Scientists who examined data from more than half a million patients may have shed some light on the peculiar association between smoking and a lower risk of developing Parkinson’s disease.
Published in JAMA Neurology, the findings suggest it’s not the nicotine that’s the culprit, but rather, the exposure to carbon monoxide that may contribute to this link.
Medical News Today. reports that the WHO estimates that the prevalence of Parkinson’s has doubled in the past 25 years.
The disease causes damage to nerve cells in an area of the brain called the substantia nigra, resulting in symptoms like tremors and co-ordination problems. Some people with Parkinson’s go on to develop dementia over time.
Experts are unsure what causes Parkinson’s at present, but believe that genetic changes or environmental exposures may play a role.
Smoking cigarettes does not actually improve Parkinson’s
Previous population studies have noticed a lower risk of Parkinson’s disease among people who smoke.
While studies in rodent models led researchers to suggest that nicotine might have some kind of protective effect, a recent randomised clinical trial found that nicotine therapy provided no benefit to people with Parkinson’s. In fact, the trial suggested the nicotine may have even made their symptoms worse.
Other studies in cells and animals have suggested that carbon monoxide, another by-product of smoking, might also play a protective role.
As a result, an international team of researchers set out to see how carbon monoxide exposure might relate to the risk of Parkinson’s disease.
The researchers examined data from 512 701 participants in the China Kadoorie Biobank, a cohort coming from 10 different urban and rural areas within China. The participants had a mean average age of 52 at the beginning of the study.
Participants provided information about their smoking history along with other aspects of their lifestyle and medical history via questionnaires. Clinicians also measured the amount of carbon monoxide they exhaled.
The researchers examined the health outcomes of the participants over a follow-up period of 12 years. During this time, they noted a total of 1 131 people developing Parkinson’s disease and 2 949 developing other forms of neurodegenerative disease.
They then looked to see if there were any patterns between these health outcomes, smoking histories, and measurements of exhaled carbon monoxide taken at the beginning of the study period.
Higher exhaled carbon monoxide linked to lower Parkinson’s risk
Exhaled carbon monoxide levels were much higher in regular smokers than those who never smoked, occasionally smoked, or previously smoked regularly.
The researchers found that regular smoking was associated with a lower risk of Parkinson’s disease, aligning with what previous population studies had found.
In those who had never smoked, however, higher exhaled carbon monoxide levels were also associated with a lower risk of Parkinson’s disease. This seemed to be dose-dependent, with the higher levels conveying a lower risk.
Higher carbon monoxide levels were also not associated with the risk of smoking-related diseases such as lung cancer in people who had not smoked, nor were they associated with the risk of other neurodegenerative diseases.
“This study demonstrates the power of longitudinal patient data,” said study author associate professor Andrea Bugarcic, PhD, from the National Centre for Naturopathic Medicine at Southern Cross University, Australia.
“Combining what patients say about their lives, such as smoking and environment, with measurements we can make as scientists, such as exhaled carbon monoxide, the study links higher exhaled carbon monoxide to a lower risk of Parkinson’s disease only, not other causes of dementia,” she added.
New clue in the mystery
The researchers believe this study is another step toward refuting the idea that tobacco smoking specifically could help protect against Parkinson’s.
“While increased exhaled carbon monoxide is linked to smoking, the current study also points out that risk levels for non-smoking and smoking patients are the same,” explained Bugarcic.
“Collectively, the study not only points out a possible mechanism for the previously observed protective effects of smoking on Parkinson’s disease risk, but it also reminds us that carbon monoxide release is a larger environmental consideration,” she said.
In a Science Media Centre debrief, Senior Research Fellow in Parkinson’s epidemiology at the University of Otago in New Zealand, Toni Pitcher, PhD, who was not involved with the study, said:
“This is the first large-scale demonstration that Parkinson’s is also less common in individuals with higher levels of exhaled carbon monoxide in the absence of a smoking history. Carbon monoxide has anti-inflammatory effects, and in the brain helps to counteract cell stress. There is the potential that individuals with higher internal levels of carbon monoxide are more able to fight off inflammatory processes and better maintain brain health.”
Limitations to be aware of
While these findings are of great interest, there are some key aspects to the study that need consideration.
One was that the participants only provided carbon monoxide measurements and smoking histories at the very beginning of the study. Their circumstances may have changed over the 12-year follow-up period.
The researchers also had no data on Parkinson’s disease from primary care settings or other institutions, relying solely on death and disease registries and the health insurance system. This means they did not have access to the full picture of what happened with their participants.
Finally, with a mean average age of 52, the cohort the researchers followed was relatively young for a Parkinson’s disease study, as most people develop the disease after 60. The follow-up period was short, too, further reducing the number of cases the researchers would see.
These limitations mean that it is harder to generalise the results to a wider population, and suggest that more research is needed to confirm these findings.
