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Direct human health risks of increased atmospheric carbon dioxide


Growing evidence suggests that environmentally relevant elevations in CO2 (<5,000 ppm) may pose direct risks for human health. Increasing atmospheric CO2 concentrations could make adverse exposures more frequent and prolonged through increases in indoor air concentrations and increased time spent indoors. We review preliminary evidence concerning the potential health risks of chronic exposure to environmentally relevant elevations in ambient CO2, including inflammation, reductions in higher-level cognitive abilities, bone demineralization, kidney calcification, oxidative stress and endothelial dysfunction. This early evidence indicates potential health risks at CO2 exposures as low as 1,000 ppm—a threshold that is already exceeded in many indoor environments with increased room occupancy and reduced building ventilation rates, and equivalent to some estimates for urban outdoor air concentrations before 2100. Continuous exposure to increased atmospheric CO2 could be an overlooked stressor of the modern and/or future environment. Further research is needed to quantify the major sources of CO2 exposure, to identify mitigation strategies to avoid adverse health effects and protect vulnerable populations, and to fully understand the potential health effects of chronic or intermittent exposure to indoor air with higher CO2 concentrations.

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Fig. 1: Flow diagram for the identification of appropriate studies from the literature.
Fig. 2: Summary of potential mechanisms by which CO2 might affect human health.


  1. 1.

    Zheutlin, A. R., Adar, S. D. & Park, S. K. Carbon dioxide emissions and change in prevalence of obesity and diabetes in the United States: an ecological study. Environ. Int. 73, 111–116 (2014).

    CAS  Google Scholar 

  2. 2.

    Zappulla, D. Environmental stress, erythrocyte dysfunctions, inflammation, and the metabolic syndrome: adaptations to CO2 increases? J. Cardiometab. Syndr. 3, 30–34 (2008).

    Google Scholar 

  3. 3.

    Costello, A. et al. Managing the health effects of climate change. Lancet 373, 1693–1733 (2009).

    Google Scholar 

  4. 4.

    Mora, C. et al. Global risk of deadly heat. Nat. Clim. Change 7, 501–506 (2017).

    Google Scholar 

  5. 5.

    Spengler, J. et al. in Climate Change, the Indoor Environment, and Health (eds Spengler, J. et al.) Ch. 4 (The National Academies Press, 2011).

  6. 6.

    Hönisch, B., Hemming, N. G., Archer, D., Siddall, M. & McManus, J. F. Atmospheric carbon dioxide concentration across the mid-Pleistocene transition. Science 324, 1551–1554 (2009).

    Google Scholar 

  7. 7.

    Hayhoe, K. et al. in Climate Science Special Report: Fourth National Climate Assessment (eds Wuebbles, D. J. et al.) 133–160 (US Global Change Research Program, 2017).

  8. 8.

    Gall, E., Cheung, T., Luhung, I., Schiavon, S. & Nazaroff, W. Real-time monitoring of personal exposures to carbon dioxide. Build. Environ. 104, 59–67 (2016).

    Google Scholar 

  9. 9.

    Kriebel, D. et al. The precautionary principle in environmental science. Environ. Health Perspect. 109, 871–876 (2001).

    CAS  Google Scholar 

  10. 10.

    Crump, D. Climate Change—Health Impacts due to Changes in the Indoor Environment (Institute of Environment and Health, 2011).

  11. 11.

    Klepeis, N. E. et al. The National Human Activity Pattern Survey (NHAPS): a resource for assessing exposure to environmental pollutants. J. Expo. Anal. Environ. Epidemiol. 11, 231–252 (2001).

    CAS  Google Scholar 

  12. 12.

    Schweizer, C. et al. Indoor time–microenvironment–activity patterns in seven regions of Europe. J. Expo. Sci. Environ. Epidemiol. 17, 170–181 (2007).

    CAS  Google Scholar 

  13. 13.

    Standard 62. 1–2013 Ventilation for Acceptable Indoor Air Quality (ANSI/ASHRAE, 2013).

  14. 14.

    Persily, A. Challenges in developing ventilation and indoor air quality standards: the story of ASHRAE Standard 62. Build. Environ. 91, 61–69 (2015).

    Google Scholar 

  15. 15.

