Quercetin: inflammatory ageing, vascular function and resistance to cellular stress

Quercetin is a plant flavonoid found in, among other things, apples, onions, berries, and green tea. It has a strong reputation as an antioxidant and anti-inflammatory agent, which makes it an interesting molecule within healthy-lifespan strategies: namely because of effects on chronic low-grade inflammation (inflammaging) and vascular health, two critical factors for healthy ageing.

At the cellular level, quercetin modulates various signalling pathways involved in inflammatory and stress responses. For instance, it inhibits activation of the NF-κB pathway, a central regulator of pro-inflammatory gene expression, which leads to reduced production of cytokines and other inflammatory mediators. In addition, quercetin affects pathways such as MAPK/ERK, which contributes to modulation of cellular stress and survival signals.¹ ⁴

These biochemical effects also translate to vascular functions. Human and animal studies suggest that quercetin can support endothelium-dependent function, among other ways by increasing the availability of nitric oxide (NO) and helping with vasodilation, thereby regulating vascular tone more favourably.² ⁶

Meta-analytic evidence shows that quercetin supplementation can lower systolic blood pressure in adults, especially at higher doses and with longer interventions, which fits the hypothesis that this flavonoid can soften cardiovascular stress factors.³ ⁶ Studies show, for example, average drops in systolic blood pressure after weeks to months of supplementation, especially in people with metabolic stress or hypertensive traits.³ ⁶

Besides blood pressure, there are indications from clinical studies that quercetin can promote endothelial function, for example by improving NO-related signalling and possibly inhibiting endothelial activation, although not every RCT shows uniform effects on markers such as VCAM-1 or ICAM-1.⁷ ⁵

Favourable effects are also described outside the cardiovascular context. In preclinical models, quercetin has shown antioxidant and anti-inflammatory effects, including strengthened cellular resistance to stress and reduction of pro-inflammatory cytokines via, among other things, NF-κB inhibition.⁸ ⁷

It is important to emphasize that quercetin is not a clinically proven “senolytic” as that concept is used in gerontology; it does not destroy senescent cells, but it does contribute to a more favourable inflammatory and stress profile within cells and tissues. This function supports an environment in which cells can cope better with chronic stressors that are characteristic of ageing.

Within a healthy-lifespan strategy, quercetin therefore mainly functions as a powerful modulator of inflammaging and vascular health: it helps inhibit inflammatory pathways, promotes endothelial signalling, and supports cellular stress responses. This contributes to a biological environment that is more robust and resilient during ageing, without being an aggressive anti-ageing intervention or having a medicinal effect.

Sources:

1. Effects of Quercetin on Vascular Endothelium, Inflammation, Cardiovascular Disease and Lipid Metabolism — Review. This recent review discusses quercetin’s antioxidant and inflammation-modulating effects via NF-κB and MAPK and possible protection of the endothelium.
   https://www.mdpi.com/2072-6643/17/9/1579
2. Acute effects of quercetin-3-O-glucoside on endothelial function and blood pressure. This study shows that quercetin can improve endothelial functions and blood-pressure regulation via NO-related pathways.
   https://pubmed.ncbi.nlm.nih.gov/27169837/
3. Effects of Quercetin on Blood Pressure: Systematic Review and Meta-analysis. The meta-analysis shows that quercetin supplementation is associated with significant reductions in systolic (and at higher doses, also diastolic) blood pressure in RCTs.
   https://pubmed.ncbi.nlm.nih.gov/27405810/
4. Recent Advances in Potential Health Benefits of Quercetin. This recent review brings together data that quercetin has cardiovascular benefits, including effects on blood pressure, the endothelium, and oxidation.
   https://pmc.ncbi.nlm.nih.gov/articles/PMC10384403/
5. Effects of Quercetin Supplementation on Blood Pressures & Endothelial Function. RCT data show that daily supplementation did not always yield significant improvements in adhesion molecules, but did for other markers relevant to endothelial health.
   https://pubmed.ncbi.nlm.nih.gov/31092175/
6. Quercetin-rich onion skin extract lowers ambulatory blood pressure. This clinical study suggests that quercetin can contribute to lower systolic ambulatory blood pressure in hypertensive subgroups.
   https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/effects-of-a-quercetinrich-onion-skin-extract-on-24-h-ambulatory-blood-pressure-and-endothelial-function-in-overweighttoobese-patients-with-prehypertension-a-randomised-doubleblinded-placebocontrolled-crossover-trial/C33CDF1F4E46BB8BCD14940B2F005615
7. Quercetin reduces transcriptional NF-κB activity. More basic evidence that quercetin can inhibit NF-κB activation and pro-inflammatory signalling in cellular models.
   https://pubmed.ncbi.nlm.nih.gov/38319443/