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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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“In line with these observations, prospective cohort and case-control studies have identified tobacco smoking as the most significant protective factor against the risk of developing PD (49–51), presumably through self-administration of NIC, although the implication of other compounds in tobacco cannot be not totally e…”
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“Although no prospective studies evaluating these premorbid features exist, meta-analyses of retrospective studies evaluating the premorbid habits of PD patients verify that caffeine use and smoking are much less common before the onset of PD compared with controls.(41) Since dopamine is involved in the reward system,…”
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“Tobacco use decreases the risk by roughly twofold (Hernán et al., 2002; Tanner et al., 2002; Ritz et al., 2007; Quik and Wonnacott, 2011).”
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“Caffeine is a broad-spectrum PDE inhibitor, and epidemiological data consistently showed that caffeine consumption reduces the risk of PD in Asian, US and European populations [29].”
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“Coffee drinkers were at a 30% lower risk of the disease as compared to non-drinkers [61], which is consistent with the latest meta-analysis from 2014 and the conclusion that the strongest positive effect (28% lower risk) was observed for the daily intake of 3 cups of coffee [52].”
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Smoking and Parkinson's Disease: Using Parental Smoking as a Proxy to Explore Causality
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“In longitudinal studies, current smokers, compared with never smokers, were found to have one-third the risk of Parkinson’s disease (5).”
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Prospective case–control study of nonfatal cancer preceding the diagnosis of parkinson’s disease
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“There is a well-documented inverse association between smoking and PD [16].”
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“caffeine and smoking (44), but those with positive associations, e.”
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“In a meta-analysis including 44 case–control and four cohort studies, the pooled relative risk of PD was 0.59 for ever smokers vs. never smokers (Hernan et al., 2002).”
BackgroundInfluentialMethylxanthines and Human Health: Epidemiological and Experimental Evidence
Beaudoin, M., & Graham, T. E. (2010) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-13443-2_21 · Cited by 54
Caffeine in Parkinson's disease: A pilot open‐label, dose‐escalation study
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“Relative risk of PD in caffeine users is reduced by approximately 30%.(8,9) Many theories exist to explain this finding, including (1) direct neuroprotective effect, (2) symptomatic effect that delays diagnosis (this could be disease modifying, if early symptomatic treatment has long-term benefit),(10) (3) reverse cau…”
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Reproductive factors and clinical features of Parkinson's disease
Cereda, E., Barichella, M., Cassani, E., Caccialanza, R., & Pezzoli, G. (2013) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2013.07.020 · Cited by 52
Bridge, M. H., Williams, E., Lyons, M. E. G., Tipton, K. F., & Linert, W. (2004) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.05.007 · Cited by 52
Fritsch, T., Smyth, K. A., Wallendal, M. S., Hyde, T., Leo, G. J., & Geldmacher, D. (2012) · Southern Medical Journal · doi:10.1097/smj.0b013e318273a60d · Cited by 52
Effects of hydroxyhydroquinone-reduced coffee on vasoreactivity and blood pressure
Ochiai, R., Chikama, A., Kataoka, K., Tokimitsu, I., Maekawa, Y., Ohishi, M., Rakugi, H., & Mikami, H. (2009) · Hypertension Research · doi:10.1038/hr.2009.132 · Cited by 55
Therapies for Parkinson’s diseases: alternatives to current pharmacological interventions
Li, S., Dong, J., Cheng, C., & Le, W. (2016) · Journal of Neural Transmission · doi:10.1007/s00702-016-1603-9 · Cited by 50
“A meta-analysis of eight case–control and five cohort studies conducted in four countries between 1968 and 2001 found a 31 % lower risk of PD in coffee drinkers than non-coffee drinkers (Hernán et al. 2002).”
BackgroundInfluentialGastrointestinal disorders in Parkinson’s disease and other Lewy body diseases
Hirayama, M., Nishiwaki, H., Hamaguchi, T., & Ohno, K. (2023) · npj Parkinson s Disease · doi:10.1038/s41531-023-00511-2 · Cited by 51
“Smoking has decreased PD development by ~50% in 44 retrospective and four prospective studies 47 .”
