Association of Coffee Consumption and Prediagnostic Caffeine Metabolites With Incident Parkinson Disease in a Population-Based Cohort

Damn it all, do something useful; give us the definition of highest caffeine intake. I want to know if my daily 12 cup pot of coffee is good enough. This is pretty much useless, we knew about this years ago, you gave us no new information.

 The other thing you should tell us; are paraxanthine and theophylline also in decaf coffee. If you had decent mentors and senior researchers they would have had you answer that question.

How coffee protects against Parkinson’s Aug. 2014 

Association of Coffee Consumption and Prediagnostic Caffeine Metabolites With Incident Parkinson Disease in a Population-Based Cohort

Yujia Zhao, MSc https://orcid.org/0000-0002-5275-0036, Yunjia Lai, PhD https://orcid.org/0000-0002-1081-0897, Hilde Konijnenberg, MSc, José María Huerta, PhD, Ana Vinagre-Aragon, MD, Jara Anna Sabin, Johnni Hansen, PhD, … Show All … , and Roel Vermeulen, PhDAuthors Info & Affiliations

April 23, 2024 issue

102 (8)

https://doi.org/10.1212/WNL.0000000000209201

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• • Abstract
  • Introduction
  • Methods
  • Results
  • Discussion
  • Glossary
  • Acknowledgment
  • Study Funding
  • Disclosure
  • Publication History
  • Appendix Authors
  • Supplementary Material
  • References
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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.

Introduction

Parkinson disease (PD) is the most common motor neurodegenerative disorder for which there is no effective prevention or curative treatment available so far. Coffee consumption has been associated with a reduced risk of PD in several prospective cohorts during the past 20 years.^1-5 The protective effect was also present for caffeine from noncoffee sources, such as tea, cola beverages, and chocolate.^2-4 By contrast, the effect was not observed for decaffeinated coffee,⁵ suggesting that the inverse association between coffee consumption and PD is largely due to caffeine and its metabolites, rather than other bioactive compounds in coffee. However, these findings were based on food questionnaire data rather than on measuring caffeine or its metabolites in predisease biological samples.

Some exploratory case-control studies have indicated that blood concentrations of caffeine and its major metabolites in humans, namely paraxanthine and theophylline, were reduced in patients with prevalent PD when compared with healthy individuals.^6-8 Following these observations, clinical trials have been initiated to investigate whether caffeine or its metabolites could slow the progression of PD. Unfortunately, these studies have shown no benefit of caffeine and its metabolites on symptom attenuation and progression in PD.^9,10 However, no studies to date have prospectively investigated the role of caffeine levels in prediagnostic samples to investigate whether caffeine and its metabolites could be protective in a prodromal state of the disease. This research question can only be investigated in very large cohorts with baseline blood samples and long follow-up available, such as in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The EPIC cohort comprises more than half million participants across Europe who have been followed up for >20 years and for which baseline blood samples were collected and ascertained in a highly standardized fashion.¹¹ During the long follow-up, several hundred participants have been diagnosed with PD.¹²

Coffee is the most widely consumed psychoactive beverage in the world. Unraveling the biological action of caffeine on PD not only carries important public health implications but also enhances our understanding of PD etiology and fosters potential prevention strategies. In this study, we aimed to investigate the relationship between caffeine and future PD risk prospectively in the EPIC cohort, using self-reported coffee consumption and direct measurement of prediagnostic caffeine and its metabolites.

 

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