CALCIUM

Calcium is the most common 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 levels in the blood and fluid surrounding the cells (extracellular fluid) must be maintained within a very narrow concentration range for normal physiological functioning. The physiological functions of calcium are so vital to survival that the body will demineralize bone to maintain normal blood calcium levels when calcium intake is inadequate. Thus, adequate dietary calcium is a critical factor in maintaining a healthy skeleton (1).

FUNCTION

Structure

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 and phosphate (2). 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 exceeds formation (1).

Cell signaling

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, such as insulin (3). 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 muscle fiber receives a nerve impulse that stimulates it to contract, calcium channels in the cell membrane open to allow a few calcium ions into the muscle cell. These calcium ions bind to activator proteins within the cell that release a flood of calcium ions from storage vesicles 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 breakdown muscle glycogen to provide energy for muscle contraction (1).

Cofactor for enzymes and proteins

Calcium is necessary to stabilize or allow for optimal activity of a number of proteins and enzymes. The binding of calcium ions is required for the activation of the seven "vitamin K-dependent" clotting factors in the coagulation cascade (see vitamin K). The term, "coagulation cascade," refers to a series of events, each dependent on the other that stops bleeding through clot formation (4).

Regulation of calcium levels

Calcium concentrations in the blood and fluid that surrounds cells are tightly controlled in order to preserve normal physiological functioning (diagram). When blood calcium decreases (e.g., in the case of inadequate calcium intake), calcium-sensing proteins in the parathyroid glands send signals resulting in the secretion of parathyroid hormone (PTH) (5). PTH stimulates the conversion of vitamin D to its active form, calcitriol, in the kidneys. Calcitriol increases the absorption of calcium from the small intestine. Together with PTH, calcitriol stimulates the release of calcium from bone by activating osteoclasts (bone resorbing cells), and decreases 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 and the kidneys begin to excrete any excess calcium in the urine. Although this complex system allows for rapid and tight control of blood calcium levels, it does so at the expense of the skeleton (1).

DEFICIENCY

A low blood calcium level usually implies abnormal parathyroid function, and is rarely due to low dietary calcium intake since the skeleton provides a large reserve of calcium for maintaining normal blood levels. Other causes of abnormally low blood calcium levels include chronic kidney failure, vitamin D deficiency, and low blood magnesium levels that occur mainly in cases of severe alcoholism. Magnesium deficiency results in a decrease in the responsiveness of osteoclasts to PTH. A chronically low calcium intake 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 the development of osteoporosis (see Disease Prevention) (1). 

Nutrient interactions

Vitamin D: Vitamin D is required for optimal calcium absorption (See Function or Vitamin D). Several other nutrients (and non-nutrients) influence the retention of calcium by the body and may affect calcium nutritional status.

Sodium: Increased sodium intake results in increased loss of calcium in the urine, possibly due to competition between sodium and calcium for reabsorption in the kidney or by an effect of sodium on parathyroid hormone (PTH) secretion. Each 2.3-gram increment of sodium (6 grams of salt; NaCl) excreted by the kidney has been found to draw about 24-40 milligrams (mg) of calcium into the urine. Because urinary losses account for about half of the difference in calcium retention among individuals, dietary sodium has a large potential to influence bone loss. 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. Although animal studies have shown bone loss to be greater with high salt intakes, no controlled clinical trials have been conducted to confirm the relationship between salt intake and bone loss in humans (1, 6). However, a 2-year study of 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 (7).

