin C) needs a specific pH to work well and feel comfortable on skin.

Concentration use ranges from 0.1-1.0% depending on the formula.

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

In a 24 hour occlusive patch test on 56 subjects, 10% sorbitan isostearate was completely non-irritating. Most formulas use less than 10%.

Because it's a fatty acid ester, it may not be fungal acne safe since the Malassezia yeast can utilize it as a nutrient source.

Your skin has cells called fibroblasts that build collagen (the stuff that keeps skin firm and smooth). Adenosine basically flips a switch on these cells that tells them to get to work making more collagen and other proteins. These cells slow down on their own as skin ages, so Adenosine helps give them a little nudge to keep going.

The clinical backing is pretty solid too.

A blind, randomized, placebo-controlled trial of 126 women aged 45-65 tested a 0.1% cream twice daily and found real improvements in crow's feet and frown lines using a precise 3D skin-mapping technique; these changes showed up by week 3 and held at 2 months.

A later study using Adenosine-loaded dissolving microneedle patches reported gains in wrinkle depth, dermal density, elasticity, and hydration.

On concentrations, South Korea's Ministry of Food and Drug Safety has set 0.04% as the approved functional anti-wrinkle level. You'll typically see this ingredient used somewhere in the 0.04-0.1% range since it works at low doses.

This ingredient has been found safe for cosmetics with the data showing no irritation or sensitization.

Overall, this is a great ingredient for any anti-aging routine and has no photosensitizing effect, so it suits both AM and PM use.

Interestingly, topically applied Palmitic Acid can be elongated into longer chain fatty acids and ceramides. A 2019 study found low levels of Palmitic Acid lead to slower development of cells, suggesting it plays a role in keeping your skin's renewal process on track.

The CIR (Cosmetic Ingredient Review) panel determined it safe as used in cosmetics at concentrations up to 13%. It is non-irritating and non-sensitizing in clinical studies.

The culprit behind fungal acne, the Malassezia yeast, feeds on fatty acids with carbon chain lengths between C11-C24. Palmitic Acid, at C16, falls right into that sweet spot.

In vitro studies have shown that Palmitic Acid is one of the fatty acids that induce rapid Malassezia growth in lab settings.

It's worth noting that what feeds yeast in a lab doesn't necessarily feed it on your face since formulation and your skin's chemistry play a bigger role.

This ingredient is an emollient, emulsifier, and penetration enhancer. As an emollient, it helps soften and hydrate skin by trapping moisture within. As an emulsifier, it prevents oil and water ingredients from separating.

Hydrogenated Lecithin can form tiny spherical structures made of phospholipid bilayers called liposomes. These liposomes are able to capture compounds inside their structure and deliver them through the skin barrier.

Because phospholipids are a natural component of our cell membranes, this ingredient is inherently compatible with skin.

A 2021 study found lecithin-based surfactants were less harsh and more tolerable comared to Sodium Lauryl Sulfate (SLS).

In skincare, it's best known as a brightening ingredient that slows down tyrosinase, the key enzyme that makes skin pigment. It also nudges the skin toward making a lighter type of pigment instead of a darker one.

This is why you'll see it in products aimed at dark spots and uneven tone.

A small number of real human trials have found a topical glutathione lotion:

The honest caveat is that the current evidence is still thin (few studies, small groups, short timelines). Glutathione also doesn't absorb into skin very easily so results tend to be modest and fade if you stop using it.

One thing worth clearing up:

The scary side effects you may have heard about come from glutathione injected intravenously, which has real safety concerns. Applying it topically is a completely different thing and has a clean track record.

Most human studies used it around 2% (as Glutathione or Glutathione Disulfide) and a 2% oxidized glutathione lotion and a 2% S-acyl glutathione cream are the concentrations with actual clinical data behind them.

There's no established "ideal" percentage yet but 1-2% is the evidence-backed range.

Allergy-wise, there is very low risk for this ingredient; it was well-tolerated across the topical trials. Only one participant had mild temporary redness that cleared up on its own and another study reported no adverse reactions at all.

One trial had ~10% of users drop out for irritation was using a combination cream that also had 10% azelaic acid so the irritation likely wasn't from the glutathione. There's no notable contact-allergy signal for topical glutathione in the literature but patch-testing before first use is still sensible for those with sensitive skin.

In skincare, PC pulls double duty:

The linoleic acid it carries gets incorporated into skin ceramides and helps reinforce the lipid matrix.

