The Non-Vitamin C Antioxidants

First Posted on June 28, 2021 in:antioxidantdecoding activesscience deep divevitamin c

The summer season is prime time to experiment with the category of antioxidants. All that extra sun means all that potential for photodamage. But all we’ve been talking about here have been very heavily Vitamin C focused, so what about all the other guys you hear about?

The Chemist Have to Do Their Annual Rant

But wait! What’s this? Another moment for the chemists to moan about the antioxidant category? 

The definition of antioxidant has truly been dragged through the mud because everything from the concoctions from your grandmother’s pantry to the grasshoppers (we’re not kidding) in your backyard have been touted as “potential antioxidants” to help preserve your youth. Oftentimes trendy antioxidants from food gets immediately picked up by skincare without real evidence substantiating its “antioxidant” claim. It’s the best example of running before you learn how to walk. 

There's actually a lot of work that needs to be done to make a case that an antioxidant actually does quench free radicals when applied topically to the skin. 

antioxidant testing timeline skincare

How to Validate a (Topical) Antioxidant

To prove an ingredient is an actual skincare antioxidant, there’s quite a few studies that need to happen:

In vitro (in a petri dish): 

  1. Testing that doesn’t involve actual human cells: A test in a test tube to screen if an ingredient has any capacity of quenching free radicals. This the most initial, basic biddy filter, but by no means conveys actual efficacy on skin or for the human body. You’d be surprised at how many plant extracts don’t make it pass the initial screen.
  2. Testing in Cell Culture: The next step is to see how these ingredients help quench free radicals in a cell model. We’re getting slightly warmer since we’re able to correlate antioxidant activity with our own human skin cells. But we’re still not there yet! How do we know that if you apply the ingredient topically, it can actually make its way to these cells and do all that good work? Sadly most antioxidant ingredients usually don’t make it past this and brands/ingredient suppliers will call it a day.
*A quick note on Lipid Peroxidation: If you start going down the antioxidant rabbit hole, you’ll probably hear about lipid peroxidation. This is a series of reactions, often initiated in skin by (surprise surprise) UVB, that eventually leads to cell membrane damage and death. This is why we find ingredients with lipid peroxidation data to be extra interesting.

In vivo Animal model: So yeah, the next and less costly way is to test topically. You’ll commonly see mouse and pig models used here. This is really the validation step to move into human clinical studies.

In vivo Human model: Woohoo! We’ve made it to the good stuff. Human clinical studies give us the best, real world scenario of how these antioxidants are going to work. However, there’s actually no standard way of testing an antioxidant since no one is going to do a 20 year study on an antioxidant to see if it really lives up to its age prevention claim. So you’ll usually see this tested in several ways:

  1. Lipid peroxidation: Similar to in vitro studies but a skin punch biopsy sample is used instead. *ouch.
  2. Photoprotective effect: Skin is irradiated with various degrees of solar simulated UV and assessed to see if the antioxidant has minimized erythema (sunbrun).
  3. Pigmentation study: This is a much more loose interpretation (read: cheaper version) to call a product an antioxidant, because if you minimize pigmentation (a skin concern induced by sun damage) it’s an antioxidant!

PHEW! Hopefully, this highlights how difficult it is to create a true skincare antioxidant superstar. So with that...let’s talk about some antioxidants! (finally!)

The More Popular Ones That We’re Iffy On

ECGC (epigallocatechin gallate): This is one we’ve talked about a lot as the main compound in green tea with the most activity. There’s actually been lots of mouse models testing everything from psoriasis, eczema, to even HPV and alopecia. But actual human clinical data be sparse! Our guess for the lack of data is because ECGC is pretty unstable like most antioxidants...sadly.

Lipoic acid: This is touted as an antioxidant but the data really only suggests this is a possibly helpful anti-aging ingredient. In a tiny study of n=15, 5% lipoic acid used twice a day for 12 weeks, topical alpha lipoic acid was found to help with the reduction of facial lines, pore size reduction, and improvement in overall skin tone and texture. 

However on the flipside, Dr. Pinnell, the scientist credited with developing the classic CE Ferulic formula, tested out 5% lipoic acid both in a bare solution of ethanol and a competitor product that contains lipoic acid(*cough Perricone MD) and put it through the same solar simulated irradiation test showing it did not have the same antioxidant protection. 

This is a pretty good example of our dilemma with antioxidants (and general plant extract). The studies are sparse, and when you do find studies they can sometimes conflict. The general takeaway here is that lipoic acid might be helpful as an anti-aging ingredient but maybe not so much as an antioxidant to combat UV damage.