Protein: As dietary protein intake increases, the urinary excretion of calcium also increases. Recommended calcium intakes for the U.S. population are higher than those for populations of less industrialized nations because protein intake in the U.S. is generally higher. The RDA for protein is 46 grams/day for adult women and 56 grams/day for adult men. However, the average intake of protein in the U.S. tends to be higher (65-70 grams/day in adult women and 90-110 grams per day in adult men) (3). Weaver and colleagues have calculated that each additional gram of protein results in an additional loss of 1.75 mg of calcium/day. Because only 30% of dietary calcium is generally absorbed, each one-gram increase in protein intake/day would require an additional 5.8 mg of calcium/day to offset the calcium loss (8). At the other end of the spectrum of protein intake, the effect of dietary protein insufficiency on bone health has received much less attention. Inadequate protein intakes have been associated with poor recovery from osteoporotic fractures and serum albumin values (an indicator of protein nutritional status) have been found to be inversely related to hip fracture risk (3).

Phosphorus: Phosphorus, which is typically found in protein-rich foods, tends to decrease the excretion of calcium in the urine. However, phosphorus-rich foods also tend to increase the calcium content of digestive secretions, resulting in increased calcium loss in the feces. Thus, phosphorus does not offset the net loss of calcium associated with increased protein intake (1). Increasing intakes of phosphates from soft drinks and food additives have caused concern among some researchers regarding the implications for bone health. Diets high in phosphorus and low in calcium have been found to increase parathyroid hormone (PTH) secretion, as have diets low in calcium.(3, 6) While the effect of high phosphorus intakes on calcium balance and bone health are presently unclear, the substitution of large quantities of soft drinks for milk or other sources of dietary calcium is cause for concern with respect to bone health in adolescents and adults.

Caffeine: 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 (9). Although one observational study found accelerated bone loss in postmenopausal women who consumed less than 744 mg of calcium/day and reported that they drank 2-3 cups of coffee/day (10), a more recent study that measured caffeine intake found no association between caffeine intake and bone loss in postmenopausal women (11). On average, one 8-ounce cup of coffee decreases calcium retention by only 2-3 mg (1).

The Adequate Intake (AI)

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 1997. The setting of an Adequate Intake level (AI) rather than a Recommended Dietary Allowance (RDA) for calcium reflects the difficulty of estimating the intake of dietary calcium that will result in optimal accumulation and retention of calcium in the skeleton when other factors such as genetics, hormones, and physical activity, also interact to affect bone health (3).

 

DISEASE PREVENTION

Colorectal Cancer

Colorectal cancer is the most common gastrointestinal cancer and the second leading cause of cancer deaths in the U.S. Colorectal cancer is caused by a combination of genetic and environmental factors, but the degree to which these two factors influence the risk of colon cancer in individuals varies widely. In individuals with familial adenomatous polyposis, the cause of colon cancer is thought to be almost entirely genetic, while dietary factors appear to influence the risk of colon cancer in others. Animal studies are strongly supportive of a protective role for calcium in preventing intestinal cancers (12). In humans, controlled clinical trials have found modest decreases in the recurrence of colorectal adenomas (precancerous polyps) with calcium supplementation of 1,200-2,000 mg/day (13, 14). However, most large prospective studies have found increased calcium intake to be only weakly associated with a decreased risk of colorectal cancer. These weak associations might be explained by the presence of groups within the population that differ in their response to calcium. A recent case-control study of 511 men found that increased calcium intake was more strongly associated with decreased colorectal cancer risk in those men with higher circulating levels of a growth factor known as IGF-1 (15). There is some evidence that individuals with increased circulating levels of IGF-1 are at increased risk of colorectal cancer, and increased calcium intake may benefit this subgroup more than others. Before conclusions can be drawn, more research is needed to clarify whether specific subgroups in the larger population have different calcium requirements with respect to decreasing the risk of colorectal cancer.

Osteoporosis

Osteoporosis is a skeletal disorder in which bone strength is 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 the year following the fracture, and one person in five dies within one year of sustaining an osteoporotic hip fracture. Although osteoporosis is most commonly diagnosed in white postmenopausal women, women of other racial groups and ages, men, and children may also develop osteoporosis (16).