Dementia with Lewy bodies: Definition, diagnosis, and pathogenic relationship to Alzheimer’s disease
Mrak, R. E., & Griffin, W. S. T. (2007) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.a936 · Cited by 49
“More intriguing are studies suggesting increased risk of Parkinson’s disease associated with traumatic head injury (Bower et al 2003), and protection against Parkinson’s disease associated with use of NSAIDs (Chen et al 2003), with physical exercise (Chen et al 2005), and with a diet rich in…”
Park, J., Kim, D., Park, Y. G., Kwon, D., Choi, M., Jung, J., & Han, K. (2019) · European Journal of Cancer · doi:10.1016/j.ejca.2019.04.033 · Cited by 49
Parkinson's disease: 10 years of progress, 1997–2007
Fahn, S. (2010) · Movement Disorders · doi:10.1002/mds.22796 · Cited by 51
Gene-Environment Interaction in Parkinson's Disease: Coffee, ADORA2A, and CYP1A2
Chuang, Y., Lill, C. M., Lee, P., Hansen, J., Lassen, C. F., Bertram, L., Greene, N., Sinsheimer, J. S., & Ritz, B. R. (2016) · Neuroepidemiology · doi:10.1159/000450855 · Cited by 49
Severity of parkinsonism associated with environmental manganese exposure
Racette, B. A., Nelson, G., Dlamini, W. W., Prathibha, P., Turner, J. R., Ushe, M., Checkoway, H., Sheppard, L. A., & Nielsen, S. S. (2021) · Environmental Health · doi:10.1186/s12940-021-00712-3 · Cited by 48
The emerging science of precision medicine and pharmacogenomics for Parkinson's disease
Payami, H. (2017) · Movement Disorders · doi:10.1002/mds.27099 · Cited by 46
Chronic Inflammation Links Cancer and Parkinson’s Disease
Li, Z., Zheng, Z., Ruan, J., Li, Z., & Tzeng, C. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00126 · Cited by 46
Singh, S., Singh, K., Patel, D. K., Singh, C., Nath, C., Singh, V. K., Singh, R. K., & Singh, M. P. (2009) · Rejuvenation Research · doi:10.1089/rej.2009.0850 · Cited by 47
Galanaud, J. ‐., Elbaz, A., Clavel, J., Vidal, J., Corrèze, J., Alpérovitch, A., & Tzourio, C. (2004) · Movement Disorders · doi:10.1002/mds.20307 · Cited by 47
“Cases Women Never 96 (56) 97 (30) 100 (16) Ever 4 (2) 3 (1) 0 (0) Men Never 40 (4) 53 (9) 63 (57) 67 (14) 54 (13) 63 (17) 72 (13) Ever 60 (6) 47 (8) 37 (33) 33 (7) 46 (11) 37 (10) 28 (5) Controls Women Never 92 (151) 95 (73) 95 (19) Ever 8 (13) 5 (4) 5 (1) Men Never 44 (18) 44 (18) 48 (96) 49 (27) 43 (22) 41 (22) 60 (…”
Ritter, L., Goushleff, N. C. I., Arbuckle, T. E., Cole, D. C., & Raizenne, M. E. (2006) · Journal of Toxicology and Environmental Health Part B · doi:10.1080/10937400600755895 · Cited by 47
Fukushima, Y., Tashiro, T., Kumagai, A., Ohyanagi, H., Horiuchi, T., Takizawa, K., Sugihara, N., Kishimoto, Y., Taguchi, C., Tani, M., et al. (2014) · Journal of Nutritional Science · doi:10.1017/jns.2014.19 · Cited by 46
Medical history, cigarette smoking and risk of acoustic neuroma: An international case‐control study
Schoemaker, M. J., Swerdlow, A. J., Auvinen, A. P., Christensen, H. C., Feychting, M., Johansen, C., Klæboe, L., Lönn, S., Salminen, T. M., & Tynes, T. (2006) · International Journal of Cancer · doi:10.1002/ijc.22272 · Cited by 46
Bensaid, M., Michel, P. P., Clark, S. D., Hirsch, É. C., & François, C. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.11.004 · Cited by 46
“3)Moreover, epidemiological studies have identified tobacco smoking as the most significant protective factor against the risk of developing PD (Hernan et al., 2002; Thacker et al., 2007).”
