Carbon dioxide improves brain function
Oxygen is the most important nutrient for your brain. If you want to become smarter, make wiser decisions, improve your focus and concentration, and reduce anxiety and worry, then you need to effectively oxygenate your brain.
Although the brain and nervous system make up only about 2% of our body weight, they use a full 20% of the oxygen we consume. This means the brain is the organ that suffers the most when we have inefficient breathing habits.
Carbon dioxide (CO2) is the primary regulator of blood flow to the brain. Lower levels of CO2, which occurs in over-breathing, cause blood vessels to constrict, reducing cerebral blood flow. This is why hyperventilation is used during brain surgery to shrink the brain and create space for surgical instruments, as well as to minimize bleeding. While this may be useful in surgery, a smaller brain is hardly something any of us want in our daily lives.
The dangers of hyperventilation for brain function
However, the clinical practice of hyperventilation in brain surgery is not based on solid research as Zhang et al. (2019) >> discuss in their review (ref1).
"We use hyperventilation to decrease elevated intracranial pressure and relax a tense brain (i.e. to make it smaller and softer) because hypocapnia (low levels of CO2) leads to reduced cerebral blood flow (CBF) and cerebral blood volume. Interestingly, this common practice is not based on robust evidence. In contrast, a randomized controlled trial performed in patients with severe head injury suggested that prolonged hyperventilation may be deleterious.
One major concern with multi-hour and forced hyperventilation is hypocapnia-induced CBF reduction. Therefore, hyperventilation is a double-edged sword that brings both benefits and risks. As ventilation is an adjustable physiological variable, it is pertinent to understand how to best manage ventilation to avoid doing more harm than good. The present review aims to summarize the relevant physiology and outcome evidence related to hyperventilation in neurological patients."
CO2 contributes to better brain health
In their pioneering 1946 study, Kety and Schmidt >> (ref 2) demonstrated that cerebral blood flow is directly related to the CO2 pressure in the blood. They found that inhaling CO2 in concentrations of 5-7% significantly increases cerebral blood flow by an average of 75%. This increase in blood flow can have a number of positive effects on brain function.
When CO2 levels in the blood rise, it causes blood vessels to dilate (widen), a process known as vasodilation. This allows for greater blood flow to the brain, ensuring that it receives a more abundant supply of oxygen and nutrients. Enhanced cerebral blood flow can improve cognitive function, memory, focus, and mental clarity.
It also supports the brain in managing waste products and toxins more efficiently, potentially contributing to better overall brain health. Increased CO2 can also help reduce symptoms of anxiety and stress by promoting a balanced autonomic nervous system, as it stimulates the body's relaxation responses.
The oxygen paradox - less is more
In contrast, the study also found that inhaling oxygen in concentrations of 85-100% led to a 13% reduction in cerebral blood flow. The reduction in blood flow occurs because a higher concentration of oxygen in the blood can lead to vasoconstriction, where the blood vessels narrow. This restricts blood flow to the brain, despite the higher oxygen levels.
Although oxygen is crucial for brain function, excessive oxygen can paradoxically reduce its availability to the brain tissue by reducing the amount of blood flowing through it. Prolonged exposure to high concentrations of oxygen can also increase the risk of oxidative stress, which may contribute to cell damage and neurodegenerative diseases over time.
In a review by Cornet et al. (2013) >> (ref 3) the authors questions the safety of routine high-dose oxygen administration.
Thus, while adequate oxygen levels are essential for brain function, the study by Kety and Schmidt highlights that maintaining a balanced CO2 level is critical for optimal cerebral blood flow and brain health. Inhaling small amounts of extra CO2 may improve the delivery of oxygen to the brain, enhancing cognitive performance and mental well-being, whereas excessive oxygen can limit blood flow and potentially have negative long-term effects on the brain.
CO2 improves brain oxygenation
A more recent study from 2010 by Feng Xu et al. >> (ref 4) found a similar effect to that of Kety and Schmidt. In their study, inhaling 5% carbon dioxide led to a significant increase in cerebral blood flow by 54.5%.