    Erdmann, C. A., Steiner, K. C. & Apte, M. G. Indoor carbon dioxide concentrations and sick building syndrome symptoms in the BASE study revisited: analyses of the 100 building dataset. Proc. Indoor Air 2002 3, 443–448 (2002).

    Google Scholar 

  16. 16.

    Nazaroff, W. W. Exploring the consequences of climate change for indoor air quality. Environ. Res. Lett. 8, 015022 (2013).

    Google Scholar 

  17. 17.

    Abdel-Salam, M. M. Investigation of PM2.5 and carbon dioxide levels in urban homes. J. Air Waste Manag. Assoc. 65, 930–936 (2015).

    CAS  Google Scholar 

  18. 18.

    Seppänen, O. A., Fisk, W. J. & Mendell, M. J. Association of ventilation rates and CO2 concentrations with health and other responses in commercial and institutional buildings. Indoor Air 9, 226–252 (1999).

    Google Scholar 

  19. 19.

    Fisk, W. J. The ventilation problem in schools: literature review. Indoor Air 27, 1039–1051 (2017).

    CAS  Google Scholar 

  20. 20.

    Newsham, G. R. et al. Do ‘green’ buildings have better indoor environments? New evidence. Build. Res. Inf. 41, 415–434 (2013).

    Google Scholar 

  21. 21.

    Liang, H.-H. et al. Satisfaction of occupants toward indoor environment quality of certified green office buildings in Taiwan. Build. Environ. 72, 232–242 (2014).

    Google Scholar 

  22. 22.

    Colton, M. D. et al. Indoor air quality in green vs conventional multifamily low-income housing. Environ. Sci. Technol. 48, 7833–7841 (2014).

    CAS  Google Scholar 

  23. 23.

    Persily, A. & de Jonge, L. Carbon dioxide generation rates for building occupants. Indoor Air 27, 868–879 (2017).

    CAS  Google Scholar 

  24. 24.

    Becerra, M., Jerez, A., Valenzuela, M., Garces, H. & Demarco, R. Life quality disparity: analysis of indoor comfort gaps for Chilean households. Energy Policy 121, 190–201 (2018).

    CAS  Google Scholar 

  25. 25.

    Mendell, M. J. & Heath, G. A. Do indoor pollutants and thermal conditions in schools influence student performance? A critical review of the literature. Indoor Air 15, 27–52 (2005).

    CAS  Google Scholar 

  26. 26.

    Boor, B. E., Spilak, M. P., Laverge, J., Novoselac, A. & Xu, Y. Human exposure to indoor air pollutants in sleep microenvironments: a literature review. Build. Environ. 125, 528–555 (2017).

    Google Scholar 

  27. 27.

    Strøm-Tejsen, P., Zukowska, D., Wargocki, P. & Wyon, D. P. The effects of bedroom air quality on sleep and next-day performance. Indoor Air 26, 679–686 (2016).

    Google Scholar 

  28. 28.

    Mishra, A. K., van Ruitenbeek, A. M., Loomans, M. G. L. C. & Kort, H. S. M. Window/door opening-mediated bedroom ventilation and its impact on sleep quality of healthy, young adults. Indoor Air 28, 339–351 (2018).

    CAS  Google Scholar 

  29. 29.

    Balvis, E., Sampedro, O., Zaragoza, S., Paredes, A. & Michinel, H. A simple model for automatic analysis and diagnosis of environmental thermal comfort in energy efficient buildings. Appl. Energy 177, 60–70 (2016).

    Google Scholar 

  30. 30.

    Ghahramani, A. et al. Personal CO2 bubble: context-dependent variations and wearable sensors usability. J. Build. Eng. 22, 295–304 (2019).

    Google Scholar 

  31. 31.

    Law, J., Watkins, S. & Alexander, D. In-Flight Carbon Dioxide Exposures and Related Symptoms: Association, Susceptibility, and Operational Implications (NASA Johnson Space Center, 2010).

  32. 32.

    Richardson, E. T. et al. Forced removals embodied as tuberculosis. Soc. Sci. Med. 161, 13–18 (2016).

    Google Scholar 

  33. 33.

    Hudda, N. & Fruin, S. A. Carbon dioxide accumulation inside vehicles: the effect of ventilation and driving conditions. Sci. Total Environ. 610–611, 1448–1456 (2018).

    Google Scholar 

  34. 34.

