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A meta‐analysis of coffee drinking, cigarette smoking, and the risk of Parkinson's disease
Abstract
We conducted a systematic review to summarize the epidemiological evidence on the association between cigarette smoking, coffee drinking, and the risk of Parkinson's disease. Case–control and cohort studies that reported the relative risk of physician‐confirmed Parkinson's disease by cigarette smoking or coffee drinking status were included. Study‐specific log relative risks were weighted by the inverse of their variances to obtain a pooled relative risk and its 95% confidence interval (CI). Results for smoking were based on 44 case–control and 4 cohort studies, and for coffee 8 case–control and 5 cohort studies. Compared with never smokers, the relative risk of Parkinson's disease was 0.59 (95% CI, 0.54–0.63) for ever smokers, 0.80 (95% CI, 0.69–0.93) for past smokers, and 0.39 (95% CI, 0.32–0.47) for current smokers. The relative risk per 10 additional pack‐years was 0.84 (95% CI, 0.81–0.88) in case–control studies and 0.78 (95% CI, 0.73–0.84) in cohort studies. Compared with non–coffee drinkers, relative risk of Parkinson's disease was 0.69 (95% CI, 0.59–0.80) for coffee drinkers. The relative risk per three additional cups of coffee per day was 0.75 (95% CI, 0.64–0.86) in case–control studies and 0.68 (95% CI, 0.46–1.00) in cohort studies. This meta‐analysis shows that there is strong epidemiological evidence that smokers and coffee drinkers have a lower risk of Parkinson's disease. Further research is required on the biological mechanisms underlying this potentially protective effect.
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“To put this into perspective, the risk reduction documented in this meta-analysis (OR ϭ 0.67) was of a similar order of magnitude to the PD risk reductions previously noted with caffeine consumption or smoking, 8”
From Does vigorous exercise have a neuroprotective effect in Parkinson disease? (2011) · cites this paper as [8]
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“Dopamine is involved in cigarette smoking addiction, and smoking has been related to decreased PD risk in numerous epidemiologic studies [4].”
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BackgroundNeuroprotective Properties of Green Tea (Camellia sinensis) in Parkinson’s Disease: A Review
Malar, D. S., Prasanth, M. I., Brimson, J. M., Sharika, R., Sivamaruthi, B. S., Chaiyasut, C., & Tencomnao, T. (2020) · Molecules · doi:10.3390/molecules25173926 · Cited by 97
“Conversely, caffeinated beverage drinkers appear to have a reduced risk of developing PD and, surprisingly, smokers are also less likely to suffer PD, although the link between these two risk factors has yet to be conclusively attributed to specific causes of PD [28].”
BackgroundExploring gene-environment interactions in Parkinson’s disease
McCulloch, C. C., Kay, D. M., Factor, S. A., Samii, A., Nutt, J. G., Higgins, D. S., Griffith, A., Roberts, J. W., Leis, B. C., Montimurro, J. S., et al. (2008) · Human Genetics · doi:10.1007/s00439-008-0466-z · Cited by 93
“While the elements of rural living remain elusive, the inverse associations with coVee and smoking are well-established and quantiWable ( Hernan et al. 2002; Powers et al. 2007).”
InfluentialDetection and assessment of Parkinson's disease based on gait analysis: A survey
Guo, Y., Yang, J., Liu, Y., Chen, X., & Yang, G. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.916971 · Cited by 91
“In addition, researchers have conducted various studies to explore the relationships between environmental factors and PD, where the incident rate of PD was proven to be correlated to smoking, caffeine intake, and other factors (Hernán et al., 2002).”
BackgroundNongenetic causes of Parkinson’s disease
Chade, A., Kasten, M., & Tanner, C. M. (2006) · Springer eBooks · doi:10.1007/978-3-211-45295-0_23 · Cited by 94
Parkinson’s disease and pesticide exposure – a new assessment
Allen, M. T., & Levy, L. S. (2013) · Critical Reviews in Toxicology · doi:10.3109/10408444.2013.798719 · Cited by 90
“Furthermore, a stratified meta-analysis reported that the RR of PD was 0.59 (95% CI, 0.54–0.63) for ever smokers, 0.80 (95% CI, 0.69–0.93) for past smokers, and 0.39 (95% CI, 0.32–0.47) for current smokers (Hernán et al., 2002).”
