Effects of Carboxytherapy on Metabolic Health: A Narrative Review
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Published:
Jan 10, 2025
Keywords:
CO2, carbon dioxide, CO2 therapy, carboxytherapy
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Abstract
Carboxytherapy is a medical technique that utilizes carbon dioxide for therapeutic purposes. The aim of this review was to assess the scientific evidence on the effects of carboxytherapy on metabolic health. The applications of carboxytherapy span various fields of medicine. Evidence shows that carbon dioxide is not only a key regulator of blood pH but also modulates gene expression, growth factors, and stimulates the production of endothelial progenitor cells. These effects are reflected in increased microcirculation in the skin (where collagen production is stimulated), in subcutaneous adipose tissue (where lipolysis and tissue reduction have been observed), in muscle (where it promotes mitochondrial biogenesis and muscle fiber differentiation), and in bone (where it stimulates repair). The activation of microcirculation is mediated by the upregulation of vascular endothelial growth factor. Despite the existing evidence, further research on the application of carboxytherapy in different medical fields is needed.
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Arellano-Salazar, M. P. (2025). Effects of Carboxytherapy on Metabolic Health: A Narrative Review. Revista De Investigaciones De La Universidad Le Cordon Bleu, 12(1), 5 - 15. https://doi.org/10.36955/RIULCB.2025v12n1.001
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References
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Akahane, S., Sakai, Y., Ueha, T., Nishimoto, H., Inoue, M., Niikura, T., & Kuroda, R. (2017). Transcutaneous carbon dioxide application accelerates muscle injury repair in rat models. International Orthopaedics, 41(5), 1007-1015. https://doi.org/10.1007/s00264-017-3417-2
Arellano, M. P. (2013). Aplicación subcutánea de dióxido de carbono para atenuación de cicatrices. Revista ECIPerú, 9(2), 42-45. https://doi.org/10.33017/RevECIPeru2012.0019/
Bagherani, N., Smoller, B. R., Tavoosidana, G., Ghanadan, A., Wollina, U., & Lotti, T. (2023). An overview of the role of carboxytherapy in dermatology. Journal of Cosmetic Dermatology, 22(9), 2399-2407. https://doi.org/10.1111/jocd.15741
Balik, O., Yilmaz, M., & Bagriyanik, A. (2011). Does Carbon Dioxide Therapy Really Diminish Localized Adiposities? Experimental Study with Rats. Aesthetic Plastic Surgery, 35(4), 470-474. https://doi.org/10.1007/s00266-010-9638-z
Body, J. P. (2014). Good indications of CO2 therapy. Journal of Japanese Society of Balneology, Climatology and Physical Medicine, 77(5), 556-557. https://doi.org/10.11390/onki.77.556
Bolevich, S., Kogan, A. H., Zivkovic, V., Djuric, D., Novikov, A. A., Vorobyev, S. I., & Jakovljevic, V. (2016). Protective role of carbon dioxide (CO2) in generation of reactive oxygen species. Molecular and Cellular Biochemistry, 411(1), 317-330. https://doi.org/10.1007/s11010-015-2594-9
Brandi, C. (2022). Carboxiterapia. Manual práctico con indicaciones clínicas y protocolos (Edición en español 2022). Amolca.