A study from 2020 by Jan Stepanek et al. >> (ref 5) found that supplemental carbon dioxide improves oxygenation in individuals experiencing acute hypoxia (low levels of oxygen). Traditionally, oxygen is viewed as the primary determinant of tissue oxygenation, but this research highlights the importance of maintaining optimum levels of CO2. The authors explored whether the addition of CO2 to a low oxygen environment could enhance arterial oxygen levels, oxygen saturation, and brain oxygenation.
The study involved 20 healthy subjects who were exposed to different gas mixtures, including an 8% oxygen mixture and oxygen mixed with either 3% or 5% CO2. Subjects underwent 5-minute intervals of exposure to the different gas mixtures, with randomized orders to ensure unbiased results. Blood gases, oxygen saturation, and brain oxygenation were measured throughout the exposure period.
The findings indicated that the addition of CO2 improved oxygenation compared to pure hypoxia. Specifically, the arterial partial pressure of oxygen (PaO2) and oxygen saturation (SaO2) were higher in both the 3% and 5% CO2-enriched groups compared to the hypoxia-only group. Additionally, brain oxygen saturation (rSO2) increased significantly in the CO2-supplemented groups, particularly with the 5% CO2 mixture.
The study suggests that CO2 supplementation enhances oxygenation by improving the efficiency of oxygen delivery to tissues, particularly in hypoxic conditions. CO2 appears to reduce the negative effects of hypocapnia (low levels of CO2), such as impaired oxygen delivery and vasoconstriction, which commonly occur during hypoxia.
In conclusion, the results highlight the potential benefit of using supplemental CO2 to improve oxygenation in individuals exposed to hypoxic environments, such as those encountered at high altitudes or in aviation.
Scientific references
Title: Hyperventilation in neurological patients: from physiology to outcome evidence
Authors: Zhong Zhang et al.
Journal: Current Opinion Anaesthesiology
Link to full text: Access here >>
Abstract: Purpose of review Hyperventilation is commonly used in neurological patients to decrease elevated intracranial pressure (ICP) or relax a tense brain. However, the potentially deleterious effects of hyperventilation may limit its clinical application. The aim of this review is to summarize the physiological and outcome evidence related to hyperventilation in neurological patients. Recent findings Physiologically, hyperventilation may adversely decrease cerebral blood flow (CBF) and the match between the cerebral metabolic rate and CBF. In patients with severe traumatic brain injury (TBI), prolonged prophylactic hyperventilation with arterial carbon dioxide tension (PaCO2) less than 25 mmHg or during the first 24 h after injury is not recommended. Most patients (>90%) with an aneurysmal subarachnoid hemorrhage undergo hyperventilation (PaCO2 <35 mmHg); however, whether hyperventilation is associated with poor outcomes in this patient population is controversial. Hyperventilation is effective for brain relaxation during craniotomy; however, this practice is not based on robust outcome evidence. Summary Although hyperventilation is commonly applied in patients with TBI or intracranial hemorrhage or in those undergoing craniotomy, its effects on patient outcomes have not been proven by quality research. Hyperventilation should be used as a temporary measure when treating elevated ICP or to relax a tense brain. Outcome research is needed to better guide the clinical use of hyperventilation in neurological patients.
Title: The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men
Authors: Seymour S. Kety and Carl F. Schmidt
Journal: The Journal of Clinical Investigation
Link to full text: Access here >>
Abstract: A method for measuring quantitatively the volume of cerebral blood flow in man by inhalation of nitrous oxide found its first application in a study of the cerebral circulatory effects of low CO2 tension achieved by hyperventilation; of high CO2 tension, and of high and low 02 tensions obtained by inhalation of appropriate gas mixtures. Only the first part of this study, the effects of active and passive hyperventilation, has been published in detail. The purpose of the present paper is to present the remainder of these findings and to derive from them, together with those of the hyperventilation experiments, evidence bearing on the intrinsic control of the human cerebral circulation as revealed by quantitative measurements.
Title: The potential harm of oxygen therapy in medical emergencies
Authors: Alexander D Cornet et al.
