- Calcium is a major constituent of bones and teeth and also plays an essential role as second messenger in cell-signaling pathways. 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. (More information)
- The recommended dietary allowance (RDA) for calcium is 1,000-1,200 mg/day for adults. (More information)
- 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 prevent the progressive demineralization of bones later in life, which leads to osteoporosis, bone fragility, and an increased risk of fractures. (More information)
- 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. (More information)
- 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 300-600 mg/day) be given supplemental calcium starting in the 20th week of pregnancy. (More information)
- Prospective cohort studies have reported an association between higher calcium intakes and lower risk of developing colorectal cancer; however, large clinical trials of calcium supplementation are needed. (More information)
- Current available data suggest that adequate calcium intakes may play a role in body weight regulation and have therapeutic benefits in the management of moderate-to-severe premenstrual symptoms. (More information)
- Adequate calcium intake is critical for maintaining a healthy skeleton. Calcium is found in a variety of foods, including dairy products, tofu, beans, and vegetables of the kale family. Yet, content and bioavailability vary among foods, and certain drugs are known to adversely affect calcium absorption. (More information)
- 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. (More information)
- 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. (More information)
Calcium is the most abundant mineral in the human body. About 99% of the calcium in the body is found in bones and teeth, while the other 1% is found in the blood and soft tissue. Calcium concentrations in the blood and fluid surrounding the cells (extracellular fluid) must be maintained within a narrow concentration range for normal physiological functioning. The physiological functions of calcium are so vital to survival that the body will stimulate bone resorption (demineralization) to maintain normal blood calcium concentrations when calcium intake is inadequate. Thus, adequate intake of calcium is a critical factor in maintaining a healthy skeleton (1).
Calcium is a major structural element in bones and teeth. The mineral component of bone consists mainly of hydroxyapatite [Ca10(PO4)6(OH)2] crystals, which contain large amounts of calcium, phosphorus, and oxygen. Bone is a dynamic tissue that is remodeled throughout life. Bone cells called osteoclasts begin the process of remodeling by dissolving or resorbing bone. Bone-forming cells called osteoblasts then synthesize new bone to replace the bone that was resorbed. During normal growth, bone formation exceeds bone resorption. Osteoporosis may result when bone resorption chronically exceeds formation (1).
Calcium concentrations in the blood and fluid that surround cells are tightly controlled in order to preserve normal physiological function. A slight drop in blood calcium levels (e.g., in the case of inadequate calcium intake) is sensed by the parathyroid glands, resulting in their increased secretion of parathyroid hormone (PTH). Elevations in PTH rapidly decrease urinary excretion of calcium but increase urinary excretion of phosphorus and stimulate bone resorption, resulting in the release of bone mineral (calcium and phosphate) — actions that restore serum calcium concentrations. Although the action is not immediate, PTH also stimulates conversion of vitamin D to its active form (1,25-dihydroxyvitamin D; calcitriol) in the kidneys. Increased circulating 1,25-dihydroxyvitamin D in turn stimulates increased intestinal absorption of both calcium and phosphorus. Like PTH, 1,25-dihydroxyvitamin D stimulates the release of calcium from bone by activating osteoclasts (bone resorbing cells) and limits the urinary excretion of calcium by increasing its reabsorption in the kidneys. When blood calcium rises to normal levels, the parathyroid glands stop secreting PTH. Finally, acute changes in blood calcium concentrations do not seem to elicit the secretion of the phosphaturic hormone fibroblast growth factor 23 (FGF-23), which is produced by bone-forming cells (osteoblasts/osteocytes) in response to increases in phosphorus intake (see the article on Phosphorus) (2). While this complex system allows for rapid and tight control of blood calcium concentrations, it does so at the expense of the skeleton (1).
Calcium plays a role in mediating the constriction and relaxation of blood vessels (vasoconstriction and vasodilation), nerve impulse transmission, muscle contraction, and the secretion of hormones like insulin (1). Excitable cells, such as skeletal muscle and nerve cells, contain voltage-dependent calcium channels in their cell membranes that allow for rapid changes in calcium concentrations. For example, when a nerve impulse stimulates a muscle fiber to contract, calcium channels in the cell membrane open to allow calcium ions into the muscle cell. Within the cell, these calcium ions bind to activator proteins, which help release a flood of calcium ions from storage vesicles of the endoplasmic reticulum (ER) inside the cell. The binding of calcium to the protein troponin-c initiates a series of steps that lead to muscle contraction. The binding of calcium to the protein calmodulin activates enzymes that break down muscle glycogen to provide energy for muscle contraction. Upon completion of the action, calcium is pumped outside the cell or into the ER until the next activation (reviewed in 3).
Regulation of protein function
Calcium is necessary to stabilize a number of proteins, including enzymes, optimizing their activities. The binding of calcium ions is required for the activation of the seven "vitamin K-dependent" clotting factors in the coagulation cascade. The term, "coagulation cascade," refers to a series of events, each dependent on the other that stops bleeding through clot formation (see the article on Vitamin K).
Vitamin D is required for optimal calcium absorption (see Function or the article on Vitamin D). Several other nutrients (and non-nutrients) influence the retention of calcium by the body and may affect calcium nutritional status.
Dietary sodium is a major determinant of urinary calcium loss (1). High-sodium intake results in increased loss of calcium in the urine, possibly due to competition between sodium and calcium for reabsorption in the kidneys or by an effect of sodium on parathyroid hormone (PTH) secretion. Every 1-gram (g) increment in sodium (2.5 g of sodium chloride; NaCl salt) excreted by the kidneys has been found to draw about 26.3 milligrams (mg) of calcium into the urine (1). A study conducted in adolescent girls reported that a high-salt diet had a greater effect on urinary sodium and calcium excretion in White compared to Black girls, suggesting differences among ethnic groups (4). In adult women, each extra gram of sodium consumed per day is projected to produce an additional rate of bone loss of 1% per year if all of the calcium loss comes from the skeleton.
A number of cross-sectional and intervention studies have suggested that high-sodium intakes are deleterious to bone health, especially in older women (5). In particular, high-sodium intake in conjunction with low-calcium intake may be especially detrimental to bone health (6-8). A two-year longitudinal study in postmenopausal women found increased urinary sodium excretion (an indicator of increased sodium intake) to be associated with decreased bone mineral density (BMD) at the hip (9). Linear regression analysis estimated that BMD could be maintained by reducing sodium intake to recommended levels (2,300 mg/day) and by increasing calcium intake to 1,200 mg/day. A second longitudinal study in postmenopausal women found that habitual high-sodium intake (approximately 3,000 mg/day) was not detrimental to bone mineral density over three years of follow-up (10). Notably, the average calcium intake in this study population was 1,300 to 1,500 mg/day. Another study in 40 postmenopausal women found that adherence to a low-sodium diet (2 g/day) for six months was associated with significant reductions in sodium excretion, calcium excretion, and aminoterminal propeptide of type I collagen, a biomarker of bone resorption. Yet, these associations were only observed in women with elevated baseline urinary sodium excretions (11). Finally, in a randomized, placebo-controlled study in 60 postmenopausal women, potassium citrate supplementation has been found to prevent an increase in calcium excretion induced by the consumption of a high-sodium diet (≥5,000 mg/day of elemental sodium) for four weeks (12).
Increasing dietary protein intake enhances intestinal calcium absorption, as well as urinary calcium excretion (13). The RDA for protein is 46 grams (g)/day for adult women and 56 g/day for adult men; however, the average intake of protein in the US tends to be higher (about 70 g/day in adult women and over 100 g per day in adult men) (14). It was initially thought that high-protein diets may result in a negative calcium balance (when the sum of urinary and fecal calcium excretion becomes greater than calcium intake) and thus increase bone loss (15). However, most observational studies have reported either no association or positive associations between protein intake and bone mineral density in children, adults, and elderly subjects (reviewed in 16). The overall calcium balance appears to be unchanged by high dietary protein intake in healthy individuals (17), and current evidence suggests that increased protein intakes in those with adequate supplies of protein, calcium, and vitamin D do not adversely affect BMD or fracture risk (18).
Phosphorus, which is typically found in protein-rich food, tends to increase the excretion of calcium in the urine. Diets with low calcium-to-phosphorus ratios (Ca:P ≤0.5) have been found to increase parathyroid hormone (PTH) secretion and urinary calcium excretion (19, 20). Also, the intestinal absorption and fecal excretion of calcium and phosphorus are influenced by calcium-to-phosphorus ratios of ingested food. Indeed, in the intestinal lumen, calcium salts can bind to phosphorus to form complexes that are excreted in the feces. This forms the basis for using calcium salts as phosphorus binders to lower phosphorus absorption in individuals with kidney insufficiency (21). Increasing phosphorus intakes from cola soft drinks (high in phosphoric acid) and food additives (high in phosphates) may have adverse effects on bone health (22). At present, there is no convincing evidence that the dietary phosphorus levels experienced in the US adversely affect bone health. Yet, the substitution of large quantities of phosphorus-containing soft drinks for milk or other sources of dietary calcium may represent a serious risk to bone health in adolescents and adults (see the article on Phosphorus).
Caffeine in large amounts increases urinary calcium content for a short time. However, caffeine intakes of 400 mg/day did not significantly change urinary calcium excretion over 24 hours in premenopausal women when compared to a placebo (23). Although one observational study found accelerated bone loss in postmenopausal women with low calcium intake and two to three daily cups of coffee (24), another study reported no association between caffeine intake and bone loss in postmenopausal women (25). On average, one 8-ounce cup of coffee decreases calcium retention by only 2-3 mg (26).
A low blood calcium level (hypocalcemia) usually implies abnormal parathyroid function since the skeleton provides a large reserve of calcium for maintaining normal blood levels, especially in the case of low dietary calcium intake. Other causes of abnormally low blood calcium concentrations include chronic kidney failure, vitamin D deficiency, and low blood magnesium levels often observed in cases of severe alcoholism. Magnesium deficiency can impair parathyroid hormone (PTH) secretion by the parathyroid glands and lower the responsiveness of osteoclasts to PTH. Thus, magnesium supplementation is required to correct hypocalcemia in people with low serum magnesium concentrations (see the article on Magnesium). Chronically low calcium intakes in growing individuals may prevent the attainment of optimal peak bone mass. Once peak bone mass is achieved, inadequate calcium intake may contribute to accelerated bone loss and ultimately to the development of osteoporosis (see Disease Prevention) (1).
The Recommended Dietary Allowance (RDA)
Updated recommendations for calcium intake based on the optimization of bone health were released by the Food and Nutrition Board (FNB) of the Institute of Medicine in 2011 (13). The Recommended Dietary Allowance (RDA) for calcium is listed in Table 1 by life stage and gender.
Table 1. Recommended Dietary Allowance (RDA) for Calcium
||71 years and older
Osteoporosis is a skeletal disorder in which bone mass and strength are compromised, resulting in an increased risk of fracture. Sustaining a hip fracture is one of the most serious consequences of osteoporosis. Nearly one-third of those who sustain osteoporotic hip fractures enter nursing homes within a year following the fracture, and one person in four dies within one year of experiencing an osteoporotic hip fracture (27). Despite being a common diagnosis in postmenopausal women, osteoporosis also affects 4-6% of men over the age of 50 years (28).
