Association between gout, hyperuricemia, and Parkinson’s disease: a systematic review and meta-analysis

Abstract

BACKGROUND The association between gout, hyperuricemia, and Parkinson's disease (PD) has been widely debated with conflicting findings across studies. Although the antioxidant properties of urate suggest a potential neuroprotective role, chronic inflammation in gout may negate this benefit. OBJECTIVES To systematically evaluate the relationship between gout, hyperuricemia, and the risk of developing PD through a comprehensive review and meta-analysis of observational studies. METHODS Following PRISMA guidelines, we systematically searched PubMed, Web of Science, Scopus, and Embase (inception-May 2024) for observational studies. Data were extracted from 19 eligible studies (N = 15,571,392 participants). Random-effects meta-analysis was used to estimate the pooled risk ratios (RRs) for PD among individuals with gout or hyperuricemia. Subgroup analyses were conducted based on sex, age, and effect size. Heterogeneity was assessed using I2 statistics, and publication bias was evaluated using funnel plots and Egger's test. RESULTS Nineteen studies were included in this meta-analysis. Eight of the eight studies reported a protective effect of hyperuricemia, whereas four of the 12 studies reported a protective effect of gout. A meta-analysis showed no significant association between gout and PD (RR 0.99, 95% CI 0.90-1.08); however, hyperuricemia was associated with a reduced risk of PD (RR 0.69, 95% CI 0.56-0.85). In the gender-stratified analysis, gout showed no significant association with PD in males (RR 0.94, 95% CI 0.84, 1.05) or females (RR 1.07, 95% CI 0.96, 1.19), whereas hyperuricemia was more protective in males (RR 0.48, 95% CI 0.24, 0.97) than in females (RR 0.84, 95% CI 0.44, 1.61). Age-based analysis indicated that both hyperuricemia and gout were associated with a lower PD risk in individuals aged < 75 years; however, no significant protective effect was observed in individuals aged ≥ 75 years. CONCLUSION This meta-analysis found no significant association between gout and PD but supports a potential neuroprotective role of hyperuricemia, particularly in males and younger individuals. However, considering the limitations of evidence in the literature, the results need to be interpreted cautiously, and further studies may be required to explore clinical relevance after adjusting for possible modifying factors.