The Cogence Clinical Pearls Series

Quercetin and Mast Cell Histamine Release

What the research says…

This paper, from PLoS One, found that the flavonoid quercetin is as effective as chromolyn sodium at inhibiting mast cell histamine release. Quercetin also more effectively inhibits the release of inflammatory cytokines IL-6, IL-8, and TNF from LAD2 mast cell lines. The authors also found that quercetin “is effective prophylactically, while cromolyn must be added together with the trigger or it rapidly loses its effect.”

Application…

In functional medicine practice, many of your most challenging patients have allergic symptoms driven by histamine. And, because histamine drives feedback loops that reinforce the immunology of allergy and food sensitivity, these patients end up caught in deeply entrenched patterns that can be hard to untangle. Quercetin can be a useful component of the strategy in working with these patients. While we’ve known about quercetin for a long time, it’s interesting to see this head to head comparison with the medication chromolyn sodium, and also interesting to see specific mechanisms by which quercetin directly mitigates cytokines of the inflammatory process.

For patients with mast cell activation syndrome (MCAS), taking up to 500mg of quercetin 30 to 40 minutes before eating can substantially reduce histamine release during meals. Other factors that can help patients with excessive histamine burden including low histamine diets and assessment and support of diamine oxidase (DAO) status. DAO supplementation can make a significant difference in the wellbeing of these patients.

Research…

Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans.

PLoS One. 2012;7(3):e33805. Weng Z, Zhang B, Theoharides TC, et al.

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Abstract

Mast cells are immune cells critical in the pathogenesis of allergic, but also inflammatory and autoimmune diseases through release of many pro-inflammatory cytokines such as IL-8 and TNF. Contact dermatitis and photosensitivity are skin conditions that involve non-immune triggers such as substance P (SP), and do not respond to conventional treatment. Inhibition of mast cell cytokine release could be effective therapy for such diseases. Unfortunately, disodium cromoglycate (cromolyn), the only compound marketed as a mast cell “stabilizer”, is not particularly effective in blocking human mast cells. Instead, flavonoids are potent anti-oxidant and anti-inflammatory compounds with mast cell inhibitory actions. Here, we first compared the flavonoid quercetin (Que) and cromolyn on cultured human mast cells. Que and cromolyn (100 µM) can effectively inhibit secretion of histamine and PGD(2). Que and cromolyn also inhibit histamine, leukotrienes and PGD(2) from primary human cord blood-derived cultured mast cells (hCBMCs) stimulated by IgE/Anti-IgE. However, Que is more effective than cromolyn in inhibiting IL-8 and TNF release from LAD2 mast cells stimulated by SP. Moreover, Que reduces IL-6 release from hCBMCs in a dose-dependent manner. Que inhibits cytosolic calcium level increase and NF-kappa B activation. Interestingly, Que is effective prophylactically, while cromolyn must be added together with the trigger or it rapidly loses its effect. In two pilot, open-label, clinical trials, Que significantly decreased contact dermatitis and photosensitivity, skin conditions that do not respond to conventional treatment. In summary, Que is a promising candidate as an effective mast cell inhibitor for allergic and inflammatory diseases, especially in formulations that permit more sufficient oral absorption.