Osteoporosis is a multifactorial disorder, and nutrition is only one factor contributing to its development and progression (29). Other factors that increase the risk of developing osteoporosis include, but are not limited to, increased age, female gender, estrogen deficiency, smoking, high alcohol intake (three or more drinks/day), metabolic disease (e.g., hyperthyroidism), and the use of certain medications (e.g., corticosteroids and anticonvulsants) (30). A predisposition to osteoporotic fracture is related to one's peak bone mass and to the rate of bone loss after peak bone mass has been attained. After adult height has been reached, the skeleton continues to accumulate bone until the third decade of life. Genetic factors exert a strong influence on peak bone mass, but lifestyle factors can also play a significant role. Strategies for reducing the risk of osteoporotic fracture include the attainment of maximal peak bone mass and the reduction of bone loss later in life. A number of lifestyle factors, including diet (especially calcium and protein intake) and physical activity, are amenable to interventions aimed at maximizing peak bone mass and limiting osteoporotic fracture risk (31).
Physical exercise is a lifestyle factor that has been associated with numerous health benefits and is likely to contribute to the prevention of osteoporosis and osteoporotic fracture. There is evidence to suggest that physical activity early in life contributes to the attainment of higher peak bone mass (31). Moreover, lifelong participation in physical activities in the presence of adequate calcium and vitamin D supply (from dietary sources and/or sunlight exposure) may have a modest effect on slowing the rate of bone loss later in life (32). Current National Osteoporosis Foundation guidelines include recommendations of regular muscle-strengthening and weight-bearing exercise to all postmenopausal women and men ages 50 and older (33). Although benefits in reducing bone loss might be limited, muscle-strengthening exercise, including weight training and other resistive exercises (e.g., yoga and Pilates) and weight-bearing exercise (e.g., walking, jogging, and stair climbing), may improve strength, posture, balance, and coordination, thus contributing to reduced risk of falls (33). One compilation of published calcium trials indicated that the beneficial skeletal effect of increased physical activity was achievable only at calcium intakes above 1,000 mg/day in women in late menopause (reviewed in 32).
The progressive loss of bone mineral density (BMD) leading to osteopenia (pre-osteoporosis) and osteoporosis is usually assessed by dual-energy x-ray absorptiometry (DEXA) at the hip and lumbar spine (34). Several randomized, placebo-controlled clinical trials have evaluated the effect of supplemental calcium in the preservation of BMD and the prevention of fracture risk in men and women ages 50 years and older. A meta-analysis of 24 studies, including over 40,000 older men and women, indicated that the supplementation of calcium alone or in combination with vitamin D was associated with a 0.54% reduction in BMD loss at the hip and a 1.19% reduction in BMD loss at the spine (35). A meta-analysis of 17 trials that reported on fracture risk found a 12% risk reduction associated with supplemental calcium with or without vitamin D (35). Additionally, one randomized, double-blind, placebo-controlled study has examined the effect of long-term calcium supplementation (>3 years) on fracture risk (36). Yet, the analysis of this five-year trial that included 1,460 postmenopausal women (mean age, 75 years) failed to find a reduction in fracture risk with the supplementation of 1,200 mg/day of calcium, possibly because 43% of participants did not adhere to their prescribed treatment (calcium or placebo) (36).
Because estrogen withdrawal significantly impairs intestinal absorption and renal reabsorption of calcium, the level of calcium requirement might depend on whether postmenopausal women receive hormone replacement therapy (32). The National Osteoporosis Foundation advises that adequate intake of calcium (1,000-1,200 mg/day) and vitamin D (800-1,000 IU/day) be included in the diet for all middle-aged men and women (33). The US Preventive Services Task Force recently conducted a meta-analysis of 11 randomized placebo-controlled trials that included 52,915 older people (of whom 69% were postmenopausal women) and reported that the supplementation of vitamin D (300-1,000 IU/day) and calcium (500-1,200 mg/day) for up to seven years resulted in a 12% reduction in the risk of any new fracture (37). However, there was no significant effect of vitamin D without calcium (37).
The role and effectiveness of vitamin D supplementation in strengthening bone and preventing fracture in older people remain controversial topics. The active form of vitamin D, 1,25-dihydroxyvitamin D, stimulates calcium absorption by promoting the synthesis of calcium-binding proteins in the intestine. While no amount of vitamin D can compensate inadequate total calcium intake, vitamin D insufficiency (defined as circulating concentrations of 25-hydroxyvitamin D below 20 ng/mL [50 nmol/L]) can lead to secondary hyperparathyroidism and an increased risk of osteoporosis (13, 38). Conversely, in postmenopausal women (ages 57-90 years) with adequate total calcium intakes (1,400 IU/day), serum 25-hydroxyvitamin D concentrations ranging from 20 ng/mL to 66 ng/mL had little effect on calcium absorption (only 6% increase over the range) (39). In a randomized, placebo-controlled trial, the supplementation of 1,000 IU/day of vitamin D to postmenopausal women (mean age, 77.2 years) for one year was found to significantly increase circulating 25-hydroxyvitamin D concentrations by 34% from baseline but failed to enhance calcium absorption in the presence of high total calcium intakes (dietary plus supplemental calcium corresponding to an average 2,100 mg/day) (40). This study also reported no significant difference in measures of BMD at the hip and total body between placebo- and vitamin D-treated women. In addition, the pooled analysis of seven randomized controlled trials, including 65,517 older individuals living in the community or in an institution, found that vitamin D (400-800 IU/day) could reduce the risk of any fracture only when combined with calcium (1,000 mg/day) (41). Interestingly, the results of a series of trials included in three recent meta-analyses (37, 42, 43) have suggested that supplemental vitamin D and calcium may have greater benefits in the prevention of fracture in institutionalized, older people who are also at increased risk of vitamin D deficiency and fractures compared to community dwellers (44, 45).
For more information about bone health and osteoporosis, see the article, Micronutrients and Bone Health, and visit the National Osteoporosis Foundation website.
Approximately 6% of women and 15% of men in industrialized countries will have a kidney stone during their lifetime. Most kidney stones are composed of calcium oxalate or calcium phosphate. Subjects with an abnormally high level of calcium in the urine (hypercalciuria) are at higher risk of developing kidney stones (a process called nephrolithiasis) (46). High urinary oxalate level is another risk factor for calcium oxalate stone formation. Most subjects with a history of kidney stones and/or idiopathic hypercalciuria have increased intestinal calcium absorption (47). Although it was initially recommended to limit dietary calcium intake in these patients, a number of prospective cohort studies have reported associations between lower total dietary calcium intake and increased risk of incident kidney stones (48-51). The prospective analyses of three large cohorts, including a total of 30,762 men and 195,865 women followed for a combined 56 years, have indicated that the risk of kidney stones was significantly lower in individuals in the highest versus lowest quintile of dietary calcium intake from dairy or nondairy sources (52). Additionally, a five-year randomized intervention study that enrolled 120 men with idiopathic hypercalciuria (mean age, 45 years) reported that those assigned to a low-calcium diet (approximately 400 mg/day) had a 51% higher risk of kidney stone recurrence compared to those on a normal-to-high calcium (1,200 mg/day), low animal-protein, low-salt diet (53).
Mechanisms by which increased dietary calcium might reduce the risk of incident kidney stones are not fully understood. An inverse relationship was reported between total calcium intake and intestinal calcium absorption in the recent cross-sectional analysis of a cohort of 5,452 postmenopausal women (47). Moreover, women with higher supplemental calcium intake and lower calcium absorption were less likely to report a history of kidney stones (47). Adequate calcium consumption may somehow reduce the absorption of dietary oxalate and lower urinary oxalate (54, 55). A recent small intervention study in 10 non-stone-forming young adults observed that the ingestion of large amounts of oxalate did not increase the risk of calcium oxalate stone occurrence in the presence of recommended level of dietary calcium (56).
However, a randomized, double-blind, placebo-controlled trial in 36,282 postmenopausal women reported that a combination of supplemental calcium (1,000 mg/day) and vitamin D (400 IU/day) was associated with a significantly increased incidence of self-reported kidney stones during a seven-year treatment period. More controlled trials may be necessary to determine whether supplemental calcium affects kidney stone risk (57). However, a systematic review of observational studies and randomized controlled trials that primarily reported on bone-related outcomes failed to find an effect of calcium supplementation on stone incidence (58). Further research is needed to verify whether osteoporosis treatment drugs (e.g., biphosphonates) rather than calcium supplements might influence the risk of stone occurrence (59).
Current data suggest that diets providing adequate dietary calcium and low levels of animal protein, oxalate, and sodium may benefit the prevention of stone recurrence in subjects with idiopathic hypercalciuria (60, 61).
Hypertensive disorders of pregnancy
Pregnancy-induced hypertensive disorders, including gestational hypertension, preeclampsia, and eclampsia, complicate approximately 10% of pregnancies and are a major health risk for pregnant women and their offspring (62). Gestational hypertension is defined as an abnormally high blood pressure that usually develops after the 20th week of pregnancy. Preeclampsia is characterized by poor placental perfusion and a systemic inflammation that may involve several organ systems, including the cardiovascular system, kidneys, liver, and hematological system (63). In addition to gestational hypertension, preeclampsia is associated with the development of severe swelling (edema) and the presence of protein in the urine (proteinuria). Eclampsia is the occurrence of seizures in association with the syndrome of preeclampsia and is a significant cause of maternal and perinatal mortality.
Although cases of preeclampsia are at high risk of developing eclampsia, one-quarter of women with eclampsia do not initially exhibit preeclamptic symptoms. Risk factors for preeclampsia include genetic predisposition, advanced maternal age, first pregnancies, multiple pregnancies (e.g., twins or triplets), obesity, diabetes, and some autoimmune diseases (63). While the pathogenesis of preeclampsia is not entirely understood, nutrition and especially calcium metabolism appear to play a role. Data from epidemiologic studies have suggested an inverse relationship between calcium intake during pregnancy and the incidence of preeclampsia (reviewed in 64). Impairment of calcium metabolism when circulating vitamin D concentration is low and/or when dietary calcium intake is inadequate may contribute to the risk of hypertension during pregnancy.
Secondary hyperparathyroidism (high PTH level) due to vitamin D deficiency in young pregnant women has been associated with high maternal blood pressure and increased risk of preeclampsia (65). The risk for elevated PTH concentration was also found to be increased in vitamin D-sufficient women with low calcium intakes (<480 mg/day) during pregnancy when compared with adequate-to-high calcium intakes (≥1,000 mg/day) (66). In addition, vitamin D deficiency may trigger hypertension through the inappropriate activation of the renin-angiotensin system (see the article on Vitamin D).
