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A Prospective Study of Bowel Movement Frequency and Risk of Parkinson's Disease
Open accessAbstract
The authors prospectively examined bowel movement frequency at baseline in relation to future Parkinson's disease risk in the Health Professionals Follow-up Study (HPFS) during 2000-2006 (33,901 men) and the Nurses' Health Study (NHS) during 1982-2006 (93,767 women). During the follow-up (6 years for the HPFS and 24 years for the NHS), the authors identified 156 incident male Parkinson's disease cases (HPFS) and 402 female cases (NHS). In the HPFS, compared with men with daily bowel movements, men with a bowel movement every 3 days or less had a multivariate-adjusted relative risk of 4.98 (95% confidence interval (CI): 2.59, 9.57) for developing Parkinson's disease in the next 6 years. In the NHS, the corresponding relative risk was 2.15 (95% CI: 0.76, 6.10), and the risk of Parkinson's disease was not elevated beyond 6 years of follow-up (relative risks = 1.25 for years 7-12, 0.54 for years 13-18, and 0.88 for years 19-24). When these 2 cohorts were combined, the pooled relative risks for Parkinson's disease in the next 6 years were 0.75, 1 (referent), 2.62, and 3.93 (95% CI: 2.26, 6.84) (P(trend) < 0.0001) across 4 bowel movement categories. In conclusion, infrequent bowel movements may antedate the onset of cardinal motor symptoms of Parkinson's disease and may contribute to the identification of populations with higher than average Parkinson's disease risk.
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“Some of these symptoms may precede the classical motor symptoms by several years (Abbott et al., 2001;Chen et al., 2015;Gao et al., 2011)”
From The Gut-Brain Axis in Parkinson’s Disease: Possibilities for Food-Based Therapies (2017) · cites this paper as Gao et al., 2011
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Klietz, M., Greten, S., Wegner, F., & Höglinger, G. U. (2019) · Drugs & Aging · doi:10.1007/s40266-019-00654-z · Cited by 63
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Hughes, K. C., Gao, X., Molsberry, S. A., Valeri, L., Schwarzschild, M. A., & Ascherio, A. (2019) · Neurology · doi:10.1212/wnl.0000000000008567 · Cited by 44
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“Fifteen other medical diagnoses were positively related to PD onset including: dementia (Aarsland et al., 2003), bowel movement (Abbott et al., 2001; Gao et al., 2011), methamphetamine-use (MU) disorders (Callaghan et al., 2010), depression (Fang et al., 2010), depression and anxiety (Jacob et al.,…”
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Non-motor features of Parkinson’s disease in a nested case–control study of US men
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“15 times more likely to develop PD than those who defecated daily [97].”
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“Examples in the fi rst group are the HAAS, 23 the Rotterdam Study, 10,21 the HPFS, 25 the NHS, 30 and the AHS.”
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Role of rodent models in advancing precision medicine for Parkinson's disease
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“Constipation was defined as self-reported bowel movement every other day or less frequently and/or laxative use at least weekly.(17) pRBD was assessed using a question adapted from the Mayo Sleep Questionnaire that asks about dream enactment behavior and violent or excessive movement during sleep that has occurred at…”
MethodPrebiotics and probiotics and Parkinson's disease
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Plasma Metabolomics Profiles in Prodromal and Clinical Parkinson's Disease
Flores‐Torres, M. H., Peng, X., Jeanfavre, S., Clish, C. B., Wang, Y., McCullough, M. L., Healy, B. C., Schwarzschild, M. A., Bjørnevik, K., & Ascherio, A. (2025) · Movement Disorders · doi:10.1002/mds.30308 · Cited by 7
Navarro‐Otano, J., Llansó, L., Alejaldre, A., Porras, L. D., Santamaría, J., & Iranzo, Á. (2024) · Journal of Neurology · doi:10.1007/s00415-024-12787-2 · Cited by 8
Controlling Gut Microbiota by Twendee X® May Contribute to Dementia Prevention
You, F., Harakawa, Y., Yoshikawa, T., & Inufusa, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242316642 · Cited by 7
Cao, Z., Song, S., Huang, X., Li, C., Luo, Z., D’Aloisio, A. A., Suárez, L., Hernandez, D. G., Singleton, A., Sandler, D. P., et al. (2023) · Journal of Parkinson s Disease · doi:10.3233/jpd-230053 · Cited by 6
“With few exceptions [39, 40], investigators often seek alternative approaches to cost-efficiently identify and confirm PD cases, for example, adjudication of selfreported diagnosis with additional diagnostic data collection from potential patients and their treating physicians [5, 20, 23, 41, 42], solely based on rout…”
BackgroundBaldin, E., Zenesini, C., Bauleo, S., Montanari, F., Santi, S., Spampinato, M., Cortelli, P., D’Alessandro, R., & Ascherio, A. (2020) · Journal of Parkinson s Disease · doi:10.3233/jpd-191868 · Cited by 6
“Constipationwasdefinedasabowelmovementfre-quency of every other day or less, and/or laxative use at least twice a week [7].”
