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Cancer of the prostate
Several epidemiological studies have found an association between high intakes of calcium, dairy foods or both and an increased risk of developing prostate cancer [68-74]. However, others have found only a weak relationship, no relationship, or a negative association between calcium intake and prostate cancer risk [75-78]. The authors of a meta-analysis of prospective studies concluded that high intakes of dairy products and calcium might slightly increase prostate cancer risk [79].

Interpretation of the available evidence is complicated by the difficulty in separating the effects of dairy products from that of calcium. But overall, results from observational studies suggest that total calcium intakes >1,500 mg/day or >2,000 mg/day may be associated with increased prostate cancer risk (particularly advanced and metastatic cancer) compared with lower amounts of calcium (500–1,000 mg/day [1,80]. Additional research is needed to clarify the effects of calcium and/or dairy products on prostate cancer risk and elucidate potential biological mechanisms.

Cardiovascular disease
Calcium has been proposed to help reduce cardiovascular disease (CVD) risk by decreasing intestinal absorption of lipids, increasing lipid excretion, lowering cholesterol levels in the blood, and promoting calcium influx into cells [1]. However, data from prospective studies of calcium's effects on CVD risk are inconsistent, and whether dietary calcium has different effects on the cardiovascular system than supplemental calcium is not clear. In the Iowa Women's Health Study, higher calcium intake from diet and/or supplements was associated with reduced ischemic heart disease mortality in postmenopausal women [81]. Conversely, in a cohort of older Swedish women, both total and dietary calcium intakes of 1,400 mg/day and higher were associated with higher rates of death from CVD and ischemic heart disease than intakes of 600–1,000 mg/day [82]. Other prospective studies have shown no significant associations between calcium intake and cardiac events or cardiovascular mortality [80]. Data for stroke are mixed, with some studies linking higher calcium intakes to lower risk of stroke, and others finding no associations or trends in the opposite direction [80,82].

Several recent studies have raised concerns about the safety of calcium supplements with respect to CVD. Xiao and colleagues reported that men who took more than 1,000 mg/day supplemental calcium had a 20% higher risk of total CVD death than men who did not take supplemental calcium, but supplemental calcium intake in women was unrelated to CVD mortality [83]. In a reanalysis of data from the Women's Health Initiative (WHI), Bolland and colleagues found that calcium supplements (1,000 mg/day) taken with or without vitamin D (400 IU/day) increased the risk of cardiovascular events in women who were not taking calcium supplements when they entered the study [84]. Other studies have also shown that people who take calcium supplements have an increased risk of cardiovascular events, including myocardial infarction [85-87] and coronary heart disease [88]. However, the authors of a 2013 analysis of WHI clinical trial data combined with data from the WHI observational study, which followed over 93,000 postmenopausal women for about 8 years, concluded that "there was little evidence for an adverse influence of calcium and vitamin D supplementation on the risk for myocardial infarction, coronary heart disease, total heart disease, stroke or total cardiovascular disease" [89].

Scientists hypothesize that any adverse effects of calcium supplementation on the cardiovascular system could be mediated through hypercalcemia which can occur when excessively high calcium intakes override normal homeostatic control of serum calcium levels [82]. Hypercalcemia has been associated with increased blood coagulation, vascular calcification, and arterial stiffness, thereby raising CVD risk [83,84,90,91]. High calcium intakes can also increase circulating levels of fibroblast growth factor 23, which is associated with an increased risk of cardiovascular events [82]. Supplemental calcium, in particular, causes an acute increase in serum calcium levels, and some researchers hypothesize that this abrupt change, rather than total calcium load, could be responsible for the observed adverse effects [84].

Many scientists have questioned the strength of the available evidence that links supplemental calcium intake with CVD risk, noting that researchers have only considered CVD outcomes in secondary analyses of trial data and these outcomes have not been the primary endpoint of any calcium supplementation trials to date [90,92]. In their 2012 review of prospective studies and randomized clinical trials, Wang and colleagues concluded that calcium intake from diet or supplements appears to have little or no effect on CVD risk but the available evidence does not allow for a definitive conclusion [90]. The possibility that calcium supplements might harm the cardiovascular system has become a topic of much debate within the scientific community and warrants further investigation.

Blood pressure and hypertension
Several clinical trials have demonstrated a relationship between increased calcium intakes and both lower blood pressure and risk of hypertension [93-95], although the reductions are inconsistent. In the Women's Health Study, calcium intake was inversely associated with risk of hypertension in middle-aged and older women [96]. However, other studies have found no association between calcium intake and incidence of hypertension [80]. The authors of a systematic review of the effects of calcium supplements for hypertension found any link to be weak at best, largely due to the poor quality of most studies and differences in methodologies [97].

Calcium's effects on blood pressure might depend upon the population being studied. In hypertensive subjects, calcium supplementation appears to lower systolic blood pressure by 2–4 mmHg, whereas in normotensive subjects, calcium appears to have no significant effect on systolic or diastolic blood pressure [80].

Other observational and experimental studies suggest that individuals who eat a vegetarian diet high in minerals (such as calcium, magnesium, and potassium) and fiber and low in fat tend to have lower blood pressure [48,98-101]. The Dietary Approaches to Stop Hypertension (DASH) study was conducted to test the effects of three different eating patterns on blood pressure: a control "typical" American diet; one high in fruits and vegetables; and a third diet high in fruits, vegetables, and low-fat dairy products. The diet containing dairy products resulted in the greatest decrease in blood pressure [102], although the contribution of calcium to this effect was not evaluated. Additional information and sample DASH menu plans are available on the National Heart, Lung, and Blood Institute Web site.

