Health Hazards of Metabolic Acidosis

by Ben Best

The structure and function of proteins, including enzymes, can be compromised by body tissues being too acidic. A study of American adults showed blood plasma acidity increasing 6-7% between the ages of 20 and 80, with most of the change occuring after age 50 [AMERICAN JOURNAL OF PHYSIOLOGY; Frassetto,LA; 271(40):F1114-F1122 (1996) and JOURNAL OF THE AMERICAN GERIATRICS SOCIETY; Berkemeyer,S; 56:1442 (2008)].

Normal arterial blood plasma is slightly alkaline (pH 7.4), whereas interstitial tissue (areas between cells) and venous blood is slightly less alkaline (pH 7.35) due to CO2 released due to tissue metabolism. Arterial blood pH above 7.4 is called alkalosis, whereas arterial pH below 7.35 is called acidosis. Severe metabolic acidosis (below pH 7.1) is treated with intravenous sodium carbonate. Within seconds of increased blood plasma acidity (such as due to diarrhea or exercise), respiration increases, causing CO2 to be exhaled (reducing the acidity). Acidity lasting longer causes the kidneys to convert carbon dioxide (CO2) into hydrogen ion (H+) and bicarbonate ion (HCO−3), excreting the H+ and reabsorbing the HCO−3 to correct the acidosis.

[Carbonic Anhydrase ]

The modern Western diet is high in animal protein (meat,eggs,cheese), which are acidifying, in contrast to fruits and vegetables, which are usually alkaline [BIOCHEMIE; Williams,RS; 124:171-177 (2016)]. A diet high in fat can also cause acidity, by ketone formation, but the acidity of dietary ketosis is mild.

The acid from protein is produced by liver oxidation of amino acid sulphydryl (thiol, R-SH) groups. Amino acid nitrogen is converted to ammonia (NH3) and then to urea in the liver. Ammonia from the liver combines with the acidic hydrogen ion to form ammonium (NH4+), which the kidney excretes. The kidney creates ammonia from the amino acid glutamine. The kidney excretes the acidic ammonium molecule by exchange with the alkaline bicarbonate (HCO3) molecule, which is reabsorbed [JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY; Paulev,PE; 56(supp 4):155 (2005)].

Bicarbonate (HCO3) is a buffer molecule which can combine with acid to form carbon dioxide (CO2) during acidosis, or release the acidic hydrogen ions (H+) during alkalosis. In acidosis the kidney reabsorbs bicarbonate and excretes acid, whereas in alkalosis, the kidney excretes bicarbonate and reabsorbs the hydrogen ions. Normally, two-thirds of acid excretion by the kidney is in the form of ammonium.

Excretion of acid (H+) can occur by reabsorption of either potassium (K+) or sodium (Na+) by the kidney. If blood Na+ is high, more H+ will be excreted in exchange for reabsorption of Na+, whereas if K+ is high, more K+ will be reabsorbed in exchange for the H+ which is excreted. Na+ reabsorption by the kidney will be matched by excretion of either H+ or K+. In acidosis, H+ excretion is increased, whereas K+ and Na+ excretion is reduced.

Blood plasma accounts for 25% of the fluid outside cells, with interstitial fluid (fluid between cells, but not in blood vessels) accounting for the other 75%. Normally, nearly all of the potassium (K+) in the body is inside cells (more than 95%), whereas only 10% of sodium (Na+) in the body is inside cells. But during acidosis, K+ is driven out of cells by H+, causing increased K+ secretion by the kidneys.

Prior to the advent of agriculture, the human diet was high in potassium and low in sodium, whereas the reverse is true in the modern Western diet [AMERICAN JOURNAL OF CLINICAL NUTRITION; Sebastian,A; 76:1308-1216 (2002)]. A high sodium/potassium ratio is predictive of high blood pressure and kidney stones [JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION; Morris,RC; 25(3):262s-270s (2006)]. If diet increases blood plasma potassium above what is requred, the kidney readily excretes it. If blood potassium is too low, the kidney does not excrete it. If conservation of potassium by the kidney is still inadequate, potassium is removed from muscle cells, but not from nervous tissue cells (neurons). Severely low potassium can cause weakness or even paralysis [ANNALS OF THE INDIAN ACADEMY OF NEUROLOGY; Sharma,CM; 17(1):100-102 (2014)].

