Dietary Chloride Deficiency Syndrome: Pathophysiology, History, and Systematic Literature Review
Facoltà di Scienze Biomediche, Università della Svizzera Italiana, 6900 Lugano, Switzerland
Pediatric Institute of Southern Switzerland, Ospedale San Giovanni, 6500 Bellinzona, Switzerland
Pediatric Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy
Italian Society for Pediatric Gastroenterology Hepatology and Nutrition (SIGENP), 20126 Milan, Italy
Pediatric Cardiology Unit, Department of Pediatrics, Centre Hospitalier Universitaire Vaudois, and University of Lausanne, 1011 Lausanne, Switzerland
Author to whom correspondence should be addressed.
Nutrients 2020, 12(11), 3436; https://doi.org/10.3390/nu12113436
Received: 23 September 2020 / Revised: 1 November 2020 / Accepted: 2 November 2020 / Published: 9 November 2020
(This article belongs to the Special Issue Influence of Nutrients on Acid-Base Balance)
Metabolic alkalosis may develop as a consequence of urinary chloride (and sodium) wasting, excessive loss of salt in the sweat, or intestinal chloride wasting, among other causes. There is also a likely underrecognized association between poor salt intake and the mentioned electrolyte and acid–base abnormality. In patients with excessive loss of salt in the sweat or poor salt intake, the maintenance of metabolic alkalosis is crucially modulated by the chloride–bicarbonate exchanger pendrin located on the renal tubular membrane of type B intercalated cells. In the late 1970s, recommendations were made to decrease the salt content of foods as part of an effort to minimize the tendency towards systemic hypertension. Hence, the baby food industry decided to remove added salt from formula milk. Some weeks later, approximately 200 infants (fed exclusively with formula milks with a chloride content of only 2–4 mmol/L), were admitted with failure to thrive, constipation, food refusal, muscular weakness, and delayed psychomotor development. The laboratory work-up disclosed metabolic alkalosis, hypokalemia, hypochloremia, and a reduced urinary chloride excretion. In all cases, both the clinical and the laboratory features remitted in ≤7 days when the infants were fed on formula milk with a normal chloride content. Since 1982, 13 further publications reported additional cases of dietary chloride depletion. It is therefore concluded that the dietary intake of chloride, which was previously considered a “mendicant” ion, plays a crucial role in acid–base and salt balance.