Journal: Critical Care
Link to full text: Access here >>
Abstract: In medical emergencies, supplemental oxygen is often administrated routinely. Most paramedics and physicians believe that high concentrations of oxygen are life-saving [1]. Over the last century, however, a plethora of studies point to possible detrimental effects of hyperoxia induced by supplemental oxygen in a variety of medical emergencies. This viewpoint provides a historical overview and questions the safety of routine high-dose oxygen administration and is based on pathophysiology and (pre)clinical findings in various medical emergencies.
Title: The influence of carbon dioxide on brain activity and metabolism in conscious humans
Authors: Feng Xu et al.
Journal: Journal of Cerebral Blood Flow & Metabolism (2011)
Link to full text: Access here >>
Abstract: A better understanding of carbon dioxide (CO2) effect on brain activity may have a profound impact on clinical studies using CO2 manipulation to assess cerebrovascular reserve and on the use of hypercapnia as a means to calibrate functional magnetic resonance imaging (fMRI) signal. This study investigates how an increase in blood CO2, via inhalation of 5% CO2, may alter brain activity in humans. Dynamic measurement of brain metabolism revealed that mild hypercapnia resulted in a suppression of cerebral metabolic rate of oxygen (CMRO2) by 13.4%±2.3% (N= 14) and, furthermore, the CMRO2 change was proportional to the subject’s end-tidal CO2 (Et-CO2) change.
When using functional connectivity MRI (fcMRI) to assess the changes in resting-state neural activity, it was found that hypercapnia resulted in a reduction in all fcMRI indices assessed including cluster volume, cross-correlation coefficient, and amplitude of the fcMRI signal in the default-mode network (DMN). The extent of the reduction was more pronounced than similar indices obtained in visual evoked fMRI, suggesting a selective suppression effect on resting-state neural activity. Scalp electroencephalogram (EEG) studies comparing hypercapnia with normocapnia conditions showed a relative increase in low frequency power in the EEG spectra, suggesting that the brain is entering a low arousal state on CO2 inhalation.
Title: Supplemental CO2 improves oxygen saturation, oxygen tension, and cerebral oxygenation in acutely hypoxic healthy subjects
Authors: Jan Stepanek et al.
Journal: Physiological Reports (2020)
Link to full text: Access here >>
Abstract: Oxygen is viewed in medicine as the sole determinant of tissue oxygenation, though carbon dioxide homeostasis is equally important and clinically often ignored. The aims of this study were as follows: (a) to examine the effects of different acute hypoxic conditions on partial pressure of arterial oxygen (PaO2), arterial oxygen saturation of hemoglobin (SaO2), and regional cerebral saturation of hemoglobin (rSO2); and (b) to evaluate supplemental CO2 as a tool to improve oxygenation in acutely hypoxic individuals. We hypothesized that exposure to gas mixtures with added CO2 would improve oxygenation in hypoxic human subjects.
Twenty healthy subjects were exposed to 5-min intervals of two gas mixtures: hypoxic gas mixture containing 8% oxygen, and a CO2-enriched mixture containing 8% oxygen plus either 3% or 5% CO2. Ten subjects received the 3% CO2-enriched mixture, and the remaining 10 subjects received the 5% CO2-enriched mixture. The order of exposure was randomized. Blood gases, pulse oximetry, end-tidal CO2, and cerebral oximetry were measured. Compared to the purely hypoxic gas group, PaO2 was increased in the 3% and 5% CO2-enriched groups by 14.9 and 9.5 mmHg, respectively.
Compared to pure hypoxia, SaO2 was increased in the 3% and 5% CO2-enriched groups by 16.8% and 12.9%, respectively. Both CO2-enriched gas groups had significantly higher end exposure rSO2 and recovered to baseline rSO2 within 1 min, compared to the pure hypoxic gas group, which returned to baseline in 5 min. These results suggest that in acutely hypoxic subjects, CO2 supplementation improves blood oxygen saturation and oxygen tension as well as cerebral oxygenation measures.
