Coffee is the most widely consumed beverage worldwide, and coffee consumption is associated with decreased risks for several chronic diseases and longer lifespans. There is a remarkable parallel between the health benefits linked to a Mediterranean diet and those linked to coffee intake, and yet the benefits of coffee are under-appreciated by the general public. Coffee contains more than 1000 different compounds and the composition varies with the roasting process, and there is some overlap in the diverse polyphenolic compounds that are found in brewed coffee extracts and foods that constitute the Mediterranean diet. Several studies have shown specific health benefits of individual compounds present in coffee (and the Mediterranean diet). However, studies on coffee consumption indicate differences in health benefits between consumption of coffee and that of decaffeinated coffee. Several studies have reported that increased consumption of coffee is associated with decreased risks for Parkinson’s disease, although some reports have not reported this association. In addition, many reports have associated increased caffeine consumption with decreased risks for Parkinson’s disease, and this has also been correlated with serum levels of urate and caffeine metabolites. The study by Zhao and coworkers have expanded this approach with a cohort (EPIC4PD) of 184,024 individuals from six European countries in which the associations between Parkinson’s disease and caffeine were assessed and quantification of plasma caffeine metabolite biomarkers was performed. The multivariable hazard ratio comparing high levels of coffee intake with no coffee consumption was 0.63, clearly demonstrating that coffee consumption was protective against Parkinson’s disease. In a subset of 351 patients with Parkinson’s disease and 351 matched controls, the serum levels of caffeine and its metabolites were quantified in both groups. There was an inverse association between the risk for Parkinson’s disease and serum levels of caffeine (OR, 0.80), paraxanthine (OR, 0.82), theophylline (OR, 0.78), and 1-methyluric acid (OR, 0.84). These data suggest a possible role for caffeine and its metabolites as potential agents that decrease the risk for Parkinson’s disease but do not negate contributions from other compounds in coffee extracts that are also known to be protective against neurotoxicity.

Abstract

BACKGROUND AND OBJECTIVES

Inverse associations between caffeine intake and Parkinson disease (PD) have been frequently implicated in human studies. However, no studies have quantified biomarkers of caffeine intake years before PD onset and investigated whether and which caffeine metabolites are related to PD.

METHODS

Associations between self-reported total coffee consumption and future PD risk were examined in the EPIC4PD study, a prospective population-based cohort including 6 European countries. Cases with PD were identified through medical records and reviewed by expert neurologists. Hazard ratios (HRs) and 95% CIs for coffee consumption and PD incidence were estimated using Cox proportional hazards models. A case-control study nested within the EPIC4PD was conducted, recruiting cases with incident PD and matching each case with a control by age, sex, study center, and fasting status at blood collection. Caffeine metabolites were quantified by high-resolution mass spectrometry in baseline collected plasma samples. Using conditional logistic regression models, odds ratios (ORs) and 95% CIs were estimated for caffeine metabolites and PD risk.

RESULTS

In the EPIC4PD cohort (comprising 184,024 individuals), the multivariable-adjusted HR comparing the highest coffee intake with nonconsumers was 0.63 (95% CI 0.46–0.88, p = 0.006). In the nested case-control study, which included 351 cases with incident PD and 351 matched controls, prediagnostic caffeine and its primary metabolites, paraxanthine and theophylline, were inversely associated with PD risk. The ORs were 0.80 (95% CI 0.67–0.95, p = 0.009), 0.82 (95% CI 0.69–0.96, p = 0.015), and 0.78 (95% CI 0.65–0.93, p = 0.005), respectively. Adjusting for smoking and alcohol consumption did not substantially change these results.

DISCUSSION

This study demonstrates that the neuroprotection of coffee on PD is attributed to caffeine and its metabolites by detailed quantification of plasma caffeine and its metabolites years before diagnosis.

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Journal Abstract