Abstract
Background Tobacco smokers have reduced Parkinson's disease (PD) risk. Some patients with PD experience constipation long before they develop mobility problems, and constipation is a frequent complaint of people who try to stop smoking. Recently, the gut microbiome has been implicated in PD. Methods In the present study, we analyzed the relationship between smoking and constipation in subjects with PD and controls. We wished to determine whether the effects of smoking and constipation were independent or whether they might be interrelated. To evaluate the relationship, we used a cohort of subjects from the UK Biobank (UKB). Results In 501,174 subjects, the decreased risk of Parkinson's disease with increased smoking was significant (p < 0.001, two-tailed Fisher's exact test). The increased risk of constipation in subjects with PD was significant (p = 0.001, two-tailed Fisher's exact test). Logistic regression was performed; sex, age, constipation, and smoking were the independent variables, and PD present or absent was the dependent variable. The PD odds ratio (OR) for males was 1.790 (95% confidence interval (CI): 1.629-1.966) times that for females, indicating that PD is more common in men. The risk of PD increased by 1.140 (95% CI: 1.131-1.149) with every year of age. Constipation increased the risk of PD by 4.043 (95% CI: 1.901-8.599). Smoking diminished PD risk by 0.772 (95% CI: 0.690-0.863). Drinking coffee was associated with a reduced risk of PD (OR: 0.815 (95% CI: 0.730-0.909). Drinking tea reduced PD risk by 0.979 (95% CI: 0.962-0.997) for each cup per day. The effects of sex, age, constipation, smoking, drinking coffee, and drinking tea were independent and significant. Conclusion Our analysis suggests that the favorable effect of smoking on PD is independent of the detrimental effect of constipation. Smoking reduces PD risk because it not only stimulates the bowel to empty and prevents constipation but also alters the gut microbiome. Another factor, perhaps the tobacco component diterpenoids, may be responsible for the PD risk-reducing effect.</p>