Potential beneficial effects of calcium in the prevention of preeclampsia have been investigated in several randomized, placebo-controlled studies. The most recent meta-analysis of 13 trials in 15,730 pregnant women found that calcium supplementation with at least 1,000 mg/day (mostly 1,500-2,000 mg/day) from about 20 weeks of pregnancy (34 weeks of pregnancy at the latest) was associated with significant reductions in the risk of high blood pressure, preeclampsia, and preterm birth (64). Greater risk reductions were reported among pregnant women at high risk of preeclampsia (5 trials; 587 women) or with low dietary calcium intake (8 trials; 10,678 women). Another recent meta-analysis of four randomized controlled trials in high-risk women indicated that lower doses of calcium supplementation (≤800 mg/day) with a co-treatment (i.e., vitamin D, linoleic acid, or aspirin) could also lower the risk of preeclampsia by 75% (67). Yet, based on the systematic review of high-quality randomized controlled trials, which used mostly high-dose calcium supplements, the World Health Organization (WHO) recently recommended that all pregnant women in areas of low-calcium intake (i.e., low-income countries with intakes around 300-600 mg/day) be given 1.5-2 g (1,500-2,000 mg)/day of elemental calcium from the 20th week of pregnancy (68).
Because excessive calcium supplementation may be harmful (see Safety), further research is required to verify whether calcium supplementation above the current IOM recommendation (1,000 mg/day for pregnant women, ages 19-50 years) would provide greater benefits to women at high risk of preeclampsia. Finally, the lack of effect of supplemental calcium on proteinuria (reported in two trials only) suggested that calcium supplementation from mid-pregnancy might be too late to oppose the genesis of preeclampsia (69, 70). A randomized, double-blind, placebo-controlled study is ongoing to evaluate the effect of calcium supplementation with 500 mg/day, starting before pregnancy and until the 20th week of pregnancy, on the risk of preeclampsia in high-risk women (71).
Colorectal cancer (CRC) is the most common gastrointestinal cancer and the second leading cause of cancer death in the US (72). CRC is caused by a combination of genetic and environmental factors, but the degree to which these two types of factors influence CRC risk in individuals varies widely. In individuals with familial adenomatous polyposis (FAP) or hereditary nonpolyposis colorectal cancer (HNPCC), the cause of CRC is almost entirely genetic, while modifiable lifestyle factors, including dietary habits, tobacco use, and physical activities, greatly influence the risk of sporadic (non hereditary) CRC.
Prospective cohort studies have consistently reported an inverse association between dairy food consumption and CRC risk. Experimental studies in cell culture and animal models have suggested plausible mechanisms underlying a role for calcium, a major nutrient in dairy products, in preventing CRC (73). In the multicenter European Prospective Investigation into Cancer and Nutrition (EPIC) prospective study of 477,122 individuals, followed for an average of 11 years, 4,513 CRC cases were documented (74). Intakes of milk, cheese, and yogurt, were inversely associated with CRC risk. The highest versus lowest quintile of total dairy intake (≥490 g/day vs. <134 g/day) was associated with a 23% lower risk of CRC. Similarly, CRC risk was 25% lower in those in the top versus bottom quintile of calcium intake from dairy food (≥839 mg/day vs. <308 mg/day). The 16-year follow-up of 41,403 women (ages 26-46 years at inclusion) from the prospective Nurses' Health Study II (NHS II) documented 2,273 diagnoses of colorectal adenomas (precancerous polyps). The analysis of the prospective cohort found that women with total calcium intake of 1,001-1,250 mg/day had a 76% lower risk of developing advanced adenomas (i.e., adenomas more likely to become malignant) compared to those with intakes equal to and below 500 mg/day (75). In addition, a dose-response analysis using data from 15 prospective studies (12,305 CRC cases among nearly 1,500,000 participants) estimated that an increase of 300 mg/day in total calcium intake was associated with an 8% reduction in CRC risk (76). Total daily intake of calcium ranged from 250 to 1,900 mg in the examined studies. Similarly, in the dose-response analysis of six prospective studies (8,839 CRC cases among 920,837 participants), CRC risk was 9% lower with a 300 mg/day increase in supplemental calcium (76).
However, the recent meta-analysis of seven randomized, double-blind, placebo-controlled studies found no evidence of an effect of calcium supplementation (≥500 mg/day) for a median period of 45 months on total cancer risk and CRC risk (77). In addition, the recent re-analysis of the Women's Health Initiative placebo-controlled trial failed to show a reduction in CRC risk in postmenopausal women supplemented with both vitamin D (400 IU/day) and calcium (1,000 mg/day) for seven years (78). Finally, the results of the meta-analysis of three randomized, placebo-controlled trials have suggested that calcium supplementation may reduce the risk of adenoma recurrence in subjects with a history of adenomas (79). At present, it is not clear whether calcium supplementation is beneficial in CRC prevention. Larger trials designed to assess primarily the effect of long-term calcium supplementation on the incidence of adenomas and/or CRC are needed before conclusions can be drawn.
Children who are chronically exposed to lead, even in small amounts, are more likely to develop learning disabilities, behavioral problems, and to have low IQs. Deficits in growth and neurological development may occur in the infants of women exposed to lead during pregnancy and lactation. In adults, lead toxicity may result in kidney damage and high blood pressure. Although the use of lead in paint products, gasoline, and food cans has been discontinued in the US, lead toxicity continues to be a significant health problem, especially in children living in urban areas (80).
In 2012, the US Centers for Disease Control and Prevention set the reference value for blood lead concentration at 5 micrograms per deciliter (μg/dL) to identify children at risk (81). Yet, there is no known blood lead concentration below which children are 100% safe. An early study of over 300 children in an urban neighborhood found that 49% of children ages 1 to 8 years had blood lead levels above the threshold of 10 μg/dL, indicating excessive lead exposure. In this study, only 59% of children ages 1-3 years and 41% of children ages 4-8 years met the recommended levels for calcium intakes (82).
Adequate calcium intake could be protective against lead toxicity in at least two ways. Increased dietary intake of calcium is known to decrease the gastrointestinal absorption of lead. Once lead enters the body it tends to accumulate in the skeleton, where it may remain for more than 20 years. Adequate calcium intake also prevents lead mobilization from the skeleton during bone demineralization. A study of circulating concentrations of lead during pregnancy found that women with inadequate calcium intake during the second half of pregnancy were more likely to have elevated blood lead levels, probably because of increased bone demineralization, leading to the release of accumulated lead into the blood (83). Lead in the blood of a pregnant woman is readily transported across the placenta resulting in fetal lead exposure at a time when the developing nervous system is highly vulnerable. In a randomized, double-blind, placebo-controlled study in 670 pregnant women (≤14 weeks' gestation) with average dietary calcium intakes of 900 mg/day, daily supplementation of 1,200 mg of calcium throughout the pregnancy period resulted in 8-14% reductions in maternal blood lead concentrations (84). Similar reductions in maternal lead concentrations in the blood and breast milk of lactating mothers supplemented with calcium were reported in earlier trials (85, 86). In postmenopausal women, factors known to decrease bone demineralization, including estrogen replacement therapy and physical activity, have been inversely associated with blood lead levels (87).
Overweight and obesity
High dietary calcium intake, usually associated with dairy product consumption, has been inversely related to body weight and central obesity in a number of cross-sectional studies (reviewed in 88). Cross-sectional baseline data analyses of a number of prospective cohort studies that were not designed and powered to examine the effect of calcium intake or dairy consumption on obesity or body fat have given inconsistent results (88). Yet, a meta-analysis of 18 cross-sectional and prospective studies predicted a reduction in body mass index (a relative measure of body weight; BMI) of 1.1 kg/m2 with an increase in calcium intake from 400 mg/day to 1,200 mg/day (88). In a placebo-controlled intervention study, 32 obese subjects were randomized to energy restriction regimens (500 kCal/day deficit) for 24 weeks with (1) a standard diet providing 400-500 mg/day of dietary calcium and a placebo supplement ("low calcium" diet), (2) a standard diet and 800 mg/day of supplemental calcium ("high calcium" diet), or (3) a high-dairy diet providing 1,200 mg/day of dietary calcium and a placebo supplement (89). Energy-restricted diets resulted in significant body weight and fat loss in all three groups. Yet, body weight and fat loss were significantly more reduced with the high-calcium diet compared to the standard diet, and further reductions were measured with the high-dairy diet compared to both high-calcium and low-calcium diets. These results suggested that while calcium intake may play a role in body weight regulation, additional benefits might be attributable to other bioactive components of dairy products, such as proteins, fatty acids, and branched chain amino acids.
Yet, several mechanisms have been proposed to explain the potential impact of calcium on body weight (reviewed in 88). The most cited mechanism is based on studies in the agouti mouse model showing that low-calcium intakes, through increasing circulating parathyroid hormone (PTH) and vitamin D, could stimulate the accumulation of fat (lipogenesis) in adipocytes (fat cells) (90). Conversely, higher intakes of calcium may reduce fat storage, stimulate the breakdown of lipids (lipolysis), and drive fat oxidation. A recent meta-analysis of randomized controlled trials estimated that high (1,300 mg/day) versus low (488 mg/day) calcium intake for a minimum of seven days increased fat oxidation by 11% (91). However, a double-blind, placebo-controlled, randomized, cross-over trial in 10 low-calcium consuming overweight or obese individuals reported that the supplementation with 800 mg/day of calcium for 5 weeks failed to modify the expression of key factors involved in fat metabolism (92). Moreover, while the model suggests a role for vitamin D in lipogenesis (fat storage), human studies have shown that vitamin D deficiency — rather than sufficiency — is often associated with obesity, and supplemental vitamin D might be effective in lowering body weight when caloric restriction is imposed (93, 94). Another mechanism suggests that high-calcium diets may limit dietary fat absorption in the intestine and increase fecal fat excretion. Indeed, in the gastrointestinal tract, calcium may trap dietary fat into insoluble calcium soaps of fatty acids that are then excreted (95). In addition, despite very limited evidence, it has also been proposed that calcium might be involved in regulating appetite and energy intake (96). Finally, a recent meta-analysis of 29 randomized controlled trials in 2,441 participants (median age, 41.4 years) found that calcium supplementation was only associated with body weight and fat loss in short-term studies (<1 year) that used energy-restricted diets (97). At present, additional research is warranted to examine the effect of calcium intake on fat metabolism, as well as its potential benefits in the management of body weight with or without caloric restriction (98).
Premenstrual Syndrome (PMS)
PMS refers to a cluster of symptoms, including but not limited to fatigue, irritability, moodiness/depression, fluid retention, and breast tenderness, that begins sometime after ovulation (mid-cycle) and subsides with the onset of menstruation (the monthly period) (99). A severe form of PMS called premenstrual dysphoric disorder (PMDD) has been described in 3-8% of women of childbearing age. PMDD interferes with normal functioning, affecting daily activities and relationships (100).
Low dietary calcium intakes have been linked to PMS in early reports, and supplemental calcium has been shown to decrease symptom severity (101). In a randomized, double-blind, placebo-controlled clinical trial of 466 women with moderate-to-severe premenstrual symptoms, supplemental calcium (1,200 mg/day) for three menstrual cycles was associated with a 48% reduction in total symptom scores, compared to a 30% reduction observed in the placebo group (102). Similar positive effects were reported in earlier double-blind, placebo-controlled, cross-over trials that administered 1,000 mg of calcium daily (103, 104). A nested case-control study within the Nurses' Health Study II (NHS II) found that women in the highest quintile of dietary (but not supplemental) calcium intake (median of 1,283 mg/day) had a 30% lower risk of developing PMS compared to those in the lowest quintile (median of 529 mg/day). Similarly, women in the highest versus lowest quintile of skim or low-fat milk intake (≥4 servings/day vs. ≤1 serving/week) had a 46% lower risk of PMS (105). Current available data indicates that daily calcium intakes of 1,000-1,200 mg from food and/or supplements have therapeutic benefits in women diagnosed with PMS or PMDD (100, 106).