    Constantin, D., Mazilescu, C.-A., Nagi, M., Draghici, A. & Mihartescu, A.-A. Perception of cabin air quality among drivers and passengers. Sustainability 8, 852 (2016).

    Google Scholar 

  35. 35.

    Cao, X. et al. The on-board carbon dioxide concentrations and ventilation performance in passenger cabins of US domestic flights. Indoor Built Environ. 28, 761–771 (2019).

    CAS  Google Scholar 

  36. 36.

    Jacobson, M. Z. Enhancement of local air pollution by urban CO2 domes. Environ. Sci. Technol. 44, 2497–2502 (2010).

    CAS  Google Scholar 

  37. 37.

    Velasco, E. & Roth, M. Cities as net sources of CO2: review of atmospheric CO2 exchange in urban environments measured by eddy covariance technique. Geogr. Compass 4, 1238–1259 (2010).

    Google Scholar 

  38. 38.

    Ward, H. C. et al. Effects of urban density on carbon dioxide exchanges: observations of dense urban, suburban and woodland areas of southern England. Environ. Pollut. 198, 186–200 (2015).

    CAS  Google Scholar 

  39. 39.

    Bergeron, O. & Strachan, I. B. CO2 sources and sinks in urban and suburban areas of a northern mid-latitude city. Atmos. Environ. 45, 1564–1573 (2011).

    CAS  Google Scholar 

  40. 40.

    Idso, C. D., Idso, S. B. & Balling, R. C. Jr An intensive two-week study of an urban CO2 dome in Phoenix, Arizona, USA. Atmos. Environ. 35, 995–1000 (2001).

    CAS  Google Scholar 

  41. 41.

    Idso, C. D., Idos, S. B. & Balling, R. C. Jr The urban CO2 dome of Phoenix, Arizona. Phys. Geogr. 19, 95–108 (1998).

    Google Scholar 

  42. 42.

    Wang, P. et al. Emission characteristics of atmospheric carbon dioxide in Xi’an, China based on the measurements of CO2 concentration, Δ14C and δ13C. Sci. Total Environ. 619–620, 1163–1169 (2018).

    Google Scholar 

  43. 43.

    W orld Urbanization Prospects: The 2018 Revision (Economic and Social Affairs, United Nations, 2018).

  44. 44.

    George, K., Ziska, L. H., Bunce, J. A. & Quebedeaux, B. Elevated atmospheric CO2 concentration and temperature across an urban–rural transect. Atmos. Environ. 41, 7654–7665 (2007).

    CAS  Google Scholar 

  45. 45.

    Esquivel-Hernandez, G. et al. Near surface carbon dioxide and methane in urban areas of Costa Rica. Open J. Air Pollut. 4, 208–223 (2015).

    CAS  Google Scholar 

  46. 46.

    Briber, B., Hutyra, L., Dunn, A., Raciti, S. & Munger, J. W. Variations in atmospheric CO2 mixing ratios across a Boston, MA urban to rural gradient. Land 3, 304–327 (2013).

    Google Scholar 

  47. 47.

    Lee, J. K., Christen, A., Ketler, R. & Nesic, Z. A mobile sensor network to map carbon dioxide emissions in urban environments. Atmos. Meas. Tech. 10, 645–665 (2017).

    CAS  Google Scholar 

  48. 48.

    Sahay, S. & Ghosh, C. Monitoring variation in greenhouse gases concentration in urban environment of Delhi. Environ. Monit. Assess. 185, 123–142 (2013).

    CAS  Google Scholar 

  49. 49.

    Majumdar, D., Rao, P. & Maske, N. Inter-seasonal and spatial distribution of ground-level greenhouse gases (CO2, CH4, N2O) over Nagpur in India and their management roadmap. Environ. Monit. Assess. 189, 121 (2017).

    Google Scholar 

  50. 50.

    Gratani, L. & Varone, L. Atmospheric carbon dioxide concentration variations in Rome: relationship with traffic level and urban park size. Urban Ecosyst. 17, 501–511 (2014).

    Google Scholar 

  51. 51.

    Persily, A. Evaluating building IAQ and ventilation with carbon dioxide. ASHRAE Trans. 103, 193–204 (1997).

    CAS  Google Scholar 

  52. 52.

