Acid-base regulation therapy is an essential component of any metabolic program in Bioregulatory Medicine. Acid-base homeostasis exerts a major influence on protein function, thereby critically affecting tissue and organ performance. Deviations of systemic acidity in either direction can have adverse consequences and, when severe, can be life-threatening. Free radicals and toxins lead to a loss of electrons, which leads to a loss of protons. Consequently, our tissues become more acidic with the deposit of acids into the extracellular matrix, while the bones and tissues lose calcium, magnesium, potassium and trace minerals to compensate for buffer loss. Through excess elimination of acids in the urine, protons are lost out of the body. To a certain extent, the body's elimination system can get rid of most excess metabolic acids; nonetheless, there is a slow deposit of acids into the extracellular matrix and finally an acidification of the cell (intra-cellular) occurs. Once the acids have entered the cell and in order to maintain electrical balance, potassium and magnesium will be excreted and washed out with the urine. Finally, an overall body (tissue) acidification takes place. In an acidic environment, all metabolic and digestive processes are slowed, kidney function is diminished, and all enzyme activity is decreased. Since an acidic bioregulatory terrain creates the ideal condition for the development of numerous chronic diseases, including cancer, it is important to develop therapeutic strategies to improve acid-base homeostasis.
The field of cellular biology has greatly advanced in the last two decades, and molecular biologists now understand that we live and die at the cellular level. All the processes, syndromes, and manifestations that are designated as diseases are, in part, a manifestation of the cell’s regulatory mechanism in creating energy, while combating, neutralizing, and excreting environmental toxins and metabolic waste.
Acid-Base Balance and its Relationship to Cellular Voltage
Cells function normally between a pH of 7.35 to 7.45. The acronym pH is the abbreviation of pondus hydrogenii and means the weight of hydrogen. PH is not only a measurement of hydrogen ion concentration, but also reflects the voltage of a solution. Pure water has a pH very close to 7 at 25 °C. Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline.
Electrons are the negatively charged particles of an atom. Together, all the electrons of an atom create a negative charge that balances the positive charge of the protons in the atomic nucleus. If a solution is an electron donor, then this is designated with a minus sign (-) in front of the measured voltage. If the solution is an electron acceptor or “stealer”, then this is designated with a plus sign (+) in front of the measured voltage. Cellular voltage is measured in millivolts (mV) and can be converted to the pH scale which ranges from 0 to 14. A pH of 0 is the same as a voltage of +414 mV and a pH of 14 is the same as a voltage of -414 mV. Hence, a pH of 7 is considered neutral, and is neither an electron donor nor an electron acceptor, since its voltage is 0 mV. A pH of 7.35 is the same as voltage of -20 mV and a pH of 7.45 is the same as -25 mV. Normal cells exist between a voltage of -20 mV and -25 mV, and, therefore, are electron donors. Cancerous cells thrive in an acidic extracellular environment. Cellular mutations and damage occurs when cellular voltage is below the normal range of -20 mV and -25 mV. Hence, a cancerous terrain occurs when cellular membrane voltage is low, and the cells become electron “stealers”.
The lower the membrane voltage goes, the lower the cell pH becomes, and this lowers the oxygen available to the cell. All these lowered levels are associated with tumor formation and degenerative disease. As cellular voltage continues to drop, cells change from electron donors to electron acceptors or stealers - this is known as an electron polarity shift. When cellular voltage drops to +30 mV, then cancerous cells may form. When the cell voltage drops to this critical level that fosters cancer, only a few substances can pass in or out of the cell, such as water and glucose and the minerals potassium, cesium and rubidium. Oxygen cannot enter a low-voltage cancer cell - even if there is an abundance of oxygen in the blood. Cesium chloride, because of its electrical properties, can still enter the cancerous cell. When it does so, because of its extreme alkalinity, the cancer cell dies. Healthy cells are not affected by cesium because their cell voltage allows them to balance themselves. This is the principal behind cesium therapy (and a topic for another day).
Healthy cells regenerate at a cellular voltage of -50 mV. To achieve this voltage, an abundance of electron donors must be present around the cell. Important electron donors in the body, or reducing agents, include the electrolyte minerals potassium and magnesium. In addition, raw materials to make new healthy cells must be available. One of the most important raw materials for cells is water. The amount of oxygen that dissolves in water is dependent upon the voltage of the water. As voltage is increased, more oxygen will be dissolved in water. Conversely, as voltage drops, oxygen is released from solution. Our cells are 70% water, and as voltage drops, oxygen is lost. Cancer thrives in an oxygen-depleted, dehydrated environment.
