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Human Physiology from Cells to Systems, Third Edition, Lauralee Sherwood, Department of Physiology, School of Medicine, West Virginia University, 530-531.

Fluid and Acid-Base Balance (Excerpt from Chapter 15.)


Fluctuations in hydrogen-ion concentration have profound effects on body chemistry

Only a narrow pH range is compatible with life because even small changes in [H+] have dramatic effects on normal cell function. The prominent consequences of fluctuations in [H+] include the following:

Hydrogen ions are continually being added to the body fluids as a result of metabolic activities.

As with any other constituent, to maintain a constant.[H+] in the body fluids, input of hydrogen ions must be balanced by an equal output. On the input side only a small amount of acid capable of dissociating to release H+ is taken in with food, such as the weak citric acid found in oranges Most H+ in the body fluids is generated internally from metabolic activities. Normally H+ is continually being added to the body fluids from the three following sources:

1. Carbonic acid formation. The major source of H+ is through H2CO3. formation from metabolically produced CO2. Cellular oxidation of nutrients yields energy, with CO2 and H2O as end products. Catalyzed by the enzyme carbonic anhydrase (ca), CO2 and H2O form H2CO3 which then partially dissociates to liberate free H+ and HCO3-:


This reaction is reversible because it can proceed in either direction, depending on the concentrations of the substances involved as dictated by the law of mass action. Within the systemic capillaries, the CO2 level in the blood increases as metabolically produced CO2 enters from the tissues. This drives the reaction to the acid side, generating H+ as well as HCO3- in the process. In the lungs, the reaction is reversed: CO2 diffuses from the blood flowing through the pulmonary capillaries into the alveoli (air sacs), from which it is expired to the atmosphere. The resultant reduction in CO2 in the blood drives the reaction toward the CO2 side. Hydrogen ion and HCO3- form H2CO3, which rapidly decomposes into CO2 and H2O once again. The CO2. is exhaled while the hydrogen ions generated at the tissue level are incorporated into H2O molecules.

When the respiratory system is able to keep pace with the rate of metabolism, there is no net gain or loss of H+ in the body fluids from metabolically produced CO2. When the rate of CO2 removal by the lungs does not match the rate of CO2 production at the tissue level, however, the resultant accumulation or deficit of CO2 in the body leads to an excess or shortage, respectively, of free H+ in the body fluids.

2. Inorganic acids produced during the breakdown of nutrients. Dietary proteins and other ingested nutrient molecules that are found abundantly in meat contain a large quantity of sulfur and phosphorus. When these molecules are broken down, sulfuric acid and phosphoric acid are produced as by-products. Being moderately strong acids, these two inorganic acids dissociate to a large extent, liberating free H+ into the body fluids. In contrast, the breakdown of fruits and vegetables produces bases that, to some extent, neutralize the acids derived from protein metabolism. Generally, however, more acids than bases are produced during the breakdown of ingested food, leading to an excess of these acids.

3. Organic acids resulting from intermediary metabolism. Numerous organic acids are produced during normal intermediary metabolism. For example, fatty acids are produced during fat metabolism, and lactic acid is produced by muscles during heavy exercise. These acids partially dissociate to yield free H+.

Hydrogen-ion generation therefore normally goes on continuously as a result of ongoing metabolic activities. Furthermore, in certain disease states, additional acids may be produced that further contribute to the total body pool of H+. For example, in diabetes mellitus, large quantities of keto acids may he produced as a result of abnormal fat metabolism. Some types of acid-producing medications may also add to the total load of H+ that must be handled by the body. Thus, input of H+ is unceasing, highly variable, and essentially unregulated.

The crux of H+ balance is maintaining the normal alkalinity of the ECF (pH 7.4) despite this constant onslaught of acid. The generated free H+ must be largely removed from solution while in the body and ultimately must be eliminated from the body so that the pH of the body fluids can remain within the narrow range compatible with life. Mechanisms must also exist to compensate rapidly for the occasional situation in which the ECF becomes too alkaline.

Three lines of defense against changes in [H+] operate to maintain the [H+] of body fluids at a nearly constant level despite unregulated input: (1) the chemical buffer systems, (2) the respiratory mechanism of pH control, and (3) the renal mechanism of pH control. We will look at each of these methods.

This page was first uploaded to The Magnesium Web Site on December 19, 2002