Salvador Ventura, PhD, a professor of biochemistry and molecular biology at the Autonomous University of Barcelona in Spain, who was not involved in the study, said: “The fact that something is associated with a lower incidence of the disease says nothing about whether administering it would slow its progression in someone who has already been diagnosed. These are two distinct questions, and this research addresses only the first.
“Before discussing clinical applications, the observation would need to be replicated in other populations and safety and efficacy demonstrated in controlled trials.
Findings do not suggest people should take up smoking
“These findings do not justify taking up smoking or delaying giving up smoking; the study itself finds, as might be expected, higher rates of lung cancer, cardiovascular disease, and mortality among smokers,” added Ventura. “Nor do they justify deliberately exposing oneself to a gas that causes severe poisoning.”
The study authors note that trials are currently under way to test a liquid drug form of low-dose carbon monoxide in people with Parkinson’s.
Aside from this, they hope that this study will encourage others to dig deeper into the origins of the disease.
“Despite the controversial outcomes and limitations of this study, my perspective is that researchers across the methodological spectrum should take on the challenge set out by this study – understand why and how exhaling more carbon monoxide links specifically to lower Parkinson’s risk,” said Bugarcic.
“This is where studies like this matter. They give a voice to patients that then mobilises all that science has to offer, from understanding why to ensuring a grounded approach to therapeutic development.”
Study details
Smoking, Exhaled Carbon Monoxide, and Risk of Parkinson Disease
Clara Bueno Lopez, Andri Iona, Iain Turnbull et al.
Published in JAMA Neurology on 8 September 2026
Key Points
Question Could carbon monoxide (CO) explain the association between smoking and lower risk of Parkinson disease (PD)?
Findings In this cohort study of 512 701 Chinese adults, regular smoking was associated with a lower risk of PD. Among individuals who never smoked, higher exhaled CO levels were associated with lower PD risk but not with risk of other smoking-related diseases.
Meaning These findings suggest that the inverse association between smoking and PD may not be attributable to tobacco smoking itself and provide evidence that CO exposure may contribute to this association.
Abstract
Importance
Smoking has been associated with lower risks of Parkinson disease (PD) in epidemiological studies, but the underlying mechanisms remain poorly elucidated.
Objective
To investigate the association of exhaled carbon monoxide (CO) with risk of PD.
Design, Setting, and Participants
This nationwide prospective cohort study leveraged data from the China Kadoorie Biobank across 10 geographically diverse areas in China. A total of 512 724 adults aged 30 to 79 years were recruited between June 2004 and July 2008. Prospective analyses were restricted to first events occurring between ages 40 and 94 years and before January 1, 2019. Data were analyzed from May 2025 to March 2026.
Exposure
Self-reported smoking status and measured exhaled CO.
Main Outcomes and Measures
During approximately 12 years’ follow-up, 1131 individuals with PD and 2949 with other neurodegenerative diseases were recorded through linkage to national death and disease registries and the health insurance system. Cox regression was used to estimate adjusted hazard ratios (HRs) for associations of smoking and, among individuals who never smoked, exhaled CO levels with PD, other neurodegenerative diseases, and several known smoking-related diseases. Covariates included sociodemographic characteristics, lifestyle factors, and other confounders (ie, solid fuel use and passive exposure to smoking).
Results
Among the 512 701 participants included in the main analyses, the mean (SD) age was 52 (11) years and 302 041 (58.9%) were female. Overall, 156 650 male individuals (74.5%) and 9944 female individuals (3.3%) ever smoked regularly, with mean exhaled CO levels higher among those who regularly smoked (11.1 ppm) than those who never smoked (3.5 ppm), those who occasionally smoked (3.8 ppm), and those who formerly smoked regularly (3.7 ppm). Regular smoking was significantly associated with elevated risks of lung cancer, ischemic heart disease, stroke, and all-cause mortality but with lower risk of PD (adjusted HR, 0.70; 95% CI, 0.62-0.79). In individuals who never smoked, higher exhaled CO levels were associated with lower HRs of PD (n = 675) in a broadly dose-dependent manner (exhaled CO <2.0 ppm: 1.00 [95% CI, 0.85-1.18]; 2.0 to <3.0: 0.85 [95% CI, 0.73-0.99]; 3.0 to <5.0: 0.62 [95% CI, 0.53-0.73]; 5.0 to <11.5: 0.68 [95% CI, 0.56-0.83]; ≥11.5: 0.65 [95% CI, 0.45-0.92]; P for trend < .001) but were not associated with risks of smoking-related diseases or other neurodegenerative diseases. The associations with PD were more pronounced in female individuals who never smoked. Similar exhaled CO-PD associations were found in those who regularly smoked.
Conclusion and Relevance
Among individuals who never smoked, higher exhaled CO levels were associated with lower PD risk. These findings demonstrate a potentially protective role of CO in PD etiology, which help explain the association between smoking and PD observed in this and other epidemiological studies and support ongoing clinical trials of CO in the treatment of PD.
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