Carbon Monoxide not nicotine Emerges as a Potential Parkinson’s Protective Factor: JAMA

The findings challenge the long-standing assumption that nicotine is responsible for the inverse association between smoking and Parkinson’s disease, raising the possibility that CO may contribute to the apparent neuroprotective effect associated with smoking. Higher CO exposure was associated with lower Parkinson’s risk even among nonsmokers, suggesting that the relationship deserves further investigation before any causal or therapeutic conclusions are drawn.

In order to assess the relationship between the level of carbon monoxide in exhalation and the onset of neurodegenerative diseases, the authors reviewed data on patients from the China Kadoorie Biobank from 10 different regions in China. In total, 512,724 individuals from 30 to 79 years old were included in the research between June 2004 and July 2008. In prospective analysis, follow-ups were limited to first instances of diseases occurring between 40 and 94 years of age before January 1, 2019, with an average 12-year period of observation.

Self-reporting on smoking was collected along with the quantification of exhaled carbon monoxide in parts per million (ppm). The primary outcome included identification of 1,131 cases of Parkinson disease and 2,949 cases of other neurodegenerative diseases using national death, disease, and health insurance registries. HRs were computed using Cox proportional hazards regression models adjusted for sociodemographic variables, solid fuel usage, and secondhand smoking exposure. Data analysis was conducted from May 2025 to March 2026.

Key findings:

• Analysis of 512,701 participants (mean [SD] age, 52 [11] years; 302,041 females [58.9%]) revealed clear quantitative associations between smoking status, exhaled CO, and disease incidence.
• Regular smoking was reported by 74.5% of male participants (156,650/210,660) and 3.3% of female participants (9,944/302,041), with mean exhaled CO levels measuring 11.1 ppm in regular smokers versus 3.5 ppm in never-smokers, 3.8 ppm in occasional smokers, and 3.7 ppm in former smokers.
• Regular smoking was associated with higher risks of lung cancer, ischemic heart disease, stroke, and overall mortality, but demonstrated a significantly lower risk of Parkinson disease (adjusted HR, 0.70; 95% CI, 0.62–0.79).
• Among 675 never-smokers who developed PD, higher exhaled CO levels demonstrated a dose-dependent reduction in disease risk compared to baseline (<2.0 ppm [HR, 1.00; 95% CI, 0.85–1.18]): 2.0 to <3.0 ppm (HR, 0.85; 95% CI, 0.73–0.99), 3.0 to <5.0 ppm (HR, 0.62; 95% CI, 0.53–0.73), 5.0 to <11.5 ppm (HR, 0.68; 95% CI, 0.56–0.83), and ≥11.5 ppm (HR, 0.65; 95% CI, 0.45–0.92; P for trend < .001).
• The inverse association between exhaled CO and Parkinson disease was most pronounced in female never-smokers, while no associations were found between exhaled CO and other neurodegenerative conditions or smoking-related vascular diseases in non-smokers.

In summary, the results reveal that increased exhaled CO is linked to a decreased risk of developing Parkinson disease in individuals who do not smoke cigarettes. The findings from this study prove that carbon monoxide is indeed capable of neuroprotection in Parkinson’s disease, providing a plausible biological mechanism for the epidemiological findings observed throughout time. These findings also support the ongoing efforts towards disease modifying therapies utilizing gases.

Reference:

Bueno Lopez C, Iona A, Turnbull I, et al. Smoking, Exhaled Carbon Monoxide, and Risk of Parkinson Disease. JAMA Neurol. Published online September 08, 2026. doi:10.1001/jamaneurol.2026.3037