Possibility of Venous Serum Cl− Concentration ([Cl−]s) as a Marker for Human Metabolic Status: Correlation of [Cl−]s to Age, Fasting Blood Sugar (FBS), and Glycated Hemoglobin (HbA1c)

Abstract

The HCO3− concentration in venous serum ([HCO3−]s) is a factor commonly used for detecting the body pH and metabolic conditions. To exactly detect [HCO3−]s, the venous CO2 pressure should be kept as it is in the vein. The [HCO3−]s measurement is technically complicated to apply for huge numbers of almost heathy persons taking only basic medical examinations. The summation of [HCO3−]s and the venous serum Cl− concentration ([Cl−]s) is approximately constant; therefore, we studied if [Cl−]s could be a marker detecting metabolic conditions instead of [HCO3−]s. Venous blood was obtained from persons taking basic medical examinations (the number of persons = 107,630). Older persons showed higher values of [Cl−]s, fasting blood sugar (FBS), and glycated hemoglobin (HbA1c) than younger ones. [Cl−]s showed positive correlation to age and negative correlation to FBS and HBA1c. The negative correlation of [Cl−]s to FBS/HbA1c was obvious in persons with high FBS/HbA1c, leading us to an idea that persons with high FBS/HbA1c show high [HCO3−]s, which might be caused by low activity of carbonic anhydrase in the lung observed in persons with diabetes mellitus under acidotic conditions. Taken together, an easily measured serum electrolyte, [Cl−]s, could be a useful marker estimating metabolic conditions.

Physiological roles of chloride ions in bodily and cellular functions

“…pH is lowered by H + and CO 2 produced in metabolic cells such as myocytes, neurons, etc., H + is produced via glycolysis, and also from CO 2 (CO 2 ↔ H + + HCO 3 − ) via TCA cycle in mitochondria: the produced H + plays various important roles in cellular functions [ 201 , 217 – 237 ]. Lowered pH disturbs various body functions such as appearance of insulin resistance, enhancement of cancer metastasis and elevation of amyloid-ß production [ 201 , 217 – 235 ].…”

“…Although the serum HCO 3 − concentration is a more direct indicator than the serum Cl − concentration, the process of accurately measuring the serum HCO 3 − concentration is clinically cumbersome and it is not practical to easily measure the serum HCO 3 − concentration in many humans. In fact, the venous serum Cl − concentration has been reported to be an indicator of metabolic status and mitochondrial function in analysis of over 100,000 healthy humans [ 237 ]. It is interesting to note that in ‘healthy’ individuals, the venous Cl − concentration increases with age, whereas the venous serum Cl − concentration decreases with increasing fasting blood glucose (sugar: FBS) and HbA1c [ 237 ].…”

“…In fact, the venous serum Cl − concentration has been reported to be an indicator of metabolic status and mitochondrial function in analysis of over 100,000 healthy humans [ 237 ]. It is interesting to note that in ‘healthy’ individuals, the venous Cl − concentration increases with age, whereas the venous serum Cl − concentration decreases with increasing fasting blood glucose (sugar: FBS) and HbA1c [ 237 ]. These phenomena suggest that in ‘healthy’ individuals aging diminishes mitochondrial function (lowering CO 2 production, and leading to lower the venous serum HCO 3 − concentration coupled with a higher venous serum Cl − concentration [ 237 ] (Fig.…”

“…5 A-a for younger persons and Fig. 5 A-b for older persons); furthermore, ‘healthy’ individuals with high FBS and HbA1c levels may have higher intracellular glucose concentrations and consequently higher mitochondrial CO 2 production, leading to elevate the venous serum HCO 3 − concentration coupled with a lower venous serum Cl − concentration [ 237 ] (Fig. 5 B).…”

Scientific Discoveries Supporting Theories in Science: From Thinking to Practice

“…A very interesting scientific article showed that the measurement of serum [Cl − ] may represent an easy and useful marker, helping to estimate metabolic condition [ 10 ].…”