= a cosmetic product whose active ingredient is meant to have a beneficial physiologic effect resulting from an enhanced pharmacologic action when compared with an inert cosmetic.

The Three Questions to Ask (according to Douglas Kligman, the "father" of cosmeceuticals):

1. Can the active ingredient penetrate the top layer of the skin (affectionately known as the stratum corneum) and be delivered in sufficient concentrations to its intended target over a time course consistent with its mechanism of action? 

2. Does the active ingredient have a specific biochemical mechanism of action in the target cell or tissue in human skin?

3). Are there published peer-reviewed, double-blinded, placebo-controlled, statistically significant clinical trials to substantiate the efficacy claims? 

(4. What does all of this mean??? Don't worry, we gotchu.)

Let's start with some basic biology. Our skin is composed of three main layers: the epidermis, the dermis, and the subcutaneous layer (fatty tissue). Obviously, this is a oversimplifying it a whole lot, but it'll do for our purposes. 

Human Skin [a very basic version] 

Within the top layers of the epidermis is a layer called the stratum corneum. This layer has a brick and mortar structure, where the bricks are protein-rich bodies called corneocytes and the mortar that glues them all together is a lipid-rich (basically a fatty) matrix composed of lipid bilayers. The layers of each "bilayer" are composed of hydrophilic (water-loving) and hydrophobic (water-fearing) regions embedded with naturally occurring ceramide, cholesterol, and fatty acid chains. 

Stratum Corneum

Question One

When it comes to penetration, size matters. So do other things.

What does this have to do with how well a product will work for you? It's simple. Most formulations can't be effective as cosmeceuticals unless the active ingredient goes beyond the superficial layers to affect the deeper basal layers. Imagine being a charged molecule trying to penetrate the SC through this lipid matrix -- half of the regions have opposite charging properties as the other half, causing you to bump into walls every turn you make. Another way through is through the thick proteinaceous bricks called corneocytes -- tough luck. Besides that, the only other way pathway is through hair follicle or sweat duct openings, which only account for 0.01% of the total surface area of skin -- barely even relevant. So you understand the difficulty of penetration...

Remember all those advertisements about how miracle cream X claimed that its revolutionary peptide technology would revitalize your skin in a snap? It's no secret to the academic community that in fact proteins, sugars, peptides, and nucleic acids with a molecular weight greater than ~1000 kd won't be able to get past the stratum corneum. The size constraint applies generally to any molecules greater than 500 Da, which happens to include the vast majority of molecules being advertised as miracle agents in skincare products. 

For example, hyaluronic acid which is found in many moisturizers hasn't been definitively shown to penetrate through even the stratum corneum. While it is true that it increases the skin's water-holding capacity, further research needs to show if it has pharmacologic effects in human skin.

Retinol is another popular ingredient, available OFC in place of stronger prescription-level retinoic acid preparations. Most OFC products contain between 0.01-1.0% retinol, and it's important to know how they work. Long story short: enzymes convert retinol to retinoic acid (the active form that works on those wrinkles) at about a 10% conversion rate. The other 90% is deemed ineffective sometimes as soon as it touches your skin where enzymatic reactions convert it into other irrelevant compounds. Another factor to keep in mind -- is your active ingredient penetrating the SC in sufficient concentrations to its intended target in the skin?

Even if some active ingredients successfully penetrate into the dermis, many molecules are diluted rapidly by microcirculation leading to no clinical effect. Take topical cellulite treatments for an example. Cellulite is a representation of the herniation (exuded fat) of subcutaneous fat storages as well as tissue degeneration of the dermis. Any topicals that get past are unlikely to have meaningful effects on such a deep process due to this microcirculation.

TL;DR 1) charging properties of molecules affect their ability to penetrate the SC's lipid-rich matrix 2) any molecule larger than 500 Da cannot mechanically penetrate the SC 3) molecules cannot benefit skin unless sufficient concentrations are delivered to target sites 4) even if sufficient concentrations reach target site, microcirculation may dilute substance, deeming it ineffective 5) these challenges can be aided in part by chemical enhancers or vehicles, discussed below.

Vehicles also matter -- you want a sports car, not a minivan.

Lately, efforts have ramped up around the formulation of chemical enhancers or vehicles that would more efficiently deliver active ingredients to dermal layers beyond the stratum corneum. More common approaches like this may focus on solubilizing the lipid matrix of the stratum corneum, in effect "loosening" the mortar for molecules to more easily pass through. Even then it must take a tortuously winding path through the lipid bilayers and we've discussed above what a pain that can be to achieve. 

Another approach is "packaging" active ingredients inside of liposomes (fat packets) to travel more fluidly through the lipid-rich matrix. Nano-delivery systems are also gaining popularity, due to their quick and easy absorption properties.

Resources: Explaining these systems will require more space than I have in a single blog post, but if you'd like to find out more in-depth information, check out the review article: "Nanotechnology-Based Cosmeceuticals" 2014 Alka Lohani et al. & "Delivery of drugs applied topically to the skin" 2014 Vania Rodrigues Leite-Silva et al. Also, a lot of the information in this post credited to Kligman and his paper "Cosmeceuticals" 2000 Douglas Kligman. 

Question Two

Are we there yet? Yes? Now what?

Continue to imagine you're that molecule. You've done the hard part -- getting past the stratum corneum. Now you've got to do the harder part -- fulfilling your biochemical or pharmacological mechanism of action to substantiate the efficacy of your marketing claim. 

This is where the biochemistry gets a little complex. I'll save you the pain of working through the convoluted play-by-play of molecular pathways and keep it simple. The main question here is -- is there enough evidence that the active ingredients being tested have a viable mechanism of action at the target site? If the answer is yes, we proceed to clinical trials. 

Question Three

The Trials

At this point, there's reason to assume that the ingredient can get past the SC to the target sites where they have a viable mechanism of action to live up to its marketing claims. It's time to see how effective this formulation really is, on human skin. 

While large companies like L'Oréal may conduct clinical trials, they don't often publish the findings. If they do, they often omit experimental variables and specific formulations. Will we give up in finding the truth about how these products actually measure up to their claims? Never. 

That's why this space exists. It's a place to build upon communal knowledge to spread the word on what works and what doesn't, for every skin type. The traditional normal, oily, dry, and combination approach is outdated. In an age of increasing personalization, you to find effective solutions that you love.

Whew, we made it! This is here so you know a little bit about the work we do behind the scenes. Leave it to us to answer these three questions and curate products that pass! You'll be on your way to a healthy glow in no time, stress-free.