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Long-term carbon dioxide toxicity and climate change: a critical
unapprehended risk for human health.
P.N. Bierwirth, PhD
Emeritus Faculty
Australian National University
First draft - Web Posted 25 February, 2014
Current Version – 2 January, 2025
ResearchGate DOI:10.13140/RG.2.2.16787.48168
Abstract
As atmospheric levels of carbon dioxide continue to escalate far beyond the range that was present
in the evolutionary period of humans, the safe level for long-term breathing is not clear given that
CO2 is known to be toxic for short-duration exposures at high concentrations. There is now
substantial evidence that permanent exposure, to the current elevated and future predicted CO2
levels, will have significant effects on humans. Carbon dioxide overload, already detected in human
population blood chemistry, is identified by ongoing changes to bicarbonate, calcium and
phosphorous levels in the body and the trends, towards unhealthy levels, predict global breathing
toxicity by around mid-century. In common indoor environments, mental impairment, altered
brainwaves and health symptoms have been observed at levels of CO2 above 600 ppm for relatively
short-term exposures. Although humans and animals are generally able to deal with breathing
elevated levels of CO2 in the short-term due to compensation mechanisms in the body, long-term
perpetual increased exposure, with no change in respiration rate, causes build-up of CO2 and a range
of potentially severe physiological consequences. Protein malfunctions in cells due to elevated CO2
and associated low pH has the potential to cause threats to life including cancer, neurological
disorders, lung disease, diabetes, etc. In particular excess CO2 causes the overexpression of carbonic
anhydrase, the enzyme that catalyses CO2 in the body, and this produces calcification in the kidneys,
arteries and tissues, along with other diseases. Although there is very low awareness of this risk, it is
likely that human physical and mental health will be progressively impacted in the near-future with
the severity dependant on CO2 emissions.
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1. Introduction
An axiom of modern science, as quoted from TS Huxley, is “do not pretend that conclusions are
certain which are not demonstrated or demonstrable”. Carbon dioxide is often assumed to be a
harmless gas. Even to refer to CO2 as a toxic gas is a surprise to many safety professionals
(Henderson 2006). In indoor environments CO2 concentration is often elevated relative to ambient
outdoor levels due to the fact that the exhaled breath from humans contains high CO2 (about 4%)
and ventilation may not be adequate to prevent the resulting increase in CO2. Despite the possible
adverse effects on health where many people occupy buildings or vehicles, there is very little
awareness of this issue in the general community.
The average ambient concentration of CO2 (in fresh air) has been rapidly increasing and is recently
426 ppm (Scripps Institution of Oceanography 2025; Schmidt 2020) (Figure 1). This increase is due to
humanity’s activities, largely resulting from the burning of fossil fuels (Eggleton 2013).
Figure 1. The atmospheric carbon dioxide concentrations (in ppm) over the last 2000 years, based on
measurements of air trapped in Antarctic ice, shown in blue-grey diamonds, and the modern Cape Grim,
Tasmania direct air measurements, shown in orange. (From Schmidt 2020).
Very early primate ancestors of humans were evolving around 23 million years ago. Although not
precise, it appears that throughout most, if not all of the ensuing period of human evolution, levels
of CO2 in the ambient atmosphere remained relatively stable at below or close to 300 parts per
million (ppm). These values were derived from a combination of studies of relict features including
air trapped in ice cores (Schmidt 2020), the composition of fossil plankton (Zachos et al. 2001) and
Carbon-13 (13C) content in fossil plant material (Cui et al. 2020).
The rapid increase in CO2 levels since about the year 1820 is an existential problem for many species
of animals, including humans, for a number of reasons. The most well publicised issue is that of
climate change causing an increase in atmospheric energy gradients, high temperatures and extreme
weather events. To many people, climate change itself may not appear to be catastrophic – for
example it might be possible to escape the effects of even a 5 degree C increase this century by
moving to a cooler and safer geographic location. However, there would be no escape if there were
a direct, toxic impact of breathing increased atmospheric CO2. CO2 levels in the earth’s atmosphere
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are already outside the range breathed by humans throughout their evolution and these new levels
are relatively evenly distributed around the globe (see Figure 2). As well, in earlier pre-primate
epochs, the effect of elevated atmospheric CO2 causing physiological stress, has been postulated to
be a cause of mass extinction events (Knoll et al. 1996).
Figure 2. Level 3 atmospheric CO2 derived from the NASA Orbiting Carbon Observatory 2 averaged over 16
days on 1–16 April 2020 at 0.5 x 0.625pixel resolution (around 50 km) (NASA 2022)
We know that breathing CO2 is toxic to humans when levels are high with numerous deaths reported
based on occupational exposure (Scott et al. 2009). Although the CO2 exposure limit for an 8-hour
period has been set at 5,000 ppm (0.5%) (OSHA 2012), this limit was decided in 1946 and based on
relatively short-term observations of fit and healthy submariners (Scott et al, 2009). The safe level
for lifetime exposure may be significantly lower than this and a number of researchers suggest there
could be toxicity effects at CO2 levels predicted in the near future with ongoing anthropogenic
emissions (Portner et al. 2004; Robertson 2006; Ezraty et al. 2011; Antic 2012; McNeil and Sasse
2016; Karnauskas et al. 2020). So, the question is: how long will it take, at present and future rates of
increase, to reach levels that will impact on human health (no matter where you live) over a
lifetime? To answer this question, the safe level of CO2, for continuous breathing in humans, needs
to be determined. The aim of this paper is to evaluate available data, and to examine the likely and
possible risks (for the near to medium-term future).
2. The role of carbon dioxide in breathing
Breathing is one part of physiological respiration and is required to sustain life (Raven et al.
2007). Aerobic organisms like birds, mammals, and reptiles, require oxygen to release energy by
cellular respiration, through the metabolism of molecules such as glucose. During aerobic
respiration, glucose is broken down by oxygen to release energy, while carbon dioxide and water are
the by-products of the reaction. Breathing delivers oxygen to where it is needed in the body and
removes carbon dioxide thereby exchanging oxygen and carbon dioxide between the body and the
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environment. Carbon dioxide (CO2) is mostly a waste product and needs to be removed from our
body. CO2 from respiring tissues enters the blood plasma and diffuses into the red cells, where it is
rapidly hydrated to H+ and bicarbonate (HCO3-) by the enzyme carbonic anhydrase (CA) (Arlot et al.
1985; Adeva-Andany et al. 2014). As such this enzyme allows metabolic activity (life) in animals by
enabling the processing of CO2 which returns to the plasma as bicarbonate, being the optimum form
of transport, and then travels to the lungs (Adeva-Andany et al. 2014). When the bicarbonate
reaches the lungs, CA in the alveoli catalyses the reverse reaction generating water and carbon
dioxide which is exhaled as a gas. CA thus allows a large pool of otherwise slowly reacting plasma
HCO3- to be utilized in CO2 excretion (Arlot et al. 1985).
There is an optimal range for the concentrations of CO2 in the air we breathe. Too little can mean
that breathing is too slow and not enough oxygen is brought into the body (Patton and Thibodeau
2009). Too much can cause acidity and compromise our ability to remove CO2 (from our bodies) as a
waste product. So, what are the effects of too much CO2 and what is the level that can cause health
problems (in humans)?
3. Known health effects from short term exposure to high levels of CO2
Breathing too much CO2 results in high levels of CO2 in the blood (hypercapnia) often associated with
a decrease in blood pH (increased acidity) that results in a condition known as acidosis. Hypercapnia
impairs lung alveolar function and lowers immunity (Shigemura et al. 2017).The decreases in blood
and tissue pH produce effects on the respiratory, cardiovascular, and central nervous systems (CNS)
(Eckenhoff and Longnecker 1995). Changes in pH act directly and indirectly on those systems
producing effects such as tremor, headache, hyperventilation, visual impairment, and CNS
impairment. In terms of worker safety, the US Occupational Safety and Health Administration has set
a permissible exposure limit (PEL) for CO2 of 5,000 parts per million (ppm) (or 0.5 %) over an 8-hour
work day (OSHA 2012). They report that exposure to levels of CO2 above this can cause problems
with concentration, an increased heart rate, breathing issues, headaches and dizziness.
