Lab Notes

Intro to Ingredient Pairings

Nutella and Banana, Pineapple and Pizza. Even in the skin, pairings can be a hit or miss. One thing is for sure, nothing beats the pair that kills Zombie cells.

Key to Perfect Pairings

A key principle of our science team here at Regimen is to start by identifying an issue, let’s say hyperpigmentation, and then do intense research on the best possible means to address that issue using skincare. That means understanding not just the symptoms, but more importantly the underlying causes, and the best available evidence on what ingredients to use and how to formulate them to best address the issue from symptom to cause and everything in between.

This may seem obvious, but it’s not the norm the world of skincare, where marketing is ruled by “hero ingredients” and “naughty lists” and where product development is ruled by “why make one product when we can get customers to buy two?”.

In this post, we’ll get into the science of some of our favorite ingredient combinations as determined by a wealth of scientific evidence.

A quick TLDR about why perfect pairings matter:

  1. Almost every “hero ingredient” needs a partner or a team to work. These dream teams have been proven in study after study to outperform those “hero ingredients” in isolation, or in suboptimal ratios.
  2. Good skincare products must begin with a deep understanding of the skin we see too many products that make a claim but are formulated only to address only one of many underlying causes, or worse, just the symptom!
  3. The body is complex! It’s okay that skincare is too.There are billions, even trillions, or interactions constantly occurring in your body. More is often better with ingredients, because that’s how we get closer to mimicking the complexity of the body. Eating “clean” and “simply” works because your body takes an ingredient like celery and breaks it down into 100s or thousands of chemicals (amino acid, In skincare, unlike in food, you should be suspicious of labels with “simple ingredients”.

Dream Teams > Hero Ingredients

Another skincare status quo is pushing “hero ingredients”. We’d like to add some nuance to the narrative. This is not because these ingredients don’t have heroic properties (they often do!) but rather because they are almost always better when used in conjunction with other ingredients. Scientists (and business geeks) call it synergy. BTW, while the word ‘synergy’ gets a bad rap, it comes to English from the Greek sunergos or “working together”. Enjoy some etymology with your chemistry today, friends!

”Hero Ingredients” can work against each other

Unfortunately, even if two ingredients produce the same results, it doesn’t mean that they should be used together. There are different factors that need to be considered when pairing ingredients: pH, molecular interactions, irritation etc.

BTW, this gets complicated fast: Let’s take pH as an example: while you’ve probably heard the term pH balanced (a marketing term that’s supposed to indicate that a product is formulated to be the same pH range as skin), you probably haven’t heard that different skincare ingredients only ‘work’ if formulated to a certain pH, and very often they are put inside formulations that render them effectively inert. We’ll cover this in another post soon!

What do we mean by mixing? Mixing is either formulating two products together, mixing two serums before application, or consecutively mixing one after another. It is important to note that there is a hierarchy of prioritization in skincare, and you should always prioritize your skin even if it means less potency for the ingredients. Here are some of the most common blunders that people make in mixing products.

Acids with Occlusives

Acids are formulated to penetrate to a particular layer of the skin where they can go to work. Occlusives increase skin hydration but in doing so they also potentiate (increase the potency of) many ingredients, including acids. Using acids at the same time as occlusives like Petroleum Jelly or masks makes the acids penetrate more than they are intended to. This can cause significant irritation.

(We know a certain DIY high percentage BHA + collagen mask is quite popular, but we advise against this. Even if your skin isn’t visibly irritated, it is likely getting damaged by this combination)

Phenolic antioxidants with Iron and Copper containing ingredients

We’re seeing a number of “antioxidant” containing color cosmetics, botanical hydrosols/extracts, and tinted sunscreens. These sound good on the surface, but these formulations typically combine phenolic antioxidants like Quercetin with Iron and Copper containing compounds like iron oxide. Mixing these has the effect of cancelling each other effect - so the sunscreen no longer has an antioxidant effect. To complicate the matter further: we’ve seen cosmetic companies mixing their antioxidant-containing serums in steel tanks or pots. The free iron and copper contained in these takes, has the effect of weakening the antioxidants included in the products, potentially quite significantly.