Is either anosmia or constipation associated with cognitive dysfunction in Parkinson’s disease?
Sheng, M.-Z., Fang, T.-C., Chen, Y.-H., Chang, M., Yang, C., & Lin, C. (2021) · PLoS ONE · doi:10.1371/journal.pone.0252451 · Cited by 6
“Constipation affects approximately 60–80% of PD patients [2,3].”
BackgroundNeilson, L. E., Quinn, J. F., & Lim, M. M. (2023) · Aging and Disease · doi:10.14336/ad.2022.1024 · Cited by 6
“The association becomes stronger with increasing severity of constipation[110].”
Septyaningtrias, D. E., Zulfa, H. A., Ramadhani, M. F., Sumaryati, Sulistyawati, D., Paramita, D. K., Sumiwi, Y. A. A., & Susilowati, R. (2023) · Journal of Histochemistry & Cytochemistry · doi:10.1369/00221554231182195 · Cited by 5
“71(6) 333 –344 © The Author(s) 2023 Article reuse guidelines: sagepub.”
Kim, Y.-J., Lee, C., Kim, S., Jang, J., Lee, S., & Lee, S.-H. (2019) · Journal of Neurology · doi:10.1007/s00415-019-09617-1 · Cited by 5
Marine Bioactive Components and Chronic Neuroinflammation: Focus on Neurodegenerative Disease
Favari, E., & Parolini, C. (2025) · Marine Drugs · doi:10.3390/md23110446 · Cited by 4
“Of note, some of these non-motor symptoms may appear many years before the occurrence of the classical motor signs [55,56] and their presence in healthy individuals has been linked to an increased risk of developing PD [57,58].”
Yun, Q., Wang, S., Li, B., Yang, Z., Wei, C., Yuan, J., Hu, J., Li, Y., Yang, Z., Sha, F., et al. (2025) · Age and Ageing · doi:10.1093/ageing/afaf257 · Cited by 4
Age, Statin Use, and the Risk for Incident Parkinson Disease—Reply
Gao, X., Simon, K. C., Schwarzschild, M. A., & Ascherio, A. (2012) · Archives of Neurology · doi:10.1001/archneurol.2012.2032 · Cited by 4
Miller‐Patterson, C., Hsu, J. Y., Chahine, L. M., Morley, J. F., & Willis, A. W. (2022) · Clinical Autonomic Research · doi:10.1007/s10286-022-00889-8 · Cited by 4
Identifying Individuals in the Prodromal Phase of Parkinson's Disease: A Prospective Cohort Study
Flores‐Torres, M. H., Hughes, K. C., Cortese, M., Hung, A. Y., Healy, B. C., Schwarzschild, M. A., Bjørnevik, K., & Ascherio, A. (2024) · Annals of Neurology · doi:10.1002/ana.27166 · Cited by 5
Exploring the Role of Food and Food-Related Compounds in Parkinson’s Disease
Trezzi, I., Rizzo, G., Giampieri, F., Battino, M. A., & Baroni, L. (2026) · Foods · doi:10.3390/foods15030514 · Cited by 4
“It can be spec‑ ulated that constipation may increase PD risk due to the prolonged retention of feces, leading to greater absorption of neurotoxicants [69].”
Wei, H., Hu, Y., & Yang, L. (2021) · Archives of Medical Science · doi:10.5114/aoms/143780 · Cited by 3
“Perturbations in miRNA expression were found in many nervous system disorders, such as PD, indicating that miRNA dysregulation is related to the pathogenesis of these diseases [11].”
Onaolapo, A. Y., Ojo, F. O., Olofinnade, A. T., Falade, J., Lawal, I. A., & Onaolapo, O. J. (2022) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527321666220903114559 · Cited by 4
Parkinson’s Disease-Related Motor and Nonmotor Symptoms in the Lancaster Amish
Goldenberg, M. D. F., Huang, X., Chen, H., Kong, L., Postolache, T. T., Stiller, J. W., Ryan, K. A., Pavlovich, M. A., Pollin, T. I., Shuldiner, A. R., et al. (2020) · Neuroepidemiology · doi:10.1159/000509394 · Cited by 2
Zhao, Q., Xu, B., Mao, W., Ren, Z., Chi, T., & Chan, P. (2024) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2024.107053 · Cited by 3
Song, S., Luo, Z., Plassman, B. L., Huang, X., Yuan, Y., Shrestha, S., Parks, C. G., Hofmann, J. N., Freeman, L. E. B., Sandler, D. P., et al. (2025) · Movement Disorders · doi:10.1002/mds.30149 · Cited by 2
“5,21 We de fi ned excessive daytime sleepiness as feeling sleepy most of the day for ≥ 1 to 2 days a week.”