The relationship between calcium intake and blood pressure has been investigated extensively over the past decades. A meta-analysis of 23 large observational studies conducted in different populations worldwide found a reduction in systolic blood pressure of 0.34 millimeters of mercury (mm Hg) per 100 mg of calcium consumed daily and a reduction in diastolic blood pressure of 0.15 mm Hg per 100 mg calcium (107). In the DASH (Dietary Approaches to Stop Hypertension) study, 549 people were randomized to one of three diets for eight weeks: (1) a control diet that was low in fruit, vegetables, and dairy products; (2) a diet rich in fruit (~5 servings/day) and vegetables (~3 servings/day); and (3) a combination diet rich in fruit and vegetables, as well as low-fat dairy products (~3 servings/day) (108). The combination diet represented an increase of about 800 mg of calcium/day over the control and fruit/vegetable-rich diets for a total of about 1,200 mg of calcium/day. Overall, the reduction in systolic blood pressure was greater with the combination diet than with the fruit/vegetable diet or the control diet. Among participants diagnosed with hypertension, the combination diet reduced systolic blood pressure by 11.4 mm Hg and diastolic pressure by 5.5 mm Hg more than the control diet, while the reduction for the fruit/vegetable diet was 7.2 mm Hg for systolic and 2.8 mm Hg for diastolic blood pressure compared to the control diet (109). This research suggested that calcium intake at the recommended level (1,000-1,200 mg/day) may be helpful in preventing and treating moderate hypertension (110).
Yet, two large systematic reviews and meta-analyses of randomized controlled trials have examined the effect of calcium supplementation on blood pressure compared to placebo in either normotensive or hypertensive individuals (111, 112). Neither of the analyses reported any significant effect of supplemental calcium on blood pressure in normotensive subjects. A small but significant reduction in systolic blood pressure, but not in diastolic blood pressure, was reported in participants with hypertension. Of note, calcium supplementation in these randomized controlled trials ranged from 400-2,200 mg/day, with 1,000-1,500 mg/day being the more common dosages. A more recent meta-analysis of 13 randomized controlled studies in 485 individuals with elevated blood pressure found a significant reduction of 2.5 mm Hg in systolic blood pressure but no change in diastolic blood pressure with calcium supplementation (113). The modest effect of calcium on blood pressure needs to be confirmed in larger, high-quality, well-controlled trials before any recommendation is made regarding the management of hypertension. Finally, a recent review of the literature on the effect of high-calcium intake (dietary and supplemental) in postmenopausal women found either no reduction or mild and transient reductions in blood pressure (114).
More information about the DASH diet is available from the National Institutes of Health (NIH).
Total dietary intakes of calcium in the US are well below the RDA for every age and gender group, especially in youth and women. Only 23% of boys and 15% of girls ages 9 to 13 years are estimated to meet the current recommendations. Also, about one-third of women and two-thirds of men ages 19-30 years meet the RDA (115). Dairy foods provide 75% of the calcium in the American diet. However, it is typically during the most critical period for peak bone mass development that adolescents tend to replace milk with soft drinks (116). Dairy products represent rich and absorbable sources of calcium, but certain vegetables and grains also provide calcium.
However, the bioavailability of the calcium must be taken into consideration. The calcium content in calcium-rich plants in the kale family (broccoli, bok choy, cabbage, mustard, and turnip greens) is as bioavailable as that in milk; however, some food components have been found to inhibit the absorption of calcium. Oxalic acid, also known as oxalate, is the most potent inhibitor of calcium absorption and is found at high concentrations in spinach and rhubarb and somewhat lower concentrations in sweet potatoes and dried beans. Phytic acid (phytate) is a less potent inhibitor of calcium absorption than oxalate. Yeast possess an enzyme (phytase) that breaks down phytate in grains during fermentation, lowering the phytate content of breads and other fermented foods. Only concentrated sources of phytate, such as wheat bran or dried beans, substantially reduce calcium absorption (117).
Additional dietary constituents may affect calcium absorption (see Nutrient interactions). Table 2 lists a number of calcium-rich foods, along with their calcium content. For more information on the nutrient content of foods, search the USDA food composition database.
Table 2. Some Food Sources of Calcium
|Tofu prepared with calcium sulfate (raw)
|Yogurt, plain, low-fat
|White beans (cooked)
|Chinese cabbage (Bok choy/Pak choi, cooked)
|Pinto beans (cooked)
|Red beans (cooked)
Most experts recommend obtaining as much calcium as possible from food because calcium in food is accompanied by other important nutrients that assist the body in utilizing calcium. However, calcium supplements may be necessary for those who have difficulty consuming enough calcium from food. No multivitamin/mineral tablet contains 100% of the recommended daily value (DV) for calcium because it is too bulky, and the resulting pill would be too large to swallow. The "Supplement Facts" label, required on all supplements marketed in the US, lists the calcium content of the supplement as elemental calcium. Calcium preparations used as supplements include calcium carbonate, calcium citrate, calcium citrate malate, calcium lactate, and calcium gluconate. To determine which calcium preparation is in your supplement, you may have to look at the ingredient list. Calcium carbonate is generally the most economical calcium supplement. To maximize absorption, take no more than 500 mg of elemental calcium at one time. Most calcium supplements should be taken with meals, although calcium citrate and calcium citrate malate can be taken anytime. Calcium citrate is the preferred calcium formulation for individuals who lack stomach acids (achlorhydria) or those treated with drugs that limit stomach acid production (H2 blockers and proton-pump inhibitors) (reviewed in 118).
Lead in calcium supplements
Several decades ago, concern was raised regarding lead concentrations in calcium supplements obtained from natural sources (oyster shell, bone meal, dolomite) (119). In 1993, investigators found measurable quantities of lead in most of the 70 different preparations they tested (120). Since then, manufacturers have reduced the amount of lead in calcium supplements to less than 0.5 micrograms (μg)/1,000 mg of elemental calcium (121). The US Food and Drug Administration (FDA) has developed provisional total tolerable intake levels (PTTI) for lead for specific age and sex groups (122). Because lead is so widespread and long lasting, no one can guarantee entirely lead-free food or supplements. A study found measurable lead in 8 out of 21 supplements, in amounts averaging 1 to 2 μg/1,000 mg of elemental calcium, which is below the tolerable limit of 7.5 μg/1,000 mg of elemental calcium (123). A more recent survey of 324 multivitamin/mineral supplements labeled for use in children or women found that most supplements would result in lead exposure ranging from 1-4% of the PTTI (124).
Calcium inhibits intestinal absorption of lead, and adequate calcium intake is protective against lead toxicity, so trace amounts of lead in calcium supplementation may pose less of a risk of excessive lead exposure than inadequate calcium consumption. While most calcium sources today are relatively safe, look for supplements approved or certified by independent testing (e.g., US Pharmacopeia, ConsumerLab.com) (118), follow label instructions, and avoid large doses of supplemental calcium (≥1,500 mg/day).
Malignancy and primary hyperparathyroidism are the most common causes of elevated calcium concentrations in the blood (hypercalcemia) (125). Hypercalcemia has not been associated with the over consumption of calcium occurring naturally in food. Hypercalcemia has been initially reported with the consumption of large quantities of calcium supplements 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 alkali). This condition is termed calcium-alkali syndrome (formerly known as milk-alkali syndrome) and has been associated with calcium supplement levels from 1.5 to 16.5 g/day for 2 days to 30 years. Since the treatment for peptic ulcers has evolved and because of the widespread use of over-the-counter calcium supplements, the demographic of this syndrome has changed in that those at greater risk are now postmenopausal women, pregnant women, transplant recipients, patients with bulimia, and patients on dialysis, rather than men with peptic ulcers (reviewed in 126). Mild hypercalcemia may be without symptoms or may result in loss of appetite, nausea, vomiting, constipation, abdominal pain, fatigue, frequent urination (polyuria), and hypertension (125). More severe hypercalcemia may result in confusion, delirium, coma, and if not treated, death (1).
In 2011, the Food and Nutrition Board of the Institute of Medicine updated the tolerable upper intake level (UL) for calcium (13). The UL is listed in Table 3 by age group.
Table 3. Tolerable Upper Intake Level (UL) for Calcium
|Infants 0-6 months
|Infants 6-12 months
|Children 1-8 years
|Children 9-13 years
|Adolescents 14-18 years
|Adults 19-50 years
|Adults 51 years and older
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 absorption of calcium in the intestine or increased excretion by the kidneys (13). Overall, increased dietary calcium intake has been associated with a decreased risk of kidney stones (see Kidney stones). Concerns have also been raised regarding the risks of prostate cancer and vascular disease with high intakes of calcium.
Do high calcium intakes increase the risk for prostate cancer?
Several epidemiological studies have raised concern that high dairy intakes are associated with increased risk of prostate cancer (127-129). Prostate cancer is the second most common cancer in men worldwide (130). A recent analysis of a prospective cohort study (2,268 men followed for nearly 25 years) conducted in Iceland, a country with a high incidence of prostate cancer, found a positive association between the consumption of milk (at least once daily) during the adolescence and developing prostate cancer later in life (131). Another large prospective cohort study in the US followed 21,660 male physicians for 28 years and found that men with daily skim or low-fat milk intake of at least 237 mL (8 oz) had a higher risk of developing prostate cancer compared to occasional consumers (132). The risk of low-grade, early-stage prostate cancer was associated with higher intake of skim milk, and the risk of developing fatal prostate cancer was linked to the regular consumption of whole milk (132).
In a cohort of 3,918 male health professionals diagnosed with prostate cancer, 229 men died of prostate cancer and 69 developed metastasized prostate cancer during a median follow-up of 7.6 years (133). The risk of prostate cancer death was found to be increased in men with high (>4 servings/week) versus low (≤3 servings/month) intakes of whole milk. Yet, no increase in risk of prostate cancer-related mortality was associated with consumption of skim and low-fat milk, total milk, low-fat dairy products, full-fat dairy products, or total dairy products (133). There is some evidence to suggest that milk consumption may result in higher circulating concentrations of insulin-like growth factor-I (IGF-I), a protein known to regulate cell proliferation (134). Circulating IGF-I concentrations have been positively correlated to the risk of developing prostate cancer in a recent meta-analysis of observational studies (135). Milk-borne IGF-I, as well as dairy proteins and calcium, may contribute to increasing circulating IGF-I in milk consumers (134). In the large EPIC study, which examined the consumption of dairy products in relation to cancer in 142,520 men, the risk of prostate cancer was found to be significantly higher in those in the top versus bottom quintile of both protein and calcium intakes from dairy foods (136). Another mechanism underlying the potential relationship between calcium intake and prostate cancer proposed that high levels of dietary calcium may lower circulating concentrations of 1,25-dihydroxyvitamin D, the active form of vitamin D, thereby suppressing vitamin D-mediated cell differentiation (137). However, epidemiological studies have provided little support for an association between vitamin D status and prostate cancer risk (reviewed in 138).
