Parkinson’s Risk and Carbon Monoxide: What a New Study Found

Non-smokers with higher exhaled carbon monoxide (CO) levels had a lower risk of Parkinson’s disease, a prospective study of more than 500,000 people in China showed.

Among people who never smoked, exhaled CO levels of 3 ppm or greater were associated with an approximately 30% lower risk of Parkinson’s (HR 0.71, 95% CI 0.59-0.84) compared with exhaled levels under 3 ppm, reported Andri Iona, DPhil, of the Nuffield Department of Population Health at the University of Oxford in England, and co-authors.

Regular smoking also was tied to a reduced risk of Parkinson’s disease (HR 0.70, 95% CI 0.62-0.79) but unlike CO measurements, was significantly associated with higher risks of lung cancer, ischemic heart disease, stroke, and all-cause mortality, the researchers wrote in JAMA Neurology.

“For the first time, this study provides robust evidence in humans supporting a potentially protective role for CO in Parkinson’s,” co-author Clara Bueno Lopez, MSc, also of Oxford, told MedPage Today.

Epidemiology research has repeatedly documented lower Parkinson’s risks among people who smoke, a finding highlighted in a study that followed 30,000 British doctors for 65 years. Nicotine was long thought to be fueling this link.

In recent years, researchers have investigated other tobacco constituents and smoking by-products. Of these, CO has emerged as a promising candidate, noted Sirwan Darweesh, MD, PhD, of Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues in an accompanying editorial.

“Carbon monoxide is formed during the burning process of cigarette smoking, as well as via incomplete combustion of carbon-containing fuels, such as gasoline,” Darweesh and colleagues explained. “Exposure to CO in the context of smoking or air pollution has been associated with multiple harmful effects on health, and individuals who smoke have markedly higher levels of carboxyhemoglobin in their blood,” they noted.

Conversely, CO is an essential signaling molecule that provides protection against oxidative damage and supports immune response and cell proliferation, survival, and death, the editorialists pointed out. “Preclinical studies and animal experiments have shown neuroprotective effects of small concentrations of CO, raising the hypothesis that CO may underlie the apparent neuroprotective effects of smoking in Parkinson’s disease.”

Studies also have investigated associations between air pollution — another leading source of environmental CO — and Parkinson’s, but these exposures are “inevitably confounded by the effects of other gases, particles, and chemicals with well-known adverse health consequences,” Iona and colleagues observed.

In the present study, the researchers assessed data from 512,701 adults in the China Kadoorie Biobank recruited between 2004 and 2008. Mean age was 52 years and 58.9% were women. Smoking status was self-reported and exhaled CO was measured at baseline.

Overall, 74.5% of men and 3.3% of women had ever smoked regularly. Mean exhaled CO levels were higher among those who regularly smoked (11.1 ppm) compared with those who never smoked (3.5 ppm), those who occasionally smoked (3.8 ppm), and those who formerly smoked regularly (3.7 ppm).

The median follow-up period was 12.1 years; in that time, 1,131 people with Parkinson’s disease and 2,949 with other neurodegenerative diseases were identified. Findings were adjusted for sociodemographic characteristics, lifestyle factors, and confounding variables like solid fuel use and passive smoking exposure.

In non-smokers, higher exhaled CO levels showed a broad dose-dependent inverse relationship with Parkinson’s risk, decreasing from HR 1.00 (95% CI 0.85-1.18) for levels under 2.0 ppm to HR 0.65 (95% CI 0.45-0.92) for levels of 11.5 ppm or more. Passive smoke exposure among never-smokers showed no clear relationship with Parkinson’s risk.

The study had several limitations, Iona and colleagues acknowledged. Participants were relatively young at baseline, and a single measurement of exhaled CO may not fully capture long-term CO exposure, they said. The possibility that nicotine or other tobacco components contributed to the association between smoking and Parkinson’s could not be excluded.

An ongoing phase IIa trial is investigating the effects of a low-dose oral CO liquid drug product in people with Parkinson’s disease, the researchers noted.