Milk-Alkali Syndrome



  • Milk-alkali syndrome results from ingestion of excessive amounts of calcium and absorbable alkali (e.g., bicarbonate and citrate salts).
  • Historically seen during self-treatment of indigestion or reflux (heartburn)
  • Also seen with treatment/prevention of postmenopausal osteoporosis, consumption of carbonated beverages and calcium salts
  • Characterized by:
    • Hypercalcemia
    • Metabolic alkalosis
      • ± Renal insufficiency
  • System(s) affected: endocrine/metabolic; gastrointestinal (GI); renal/urologic
  • Synonym(s): Burnett syndrome; Cope syndrome; milk poisoning; milk drinker syndrome; calcium alkali syndrome



  • Third most common cause of hypercalcemia
  • Recent increase associated with treatment for prevention of osteoporosis

Infrequent in the outpatient setting but 9–12% among hospitalized patients who have hypercalcemia

Etiology and Pathophysiology

  • Cyclic process between intestines and kidneys: hypercalcemia from high-calcium intake (usually >4 g/day) believed secondary to inadequate response to calcitriol
  • Hypercalcemia leads to vasoconstriction ultimately decreasing glomerular filtration.
  • Activation of calcium-sensing receptors increases calcium reabsorption, absorption of bicarbonate, and natriuresis (maintaining alkalotic state).
  • Blockade of antidiuretic hormone leads to increased diuresis.

Risk Factors

  • Use of calcium-containing antacids or supplements
  • Chronic kidney disease
  • Simultaneous vitamin D supplementation
  • Thiazide diuretic therapy
  • Pregnancy (increased GI calcium absorption)
  • Elderly
  • Postmenopausal women (more common overall in women)
  • Nicotine substitute chewing gum in large quantities

General Prevention

  • Avoid excess milk and/or absorbable antacids.
  • Use noncarbonate salts for calcium supplementation.
  • Caution in elderly treated with ACE-I/ARB, NSAIDs, and diuretic

Commonly Associated Conditions

  • Peptic ulcer disease
  • Hiatal hernia
  • Gastroesophageal reflux
  • Osteoporosis
  • Hypertension
  • Hyperparathyroidism
  • Hypercalcemia of malignancy

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