The Ingredients List series
Our Ingredients List series is way more than just a list of ingredients. It’s a set of articles that’ll dive into every active and filler used in skincare – whether you find them in Re-Dox or not – so you can better understand how, when and why they work, see through the myths about them, and create a routine that is effective for you.
Quercetin in skincare
It is a well-known phenomenon in the anti-ageing research community that low-level stresses (such as metabolic stress or free radicals) will kick start cellular defence mechanisms that promote DNA repair and increase the cell’s own production of antioxidants. It's the very adaptation to low-level stress that promotes cell survival and the cell is now able to function more efficiently, in a way which mimics younger cells.
Let’s put this in the context of the skin and the chief cell type that is responsible for maintaining the skin's structure — dermal fibroblasts.
Dermal fibroblasts are highly mobile cells that are responsible for maintaining skin extracellular material, like the production of collagen, elastin and hyaluronic acid (among a myriad of other things). With age, dermal fibroblasts become sluggish and less metabolically active.
In fact, some researchers have called aged dermal fibroblasts ‘cells with a lost identity’, as they no long appear or function like younger fibroblasts and instead resemble fat cells. Not only do aged fibroblasts make less collagen, but they make it clumsily, in disorganised ways, and this ultimately affects the skin’s integrity and structure.
What causes this drastic age-related change in dermal fibroblasts?
It’s chiefly the accumulation of DNA damage and reduced antioxidant defence systems in aged cells which eventually forces cells into ‘senescence’ — a state of gradual deterioration of function.
So, it stands to reason; if one were able to repair DNA and boost endogenous antioxidant production, the very signs of ageing can be reversed — at least functionally.
Luckily, the scientific literature and evidence largely supports this approach and this is where quercetin fits into the picture.
Quercetin is long described as an antioxidant with proven protection against the oxidation of of lipids from free radicals. Though the antioxidant activity of quercetin is unlikely to be the mechanism by which quercetin improves cell health. It's more likely that quercetin is paradoxically acting as a stressor to cells.
Quercetin rapidly oxidises within cells and transforms into a oxidant (aka pro-oxidant). This might sound harmful, but under the right circumstances pro-oxidants can place just enough stress on cells to improve their function (much like exercising at the gym) — and this is where quercetin’s action comes into play.
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How does quercetin protect cells while acting as a pro-oxidant?
Quercetin rapidly oxidises in cells and in this form, it binds to the endogenous antioxidant, glutathione and forms the quercetin-glutathione complex.
Glutathione is a critical cell antioxidant, but when bound to quercetin, becomes useless and the quercetin-glutathione conjugate is eventually kicked out of the cell.
This results in a temporary depletion of glutathione levels within the cell, causing a low-level stress environment due to an imbalance of oxidants and antioxidants.
The cells respond to this low-level stress by upregulating more antioxidant defence systems, to not only restore glutathione levels, but improve its agility to respond to subsequent oxidant challenges.
In short, quercetin may increase the cell’s own antioxidant defence system by paradoxically acting as a pro-oxidant.
What about DNA repair?
DNA repair plays a critical role in preventing the accumulation of DNA damage and subsequent loss of cellular function. One key mechanism to kickstart DNA repair in cells is the upregulation of SIRT1 — a key enzyme that regulates metabolic pathways, cell survival, DNA repair, and is ultimately associated with anti-ageing functions. In fact, SIRT1 is so intrinsically related to aging that the cosmeceutical research space considers this to be a marker of effectiveness for newly developed ingredients.
SIRT1 levels gradually decline as we age, and this has a real impact on the ability of cells to undergo maintenance repair for continual optimal function. While there are several ‘hacks’ to increase our SIRT1 levels, such as calorie restriction, fasting and exercise, scientists have identified certain naturally occurring compounds that can increase and even activate SIRT1 in cells to a significant degree. These compounds are called ‘Sirtuin-Activating Compounds’, or STACs for short.
Quercetin is a STAC compound, due to its ability to target and activate SIRT1, therefore initiating DNA repair and prevent age-related dysfunction of cells.
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A recent study showed that quercetin enhances the proliferation and migration of dermal fibroblasts via activation of the Wnt/β-catenin signalling pathway. The Wnt/β-catenin pathway is critical for cutaneous wound healing, and quercetin was shown to not only improve wound to accelerate the formation of collagen.
Another study on aged dermal fibroblasts showed that quercetin was both able to both restore cellular antioxidant levels, improve mitochondria function, and downregulate cellular senescence activity — all of which relate to the ‘youthfulness’ of cells.
Caveat of topical quercetin
Quercetin cannot be used in conjunction with physical sunscreens containing zinc oxide. This causes a temporary tanning effect on the skin — which although harmless is nonetheless undesirable from a cosmetic perspective.
Formulators should be aware of this and inform their customers not to concurrently apply zinc oxide-containing products. It would be a shame to omit the use of quercetin in skincare due to incorrect use that may otherwise stain its reputation as a potent anti-ageing ingredient.
Summary
Quercetin is an anti-aging flavonoid which can improve cellular antioxidant function, enhance dermal fibroblast activity, and activate SIRT1 pathways – all of which make it a novel cosmeceutical ingredient.
The evidence is rapidly mounting for quercetin as not only a useful antioxidant but a potent ‘bio-stimulator’, capable of improving dermal fibroblast function with likely anti-ageing activity. However, it’s application in skincare is few and far between. A quick search using the EWG database of almost 99,000 skincare products shows that only two face serums contain quercetin*.
While quercetin is growing in popularity as an oral supplement, it is likely that in the next few years we will too see a sharp rise in quercetin-containing skincare products.
