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Safety of calcium

Toxicity

Abnormally elevated blood calcium (hypercalcemia) resulting from the over consumption of calcium has never been documented to occur from foods, only from calcium supplements. Mild hypercalcemia may be without symptoms, or may result in loss of appetite, nausea, vomiting, constipation, abdominal pain, dry mouth, thirst, and frequent urination. More severe hypercalcemia may result in confusion, delirium, coma, and if not treated, death. Hypercalcemia has been reported only with the consumption of large quantities of calcium supplements usually in combination with antacids, particularly in the days when peptic ulcers were treated with large quantities of milk, calcium carbonate (antacid) and sodium bicarbonate (absorbable alkalai) (1). This condition was termed milk alkalai syndrome, and has been reported at calcium supplement levels from 1.5 to 16.5 grams/day for 2 days to 30 years. Since the treatment for peptic ulcers has changed, the incidence of this syndrome has decreased considerably (3). 

Although the risk of forming kidney stones is increased in individuals with abnormally elevated urinary calcium (hypercalciuria), this condition is not usually related to calcium intake, but rather to increased excretion of calcium by the kidneys. Overall, increased dietary calcium has been associated with a decreased risk of kidney stones. However, in a large prospective study, the risk of developing kidney stones in women taking supplemental calcium was 20% higher than in those who did not (21). This effect may be related to the fact that calcium supplements can be taken without food, eliminating their beneficial effect of decreasing intestinal oxalate absorption.

Based on the adverse effects above, as well as the potential for decreased absorption of other essential minerals (see below), the Food and Nutrition Board of the Institute of Medicine set the tolerable upper level (UL) of intake for calcium in adults at 2,500 milligrams (mg) of calcium/day (3).

*Source of intake should be from food and formula only.

Do high calcium intakes increase the risk of prostate cancer?

Recent epidemiologic studies have raised concern that high calcium intakes are associated with increased risk of prostate cancer. A large prospective cohort study in the U.S. followed more than 50,000 male health professionals for 8 years and found that men whose calcium intake was 2,000 mg/day or more had a risk of developing advanced prostate cancer that was 3 times higher than men whose calcium intake was less than 500 mg/day and a risk of developing metastasized prostate cancer that was more than 4 times greater (39). The results of a case-control study in Sweden that compared the calcium consumption of 526 men diagnosed with prostate cancer to that of 536 controls were similar (40). Neither study found calcium intake to be associated with an increased risk of total prostate cancer or non-advanced prostate cancer. More recently, another prospective study of U.S. physicians found that increased intake of calcium from dairy foods was associated with an increased risk of prostate cancer (41). Although this study did not examine supplement use, each 500 mg/day increase in calcium from dairy foods was associated with a 16% increase in the risk of prostate cancer (advanced and non-advanced). The physiologic mechanisms underlying the relationship between calcium intake and prostate cancer are not yet clear. High levels of dietary calcium may lead to decreased circulating levels of calcitriol, the active form of vitamin D. In experimental studies conducted in prostate cancer cell lines and animal models, calcitriol has been found to have protective effects. However, the findings of studies conducted in humans on serum calcitriol levels and prostate cancer risk have been much less consistent. 

Not all epidemiologic studies have demonstrated an association between calcium intake and prostate cancer. In total, 7 out of 14 case-control studies and 5 out of 9 prospective cohort studies have reported statistically significant positive associations between prostate cancer and some measure of dairy product consumption. Of those studies that have examined calcium intake, 3 out of 6 case-control studies and 2 out of 4 cohort studies reported statistically significant associations between prostate cancer and calcium intake (42). One Serbian case-control study found increased calcium intake to be associated with a decreased risk of prostate cancer (43). The lack of agreement among these studies suggests complex interactions among risk factors for prostate cancer. Until the relationship between calcium and prostate cancer is clarified, it is reasonable for men to consume a total of 1,000 to 1,200 mg/day of calcium (diet and supplements combined), which is the adequate intake level recommended by the Food and Nutrition Board of the Institute of Medicine (3).

Drug Interactions

Taking calcium supplements in combination with thiazide diuretics (e.g., hydrochlorthiazide) increases the risk of developing hypercalcemia due to increased reabsorption of calcium in the kidneys. High doses of supplemental calcium could increase the likelihood of abnormal heart rhythms in people taking digitalis (digoxin) for heart failure. Calcium supplements may also decrease the efficacy of calcium channel blockers. Calcium may decrease the absorption of tetracycline and quinolone class antibiotics, bisphosphonates, and levothyroxine, so it is advisable to separate doses of these medications and calcium rich foods or supplements by two hours. Use of H₂ blockers (e.g., cimetidine) and proton pump inhibitors (e.g. omeprazole) may decrease the absorption of calcium carbonate and calcium phosphate (36, 44).

Nutrient Interactions

The presence of calcium decreases iron absorption from nonheme sources (i.e., most supplements and food sources other than meat). However, up to 12 weeks of calcium supplementation has not been found to change iron nutritional status, probably due to a compensatory increase in iron absorption. Individuals taking iron supplements should take them two hours apart from calcium rich foods or supplements to maximize iron absorption. High calcium intakes in rats have produced relative magnesium deficiencies, but calcium intake was not found to affect magnesium retention in humans (1). Although, a number of studies did not find high calcium intakes to affect zinc absorption or zinc nutritional status, a recent study in 10 men and women indicated that 600 mg of calcium consumed with a meal decreased the absorption of zinc from that meal by 50% (45).

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