Exposures to 1-5 % CO2 for short-term periods have been documented to produce symptoms on
humans and animals such as dyspnea (shortness of breath), modified breathing, acidosis, tremor,
intercostal pain, headaches, visual impairment, lung damage, increased blood pressure, bone
degradation, reduced fertility, alterations to urine and blood chemistry as well as erratic behaviour
(Halperin 2007; Rice 2004; Guais et al. 2011; Schaefer et al. 1963a; Yang et al. 1997). These levels of
CO2 also induce panic attacks, interrupt the processes of metabolic enzymes and disrupt normal cell
division processes (Colasanti et al. 2008; Guais et al. 2011; Abolhassani et al. 2009).
Health risks continue to escalate, with progressively higher CO2 concentrations causing more severe
reactions and faster responses. A value of 40,000 ppm is considered immediately dangerous to life
and health given that a 30-minute exposure to 50,000 ppm produces intoxication, and
concentrations around 70,000 ppm produce unconsciousness (NIOSH 1996). Additionally, acute
toxicity data show the lethal concentration for CO2 is 90,000 ppm (9%) for a 5-minute exposure.
There are indoor situations where exhaled human breath and restricted air flow can produce
extreme and dangerous levels of CO2. For example, infant deaths have been associated with levels of
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up to 8% (80,000 ppm) CO2 for an infant covered by blankets (Campbell et al. 1996).
4. Physiological compensation for elevated CO2
Given that CO2 and pH levels need to be maintained within tight limits to allow cellular processes to
function normally, the body has developed compensation mechanisms that regulate CO2 and acidity
in the blood, and these can change over time with persistent exposure. The lowering of blood pH
triggers various compensatory mechanisms, including pH buffering systems in the blood, increased
breathing to reduce excess CO2 in the bloodstream, storage of CO2 in bones, increased excretion of
acid by the kidneys to restore acid-base balance, and nervous system stimulation to counteract the
direct effects of pH changes on heart contractility and vasodilation (widening of the blood vessels)
(Burton 1978; Eckenhoff and Longnecker 1995). In respiratory acidosis, the bones provide an early
compensation mechanism by storing CO2 as bicarbonate and carbonate (Stumm 2023; Schaefer
1979) as well as chemically buffering blood pH - bicarbonate and a positive ion (Ca2+, K+, Na+) are
exchanged for H+. After a period of time, which could be up to 20 to 40 days (Holy et al. 2012;
Schaefer 1979), the bones become ineffective at compensation and the kidneys begin to retain
bicarbonate helping to normalise the pH of the blood as it passes through them. With continued
high levels of CO2 in the blood, metabolic acidosis occurs and the kidneys do not respond in
producing bicarbonate (Schaefer et al 1979a). The kidneys are involved in a wider array of
physiological compensation responses to CO2 induced pH imbalance (acidosis). The kidney tubule
recovers filtered bicarbonate or secretes bicarbonate into the urine to help maintain acid-base
balance in the blood and this again involves the CA enzyme (Adeva-Andany 2014).
5. Health effects at common indoor CO2 concentrations
5.1 Classrooms
There is a large volume of recent literature that has documented the occurrence and levels of CO2 in
classrooms across the world including kindergartens, day-care centres, primary schools, high schools
and universities (Bako-Biro et al 2011; Widory and Javoy 2003; Kukadia et al. 2005; Dijken et al.
2005; Branco et al. 2015; Heudorf et al. 2009; Santamouris et al. 2008; Ferreira and Cardoso 2014;
Gaihre et al. 2014; Jurado, et al. 2014; Lee and Chang 2000; Muscatiello et al 2015; Carreiro-Martins
et al. 2014). There is general agreement that the levels of CO2 in 20-50% of classrooms commonly
exceed 1,000 ppm and are often much higher, sometimes reaching levels as high as 6,000 ppm for
extended periods. A number of studies have identified CO2 associated symptoms and respiratory
diseases such as sneezing, rales, wheezing, rhinitis, and asthma (Carreiro-Martins et al. 2014;
Ferreira and Cardoso 2014). Other symptoms; i.e. cough, headache, and irritation of mucous
membranes, were also identified (Ferreira and Cardoso 2014). Lack of concentration was associated
with CO2 levels above 1,000 ppm. Gaihre et al. (2014) found that CO2 concentrations exceeding 1000
ppm is associated with reduced school attendance. Teachers also report neuro-physiologic
symptoms (i.e., headache, fatigue, difficulty concentrating) at CO2 levels greater than 1000 ppm
(Muscatiello et al. 2015).
5.2 Offices
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Offices have levels of CO2 similar to classrooms depending on the number or density of workers and
the types of ventilation systems (Lu et al. 2015; Tsai et al. 2012, Seppanen et al. 1999). These studies
have found strong evidence of the relationship between CO2 levels in offices and Sick Building
Syndrome (SBS) health effects such as headaches, dizziness, fatigue, respiratory tract symptoms, eye
symptoms, nasal and mucous membrane symptoms (Seppanen et al. 1999; Lu et al. 2015; Tsai et al.
2012; Vehviläinen et al. 2016; MacNaughton et al. 2016). Seppanen et al. (1999) conducted a review
of available literature and were careful to eliminate other confounding airborne building
contaminants. The reviewed studies included over 30,000 human subjects, and they concluded that
the risk of SBS symptoms decreased significantly with carbon dioxide concentrations below 800
ppm. Whether CO2 itself is responsible for the health symptoms is still a subject of debate since
historically it has been assumed, despite lack of direct evidence, that other airborne contaminants
are the cause (Zhang et al. 2017).
More recently a number of studies have demonstrated that CO2 has direct impacts on human
physiology at levels commonly found in indoor environments (Azuma et al. 2018). Symptoms such
as fatigue and drowsiness caused directly by CO2 have been demonstrated by the use of
electroencephalogram (EEG) techniques (Snow et al. 2018; Pang et al. 2020). In a study of office
workers, a 20% increase in blood CO2, to significantly above normal levels, was measured along with
sleepiness, headaches, heart rate variation and poor concentration in air that averaged 2,800 ppm
CO2 (Vehviläinen et al. 2016) while lowered heart rate and arousal level (fatigue) is clear at 4000
ppm (Xia et al. 2020). Increases in blood CO2 were associated with restricted lung function at levels
between 2,000 and 3,000 ppm CO2 (Shriram et al. 2019). Zheutlin et al. (2014) used biochemistry
data to determine an increasing trend in the average levels of CO2 in the blood for a national sample
of around 7,000 people from 1999 to 2012 (this is explored further in Section 9). Heart rate variation
at 2,700 ppm is confirmed by Snow et al. (2019) for 10-minute exposure. MacNaughton et al. (2016)
found that a 1,000 ppm increase in CO2 from background levels was associated with a 2.3 bpm
increase in heart rate after adjusting for potential confounders. Another older study (Goromosov
1968) reported harmful physiological effects on humans at only 1,000 ppm CO2 with changes in
respiration, circulation, and cerebral electrical activity. These physiological effects are being
observed at much lower levels of CO2 than previously anticipated (Azuma et al. 2018).
