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June 3, 2022

Electrolyte Biomarkers: Bicarbonate, CO2

Optimal Takeaways

Serum bicarbonate, reported as CO2, is an important buffering compound that helps maintain acid-base balance and optimal pH. Consequences of low bicarbonate and accompanying metabolic acidosis include inflammation, insulin resistance, hypertension, compromised kidney function, and loss of muscle and bone. An excess of bicarbonate may represent metabolic alkalosis and is associated with increased risk of mortality.

Conventional Lab Range: 19 - 30 mEq/L

Optimal Dx’s Optimal Range: 25 - 30 mEq/L

Low serum levels of CO2 are associated with metabolic acidosis, diabetic ketoacidosis, renal failure, shock, starvation, and salicylate toxicity. Medications that may decrease serum CO2 include antibiotics, thiazide diuretics, and triamterene (Pagana 2019).

High serum levels of CO2 are associated with metabolic alkalosis, severe diarrhea or vomiting, gastric suctioning, starvation, emphysema, and aldosteronism. Medications that may increase serum CO2 include aldosterone, bicarbonates, hydrocortisone, loop and mercurial diuretics, steroids, hydrocortisone, and barbiturates (Pagana 2019).


Serum bicarbonate is part of an important buffering system in the body. When the carbon dioxide produced from cellular respiration combines with water, the resulting carbonic acid can then dissociate into bicarbonate and hydrogen and help maintain pH within a narrow physiologically desirable range (Hopkins 2021).

Measurement of total serum CO2 content can be considered a surrogate marker for how much alkalizing bicarbonate is in peripheral venous blood. Bicarbonate directly affects acid-base balance with an elevated bicarbonate leading to metabolic alkalosis, while reduced bicarbonate leads to metabolic acidosis (Pagana 2019). Abnormal serum CO2 measurements should be investigated further in order to determine if acidosis or alkalosis are present and persistent.

Consequences of metabolic acidosis, characterized by a low serum bicarbonate, include inflammation, protein catabolism, muscle loss, demineralization of bone, and increased risk of chronic kidney disease. In the NHANES III study, a serum bicarbonate below 22 mEq/L was associated with 76% higher mortality than those with levels within standard range. Review of data from a cohort study of 2,287 healthy older adults revealed that lowest mortality rates were observed with a calculated serum bicarbonate of 26 mEq/L and mortality increased as bicarbonate decreased, especially below 23 mEq/L. Mortality was also significantly increased with an elevated bicarbonate above 32 mEq/L (Raphael 2016).    

Reduced serum bicarbonate and increased acidosis are also associated with high blood pressure, insulin resistance, and consumption of an acidogenic Western-style diet. Review of NHANES data for those 20-49 years old revealed that serum bicarbonate levels below 24 mEq/L were associated with compromised cardiorespiratory fitness. Lower bicarbonate was also associated with elevated CRP and anion gap, higher BMI, hypertension, female gender, and greater soft drink consumption (Abramowitz 2012).

Prospective evaluation of data from the Nurses’ Health Study found that higher serum bicarbonate, above the mean of 22.4 mEq/l, was associated with a reduced risk of developing type 2 diabetes. For each 1 unit increase in plasma bicarbonate, diabetes risk decreased by 4% (Mandel 2012).

Chronic low-level acidosis may activate the immune system and contribute to low-level inflammation which is associated with chronic diseases including cardiovascular disease and diabetes. Review of NHANES data for 4525 healthy individuals associated lower serum bicarbonate with higher CRP, ferritin, total white blood cells, platelet count, and mean platelet volume. As serum bicarbonate decreased, anion gap increased (Farwell 2010).

Researchers suggest tightening the Conventional Lab Range: for serum CO2 to avoid missing underlying acid-base disorders and recommend increasing the lowest acceptable range to at least 23 mEq/L (Kraut 2018).


Abramowitz, Matthew K et al. “Lower serum bicarbonate and a higher anion gap are associated with lower cardiorespiratory fitness in young adults.” Kidney international vol. 81,10 (2012): 1033-1042. doi:10.1038/ki.2011.479

Farwell, Wildon R, and Eric N Taylor. “Serum anion gap, bicarbonate and biomarkers of inflammation in healthy individuals in a national survey.” CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne vol. 182,2 (2010): 137-41. doi:10.1503/cmaj.090329

Hopkins, Erin, et al. “Physiology, Acid Base Balance.” StatPearls, StatPearls Publishing, 14 September 2021.

Kraut, Jeffrey A, and Nicolaos E Madias. “Re-Evaluation of the Normal Range of Serum Total CO2 Concentration.” Clinical journal of the American Society of Nephrology : CJASN vol. 13,2 (2018): 343-347. doi:10.2215/CJN.11941017

Mandel, Ernest I et al. “Plasma bicarbonate and risk of type 2 diabetes mellitus.” CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne vol. 184,13 (2012): E719-25. doi:10.1503/cmaj.120438

Pagana, Kathleen Deska; Pagana, Timothy J.; Pagana, Theresa N. Mosby's Diagnostic and Laboratory Test Reference. Elsevier Health Sciences. 2019.

Raphael, Kalani L et al. “Bicarbonate Concentration, Acid-Base Status, and Mortality in the Health, Aging, and Body Composition Study.” Clinical journal of the American Society of Nephrology : CJASN vol. 11,2 (2016): 308-16. doi:10.2215/CJN.06200615

Tag(s): Biomarkers

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