Most of us in medicine are familiar with the popularized version of Paracelsus’ well-known claim that dose is what determines whether a substance is a medicine or a poison.
And while there is an undeniable truth to the phrase, it’s only part of the story.
The Importance of Metabolism
Besides dose, what your body does with a particular substance, how it gets metabolized, and the biologic effect those metabolites exert are all critical factors in determining if that substance is truly friend or foe.
And so, one of the most important considerations when selecting a dietary supplement is not only that a product has a meaningful dose of the featured—or primary—ingredients, but it is also equally important that the formula includes the necessary secondary nutrients to facilitate safe metabolism and improve overall clinical efficacy.
Quercetin Dose, Metabolism and Toxic Metabolites
Quercetin is one such example where both dose and metabolism are determining factors in achieving the desired clinical outcome safely and effectively.
As a potent bioflavonoid, quercetin supports the immune system in a dose-dependent manner. But when delivered by itself, without the addition of select antioxidants, quercetin can quickly oxidize. Oxidized quercetin forms quinones. In the presence of protein thiol groups, these quercetin-quinones will form toxic compounds that go on to exert pro-oxidant effects and cause damage throughout the body.
Creating Safe Quercetin Metabolites
Instead, well-designed formulas include the nutrients that are necessary to protect quercetin and create safe quercetin metabolites. Delivering quercetin with vitamin C in the presence of healthy glutathione status will increase quercetin’s clinical efficacy in two critical ways.
1. Vitamin C potentiates the activity of quercetin by recycling quercetin back to its reduced form. This increases quercetin’s bioavailability and effectiveness as an antioxidant.
2. N-acetyl cysteine (NAC) supports healthy glutathione status and will shunt quercetin down safer metabolic pathways. This stimulates the body to conjugate quercetin quinones via Phase II detoxification pathways.
Adapted from: Colunga Biancatelli RML, Berrill M, Catravas JD, Marik PE. Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19). Front Immunol. 2020;11:1451.
The Quercetin Paradox
This duality in quercetin—and its potential to be metabolized down one of two very different pathways—is known as the "quercetin paradox." Because quercetin can oxidize so easily, forming pro-oxidant, toxic metabolites, special care must be given to how quercetin-containing products are formulated. This is why quercetin should always be co-administered with vitamin C and NAC.
The Bottom Line
When taken together, these nutrients have a synergistic effect beyond what any of them can provide individually. Plus, mounting evidence supports their use for safe and effective immune support through their influence on improved barrier function, NK cell activity, and B-cell and T-cell maturation and differentiation.
Katrina Wilhelm, ND is a board-certified naturopathic physician with a passion for functional medicine. With over fifteen years of clinical and industry experience, she has worked with patients and providers alike, educating them on the role that dietary supplements and personalized lifestyle medicine play in creating optimal health.