Brandi, C., D’Aniello, C., Grimaldi, L., Bosi, B., Dei, I., Lattarulo, P., & Alessandrini, C. (2001). Carbon dioxide therapy in the treatment of localized adiposities: Clinical study and histopathological correlations. Aesthetic Plastic Surgery, 25(3), 170-174. https://doi.org/10.1007/s002660010116
Brochado, T. M. M., De Carvalho Schweich, L., Di Pietro Simões, N., Oliveira, R. J., & Antoniolli‐Silva, A. C. M. B. (2019). Carboxytherapy: Controls the inflammation and enhances the production of fibronectin on wound healing under venous insufficiency. International Wound Journal, 16(2), 316-324. https://doi.org/10.1111/iwj.13031
Costa, C. S., Otoch, J. P., Seelaender, M. C. L., Neves, R. X. das, Martinez, C. A. R., y Margarido, N. F. (2011). Avaliação citométrica dos adipócitos localizados no tecido subcutâneo da parede anterior do abdome após infiltração percutânea de CO2. Revista do Colégio Brasileiro de Cirurgiões, 38(1), 15-23. https://doi.org/10.1590/S0100-69912011000100004
Cummins, E. P., Selfridge, A. C., Sporn, P. H., Sznajder, J. I., & Taylor, C. T. (2014). Carbon dioxide-sensing in organisms and its implications for human disease. Cellular and Molecular Life Sciences, 71(5), 831-845. https://doi.org/10.1007/s00018-013-1470-6
Diji, A., & Greenfield, A. D. M. (1960). The local effect of carbon dioxide on human blood vessels. American Heart Journal, 60(6), 907-914. https://doi.org/10.1016/0002-8703(60)90122-8
Dogliotti, G., Galliera, E., Iorio, E., De Bernardi Di Valserra, M., Solimene, U., & Corsi, M. M. (2011). Effect of immersion in CO2-enriched water on free radical release and total antioxidant status in peripheral arterial occlusive disease. International Angiology, 30(1), 12-17. https://pubmed.ncbi.nlm.nih.gov/21248668/
Engin, A. B. (2017). What Is Lipotoxicity? En A. B. Engin & A. Engin (Eds.), Obesity and Lipotoxicity. Springer International Publishing, 960, 197-220. https://doi.org/10.1007/978-3-319-48382-5_8
Fabry, R., Monnet, P., Schmidt, J., & Baguet, J.-C. (2006). Carbothérapie Et Phénomènes De Raynaud Un Essai Clinique Randomisé En Double Insu, Mené À Royat. La Presse thermale et climatique, 143, 127-138. https://www.auvergne-thermale.com/download/dp-2010-thermauvergne-2-pdf.pdf
Ferreira, J. C. T., Haddad, A., & Tavares, S. A. N. (2008). Increase in collagen turnover induced by intradermal injection of carbon dioxide in rats. Journal of Drugs in Dermatology, 7(3), 201-206. https://pubmed.ncbi.nlm.nih.gov/18380201/
Galganska, H., Jarmuszkiewicz, W., & Galganski, L. (2021). Carbon dioxide inhibits COVID-19-type proinflammatory responses through extracellular signal-regulated kinases 1 and 2, novel carbon dioxide sensors. Cellular and Molecular Life Sciences, 78(24), 8229-8242. https://doi.org/10.1007/s00018-021-04005-3
Gałgańska, H., Jarmuszkiewicz, W., & Gałgański, Ł. (2023). Carbon dioxide and MAPK signalling: Towards therapy for inflammation. Cell Communication and Signaling, 21(1), 280. https://doi.org/10.1186/s12964-023-01306-x
Hall, J. E., Hall, J. E., & Guyton, A. C. (2011). Guyton and Hall textbook of medical physiology: Student consult. Activate at studentconsult.com. Searchable full text online (12. ed). Saunders, Elsevier.
Hartmann, B., Drews, B., Kürten, B., & Bassenge, E. (1989). CO2-induced increase in skin circulation and transcutaneous oxygen partial pressure of the top of the foot in patients with intermittent claudication. VASA. Supplementum, 27, 251-252.
