TY - JOUR T1 - Low-grade metabolic acidosis as a driver of insulin resistance JF - Open Heart JO - Open Heart DO - 10.1136/openhrt-2021-001788 VL - 8 IS - 2 SP - e001788 AU - James J DiNicolantonio AU - James H O'Keefe Y1 - 2021/09/01 UR - http://openheart.bmj.com/content/8/2/e001788.abstract N2 - Metabolic acidosis occurs when there is retention of acid in the body which leads to a drop in the acid buffering capacity of the body. However, acid retention can occur even when serum bicarbonate is normal.1 There are four mechanisms through which the body can develop metabolic acidosis: (1) increased ingestion of dietary acid, (2) increased production of fixed acid such as in diabetic ketoacidosis, alcoholic ketoacidosis or prolonged fasting, (3) increased loss of base (ie, diarrhoea) and (4) reduced kidney excretion of acid. Additionally, specific medications can cause or contribute to metabolic acidosis.There are two major types of acid in the body, carbonic acid and non-carbonic acid. Carbonic acid is formed when a bicarbonate molecule combines with a hydrogen ion. Eventually carbonic acid is turned into water and carbon dioxide. Thus, if we create bicarbonate in the body from alkalinity supplied by the diet then we can breathe out the acid without depleting our own bicarbonate levels. Non-carbonic acids are fixed acids and cannot be exhaled via the lungs. They include lactic acid, phosphoric acid, sulfuric acid, uric acid and the ketoacids acetoacetic acid and beta-hydroxybutyric acid. Some of these fixed acids can be excreted in the urine in their free form, however, the urine pH can only drop to around 4.4 and hence only negligible quantities of strong acids, like sulfuric acid, can be eliminated in its free titratable form.2 So, 99% of the time sulfuric acid must be turned into hydrogen ions and sulfate and then it can be eliminated by the body.When we eat animal protein high in sulfur-containing amino acids such as methionine, cysteine and taurine, we form sulfuric acid, which gets broken down into two hydrogen ions and one sulfate molecule. If we consume a large amount of animal protein, … ER -