Definition:

• Calcium is a major constituent of bones and teeth and also plays an essential role as a second messenger in cell signaling Circulating calcium concentrations are tightly controlled by the parathyroid hormone (PTH) and vitamin D at the expense of the skeleton when dietary calcium intakes are inadequate.
• The skeleton is a reserve of calcium drawn upon to maintain normal serum calcium in case of inadequate dietary calcium. Thus, calcium sufficiency is required to maximize the attainment of peak bone mass during growth and to limit the progressive demineralization of bones later in life, which leads to osteoporosis, bone fragility, and an increased risk of fractures.
• High concentrations of calcium and oxalate in the urine are major risk factors for the formation of calcium oxalate stones in the kidneys. Because dietary calcium intake has been inversely associated with stone occurrence, it is thought that adequate calcium consumption may reduce the absorption of dietary oxalate, thus reducing urinary oxalate and kidney stone formation.
• Data from observational studies and randomized controlled trials support calcium supplementation in reducing the risk of high blood pressure and preeclampsia in pregnant women. The World Health Organization advises that all pregnant women in areas of low calcium intake (i.e., low-income countries with intakes around 300 to 600 mg/day) be given supplemental calcium starting in the 20^th week of pregnancy.
• Some studies have reported an association between higher calcium intakes and a lower risk of developing colorectal cancer; however, large clinical trials of calcium supplementation are needed.
• Currently, available data suggest that adequate calcium intake may play a role in body weight regulation and have therapeutic benefits in the management of moderate-to-severe premenstrual symptoms.
• Adequate calcium intake is critical for maintaining a healthy skeleton. Calcium is found in a variety of foods, including dairy products, beans, and vegetables of the kale family. Yet, content and bioavailability vary among foods, and certain drugs are known to adversely affect calcium absorption.
• Hypercalcemia, a condition of abnormally high concentrations of calcium in blood, is usually due to malignancy or primary hyperparathyroidism. However, the use of large doses of supplemental calcium, together with absorbable alkali, increases the risk of hypercalcemia, especially in postmenopausal women. Often associated with gastrointestinal disturbances, hypercalcemia can be fatal if left untreated.
• High calcium intakes — either from dairy foods or from supplements — have been associated with increased risks of prostate cancer and cardiovascular events in some, but not all, observational and intervention studies. However, there is currently no evidence of such detrimental effects when people consume a total of 1,000 to 1,200 mg/day of calcium (diet and supplements combined), as recommended by the Food and Nutrition Board of the Institute of Medicine.
• It is recommended that most people taking supplemental calcium should also supplement with magnesium. Many practitioners administer calcium and magnesium in a ratio approximating 2:1.

Drug interactions

• Acid-suppressive therapy: Treatment with a proton pump inhibitor (omeprazole) decreased the absorption of calcium carbonate in the fasting state, presumably because gastric acid is required to absorb this form of calcium.
• Gastrointestinal absorption of calcium was low in patients taking anticonvulsant drugs, presumably because of drug-induced vitamin D deficiency.
• Bile salt sequestrants: Bile salt sequestrants such as cholestyramine and colestipol decrease the intestinal absorption of some nutrients (mainly fat-soluble nutrients). Administration of cholestyramine resulted in negative calcium balance in rats.
• Thiazide diuretics decrease urinary calcium excretion. The use of thiazide diuretics might increase the risk of developing hypercalcemia in patients taking large doses of calcium and vitamin D.
• Fluoroquinolone antibiotics: Calcium and some other minerals can bind to fluoroquinolones (such as ciprofloxacin, norfloxacin, levofloxacin, and gemifloxacin) and markedly reduce their absorption. It is recommended that mineral-containing supplements not be taken within 1–2 hours before or 2–6 hours after taking fluoroquinolones (recommendations vary according to the drug being used). These recommendations also apply to high-calcium foods such as milk and calcium-fortified orange juice.
• Simultaneous ingestion of calcium carbonate has been shown to inhibit the absorption of levothyroxine. It is recommended that levothyroxine be taken at least 1 hour before or 2–4 hours after the ingestion of substances that interfere with its absorption.
• Concurrent administration of calcium or certain other minerals with tetracyclines may interfere with the absorption of the drugs.
• Supplementation with calcium and/or vitamin D can cause a recurrence of atrial fibrillation in patients receiving verapamil.

Dosage and administration

• Supplemental calcium is often given in doses of 400–1,200 mg/day. Calcium supplements are better absorbed when administered in divided doses than when taken as a single daily dose, and when taken with food than when taken on an empty stomach. In addition, taking calcium with food is generally preferable with respect to kidney stone risk.