Irie, H., Tatsumi, T., Takamiya, M., Zen, K., Takahashi, T., Azuma, A., Tateishi, K., Nomura, T., Hayashi, H., Nakajima, N., Okigaki, M., & Matsubara, H. (2005). Carbon Dioxide–Rich Water Bathing Enhances Collateral Blood Flow in Ischemic Hindlimb via Mobilization of Endothelial Progenitor Cells and Activation of NO-cGMP System. Circulation, 111(12), 1523-1529. https://doi.org/10.1161/01.CIR.0000159329.40098.66
Kołodziejczak, A., Rybak, A., & Rotsztejn, H. (2025). The Impact of Carboxytherapy in Monotherapy and in Combination with Lactobionic or Ferulic Acid and Ascorbic Acid on the Hydration and Viscoelasticity of the Skin Around the Eyes. Applied Sciences, 15(4), 1876. https://doi.org/10.3390/app15041876
Kuroiwa, Y., Fukui, T., Takahara, S., Lee, S. Y., Oe, K., Arakura, M., Kumabe, Y., Oda, T., Matsumoto, T., Matsushita, T., Akisue, T., Sakai, Y., Kuroda, R., & Niikura, T. (2019). Topical cutaneous application of CO2 accelerates bone healing in a rat femoral defect model. BMC Musculoskeletal Disorders, 20(1), 237. https://doi.org/10.1186/s12891-019-2601-5
Macura, M., Ban Frangez, H., Cankar, K., Finžgar, M., & Frangez, I. (2020). The effect of transcutaneous application of gaseous CO2 on diabetic chronic wound healing—A double-blind randomized clinical trial. International Wound Journal, 17(6), 1607-1614. https://doi.org/10.1111/iwj.13436
Minamiyama, M., & Yamamoto, A. (2010). Direct evidence of the vasodilator action of carbon dioxide on subcutaneous microvasculature in rats by use of intra-vital video-microscopy. Journal of Biorheology, 24(1), 42-46. https://doi.org/10.1007/s12573-010-0023-y
Niikura, T., Iwakura, T., Omori, T., Lee, S. Y., Sakai, Y., Akisue, T., Oe, K., Fukui, T., Matsushita, T., Matsumoto, T., & Kuroda, R. (2019). Topical cutaneous application of carbon dioxide via a hydrogel for improved fracture repair: Results of phase I clinical safety trial. BMC Musculoskeletal Disorders, 20(1), 563. https://doi.org/10.1186/s12891-019-2911-7
Nishida, R., Fukui, T., Niikura, T., Kumabe, Y., Yoshikawa, R., Takase, K., Yamamoto, Y., Kuroda, R., & Oe, K. (2024). Preventive effects of transcutaneous CO2 application on disuse osteoporosis and muscle atrophy in a rat hindlimb suspension model. Bone, 189, 117262. https://doi.org/10.1016/j.bone.2024.117262
Oe, K., Ueha, T., Sakai, Y., Niikura, T., Lee, S. Y., Koh, A., Hasegawa, T., Tanaka, M., Miwa, M., & Kurosaka, M. (2011). The effect of transcutaneous application of carbon dioxide (CO2) on skeletal muscle. Biochemical and Biophysical Research Communications, 407(1), 148-152. https://doi.org/10.1016/j.bbrc.2011.02.128
Oliveira, S. M. D., Rocha, L. B., da Cunha, M. T. R., Cintra, M. M. M., Pinheiro, N. M., & Mendonça, A. C. (2020). Effects of carboxytherapy on skin laxity. Journal of Cosmetic Dermatology, 19(11), 3007-3013. https://doi.org/10.1111/jocd.13337
Park, J. H., Wee, S. Y., Chang, J., Hong, S., Lee, J. H., Cho, K. W., & Choi, C. Y. (2018). Carboxytherapy-Induced Fat loss is Associated with VEGF-Mediated Vascularization. Aesthetic Plastic Surgery, 42(6), 1681-1688. https://doi.org/10.1007/s00266-018-1222-y
Prazeres, J., Lima, A., & Ribeiro, G. (2025). Effects of Carbon Dioxide Therapy on Skin Wound Healing. Biomedicines, 13(1), 228. https://doi.org/10.3390/biomedicines13010228
Saito, K., & Nonomura, M. (2006). Carbon dioxide rich water bathing increases local vegf secretion and CD34+CD33+ endothelial progenitor cells in ischemic lower limbs of DM and ASO patients. Bone, 38(3), 37. https://doi.org/10.1016/j.bone.2006.01.138
Sakai, Y., Miwa, M., Oe, K., Ueha, T., Lee, S. Y., Koh, A., Niikura, T., Kuroda, R., & Kurosaka, M. (2012). The Effect of Transcutaneous Carbon Dioxide Application on the Recovery from Muscle Fatigue. Poster N° 1278. ORS 2012 Annual Meeting, Japon.