Kidney stones
Kidney stones in the urinary tract are most commonly composed of calcium oxalate. Some, but not all, studies suggest a positive association between supplemental calcium intake and the risk of kidney stones, and these findings were used as the basis for setting the calcium UL in adults [1]. In the Women's Health Initiative, postmenopausal women who consumed 1,000 mg of supplemental calcium and 400 IU of vitamin D per day for 7 years had a 17% higher risk of kidney stones than subjects taking a placebo [103]. The Nurses' Health Study also showed a positive association between supplemental calcium intake and kidney stone formation [104]. High intakes of dietary calcium, on the other hand, do not appear to cause kidney stones and may actually protect against developing them [1,104-107]. For most individuals, other risk factors for kidney stones, such as high intakes of oxalates from food and low intakes of fluid, probably play a bigger role than calcium intake [108].

Weight management
Several studies have linked higher calcium intakes to lower body weight or less weight gain over time [109-112]. Two explanations have been proposed. First, high calcium intakes might reduce calcium concentrations in fat cells by decreasing the production of two hormones (parathyroid hormone and an active form of vitamin D) that increase fat breakdown in these cells and discourage fat accumulation [111]. Secondly, calcium from food or supplements might bind to small amounts of dietary fat in the digestive tract and prevent its absorption [111,113,114]. Dairy products, in particular, might contain additional components that have even greater effects on body weight than their calcium content alone would suggest [115-120].

Despite these findings, the results from clinical trials have been largely negative. For example, dietary supplementation with 1,500 mg/day of calcium (from calcium carbonate) for 2 years was found to have no clinically significant effects on weight in 340 overweight and obese adults as compared with placebo [121]. Three reviews of published studies on calcium from supplements or dairy products on weight management came to similar conclusions [80,122,123]. A meta-analysis of 13 randomized controlled trials published in 2006 concluded that neither calcium supplementation nor increased dairy product consumption had a statistically significant effect on weight reduction [122]. More recently, a 2009 evidence report from the Agency for Healthcare Research and Quality concluded that, overall, clinical trial results do not support an effect of calcium supplementation on weight loss [80]. Also, a 2012 meta-analysis of 29 randomized controlled trials found no benefit of an increased consumption of dairy products on body weight and fat loss in long-term studies [123]. Overall, the results from clinical trials do not support a link between higher calcium intakes and lower body weight or weight loss.

Health Risks from Excessive Calcium

Excessively high levels of calcium in the blood known as hypercalcemia can cause renal insufficiency, vascular and soft tissue calcification, hypercalciuria (high levels of calcium in the urine) and kidney stones [1]. Although very high calcium intakes have the potential to cause hypercalcemia [82], it is most commonly associated with primary hyperparathyroidism or malignancy [1].

High calcium intake can cause constipation. It might also interfere with the absorption of iron and zinc, though this effect is not well established [1]. High intake of calcium from supplements, but not foods, has been associated with increased risk of kidney stones [1,103,104]. Some evidence links higher calcium intake with increased risk of prostate cancer, but this effect is not well understood, in part because it is challenging to separate the potential effect of dairy products from that of calcium [1]. Some studies also link high calcium intake, particularly from supplements, with increased risk of cardiovascular disease [82-88].

The Tolerable Upper Intake Levels (ULs) for calcium established by the Food and Nutrition Board are listed in Table 3 in milligrams (mg) per day. Getting too much calcium from foods is rare; excess intakes are more likely to be caused by the use of calcium supplements. NHANES data from 2003–2006 indicate that approximately 5% of women older than 50 years have estimated total calcium intakes (from foods and supplements) that exceed the UL by about 300–365 mg [1,6].

Interactions with Medications

Calcium supplements have the potential to interact with several types of medications. This section provides a few examples. Individuals taking these medications on a regular basis should discuss their calcium intake with their healthcare providers.

Calcium can decrease absorption of the following drugs when taken together: biphosphonates (to treat osteoporosis), the fluoroquinolone and tetracycline classes of antibiotics, levothyroxine, phenytoin (an anticonvulsant), and tiludronate disodium (to treat Paget's disease) [124-126].

Thiazide-type diuretics can interact with calcium carbonate and vitamin D supplements, increasing the risks of hypercalcemia and hypercalciuria [125].

Both aluminum- and magnesium-containing antacids increase urinary calcium excretion. Mineral oil and stimulant laxatives decrease calcium absorption. Glucocorticoids, such as prednisone, can cause calcium depletion and eventually osteoporosis when they are used for months [125].

Calcium and Healthful Diets

The federal government's 2010 Dietary Guidelines for Americans notes that "nutrients should come primarily from foods. Foods in nutrient-dense, mostly intact forms contain not only the essential vitamins and minerals that are often contained in nutrient supplements, but also dietary fiber and other naturally occurring substances that may have positive health effects. ...Dietary supplements...may be advantageous in specific situations to increase intake of a specific vitamin or mineral."

For more information about building a healthful diet, refer to the Dietary Guidelines for Americans and the U.S. Department of Agriculture's food guidance system, MyPlate.

The Dietary Guidelines for Americans describes a healthy diet as one that:

• Emphasizes a variety of fruits, vegetables, whole grains, and fat-free or low-fat milk and milk products.Many dairy products, such as milk, cheese, and yogurt, are rich sources of calcium. Some vegetables provide significant amounts of calcium, as do some fortified cereals and juices.
• Includes lean meats, poultry, fish, beans, eggs, and nuts.Tofu made with calcium salts is a good source of calcium (check the label), as are canned sardines and canned salmon with edible bones.
• Is low in saturated fats, trans fats, cholesterol, salt (sodium), and added sugars.Low-fat and nonfat dairy products provide amounts of calcium that are roughly similar to the amounts in their full-fat versions.
• Stays within your daily calorie needs.