In a multicenter, double-blind, placebo-controlled trial, 672 healthy men (mean age of 61.8 years) were randomized to daily calcium supplementation (1,200 mg) for four years. While no increase in the risk for prostate cancer has been reported during a 10.3-year follow-up, calcium supplementation resulted in a significant risk reduction in the period spanning from two years after treatment started to two years after treatment ended (139). In a review of the literature published in 2009, the US Agency for Healthcare Research and Quality indicated that not all epidemiological studies found an association between calcium intake and prostate cancer (140). The review reported that 6 out of 11 observational studies failed to find statistically significant positive associations between prostate cancer and calcium intake. Yet, in five studies, daily intakes of 921-2,000 mg of calcium were found to be associated with an increased risk of developing prostate cancer when compared to intakes ranging from 455 to 1,000 mg/day (140). Inconsistencies among studies suggest complex interactions between the risk factors for prostate cancer, as well as reflect the difficulties of assessing the effect of calcium intake in free-living individuals. For example, the fact that individuals with higher dairy and/or calcium intakes were found to be more likely to be engaged in healthy lifestyles or more keen to seek medical attention can mitigate the statistical significance of an association with prostate cancer risk (141). 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 recommended by the Food and Nutrition Board of the Institute of Medicine (see RDA) (13).
Do calcium supplements increase the risk for cardiovascular disease?
Several observational studies and randomized controlled trials have raised concerns regarding the potential adverse effects of calcium supplements on cardiovascular risk. The analysis of data from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) prospective study found that users of calcium supplements amongst 10,555 Finnish women (ages 52-62 years) had a 14% greater risk of developing coronary artery disease compared to non-supplement users during a mean follow-up of 6.75 years (142). The prospective study of 23,980 participants (35-64 years old) of the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition cohort (EPIC-Heidelberg) observed that supplemental calcium intake was positively associated with the risk of myocardial infarction (heart attack) but not with the risk of stroke or cardiovascular disease (CVD)-related mortality after a mean follow-up of 11 years (143). Yet, the use of calcium supplements (≥400 mg/day vs. 0 mg/day) was associated with an increased risk of CVD-related mortality in 219,059 men, but not in 169,170 women, included in the National Institute of Health (NIH)-AARP Diet and Health study and followed for a mean period of 12 years. CVD mortality in men was also found to be significantly higher with total (dietary plus supplemental) calcium intakes of 1,500 mg/day and above (144).
The secondary analyses of two randomized placebo-controlled trials initially designed to assess the effect of calcium on bone health outcomes also suggested an increased risk of CVD in participants daily supplemented with 1,000 mg of calcium for five to seven years (145, 146). In the Auckland Calcium Study of 1,471 healthy postmenopausal women (ages ≥55 years), calcium supplementation resulted in increased risks of myocardial infarction and of a composite cardiovascular endpoint, including myocardial infarction, stroke, or sudden death (145). The analysis of data from 36,282 healthy postmenopausal women randomized to receive a combination of calcium (1,000 mg/day) and vitamin D (400 IU/day) or a placebo in the Women's Health Initiative/Calcium-Vitamin D supplementation study (WHI/CaD study) initially reported no adverse effect on any cardiovascular endpoints with calcium (and vitamin D) compared to placebo (147). A re-analysis was performed with data from 16,718 women who did not take personal calcium supplements (outside protocol) during the five-year study (146). Although criticized on the approach taken (148, 149), the investigators estimated that women supplemented with calcium and vitamin D had a 16% increased risk of clinical myocardial infarction or stroke and a 21% increased risk of myocardial infarction compared to those who received a placebo (146). However, in another randomized, double-blind, placebo-controlled trial — the Calcium Intake Fracture Outcome (CAIFOS) study — in elderly women (median age, 75.1 years), the supplementation of 1,200 mg/day of calcium for five years was not found to increase the risk of vascular disease or related mortality (150). The WHI/CaD data re-analysis also failed to show an increased risk of mortality due to myocardial infarction or coronary artery disease with calcium therapy (145). Also, after an additional follow-up of 4.5 years at the end of the treatment period in the CAIFOS trial, the investigators reported fewer cases of heart failure-related deaths with supplemental calcium compared to placebo (150). In another randomized, placebo-controlled trial of calcium and/or vitamin D3 (RECORD trial), the evaluation of the effect of 1,000 mg/day of calcium (alone or with 800 IU/day of vitamin D) reported no significant increase in the rate of mortality due to vascular disease in 5,292 participants ages 70 years and older (151). A recent cross-sectional analysis of the Third National Health and Nutrition Examination Survey (NHANES III) evaluated the association between calcium intakes and cardiovascular mortality in 18,714 adults with no history of heart disease. No evidence of an association was observed between dietary calcium intake, supplemental calcium intake, or total calcium intake and cardiovascular mortality in either men or women (152).
A few prospective studies have reported positive correlations between high calcium concentrations in the blood and increased rates of cardiovascular events (153, 154). Because supplemental calcium may have a greater effect than dietary calcium on circulating calcium concentrations (see Toxicity), it has been speculated that the use of calcium supplements might promote vascular calcification — a major risk factor for cardiovascular events — by raising calcium serum concentrations. In 1,471 older women from the Auckland Calcium Study and 323 healthy older men from another randomized, placebo-controlled trial of daily calcium supplementation (600 mg or 1,200 mg) for two years, serum calcium concentrations were found to be positively correlated with abdominal aortic calcification or coronary artery calcification (155). However, there was no effect of calcium supplementation on measures of vascular calcification scores in men or women. Data from 1,201 participants of the Framingham Offspring study were also used to assess the relationship between calcium intake and vascular calcification. Again, no association was found between coronary calcium scores and total, dietary, or supplemental calcium intake in men or women (156). An assessment of atherosclerotic lesions in the carotid artery wall of 1,103 participants in the CAIFOS trial was also conducted after three years of supplementation (157). When compared with placebo, calcium supplementation showed no effect on carotid artery intimal medial thickness (CIMT) and carotid atherosclerosis. Yet, carotid atherosclerosis (but not CIMT) was significantly reduced in women in the highest versus lowest tertile of total (diet and supplements) calcium intakes (≥1,795 mg/day vs. <1,010 mg/day) (157).
The most recent meta-analysis of 18 randomized clinical trials, including a total of 63,563 postmenopausal women, found no evidence of an increased risk for coronary artery disease and all-cause mortality with calcium (≥500 mg/day) supplementation for at least one year (158). Because these clinical trial data are limited to analyses of secondary endpoints, meta-analyses should be interpreted with caution. There is a need for studies designed to examine the effect of calcium supplements on CVD risk as a primary outcome before definite conclusions can be drawn. At present, experts support the use of supplemental calcium for generally healthy individuals who do not consume enough calcium-rich food to meet the current daily recommendations (159).
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 (160). Calcium, when provided intravenously, may decrease the efficacy of calcium channel blockers (161). However, dietary and oral supplemental calcium do not appear to affect the action of calcium channel blockers (162). Calcium may decrease the absorption of tetracycline, quinolone class antibiotics, bisphosphonates, and levothyroxine; therefore, it is advisable to separate doses of these medications and calcium-rich food 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 (reviewed in 163). Glucocorticoid therapy may affect intestinal calcium absorption and increase the risk for osteoporosis (164). Low and high doses of the glucocorticoid prednisone — prescribed to prevent the rejection of transplanted organs — have been associated with low blood calcium concentrations and bone loss, especially bone loss caused by a reduction in bone formation (165, 166).
The presence of calcium decreases iron absorption from nonheme sources (i.e., most supplements and food sources other than meat). However, calcium supplementation up to 12 weeks has not been found to change iron nutritional status, probably due to a compensatory increase in iron absorption (1). Individuals taking iron supplements should take them two hours apart from calcium-rich food or supplements to maximize iron absorption. Although high calcium intakes have not been associated with reduced zinc absorption or zinc nutritional status, an early study in 10 men and women found that 600 mg of calcium consumed with a meal halved the absorption of zinc from that meal (see the article on Zinc) (167).
Linus Pauling Institute Recommendation
The Linus Pauling Institute supports the recommended dietary allowance (RDA) set by the Food and Nutrition Board of the Institute of Medicine. Following these recommendations should provide adequate calcium to promote skeletal health and may also decrease the risks of some chronic diseases.
Children and adolescents (9-18 years)
To promote the attainment of maximal peak bone mass, children and adolescents should consume a total (diet plus supplements) of 1,300 mg/day of calcium.
Adults (women: 19-50 years; men: 19-70 years)
After adult height has been reached, the skeleton continues to accumulate bone until the third decade of life when peak bone mass is attained. To promote the attainment of maximal peak bone mass and to minimize bone loss later in life, adult women (50 years of age and younger) and adult men (70 years of age and younger) should consume a total (diet plus supplements) of 1,000 mg/day of calcium.
Older women (>50 years)
To minimize bone loss, postmenopausal women should consume a total (diet plus supplements) of 1,200 mg/day of calcium. Taking a multivitamin/mineral supplement containing at least 10 μg (400 IU)/day of vitamin D will help to ensure adequate calcium absorption (see the article on Vitamin D).
Older men (>70 years)
To minimize bone loss, older men should consume a total (diet plus supplements) of 1,200 mg/day of calcium. Taking a multivitamin/mineral supplement containing at least 10 μg (400 IU)/day of vitamin D will help to ensure adequate calcium absorption (see the article on Vitamin D).
Pregnant and breast-feeding women
Pregnant and breast-feeding adolescents (<19 years) should consume a total of 1,300 mg/day of calcium, while pregnant and breast-feeding adults (≥19 years) should consume a total of 1,000 mg/day of calcium.
Authors and Reviewers
Originally written in 2001 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University
Updated in April 2003 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University
Updated in October 2007 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University
Updated in August 2014 by:
Barbara Delage, Ph.D.
Linus Pauling Institute
Oregon State University
Reviewed in November 2014 by:
Connie M. Weaver, Ph.D.
Distinguished Professor and Head of Foods and Nutrition
Last updated 8/4/15 Copyright 2001-2017 Linus Pauling Institute
1. Weaver CM. Calcium. In: Erdman JJ, Macdonald I, Zeisel S, eds. Present Knowledge in Nutrition. 10th ed: John Wiley & Sons, Inc.; 2012.