When blood volume is low, aldosterone release stimulates the sodium-potassium pump in the kidney to excrete more potassium and reabsorb more sodium. Aldosterone has the same effect when blood potassium is high [CLINCIAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY; Palmer,BF; 10(6):1050-1060 (2015)].

Metabolic acidosis increases insulin resistance and the likelihood of type 2 diabetes [JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY; Paulev,PE; 56(supp 4):155 (2005)]. Metabolic acidosis is both a cause and a consequence of insulin resistance and type 2 diabetes [WORLD JOURNAL OF DIABETES; Marunaka,Y; 6(1):125 (2015)]. The metabolic acidosis of type 2 causes uric acid kidney stones  [CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY; Maalouf,NM; 5:1277-1281 (2010)].

Metabolic acidosis increases inflammation, heart arrhythmias, osteoporosis, calcium kidney stones, and muscle wasting [EPILEPSY & BEHAVIOR; Yuen,AWC; 74:15-21 (2017)]. Metabolic acidosis increases the stress hormone cortisol in females [JOURNAL OF NUTRITION; Remer,T; 138:426s-430s (2008)]. Cancer cells use an acidic environment to resist cell death (apoptosis), to spread (metastasize), to escape the immune system, and to promote new blood vessels that can support the growing tumor [CELLULAR AND MOLECULAR LIFE SCIENCES; Peppicelli,S; 74(15):2761-2771 (2017)].

Bones become demineralized in response to acidosis, which results in osteoporosis and bone fracture. The problem is worsened by excessive dietary table salt (sodium chloride) [JOURNAL OF NUTRITION; Frasseto,LA; 138:419s-422s (2008)].

Seventy percent of people over age 80 are affected by osteoporosis. Osteoporosis is about 3 times as prevalent in women as in men [ARCHIVES OF OSTEOPOROSIS; Wade,SW; 9:182 (2014)], especially due to reduced plasma estrogen after menopause [AMERICAN JOURNAL OF CLINICAL NUTRITION; McTiernan,A; 89(6):1864-1876 (2009)].

Calcium and sodium compete for reabsorption in the kidney, but sodium chloride (table salt) causes more calcium excretion than sodium alone. Sodium chloride increases metabolic acidosis and decreases kidney reabsorption of alkaline bicarbonate by the increase in parathyroid hormone (which is secreted to induce calcium release from bone to compensate for calcium excretion by the kidney) [JOURNAL OF BONE AND MINERAL RESEARCH; Frings-Muethen,P; 23(4):517-524 (2008)]. High salt (sodium) intake can increase blood pressure and kidney disease [KIDNEY RESEARCH AND CLINICAL PRACTICE; Frame,AA; 36:117-131 (2017)]. Persons whose blood pressure is most increased by salt are the persons whose metabolic acidosis is most increased by salt [HYPERTENSION; Sharma,AM; 16(4):407-413 (1990)]. Most Americans consume more than double the minimum daily intake of sodium recommended by the American Heart Association [MAYO CLINIC PROCEEDINGS; Clegg,DJ; 92(8):1248-1260 (2017)].

Moderate protein (between 10-20% of calories) may maintain bone in post-menopausal women [AMERICAN JOURNAL OF CLINICAL NUTRITION; Hunt,JR; 89(5):1357-1365 (2009)]. Alkalinization by potassium bicarbonate promotes maintenance of muscle and bone in older adults [JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; Dawson-Hughes; 94(1):96-102 (2009) and JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; Ceglia,L; 94(2):645-653 (2009)]. Calcium, Vitamin D, and potassium-rich fruits and vegetables reduce muscle wasting and preserve muscle mass in the elderly  [AMERICAN JOURNAL OF CLINICAL NUTRITION; Dawson-Hughes,B; 87(3):662-665 (2008)].

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