Milk-Alkali Syndrome

Abstract

Milk-alkali syndrome (MAS) consists of hypercalcemia, various degrees of renal failure, and metabolic alkalosis due to ingestion of large amounts of calcium and absorbable alkali. This syndrome was first identified after medical treatment of peptic ulcer disease with milk and alkali was widely adopted at the beginning of the 20th century. With the introduction of histamine2 blockers and proton pump inhibitors, the occurrence of MAS became rare; however, a resurgence of MAS has been witnessed because of the wide availability and increasing use of calcium carbonate, mostly for osteoporosis prevention. The aim of this review was to determine the incidence, pathogenesis, histologic findings, diagnosis, and clinical course of MAS. A MEDLINE search was performed with the keyword milk-alkali syndrome using the PubMed search engine. All relevant English language articles were reviewed. The exact pathomechanism of MAS remains uncertain, but a unique interplay between hypercalcemia and alkalosis in the kidneys seems to lead to a self-reinforcing cycle, resulting in the clinical picture of MAS. Treatment is supportive and involves hydration and withdrawal of the offending agents. Physicians and the public need to be aware of the potential adverse effects of ingesting excessive amounts of calcium carbonate.

Drug-induced acid-base disorders

“…Vitamin D supplementation to prevent vitamin-D-deficient rickets in children is generally recommended [180], but there are some reports of children with hypercalcemia after treatment with vitamin D [181]. The classic symptoms consist of hypercalcemia, various degrees of renal failure, and metabolic alkalosis [182]. There are several risk factors for development of CAS: The use of thiazide diuretics predisposes to CAS by increasing Ca 2+ reabsorption in combination with volume depletion and metabolic alkalosis.…”

Got Calcium? Welcome to the Calcium-Alkali Syndrome

“…13 In contrast, the modern version of calcium-alkali syndrome associates with hypophosphatemia or lownormal serum phosphorus levels as a result of the phosphorus-binding properties of calcium carbonate. 5,11,14 This hypophosphatemia is more pronounced in elderly patients 14 or those with eating disorders, 15 who tend to have relatively low consumption of protein and therefore phosphorus; low phosphate levels stimulate the renal metabolism of calcitriol and, consequently, absorption of calcium by the gut. 16 Levels of 1,25-hydroxyvitamin D in patients with the calcium-alkali syndrome, of course, are generally low in the setting of hypercalcemia, although some are in the lownormal range and perhaps inappropriPublished online ahead of print.…”

“…11,14 These latter levels may depend on previous exposure to vitamin D supplementation, because vitamin D is often added to some over-the-counter calcium preparations, but more epidemiology is needed to clarify this exposure.…”

“…The integral feature of the calcium-alkali syndrome is a history of excessive ingestion of calcium and often absorbable alkali, producing the classic triad of hypercalcemia, metabolic alkalosis, and varying degrees of renal insufficiency. 5,11,12 The earlier milk-alkali syndrome using the Sippy diet often presented with hyperphosphatemia after prolonged ingestion of phosphorus-containing milk with cream. 13 In contrast, the modern version of calcium-alkali syndrome associates with hypophosphatemia or lownormal serum phosphorus levels as a result of the phosphorus-binding properties of calcium carbonate.…”

“…7,11,14,17 Older patients with aging bone metabolism are susceptible to targeted advertising for their health care advice regarding the use of calcium supplements for the treatment of osteoporosis. 18,19 Pregnant women have an increased susceptibility to developing calcium-alkali syndrome as a result of hyperemesis, causing volume depletion and enhanced calcium absorption through the gut, possibly aggravated by prolactin or placental lactogen signaling.…”