5.3 Vehicles
Although rarely studied for health effects, vehicles can often contain even higher levels of CO2
particularly where there are multiple passengers for relatively long journey times. CO2 levels can
build up to 5,000 ppm after less than an hour of driving with two people in a car with only internal
air (Gładyszewska-Fiedoruk 2011). With five people in a car with recirculated air levels of CO2 can
exceed 10,000 ppm (1%) after only 28 minutes, this being a level that is known to result in
respiratory acidosis (Constantin et al. 2016). Experiments have shown reduced driving performance
at levels as low as 1800 ppm CO2 after 18 minutes (Wang et al. 2022; Wang et al. 2024). Buses with
high numbers of passengers consistently reach average CO2 concentrations of > 2500 ppm (Chiu et al
2015). Airliners can contain levels of around 2,000 ppm for the duration of the flight (Gładyszewska-
Fiedoruk 2012). Measurements on an Italian submarine showed a steady increase to 5,000 ppm CO2
after 2 hours of being submerged (Ferrari et al. 2005). Extremely high CO2 concentrations (10,000-
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20,000 ppm) are commonly found inside motorcycle helmets in both stationary and moving
situations (Bruhwiler et al. 2005).
5.4 Cognitive impairment and anxiety in elevated CO2 environments
There is now a significant body of research studies involving the detrimental effect of CO2 on
learning and cognitive abilities in humans at common indoor concentrations (Du et al. 2020; Lee et
al. 2022). Testing of students has found that CO2 can negatively affect attention, memory,
concentration and learning ability impacting on academic performance (Bako-Biro et al. 2011; Coley
et al. 2007). Several recent university studies of cognitive effects of CO2 have been notable in their
strong research design (Satish et al. 2012; Allen et al. 2016; Allen et al. 2018; Scully et al. 2019) with
the testing environments injected with pure CO2 meaning that the analysis of CO2 effects was not
confounded by the presence of other substances. These studies showed that low level CO2 (between
950 ppm and 2,500 ppm CO2) affected the cognitive abilities of students, information professionals
and pilots in the indoor environment. Satish el al. (2012) tested only variations in CO2 over periods
of 2.5 hours of exposure. For seven of nine scales of decision-making performance (basic activity,
applied activity, task orientation, initiative, information usage, breadth of approach, and basic
strategy), performance was significantly impaired in a dose-response manner with higher CO2 levels.
For example, compared with mean raw scores at 600 ppm CO2, mean raw scores at 1,000 ppm CO2
were 11–23% lower, and at 2,500 ppm CO2 were 44–94% lower. As part of a larger study that
included volatile organic compounds (VOCs), Allen et al. (2016) found that, after CO2 was
independently modified (from a baseline of 480-600 ppm) for individual 8-hour exposures, cognitive
function scores were 15% lower at 950 ppm and 50% lower at 1,400 ppm. This study used similar
methodology to score cognitive function and the results largely repeated the findings of the earlier
work (Satish et al 2012). However, one difference was that, at 1,500 ppm CO2, even focussed activity
was found to have declined (Allen et al 2016). In a study of pilots’ performance, Allen et al. (2018)
found that negative impacts on cognitive function were observed between 700 ppm and 1500 ppm
CO2. Another study found similar negative effects on human cognitive abilities, in experiments
involving 140-minute sessions, as well as increased fatigue at levels of 3,000 ppm CO2 compared with
600 ppm (Kajtar and Herczeg 2012). This study also measured some physiological parameters with
heart rate analysis suggesting significantly increased mental effort at 3,000-4,000 ppm. Lu et al.
(2024) found that cognitive impairment, after 2 hours exposed to 2,500 ppm, was associated with
the activation of circulating neutrophils (white blood cells associated with inflammation), reduced
cellular metabolism and increased production of reactive oxygen species (ROS).
These studies are further supported by the finding of CO2-induced changes in human brainwaves,
measured by electroencephalography (EEG), that have known associations with mental impairment
(Lee et. al. 2022). EEG combined with cognitive tests provided evidence of brainwave changes in
frontal, parietal and occipital lobes that showed negative impacts, at levels as low as 1,000 ppm CO2,
on working memory, mental workload and visual concentration after only 15 minutes of exposure.
This is physiological evidence for the effect of CO2 on cognitive decline.
Cognitive and neurological effects are also observed in animal studies. Mice exposed from birth to
1,000 ppm CO2 for 38 days had decreased Insulin-like Growth Factor-1 (IGF-1) which resulted in
greater anxiety and reduced cognitive function (Kiray et al. 2014). Neurons were reduced in number
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and were malformed at this CO2 level for several areas of the brain, with the largest effect for those
areas associated with learning and memory. Mice exposed to only 890 ppm from preconception to 3
months of age showed increased levels of the stress hormone corticosterone in the blood and brain
(Wyrwoll et al. 2022). In humans, Yang et al. (2024) found increased levels of salivary cortisol,
combined with negative effects on emotional processing, after only 90 minutes exposure at 5,000
ppm CO2. Along with anxiety, chronic elevation of brain corticoids associates with cognitive
impairment and could harm the developing brain (Stolp 2022).
5.5 Sleep impacts
Sleep quality is reduced at 1,900 ppm CO2 when compared to 800 ppm in both subjective indices and
electroencephalogram (EEG) measurements of brain activity (Xu et al. 2020). At 1,900 ppm CO2,
slow-wave sleep (or deep restorative sleep) was significantly reduced. Strøm-Tejsen et al. (2016)
measured reduced sleep quality after night-time level of 2,500 ppm CO2, followed by reduced
cognitive performance the next day. When CO2 in arterial blood rises to a certain extent, it will
produce carbon dioxide narcosis respiratory inhibition, weakened respiration, and hypoxia of human
cells resulting in poor sleep quality (Xu et al. 2020).
Another example is people affected by sleep disordered breathing (SDB). Brillante et al (2012) found
that the development of nocturnal hypercapnia in normal indoor CO2 air concentration, quantitated
by a large difference in carbon dioxide in the blood between morning and evening, predicted
increased mortality in SDB patients. This is a result of the lack of efficacy of an individual’s
respiratory regulatory system in sleep for maintaining normal blood gas tensions (Brillante et al.
2012). As CO2 levels in the atmosphere increase into the future, the impacts on and number of
affected individuals will logically increase.
6. Health effects from long term exposure to elevated CO2 levels below 1%
Where indoor levels of CO2 are relatively high and affecting health, it is generally possible to obtain
relief by going outdoors. However, this may not be the case in a climate change future where
ambient CO2 is persistently high and effects of continuous long-term exposure must be considered.
There have been very few studies related to long-term exposure at lower CO2 levels, elevated above
ambient, perhaps for logistical reasons since it is difficult to arrange an experiment for relevantly
long timeframes. We are looking for information on the effect on humans of CO2 levels at 1,000
ppm or less – noting that this is the level that some feasible models predict could be reached in the
ambient atmosphere in less than 100 years (Smith and Woodward 2014). Given the lack of research
at these CO2 levels, it seems reasonable to examine the research available for medium-term studies
on levels of CO2 less than 10,000 ppm (1%). Table 1 provides a summary of health effects, found in
the published literature and discussed in this paper, resulting from breathing CO2 at levels at or
below 1%.
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Table1. Documented health effects from breathing CO2 at concentrations at or below 1%.