    Keun Kim, M. & Choi, J. Can increased outdoor CO2 concentrations impact on the ventilation and energy in buildings? A case study in Shanghai, China. Atmos. Environ. 210, 220–230 (2019).

    Google Scholar 

  53. 53.

    Okobia, L. E., Hassan, S. M. & Peter, A. Increase in outdoor carbon dioxide and its effects on the environment and human health in Kuje FCT Nigeria. Environ. Health Rev. 60, 104–112 (2017).

    Google Scholar 

  54. 54.

    Arceo, E., Hanna, R. & Oliva, P. Does the effect of pollution on infant mortality differ between developing and developed countries? Evidence from Mexico City. Econ. J. 126, 257–280 (2016).

    Google Scholar 

  55. 55.

    Lu, R. & Turco, R. P. Air pollutant transport in a coastal environment. Part 1: Two-dimensional simulations of sea-breeze and mountain effects. J. Atmos. Sci. 51, 2285–2308 (1994).

    Google Scholar 

  56. 56.

    Bell, M. L. & Davis, D. L. Reassessment of the lethal London fog of 1952: novel indicators of acute and chronic consequences of acute exposure to air pollution. Environ. Health Perspect. 109, 389–394 (2001).

    CAS  Google Scholar 

  57. 57.

    Rendon, A. M., Salazar, J. F. & Palacio, C. A. Effects of urbanization on the temperature inversion breakup in a mountain valley with implications for air quality. J. Appl. Meteorol. Climatol. 53, 840–858 (2014).

    Google Scholar 

  58. 58.

    Gago, E. J., Roldan, J., Pacheco-Torres, R. & Ordonez, J. The city and urban heat islands: a review of strategies to mitigate adverse effects. Renew. Sustain. Energy Rev. 25, 749–758 (2013).

    Google Scholar 

  59. 59.

    Lietzke, B. & Vogt, R. Variability of CO2 concentrations and fluxes in and above an urban street canyon. Atmos. Environ. 74, 60–72 (2013).

    CAS  Google Scholar 

  60. 60.

    Velasco, E. et al. Sources and sinks of carbon dioxide in a neighborhood of Mexico City. Atmos. Environ. 97, 226–238 (2014).

    CAS  Google Scholar 

  61. 61.

    Robertson, D. S. The rise in the atmospheric concentration of carbon dioxide and the effects on human health. Med. Hypotheses 56, 513–518 (2001).

    CAS  Google Scholar 

  62. 62.

    Spengler, J. D. Climate change, indoor environments, and health. Indoor Air 22, 89–95 (2012).

    Google Scholar 

  63. 63.

    Lowe, R. J., Huebner, G. M. & Oreszczyn, T. Possible future impacts of elevated levels of atmospheric CO2 on human cognitive performance and on the design and operation of ventilation systems in buildings. Build. Serv. Eng. Res. Technol. 39, 698–711 (2018).

    Google Scholar 

  64. 64.

    Carlton, E. J. et al. Relationships between home ventilation rates and respiratory health in the Colorado Home Energy Efficiency and Respiratory Health (CHEER) study. Environ. Res. 169, 297–307 (2019).

    CAS  Google Scholar 

  65. 65.

    Chen, J., Brager, G. S., Augenbroe, G. & Song, X. Impact of outdoor air quality on the natural ventilation usage of commercial buildings in the US. Appl. Energy 235, 673–684 (2019).

    CAS  Google Scholar 

  66. 66.

    Shrubsole, C. et al. Bridging the gap: the need for a systems thinking approach in understanding and addressing energy and environmental performance in buildings. Indoor Built Environ. 28, 100–117 (2019).

    Google Scholar 

  67. 67.

    Vardoulakis, S. et al. Impact of climate change on the domestic indoor environment and associated health risks in the UK. Environ. Int. 85, 299–313 (2015).

    CAS  Google Scholar 

  68. 68.

    Steinemann, A., Wargocki, P. & Rismanchi, B. Ten questions concerning green buildings and indoor air quality. Build. Environ. 112, 351–358 (2016).

    Google Scholar 

  69. 69.

    Zappulla, D. in Air Pollution - Sources, Prevention, and Health Effects (ed. Sethi, R.) Ch. 16 (Nova Science, 2013).

  70. 70.

    Leung, D. Y. C. Outdoor-indoor air pollution in urban environment: challenges and opportunity. Front. Environ. Sci. 2, 69 (2015).

