Smokers Have Lower Parkinson’s Risk. Scientists May Know Why - Newsweek

In recent years, research has indicated that rates of Parkinson's disease are lower among cigarette smokers and tobacco users than the general population. Now, a new study could have uncovered one reason why that might be the case.

Several large studies have found a consistent inverse relationship between cigarette smoking and the risk of developing Parkinson’s disease—meaning that the more a person smokes, the less likely they are to develop Parkinson's disease.

One of these studies included a 65-year follow up of more than 30,000 British doctors which found that smokers had a 30 to 40 percent lower risk of developing Parkinson's compared to those who had never smoked. The study was published in 2020 in the journal Neurology.

Another study, published in 2002 in the journal Neurology, investigated Parkinson's disease risk among identical twins and noticed that those without Parkinson's disease tended to smoke more than those with the disease, leading the researchers to conclude smoking could even be protective against Parkinson's disease.

This month, a new study has suggested carbon monoxide could be one explanation behind the surprising association.

However, “the association does not mean smoking is good for the brain," Dr. Michael Okun, a professor of neurology at the University of Florida, told Newsweek.

Smoking is considered a major public health concern by the Centers for Disease Control and Prevention (CDC). The agency reports that over 16 million Americans live with a smoking-related disease and that smoking and secondhand smoke exposure cause over 480,000 deaths in the U.S. each year. It is known to cause cancer, heart disease, stroke, lung diseases, type 2 diabetes, as well as many other diseases.

Parkinson's disease is a disorder of the nervous system that affects movement and gets worse over time. Symptoms commonly include tremors and shaking, muscle tightening, slower movement, fewer facial expressions, and postural instability, as well as a host of other symptoms like pain, fatigue, speech changes, changes to mental health, digestive problems, sleep problems, dementia and many others.

An estimated 1.1 million people in the U.S. are living with Parkinson's disease, with forecasts predicting that number will rise to 1.2 million by 2030, according to the non-profit organization Parkinson's Foundation. It is the second-most common neurodegenerative disease after Alzheimer's disease in the U.S.

Experts from the University of Oxford, U.K., and from Tongxiang and Beijing, China, found that individuals who never smoked but had higher exhaled carbon monoxide levels were associated with lower Parkinson's disease risk. The findings were published in JAMA Neurology on September 8, and more than 500,000 participants were involved in the study.

This prompted the researchers to conclude that the association may not be with tobacco smoking itself, but with carbon monoxide instead.

Carbon monoxide is a poisonous, flammable gas that is colorless and odorless. It can make someone extremely unwell if they breathe it in. It can be produced by fires and appliances that burn gas, wood, oil or coal.

“We normally think of carbon monoxide as a poison, and at high levels it absolutely is, but our bodies also produce small amounts of it naturally as a signaling molecule," Okun said.

Different people will exhale different amounts of carbon monoxide depending on various factors such as if they are a smoker or are exposed to higher levels of carbon monoxide in the environment. Smokers tend to have higher levels of carbon monoxide in their breath, as the gas is found in cigarette smoke.

"At low concentrations it may influence oxidative stress, inflammation and cell survival, so the intriguing question is whether those pathways could somehow protect vulnerable dopamine-producing brain cells," he added.

Okun said that "the eye-opening finding" of the study was "a dose-related association in people who had never smoked: those with exhaled carbon monoxide levels of 3 ppm or higher had about a 30 percent lower risk of Parkinson’s."

"This does not prove carbon monoxide prevents Parkinson’s, but it gives us a specific biological clue to chase, and importantly, carbon monoxide-based approaches are already moving into clinical testing," he said.

Other experts say it comes down to the tobacco, given that smokeless tobacco use has also been associated with reduced risk of Parkinson's disease.

One study, published in the American Journal of Epidemiology in 2016, found that those who used Swedish moist snuff (a pouch of tobacco leaves that sit under the lip for nicotine to be absorbed through the oral mucosa, i.e. the lining of the mouth) also had a lower risk of Parkinson's disease, suggesting the association extended to smokeless tobacco.

Similar findings had been found by researchers in 2005, and in a study published in Wiley InterScience, they even found that the association between smokeless tobacco use and a reduced risk of Parkinson's disease was greater than that found among cigarette smokers.

Dr. Alberto Ascherio, a professor of medicine at Harvard Medical School who was involved in the 2005 study, told Newsweek he suspected "some component of tobacco leaves is neuroprotective." He said that this could include compounds that inhibit the monoamine oxidase (MAO) B enzyme produced by the human body.

The MAO-B breaks down several chemicals in the brain, including dopamine, meaning inhibitors of the enzyme allow more dopamine—a chemical messenger crucial for movement—to be available for the brain. This is notable as most symptoms of Parkinson's disease arise when nerve cells in the brain weaken, become damaged and die, impacting the part of the brain that produces dopamine.

This means that MAO-B inhibitors are believed to modestly improve many Parkinson's disease movement symptoms, according to the Parkinson's Foundation.

However, Ascherio added that "the bottom line is that we do not know which compounds are most relevant."

Other research points to the nicotine. Okun said “nicotine is one of the leading suspects because it acts on nicotinic acetylcholine receptors in brain circuits involving dopamine and may influence inflammation, mitochondrial function and the survival of dopamine-producing cells."

Acetylcholine is a neurotransmitter that plays a role in memory, attention and involuntary muscle movement, and animal-based studies have indicated that nicotine could protect against cell damage in dopamine neurons, according to the American Parkinson Disease Association.

The research behind the association between smoking and Parkinson's disease "strongly suggests that Parkinson's disease could be prevented if we identify the relevant mechanisms," Ascherio said.

However, that's not to say experts believe smoking could be a strategy to prevent the disease. More research needs to be done, particularly "systematic studies screening several components of tobacco for potential protective effects," Ascherio added.

Okun said that "the exciting message is not that people should smoke; it is that this unusual relationship may provide biological clues we can exploit.

"If we can identify exactly what appears protective and separate it from the enormous harms of tobacco, we may uncover new targets for preventing or slowing Parkinson’s," he said.