Recently ASAP Science released a video called “The ONLY face cream that works! – according to science”. A lot of people asked me to do a response, so here it is on YouTube (keep scrolling for the text version).

So the idea of the video is that there’s lots of misleading marketing in skincare .The video is loosely based off the Ageing Skin chapter of Monty Lyman’s book The Remarkable Life of Skin.

(It’s actually really exciting for me to do a response to a video that’s made by science nerds, because usually it’s 5 Minute Crafts).

Unsurprisingly, since ASAP Science is a science channel and the book is by a doctor (though not a dermatologist), most of the messages in the video are largely correct:

• There IS tons of misinformation in the skincare industry, and a lot of brands are trying to sell you hopes and dreams in the form of products that can’t plausibly work.
• Terms like dermatologically tested, clinically proven and active ingredients don’t mean much.
• A lot of the BS around skincare products is indeed because your skin is an excellent barrier, and this goes both ways. Potentially useful active ingredients can’t easily get through your skin to where they might need to be to work. On the other hand, it also means that potentially harmful ingredients have a hard time getting through your skin into your bloodstream, so a lot of the fearmongering is just BS.

But I think a few misconceptions did come up in the video…

Ingredient lists don’t tell you if products will work

The premise of the main part of the video is that Greg (who doesn’t use skincare) is showing different products to Mitch (who does use skincare), and Mitch has to decide based on the ingredient lists which product will have a better effect on skin.

The problem here: you can’t tell just from the ingredients list whether or not a product is going to work.

The ingredients list tells you what ingredients are in the product, so you can see if it could potentially do what it’s claiming to do… but that’s about it.

There are some other important things you need to know if you want to figure out if a product will actually work:

Dose

The ingredients list usually doesn’t tell you what the concentration of the active ingredient is. You need a minimum amount of an ingredient to work, and in general there’s a dose-response relationship where a higher dose means a larger response, up to a certain point.  Generally if you go too high the benefits start to level off but the side effects increase, and eventually the benefits aren’t worth the side effects anymore (I talked about this concept a bit when I discussed why The Ordinary’s 100% powders aren’t a good idea).

Even if you look at the relative positions of the ingredients, it doesn’t tell you that much. At one point Mitch picks a cream with glycerin at position 3 over the cream with it at position 6.

In most countries, skincare ingredient lists are ordered in reverse order for ingredients included above 1%, so the thing at the top has the highest concentration. But there’s a lot of wiggle room – you can definitely have a product where the 3rd ingredient is present at a lower concentration than in a product where it’s the 6th ingredient:

Pharmacokinetics

The ingredients list also doesn’t tell you much about the delivery system – in other words, if the other ingredients in the product will help the active ingredient get into the skin where it needs to be to work (in medicinal chemistry, we call this pharmacokinetics).

You can sometimes tell a little bit, like if there’s a penetration enhancer in the product that can help the active ingredient absorb through the skin barrier. But it can’t tell you if there’s enough of the penetration enhancer to work, given everything else that’s going on in the product, or if the ingredients are arranged into a special delivery system or if they’re just mashed up in there. Getting stuff through the skin is a whole area of pharmacology, with whole textbooks written about it. It’s a pretty complex topic and the ingredients list doesn’t tell the whole story.

What ingredients “work”?

We then go into looking for active ingredients in different products, and discussing whether or not they “work” – and the conclusion is that only retinoids will work.

So here’s where I think definitions are really important. Basically ASAP Science’s requirement for an ingredient to “work” is that there has to be a scientific consensus that it can go through skin to the dermis, and increase collagen to decrease wrinkles.

I think there are a few problems with this definition.

Collagen

Firstly, losing collagen isn’t the only reason wrinkles form – there’s also the loss of other substances in skin like glycosaminoglycans (e.g. hyaluronic acid), changes in the types of collagen and elastin in the dermis, and thickening and dehydration of the stratum corneum.

Wrinkles

And wrinkles aren’t the only thing that matter for skincare. There are tons of different reasons why people use skincare products, like acne, fading pigment, and treating dry skin.

Even if we stick to anti-aging, wrinkles aren’t the only thing that happen. It’s one of the things that gets talked about the most, but in dermatology anti-aging includes other aspects. This is especially the case in people who aren’t white, where pigment changes like uneven pigment, age spots and sun spots are a much bigger issue than wrinkles.

Dermal penetration

Ingredients also don’t necessarily need to make it to the dermis to “work”.

Again, if we look at all the reasons that people use skincare, we have things like moisturisers. Moisturisers work mostly on the top layers of the skin (the so-called “dead” stratum corneum), to smooth it out and increase the water content. This can actually reduce the depth of wrinkles.

And even though moisturising might seem like it only has a minor surface level effect, it can actually have a pretty big impact!

In one study on patients with atopic dermatitis, petroleum jelly (which mostly just sits on the surface of the skin and seals in water) actually increased the production of antimicrobial peptides, thickened the stratum corneum and changed the way that skin cells developed.

Even something like silicone sheeting (literally a silicone sticker on your skin) can change the structure of scars that are quite old – and it mostly does this just by keeping the scar hydrated.