2. Wesseling-Perry K, Wang H, Elashoff R, Gales B, Juppner H, Salusky IB. Lack of FGF23 response to acute changes in serum calcium and PTH in humans. J Clin Endocrinol Metab. 2014:99(10):E1951-E1956. (PubMed)
3. Clapham DE. Calcium signaling. Cell. 2007;131(6):1047-1058. (PubMed)
4. Wigertz K, Palacios C, Jackman LA, et al. Racial differences in calcium retention in response to dietary salt in adolescent girls. Am J Clin Nutr. 2005;81(4):845-850. (PubMed)
5. Frassetto LA, Morris RC, Jr., Sellmeyer DE, Sebastian A. Adverse effects of sodium chloride on bone in the aging human population resulting from habitual consumption of typical American diets. J Nutr. 2008;138(2):419S-422S. (PubMed)
6. Heaney RP. Role of dietary sodium in osteoporosis. J Am Coll Nutr. 2006;25(3 Suppl):271S-276S. (PubMed)
7. Bedford JL, Barr SI. Higher urinary sodium, a proxy for intake, is associated with increased calcium excretion and lower hip bone density in healthy young women with lower calcium intakes. Nutrients. 2011;3(11):951-961. (PubMed)
8. Park SM, Jee J, Joung JY, et al. High dietary sodium intake assessed by 24-hour urine specimen increase urinary calcium excretion and bone resorption marker. J Bone Metab. 2014;21(3):189-194. (PubMed)
9. Devine A, Criddle RA, Dick IM, Kerr DA, Prince RL. A longitudinal study of the effect of sodium and calcium intakes on regional bone density in postmenopausal women. Am J Clin Nutr. 1995;62(4):740-745. (PubMed)
10. Ilich JZ, Brownbill RA, Coster DC. Higher habitual sodium intake is not detrimental for bones in older women with adequate calcium intake. Eur J Appl Physiol. 2010;109(4):745-755. (PubMed)
11. Carbone LD, Barrow KD, Bush AJ, et al. Effects of a low sodium diet on bone metabolism. J Bone Miner Metab. 2005;23(6):506-513. (PubMed)
12. Sellmeyer DE, Schloetter M, Sebastian A. Potassium citrate prevents increased urine calcium excretion and bone resorption induced by a high sodium chloride diet. J Clin Endocrinol Metab. 2002;87(5):2008-2012. (PubMed)
13. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, D.C.: The National Academies Press; 2011. (The National Academies Press)
14. Fulgoni VL, 3rd. Current protein intake in America: analysis of the National Health and Nutrition Examination Survey, 2003-2004. Am J Clin Nutr. 2008;87(5):1554S-1557S. (PubMed)
15. Ince BA, Anderson EJ, Neer RM. Lowering dietary protein to US Recommended dietary allowance levels reduces urinary calcium excretion and bone resorption in young women. J Clin Endocrinol Metab. 2004;89(8):3801-3807. (PubMed)
16. Calvez J, Poupin N, Chesneau C, Lassale C, Tome D. Protein intake, calcium balance and health consequences. Eur J Clin Nutr. 2012;66(3):281-295. (PubMed)
17. Kerstetter JE, O'Brien KO, Caseria DM, Wall DE, Insogna KL. The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women. J Clin Endocrinol Metab. 2005;90(1):26-31. (PubMed)
18. Darling AL, Millward DJ, Torgerson DJ, Hewitt CE, Lanham-New SA. Dietary protein and bone health: a systematic review and meta-analysis. Am J Clin Nutr. 2009;90(6):1674-1692. (PubMed)
19. Grimm M, Muller A, Hein G, Funfstuck R, Jahreis G. High phosphorus intake only slightly affects serum minerals, urinary pyridinium crosslinks and renal function in young women. Eur J Clin Nutr. 2001;55(3):153-161. (PubMed)
20. Kemi VE, Karkkainen MU, Rita HJ, Laaksonen MM, Outila TA, Lamberg-Allardt CJ. Low calcium:phosphorus ratio in habitual diets affects serum parathyroid hormone concentration and calcium metabolism in healthy women with adequate calcium intake. Br J Nutr. 2010;103(4):561-568. (PubMed)
21. Heaney RP. Phosphorus. In: Erdman JJ, Macdonald I, Zeisel S, eds. Present Knowledge in Nutrition. 10th ed: John Wiley & Sons, Inc.; 2012: 447-458.
22. Calvo MS, Moshfegh AJ, Tucker KL. Assessing the health impact of phosphorus in the food supply: issues and considerations. Adv Nutr. 2014;5(1):104-113. (PubMed)
23. Barger-Lux MJ, Heaney RP, Stegman MR. Effects of moderate caffeine intake on the calcium economy of premenopausal women. Am J Clin Nutr. 1990;52(4):722-725. (PubMed)
24. Harris SS, Dawson-Hughes B. Caffeine and bone loss in healthy postmenopausal women. Am J Clin Nutr. 1994;60(4):573-578. (PubMed)
25. Lloyd T, Johnson-Rollings N, Eggli DF, Kieselhorst K, Mauger EA, Cusatis DC. Bone status among postmenopausal women with different habitual caffeine intakes: a longitudinal investigation. J Am Coll Nutr. 2000;19(2):256-261. (PubMed)
26. Heaney RP. Bone mass, nutrition, and other lifestyle factors. Nutr Rev. 1996;54(4 Pt 2):S3-S10. (PubMed)
27. Haleem S, Lutchman L, Mayahi R, Grice JE, Parker MJ. Mortality following hip fracture: trends and geographical variations over the last 40 years. Injury. 2008;39(10):1157-1163. (PubMed)
28. Kaufman JM, Reginster JY, Boonen S, et al. Treatment of osteoporosis in men. Bone. 2013;53(1):134-144. (PubMed)
29. Heaney RP. Calcium, dairy products and osteoporosis. J Am Coll Nutr. 2000;19(2 Suppl):83S-99S. (PubMed)
30. Crandall CJ, Newberry SJ, Diamant A, et al. Treatment To Prevent Fractures in Men and Women With Low Bone Density or Osteoporosis: Update of a 2007 Report. Rockville (MD); 2012; Mar. Report No.: 12-EHC023-EF. (PubMed)
31. Rizzoli R, Bianchi ML, Garabedian M, McKay HA, Moreno LA. Maximizing bone mineral mass gain during growth for the prevention of fractures in the adolescents and the elderly. Bone. 2010;46(2):294-305. (PubMed)
32. Borer KT. Physical activity in the prevention and amelioration of osteoporosis in women : interaction of mechanical, hormonal and dietary factors. Sports Med. 2005;35(9):779-830. (PubMed)
33. Natural Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis. Washington, D.C. 2014. Available at: http://nof.org/files/nof/public/content/file/2791/upload/919.pdf
34. Levis S, Theodore G. Summary of AHRQ's comparative effectiveness review of treatment to prevent fractures in men and women with low bone density or osteoporosis: update of the 2007 report. J Manag Care Pharm. 2012;18(4 Suppl B):S1-15; discussion S13. (PubMed)
35. Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007;370(9588):657-666. (PubMed)
36. Prince RL, Devine A, Dhaliwal SS, Dick IM. Effects of calcium supplementation on clinical fracture and bone structure: results of a 5-year, double-blind, placebo-controlled trial in elderly women. Arch Intern Med. 2006;166(8):869-875. (PubMed)
37. Chung M, Lee J, Terasawa T, Lau J, Trikalinos TA. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the US Preventive Services Task Force. Ann Intern Med. 2011;155(12):827-838. (PubMed)
38. Lips P, van Schoor NM. The effect of vitamin D on bone and osteoporosis. Best Pract Res Clin Endocrinol Metab. 2011;25(4):585-591. (PubMed)
39. Gallagher JC, Yalamanchili V, Smith LM. The effect of vitamin D on calcium absorption in older women. J Clin Endocrinol Metab. 2012;97(10):3550-3556. (PubMed)
40. Zhu K, Bruce D, Austin N, Devine A, Ebeling PR, Prince RL. Randomized controlled trial of the effects of calcium with or without vitamin D on bone structure and bone-related chemistry in elderly women with vitamin D insufficiency. J Bone Miner Res. 2008;23(8):1343-1348. (PubMed)
41. DIPART (Vitamin D Individual Patient Analysis of Randomized Trials) Group. Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ. 2010;340:b5463. (PubMed)
42. Avenell A, Mak JC, O'Connell D. Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database Syst Rev. 2014;4:CD000227. (PubMed)
43. Bischoff-Ferrari HA, Willett WC, Orav EJ, et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012;367(1):40-49. (PubMed)
44. Aspray TJ, Francis RM. Fracture prevention in care home residents: is vitamin D supplementation enough? Age Ageing. 2006;35(5):455-456. (PubMed)
45. Murad MH, Elamin KB, Abu Elnour NO, et al. Clinical review: The effect of vitamin D on falls: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96(10):2997-3006. (PubMed)
46. Lerolle N, Lantz B, Paillard F, et al. Risk factors for nephrolithiasis in patients with familial idiopathic hypercalciuria. Am J Med. 2002;113(2):99-103. (PubMed)
47. Sorensen MD, Eisner BH, Stone KL, et al. Impact of calcium intake and intestinal calcium absorption on kidney stones in older women: the study of osteoporotic fractures. J Urol. 2012;187(4):1287-1292. (PubMed)
48. Curhan GC, Willett WC, Knight EL, Stampfer MJ. Dietary factors and the risk of incident kidney stones in younger women: Nurses' Health Study II. Arch Intern Med. 2004;164(8):885-891. (PubMed)
49. Curhan GC, Willett WC, Rimm EB, Stampfer MJ. A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. N Engl J Med. 1993;328(12):833-838. (PubMed)
50. Curhan GC, Willett WC, Speizer FE, Spiegelman D, Stampfer MJ. Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Intern Med. 1997;126(7):497-504. (PubMed)
51. Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol. 2004;15(12):3225-3232. (PubMed)
52. Taylor EN, Curhan GC. Dietary calcium from dairy and nondairy sources, and risk of symptomatic kidney stones. J Urol. 2013;190(4):1255-1259. (PubMed)
53. Borghi L, Schianchi T, Meschi T, et al. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med. 2002;346(2):77-84. (PubMed)
54. Hess B, Jost C, Zipperle L, Takkinen R, Jaeger P. High-calcium intake abolishes hyperoxaluria and reduces urinary crystallization during a 20-fold normal oxalate load in humans. Nephrol Dial Transplant. 1998;13(9):2241-2247. (PubMed)
55. Liebman M, Chai W. Effect of dietary calcium on urinary oxalate excretion after oxalate loads. Am J Clin Nutr. 1997;65(5):1453-1459. (PubMed)
56. Lange JN, Wood KD, Mufarrij PW, et al. The impact of dietary calcium and oxalate ratios on stone risk. Urology. 2012;79(6):1226-1229. (PubMed)
57. Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354(7):669-683. (PubMed)
58. Heaney RP. Calcium supplementation and incident kidney stone risk: a systematic review. J Am Coll Nutr. 2008;27(5):519-527. (PubMed)
59. Candelas G, Martinez-Lopez JA, Rosario MP, Carmona L, Loza E. Calcium supplementation and kidney stone risk in osteoporosis: a systematic literature review. Clin Exp Rheumatol. 2012;30(6):954-961. (PubMed)
60. Escribano J, Balaguer A, Roque i Figuls M, Feliu A, Ferre N. Dietary interventions for preventing complications in idiopathic hypercalciuria. Cochrane Database Syst Rev. 2014;2:CD006022. (PubMed)
61. Heilberg IP, Goldfarb DS. Optimum nutrition for kidney stone disease. Adv Chronic Kidney Dis. 2013;20(2):165-174. (PubMed)
62. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009;33(3):130-137. (PubMed)
63. Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet. 2010;376(9741):631-644. (PubMed)
64. Hofmeyr GJ, Lawrie TA, Atallah AN, Duley L, Torloni MR. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev. 2014;6:CD001059. (PubMed)
65. Scholl TO, Chen X, Stein TP. Vitamin D, secondary hyperparathyroidism, and preeclampsia. Am J Clin Nutr. 2013;98(3):787-793. (PubMed)
66. Scholl TO, Chen X, Stein TP. Maternal calcium metabolic stress and fetal growth. Am J Clin Nutr. 2014;99(4):918-925. (PubMed)
67. Hofmeyr GJ, Belizan JM, von Dadelszen P, Calcium, Pre-eclampsia Study G. Low-dose calcium supplementation for preventing pre-eclampsia: a systematic review and commentary. BJOG. 2014;121(8):951-957. (PubMed)
68. World Health Organization. Calcium supplementation in pregnant women; 2013. Available at: http://www.who.int/nutrition/publications/micronutrients/guidelines/calcium_supplementation/en/.
