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bmjopenrespres.bmj.com - Randomised clinical trial to determine the safety of quercetin ...

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Introduction

Chronic obstructive pulmonary disease (COPD) is the major cause of mortality and morbidity in the USA and growing cause of chronic disease globally. The current pharmacological therapies for COPD, such as corticosteroids and β2 agonists, may provide symptom relief, reduce the rate of exacerbations, hospitalisations and possibly mortality, but despite this, many patients still experience symptoms, exacerbations and disease progression. Although the exact cellular mechanisms underlying COPD pathogenesis are not completely understood, the consensus is that oxidative stress and inflammation induced by exposure to cigarette smoke or other environmental or occupational hazards are responsible for development of COPD.1 Therefore, a neutraceutical with potent antioxidant and anti-inflammatory properties and relatively few side effects could be an attractive treatment option for COPD. Quercetin (3,3′,4′,5,7-pentahydroxyflavone) is a dietary flavonoid and has potent antioxidant and anti-inflammatory properties. We have demonstrated that oral treatment with a low dose of quercetin decreases inflammation, oxidative stress and matrix metalloproteinase production in a mouse model of COPD.2 Quercetin supplemented diet also alleviates rhinovirus-induced lung inflammation in mice with COPD phenotype.3 Recent studies have also demonstrated amelioration of hyperglycaemia, reduction of blood pressure and improvement of cardiovascular health by inhibiting platelet aggregation in experimental models. Accumulating epidemiological evidence suggests that quercetin-rich diets are associated with lower incidence of asthma4 and reduce disease severity in subjects with COPD.5 Treatment with quercetin decreased markers of oxidative stress and inflammation in plasma of patients with pulmonary sarcoidosis, another chronic lung inflammatory disease driven by oxidative stress.6 7 In another study, quercetin was shown to reduce blood pressure and plasma lipids in overweight or obese subjects with a high cardiovascular disease risk.8 Daily intake of quercetin-rich onion peel extract (equivalent to 100 mg of quercetin/day) for 10 weeks decreased blood pressure, serum lipids and blood glucose levels in male smokers.9 Additionally, treatment with quercetin for 12 weeks reduced the risk of acquiring upper respiratory infection in a large population of healthy adults.10 The latter study also suggests that quercetin treatment in healthy volunteers has no adverse effects. Furthermore, a meta-analysis of randomised controlled trials indicated treatment with quercetin reduces plasma C reactive protein11 and blood pressure in hypertensive subjects.12 Despite these epidemiological and experimental pieces of evidence, there have been no clinical trials examining the therapeutic effects of quercetin in COPD. An objective of this study was to determine the safety of quercetin supplementation in patients with COPD, because it is the first step towards using quercetin as a therapeutic agent in these patients.

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