There are also quite a few skincare ingredients that work well enough to be classified as drugs, and these generally don’t have to make it to the dermis to work:

• Dimethicone is classified as a skin protectant and sits on top on skin
• Benzoyl peroxide is a great anti-acne drug that mostly works on acne bacteria on the surface of the skin and in pores
• Sunscreen forms a layer on the top of your skin to protect against UV rays, which is enough for it to be legally classified as an anti-aging drug in Australia

Scientific consensus

There’s a good reason there isn’t much of a scientific consensus for a lot of skincare ingredients compared to, say, medical treatments.

Skincare products are largely cosmetics, which means they aren’t really meant to go into your dermis and change how it functions. If they actually did this, they should really be classified as drugs.

The US’s Food, Drug & Cosmetic Act defines drugs and cosmetics (most countries have a similar definition):

Drug

• intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease
• intended to affect the structure or any function of the body of man or other animals

Cosmetic

• for cleansing, beautifying, promoting attractiveness, or altering the appearance

One really frustrating thing about this definition is that it doesn’t really reflect what happens when you actually put stuff on skin. Putting water on your skin will change how well your skin conducts electricity (i.e. a function), but it would make no sense to regulate water as a drug.

So it’s usually the intended effect of a skincare product – how it comes across in labeling or marketing – that determines whether it’s classified as a drug or a cosmetic.

When a company gets fined for breaking this regulation, it’s usually because their product makes drug-like claims, and not because their product acts like a drug. Saying that a product “reduces wrinkles” is a drug claim, but rewording that to “reduces the appearance of wrinkles” makes it a cosmetic, even though it’s the same product in different packaging.

The big difference for a company between a drug and a cosmetic is how the product is regulated. It’s a lot easier and cheaper to sell a product as a cosmetic. Drugs have to go through years of testing for safety and effectiveness before launching onto the market, which can take millions of dollars. A cosmetic product doesn’t need official approval, so if customers are going to buy it anyway, there’s not much incentive to go through all of this effort to make it a drug.

So we’re in this weird regulatory situation where there are a lot of skincare products that definitely do more than a cosmetic should – there are all sorts of studies that show that some formulations can change the structure or function of skin – but no one really wants to say it out loud.

Some countries like Japan have tried to get around this by adding an extra category: cosmeceuticals or quasi-drugs. But in most Western countries this hasn’t happened.

That means the only ingredients where there’s a strong scientific consensus that they work like drugs… are ingredients that are actually classified as drugs.

A product can’t actually claim that it reduces pigment even if there’s pretty darn good evidence showing that it does, and even if it’s been classified as a quasi-drug in Japan (meaning their government is pretty satisfied that it works in a drug-like way).

So because of the very narrow definition of the word “work” used here, it’s really only retinoids (vitamin A derivatives) that fall into this category. But even then, there’s still a bit of extra complexity here!

Retinoids aren’t all the same

There are a range of different retinoid ingredients, and not all of them work the same way and not all of them have the same level of evidence to support how effective they are, so we can’t treat them all as the same.

Not all retinoids are regulated as drugs, and the ones that ASAP Science talk about in their video – retinol and retinyl palmitate – aren’t actually regulated as drugs.

Retinol’s definitely one of the ingredients that that most people in skincare (including me) recognize has a lot of evidence behind it, and it’s approved as a wrinkle-reducing quasi-drug ingredient in Japan.

But to work it has to be absorbed into skin and converted in two steps to its active form, tretinoin, which is actually regulated as a drug. Retinyl palmitate needs an extra step to turn into tretinoin so it’s even less well-supported.

Non-drug = no guarantee of efficacy

There’s also the issue that just having retinol in a product doesn’t mean that it works. For drugs, the final formula has been tested to work on people’s skin.

But for non-drug ingredients like retinol, since it’s regulated as a cosmetic, the final formula hasn’t necessarily been tested for effectiveness. It isn’t something that you can tell from the ingredients list, and so there’s no guarantee that it’ll work.

If “retinol” is on the ingredients list, all you know is that at some point they chucked in some retinol. It might not get into the dermis, not much might get through skin – it might not go through skin at all. There might not even be any retinol in the product by the time you get it (retinol is pretty unstable, so there’s a decent possibility that it would’ve all decomposed by the time you get it). So just seeing the word “retinol” on the label doesn’t mean you have a product that definitely “works”.

So now I’m going to talk about the other ingredients that ASAP Science mentioned in their video…

Collagen is 100% BS?

The first product comparison is with a collagen cream, and Greg says anything with collagen is 100% BS. I pretty much agree with this – collagen is pretty overrated – but I’d probably downgrade that rating to 90% BS.

Collagen is in a lot of products and it’s definitely in there mostly to tell a good story. As Greg points out, collagen is too big to get through skin. There’s no evidence that any delivery system is in the product to get it through your skin, and even if it gets there, it’s questionable whether it’s doing anything. You do have collagen inside your skin and losing collagen is linked to thinning skin and wrinkles, but shoving random bits of collagen in there doesn’t necessarily do much. It’s like how sprinkling hair on a bald patch isn’t going to make you hairier (in the right way at least).