CO2 Level Health effect Exposure Source
10,000 ppm
(1%)
Kidney calcification, decreased bone formation and
increased bone resorption in guinea pigs
6 weeks Schaefer et al. 1979a
10,000 ppm
(1%)
Cognitive impairment, increased diastolic blood
pressure
75 min Tu et al. 2020
8500 ppm Increased lung dead space volume 20 days Rice 2004
7000-7500 Increased blood CO2 and bicarbonate, mild
respiratory acidosis in submarines
20 days Holy et al. 2012
7000 ppm
(0.7%)
35% increase in cerebral blood flow (implications for
cognitive effects seen in other studies)
23 days Sliwka et al. 1998
6180 ppm Respiratory acidosis (calculated) Immediate Stumm 2023
5000-6600
ppm
Headaches, lethargy, moodiness, mental slowness,
emotional irritation, sleep disruption
Short-term Chronin et al. 2012; Law et
al. 2010
5000 ppm Kidney calcification, bone degradation in guinea pigs 8 weeks Schaefer et al 1979b
5000 ppm Elevated blood CO2 levels in astronauts 4 months Hughson et al. 2016
5000 ppm Current allowable levels for continuous exposure in
submarines and spacecraft
Operational
continuous
Halperin et al. 2007; Chronin
et al 2012
5000 ppm Permissible exposure limit (PEL) for a work day 8 hours OSHA 2012
5000 ppm Vascular and neurological changes 15 minutes Bright et al. 2020
5000 ppm Elevated cortisol levels related to anxiety, reduced
cognitive emotional processing in humans
90 minutes Yang et al. 2024
4000 ppm Increase in heart rate, lowered arousal level/
increased fatigue and sleepiness
17 minutes Xia et al. 2020
3500 ppm Cognitive impairment, reduced human vigilance
(increased sleepiness)
4 hours Pang et al. 2020, Zhang et
al. 2020
3000 ppm Cognitive impairment, anxiety, neural damage,
oxidative stress in mice
38 days Kiray et al. 2014
3000 ppm Impaired visual attention, decision making and
executive ability
Short-term Cao et.al. 2022
3000 ppm Systemic inflammation and physiological stress in
rodents
9-13 days Beheshti et al. 2018
10
3000 ppm Onset of hypercapnic blood pH levels, abnormal
blood CO2 levels in humans (calculated)
Immediate Stumm 2023
2700 ppm Drowsiness measured by EEG 10 min Snow et al. 2018
2700 ppm Increase in heart rate 10 min Snow et al. 2019
2500 ppm Cognitive impairment, activation of circulating
neutrophils (white blood cells associated with
inflammation), reduced cellular metabolism
2 hours Lu et al. 2024
2000-4000
ppm
Unhealthy blood CO2 levels - 15% above normal
range, sleepiness, headaches, heart rate variations
4 hours Vehviläinen et al. 2016
2000-4000
ppm
Inflammation and vascular damage in mice 2 hours Thom et al.2017
2000-3000
ppm
Restrictive lung behaviour and elevated blood CO2 3 hours Shriram et al. 2019
2000 ppm Kidney effects in animals (likely calcification) -
incomplete study
Chronic
studies
Schaefer 1982
1900 ppm Reduced deep sleep and general sleep quality, EEG
brainwave alterations
8 hours Xu et al. 2020
1400-3000
ppm
Significant impairment of cognitive function
including fatigue
2.5 to 8
hours
Satish et al 2012; Allen et al
2016; Kajtar & Herczeg 2012
1200 ppm Reduced cognitive function 2.5 hours Scully et al. 2019
1000 ppm Harmful changes in respiration, circulation, and the
cerebral cortex
A short time Goromosov 1968
1000 ppm Oxidative stress and damage to DNA in bacteria
(implications for cancer diseases in humans)
3 hours Ezraty et al. 2011
1000 ppm Cognitive impairment, anxiety, neural damage,
oxidative stress in mice
38 days Kiray et al. 2014
1000 ppm Level associated with respiratory diseases,
headache, fatigue, difficulty concentrating in
classrooms
Short-term Carreiro-Martins et al. 2014;
Ferreira and Cardoso 2014;
Seppanen et al. 1999
1000 ppm EEG changes in brainwaves associated with mental
impairment
15 min Lee et. al. 2022
950-1400
ppm
Health symptoms (respiratory, skin, eyes, headaches,
cognitive, dizziness, sensory), increase in heart rate
30 min MacNaughton et al. 2016
950-1000
ppm
Moderate impairment of cognitive function 2.5 to 8
hours
Satish et al 2012; Allen et al
2016; Allen et al 2018
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890 ppm Impaired lung function in new-born female mice,
slightly lower blood pH. Reduced growth,
hyperactivity, increased stress hormone, anxiety
associated with cognitive impairment
3 months Larcombe et al. 2021;
Wyrwoll et al. 2022
800 ppm Level associated with Sick Building Syndrome -
headaches, dizziness, fatigue, respiratory tract, eye,
nasal and mucous membrane symptoms
Short-term Seppanen et al. 1999; Lu et
al. 2015; Tsai et al. 2012
700-900 ppm Gastropods: reduced growth, reduced food
absorption and oxygen uptake, reproductive failure
6-10 months Navarro et al. 2022;
Mardones et al. 2022
700 ppm Modification of behaviour, stress hormone and
respiratory muscle structure in rats
15 days,
6hrs/day
Martrette et al. 2017
400-1000
ppm (?)
Significant alterations in human blood chemistry
from combined indoor/outdoor exposure
20 years Zheutlin et al. 2014;
Bierwirth 2025
420 ppm Current average outdoor air concentration – no clear
effect, possible increase in disease and anxiety
Lifetime NOAA Global Monitoring
Laboratory
280-300 ppm Pre-industrial outdoor level from about 1820 to at
least 25 million years ago - no effect
Lifetime Beerling and Royer 2011;
Zachos 2001.
6.1 Spacecraft and Submarines
Studies of human exposures to significantly elevated levels of CO2 from 5000 to 15,000 ppm for
short periods of time on spacecraft and submarines do exist from which long-term effects of
exposure to lower CO2 concentrations can be extrapolated (Stumm 2023). NASA sought to
determine the safe levels for long-term exposure to CO2, but initially found little research focused on
levels below 10,000 ppm CO2; as such, there was no definitive study available to guide standards
(Cronyn et al. 2012). They set the maximum allowable CO2 concentration limits, for long term (1,000
days) habitation of submarines and spacecraft, at 5000 ppm (James and Macatangay 2009).
International Space Station (ISS) crew members have repeatedly reported symptoms associated with
acute CO2 exposure at levels of 5,000 to 6,600 ppm CO2 (see Table 1). The most commonly reported
symptom was headache; other symptoms reported included lethargy, mental slowness, emotional
irritation, and sleep disruption (Law et al. 2010). Measurements of end-tidal PCO2 show a significant
increase of CO2 in human blood during tests conducted on astronauts after 4 months continually
exposed to about 5,000 ppm (Hughson et al. 2016). For space flight, Cronyn et al. (2012) identified
three potential areas of operational impact of elevated CO2: renal calculi (kidney calcification) and
bone reabsorption; cerebral blood flow; and mission performance.
In submarines where humans were exposed to 0.7 – 1% CO2 (7,000 to 10,000 ppm) for 50-60 days,
significant changes in lung volume, dead space and vital capacity were observed (Schaefer 1979).
Acid-base measurements showed cyclic changes in blood pH and bicarbonate explained by CO2
uptake and release in bones (Schaefer 1979). Another study of 20 healthy submariners submerged
continuously for 2 months, at levels of 7,000 to 7,500 ppm CO2, showed significant changes in blood
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and bone blood chemistry after 20 days (Holy et al 2012). Blood levels of CO2 increased by 22%,
bicarbonate increased by 16% and pH reduced from 7.41 to 7.37 producing mild respiratory acidosis.
Bone marker chemistry showed significant bone degradation due to the role of the bones in
compensation for mild acidosis. These effects on the bones can take many months to recover from
once the sailors are back in “fresh” air. This study also shows kidney involvement in acid-base
compensation starting between 40 and 58 days; almost at the limit of the study (Holy et al 2012).
Halperin (2007) reports that exposures to CO2 levels as low as 7,000 ppm can lower blood pH by up
to 0.05 units and induce renal (kidney) compensation in healthy subjects. Given that kidney
compensation cannot occur indefinitely, there is some doubt about whether submariners could
sustain these operational levels of CO2 if they spent years exposed to it.