Pycnogenol (French maritime bark extract): Pycnogenol actually has quite a library of studies. Testing anything from being an antimicrobial, melasma, and even erectile dysfunction. In terms of skincare, there’s even data in UV protection, but there’s a catch! All the good data is of pycnogenol as an oral ingestible, sooo with that...for now we’re more interested in this as an ingestible than topically. Sorry Ordinary...

Ubiquinone (Co-Q10): This is probably the one antioxidant that constantly puzzles us. It seems to carry this legacy of being a good skincare antioxidant and yet we can’t seem to find a single piece of data that tells us why. But wait! Dr. Pinnel is back again with a vengeance. His lab looked at a couple Co-Q10 analogs, 1.0% ubiquinone, 1.0% idebenone, and 0.5% kinetin and even a commercial product to see if it functioned as a UV fighting antioxidant but found that all of them failed in comparison to CE Ferulic. While this is only one single study, of the ones in this group, this is probably the one we wouldn’t recommend just given its long history of use and lack of findings...unless some new data says differently. I guess we’ll keep waiting. 

The Interesting Ones with Potential

Resveratrol: If you’ve listened to our podcasts, then you know that we appreciate this compound’s red wine (and champagne) origin. But this one actually does have some promising data as an antioxidant and pigmentation fighter. The one catch is that the ingredient itself is pretty expensive and you often end up getting only a cat sneeze worth in your product. Definitely look for brands that share their concentrations of resveratrol like Skinceuticals or The Ordinary. 

Baicalin: An isolated compound stemming from traditional chinese medicine. Proprietary to L’Oreal, you’ll find this in some of La Roche Posay’s sunscreen formulas. In mouse models it has been shown to help reduce photoaging from UVB damage. Ultimately this is a nice secondary active you’ll find in only LRP sunscreens. Think of this more as a nice added bonus.

EUK-134 (Ethylbisiminomethylguaiacol manganese chloride): This is a synthetic molecule that’s meant to follow the same pathway as superoxide dismutase in quenching. Hence why you hear it get called a “mimetic”. The nice thing is, Estee Lauder has done a pretty in depth study on this guy. Testing it at 0.05% and 0.1% on the skin to see if it actually reduces lipid peroxides aka. legit free radical production. You can find this in products like the Ordinary and La Mer Serum.  

Last notes

As you can see from this article, this is a deep rabbit hole. There are just way too many promising new ingredients that never actually make it out of the initial screening phase into practical application tests. The truth is, even the ingredients listed as “iffy” here have wayyy more data than your average trendy, hype “grasshopper extract”.

That said, having a solid antioxidant in your routine is an important part of your long term, graceful aging strategy. Antioxidants are a great pairing with sunscreens in your daytime routine. Most are in aqueous serums so layer this in the beginning portion of your routine.

antioxidants chemist interest ranking


  • The chemists have a lot of issues with claimed “antioxidants”.
  • Kidding. But it takes a lot to prove an ingredient is a true antioxidant.
  • Look for clinical data to help your shopping purchase.
  • The ingredients listed here (even the iffy ones) are still better than a lot of claimed antioxidants such as your blueberry extracts and your avocado oil.


Declercq, L., Sente, I., Hellemans, L., Corstjens, H., & Maes, D. (2004). Use of the synthetic superoxide dismutase/catalase mimetic EUK-134 to compensate for seasonal antioxidant deficiency by reducing pre-existing lipid peroxides at the human skin surface. International Journal of Cosmetic Science, 26(5), 255–263. doi:10.1111/j.1467-2494.2004.00234.x 

Lin, J.-Y., Lin, F.-H., Burch, J. A., Angelica Selim, M., Monteiro-Riviere, N. A., Grichnik, J. M., & Pinnell, S. R. (2004). α-Lipoic Acid Is Ineffective as a Topical Antioxidant for Photoprotection of Skin11This work was done in Durham, North Carolina, USA. Journal of Investigative Dermatology, 123(5), 996–998. doi:10.1111/j.0022-202x.2004.23446.x 

Grether-Beck, S., Marini, A., Jaenicke, T., & Krutmann, J. (2015). French Maritime Pine Bark Extract (Pycnogenol®) Effects on Human Skin: Clinical and Molecular Evidence. Skin Pharmacology and Physiology, 29(1), 13–17.doi:10.1159/000441039 

Farris P, Yatskayer M, Chen N, Krol Y, Oresajo C. Evaluation of efficacy and tolerance of a nighttime topical antioxidant containing resveratrol, baicalin, and vitamin e for treatment of mild to moderately photodamaged skin. Journal of Drugs in Dermatology : JDD. 2014 Dec;13(12):1467-1472.


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