Barrier Lipid formulation with botanical oils.

A lot of barrier creams contain botanical oils, which is a very questionable decision because these botanical oils throw off the delicate balance of fatty acids necessary to properly support the skin barrier (we talk a lot about the important 3:1:1:1 ratio on Instagram- we’ll do a deep dive on that soon). The science behind this? Research shows us that oils in the form of triglycerides (the kind in botanical oils) convert to free fatty acids in the skin. Increased fatty acids in the stratum granulosum “mess up” the scaffolding for the lamellar bodies, resulting in improperly formed lamellar layers. Note: some fatty acids may be conjugated in a very large molecule and cannot penetrate the skin.

So what are the perfect pairings?

Perfect Pair 1:

Tranexamic Acid + Betaine - “The Zombie Cell Fighters”

You’ll be hearing the term “zombie cells” more and more in the future. What are they? Recent discoveries show that certain senescent cells (cells that are not alive, but not quite dead either - hence zombie cells) are capable of encouraging other cells to atrophy and become scenecent (zombified) as well. They produce pro-inflammatory molecules that lead to aging.

Our skin removes these cells through autophagy (self-eating); however, in the presence of pro-oxidants, autophagy cannot remove these senescent cells.

Tranexamic Acid and Betaine were shown to upregulate, or promote, Autophagy, leading to increased removal of these zombie cells. These two help not only in preventing the damages from oxidative stress but at the same time lessen signs of skin aging.

Perfect Pair 2:
Ceramides and Lactic acid - “The Barrier Boosters”

We know that ceramides are an important part of our barrier lipids together with Cholesterol, and Fatty acids.

Lactic acid hyperacidifies the skin which encourages lamellar body production. In addition to this, our skin is able to convert lactic acid to Acetyl-CoA which is the building block of Ceramides.

Application of Lactic acid is able to increase the amount of ceramides in the skin.

Perfect Pair 3:
Radical Scavengers + Physical Quenchers - “No Cool Name Needed bc they already have one”

Antioxidants like L-Ascorbic acid are great at scavenging radicals by absorbing their excited energy. The disadvantage to some of them is that they can turn into pro-oxidants and release a radical themselves. It is therefore critical to use other ingredients and design a system where their energy can be quenched by either physical or chemical quenchers.

In plain(er) English: antioxidants are good, but some of them can have the opposite of their intended effect. Research tells us that we must use multiple antioxidants in concert to mitigate any of the ‘opposite’ reactions that can occur when using just a single antioxidant ingredient.

In geek speak: L-Ascorbic acid especially becomes a pro-oxidant through the Fenton Reaction in the presence of free iron. This defeats the purpose of scavenging radicals. It is therefore critical to use other ingredients and design a system where their energy can be quenched by either physical or chemical quenchers.

  • Chemical Quenchers absorb energy from radicals and they get consumed during the process
  • Physical Quenchers absorb energy from radicals but are able to regain their quenching ability so they can absorb energy multiple times

(And in case you are wondering, that is exactly what we do. Regimen formulates our antioxidant system so that some antioxidants can be regenerated.)

4. The Ultimate Perfect Pair:
Niacinamide + Resveratol - “The Regulators”

One of the determinants of aging is genetic damage. The more errors in our DNA, the more degradation in our skin and body. These errors usually occur during DNA replication and our body repairs them through DNA repair enzymes.

The stability and fidelity of the new DNA strand is dependent on many factors, but recent studies show that Sirtuins appear to play a significant role in keeping the DNA structure stable and in regulating DNA repair. Sirtuins control numerous processes through histone deacetylation. They ensure that DNA is tightly bound together if genes do not need to be accessed, which in turn ensures DNA is stable and fewer errors occur.

Niacinamide temporarily inhibits Sirtuins then it gets converted to NAD+ which activates Sirtuins. Resveratrol on the other hand activates Sirtuins which promote DNA stability and proper repair. Using these two in combination encourages your DNA to chill and repair itself.

There are more pairs, throuples or quadrouples out there that vibe together in ensuring your skin stays healthy and glowing. Skincare definitely works better when the ingredients used work in harmony. Stay tuned for our next Lab Note