7. Protein malfunctions caused by elevated CO2 in the body
Carbon dioxide is a fundamental physiological gas known to profoundly influence the behaviour and
health of millions of species within the plant and animal kingdoms (Phelan et al 2021). It is known
that CO2 plays a major role in sensing and signalling on a cellular level although the physiological
response is complex and not well understood. Research has found that increases in CO2 resulting in
reduced pH alters mitochondrial metabolism reducing oxygen consumption and releasing
intracellular calcium stores (Phelan et al 2021).
The endoplasmic reticulum (ER) is a large dynamic structure within cells that serves many roles
including protein synthesis and calcium storage. Elevated CO2 levels cause protein malfunctions by
altering ER folding machinery. These malfunctions are associated with ER stress triggering
maladaptive responses and effecting a range of diseases e.g., chronic lung disease and reduced
immunity, tissue and organ malfunction (Kryvenko and Vadasz 2021; Duarte et al. 2020)
7.1 Elevated CO2 causes carbonic anhydrase enzyme disfunction and related diseases
Carbonic anhydrase (CA) enzymes are widely expressed in the nervous system and tissues
throughout the body where they play important physiological roles (Aspatwar et al 2021). The
reaction that CA catalyses, the reversible hydration of CO2 to bicarbonate and a proton, lies at the
heart of a wide range of vital physiological processes (Chegwidden and Carter 2021; Aspatwar et al
2021). Abnormal regulation of carbonic anhydrase-related proteins causes a range of diseases
conditions including cancer, Alzheimer’s, cardiovascular disease, diabetes, glaucoma, epilepsy,
stroke, bipolar disorder etc. The use of CA isozyme inhibitor drugs for treating these diseases is now
a major science (Celebioglu et al 2021; Lemon et al 2021). However, CA inhibitors can cause CO2
retention and result in cellular malfunctions (Phelan et al 2021). The progressive increase in CA
disfunction due to increasing atmospheric CO2 will result in worsening outcomes for the diseases
mentioned above.
7.2 CO2 induced deposits of calcium in the body
Carbonic anhydrase (CA) enzymes participate in metabolic reactions that convert CO2 and result in
the precipitation of calcium carbonate (Adeva-Andany et al. 2015; Kim et al. 2012; Tan et al. 2018).
CA is implicated in calcification of human tissues, including bone and soft-tissue calcification (Adeva-
Andany et al. 2015). The enzyme may be also involved in bile and kidney stone formation and
13
carcinoma-associated micro-calcifications. The molecular mechanisms regulating the development
of calcification in human tissues and arteries are similar to those that regulate physiological
mineralization in bone tissue, being poorly understood (Adeva-Andany et al. 2015). Carbon dioxide
conversion by the CA enzyme provides bicarbonate and hydrogen ions that fuel the uptake of
ionized calcium which is then deposited in the body tissues as calcium carbonate. With elevated CO2
there is increased body retention of calcium (Carr et al 2024) and release of calcium in cells from the
ER (Kryvenko and Vadasz 2021).
Kidney calcification is known to occur with longer term exposure to elevated CO2 levels (Rice 2004;
Schaefer et al., 1979a). A similar causal link between the activity of CA enzyme, which is mainly
responsible for the reversible breakdown of CO2, and calcium deposits has also been established for
arteries (Adeva-Andany et al. 2014). It has been demonstrated that CA protein levels are significantly
correlated with atherosclerosis development in mice (Garcia-Llorca 2024). As part of a US Navy
experimental program in the 1960’s and 1970’s investigating impacts of long-term CO2 exposure,
Schaefer et al (1979b) found that, in a study of guinea pigs in an enclosed environment breathing
5,000 ppm CO2 for 8 weeks, the kidneys started to calcify along with bone degradation (see Table 1).
Schaefer (1982) also indicated that preliminary experiments had found kidney calcification effects in
animal studies for CO2 concentration as low as 2,000 ppm. Although these studies did not identify a
mechanism, they established the casual link between CO2 and kidney calcification. More recent
studies have found that tissue calcification is promoted where CA is overexpressed due to increased
CO2 in the body (Song et al 2021; Phelan et al 2021). Increased CA activity is also linked to cancer
where the enzyme helps create a hostile, low pH environment suitable for cancers to flourish in
(Hulikova et al. 2014; Logozzi et al. 2019; Di Fiore et al. 2020).
8. Other important physiological CO2 effects on health
8.1 Impaired growth and muscle development
Female mice exposed to 890 ppm CO2 for 3 months from pre-pregnancy showed reduced growth
(Wyrwoll et al 2022) and a range of lung and respiratory impairments including lower lung
compliance (Larcombe et al. 2021). Prolonged exposure to CO2 on behaviour, hormone secretion
and respiratory muscles in young female rats exposed at 700 ppm CO2 during 6 hours per day for 15
days (Martrette et al. 2017) (see Table 1). CO2 exposure, though not continuous, produced
significant disturbances in behaviour and was accompanied by increased plasma levels of
corticosterone, suggesting that prolonged exposure to CO2 was stressful producing anxiety.
Increased corticosterone associated with hyperactivity in mice was also found from long-term
exposure to 890 ppm CO2 (Wyrwoll et al 2022).
8.2 Increased cerebral blood flow
Cerebral blood flow (CBF) effects from breathing CO2 are a significant issue for humans. As CO2 in the
blood increases, CBF increases to effectively wash out CO2 from brain tissue and helps regulate
central pH (Ainslie and Duffin, 2009). In a 23-day experiment on humans, Sliwka et al. (1998) found
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that cerebral blood flow is increased in the presence of 7,000 ppm (0.7%) CO2 by as much as 35%
(see Table 1) and that CBF remained elevated until the end of the evaluation period, 2 weeks after
the exposure. The impacts of persistent increase in CBF are unclear although there may be a risk of
raised intracranial pressure (ICP) which can compress and damage delicate brain tissue. There is also
evidence that the CBF response to increased CO2 is impaired in Alzheimer’s patients and that this is
linked to the decline in cognitive abilities (Glodzik et al 2013) which will worsen as CO2 in the
atmosphere increases.
8.3 Oxidative Stress
In humans, carbon dioxide is also known to play a role in oxidative stress caused by reactive oxygen
species (ROS) (Ezraty et al. 2011; Kiray et al. 2014). ROS are produced by aerobic metabolism of
molecular oxygen and play a major role in various clinical conditions including malignant diseases,
diabetes, atherosclerosis, chronic inflammation and neurological disorders such as Parkinson’s and
Alzheimer’s diseases (Waris and Ahsan 2006). In particular, oxidative damage to cellular DNA can
lead to mutations resulting in the initiation and progression of cancer. Ezraty et al (2011)
demonstrated that current atmospheric CO2 levels play a role in oxidative stress and that increasing
CO2 levels between 400 and 1,000 ppm exacerbated oxidative stress and damage to DNA in bacteria.
Kiray et al. (2014) concluded that 1,000 ppm CO2 is associated with oxidative stress and oxidative
damage to brain tissue in mice together with low Insulin-like Growth Factor 1 (IGF-1) levels
impacting the growth of bones and tissues. Increased CO2 promotes the production of ROS leading
to greater incidence of cancers and other diseases including the promotion of virus activity (Waris
and Ahsan 2006). Ezraty et et al (2011) concluded that with higher atmospheric CO2 concentrations,
this exacerbation might be of great ecological concern with important implications for life on Earth.
8.4 Inflammation
Inflammation is a serious illness that is known to be caused by elevated CO2 exposure in humans and
animals (Thom et al. 2018; Beheshti et al. 2018; Zappulla 2008; Jacobson et al. 2019). CO2 increases
result in higher levels of Interleukin, a protein involved in regulating immune responses, which
causes inflammation and vascular damage in mice (Thom et al. 2017). Rodents exposed to 3,000
ppm CO2 in spacecraft experiments for 9-13 days showed evidence of inflammation and
physiological stress (Beheshti et al. 2018). Physiological compensation adaptations to maintaining pH
homeostasis eventually fail turning into inflammation and metabolic syndrome (Zappulla 2008). In
humans exposed to 2500 ppm for 2 hours, the activation of circulating neutrophils (white blood cells
associated with inflammation) was observed (Lu et al. 2024) along with loss of mitochondrial
respiratory capacity and increased production of ROS.