But collagen is actually a pretty good humectant moisturiser – just like glycerin that Greg mentions in the competing product. Humectants are good at grabbing onto water and keeping on your skin, which makes it feel hydrated and smooth and flexible. Humectants can have this effect while still on the surface of skin, since it’s the stratum corneum, the top “dead” layer of skin cells, that’s actually the bit that dries out and goes flaky. So big chunky collagen still works even though it can’t get down very far.

Vitamin C doesn’t work?

So they talk about antioxidants in creams, and how there isn’t really a scientific consensus on whether antioxidants work. Because of that, Greg says that a product with two forms of vitamin E is better than a product with vitamin C.

The problem here is a bit like the problem with the retinoid discussion – not all antioxidants are the same.

Different antioxidants have different antioxidant abilities, with some being more powerful than others.

Antioxidants will also distribute differently in the skin. For example, oil-soluble antioxidants like vitamin E tend to end up in the cell membranes, while water-soluble antioxidants like vitamin C tend to work in watery spaces like the insides of cells.

Antioxidants also have different molecular sizes and polarities, which affect their ability to penetrate into skin, and there’s a HUGE range of sizes used in skincare products (Da is a measure of their size):

There are also different levels of evidence to support their ability to work on skin, and I’ve discussed some different antioxidants in a previous post.

Vitamin C is actually one of the ingredients with a decent amount of evidence to back it up. It has properties aside from just being an antioxidant, and it’s actually regulated as a quasi-drug in Japan for its pigment-fading abilities.

There’s also evidence that it can increase collagen in skin when it’s in skincare products. There are some clinical trials where volunteers applied a vitamin C product to one side of their face but not the other, then biopsies were taken of both sides. The little chunks of skin were analysed, and there was more collagen in the vitamin C side.

There’s some evidence that Vitamin E can fade pigment, but nowhere near as strong, and there’s nothing convincing on vitamin E and collagen.

Palmitoyl polypeptides?

One group of ingredient that ASAP Science does recommend, alongside antioxidants and retinol, are palmitoyl polypeptides – if you use all three then you’re checking all the boxes for science-backed anti-aging skincare.

If you’re a skincare nerd, you’ll probably also have been a bit confused about this – palmitoyl polypeptides (and peptides in general) don’t really have a lot of research to back them up. There are a lot of ingredients in between palmitoyl polypeptides and retinoids when it comes to evidence of them working (niacinamide, alpha hydroxy acids, hydroquinone, arbutin…).

The reason I think they included palmitoyl polypeptides is that in Monty Lyman’s book, synthetic peptides are highlighted as an interesting and rapidly evolving area. I don’t think he meant to imply that there’s a lot more evidence for them being useful than the other ingredients he only mentioned in passing, just that it’s an example of an ingredient category that might be interesting to look out for.

He also talks about a clinical trial that was done on Boots No7 Protect And Perfect Intense Advanced Serum. This trial is actually quite impressive because very few trials on cosmetic products go on for 12 months. But there’s one big problem – the product they tested had this list of potential anti-aging active ingredients:

• sodium ascorbyl phosphate
• Panax ginseng
• Morus alba
• Lupinus alba
• tocopherol
• palmitoyl oligopeptide
• palmitoyl tetrapeptide‐7
• Medicago sativa
• retinyl palmitate

It’s impossible to pinpoint which of these ingredients actually did the heavy lifting in this trial.

And again, palmitoyl polypeptides are a diverse group. They all have a palmitic acid attached to a string of amino acids, but the actual amino acids are really important when it comes to what the peptide does to your skin – You can’t stick any amino acids together and hope for a good effect. And of course they all have different levels of evidence as well.

There were a few other things I picked up, but I think this is long enough – the overall message is good, but I think there are some nuances missed that I think are pretty common misconceptions when it comes to science and skincare. What are your thoughts?

References

Czarnowicki T, Malajian D, Khattri S, et al. Petrolatum: Barrier repair and antimicrobial responses underlying this “inert” moisturizer. J Allergy Clin Immunol. 2016;137(4):1091-1102.e7. doi:10.1016/j.jaci.2015.08.013

Mustoe TA. Evolution of silicone therapy and mechanism of action in scar management. Aesthetic Plast Surg. 2008;32(1):82-92. doi:10.1007/s00266-007-9030-9

Ando H, Matsui MS, Ichihashi M. Quasi-drugs developed in Japan for the prevention or treatment of hyperpigmentary disorders. Int J Mol Sci. 2010;11(6):2566-2575. Published 2010 Jun 18. doi:10.3390/ijms11062566

Fitzpatrick RE, Rostan EF. Double-blind, half-face study comparing topical vitamin C and vehicle for rejuvenation of photodamage. Dermatol Surg. 2002;28(3):231-236. doi:10.1046/j.1524-4725.2002.01129.x

Nusgens BV, Humbert P, Rougier A, Richard A, Lapière CM. Stimulation of collagen biosynthesis by topically applied vitamin C. Eur J Dermatol. 2002;12(4):XXXII-XXXIV.