BackgroundInfluentialPesticide use and incident Parkinson's disease in a cohort of farmers and their spouses
Shrestha, S., Parks, C. G., Umbach, D. M., Richards-Barber, M., Hofmann, J. N., Chen, H., Blair, A. E., Freeman, L. E. B., & Sandler, D. P. (2020) · Environmental Research · doi:10.1016/j.envres.2020.110186 · Cited by 90
Gut Inflammation in Association With Pathogenesis of Parkinson’s Disease
Chen, Q.-Q., Haikal, C., Li, W., & Li, J. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00218 · Cited by 88
van der Mark, M., Nijssen, P. C. G., Vlaanderen, J. J., Huss, A., Mulleners, W. M., Sas, A. M. G., van Laar, T., Kromhout, H., & Vermeulen, R. C. H. (2014) · PLoS ONE · doi:10.1371/journal.pone.0095297 · Cited by 89
“The evidence for an association between cigarette smoking and PD risk is particularly strong with studies consistently showing an exposure dependent reduction in risk with total lifetime exposure to cigarette smoke, the product of (average daily) smoking intensity and duration of smoking [2–4].”
Sääksjärvi, K., Knekt, P., Männistö, S., Lyytinen, J., Jääskeläinen, T., Kanerva, N., & Heliövaara, M. (2014) · European Journal of Epidemiology · doi:10.1007/s10654-014-9887-2 · Cited by 88
Alcohol consumption and the incidence of Parkinson's disease
Hernán, M. Á., Chen, H., Schwarzschild, M. A., & Ascherio, A. (2003) · Annals of Neurology · doi:10.1002/ana.10611 · Cited by 87
“Common addictive behaviors such as cigarette smoking and caffeine consumption are strongly associated to a decreased incidence of idiopathic Parkinson’s disease (PD).(1) Although several proposed biological mechanisms may be consistent with the existence of neuroprotective effects of cigarette smoke and caffeine, an a…”
BackgroundSelf-citationVitamin D from different sources is inversely associated with Parkinson disease
Wang, L., Evatt, M. L., Maldonado, L. G., Perry, W. R., Ritchie, J., Beecham, G. W., Martin, E. R., Haines, J. L., Pericak‐Vance, M. A., Vance, J. M., et al. (2014) · Movement Disorders · doi:10.1002/mds.26117 · Cited by 89
Ong, E. L., Goldacre, R., & Goldacre, M. J. (2014) · European Journal of Cancer · doi:10.1016/j.ejca.2014.06.018 · Cited by 86
Quercetin, not caffeine, is a major neuroprotective component in coffee
Lee, M., McGeer, E. G., & McGeer, P. L. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.06.015 · Cited by 86
“Caffeine was assumed to be the active agent (Arendash and Cao, 2010; Eskelinen and Kivipelto, 2010; Hernán et al., 2002).”
β2‐adrenoreceptor medications and risk of Parkinson disease
Nielsen, S. S., Gross, A., Camacho‐Soto, A., Willis, A. W., & Racette, B. A. (2018) · Annals of Neurology · doi:10.1002/ana.25341 · Cited by 86
Interaction between genes and environment in neurodegenerative diseases
Elbaz, A., Dufouil, C., & Alpérovitch, A. (2007) · Comptes Rendus Biologies · doi:10.1016/j.crvi.2007.02.018 · Cited by 85
“7) for ever smoking and a dose–effect relation [23].”
BackgroundReproductive factors, exogenous estrogen use, and risk of Parkinson's disease
Simon, K. C., Chen, H., Gao, X., Schwarzschild, M. A., & Ascherio, A. (2009) · Movement Disorders · doi:10.1002/mds.22619 · Cited by 87
Survival of Parkinson's disease patients in a large prospective cohort of male health professionals
Chen, H., Zhang, S. M., Schwarzschild, M. A., Hernán, M. Á., & Ascherio, A. (2006) · Movement Disorders · doi:10.1002/mds.20881 · Cited by 85
Self-citationBogaerts, V., Theuns, J., & Broeckhoven, C. V. (2007) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2007.00342.x · Cited by 91
“Conversely, cigarette smoking and coffee drinking are inversely associated with the risk for developing PD (Hancock et al. 2007; Hernan et al. 2002).”
BackgroundTea Polyphenols in Parkinson’s Disease
Caruana, M., & Vassallo, N. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-18365-7_6 · Cited by 88
Interactions between Calcium and Alpha-Synuclein in Neurodegeneration
Rcom-H'cheo-Gauthier, A. N., Goodwin, J., & Pountney, D. L. (2014) · Biomolecules · doi:10.3390/biom4030795 · Cited by 85
“Cigarette smoking and caffeine have both been shown to be protective [16], and while the mechanism of caffeine protection is unclear the caloric restriction associated with smoking with a subsequent decrease in metabolic oxidative stress may be a factor.”