8.5 Stroke
Another study has shown that increased CO2 in the blood of patients can increase the severity of
Subarachnoid haemorrhage; a life-threatening form of stroke, due to the dilatation of arterial
cerebral vessels (Reiff et al 2020).
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9. Evidence from biochemical data
Long-term exposure to environmentally relevant levels of CO2 leads to increases in the levels of CO2
in human blood (Zheutlin et al. 2014; Hughson et al. 2016; Vehviläinen et al. 2016). The Zheutlin et
al. (2014) study used data from the U.S. National Health and Nutrition Examination Survey (NHANES)
from 1999 to 2012 looking at the average blood bicarbonate levels, being a measure of how much
CO2 is in the body, in about 7,000 people. This trend analysis has been extended here, summarised
from Bierwirth (2025), to include more recent data (see Figure 3) and the trend of increasing
bicarbonate levels has clearly continued. As the levels of CO2 in our blood will continue to increase as
atmospheric levels rise (see Figure 3), this represents a permanent and growing change in human
blood chemistry and physiology which is a huge risk to population health.
Figure 3. Comparison between temporal trend in population serum bicarbonate (circles) in U.S. adults from the
NHANES biochemistry database and measured atmospheric concentration CO2 (boxes) at Mauna Loa, Hawaii
(Scripps Institution of Oceanography).
The upper limit for healthy ranges of bicarbonate varies between 29 and 32 mmol/l although it has
been recommended to be 30 mmol/l (Kraut et al. 2018). The estimation of the safe or healthy level
requires further scrutiny particularly given that the high bicarbonate condition would be perpetual in
the future as atmospheric levels continue to increase. Assuming a linear relationship, the calculated
trendline in Figure 3 predicts that the limits of 29-32 mmol/l bicarbonate will be reached in the years
2063-2100. This means that beyond the year 2063 humans may have unhealthy blood bicarbonate
levels that will progressively worsen.
Further analysis of the NHANES dataset also revealed declining trends in both serum calcium (Ca)
and Phosphorus (P). Figure 4 shows the NHANES population data for average serum calcium and
phosphorus over a 20-year period ending in the year 2020. Calcium shows a statistically significant
(R2 = 0.74) trend while phosphorus also declines (R2 = 0.72).
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Figure 4. The temporal trend in population serum (a) calcium and (b) phosphorus in U.S. adults from the
NHANES biochemistry database between the years 2000 and 2020.
The lower limit for healthy ranges of calcium and phosphorous in human blood are listed as 2.1 and
0.81 mmol/L respectively (IAPAC 2025). Assuming a linear relationship, the calculated trendline in
Figure 4 predicts that the standard health limits for calcium and phosphorous (IAPAC 2025) would be
reached in the years 2099 and 2085 respectively although this is an estimation given the variability in
the data and that physiological processes are not well understood. As with bicarbonate, this
threshold could possibly be reached earlier. Beyond this limit humans will have unhealthy blood
calcium and phosphorous levels that will progressively worsen.
10. Discussion
Evidence reviewed in this paper suggests that there is a direct risk to the human species posed by
the long-term breathing of ambient atmospheric CO2 concentrations that are rapidly increasing. The
level of ambient atmospheric CO2 that provides unacceptable risk and the exact effect on physiology
are not clearly determined. If this level is reached in the near future, the global human society
should be concerned. Some climate models suggest that atmospheric CO2 levels could be as high as
1,000 ppm in this century. This is completely unknown for the whole primate evolutionary lineage
which has only experienced levels well below and recently up to the current level of around 426
ppm.
The detection of trends in human population blood chemistry is particularly disturbing since
bicarbonate, calcium and phosphorous levels are on a trajectory toward unhealthy levels (Bierwirth
2025). Previous research suggests that calcium and phosphorous are involved in chemical exchange
between the blood and the bones as part of early physiological compensation for elevated CO2 in the
body (Schaefer et al. 1963b; Schaefer et al. 1979; Holy et al. 2012). In the situation of CO2 overload,
the bones provide compensation by storing CO2 as bicarbonate and calcium phosphate carbonates
(Stumm 2023; Schaefer 1979) and thus reducing Ca and P levels in the blood (Bierwirth 2025). The
trends observed above in bicarbonate, calcium and phosphorous are indicating that human
physiology is being progressively and consistently altered. These component changes are consistent
with effects that might occur with the breathing of increasing levels of atmospheric CO2 in combined
indoor and outdoor environments. Increasing levels of bicarbonate in the blood indicates that CO2 is
17
building up in the human body. Under normal circumstances, CO2 is excreted from the body via
breathing and the respiration rate determined by chemoreceptors measuring levels of pH in the
blood (Eckenhoff and Longnecker 1995). This is likely a system that has been tuned to the usually
stable level of atmospheric CO2 at around 280 ppm throughout our evolution. However, the CO2
concentration in air is now rising rapidly (above 420 ppm), blood pH is likely to remain neutral due to
compensation by the kidneys in excreting acid, hence respiration rates remain the same and the
excess CO2 is retained in the body. The human system attempts to store the overloading CO2,
starting with in the bones. As the levels in the atmosphere continue to increase at some stage the
bones will reach capacity for CO2 storage and the calcification will occur in the kidneys and other
tissues such as arteries although it can’t be certain that this is not already happening to some
degree.
As discussed previously and shown in Figure 4, it is likely that Ca and P are decreasing in human
blood as they are being taken up by the process of storing bicarbonate and carbon dioxide in the
bones. This means that these elements are becoming less available for important functions in the
body. Calcium is essential to maintaining total body health, being essential in muscle contraction,
oocyte activation, building strong bones and teeth, blood clotting, nerve impulse, transmission,
regulating heart beat and fluid balance within cells (Pravina et al. 2013). The requirements are
greatest during the period of growth such as childhood. Low blood calcium (hypocalcemia), produces
symptoms including muscle cramps, lethargy, numbness and tingling in the fingers, and problems
with heart rhythm. Systemic Ca2+ is regarded as a hormone itself, as it can modulate the function of
the parathyroid gland, the thyroid gland, the kidney, and other organs and cells via the calcium-
sensing receptor (Proudfoot 2019). Phosphorus plays a critical role in metabolic processes within the
cell including energy metabolism and protein phosphorylation which is a key mechanism that
controls many cellular functions, including metabolism, growth, and muscle contraction (Portale
2013). Phosphorus also plays a role in nucleotide metabolism which is used to build DNA, RNA, and
for cellular energy, being a vital pathway involved in cell growth and division. It also influences
phospholipid metabolism that forms a vital part of cell growth and function (Portale 2013). As such,
continued reductions in blood Ca and P, due to CO2 overload, may cause significant health problems
There are few long-term physiological studies of human exposure to 1,000 -2,000 ppm CO2
or less.
However, there are short-term exposure studies describing disease symptoms and physiological
effects as well as reduced cognitive ability in humans at levels around 800 - 950 ppm CO2; these are
CO2 levels that are typically present in offices, classrooms and apartments (Gall et al. 2016). It
appears that many of the physiological effects of CO2 are due to increased stress and stimulation of
the autonomic nervous system resulting in elevated blood pressure, respiration, and heart rate
(MacNaughton et al. 2016; Fisk et al. 2019) and this is also associated with a decline in cognitive
ability due to increased Cerebral Blood Flow (CBF) with resulting effects on central nervous system
and brain cortical function (Satish et al 2012; Glodzik et al 2013; Bright et al. 2020). The effect on
cortical function is supported by a study of infants that showed an inverse relationship between blood
CO2 and electrocortical activity (Wikstrom et al. 2011).