69. Hofmeyr GJ, Mlokoti Z, Nikodem VC, et al. Calcium supplementation during pregnancy for preventing hypertensive disorders is not associated with changes in platelet count, urate, and urinary protein: a randomized control trial. Hypertens Pregnancy. 2008;27(3):299-304. (PubMed)
70. Villar J, Abdel-Aleem H, Merialdi M, et al. World Health Organization randomized trial of calcium supplementation among low calcium intake pregnant women. Am J Obstet Gynecol. 2006;194(3):639-649. (PubMed)
71. Hofmeyr GJ, Novikova N, Singata M, et al. Protocol 11PRT/4028: Long term calcium supplementation in women at high risk of pre-eclampsia: a randomised, placebo-controlled trial (PACTR201105000267371). The Lancet; 2011. Available at: http://www.thelancet.com/protocol-reviews/11PRT-4028.
72. Centers for Disease Control and Prevention. Colorectal cancer statistics. [Web page] Available at: http://www.cdc.gov/cancer/colorectal/statistics/. Accessed 11/13/14.
73. Whitfield JF. Calcium, calcium-sensing receptor and colon cancer. Cancer Lett. 2009;275(1):9-16. (PubMed)
74. Murphy N, Norat T, Ferrari P, et al. Consumption of dairy products and colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). PLoS One. 2013;8(9):e72715. (PubMed)
75. Massa J, Cho E, Orav EJ, Willett WC, Wu K, Giovannucci EL. Total calcium intake and colorectal adenoma in young women. Cancer Causes Control. 2014;25(4):451-460. (PubMed)
76. Keum N, Aune D, Greenwood DC, Ju W, Giovannucci EL. Calcium intake and colorectal cancer risk: Dose-response meta-analysis of prospective observational studies. Int J Cancer. 2014;135(8):1940-1948. (PubMed)
77. Bristow SM, Bolland MJ, MacLennan GS, et al. Calcium supplements and cancer risk: a meta-analysis of randomised controlled trials. Br J Nutr. 2013;110(8):1384-1393. (PubMed)
78. Bolland MJ, Grey A, Gamble GD, Reid IR. Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women's Health Initiative (WHI) limited-access data set. Am J Clin Nutr. 2011;94(4):1144-1149. (PubMed)
79. Carroll C, Cooper K, Papaioannou D, Hind D, Pilgrim H, Tappenden P. Supplemental calcium in the chemoprevention of colorectal cancer: a systematic review and meta-analysis. Clin Ther. 2010;32(5):789-803. (PubMed)
80. Mielke HW, Gonzales C, Powell E, Mielke PW. Evolving from reactive to proactive medicine: community lead (Pb) and clinical disparities in pre- and post-Katrina New Orleans. Int J Environ Res Public Health. 2014;11(7):7482-7491. (PubMed)
81. Centers for Disease Control and Prevention. New blood lead level information. Available at: http://www.cdc.gov/nceh/lead/acclpp/blood_lead_levels.htm. Accessed 8/15/14.
82. Bruening K, Kemp FW, Simone N, Holding Y, Louria DB, Bogden JD. Dietary calcium intakes of urban children at risk of lead poisoning. Environ Health Perspect. 1999;107(6):431-435. (PubMed)
83. Hertz-Picciotto I, Schramm M, Watt-Morse M, Chantala K, Anderson J, Osterloh J. Patterns and determinants of blood lead during pregnancy. Am J Epidemiol. 2000;152(9):829-837. (PubMed)
84. Ettinger AS, Lamadrid-Figueroa H, Tellez-Rojo MM, et al. Effect of calcium supplementation on blood lead levels in pregnancy: a randomized placebo-controlled trial. Environ Health Perspect. 2009;117(1):26-31. (PubMed)
85. Ettinger AS, Tellez-Rojo MM, Amarasiriwardena C, et al. Influence of maternal bone lead burden and calcium intake on levels of lead in breast milk over the course of lactation. Am J Epidemiol. 2006;163(1):48-56. (PubMed)
86. Hernandez-Avila M, Gonzalez-Cossio T, Hernandez-Avila JE, et al. Dietary calcium supplements to lower blood lead levels in lactating women: a randomized placebo-controlled trial. Epidemiology. 2003;14(2):206-212. (PubMed)
87. Muldoon SB, Cauley JA, Kuller LH, Scott J, Rohay J. Lifestyle and sociodemographic factors as determinants of blood lead levels in elderly women. Am J Epidemiol. 1994;139(6):599-608. (PubMed)
88. Dougkas A, Reynolds CK, Givens ID, Elwood PC, Minihane AM. Associations between dairy consumption and body weight: a review of the evidence and underlying mechanisms. Nutr Res Rev. 2011;24(1):72-95. (PubMed)
89. Zemel MB, Thompson W, Milstead A, Morris K, Campbell P. Calcium and dairy acceleration of weight and fat loss during energy restriction in obese adults. Obes Res. 2004;12(4):582-590. (PubMed)
90. Zemel MB, Shi H, Greer B, Dirienzo D, Zemel PC. Regulation of adiposity by dietary calcium. FASEB J. 2000;14(9):1132-1138. (PubMed)
91. Gonzalez JT, Rumbold PL, Stevenson EJ. Effect of calcium intake on fat oxidation in adults: a meta-analysis of randomized, controlled trials. Obes Rev. 2012;13(10):848-857. (PubMed)
92. Bortolotti M, Rudelle S, Schneiter P, et al. Dairy calcium supplementation in overweight or obese persons: its effect on markers of fat metabolism. Am J Clin Nutr. 2008;88(4):877-885. (PubMed)
93. Gallagher JC, Yalamanchili V, Smith LM. The effect of vitamin D supplementation on serum 25(OH)D in thin and obese women. J Steroid Biochem Mol Biol. 2013;136:195-200. (PubMed)
94. Pathak K, Soares MJ, Calton EK, Zhao Y, Hallett J. Vitamin D supplementation and body weight status: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2014;15(6):528-537. (PubMed)
95. Christensen R, Lorenzen JK, Svith CR, et al. Effect of calcium from dairy and dietary supplements on faecal fat excretion: a meta-analysis of randomized controlled trials. Obes Rev. 2009;10(4):475-486. (PubMed)
96. Tordoff MG. Calcium: taste, intake, and appetite. Physiol Rev. 2001;81(4):1567-1597. (PubMed)
97. Chen M, Pan A, Malik VS, Hu FB. Effects of dairy intake on body weight and fat: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2012;96(4):735-747. (PubMed)
98. Soares MJ, Pathak K, Calton EK. Calcium and vitamin D in the regulation of energy balance: where do we stand? Int J Mol Sci. 2014;15(3):4938-4945. (PubMed)
99. Freeman EW. Premenstrual syndrome and premenstrual dysphoric disorder: definitions and diagnosis. Psychoneuroendocrinology. 2003;28 Suppl 3:25-37. (PubMed)
100. Pearlstein T, Steiner M. Premenstrual dysphoric disorder: burden of illness and treatment update. J Psychiatry Neurosci. 2008;33(4):291-301. (PubMed)
101. Bendich A. The potential for dietary supplements to reduce premenstrual syndrome (PMS) symptoms. J Am Coll Nutr. 2000;19(1):3-12. (PubMed)
102. Thys-Jacobs S, Starkey P, Bernstein D, Tian J. Calcium carbonate and the premenstrual syndrome: effects on premenstrual and menstrual symptoms. Premenstrual Syndrome Study Group. Am J Obstet Gynecol. 1998;179(2):444-452. (PubMed)
103. Thys-Jacobs S, Ceccarelli S, Bierman A, Weisman H, Cohen MA, Alvir J. Calcium supplementation in premenstrual syndrome: a randomized crossover trial. J Gen Intern Med. 1989;4(3):183-189. (PubMed)
104. Alvir JM, Thys-Jacobs S. Premenstrual and menstrual symptom clusters and response to calcium treatment. Psychopharmacol Bull. 1991;27(2):145-148. (PubMed)
105. Bertone-Johnson ER, Hankinson SE, Bendich A, Johnson SR, Willett WC, Manson JE. Calcium and vitamin D intake and risk of incident premenstrual syndrome. Arch Intern Med. 2005;165(11):1246-1252. (PubMed)
106. Whelan AM, Jurgens TM, Naylor H. Herbs, vitamins and minerals in the treatment of premenstrual syndrome: a systematic review. Can J Clin Pharmacol. 2009;16(3):e407-429. (PubMed)
107. Cappuccio FP, Elliott P, Allender PS, Pryer J, Follman DA, Cutler JA. Epidemiologic association between dietary calcium intake and blood pressure: a meta-analysis of published data. Am J Epidemiol. 1995;142(9):935-945. (PubMed)
108. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Engl J Med. 1997;336(16):1117-1124. (PubMed)
109. Conlin PR, Chow D, Miller ER, 3rd, et al. The effect of dietary patterns on blood pressure control in hypertensive patients: results from the Dietary Approaches to Stop Hypertension (DASH) trial. Am J Hypertens. 2000;13(9):949-955. (PubMed)
110. Miller GD, DiRienzo DD, Reusser ME, McCarron DA. Benefits of dairy product consumption on blood pressure in humans: a summary of the biomedical literature. J Am Coll Nutr. 2000;19(2 Suppl):147S-164S. (PubMed)
111. Allender PS, Cutler JA, Follmann D, Cappuccio FP, Pryer J, Elliott P. Dietary calcium and blood pressure: a meta-analysis of randomized clinical trials. Ann Intern Med. 1996;124(9):825-831. (PubMed)
112. Bucher HC, Cook RJ, Guyatt GH, et al. Effects of dietary calcium supplementation on blood pressure. A meta-analysis of randomized controlled trials. JAMA. 1996;275(13):1016-1022. (PubMed)
113. Dickinson HO, Nicolson DJ, Cook JV, et al. Calcium supplementation for the management of primary hypertension in adults. Cochrane Database Syst Rev. 2006(2):CD004639. (PubMed)
114. Challoumas D, Cobbold C, Dimitrakakis G. Effects of calcium intake on the cardiovascular system in postmenopausal women. Atherosclerosis. 2013;231(1):1-7. (PubMed)
115. Bailey RL, Dodd KW, Goldman JA, et al. Estimation of total usual calcium and vitamin D intakes in the United States. J Nutr. 2010;140(4):817-822. (PubMed)
116. Kit BK, Fakhouri TH, Park S, Nielsen SJ, Ogden CL. Trends in sugar-sweetened beverage consumption among youth and adults in the United States: 1999-2010. Am J Clin Nutr. 2013;98(1):180-188. (PubMed)
117. Zhu K, Prince RL. Calcium and bone. Clin Biochem. 2012;45(12):936-942. (PubMed)
118. Straub DA. Calcium supplementation in clinical practice: a review of forms, doses, and indications. Nutr Clin Pract. 2007;22(3):286-296. (PubMed)
119. Roberts HJ. Potential toxicity due to dolomite and bonemeal. South Med J. 1983;76(5):556-559. (PubMed)
120. Bourgoin BP, Evans DR, Cornett JR, Lingard SM, Quattrone AJ. Lead content in 70 brands of dietary calcium supplements. Am J Public Health. 1993;83(8):1155-1160. (PubMed)
121. Scelfo GM, Flegal AR. Lead in calcium supplements. Environ Health Perspect. 2000;108(4):309-313. (PubMed)
122. Carrington CD, Bolger PM. An assessment of the hazards of lead in food. Regul Toxicol Pharmacol. 1992;16(3):265-272. (PubMed)
123. Ross EA, Szabo NJ, Tebbett IR. Lead content of calcium supplements. JAMA. 2000;284(11):1425-1429. (PubMed)
124. Mindak WR, Cheng J, Canas BJ, Bolger PM. Lead in women's and children's vitamins. J Agric Food Chem. 2008;56(16):6892-6896. (PubMed)
125. Moe SM. Disorders involving calcium, phosphorus, and magnesium. Prim Care. 2008;35(2):215-237, v-vi. (PubMed)
126. Patel AM, Goldfarb S. Got calcium? Welcome to the calcium-alkali syndrome. J Am Soc Nephrol. 2010;21(9):1440-1443. (PubMed)
127. Gonzalez CA, Riboli E. Diet and cancer prevention: Contributions from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Eur J Cancer. 2010;46(14):2555-2562. (PubMed)
128. Kurahashi N, Inoue M, Iwasaki M, Sasazuki S, Tsugane AS, Japan Public Health Center-Based Prospective Study G. Dairy product, saturated fatty acid, and calcium intake and prostate cancer in a prospective cohort of Japanese men. Cancer Epidemiol Biomarkers Prev. 2008;17(4):930-937. (PubMed)
129. Raimondi S, Mabrouk JB, Shatenstein B, Maisonneuve P, Ghadirian P. Diet and prostate cancer risk with specific focus on dairy products and dietary calcium: a case-control study. Prostate. 2010;70(10):1054-1065. (PubMed)
130. World Health Organization. GLOBOCAN 2012: estimated cancer incidence, mortality, and prevalence worldwide in 2012: International agency for research on cancer; 2012. Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed 11/13/14.
