The myth that “60% of what’s applied to your skin is absorbed into your bloodstream” is one of my pet peeves. It’s so far from the truth, and it’s cited with such an air of authority that it really ticks me off.

It also tends to be cited by the sorts of people who push “non-toxic” products, which is very much a BS marketing tactic.

Let’s break down how human skin works, and why this myth is just plain wrong.

Skin is not a sponge

One of your skin’s main functions is to act as a barrier – that is, it blocks substances from getting into the deeper living layers of your body. If things were so easily absorbed into skin, humans would’ve died a long time ago (probably from exploding after absorbing a tree or something). Thank you, evolution!

spongebob

So by default, the amount of substances absorbed is going to be closer to 0% than 100%.

You can see this in everyday life as well:

You don’t get massively heavier after you take a bath.
You don’t absorb your clothes.
You still have make-up to remove at the end of the day.
You can’t just slap food you don’t like on your skin to get around eating it.

Medicated creams and patches

At this point in my rant, people who promote the 60% absorption myth like to bring up medicated creams and patches. If skin’s such a great barrier, they say, why do medicated creams and patches work?

(They smile smugly as I take a sip of water. “Got her!” they think. But they’ve made a huge mistake. Medicinal chemistry is MY home turf.)

Transdermal medications have a few advantages.

One of the biggest headaches in designing medications is first pass metabolism, which is when your digestive system metabolises and gets rid of oral medications before they get absorbed into your bloodstream. To compensate for this, you have to take a lot more of the medication so that enough of it makes it to your bloodstream to have an effect. Alternatively, you can avoid the digestive system altogether with IV drips, injections, suppositories etc. – or transdermal delivery.

Transdermal products can be designed to release the drug more slowly and consistently than other methods. They’re also easier to administer to uncooperative patients.

But while transdermal medications sound great, it actually takes a lot of effort to get drugs through your skin and into your bloodstream. Compared to the total number of medications on the market, the number of transdermal medications are extremely limited, and lots of formulating tricks are used to get them through the skin.

Take transdermal patches, like nicotine patches – as well as lots of penetration enhancers that help the nicotine get through skin, they also need a liner to protect the ingredients from rubbing off.

Even with all this intentional effort and design, there’s still 10-95% of the drug remaining on the surface of the skin with the transdermal drug products currently on the market.

Absorption depends on a lot of different things

So why do some things get through skin into the bloodstream? If skin is such a good barrier, does that mean skincare doesn’t work?

Well, how much of a substance absorbs into skin depends on a ton of things (which is why the blanket statement of 60% rings alarm bells for us pharma nerds).

What is it?

How well a substance gets through your skin into the blood depends on the structure of the substance itself.

Firstly, molecular size is important. The smaller the molecule, the more easily it squeezes in between all the substances already in your skin, sort of like how you try to make yourself as small as possible to get through a crowd.

tape-measure-ruler

Your skin is also both watery and oily at the same time, and things that dissolve in water tend not to dissolve in oil. It has to have the right balance of hydrophilic and lipophilic (the right polarity) to get into the skin, then leave the skin and enter the blood.

water-oil

As you’d expect, drugs that can be delivered transdermally tick these boxes – but most drugs don’t, and it’s the same for other substances that encounter your skin.

Where are you putting it?

Your skin doesn’t have the same permeability all over, so skin absorption depends on the location of application.

For example, here’s a table (from this book) showing the permeabilities of hydrocortisone and two pesticides through skin in different locations.

Anatomical region	Dose absorbed (%) hydrocortisone	Dose absorbed (%) parathion	Dose absorbed (%) malathion
Forearm	1.0	8.6	6.8
Palm	0.8	11.8	5.8
Foot, ball	0.2	13.5	6.8
Abdomen	1.3	18.5	9.4
Hand, dorsum	-	21.0	12.5
Forehead	7.6	36.3	23.2
Axilla	3.1	64.0	28.7
Jaw angle	12.2	33.9	69.9
Fossal cubitalis	-	28.4
Scalp	4.4	32.1
Ear canal	-	46.6
Scrotum	36.2	101.6

You can see that the different substances have different permeabilities, and you can see some areas are better at absorbing things (armpit (axilla), jaw angle, ear canal and, uh, scrotum… I’m assuming the additional 101.6% for parathion is experimental error), while others are pretty impermeable (foot, palm, forearm).

Note that this table only shows percutaneous absorption – in other words, absorption through the skin. Getting through the skin doesn’t necessarily mean that the substance ends up in the blood, since not all locations have the same blood flow, and the blood vessels are at different depths, so the actual amounts of these substances that get to the blood are much lower.

What are you putting it on with? How are you applying it?

There are some other things you can do with an ingredient to enhance how well it absorbs into skin. Transdermal patches and creams exploit a few of these. For example, occlusion (covering up your skin) will help underlying substances penetrate the skin.

A lot of medicated creams and skincare products also include penetration enhancers. These ingredients help substances absorb better. Some of them will make the stratum corneum (the dead outer layer of your skin) more fluid, others will disrupt the proteins and oils on your skin, or hydrate your skin. Penetration-enhancing ingredients include alcohols, essential oils, fatty acids, urea and just plain water.

You can also use tools to increase penetration, like ultrasound, electroporation, iontophoresis, heating and microneedles. Depending on the technique, these drive the ingredients into the skin or disrupt the skin barrier.

Dissolving Microneedle Patches: Science and Review (Vice Reversa)

But in your standard beauty products, you rarely have many of these special tricks in place. In fact, some products are specially formulated to stay on top of your skin. Sunscreens, for example, are designed to sit in a layer on top of your skin, since they’re useless if it’s under your skin.

Does this mean skincare doesn’t work?

So if skin is such a good barrier, does that mean skincare won’t absorb and therefore won’t work? Luckily for us skincare enthusiasts, not necessarily!

Skincare is for skin, not blood

As previously mentioned, most things that do get absorbed into your skin don’t make it past the first few layers of the dead stratum corneum. Even less make it through the epidermis to the deeper dermis, where your blood vessels are. But for skincare, that’s fine – you want generally want it in to stay in the top layers of your skin where you apply it! Moisturisers are meant to work to hydrate the stratum corneum, and most actives work in the epidermis.

Ingredient selection

Most of the active ingredients used in skincare, like ascorbic acid and tretinoin, are small enough to penetrate into skin. Larger ingredients like collagen, hyaluronic acid, petrolatum and sunscreens work at the surface of the skin, so they don’t need to penetrate.

Formulations can help ingredients penetrate

Skincare products can be purposely formulated so the ingredients have the best chance of penetrating through the dead stratum corneum into the living layers of the skin.

The most common method is the use of penetration enhancers. The same ingredients used in transdermal medications show up in skincare as well – that’s one of the reasons why denatured alcohol is in a lot of products.

Another factor is pH. If there’s an acidic ingredient, a low pH will generally help it penetrate skin, while higher pH usually makes it too polar (water-soluble).

There are some less commonly used strategies as well, like liposomal delivery – but these aren’t common in skincare products.

Verdict

There are a few freak things that absorb 60% or more, but for the vast majority of ingredients and situations, 60% is a massive overestimate. Phew!

Dawn Siler

Sunday, August 25, 2019

The “60% of products absorb into your bloodstream” myth