4. Discussion
hyperuricemia, atherosclerotic diseases, dyslipidemia, hyperlipidemia
HYPERLIPIDEMIA, CVD, METABOLIC DISEASES, HYPERURICEMIA, SECONDARY, ENZYME INHIBITION, OXIDATIVE STRESS, DYSLIPIDEMIA
In this trial, we demonstrated that resveratrol had no significant effect on lipid profile but reduced serum uric acid and XO activity in a dose-response manner in subjects with dyslipidemia. A significant decrease of serum uric acid at eight weeks was observed in the 300 mg/d and 600 mg/d resveratrol groups but not in the 100 mg/d group, indicating resveratrol supplementation of 300 mg/d or more could produce a uric acid-lowering effect in subjects with dyslipidemia.Current evidence suggests that hyperlipidemia is closely related to hyperuricemia. Indeed, it is well-established that hyperlipidemia and hyperuricemia are independent risk factors for CVD. Several epidemiological studies have revealed an independent relationship between elevated serum uric acid concentration and increased morbidity or mortality from atherosclerotic diseases [Resveratrol is a polyphenol whose beneficial effects on dyslipidemia and hyperuricemia have been demonstrated in animal models. However, clinical trials have yielded inconclusive findings on its effect on dyslipidemia, which may be attributed to the heterogeneity in drug doses across studies. For example, Simental et al. [Regarding the effect of resveratrol on hyperuricemia, animal studies showed that resveratrol reduced serum uric acid concentration by inhibiting XO to reduce uric acid production [Overall, the discrepancies reported above can be attributed to the heterogeneity in doses of resveratrol, intervention duration, and study subjects. Besides, no study has compared the effect of resveratrol with multiple doses. The present study provided hitherto undocumented evidence that 300 mg/d and 600 mg/d of resveratrol could reduce serum uric acid concentration in subjects with dyslipidemia, but no significant change was observed with 100 mg/d resveratrol.In terms of the mechanism, many in vitro enzyme inhibition experiments have confirmed that resveratrol could significantly inhibit XO activity [In addition, uric acid is widely acknowledged as an oxypurine with antioxidant properties and a major endogenous antioxidant in the human body. Resveratrol, as a natural exogenous antioxidant, may decrease the production of uric acid by reducing oxidative stress. In this regard, Xiao et al. [Importantly, the randomized, double-blinded, placebo-controlled trial design of this study minimized potential biases and maximized the homogeneity of subjects and comparability among groups. Moreover, precautions were taken to ensure study rigor throughout the data collection and analytical phases. Nevertheless, the most significant limitation of our study is that it was not designed or conducted to distinguish hyperlipidemia patients with hyperuricemia; instead, uric acid and XO activity were used as secondary outcomes. Therefore, it is unclear whether the dose and duration of resveratrol in the present trial are optimal for patients with hyperuricemia alone or with other metabolic diseases. Furthermore, we failed to detect resveratrol or its metabolites in subjects’ blood samples to assess their adherence since the subjects had consumed capsules ≥ 20 h before blood sample collection. In this respect, resveratrol reportedly has a plasma half-life of only 9.2 h [