Shtroblia, V., Filip, S., & Lutsenko, R. (2023). Versatile application of carboxytherapy in medicine. Actual Problems of the Modern Medicine: Bulletin of Ukrainian Medical Stomatological Academy, 23(3), 231-236. https://doi.org/10.31718/2077-1096.23.3.231
Wollina, U., Heinig, B., & Uhlemann, C. (2004). Transdermal CO2 Application in Chronic Wounds. The International Journal of Lower Extremity Wounds, 3(2), 103-106. https://doi.org/10.1177/1534734604265142
Ahmad, A., Abu Soliman, A., Shaheen, E., & Obaya, H. (2022). Effect of adding high-intensity interval training to diet and carboxytherapy on metabolic cardiovascular risk factors in women with metabolic syndrome. Gastroenterology Review, 17(4), 280-287. https://doi.org/10.5114/pg.2022.121822
Akahane, S., Sakai, Y., Ueha, T., Nishimoto, H., Inoue, M., Niikura, T., & Kuroda, R. (2017). Transcutaneous carbon dioxide application accelerates muscle injury repair in rat models. International Orthopaedics, 41(5), 1007-1015. https://doi.org/10.1007/s00264-017-3417-2
Arellano, M. P. (2013). Aplicación subcutánea de dióxido de carbono para atenuación de cicatrices. Revista ECIPerú, 9(2), 42-45. https://doi.org/10.33017/RevECIPeru2012.0019/
Bagherani, N., Smoller, B. R., Tavoosidana, G., Ghanadan, A., Wollina, U., & Lotti, T. (2023). An overview of the role of carboxytherapy in dermatology. Journal of Cosmetic Dermatology, 22(9), 2399-2407. https://doi.org/10.1111/jocd.15741
Balik, O., Yilmaz, M., & Bagriyanik, A. (2011). Does Carbon Dioxide Therapy Really Diminish Localized Adiposities? Experimental Study with Rats. Aesthetic Plastic Surgery, 35(4), 470-474. https://doi.org/10.1007/s00266-010-9638-z
Body, J. P. (2014). Good indications of CO2 therapy. Journal of Japanese Society of Balneology, Climatology and Physical Medicine, 77(5), 556-557. https://doi.org/10.11390/onki.77.556
Bolevich, S., Kogan, A. H., Zivkovic, V., Djuric, D., Novikov, A. A., Vorobyev, S. I., & Jakovljevic, V. (2016). Protective role of carbon dioxide (CO2) in generation of reactive oxygen species. Molecular and Cellular Biochemistry, 411(1), 317-330. https://doi.org/10.1007/s11010-015-2594-9
Brandi, C. (2022). Carboxiterapia. Manual práctico con indicaciones clínicas y protocolos (Edición en español 2022). Amolca.
Brandi, C., D’Aniello, C., Grimaldi, L., Bosi, B., Dei, I., Lattarulo, P., & Alessandrini, C. (2001). Carbon dioxide therapy in the treatment of localized adiposities: Clinical study and histopathological correlations. Aesthetic Plastic Surgery, 25(3), 170-174. https://doi.org/10.1007/s002660010116
Brochado, T. M. M., De Carvalho Schweich, L., Di Pietro Simões, N., Oliveira, R. J., & Antoniolli‐Silva, A. C. M. B. (2019). Carboxytherapy: Controls the inflammation and enhances the production of fibronectin on wound healing under venous insufficiency. International Wound Journal, 16(2), 316-324. https://doi.org/10.1111/iwj.13031
Costa, C. S., Otoch, J. P., Seelaender, M. C. L., Neves, R. X. das, Martinez, C. A. R., y Margarido, N. F. (2011). Avaliação citométrica dos adipócitos localizados no tecido subcutâneo da parede anterior do abdome após infiltração percutânea de CO2. Revista do Colégio Brasileiro de Cirurgiões, 38(1), 15-23. https://doi.org/10.1590/S0100-69912011000100004