pH Regulation and Body Buffers
The cells of the body can only live within a certain narrow pH range, or they will die. The pH scale ranges from 0 to 14, with numbers below 7 representing an acidic condition and above 7 representing an alkaline condition. Slight changes in pH value can cause marked alterations in the rates of chemical reactions in the cells, some being depressed, and others accelerated. For this reason, the regulation of pH is one of the most important aspects of homeostasis. PH is tightly controlled by buffering systems both inside the cells and outside the cells in the extracellular matrix. Thus, intracellular and extracellular buffers are the most immediate mechanism of defense against changes in systemic pH. Bone and proteins constitute a substantial proportion of these buffers. Additionally, organs such as the kidneys, lungs and liver play an important role in eliminating metabolic acids. The pH of the cells, although slightly lower than in the extracellular fluid, nevertheless changes approximately in proportion to extracellular fluid pH changes. Hence, if there are more acid waste deposits in the extracellular matrix, the cells become impregnated with acids and this can cause destructive intercellular processes to occur. Important extracellular buffers include bicarbonate and ammonia. The bicarbonate buffering system is especially important, as carbon dioxide can be shifted through carbonic acid to form hydrogen ions and bicarbonate (through a zinc-dependent enzyme process). Potassium, magnesium and phosphate act as intracellular buffers. The phosphate buffer system also plays a major role in buffering renal tubular fluid. If the system becomes depleted in potassium and magnesium, the body will use calcium from the skeletal tissues to act as a secondary buffer - leading to loss of bone density. In the red blood cells, hemoglobin is an important buffer.
Typical high-animal protein Western diets and endogenous metabolism produce acid, typically on the order of 1 mEq/kg body wt per day or approximately 70 mEq/d for a 70-kg person. Phosphoric acid and sulfuric acid are significant products of this normal metabolism of dietary nutrients, such as proteins and phospholipids. To maintain acid-base homeostasis, these nonvolatile acids must be excreted by the kidney. The kidneys are responsible for excretion of the fixed acids and this is also a critical role even though the amount involved (70-100 mmols/day) is small. The main reason for this renal importance is because there is no other way to excrete these acids. The amounts involved are still very large when compared to the plasma [H+] of only 40 nanomoles/liter. Thus, the kidneys play an extremely important role in acid-base balance, namely the reabsorption of the filtered bicarbonate. Again, bicarbonate is the predominant extracellular buffer against the fixed acids and it important that its plasma concentration should be defended against renal loss.
In acid-base balance, the kidney is responsible for two major activities:
Reabsorption of filtered bicarbonate: 4,000 to 5,000 mmol/day
Excretion of the fixed acids (acid anion and associated H+): about 1 mmol/kg/day
Both these processes involve secretion of H+ into the lumen by the renal tubule cells but only the second leads to excretion of H+ (protons) from the body. Anything consumed will affect our body's pH values. When we take in something acidic or of low pH (low oxygen) values, the body either must pull alkaline minerals from within it to neutralize the acid or store the acid somewhere in the tissue. If consuming an acidic soda at pH 2.5, it takes 32 glasses of water at pH 10 to neutralize the acid. As the pH drops, the cells' oxygen levels also drop, and their ability to function properly diminishes drastically.
Free Radical Pathology and Cellular Energy
A free radical can be defined as any molecular species capable of independent existence that contains an unpaired electron in an atomic orbital. The presence of an unpaired electron results in certain common properties that are shared by most radicals. Many radicals are unstable and highly reactive. Technically, they can either donate an electron to - or accept an electron from - other molecules, therefore behaving as oxidants or reductants. However, the free radical molecules that are missing electrons can damage cells by accepting electrons. In “stealing” electrons, these free radicals lower the voltage of cellular membranes. Free radicals can also deplete cellular energy by interfering with mitochondrial function and contribute to shortened lifespan. Cellular energy generation in the mitochondria is both a key source and key target of oxidative stress in the cells.
Damage occurs when the free radical encounters another molecule and seeks to find another electron to pair with its unpaired electron. The free radical often pulls an electron off a neighboring molecule, causing the affected molecule to become a free radical itself. The new free radical can then pull an electron off the next molecule, and a chemical chain reaction of radical production occurs. Such an event causes damage to the molecule, and thus to the cell that contains it, since the molecule often becomes dysfunctional. Cancer and degenerative diseases coexist with many types of free radicals, especially oxidative free radicals. The most important oxygen-containing free radicals in many disease states are hydroxyl radicals, superoxide anion radicals, hydrogen peroxide, oxygen singlet, hypochlorite, nitric oxide radicals, and peroxynitrite radicals. These are highly reactive species, capable in the nucleus, and in the membranes of cells, of damaging biologically relevant molecules such as DNA, proteins, carbohydrates, and lipids, which is associated with changes in their structure and functions.