    Google Scholar 

  71. 71.

    Fitzpatrick, M. C. & Dunn, R. R. Contemporary climatic analogs for 540 North American urban areas in the late 21st century. Nat. Commun. 10, 614 (2019).

    Google Scholar 

  72. 72.

    King, A. D. & Harrington, L. J. The inequality of climate change from 1.5 to 2 °C of global warming. Geophys. Res. Lett. 45, 5030–5033 (2018).

    Google Scholar 

  73. 73.

    Zhang, X., Wargocki, P. & Lian, Z. Physiological responses during exposure to carbon dioxide and bioeffluents at levels typically occurring indoors. Indoor Air 27, 65–77 (2017).

    Google Scholar 

  74. 74.

    Zhang, X., Wargocki, P., Lian, Z. & Thyregod, C. Effects of exposure to carbon dioxide and bioeffluents on perceived air quality, self-assessed acute health symptoms, and cognitive performance. Indoor Air 27, 47–64 (2017).

    CAS  Google Scholar 

  75. 75.

    Zhang, X., Wargocki, P. & Lian, Z. Human responses to carbon dioxide, a follow-up study at recommended exposure limits in non-industrial environments. Build. Environ. 100, 162–171 (2016).

    Google Scholar 

  76. 76.

    Shiraram, S., Ramamurthy, K. & Ramakrishnan, S. Effect of occupant-induced indoor CO2 concentration and bioeffluents on human phyiology using a spirometric test. Build. Environ. 149, 58–67 (2019).

    Google Scholar 

  77. 77.

    Vehvilainen, T. et al. High indoor CO2 concentrations in an office environment increases the transcutaneous CO2 level and sleepiness during cognitive work. J. Occup. Environ. Hyg. 13, 19–29 (2016).

    CAS  Google Scholar 

  78. 78.

    Hughson, R. L., Yee, N. J. & Greaves, D. K. Elevated end-tidal PCO2 during long-duration spaceflight. Aerosp. Med. Hum. Perform. 87, 894–897 (2016).

    Google Scholar 

  79. 79.

    Law, J. et al. Relationship between carbon dioxide levels and reported headaches on the international space station. J. Occup. Environ. Med. 56, 477–483 (2014).

    CAS  Google Scholar 

  80. 80.

    Thom, S. R., Bhopale, V. M., Hu, J. & Yang, M. Inflammatory responses to acute elevations of carbon dioxide in mice. J. Appl. Physiol. 123, 297–302 (2017).

    CAS  Google Scholar 

  81. 81.

    Thom, S. R., Bhopale, V. M., Hu, J. & Yang, M. Increased carbon dioxide levels stimulate neutrophils to produce microparticles and activate the nucleotide-binding domain-like receptor 3 inflammasome. Free Radic. Biol. Med. 106, 406–416 (2017).

    CAS  Google Scholar 

  82. 82.

    Schneberger, D., DeVasure, J. M., Bailey, K. L., Romberger, D. J. & Wyatt, T. A. Effect of low-level CO2 on innate inflammatory protein response to organic dust from swine confinement barns. J. Occup. Med. Toxicol. 12, 9 (2017).

    Google Scholar 

  83. 83.

    Hutter, H. P. et al. Semivolatile compounds in schools and their influence on cognitive performance of children. Int. J. Occup. Med. Environ. Health 26, 628–635 (2013).

    Google Scholar 

  84. 84.

    Azuma, K., Kagi, N., Yanagi, U. & Osawa, H. Effects of low-level inhalation exposure to carbon dioxide in indoor environments: a short review on human health and pscyhomotor performance. Environ. Int. 121, 51–56 (2018).

    CAS  Google Scholar 

  85. 85.

    Kajtar, L. & Herczeg, L. Influence of carbon-dioxide concentration on human well-being and intensity of mental work. Idojaras 116, 145–169 (2012).

    Google Scholar 

  86. 86.

    Satish, U. et al. Is CO2 an indoor pollutant? Direct effects of low-to-moderate CO2 concentrations on human decision-making performance. Environ. Health Perspect. 120, 1671–1677 (2012).

    CAS  Google Scholar 

  87. 87.

