Milk-alkali syndrome

Overview

Milk-alkali syndrome is a rare but potentially serious metabolic condition characterized by the triad of hypercalcemia (elevated blood calcium levels), metabolic alkalosis (increased blood pH), and renal impairment. It is most commonly caused by the excessive intake of calcium and absorbable alkali, typically from dietary supplements or antacids containing calcium carbonate. Historically, the syndrome was first observed in the early 20th century in patients treated for peptic ulcer disease with the “Sippy diet,” which included milk and alkaline powders.

Although its incidence declined with the advent of modern ulcer treatments, milk-alkali syndrome has re-emerged due to the increased use of over-the-counter calcium supplements for osteoporosis prevention and acid reflux management. If left untreated, it can lead to severe kidney dysfunction, calcification of soft tissues, and other complications related to calcium imbalance.

Causes

The primary cause of milk-alkali syndrome is excessive intake of calcium and absorbable alkali, most commonly in the form of:

• Calcium carbonate supplements: Widely used for bone health and acid reflux

• Milk or dairy products: High in calcium, especially when consumed in large quantities

• Antacids containing sodium bicarbonate or calcium carbonate: Often overused for heartburn or dyspepsia

Several risk factors increase susceptibility to milk-alkali syndrome:

• Postmenopausal women (often taking calcium for osteoporosis)

• Chronic kidney disease (reduced ability to excrete calcium)

• Thiazide diuretics (reduce urinary calcium excretion)

• Dehydration or reduced fluid intake

• Use of vitamin D supplements (enhance calcium absorption)

In susceptible individuals, even moderately high calcium intake can disrupt calcium homeostasis, leading to hypercalcemia and subsequent metabolic and renal disturbances.

Symptoms

The symptoms of milk-alkali syndrome are primarily related to elevated calcium levels and may vary from mild to severe. Common clinical features include:

Gastrointestinal Symptoms

• Nausea and vomiting

• Loss of appetite

• Constipation

• Abdominal pain

Neurological and Muscular Symptoms

• Fatigue

• Muscle weakness

• Confusion or altered mental status

• Headache

Renal Symptoms

• Polyuria (excessive urination)

• Polydipsia (excessive thirst)

• Dehydration

• Progressive kidney dysfunction or acute kidney injury

In severe cases, hypercalcemia may lead to cardiac arrhythmias, nephrocalcinosis (calcium deposition in the kidneys), and even coma.

Diagnosis

Diagnosis of milk-alkali syndrome is based on a combination of clinical history, laboratory findings, and exclusion of other causes of hypercalcemia. Diagnostic steps include:

• Medical history: Detailed review of calcium and antacid intake, use of supplements, and predisposing conditions

• Serum calcium: Elevated total and ionized calcium levels

• Serum bicarbonate: Elevated, indicating metabolic alkalosis

• Serum creatinine and BUN: May show signs of renal impairment

• Serum phosphorus: Often low or normal

• Parathyroid hormone (PTH): Suppressed due to hypercalcemia (helps distinguish from primary hyperparathyroidism)

• Vitamin D levels: To exclude hypervitaminosis D

Imaging such as renal ultrasound may be used to assess for nephrocalcinosis or kidney stones if kidney damage is suspected.

Treatment

Treatment of milk-alkali syndrome focuses on discontinuing the source of excess calcium and correcting the metabolic disturbances. Key treatment strategies include:

Immediate Measures

• Discontinue calcium and alkali intake: Stop supplements and antacids immediately

• Intravenous hydration: Administer isotonic saline to correct dehydration and promote urinary calcium excretion

• Loop diuretics: Such as furosemide, may be used after rehydration to enhance calcium excretion (only if volume status is corrected)

Supportive and Monitoring Care

• Monitor electrolytes, renal function, and calcium levels regularly

• Treat any underlying or contributing conditions (e.g., adjust medications like thiazides or vitamin D)

Severe Cases

• Hemodialysis: May be necessary in cases of life-threatening hypercalcemia or renal failure unresponsive to conservative measures

Education on safe supplement use and follow-up with a healthcare provider is crucial to prevent recurrence.

Prognosis

The prognosis of milk-alkali syndrome is generally good if identified and treated early. Most patients experience full recovery of renal function and normalization of calcium levels with prompt discontinuation of offending agents and appropriate fluid management.

However, prolonged or recurrent exposure to high calcium and alkali can lead to permanent kidney damage, including chronic kidney disease and nephrocalcinosis. Risk of recurrence is high if the underlying behavior (e.g., excessive calcium supplement use) is not addressed.

With growing awareness and careful management of calcium supplementation, milk-alkali syndrome is preventable and treatable in the vast majority of cases.