Free radicals and other reactive oxygen species rob cells of electrons. They are derived from either byproducts of metabolism, essential metabolic processes in the human body, or from external sources, such as radiation, cigarette smoking, air pollutants, fluoridated or chlorinated water, industrial chemicals, etc. Free radical formation occurs continuously in the cells because of both enzymatic and non-enzymatic reactions. Enzymatic reactions include those involved in the respiratory chain, in phagocytosis, in prostaglandin synthesis, and in the cytochrome P-450 system (to name a few). Free radicals can also be formed in non-enzymatic reactions of oxygen with organic compounds as well as those initiated by ionizing reactions.
Antioxidants are molecules that donate electrons to cells and are very therapeutic for neutralizing free radicals in a cancerous terrain. Hence, one of the primary ways antioxidants protect against free radicals is by donating an electron to the free radical, so it no longer acts as a hungry scavenger stealing electrons from our tissues. Many minerals are also capable of donating electrons as well. Antioxidants prevent free radical induced tissue damage by preventing the formation of radicals, scavenging them, or by promoting their decomposition. Synthetic antioxidants are recently reported to be dangerous to human health. Thus, the search for effective, nontoxic natural compounds with antioxidative activity has been intensified in recent years. In addition to endogenous antioxidant defense systems, consumption of dietary and plant-derived antioxidants appears to be a suitable alternative. Dietary and other components of plants form a major source of antioxidants.
Acid-base homeostasis is critical for normal physiology and health. Hence, multiple, often redundant pathways and processes exist to control systemic pH. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys. Nowadays it is beyond dispute that most of civilization’s diseases are conditioned by our poor nutritional habits. It is well established that diet and certain food components have a clear impact on acid-base balance. Several factors are involved with acid-base regulation, particularly the chemical composition of foods (i.e., their content of protein, and minerals such as chloride, phosphorus, sodium, potassium, calcium, and magnesium), the different intestinal absorption rates of the relevant nutrients, and importantly, the integrity of the intestinal microbiome. The gut microbial community includes approximately 1014 bacteria that normally reside in the gastrointestinal tract, reaching a microbial cell number that greatly exceeds the number of human cells of the body. These organisms play an important part in maintaining acid-base homeostasis.
Today’s civilization manifests diseases which are associated with extracellular matrix acidosis and loss of cellular voltage. These are sure criteria for metabolic derailment, with the danger of acute or chronic disease. By changing one’s nutrition to more mineral rich organic foods, getting adequate hydration, supplementing alkaline minerals and antioxidants into the diet, and deep breathing, pH balance and cellular voltage may be better restored.
Adrogue HJ, Madias NE: Tools for clinical assessment. In: Acid-Base Disorders and Their Treatment, edited by Gennari FJ, Adrogue HJ, Galla JH, Madias NE, editors, Boca Baton, FL, Taylor and Francis Group, 2005, pp 801–816.
Barnett, Y. A., & King, C. M. (1995). Investigation of antioxidant status. DNA-repair capacity and mutation as a function of age in humans. Mut. Res., 338, 115–128.
Bergendi, L., Benes, L., Durackova, Z., & Ferencik, M. (1999). Chemistry, physiology and pathology of free radicals. Life Sci., 65, 1865–1874.
Cadenas, E. (1997). Basic mechanisms of antioxidant activity. Biofactors, 6, 391–397
Goraya N, Wesson DE: Dietary interventions to improve outcomes in chronic kidney disease. Curr Opin Nephrol Hypertens 24: 505–510, 2015 [PubMed]
Hamm LL, Simon EE: Roles and mechanisms of urinary buffer excretion. Am J Physiol 253: F595–F605, 1987 [PubMed]
Hood VL, Tannen RL: Protection of acid-base balance by pH regulation of acid production. N Engl J Med 339: 819–826, 1998 [PubMed]
Lemann J, Jr., Bushinsky DA, Hamm LL: Bone buffering of acid and base in humans. Am J Physiol Renal Physiol 285: F811–F832, 2003 [PubMed]
Remer T, Manz F: Potential renal acid load of foods and its influence on urine pH. J Am Diet Assoc 95: 791–797, 1995 [PubMed]
Rooth G. Acid-Base and Electrolyte Balance. Lund: Studentlitteratur, 1975
Ruffin VA, Salameh AI, Boron WF, Parker MD: Intracellular pH regulation by acid-base transporters in mammalian neurons. Front Physiol 5: 43, 2014 [PMC free article] [PubMed
Siggaard-Andersen O. The Acid-Base Status of the Blood. 4th ed. Copenhagen: Munksgaard, 1974, and Baltimore: William & Wilkins Company, 1974.
Thomson WST, Adams JF, Cowan RA. Clinical Acid-Base Balance. New York: Oxford University Press, 1997.