    Allen, J. G. et al. Associations of cognitive function scores with carbon dioxide, ventilation, and volatile organic compound exposures in office workers: a controlled exposure study of green and conventional office environments. Environ. Health Perspect. 124, 805–812 (2016).

    CAS  Google Scholar 

  88. 88.

    Allen, J. G. et al. Airplane pilot flight performance on 21 maneuvers in a flight simulator under varying carbon dioxide concentrations. J. Expo. Sci. Environ. Epidemiol. 29, 457–468 (2019).

    CAS  Google Scholar 

  89. 89.

    Cao, X. et al. Heart rate variability and performance of commercial airline pilots during flight simulations. Int. J. Environ. Res. Public Health 16, 237 (2019).

    CAS  Google Scholar 

  90. 90.

    Snow, S. et al. Exploring the physiological, neurophysiological and cognitive performance effects of elevated carbon dioxide concentrations indoors. Build. Environ. 156, 243–252 (2019).

    Google Scholar 

  91. 91.

    Rodeheffer, C. D., Chabal, S., Clarke, J. M. & Fothergill, D. M. Acute exposure to low-to-moderate carbon dioxide levels and submariner decision making. Aerosp. Med. Hum. Perform. 89, 520–525 (2018).

    Google Scholar 

  92. 92.

    Snow, S. et al. Using EEG to characterise drowsiness during short duration exposure to elevated indoor carbon dioxide concentrations. Preprint at bioRxiv (2018).

  93. 93.

    MacNaughton, P. et al. Environmental perceptions and health before and after relocation to a green building. Build. Environ. 104, 138–144 (2016).

    Google Scholar 

  94. 94.

    Miller, A. H. & Raison, C. L. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat. Rev. Immunol. 16, 22–34 (2016).

    CAS  Google Scholar 

  95. 95.

    Cronym, P. D., Watkins, S. & Alexander, D. J. Chronic Exposure to Moderately Elevated CO 2 During Long-Duration Space Flight (NASA Center for AeroSpace Information, 2012).

  96. 96.

    Bloch-Salisbury, E., Lansing, R. & Shea, S. A. Acute changes in carbon dioxide levels alter the electroencephalogram without affecting cognitive function. Psychophysiology 37, 418–426 (2000).

    CAS  Google Scholar 

  97. 97.

    Zouboules, S. M. & Day, T. A. The exhausting work of acclimating to chronically elevated CO2. J. Physiol. 597, 1421–1423 (2019).

    CAS  Google Scholar 

  98. 98.

    Wang, D., Thomas, R. J., Yee, B. J. & Grunstein, R. R. Hypercapnia is more important than hypoxia in the neuro-outcomes of sleep-disordered breathing. J. Appl. Physiol. 120, 1484–1486 (2016).

    CAS  Google Scholar 

  99. 99.

    Burgraff, N. J. et al. Ventilatory and integrated physiological responses to chronic hypercapnia in goats. J. Physiol. 596, 5343–5363 (2018).

    CAS  Google Scholar 

  100. 100.

    Miller, J. et al. Comorbidity, systemic inflammation and outcomes in the ECLIPSE cohort. Resp. Med. 107, 1376–1384 (2013).

    Google Scholar 

  101. 101.

    Beheshti, A., Cekanaviciute, E., Smith, D. J. & Costes, S. V. Global transcriptomic analysis suggests carbon dioxide as an environmental stressor in spaceflight: a systems biology GeneLab case study. Sci. Rep. 8, 4191 (2018).

    Google Scholar 

  102. 102.

    Schaefer, K. E. Effects of increased ambient CO2 levels on human and animal health. Experientia 38, 1163–1168 (1982).

    CAS  Google Scholar 

  103. 103.

    Schaefer, K. E., Douglas, W. H. J., Messier, A. A., Shea, M. L. & Gohman, P. A. Effect of prolonged exposure to 0.5% CO2 on kidney calcification and ultrastructure of lungs. Undersea Biomed. Res. 6, S155–S161 (1979).

    Google Scholar 

  104. 104.

    Wade, C. E., Wang, T. J., Lang, K. C., Corbin, B. J. & Steele, M. K. Rat growth, body composition, and renal function during 30 days increased ambient CO2 exposure. Aviat. Space Environ. Med. 71, 599–609 (2000).

    CAS  Google Scholar 

  105. 105.