BackgroundRisk of stroke in patients with idiopathic Parkinson disease
Becker, C., Jick, S. S., & Meier, C. R. (2009) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2009.06.005 · Cited by 81
“The patients enrolled in the GPRD are representative of the UK-population with regard to age, gender, geographic distribution and annual turnover rate [7], and GPRD data have been used in previous studies on PD [11–15].”
MethodMadeira, M. H., Boia, R., Ambrósio, A. F., & Santiago, A. R. (2017) · Mediators of Inflammation · doi:10.1155/2017/4761081 · Cited by 87
Liu, W.-M., Wu, R., Lin, J., Liu, Y.-C., Chang, C., & Lin, C. (2015) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2015.05.014 · Cited by 81
The Health Effect of Psychostimulants: A Literature Review
Favrod-Coune, T., & Broers, B. (2010) · Pharmaceuticals · doi:10.3390/ph3072333 · Cited by 84
“A dose-effect relationship for the protection towards Parkinson’s disease [23] has been suggested, as is an association with a reduction of risk for Alzheimer’s disease [24] (relative risk of 0.”
Backgroundβ-adrenoreceptors and the risk of Parkinson's disease
Hopfner, F., Höglinger, G. U., Kuhlenbäumer, G., Pottegård, A., Wod, M., Christensen, K., Tanner, C. M., & Deuschl, G. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30400-4 · Cited by 79
Treatment of Parkinson???s Disease
Wu, S., & Frucht, S. J. (2005) · CNS Drugs · doi:10.2165/00023210-200519090-00001 · Cited by 78
Dopamine agonists and neuroprotection in Parkinson's disease
Schapira, A. H. V. (2002) · European Journal of Neurology · doi:10.1046/j.1468-1331.9.s3.9.x · Cited by 77
Nonsteroidal Anti-Inflammatory Drugs and the Risk of Parkinson Disease
Bornebroek, M., de Lau, L. M. L., Haag, M. D. M., Koudstaal, P. J., Albert Hofman, D., Stricker, B. H. C., & Breteler, M. M. B. (2007) · Neuroepidemiology · doi:10.1159/000108110 · Cited by 77
Role of Microglia Adenosine A2AReceptors in Retinal and Brain Neurodegenerative Diseases
Santiago, A. R., Baptista, F. I., Santos, P. F., Cristóvão, G., Ambrósio, A. F., Cunha, R. A., & Gomes, C. A. (2014) · Mediators of Inflammation · doi:10.1155/2014/465694 · Cited by 81
“This review aims to compare inflammatory features of Parkinson’s and Alzheimer’s diseases with glaucoma and diabetic retinopathy, discussing the therapeutic potential of A2AR in these degenerative conditions.”
Backgroundmetabolic profiling of Parkinson's disease and mild cognitive impairment
Burté, F., Houghton, D. J., Lowes, H., Pyle, A., Nesbitt, S., Yarnall, A. J., Yu‐Wai‐Man, P., Burn, D. J., Santibanez‐Koref, M., & Hudson, G. (2017) · Movement Disorders · doi:10.1002/mds.26992 · Cited by 74
“Xanthine metabolism and lysolipid metabolism were both reduced in our early-stage PD cases, characterized by a reduction in 1-myristoyl-glycero-3phosphocholin, 2-myristoyl-glycero-3-phosphocholin and 1,3-dimethylurate, supporting previous observations in PD LRRK2 mutation carriers(10) and indicating that caffeine abso…”
ResultInfluential
Metadata
- Authors
- Hernán, M. A., Takkouche, B., Caamaño‐Isorna, F., & Gestal‐Otero, J. J.
- Affiliations
- Universidade de Santiago de Compostela (ES)
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2002-05-29
- Volume
- 52
- Issue
- 3
- Pages
- 276-284
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2053969387
- Cited by
- 818
- References
- 62
- Citations by year
- 2026: 21 · 2025: 28 · 2024: 24 · 2023: 35 · 2022: 28 · 2021: 48 · 2020: 41 · 2019: 36 · 2018: 31 · 2017: 43 · 2016: 36 · 2015: 44 · 2014: 43 · 2013: 40 · 2012: 35
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Pharmacology (medical) › Coffee research and impacts
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, coffee consumption, cigarette smoking, pack-years, disease risk, protective factors, neurodegeneration
- MeSH terms
- Coffee, Humans, Parkinson Disease, Risk Factors, Smoking, Cohort Studies, Case-Control Studies
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