Some authors have attempted to calculate the impact of rising atmospheric CO2 on blood CO2 and pH
levels. Stumm (2023) used projected future CO2 levels converted to the inspired and arterial partial
pressures (PCO2) together with the Henderson-Hasselbalch equation to obtain pH values. Levels of
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atmospheric CO2 that cause hypercapnia (high CO2) and acidosis (low pH) under short-term
exposures were calculated to be around 0.3% (3,000 ppm) and 0.6% (6,000 ppm) respectively. In an
editorial (Malte and Wang 2023) responding to recent peer-reviewed studies that detail direct
threats to human and animal health from rising atmospheric CO2, it is suggested that this rise in CO2
poses no risk for acid–base balance in humans. Their graphed results suggest that acidosis would
occur at around 8,000 ppm but it’s not clear how realistic this is and given the importance, it
requires further verification and peer review. Surprisingly, Malte and Wang (2023) advocate a
change in human breathing to accommodate future rises in atmospheric CO2 and also that ongoing
renal (kidney) compensation may be required although neither of these strategies are practical in
the long-term. These authors also overlook the potential impacts of increasing blood CO2
(hypercapnia) on the human system. Robertson (2006) assessed that the Henderson-Hasselbalch
equation may not be valid for realistic calculations of pH due to the presence of various ions and
salts in the blood. They determined that blood pH would be reduced to dangerous levels, if there
were no physiological compensation, at atmospheric CO2 levels of about 426 ppm (Robertson 2006;
Robertson 2001) implying that ongoing compensation, causing disease, would occur at this level that
has recently been reached (Scripps 2025). The actual thresholds of inspired CO2 that cause pH and
hypercapnic health effects remain unclear as atmospheric levels continue to rise unabated.
Increased CO2 in the blood also affects protein behaviour causing inflammation (Thom et al. 2018),
calcification (Schaefer 1982) of body tissue and a range of demonstrated pH-related protein
malfunctions (Duarte et al. 2020), all with potentially serious outcomes. Reduced pH due to CO2 has
been found to alter mitochondrial metabolism affecting oxygen consumption (Phelan et al. 2021).
Elevated CO2 causing protein malfunctions can trigger diseases including cancer, neurological
disorders, lung disease, reduced immunity and organ failure (Duarte et al 2020; Kryvenko and
Vadász 2021). Perhaps the most significant protein malfunction is the overexpression of the CA
enzyme due to increased CO2 in the body. This widely distributed enzyme plays a vital role allowing
for respiration and the processing of CO2 in all animals and plants. New research is showing that CA
malfunction due to elevated CO2 causes a range of health problems including cancer and diabetes
(Aspatwar et al 2021). Perhaps the most serious of these is tissue calcification which can result in
kidney and cardiovascular failure. Furthermore, the incidence and prevalence of human kidney
calcification (i.e. stones) is increasing globally (Romero et al. 2010; Turney et al. 2011;
Kittanamongkolchai et al. 2018) and in submariners (Holy et al. 2012). It is possible that higher
indoor CO2 levels (boosted by increasing ambient CO2) is the contributing cause.
Perhaps the most informative study about CA behaviour is that of Rodriguez-Navarro et al. (2019).
CA catalyses the formation of the reactive precursors (i.e., HCO3− and CO32− ions) required for
mineralization and accelerates the precipitation of metastable amorphous calcium carbonates. Ca+
and CO32− ions promote the partial unfolding and oligomerization of CA, resulting in fibril- and sheet-
like supramolecular assemblies that template nanostructured calcium carbonate crystallization. The
enzyme then loses its CO2 hydration catalytic activity and elicits a mechanism for arresting calcium
carbonate mineralization. Such a negative feedback mechanism would first help jump-start CaCO3
mineralization and subsequently contribute to the arrest of this process, offering a simple
mechanism for organisms to control CaCO3 biomineralization. Otherwise, if CA endlessly remained
catalytically active once secreted, it would be difficult for an organism to stop the biomineralization
process (Rodriguez-Navarro et al 2019). Despite the significant reduction observed, some enzyme
19
activity remains even after precipitation of calcite. In a future where increasing atmospheric CO2 will
potentially result in excess CO2 in the body, as appears to be already happening (see Section 9, this
paper), the resulting excess CA will be converted into calcium carbonate factories creating an
ongoing calcification problem.
What level of permanent CO2 will cause significant calcification and other protein malfunction
effects? Ambient conditions appear to be already close to CO2 levels that cause these dangerous
health problems, given the NHANES biochemical evidence that CO2 overload is already occurring and
particularly when considering the additive effect of increased ambient levels on indoor CO2
concentrations. In the final paper of the US Navy CO2 research program in the 1960’s and 1970’s,
Schaefer (1982) indicated that this issue had “become the concern of the Department of Energy and
other US government agencies” although it appears to have been largely forgotten since. If allowed
to persist, problems such as kidney and artery calcification could lead to cardiovascular failure. In the
extreme case, lifespans could become shorter than the time required to reach reproductive age.
Calcification of kidneys and arteries can be fatal through renal and cardiovascular failure. This could
threaten the viability of human and animal species without interventions such as the creation of
artificial living environments.
Extended exposures to elevations in CO2 can be detrimental to cerebral health (Carr et al. 2024).
Cognitive decline due to CO2, evidenced by definitive studies (Satish et al. 2012; Allen et al. 2016;
Allen et al 2018) of indoor environments, would logically produce lower intelligence in humans
which is now being measured around the world (Bratsberg and Rogeberg 2018). It is feasible that
rising outdoor CO2 levels are the cause of the measured decline in human intelligence (Bierwirth
2018). It is possible that such effects occur without recognition in daily life (Satish et al. 2012). The
modest reductions in multiple aspects of decision making, seen as low as 950 ppm (Allen et al. 2016),
may not be critical to individuals, but at a societal level or for employers an exposure that reduces
performance even slightly could be economically significant. The observation of brainwave changes
at elevated levels of CO2 (around 1,000 ppm and greater) (Lee et al. 2022; Zhang et al. 2024) is
significant being physiological evidence of cognitive impairment. This is concerning since it suggests
our brains may be increasingly affected by rising environmental CO2 levels and prolonged exposure
may exacerbate the adverse effects (Fan et al 2023). Although the exact mechanism for CO2 effects
on cognitive ability is not clear, Stumm (2023) postulates that CO2-induced increase of extracellular
calcium ions may restrict the movement of sodium ions thereby reducing neuron excitability.
Highton et al. (2024) determined that Increased CO2 reduces mitochondrial oxygen metabolism in
the brain which would impact cognitive function. Lu et al. (2024) observed cognitive decline
associated with inflammation and reduced cellular metabolism. These effects have been associated
with vascular leakage in the brain (Thom et al. 2017) which is related to cognitive decline (Li et al.
2021). Another explanation may be that CO2 signalling activates the autonomic system causing stress
affecting cognitive performance (Azuma et al. 2017). Brain activity holds paramount importance for
human functioning, acting as the central regulator that coordinates various bodily functions and
cognitive processes (Zhang et al. 2024) and given that CO2 exposure at moderate levels appears to
prove detrimental to brain activity, it poses a serious threat to both human health and productivity.
Indeed, modelling indicates that even under the current raised atmospheric CO2 levels there may be
disruptions in neural activity, together with altered neurotransmitter profiles, indicating potential
20
cognitive consequences (Alqarni and Almarwaey, 2024). As atmospheric CO2 levels continue to rise,
the cognitive impact on humans will amplify.