    Hacquemand, R. et al. Effects of CO2 inhalation exposure on mice vomeronasal epithelium. Cell Biol. Toxicol. 26, 309–317 (2010).

    CAS  Google Scholar 

  106. 106.

    Robertson, D. S. Health effects of increase in concentration of carbon dioxide in the atmosphere. Curr. Sci. 90, 1607–1609 (2006).

    CAS  Google Scholar 

  107. 107.

    Robertson, D. S. Palaeo-variations in the atmospheric concentration of carbon dioxide and the relationship to extinctions. Speculat. Sci. Technol. 21, 171–185 (1999).

    Google Scholar 

  108. 108.

    Guais, A. et al. Toxicity of carbon dioxide: a review. Chem. Res. Toxicol. 24, 2061–2070 (2011).

    CAS  Google Scholar 

  109. 109.

    Carnauba, R. A., Baptistella, A. B., Paschoal, V. & Hübscher, G. H. Diet-induced low-grade metabolic acidosis and clinical outcomes: a review. Nutrients 9, 538 (2017).

    Google Scholar 

  110. 110.

    Frassetto, L., Banerjee, T., Powe, N. & Sebastian, A. Acid balance, dietary acid load, and bone effects-a controversial subject. Nutrients 10, 517 (2018).

    Google Scholar 

  111. 111.

    Martrette, J. M. et al. Effects of prolonged exposure to CO2 on behaviour, hormone secretion and respiratory muscles in young female rats. Physiol. Behav. 177, 257–262 (2017).

    CAS  Google Scholar 

  112. 112.

    Kiray, M. et al. Effects of carbon dioxide exposure on early brain development in rats. Biotech. Histochem. 89, 371–383 (2014).

    CAS  Google Scholar 

  113. 113.

    Hersoug, L. G., Sjödin, A. & Astrup, A. A proposed potential role for increasing atmospheric CO2 as a promoter of weight gain and obesity. Nutr. Diabetes 2, e31 (2012).

    Google Scholar 

  114. 114.

    Kikuchi, R. et al. Hypercapnia accelerates adipogenesis: a novel role of high CO2 in exacerbating obesity. Am. J. Resp. Cell Mol. Biol. 57, 570–580 (2017).

    CAS  Google Scholar 

  115. 115.

    Medinas, D. B., Cerchiaro, G., Trindade, D. F. & Augusto, O. The carbonate radical and related oxidants derived from bicarbonate buffer. IUBMB Life 59, 255–262 (2007).

    CAS  Google Scholar 

  116. 116.

    Ezraty, B., Chabalier, M., Ducret, A., Maisonneuve, E. & Dukan, S. CO2 exacerbates oxygen toxicity. EMBO Rep. 12, 321–326 (2011).

    CAS  Google Scholar 

  117. 117.

    Veselá, A. & Wilhelm, J. The role of carbon dioxide in free radical reactions of the organism. Physiol. Res. 51, 335–339 (2002).

    Google Scholar 

  118. 118.

    Zuj, K. A. et al. Impaired cerebrovascular autoregulation and reduced CO2 reactivity after long duration spaceflight. Am. J. Physiol. Heart Circ. Physiol. 302, H2592–H2598 (2012).

    CAS  Google Scholar 

  119. 119.

    Zwart, S. R. et al. Astronaut ophthalmic syndrome. FASEB J. 31, 3746–3756 (2017).

    CAS  Google Scholar 

  120. 120.

    Michael, A. P. & Marshall-Bowman, K. Spaceflight-induced intracranial hypertension. Aerosp. Med. Hum. Perform. 86, 557–562 (2015).

    Google Scholar 

  121. 121.

    Laurie, S. S. et al. Effects of short-term mild hypercapnia during head-down tilt on intracranial pressure and ocular structures in healthy human subjects. Physiol. Rep. 5, e13302 (2017).

    Google Scholar 

  122. 122.

    Faustman, E. M., Silbernagel, S. M., Fenske, R. A., Burbacher, T. M. & Ponce, R. A. Mechanisms underlying children’s susceptibility to environmental toxicants. Environ. Health Perspect. 108, 13–21 (2000).

    CAS  Google Scholar 

  123. 123.

    Rice, S. A. Human health risk assessment of CO2: survivors of acute high-level exposure and populations sensitive to prolonged low-level exposure. In Third Annual Conference on Carbon Sequestration (2004);

  124. 124.