Cummins, E. P., Selfridge, A. C., Sporn, P. H., Sznajder, J. I., & Taylor, C. T. (2014). Carbon dioxide-sensing in organisms and its implications for human disease. Cellular and Molecular Life Sciences, 71(5), 831-845. https://doi.org/10.1007/s00018-013-1470-6
Diji, A., & Greenfield, A. D. M. (1960). The local effect of carbon dioxide on human blood vessels. American Heart Journal, 60(6), 907-914. https://doi.org/10.1016/0002-8703(60)90122-8
Dogliotti, G., Galliera, E., Iorio, E., De Bernardi Di Valserra, M., Solimene, U., & Corsi, M. M. (2011). Effect of immersion in CO2-enriched water on free radical release and total antioxidant status in peripheral arterial occlusive disease. International Angiology, 30(1), 12-17. https://pubmed.ncbi.nlm.nih.gov/21248668/
Engin, A. B. (2017). What Is Lipotoxicity? En A. B. Engin & A. Engin (Eds.), Obesity and Lipotoxicity. Springer International Publishing, 960, 197-220. https://doi.org/10.1007/978-3-319-48382-5_8
Fabry, R., Monnet, P., Schmidt, J., & Baguet, J.-C. (2006). Carbothérapie Et Phénomènes De Raynaud Un Essai Clinique Randomisé En Double Insu, Mené À Royat. La Presse thermale et climatique, 143, 127-138. https://www.auvergne-thermale.com/download/dp-2010-thermauvergne-2-pdf.pdf
Ferreira, J. C. T., Haddad, A., & Tavares, S. A. N. (2008). Increase in collagen turnover induced by intradermal injection of carbon dioxide in rats. Journal of Drugs in Dermatology, 7(3), 201-206. https://pubmed.ncbi.nlm.nih.gov/18380201/
Galganska, H., Jarmuszkiewicz, W., & Galganski, L. (2021). Carbon dioxide inhibits COVID-19-type proinflammatory responses through extracellular signal-regulated kinases 1 and 2, novel carbon dioxide sensors. Cellular and Molecular Life Sciences, 78(24), 8229-8242. https://doi.org/10.1007/s00018-021-04005-3
Gałgańska, H., Jarmuszkiewicz, W., & Gałgański, Ł. (2023). Carbon dioxide and MAPK signalling: Towards therapy for inflammation. Cell Communication and Signaling, 21(1), 280. https://doi.org/10.1186/s12964-023-01306-x
Hall, J. E., Hall, J. E., & Guyton, A. C. (2011). Guyton and Hall textbook of medical physiology: Student consult. Activate at studentconsult.com. Searchable full text online (12. ed). Saunders, Elsevier.
Hartmann, B., Drews, B., Kürten, B., & Bassenge, E. (1989). CO2-induced increase in skin circulation and transcutaneous oxygen partial pressure of the top of the foot in patients with intermittent claudication. VASA. Supplementum, 27, 251-252.
Irie, H., Tatsumi, T., Takamiya, M., Zen, K., Takahashi, T., Azuma, A., Tateishi, K., Nomura, T., Hayashi, H., Nakajima, N., Okigaki, M., & Matsubara, H. (2005). Carbon Dioxide–Rich Water Bathing Enhances Collateral Blood Flow in Ischemic Hindlimb via Mobilization of Endothelial Progenitor Cells and Activation of NO-cGMP System. Circulation, 111(12), 1523-1529. https://doi.org/10.1161/01.CIR.0000159329.40098.66
Kołodziejczak, A., Rybak, A., & Rotsztejn, H. (2025). The Impact of Carboxytherapy in Monotherapy and in Combination with Lactobionic or Ferulic Acid and Ascorbic Acid on the Hydration and Viscoelasticity of the Skin Around the Eyes. Applied Sciences, 15(4), 1876. https://doi.org/10.3390/app15041876
Kuroiwa, Y., Fukui, T., Takahara, S., Lee, S. Y., Oe, K., Arakura, M., Kumabe, Y., Oda, T., Matsumoto, T., Matsushita, T., Akisue, T., Sakai, Y., Kuroda, R., & Niikura, T. (2019). Topical cutaneous application of CO2 accelerates bone healing in a rat femoral defect model. BMC Musculoskeletal Disorders, 20(1), 237. https://doi.org/10.1186/s12891-019-2601-5
