A study of more than half a million adults has found that higher levels of exhaled carbon monoxide were associated with a lower risk of Parkinson’s disease. The findings, published in JAMA Neurology, uncover a possible new explanation for the consistently lower rates of Parkinson’s among smokers that have long puzzled scientists.
Parkinson’s is the second most common neurodegenerative condition worldwide. It affects more than 10 million adults globally and its prevalence is on the rise, partly due to an ageing population. Although smoking has long been associated with a lower risk of the disease, previous research has not established whether nicotine or any other component of tobacco smoke is behind the association.
Focus on carbon monoxide
This study, led by researchers from Oxford Population Health and collaborators at Peking University, focused on whether carbon monoxide (CO), a well-known by-product of smoking, might explain why smokers appear to develop Parkinson’s less often than non-smokers.
Usually thought of as a harmful gas, high levels of CO are dangerous, but the body naturally produces small amounts of CO that help prevent damage to the cells, reduce inflammation and support immune response. Previous laboratory and animal studies have suggested that low doses of CO might have a protective effect on brain health, but evidence in humans was lacking. No previous study has measured exhaled CO levels in a large number of individuals and traced their development of Parkinson’s over time.
The researchers drew on detailed information about the smoking habits of half a million adults in the China Kadoorie Biobank (CKB), as well as measurements of the amount of CO in their exhaled breath (a marker of recent CO exposure, including from smoking). They then used death registries and health insurance records to track which participants developed Parkinson’s and other diseases over 12 years of follow up.
Potential new avenue for treatment
The researchers found that regular smokers had both significantly higher levels of exhaled CO and about a 30% lower risk of developing Parkinson’s than non-smokers. However, the association between levels of exhaled CO and Parkinson’s risk was also evident among participants who had never smoked, even after the researchers accounted for environmental sources of CO such as burning coal or wood indoors and passive smoking.
The findings challenge the idea that smoking itself has a protective effect for Parkinson’s. Instead, they point to the protective role of carbon monoxide and suggest that it may offer a promising new area for the development of interventions.
David Dexter, Research Director at Parkinson’s UK, the main Parkinson’s support and research charity in the UK, said ‘For the first time, this study has provided robust evidence that carbon monoxide may be the neuroprotective factor in cigarette smoke. [It] demonstrated that people who have never smoked, but who naturally produce higher CO levels also have a lower risk of developing Parkinson's. This opens up an exciting possibility that low levels of CO could be a neuroprotective therapy for Parkinson's.’
More than two thirds of men in the study smoked tobacco regularly compared with only 2% to 3% of women participants. The relationship between higher levels of exhaled CO and lower risk of Parkinson’s was more pronounced among women who had never smoked than men. The researchers suggest this could reflect biological differences in how men and women produce CO naturally.
Clara Bueno Lopez, a DPhil candidate at Oxford Population Health and first author of the study, said ‘This study provides an exciting clue about the biological pathways that may be involved in Parkinson’s which will serve as a springboard to further investigate how CO-related biology may affect Parkinson’s risk.’
While smoking was associated with higher levels of exhaled CO and higher risks of lung cancer, heart disease and stroke, among never smokers, higher CO levels were not associated with risks of these smoking-related diseases, nor with most other neurodegenerative diseases. This suggests that the effect of CO is specific to Parkinson’s.
Professor Zhengming Chen, Principal Investigator for CKB in the UK and a senior author of the study, said ‘Our study has provided the first human evidence supporting the scientific rationale for administering low doses of CO to patients with Parkinson’s disease, which is in the early stage of clinical trials. If successful, this new treatment could contribute to substantially reducing the global burden of Parkinson’s.’
The researchers acknowledged that although they adjusted for major sources of CO exposure, they could not fully account for all environmental exposures or reliably distinguish between external exposure and internal production of CO. They also noted that the results need to be replicated in other populations before they can be considered generalisable.