Interestingly, it can help top of the omega-6 fatty acid that's often low in acne-prone and atopic skin. There's a sizeable body of literature that supports its use in dry, barrier-impaired, and breakout-prone skin.

There are two kinds of PC you'll see on ingredient lists.

Use levels range from <1% as a liposomal carrier and between 20-40% in lamellar matrix sytems.

On the emulsifier side, it keeps your formula smooth and well-mixed by playing peacekeeper for ingredients that don't naturally get along (like oil and water).

Because it has a C12 (lauric acid) fatty acid chain, this ingredient can potentially feed the Malassezia yeast that causes fungal acne. The Malassezia yeast prefers esters with C11-C24 fatty acids.

This ingredient is an ester of lauric acid and Polyglycerin-10.

As an antioxidant, it helps fight free-radical molecules. Free-radical molecules are capable of damaging our cells and other genetic material. Thus, antioxidants may reduce the signs of aging.

This ingredient is oil-soluble.

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.

Madecassoside pairs well with other hydrating or antioxidant ingredients like Ascorbic Acid or Hyaluronic Acid.

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

Fun fact: Cellulose is the most abundant form of organic polymer on Earth.

It is synthetic and reported use concentrations are very low (up to 0.086% in face powders).

Fun fact: Polyglutamic Acid is found in the Japanese food, natto. It is also being used in cancer treatment studies.

In cosmetics, it mainly functions as a bulking agent, viscosity controller, binder, and absorbent. It helps thicken products, stabilize powders, and get certain textures a less "wet" feel.

This ingredient has a pretty solid safety profile; it's recognized as a safe food additive and its large molecular size means it doesn't meaningfully penetrate skin.

Human repeat insult patch tests using a rinse-off facial product containing 42.69% dextrin found no skin irritation or sensitization in 54 subjects.

Typical real-world usage is much lower: usually under 1% as a texture modifier and up to 40% in masks (rinse off products use less).

You'll usually find this in concentrations between 0.2-5%.

Typical use concentrations for this ingredient are usually quite low (under 5% in leave-on skincare).

Safety data on cysteine specifically shows it's not a skin or eye irritant.

Topically applied tocopherol has been shown to protect against UV damage by ramping up the skin's own natural defense enzymes.

It also acts as a skin conditioning agent; some studies show that regular topical use can improve the skin's water-binding capacity over 2-4 weeks.

This ingredient is especially loved for being a team player. When combined with Vitamin C, the photoprotective effect of both ingredients roughly doubles and the combo also helps reduce UV-induced DNA damage.

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.

In formulations, it also serves as a stabilizer that helps protect other oxidation-prone ingredients from degrading.

Concentrations usually range from 0.1-1% in most leave-on products.

In a formula, it does the 3 classic vitamin C jobs: it acts as an antioxidant, helps brighten skin tone by inhibiting tyrosinase, and supports collagen.

The evidence is reasonably solid for a cosmetic ingredient; Liao and colleagues (2018) showed it's significantly more stable than ascorbic acid while still being effective.

A 2021 study by Zerbinati and colleagues tested a serum with 30% 3-O-ethyl-l-ascorbic acid and 1% lactic acid significantly increased collagen production, reduced UVB-induced DNA damage, and decreased melanin on a reconstructed pigmented skin model.

Typical real world usage sits around 0.5-5% (and 1-2% is common for daily serums).

Amounts up to 30% have been shown to be non-irritating on human skin samples, but two isolated cases reported allergic contact dermatitis so a patch test is sensible if you have reactive skin.

It works mainly by inhibiting tyrosinase, the enzyme your skin uses to make melanin. This means less new pigment gets produced over time.

There are two forms you'll see on labels: beta-arbutin (listed as just "Arbutin") and alpha-arbutin (the more stable and effective of the two).

The evidence behind this is solid: it's less cytotoxic to melanocytes than hydroquinone and comparably effective with kojic acid for hyperpigmentation.

One human study using a 10% solution reduced UVR-induced hyperpigmentation by 43.5% (jumping to 63.3% when paired with aloesin).

More recent clinical work backs it up too; a 2025 study on a 5% alpha-arbutin + 2% kojic acid cream found it comparable to triple combination prescription formulas but with lower recurrence for melasma.

Typical usage in cosmetics serums land in the 1-2% range.

It's a well-tolerated, non-irritating, and non-photoreactive ingredient that also gives some antioxidant benefits too.

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.