Macura, M., Ban Frangez, H., Cankar, K., Finžgar, M., & Frangez, I. (2020). The effect of transcutaneous application of gaseous CO2 on diabetic chronic wound healing—A double-blind randomized clinical trial. International Wound Journal, 17(6), 1607-1614. https://doi.org/10.1111/iwj.13436
Minamiyama, M., & Yamamoto, A. (2010). Direct evidence of the vasodilator action of carbon dioxide on subcutaneous microvasculature in rats by use of intra-vital video-microscopy. Journal of Biorheology, 24(1), 42-46. https://doi.org/10.1007/s12573-010-0023-y
Niikura, T., Iwakura, T., Omori, T., Lee, S. Y., Sakai, Y., Akisue, T., Oe, K., Fukui, T., Matsushita, T., Matsumoto, T., & Kuroda, R. (2019). Topical cutaneous application of carbon dioxide via a hydrogel for improved fracture repair: Results of phase I clinical safety trial. BMC Musculoskeletal Disorders, 20(1), 563. https://doi.org/10.1186/s12891-019-2911-7
Nishida, R., Fukui, T., Niikura, T., Kumabe, Y., Yoshikawa, R., Takase, K., Yamamoto, Y., Kuroda, R., & Oe, K. (2024). Preventive effects of transcutaneous CO2 application on disuse osteoporosis and muscle atrophy in a rat hindlimb suspension model. Bone, 189, 117262. https://doi.org/10.1016/j.bone.2024.117262
Oe, K., Ueha, T., Sakai, Y., Niikura, T., Lee, S. Y., Koh, A., Hasegawa, T., Tanaka, M., Miwa, M., & Kurosaka, M. (2011). The effect of transcutaneous application of carbon dioxide (CO2) on skeletal muscle. Biochemical and Biophysical Research Communications, 407(1), 148-152. https://doi.org/10.1016/j.bbrc.2011.02.128
Oliveira, S. M. D., Rocha, L. B., da Cunha, M. T. R., Cintra, M. M. M., Pinheiro, N. M., & Mendonça, A. C. (2020). Effects of carboxytherapy on skin laxity. Journal of Cosmetic Dermatology, 19(11), 3007-3013. https://doi.org/10.1111/jocd.13337
Park, J. H., Wee, S. Y., Chang, J., Hong, S., Lee, J. H., Cho, K. W., & Choi, C. Y. (2018). Carboxytherapy-Induced Fat loss is Associated with VEGF-Mediated Vascularization. Aesthetic Plastic Surgery, 42(6), 1681-1688. https://doi.org/10.1007/s00266-018-1222-y
Prazeres, J., Lima, A., & Ribeiro, G. (2025). Effects of Carbon Dioxide Therapy on Skin Wound Healing. Biomedicines, 13(1), 228. https://doi.org/10.3390/biomedicines13010228
Saito, K., & Nonomura, M. (2006). Carbon dioxide rich water bathing increases local vegf secretion and CD34+CD33+ endothelial progenitor cells in ischemic lower limbs of DM and ASO patients. Bone, 38(3), 37. https://doi.org/10.1016/j.bone.2006.01.138
Sakai, Y., Miwa, M., Oe, K., Ueha, T., Lee, S. Y., Koh, A., Niikura, T., Kuroda, R., & Kurosaka, M. (2012). The Effect of Transcutaneous Carbon Dioxide Application on the Recovery from Muscle Fatigue. Poster N° 1278. ORS 2012 Annual Meeting, Japon.
Shtroblia, V., Filip, S., & Lutsenko, R. (2023). Versatile application of carboxytherapy in medicine. Actual Problems of the Modern Medicine: Bulletin of Ukrainian Medical Stomatological Academy, 23(3), 231-236. https://doi.org/10.31718/2077-1096.23.3.231
Wollina, U., Heinig, B., & Uhlemann, C. (2004). Transdermal CO2 Application in Chronic Wounds. The International Journal of Lower Extremity Wounds, 3(2), 103-106. https://doi.org/10.1177/1534734604265142