Actives Pairings With Clinical Testing Behind Them

*Updated as of 5/17/2022

When you start dabbling in actives, you’ll easily fall into the rabbit hole of what you can and can’t layer. One of the complicated aspects of trying to figure out actives layering and why brands may not even be able to give clear answers is simply the fact it hasn’t gone through enough testing to truly know. Not to mention, the formulas these actives sit in can add another layer of complexity.

The good thing is there are some active combinations that have been looked at for their benefits. Some have even been found to have a synergistic effect.  Synergistic benefits, in chemist speak - essentially means 1 + 1 = 3 or 4 or 5!...you get our drift.

So here’s a running list of tested active combinations. We’ll continue to populate as we continue to go down more skincare science rabbit holes. We try to choose ingredients you can readily find on the shelves. If there’s any combo you’re curious about, leave us a comment!

Vitamin C (Ascorbic Acid) + Madecassoside

A French lab tested a combination of 5% ascorbic acid and 0.1% madecassoside (one of the acitve components in centella asiatica extract or “cica” products) in a double-blinded study looking at photoaged skin of 20 female subjects. After a whopping 6 months of treatment, they found significant improvements in clinical scores for both superficial and deep wrinkles, suppleness, firmness, roughness, and skin hydration. These results were further supported by instrumental measurements for skin elasticity and histological assessment of the papillary dermis (this means that they looked at changes in the deep layers of skin with a microscope).

State of the Evidence: More data needed. 6 months is impressive, but ultimately it’s a small study and we haven’t seen another one on this particular combination.

Reference Study: https://doi.org/10.1111/j.1600-0625.2008.00732.x

Adapalene + BPO

Adapalene + BPO is the latest and greatest acne treatment duo simply for its significantly less irritating use experience without too much of a compromise in efficacy. 

One review paper looked at data pooled from 3 randomized controlled studies. They looked at Epiduo (0.1% adapalene + 2.5% BPO), 0.1% adapalene alone, 2.5% BPO alone, AND just a placebo gel with no active ingredients. The exciting thing is that there are over 900 subjects per group!

Unsurprisingly, the combination was much more effective at reducing lesion counts by the end of week 12. Another takeaway that we sort of knew is that cocktails become especially helpful for more severe breakouts. This combo has even been tested for postmarks and scarring.

State of the Evidence: Robust!

Reference Study: https://doi.org/10.1016/j.jaad.2010.03.036

*There are many others looking at this combination.

Sodium Ascorbyl Phosphate (SAP) + Retinol

A lab in Thailand looked at 5% SAP (sodium ascorbyl phosphate) with 0.2% retinol. There were 3 test groups with 10 subjects each, one group used SAP only, one retinol only, and one with the combination. The study was 8 weeks long. Retinol was used once daily while SAP was used morning & night.

All three groups saw acne lesion reduction. Retinol & SAP alone both had ~50% reduction by 8 weeks, while the combo group had 63% reduction. Even though each group was small, we appreciated that they looked at each combination separately. We see a lot of "combo" studies with no comparison with the individual actives so it's hard to gauge whether or not the combo adds anything synergistically. While this study alone doesn't mean you should replace your current acne regimen with this specific combination, we really want to highlight the benefit of tackling acne from a few different angles!

State of Evidence: Promising!

Reference Study: https://doi.org/10.1111/j.1468-2494.2008.00479.x

Niacinamide + Hexylresorcinol

Unilever looked at a 0.4% 4-hexylresorcinol and 3% niacinamide in a 12 week clinical study. 44 subjects of Chinese origin, between the ages of 35-60 years old with at least 3 hyperpigmentation spots applied two products half face. 1 product only had 3% niacinamide while the other had the combo of 3% niacinamide and 0.4% hexylresorcinol. The combination showed significant improvements in hyperpigmentation, fine lines, crows feet, and skin firmness.

State of Evidence: Promising!

Reference Study: https://onlinelibrary.wiley.com/doi/epdf/10.1111/ics.12759

*More to come!