Caffeinated clues from epidemiology of Parkinson’s disease
Ascherio, A., & Chen, H. (2003) · Neurology · doi:10.1212/01.wnl.0000095213.86899.21 · Cited by 47
Correction: Serum Iron Levels and the Risk of Parkinson Disease: A Mendelian Randomization Study
Pichler, I., Fabiola Del Greco, M., Gögele, M., Lill, C. M., Bertram, L., Do, C. B., Eriksson, N., Foroud, T., Myers, R. H., Nalls, M. A., et al. (2013) · PLoS Medicine · doi:10.1371/annotation/c4d81646-0c0e-4a3e-9425-b220bae2d8b6 · Cited by 47
Schepici, G., Silvestro, S., Bramanti, P., & Mazzon, E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134766 · Cited by 48
“in eight case-control studies and four cohort studies observed that daily coffee consumers, compared to non-consumers, had a lower risk of PD [120].”
BackgroundParaquat (herbicide) as a cause of Parkinson's Disease
Sharma, P., & Mittal, P. (2023) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2023.105932 · Cited by 45
Understanding the link between cancer and neurodegeneration
Driver, J. A. (2011) · Journal of Geriatric Oncology · doi:10.1016/j.jgo.2011.11.007 · Cited by 46
A systematic review of nutritional risk factors of Parkinson's disease
Ishihara, L., & Brayne, C. (2005) · Nutrition Research Reviews · doi:10.1079/nrr2005108 · Cited by 45
“The titles and abstracts of possible systematic reviews and meta-analyses were reviewed, and one meta-analysis each for coffee drinking and antioxidants were identified (Hernan et al. 2002; Etminan et al. 2005).”
BackgroundResultInfluentialUpdate: Protective and risk factors for Parkinson disease
Grotewold, N., & Albin, R. L. (2024) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2024.107026 · Cited by 53
Cognitive and Neuropsychiatric Features of Early Parkinson's Disease
Getz, S. J., & Levin, B. E. (2017) · Archives of Clinical Neuropsychology · doi:10.1093/arclin/acx091 · Cited by 47
Novel Pharmacotherapies in Parkinson’s Disease
Tizabi, Y., Getachew, B., & Aschner, M. (2021) · Neurotoxicity Research · doi:10.1007/s12640-021-00375-5 · Cited by 43
“The inverse relationship between PD incidence and any form of nicotine intake such as cigarette smoking (Hernán et al. 2002; Ritz et al. 2007; Li et al. 2015), smokeless tobacco (O’Reilly et al.”
BackgroundCopeland, R., Leggett, Y. A., KANAAN, Y. M., Taylor, R. E., & Tizabi, Y. (2005) · Neurotoxicity Research · doi:10.1007/bf03033982 · Cited by 43
“© 2005 FP Graham Publishing Co., www.NeurotoxicityResearch.com 1999; Hernan et al., 2002; Wirdefeldt et al., 2005).”
BackgroundCoffee bean polyphenols ameliorate postprandial endothelial dysfunction in healthy male adults
Ochiai, R., Sugiura, Y., Otsuka, K., Katsuragi, Y., & Hashiguchi, T. (2015) · International Journal of Food Sciences and Nutrition · doi:10.3109/09637486.2015.1007453 · Cited by 42
“Coffee intake has been shown to produce protective effects against various diseases, such as type 2 diabetes, hypertension, Alzheimer’s disease and Parkinson’s disease, in epidemiological studies (Eskelinen et al., 2009; Hernan et al., 2002; Jee et al., 1999; van Dam et al., 2002).”
BackgroundDiet and medical foods in Parkinson’s disease
Lange, K. W., NAKAMURA, Y., Chen, N., Guo, J., Kanaya, S., Lange, K. M., & Li, S. (2019) · Food Science and Human Wellness · doi:10.1016/j.fshw.2019.03.006 · Cited by 43
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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