After an average of 14 years of follow-up, we documented 248 incident cases of PD. Participants with a higher dietary urate index were more likely to smoke, more likely to take diuretics, and consumed larger amounts of caffeine and energy than those with a low urate index () but did not differ from persons with a lower urate index with regard to other covariates.
Baseline characteristics of participants in the Health Professionals Follow-up Study according to quintile of dietary urate index, 1986*
Overall, we found that a higher dietary urate index was associated with a lower risk of PD. Comparing the top quintile of the index with the bottom quintile, the age- and smoking-adjusted relative risk of PD was 0.47 (95 percent confidence interval (CI): 0.30, 0.74; p-trend = 0.001). The results were not changed (relative risk (RR) = 0.47) after further adjustment for caffeine, body mass index, caloric intake, and other potential confounders (). To examine whether this association could be explained by any of the dietary factors included in the urate index, we further adjusted the analyses for each component of the index, one at a time. The relative risk for the highest quintile of the urate index versus the lowest remained significantly elevated after adjustment for vitamin C (RR = 0.39, 95 percent CI: 0.24, 0.64), dairy protein (RR = 0.53, 95 percent CI: 0.31, 0.88), fructose (RR = 0.49, 95 percent CI: 0.30, 0.78), and alcohol (RR = 0.45, 95 percent CI: 0.24, 0.83).
FIGURE 1 Relative risk (RR) of Parkinson’s disease according to quintile (Q) of baseline dietary urate index in the Health Professionals Follow-up Study, 1986-2000. Results were adjusted for age (in months), smoking status (never smoker, past smoker, or (more ...)
When considered individually, fructose, dairy protein, and alcohol were significantly or marginally significantly associated with PD risk in the direction consistent with their estimated effects on plasma urate level (). Vitamin C was not related to PD risk. After further adjustment for the dietary urate index, greater intake of fructose remained a significant predictor of a lower PD risk, but the associations between dairy protein and alcohol and PD were much attenuated. In contrast, vitamin C intake became significantly associated with a lower risk of PD (for comparison of the two extreme categories, adjusted RR = 0.46, 95 percent CI: 0.21, 0.98; p-trend = 0.04).
Relative risk* of Parkinson’s disease according to baseline intakes of fructose, dairy protein, vitamin C, and alcohol, Health Professionals Follow-up Study, 1986-2000
We conducted several sensitivity analyses to examine the robustness of our findings and observed similar significant associations. When we used an alternative urate index which further included meat and seafood, the results did not materially change. The multivariate-adjusted relative risk for the highest urate index quintile versus the lowest was 0.44 (95 percent CI: 0.27, 0.70; p-trend = 0.0002). After exclusion of subjects with gout at baseline, the relative risk for the highest urate index quintile versus the lowest was 0.46 (95 percent CI: 0.28, 0.75; p-trend = 0.001). In the 4-year lag analyses, the multivariate relative risks changed slightly, relative to the primary analyses. The relative risks were 1.0 (referent), 0.73, 0.94, 0.58, and 0.42 (95 percent CI: 0.25, 0.71; p-trend = 0.0007) for quintiles 1-5 of the urate index. When we excluded participants with a body mass index ≥30 or with reported hypertension, the multivariate-adjusted relative risks across quintiles of the index were 1.0 (referent), 0.64, 0.85, 0.58, and 0.38 (95 percent CI: 0.21, 0.69; p-trend = 0.001). Similar significant results were obtained when we used the cumulative average dietary urate index (for highest quintile vs. lowest, RR 0.55, 95 percent CI: 0.35, 0.87; p-trend = 0.01) and when we censored participants at the age of 75 years (for highest quintile vs. lowest, RR = 0.45, 95 percent CI: 0.26, 0.76; p-trend = 0.001). Similar patterns were seen for PD cases diagnosed by neurologists and PD cases diagnosed by nonneurologists. The adjusted relative risks across quintiles of the index were 1.0 (referent), 0.68, 0.84, 0.61, and 0.42 (p-trend = 0.001) for cases diagnosed by neurologists and 1.0 (referent), 0.63, 0.76, 0.55, and 0.55 for cases diagnosed by nonneurologists (p-trend = 0.20).
We did not find significant interactions between the dietary urate index and age, smoking status, body mass index, or caffeine intake at baseline (). The association between a higher urate index and a lower PD risk was evident in subgroup analyses carried out according to age, smoking status, body mass index, and caffeine intake.
Relative risk* of Parkinson’s disease in the fifth quintile of dietary urate index versus the first, according to baseline age, smoking status, body mass index, and caffeine intake, Health Professionals Follow-up Study, 1986-2000