The impacts on students including sickness, reduced attendance and reduced learning abilities
should also be a concern for society. Moreover, the relatively high levels of CO2 in vehicles
associated with declining concentration and fatigue has serious implications for the safety of drivers
and their passengers. This is an issue that does not appear to have been raised in research on driver
fatigue illustrating the general lack of awareness about CO2 effects.
Carbon dioxide is known to cause anxiety and panic attacks in humans (Battaglia 2017). CO2
sensitivity is one of the most basic and general alarm/avoidance systems within the realm of biology.
Once it permeates the blood–brain barrier, CO2 causes temporary acidification of extracellular brain
fluids resulting in enhanced arousal, and subsequent anxiety (Battaglia 2017). While panic and
anxiety attacks generally occur at high levels of CO2, the distribution of liability to CO2 sensitivity is
continuous and normally distributed in humans and animals. This means that there are potentially
small anxiety effects even at the current and near-future elevated levels of atmospheric CO2. To this
effect, increased hormones associated with anxiety have been observed in mammals at levels of CO2
in the range 700 -1,000 ppm (Martrette et al. 2017; Wyrwoll et al. 2022; Kiray et al. 2014). Even a small
permanent increase in global human anxiety could have a serious impact on societies – fear, mental
disturbance, conflicts, etc.
The human species is already impaired in indoor environments and this is likely to get worse as rising
outdoor levels of CO2 contribute to increased indoor concentrations (Azuma et al. 2018). It is not
only humans that are at risk. It has been demonstrated that animals have varying degrees of
susceptibility to carbon dioxide (Schaefer et al. 1971). The impacts of elevated CO2 are even greater
for water breathing animals than air breathing animals. In general, land animals have much higher
blood CO2 than aquatic animals and can compensate for hypercapnia by increasing ventilation. In
aquatic animals, compensation by increased ventilation is rare and a small increase in ambient CO2
causes hypercapnic acidosis (Portner et al. 2004; Knoll et al. 1996; McNeil and Sasse 2016). Studies
have shown that hypercapnia in fish produces substantial neurological, behavioural and
physiological effects (Ishimatsu et al. 2005; Heuer and Grosell 2014; Nilsson et al. 2012) for even
short-term exposures at a CO2 concentration predicted to be persistent in the ocean before the year
2100; this level corresponding with an atmospheric concentration of 650 ppm CO2 (McNeil and Sasse
2016).
Given the critical nature of the risks identified in this paper an important question has to be: why is
there no societal discussion of this issue uniquely or in relation to climate change? With the startling
rapid rise of CO2; the permanent changing of our breathable air composition, one would surely
expect the question of whether we can physiologically deal with future projected levels of CO2, to at
least be examined. It appears though that the issue is not even thought of. One explanation for this
is that CO2 is at trace levels in the atmosphere, a mere 0.04% and there is an anecdotal perception
that such a small amount is unlikely to have an effect. However, considering that the current
documented safe level of CO2 for an 8-hour period is just 0.5% (OSHA 2012), CO2 is clearly a highly
toxic substance. There is also an assumption even among scientists that if this was a real issue it
would have already been researched, i.e., we would know about it, though this perception is not
21
scientific and precludes novel investigation. It appears that the issue of long-term CO2 elevated
toxicity has never been significantly investigated since we have never been in this situation before.
Our body’s CO2 compensation system, as discussed earlier, has been perfectly adequate to deal with
acute exposures and the previous stable level of atmospheric CO2, but when levels remain elevated
indefinitely the ability of the body to sustain a healthy metabolism over time comes into question
(Duarte et al. 2020; Stumm 2023). It is also possible that climate change has become the main focus
of rising CO2 levels and there is a lack of vested interest amongst climate scientists about the
potential dangers of long-term exposure to elevated CO2. The most recent IPCC report on the health
impacts of climate change didn’t discuss the issue at all (IPCC 2022). This is surprising since the
previous IPCC report (Smith and Woodward 2014) described the findings of Satich et al. (2012) as a
reported “reduction in mental performance at 1,000 ppm CO2 and above, within the range that all of
humanity would experience in some extreme climate scenarios by 2100”. Since the earlier report
there have been many more studies of cognitive decline (Du et al. 2020) and the damaging effects of
elevated CO2 on physiology (this paper). It is therefore disappointing that the latest IPCC report
failed to recognise this serious and fundamental aspect of climate change. CO2 toxicity at elevated
levels is a discipline of environmental medicine which has not focussed on the potential problem
because chronic impacts of increasing environmental CO2 have not yet been recognised. This may
also help to explain why there are very few researchers involved at this stage and public awareness
is close to non-existent.
Most of the problems associated with elevated indoor CO2 levels greater than about 800 ppm, can
be alleviated by spending time in fresh air. The indoor environments can be restored to acceptable
CO2 levels with effective ventilation although this is often not being achieved. The available resource
of fresh air may be the underlying misguided reason why there is a lack of concern for pollution and
its effects. Significantly this resource may not be available in the future as rising atmospheric CO2
associated with climate change could exceed the 800-ppm level in the current century (Smith and
Woodward, 2014). At that stage, there would be no outdoor escape from the described symptoms.
Under such a condition of permanent exposure, there could be health impacts at levels less than 800
ppm.
10. Conclusions
There is now a significant body of research work that demonstrate (1) current health impacts of
rising CO2 levels and (2) more serious CO2 health impacts for humans in the near future.
Current impacts of short-term exposures of elevated and increasing ambient CO2 in indoor
environments include inflammation, respiratory diseases, headaches, fatigue, increased heart rate,
increased blood pressure, and other symptoms at levels above about 800 ppm. This finding together
with the impairment of cognitive abilities at CO2 levels just above ambient (between 600 and 950
ppm), along with observed associated brainwave patterns, is significant in that it has implications at
a societal level for human function particularly for jobs with critical responsibility (e.g., surgery, air-
traffic controllers, drivers etc.) together with the impact on learning, human development and
economies. It also appears likely that there will be growing global levels of human anxiety from
breathing higher levels of CO2. Physiological CO2 effects will be increased and more permanent in a
future with elevated outdoor ambient CO2 concentrations. Ongoing impacts may include the
22
exacerbation by CO2 of cellular oxidative stress and protein malfunctions resulting in an increase in
cancers, neurological diseases, viruses and many other conditions. Studies of health effects at higher
levels of CO2 at around 2,000-5,000 ppm demonstrate the impact of the inability of the body to fully
compensate for increased CO2 and acidity in the blood. These effects include human tissue
calcification and bone degradation; the former, associated with the overexpression of the enzyme
carbonic anhydrase that is responsible for processing CO2, might represent the greatest existential
threat for many animals. Given there is a lack of studies in humans at lower but elevated CO2 levels,
demonstrated effects in animals and symptoms experienced by humans indicate that longer-term
mechanisms compensating for increased blood CO2 are active when breathing at around 800-1,000
ppm CO2. Long-term exposure to these and potentially lower levels would likely cause severe illness.
These levels are predicted for the ambient atmosphere by the end of the century in a “business as
usual” world. At some stage in the near future humans could be experiencing persistent
physiological effects resulting in serious health problems.
Significantly and disturbingly, increasing levels of blood CO2 in human populations have already been
detected. The buildup of CO2 in humans is due to our inability to expel the increased inhaled CO2
because breathing rates are unchanged. The analysis of average blood bicarbonate, calcium and
phosphorous levels in a large human population shows significant changes between the years 2000
and 2020 with the limit of healthy ranges predicted near the middle of this century. However, it’s
possible that these alterations in human physiology are accelerating and the risk for human and
animal health in the near-future is extremely high with the survival of species potentially under
threat. Communication and global awareness of this issue alongside climate change would further
strengthen the need to drastically reduce CO2 emissions. New research on the health effects of
long-term exposure to realistic future atmospheric CO2 levels is urgently needed to quantify this risk.
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