Calcium is an essential mineral responsible for many physiological functions in the body. It is stored in the bones and helps maintain bone structure. Calcium also plays an important role in cell signaling and muscle contraction. Dietary sources of calcium include dairy products, dark greens, legumes, nuts and fish. Natural supplements are derived from minerals, oyster shells and occasionally corals.

The effects of calcium have been studied for a range of conditions including cardiovascular disease ^{(1) (2) (3) (4) (5)}, osteoporosis ⁽⁶⁾, bone density loss ⁽⁷⁾, fracture prevention ⁽⁸⁾, premenstrual syndrome ⁽⁹⁾, pre-eclampsia ^{(10) (11) (87)}, lead poisoning ⁽¹²⁾, and various cancers ^{(13) (14) (15)}.

Long-term calcium supplement use was reported to be associated with an increased risk of coronary artery calcification ⁽⁷⁷⁾. Some studies suggest that supplementation could lead to cardiovascular disease (CVD) ^{(1) (2) (3) (5)}, but findings remain debatable ^{(16) (17) (18)}. In a Women’s Health Initiative sub-study, calcium plus vitamin D supplementation and hormone therapy yielded greater reductions in LDL-C than either intervention alone or placebo ⁽⁸¹⁾; but supplementation did not always modify the effects of hormonal therapy on CVD events ⁽⁸⁸⁾. Calcium and vitamin D supplementation may also benefit postmenopausal women who do not have pre-existing risk factors such as coronary heart disease, diabetes, or hypertension ⁽¹⁹⁾; and large long-term studies in women did not find adverse cardiovascular associations with calcium supplementation ^(4) (20), but a meta analysis reported an increase in the risk of CVD ⁽⁹⁴⁾. High intake of supplements also increased cardiovascular mortality in men ⁽²¹⁾. Another study found supplementation to be associated with dementia in women following stroke ⁽⁷⁵⁾, but dietary intake of vitamin D and calcium were reported useful in maintaining cognitive performance in older females  ⁽⁹⁰⁾.

There is also conflicting evidence surrounding the benefits of calcium or calcium plus vitamin D supplements for bone health ^{(22) (23) (24) (42) (53) (82)}. The US Preventive Services Task Force reports did not find any associations between calcium plus vitamin D supplementation and reduced falls or fracture incidence in community-dwelling older adults without known deficiencies, osteoporosis, or history of fracture ^(83) (84). In postmenopausal women, neither dietary calcium ⁽²⁵⁾ nor calcium plus vitamin D supplements ⁽²⁶⁾ reduced risk of hip fracture, although the latter study found significant reductions at 7 years ⁽²⁷⁾. Subgroup analysis further suggested that supplementation along with estrogen therapy conferred additive protection against hip fractures ⁽²⁸⁾. However, there appears to be no preventive benefits with calcium and vitamin D supplementation for bone mineral density loss in breast cancer patients ⁽⁷⁾, in older adults ⁽⁷⁸⁾, or in healthy men ⁽⁷⁹⁾. But in a study of pediatric cancer survivors, hypocalcemia induced by standard osteoporotic medication was treated with continuous calcium supplementation ⁽⁹¹⁾. Calcium plus vitamin D were also reported to mitigate bone density loss associated with antiretroviral therapy in HIV patients ^(72) (92).

Definitive data are needed to determine the role of calcium in cancer prevention and treatment. Both dietary and supplemental forms were found to be linked with lower risk of colorectal cancer ^{(13) (29) (93)}, with dietary calcium shown to be beneficial in reducing the risk of incidence and recurrence of colorectal and advanced adenomas ⁽⁹⁵⁾. For men, calcium intake is associated with increased risk for prostate cancer ^(30) (31); a genetic disposition for high intestinal absorption of calcium among African-American men has also been noted ^(32) (33). Long-term studies suggest risks associated with calcium in prostate cancers are less strong when phosphorus intake is also considered ^(34) (35).

In women, studies on calcium plus vitamin D supplements for reduced risk yielded conflicting data for colorectal cancers ^(38) (85), all cancer types ^(36) (86), and mortality ^(26) (37). Other trials suggest benefits against hematologic ⁽⁸⁰⁾ but not invasive cancers ⁽³⁹⁾.

In general, the evidence is insufficient to assess benefits of calcium plus vitamin D supplementation for those receiving androgen deprivation therapy, aromatase inhibitors, or undergoing chemotherapy-induced menopause ^{(7) (43) (44)}. Patients should consult with their oncologists or oncology healthcare teams, especially since calcium supplements can interact with a number of prescription medications.

A proper diet to achieve a balance among nutrients including sodium, potassium, magnesium, calcium and vitamin D is important to affect risks for hypertension as well as cardiovascular and cerebrovascular events ⁽⁴⁰⁾. The risk-benefit ratio of supplementation is likely to vary, depending on dietary calcium intake, sex, age, ethnicity, and individual risks for cardiovascular disease and osteoporosis ^(41) (73). In individuals with normal calcium levels, genetic predisposition to higher serum levels does not affect bone mineral density nor protect against fractures ⁽⁸⁹⁾. Intake of high-dose calcium supplements (>1 g/day) can also increase the risk of ischemic stroke ⁽⁷⁶⁾, and calcium plus vitamin D supplementation may elevate the risk for kidney stones ^{(42) (48) (53) (84)}.