Studies find EGF help with:

In South Korea and China, EGF is considered a controversial ingredient. The South Korean Ministry of Food and Drug Safety has cracked down on companies with products including EGF due to false advertisement claims.

According to Dr. Zoe Draelos, growth factors have some drawbacks:

There is also controversy surrounding growth factors. The controversy is due to their mitogenic activity, or their ability to increase the number of cells. It is best to avoid using growth factors if you have psoriasis or are at risk of skin cancer. However, it should be noted EGF are not mutagenic - meaning they will not cause cancer.

There is also controversy surrounding EGF. The controversy is due to their mitogenic activity, or their ability to increase the number of cells. It is best to avoid using growth factors if you have psoriasis or are at risk of skin cancer. However, it should be noted EGF are not mutagenic - meaning they will not cause cancer.

This is a great ingredient for dry, compromised, or aging skin; our skin starts to produce less cholesterol with age.

Research shows cholesterol works best in combination with ceramides and fatty acids, the other two major components in your skin barrier.

Cholesterol is also a well-establish penetration enhancer and can help other actives absorb more effectively.

Cosmetic-grade cholesterol is usually derived from lanolin but plant and synthetic options also exist. We recommend reaching out to the brand if you have questions about their source of cholesterol.

Topical vitamin C has been shown to help neutralize oxidative stress from UV and pollution, helping to improve photoaging and hyperpigmentation when used consistently.

One clinical study found that using 5% topical vitamin C for six months improved signs of photodamaged skin, both on the surface and in the deeper structural layers of the skin.

While vitamin C doesn’t replace sunscreen, studies show it can boost photoprotection when combined with Vitamin E and ferulic acid. These two ingredients help improve stability and protective effects.

The big downside of this ingredient is formulation difficulty. Vitamin C is prone to oxidation and doesn't penetrate the skin unless formulated correctly. Research found that vitamin C absorbs into the skin best at a low pH (< 3.5) with about 20% being the upper limit for effective absorption.

Skin levels can saturate after repeated application; this means your skin won’t keep absorbing more once it’s full of vitamin C. This is why more isn’t always better with vitamin C and why very high concentrations don’t necessarily give extra benefits.

Ascorbic acid generally works well with many skincare ingredients but can be irritating when combined with other active ingredients. Strong oxidizing acne treatments like benzoyl peroxide can reduce the effectiveness of vitamin C if they are used at the same time; they are often recommended for use at different times of day.

Read more about other types of Vitamin C:

Foods rich with vitamin C include oranges, strawberries, broccoli, bell peppers, and more. When consuming Vitamin C, your skin receives a portion of the nutrients.

Once on your skin, the enzyme alpha-glucosidase snips off the glucose and gradually releases active ascorbic acid right where it's needed. Basically, it behaves like a slow-release pro-vitamin C with less of a stinging that high-strength ascorbic acid can cause.

The research supports the classic vitamin C benefits as well. In lab and human studies, AA-2G slowed down the skin's production of melanin (the pigment behind dark spots) and helped shield skin cells against sun damage better than ascorbyl phosphate.

These studies also showed AA-2G released vitamin C over a longer period.

A frequently cited manufacturer trial found that a 2% AA-2G face cream significantly improved wrinkle depth and skin roughness after 45 days.

And in 2009, a clinical trial showed it meaningfully lightened dark patches on the gums compared to a placebo.

There's also collagen-synthesis support (since vitamin C is a required cofactor for that) and an antioxidant effect too.

Typical usage is usually between 0.5-5% and most studies/products land around 2%.

AA-2G performs best when formulated at a mildly acidic pH (~5-7) which is much gentler than the pH that pure vitamin C demands (~2.5-3.5).

Just one thing worth knowing: the in-skin conversation rate is only about 55-60% by weight. So a 5% AA-2G product delivers roughly 2.75-3% of actual active vitamin C. On top of that, skin absorption is relatively low because the ingredient is water-soluble.

This ceramide works by slotting into gaps within the stratum corneum's lipid matrix to limit trans-epidermal water loss (TEWL) and shield the skin against external irritants.

A study with 312 patients found that using a ceramide-containing routine for 4 weeks reduced the severity of atopic dermatitis by over 61%.

Another clinical study in subjects aged 60 and older found that a ceramide body wash and moisturizer improved skin dryness and itchy skin in 15 days.

Overall, ceramides are considered non-irritating and safety tests have found little to no observable adverse effects from using this ingredient.

Ceramide NP is usually sourced from plants (like soybean or rice bran), or produced synthetically.

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.