    Glodzik, L., Randall, C., Rusinek, H. & de Leon, M. J. Cerebrovascular reactivity to carbon dioxide in Alzheimer’s disease. J. Alzheimers Dis. 35, 427–440 (2013).

    CAS  Google Scholar 

  125. 125.

    Holy, X., Collombet, J. M., Labarthe, F., Granger-Veyron, N. & Bégot, L. Effects of seasonal vitamin D deficiency and respiratory acidosis on bone metabolism markers in submarine crewmembers during prolonged patrols. J. Appl. Physiol. 112, 587–596 (2012).

    CAS  Google Scholar 

  126. 126.

    Battaglia, M. & Khan, W. U. in Biomarkers in Psychiatry. Current Topics in Behavioral Neurosciences Vol. 40 (eds Pratt, J. & Hall, J.) 195–217 (Springer, 2018).

  127. 127.

    Kim, J., Kong, M., Hong, T., Jeong, K. & Lee, M. Physiological response of building occupants based on their activity and the indoor environmental quality condition changes. Build. Environ. 145, 96–103 (2018).

    Google Scholar 

  128. 128.

    Anderson, D. E. Cardiorenal effects of behavioral inhibition of breathing. Biol. Psychol. 49, 151–163 (1998).

    CAS  Google Scholar 

  129. 129.

    Anderson, D. E. & Chesney, M. A. Gender-specific association of perceived stress and inhibited breathing pattern. Int. J. Behav. Med. 9, 216–227 (2002).

    Google Scholar 

  130. 130.

    Scholz, L. et al. Miniature low-cost carbon dioxide sensor for mobile devices. IEEE Sens. J. 17, 2889–2895 (2017).

    CAS  Google Scholar 

  131. 131.

    Stingone, J. A. et al. Toward greater implementation of the exposome research paradigm within environmental epidemiology. Annu. Rev. Public Health 38, 315–327 (2017).

    Google Scholar 

  132. 132.

    Go, Y. M., Chandler, J. D. & Jones, D. P. The cysteine proteome. Free Radic. Biol. Med. 84, 227–245 (2015).

    CAS  Google Scholar 

  133. 133.

    Ghaffarianhoseini, A. et al. Sick building syndrome: are we doing enough? Archit. Sci. Rev. 61, 99–121 (2018).

    Google Scholar 

  134. 134.

    Heidari, L., Younger, M., Chandler, G., Gooch, J. & Schramm, P. Integrating health into buildings of the future. ASME J. Sol. Energy Eng. 139, 010802 (2017).

    Google Scholar 

  135. 135.

    Carrer, P. et al. On the development of health-based ventilation guidelines: principles and framework. Int. J. Environ. Res. Public Health 15, 1360 (2018).

    Google Scholar 

  136. 136.

    MacNaughton, P. et al. The impact of working in a green certified building on cognitive function and health. Build. Environ. 114, 178–186 (2017).

    Google Scholar 

  137. 137.

    Shrubsole, C. Systems thinking in the built environment: seeing the bigger picture, understanding the detail. Indoor Built Environ. 27, 439–441 (2018).

    Google Scholar 

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The authors thank B. Money, medical student at Nova Southeastern University, for early contributions. We also thank Q. E. Wafford, Research Librarian of the Galter Health Sciences Library at Northwestern University, for helpful guidance on performing the systematic search of the literature, and D. Tenenbaum, Science Writer at the University of Wisconsin–Madison, for helping with editing the manuscript. Finally, we thank the following colleagues at the University of Wisconsin–Madison for their early discussions and feedback: R. Podein, L. Fortney, B. Barrett, E. Ranheim, C. Raison, J. A. Dempsey, W. Porter and C. R. Boardman.

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T.A.J., J.S.K. and M.T.H. wrote the initial version of this manuscript, with significant feedback and guidance from R.K.B., K.C.M. and W.E.F. M.T.H. conceptualized the paper. All authors made substantial contributions to the intellectual content, analysis and interpretation of the literature review, and editing of the manuscript.

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Correspondence to Michael T. Hernke.

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Jacobson, T.A., Kler, J.S., Hernke, M.T. et al. Direct human health risks of increased atmospheric carbon dioxide. Nat Sustain 2, 691–701 (2019).

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