131. Torfadottir JE, Steingrimsdottir L, Mucci L, et al. Milk intake in early life and risk of advanced prostate cancer. Am J Epidemiol. 2012;175(2):144-153. (PubMed)
132. Song Y, Chavarro JE, Cao Y, et al. Whole milk intake is associated with prostate cancer-specific mortality among US male physicians. J Nutr. 2013;143(2):189-196. (PubMed)
133. Pettersson A, Kasperzyk JL, Kenfield SA, et al. Milk and dairy consumption among men with prostate cancer and risk of metastases and prostate cancer death. Cancer Epidemiol Biomarkers Prev. 2012;21(3):428-436. (PubMed)
134. Qin LQ, He K, Xu JY. Milk consumption and circulating insulin-like growth factor-I level: a systematic literature review. Int J Food Sci Nutr. 2009;60 Suppl 7:330-340. (PubMed)
135. Rowlands MA, Gunnell D, Harris R, Vatten LJ, Holly JM, Martin RM. Circulating insulin-like growth factor peptides and prostate cancer risk: a systematic review and meta-analysis. Int J Cancer. 2009;124(10):2416-2429. (PubMed)
136. Allen NE, Key TJ, Appleby PN, et al. Animal foods, protein, calcium and prostate cancer risk: the European Prospective Investigation into Cancer and Nutrition. Br J Cancer. 2008;98(9):1574-1581. (PubMed)
137. Moreno J, Krishnan AV, Peehl DM, Feldman D. Mechanisms of vitamin D-mediated growth inhibition in prostate cancer cells: inhibition of the prostaglandin pathway. Anticancer Res. 2006;26(4A):2525-2530. (PubMed)
138. Mandair D, Rossi RE, Pericleous M, Whyand T, Caplin ME. Prostate cancer and the influence of dietary factors and supplements: a systematic review. Nutr Metab (Lond). 2014;11:30. (PubMed)
139. Baron JA, Beach M, Wallace K, et al. Risk of prostate cancer in a randomized clinical trial of calcium supplementation. Cancer Epidemiol Biomarkers Prev. 2005;14(3):586-589. (PubMed)
140. Chung M, Balk EM, Brendel M, et al. Vitamin D and calcium: a systematic review of health outcomes. Evid Rep Technol Assess (Full Rep). 2009(183):1-420. (PubMed)
141. Huncharek M, Muscat J, Kupelnick B. Dairy products, dietary calcium and vitamin D intake as risk factors for prostate cancer: a meta-analysis of 26,769 cases from 45 observational studies. Nutr Cancer. 2008;60(4):421-441. (PubMed)
142. Pentti K, Tuppurainen MT, Honkanen R, et al. Use of calcium supplements and the risk of coronary heart disease in 52-62-year-old women: The Kuopio Osteoporosis Risk Factor and Prevention Study. Maturitas. 2009;63(1):73-78. (PubMed)
143. Li K, Kaaks R, Linseisen J, Rohrmann S. Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg). Heart. 2012;98(12):920-925. (PubMed)
144. Xiao Q, Murphy RA, Houston DK, Harris TB, Chow WH, Park Y. Dietary and supplemental calcium intake and cardiovascular disease mortality: the National Institutes of Health-AARP diet and health study. JAMA Intern Med. 2013;173(8):639-646. (PubMed)
145. Bolland MJ, Barber PA, Doughty RN, et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ. 2008;336(7638):262-266. (PubMed)
146. Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women's Health Initiative limited access dataset and meta-analysis. BMJ. 2011;342:d2040. (PubMed)
147. Hsia J, Heiss G, Ren H, et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation. 2007;115(7):846-854. (PubMed)
148. Abrahamsen B, Sahota O. Do calcium plus vitamin D supplements increase cardiovascular risk? BMJ. 2011;342:d2080. (PubMed)
149. Lewis JR, Zhu K, Prince RL. Adverse events from calcium supplementation: relationship to errors in myocardial infarction self-reporting in randomized controlled trials of calcium supplementation. J Bone Miner Res. 2012;27(3):719-722. (PubMed)
150. Lewis JR, Calver J, Zhu K, Flicker L, Prince RL. Calcium supplementation and the risks of atherosclerotic vascular disease in older women: results of a 5-year RCT and a 4.5-year follow-up. J Bone Miner Res. 2011;26(1):35-41. (PubMed)
151. Avenell A, MacLennan GS, Jenkinson DJ, et al. Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium (RECORD trial). J Clin Endocrinol Metab. 2012;97(2):614-622. (PubMed)
152. Van Hemelrijck M, Michaelsson K, Linseisen J, Rohrmann S. Calcium intake and serum concentration in relation to risk of cardiovascular death in NHANES III. PLoS One. 2013;8(4):e61037. (PubMed)
153. Foley RN, Collins AJ, Ishani A, Kalra PA. Calcium-phosphate levels and cardiovascular disease in community-dwelling adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J. 2008;156(3):556-563. (PubMed)
154. Lutsey PL, Alonso A, Michos ED, et al. Serum magnesium, phosphorus, and calcium are associated with risk of incident heart failure: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Clin Nutr. 2014;100(3):756-764. (PubMed)
155. Wang TK, Bolland MJ, van Pelt NC, et al. Relationships between vascular calcification, calcium metabolism, bone density, and fractures. J Bone Miner Res. 2010;25(12):2777-2785. (PubMed)
156. Samelson EJ, Booth SL, Fox CS, et al. Calcium intake is not associated with increased coronary artery calcification: the Framingham Study. Am J Clin Nutr. 2012;96(6):1274-1280. (PubMed)
157. Lewis JR, Zhu K, Thompson PL, Prince RL. The effects of 3 years of calcium supplementation on common carotid artery intimal medial thickness and carotid atherosclerosis in older women: an ancillary study of the CAIFOS randomized controlled trial. J Bone Miner Res. 2014;29(3):534-541. (PubMed)
158. Lewis JR, Radavelli-Bagatini S, Rejnmark L, et al. The Effects of Calcium Supplementation on Verified Coronary Heart Disease Hospitalization and Death in Postmenopausal Women: A Collaborative Meta-Analysis of Randomized Controlled Trials. J Bone Miner Res. 2014; doi: 10.1002/jbmr.2311 [Epub ahead of print]. (PubMed)
159. Spence LA, Weaver CM. Calcium intake, vascular calcification, and vascular disease. Nutr Rev. 2013;71(1):15-22. (PubMed)
160. Vella A, Gerber TC, Hayes DL, Reeder GS. Digoxin, hypercalcaemia, and cardiac conduction. Postgrad Med J. 1999;75(887):554-556. (PubMed)
161. Moser LR, Smythe MA, Tisdale JE. The use of calcium salts in the prevention and management of verapamil-induced hypotension. Ann Pharmacother. 2000;34(5):622-629. (PubMed)
162. Bania TC, Blaufeux B, Hughes S, Almond GL, Homel P. Calcium and digoxin vs. calcium alone for severe verapamil toxicity. Acad Emerg Med. 2000;7(10):1089-1096. (PubMed)
163. Wright MJ, Proctor DD, Insogna KL, Kerstetter JE. Proton pump-inhibiting drugs, calcium homeostasis, and bone health. Nutr Rev. 2008;66(2):103-108. (PubMed)
164. Gennari C. Differential effect of glucocorticoids on calcium absorption and bone mass. Br J Rheumatol. 1993;32 Suppl 2:11-14. (PubMed)
165. Lems WF, Jacobs JW, Van Rijn HJ, Bijlsma JW. Changes in calcium and bone metabolism during treatment with low dose prednisone in young, healthy, male volunteers. Clin Rheumatol. 1995;14(4):420-424. (PubMed)
166. Lems WF, Van Veen GJ, Gerrits MI, et al. Effect of low-dose prednisone (with calcium and calcitriol supplementation) on calcium and bone metabolism in healthy volunteers. Br J Rheumatol. 1998;37(1):27-33. (PubMed)
167. Wood RJ, Zheng JJ. High dietary calcium intakes reduce zinc absorption and balance in humans. Am J Clin Nutr. 1997;65(6):1803-1809. (PubMed)