Manipulating how much carbon dioxide a person breathes can crank up the brain’s ‘sewage system‘, researchers have found.
The proof-of-concept study, led by neuroscientists at the University of New Mexico (UNM) and The Mind Research Network in the US, offers a tantalizing possibility for a crucial clearance system that was only identified in humans in the last decade.
The findings suggest that intermittently increasing CO2 levels in the blood could help flush toxic waste products out of the brain – maybe even preventing neurological diseases associated with these toxins, like Parkinson’s or Alzheimer’s.
In recent experiments with healthy participants and people with Parkinson’s disease, researchers found that delivering rhythmic pulses of CO2-rich air for short periods improved the flow of their brain’s waste-clearance system.
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Scientists aren’t yet sure why that happens, but fluctuating CO2 levels can cause blood vessels to dilate and constrict. This movement could be pushing along the nearby circulation of cerebrospinal fluid – the clear liquid behind the glymphatic system that bathes our brain and spinal cord.
Typically, as a person sleeps, hidden waves of cerebrospinal fluid gradually flush waste material from their brain. But sleep issues are commonly seen in patients with Parkinson’s, possibly leading to a buildup of misfolded proteins.
Cerebral blood flow also seems less adjustable in cases of Parkinson’s, and the brain typically contains greater concentrations of misfolded proteins with potentially toxic effects.
As such, some researchers have hypothesized that the brain’s sewage system underlies the neurological disease.
Now, scientists want to figure out how to manipulate the glymphatic system to keep the brain fighting fit. Carbon dioxide could be a nifty way to do just that.
“We brainstormed how we could boost this response,” says neuropsychologist Sephira Ryman at UNM. “That is when we realized that we could reproduce, in the awake state, the glymphatic clearing response usually linked to deep sleep using intermittent CO2.”
In experiments, 63 older adults, 30 of whom had Parkinson’s, underwent MRI-BOLD brain imaging while breathing in cycles of brief CO₂ elevation for about 35 seconds, followed by normal air.
This intervention, known as intermittent hypercapnia, temporarily increases blood CO₂ levels. In both healthy participants and those with Parkinson’s, it altered cerebrospinal fluid flow.
In another experiment, involving 10 participants, 5 of whom had Parkinson’s, participants underwent three 10-minute sessions of intermittent hypercapnia. The levels of CO₂ in their blood were then measured approximately 45, 90, and 150 minutes later.
Both healthy participants and those with Parkinson’s showed increased cerebrospinal flow and glymphatic clearance. Waste products from the brain also increased in the blood, suggesting improved clearance.
One participant in the study showed evidence of amyloid-beta proteins in their blood, which is a biomarker of Alzheimer’s disease. After intermittent hypercapnia sessions, their plasma levels for these toxins rose robustly.
“Intermittent hypercapnia may be able to clear peptides and proteins implicated in Alzheimer’s, highlighting its potential as a disease-modifying therapy for Alzheimer’s patients,” the authors speculate.
Whether these changes are lasting or have a significant impact on disease pathology is unknown.
While toxins in the brain are associated with Alzheimer’s and Parkinson’s, it is unclear if they are active players in disease progression or merely byproducts.
Ryman and her colleagues are now investigating whether practices that focus on abdominal breathing, such as yoga, tai chi, and qigong, can also impact carbon dioxide levels and brain clearance in a similar way.
The study was published in NPJ Parkinson’s.
