Research Blog

June 3, 2022

Electrolyte Biomarkers: Bicarbonate, CO2

Optimal Takeaways

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

Standard Range: 19 - 30 mEq/L

The ODX Range: 25 - 30 mEq/L

Low serum levels of CO2 are associated with low-grade metabolic acidosis (DiNicolantonio 2021), metabolic acidosis, diabetic ketoacidosis, renal failure, shock, starvation, and salicylate toxicity. Medications that may decrease serum CO2 include antibiotics, thiazide diuretics, and triamterene (Pagana 2021).

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, loop and mercurial diuretics, steroids, hydrocortisone, and barbiturates (Pagana 2021).


Serum bicarbonate is part of the metabolic 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 serum pH within a narrow physiologically desirable range (Hopkins 2021). However, metabolic acidosis can still occur even at normal blood pH, i.e., 7.35-7.45. An optimal serum bicarbonate ranges from 25-30 mEq/L, preferably 27-30 mEq/L. Lower levels should be investigated further, especially if accompanied by a urinary pH below 6.8 (DiNicolantonio 2021).

Measurement of total serum CO2 can be considered a surrogate marker for how much alkalizing bicarbonate is in peripheral venous blood. Bicarbonate directly affects acid-base balance, with elevated bicarbonate leading to metabolic alkalosis, while reduced bicarbonate leads to metabolic acidosis. Serum bicarbonate is regulated by the kidneys (Pagana 2021). Abnormal serum bicarbonate measurements should be investigated further to determine if acidosis or alkalosis is present and persistent.

Consequences of metabolic acidosis, characterized by low serum bicarbonate, include inflammation, protein catabolism, muscle loss, demineralization of bone, and increased risk of chronic kidney disease. In the NHANES III study, serum bicarbonate below 22 mEq/L was associated with 76% higher mortality than those with levels within the standard range. A review of data from a cohort study of 2,287 healthy older adults revealed that the lowest mortality rates were observed with a calculated serum bicarbonate of 26 mEq/L, and mortality increased as bicarbonate decreased, especially below a level of 23 mEq/L. Mortality was also significantly increased with 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. A 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 the Nurses’ Health Study data found that higher serum bicarbonate, above the mean of 22.4 mEq/l, was associated with a reduced risk of developing type 2 diabetes, and 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 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, the anion gap increased (Farwell 2010). Fruits and vegetables contain organic ions that can be converted to bicarbonate in the body and help neutralize acidosis. On the other hand, animal protein generates excess acid in the body and contributes to metabolic acidosis if not balanced with alkalizing foods (DiNicolantonio 2021).

Researchers recommend increasing the lowest acceptable range for bicarbonate to at least 23 mEq/L to avoid missing underlying acid-base disorders (Kraut 2018).

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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

DiNicolantonio, James J, and James O'Keefe. “Low-grade metabolic acidosis as a driver of chronic disease: a 21st century public health crisis.” Open heart vol. 8,2 (2021): e001730. doi:10.1136/openhrt-2021-001730

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, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

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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