Mashiningan extract disturbs water absorption by decreasing aquaporin-3 expression in the colon
Kon, R., Inoue, N., Yamamoto, M., Deguchi, M., Sato, Y., Nishimoto, S., Yonamine, S., Iwasaki, Y., Harada, Y., Fujitsuka, N., et al. (2025) · Fitoterapia · doi:10.1016/j.fitote.2025.106659 · Cited by 2
Intestinal Dysfunction in Parkinson’s Disease
Pfeiffer, R. F. (2012) · Humana Press eBooks · doi:10.1007/978-1-60761-429-6_10 · Cited by 2
Gut-brain axis: Review on the association between Parkinson’s disease and plant lectins
Moin, K., Funk, C. M., & Josephs, M. (2022) · Archive of Clinical Cases · doi:10.22551/2022.37.0904.10228 · Cited by 2
“As mentioned, constipation is the earliest and most crucial prodromal symptom of PD [68-70].”
BackgroundZhang, J., Shi, M., Zhang, Q., Chen, Y., Yin, X., Wang, X., & Zhang, Y. (2024) · Neuroepidemiology · doi:10.1159/000540955 · Cited by 1
“For example, some studies have shown that infrequent bowel movements were associated with an increased risk of PD [18 – 20], while the Nurses ’ Health Study [20] failed to replicate the deleterious effects of infrequent bowel movements on PD.”
InfluentialParkinson’s Disease in Humans and in Nonhuman Primate Aging and Neurotoxin Models
Metzger, J. M., Jones, C. A., & Emborg, M. E. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811353-0.00046-4 · Cited by 1
Epidemiology of Parkinson’s Disease—Current Understanding of Causation and Risk Factors
Patil, R. R. (2021) · Series in bioengineering · doi:10.1007/978-981-16-3056-9_3 · Cited by 4
The role of the gut microbiota in Parkinson’s disease
Verugina, N. I., Levin, O. S., & Lyashenko, E. A. (2021) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro202112110286 · Cited by 1
Effects of Physical Activity on Pakinson's Disease Patients
Smimih, K., El‐Mansoury, B., Laadraoui, J., Saad, F. E.-Z., Merzouki, M., Ammouta, L., Khanouchi, M., Aimrane, A., Azzouhri, C., Zouhairi, N., et al. (2023) · Advances in medical diagnosis, treatment, and care (AMDTC) book series · doi:10.4018/978-1-6684-5156-4.ch016 · Cited by 1
A Prospective Study of Bowel Movement Frequency and Risk of Parkinson's Disease
Talley, N. J. (2012) · Yearbook of Medicine · doi:10.1016/s0084-3873(12)00283-0 · Cited by 1
Ovallath, S., & Sulthana, B. (2018) · Annals of Movement Disorders · doi:10.4103/aomd.aomd_4_18 · Cited by 1
“[12-14] It has been postulated that lesser bowel movements were associated with a higher risk of developing PD compared to regular bowel movements, and the risk being five times more in males compared to three times in females.[15,16] Some studies show that the constipated individuals are twice more likely to develop…”
BackgroundKesoyan., A. A., Arakelyan, N. L., Aloyan, D. A., Karapetyan, A. A., & Manvelyan, H. M. (2022) · THE NEW ARMENIAN MEDICAL JOURNAL · doi:10.56936/18290825-2022.16.4-23 · Cited by 1
Metadata
- Authors
- Gao, X., Chen, H., Schwarzschild, M. A., & Ascherio, A.
- Affiliations
- Brigham and Women's Hospital (US)
- National Institutes of Health (US)
- Harvard University (US)
- Corresponding author
- Gao, X.
- Venue
- American Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-06-30
- Volume
- 174
- Issue
- 5
- Pages
- 546-551
- ISSN
- 0002-9262 (ISSN-L)
- 1476-6256
- PMC
- PMC3202149
- OpenAlex
- W2103939473
- Cited by
- 115
- References
- 25
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 4 · 2023: 13 · 2022: 9 · 2021: 10 · 2020: 11 · 2019: 10 · 2018: 11 · 2017: 8 · 2016: 6 · 2015: 4 · 2014: 5 · 2013: 5 · 2012: 10
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Epidemiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1z01es101986-03, Z01-ES101986)
- National Institute of Neurological Disorders and Stroke (R01NS061858, K24NS060991, R01NS048517)
- National Institute of Environmental Health Sciences (Z01-ES 101986)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Parkinson's disease, stool frequency, constipation, risk factors, men, women, Health Professionals Follow-up Study, Nurses' Health Study
- MeSH terms
- Adult, Aged, Constipation, Defecation, Female, Humans, Male, Middle Aged, Parkinson Disease, Risk Factors
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