In these 2 large prospective cohorts of men and women, we found that the prudent dietary pattern, characterized by high intakes of fruit, vegetables, whole grains, legumes, poultry, and fish was associated with a lower risk of PD. Similar results were obtained for higher AHEI or aMED scores, which suggests that a healthy dietary pattern with greater intakes of plant food and fish and moderate intakes of alcohol is inversely associated with PD risk. The associations were independent of smoking, caffeine intake, and other PD risk factors.
Compared with traditional single-food or nutrient methods, the dietary pattern approach is appealing for several reasons. In reality, people eat combinations of food and nutrients, which leads to a high collinearity among many of the nutrients and foods. It is often difficult to identify the effect of a single food or nutrient on health outcomes. Dietary patterns represent a combination of nutrients and foods; thus, they may be a more powerful predictor of health outcomes than any single nutrient alone (9
). Furthermore, a dietary pattern analysis offers an approach for better understanding the complexities of eating behaviors of different population groups and subgroups and may be used to effectively develop dietary intervention strategies for target groups (30
The healthy diet, as identified in our analysis, was characterized by a high consumption of fruit, vegetables, legumes, and cereals and a low consumption of meats. This diet provides plenty of dietary antioxidants and folate and a limited amount of saturated fat, which may contribute to the lower PD risk of individuals with healthy diets. There is substantial evidence of a role of oxidative stress in PD (34
), including increased oxidation in autopsy samples of substantia nigra from brains of persons with PD (34
), and that oxidative stress promotes α-synuclein aggregation, which is most likely an important event in the pathogenesis of PD (36
). We previously observed an inverse association between dietary intakes of vitamin E, but not of vitamin E from supplements, and PD risk in the NHS and HPFS population (7
). A recent meta-analysis also suggested that greater dietary vitamin E intakes might protect against PD (2
). The apparent discrepancy between vitamin E from foods and from supplements, however, remains unexplained.
The plasma homocysteine concentration has been shown to be inversely associated with the prudent dietary pattern factor in a subgroup of the HPFS (17
). In an animal model, folate deficiency and elevated homocysteine significantly sensitized dopaminergic neurons to a subtoxic dose of 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (37
). Homocysteine may have a neurotoxic effect by activating the N
-methyl-D-aspartate receptor, which leads to cell death (38
), or may be converted into homocysteic acid, which also has an excitotoxic effect on neurons (38
). Polymorphism of methylenetetrahydrofolate reductase C677T, a major determinant of plasma homocysteine, has been shown to be associated with risk of PD in the Rotterdam Study (41
), although no significant association was seen in a case-control study conducted in Germany (42
Our previous analysis indicated that the prudent dietary pattern or higher AHEI and aMED scores were significantly associated with lower plasma inflammatory biomarker concentrations (18
), which may further contribute to lower PD risk among individuals with such a diet. Chronic neuroinflammation may play a role in the pathogenesis of PD (43
) and we previously reported that the use of a nonsteroidal antiinflammatory drug was associated with a lower risk of PD in this cohort and in another prospective cohort (28
We did not observe a significant association between the Western dietary pattern and risk of PD. The Western dietary pattern has been shown to be significantly associated with high plasma homocysteine and inflammatory biomarkers in the HPFS and NHS (17
). However, in some case-control studies individuals with PD had significantly lower intakes of meat and eggs than did controls (45
). A greater intake of red meats or processed meats, which are major dietary sources of purine, has been reported to be associated with higher plasma uric acid concentrations (47
). Two prospective studies showed that a higher plasma uric acid concentration was significantly associated with a lower risk of PD (48
). After further adjustment for a dietary urate index, which reflects the effect of diet on plasma urate, the association between a Western dietary pattern and PD risk became slightly stronger (RR for quintile 5 versus quintile 1 increased from 1.29 to 1.35), although it remained nonsignificant (P
for trend = 0.4). Furthermore, we cannot exclude the possibility that a lack of association between the Western dietary pattern and PD risk was due to chance. More studies are needed to clarify this.
Because of the prospective design of the study, our results are unlikely to be significantly affected by recall or selection bias. We also carried out several sensitivity analyses that produced similar significant results. Known PD risk factors were adjusted in our analysis; however, we cannot exclude the possibility of residual confounding by unknown risk factors. Moreover, the dietary patterns defined by principal components analysis were data-driven but not established a priori. The prudent pattern, therefore, does not necessarily define an optimal diet. However, similar results were obtained using a priori defined dietary indexes that measured adherence to a healthy diet.
In conclusion, the results of this large prospective study suggest that dietary patterns with a high intake of fruit, vegetables, legumes, whole grains, nuts, fish, and poultry and a low intake of saturated fat and moderate intake of alcohol may protect against PD. The benefits of a plant-based dietary pattern including fish to PD merit further investigation.