Serum Anion Gap, Bicarbonate and Biomarkers of Inflammation in Healthy Individuals in a National Survey

Background: In vitro data suggest that lower extracellular pH activates the immune system. We conducted a population-based study of the relation between serum acid-base status and inflammation.

Methods: We examined the serum anion gap and serum levels of bicarbonate and inflammatory biomarkers in 4525 healthy adults who participated in the National Health and Nutrition Examination Survey during 1999-2006. We excluded participants who had chronic disease, recent infection and an estimated glomerular filtration rate of less than 60 mL/min per 1.73 m2.

Results: The mean values of serum anion gap, bicarbonate level, leukocyte count and C-reactive protein level were all within normal limits. After adjustment for age, sex, ethnic background, body mass index, serum albumin level and other factors, we found that a higher anion gap and lower bicarbonate level were associated with a higher leukocyte count and higher C-reactive protein level. Compared with participants in the lowest quartile of anion gap, those in the highest quartile had a leukocyte count that was 1.0x10(9)/L higher and a C-reactive protein level that was 10.9 nmol/L higher (p<0.01). Compared with participants in the highest quartile of bicarbonate level, those in the lowest quartile had a leukocyte count that was 0.7x10(9)/L higher and a C-reactive protein level that was 4.0 nmol/L higher (p<or=0.02). A higher anion gap and lower bicarbonate level were also associated with a higher platelet count, a larger mean platelet volume and a higher ferritin level.

Interpretation: A higher serum anion gap and lower bicarbonate level were associated with higher levels of inflammatory biomarkers in a healthy sample of the general population. Further studies are needed to elucidate the relation between acid-base status and inflammation.