Effects of quercetin on exercise potential and exercise-induced cytokines in the horse

Inflammation, the common physiological response to a wide variety of injuries and irritations, has been studied in one form or another for literally thousands of years. Most non-steroidal anti-inflammatory drugs (NSAIDS) work by inhibiting the production of prostaglandins (PG) via inactivation or modification of the cyclooxygenase (COX) enzyme. Unfortunately disruption of the COX pathway can have unintended consequences, such as an increase in tumor necrosis factor alpha (TNF-α) levels. In vitro studies consistently show reductions in inflammatory cytokines, including TNF-α and interkeukin-1 (IL-1), in cultures of immune cells after treatment with quercetin. Studies run in vivo have been less decisive. Hence, our goal in this experiment was to test the hypothesis that quercetin, in sufficient dosage, will increase athletic performance in the horse by decreasing exercise-induced inflammation via inhibition of the production of inflammatory cytokines. Six healthy, unfit Standardbred mares (~500 kg, age 4-5 years) were assigned to one of two groups in a crossover fashion. The horses were dosed via a nasogastric tube BID (8 am and 8 pm) with 6 g of quercetin in tap water for 3.5 days. Two hours after the seventh and final dose, a graded exercise test (GXT) was run. During the test the treadmill remained at a fixed 6% grade. At T = 0 the treadmill was started at a speed of 4 m/sec. Each following minute the treadmill speed was increased by 1 m/sec, up to a maximum speed of 11 m/sec. Blood and muscle samples were collected to measure markers of inflammation. There was a small but significant increase in run time when the horses were dosed with quercetin, and recovery time was shortened significantly when compared to water-treated trials. There were exercise-induced increases in plasma TNF-α, IL-1, interferon-γ, granzyme-B (GrB), hematocrit, total protein, glucose, and lactate, but only with GrB was there a significant drug effect in the quercetin group. Intramuscular levels of IL-1 and GrB also increased significantly with exercise, but there was no effect from quercetin treatment. This study provides compelling evidence that quercetin could be useful in enhancing exercise performance, although the mechanism for this enhancement is unclear. While this study alone is not sufficient to recommend quercetin for mainstream usage, it adds to a growing body of literature supporting the drug's effectiveness.M.S.Includes bibliographical referencesby James Baldassar