Osteoporosis is a multifactorial disorder, and nutrition is only one factor contributing to its development and progression (2). Other factors that increase the risk of developing osteoporosis include, but are not limited to, increased age, female gender, estrogen deficiency, smoking, metabolic disease (e.g., hyperthyroidism), and the use of certain medications (e.g., corticosteroids and anticonvulsants). 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 life style 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. Although, calcium is the nutrient consistently found to be most important for attaining peak bone mass and preventing osteoporosis, adequate vitamin D intake is also required for optimal calcium absorption (16).

Physical exercise is another lifestyle factor of benefit in 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. Exercise in the presence of adequate calcium and vitamin D intake probably has a modest effect on slowing the rate of bone loss later in life. 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 (17). High impact exercise and resistance exercise (weights) are likely the most beneficial for reducing bone loss. Lower impact exercise like walking, swimming, and cycling have beneficial effects on other aspects of health and function, but their effects on bone loss have been minimal. However, exercise later in life, even beyond 90 years of age, can still increase strength and reduce the likelihood of a fall, another important risk factor for hip fracture (16). Supplemental calcium alone cannot usually restore lost bone in individuals with osteoporosis. However, optimal treatment of osteoporosis with any drug therapy also requires adequate intake of calcium (1,200 mg/day) and vitamin D (600 IU/day) (2, 16). For more information about osteoporosis, visit the National Osteoporosis Foundation Web site.

Kidney stones

Approximately 12% of the U.S. population will have a kidney stone at some time. Most kidney stones are composed of calcium oxalate or calcium phosphate. Although their cause is usually unknown, abnormally elevated urinary calcium (hypercalciuria) increases the risk of developing calcium stones. Increasing dietary calcium increases urinary calcium slightly, and the rise is more pronounced in those with hypercalciuria. However, other dietary factors such as sodium and protein are also known to increase urinary calcium (18, 19). A large prospective study that followed men over a period of twelve years found the incidence of symptomatic kidney stones to be 44% lower in men in the highest quintile (1/5) of calcium intake, averaging 1,326 mg/day, compared with men in the lowest quintile of calcium intake, averaging 516 mg/day (20). Similar results were observed in a large prospective study of women over four years (21). The authors of the two studies suggested that increased dietary calcium might inhibit the absorption of dietary oxalate and reduce urinary oxalate, a risk factor for calcium oxalate stones. Support for this idea comes from a study in which people ingested oxalate with or without supplemental calcium (22). Providing 200 mg of elemental calcium along with the oxalate significantly reduced its absorption and urinary oxalate excretion. 

Although calcium stone formers have been advised to restrict calcium intake in the past, a cross-sectional study of 282 patients with calcium oxalate stones found that dietary salt, as measured by urinary sodium excretion, was the dietary factor most strongly associated with urinary calcium excretion (23). A study of 85 calcium stone forming patients found that those with low bone mineral density were significantly more likely to have higher salt intake and higher urinary sodium excretion, leading the authors to suggest that reduced salt intake should be recommended for calcium stone forming patients (24). Findings that calcium stone forming patients with lower calcium intakes are more likely to have decreased bone mineral density also call into question the therapeutic use of dietary calcium restriction. At present, the only dietary change proven effective in reducing kidney stone recurrence is increasing fluid intake, although no controlled clinical trials of calcium supplementation or restriction have been reported in the literature (1, 18).

Pregnancy-induced hypertension (preeclampsia)

Pregnancy-induced hypertension (PIH) occurs in 10% of pregnancies, and is a major health risk for pregnant women and their unborn children. PIH is a term that includes gestational hypertension, preeclampsia, and eclampsia. Gestational hypertension is defined as an abnormally high blood pressure that usually develops after the 20th week of pregnancy. In addition to gestational hypertension, preeclampsia includes the development of edema (severe swelling) and proteinuria (protein in the urine). Preeclampsia may progress to eclampsia (also called toxemia) in which life-threatening convulsions and coma may occur (25). Although the cause of PIH is not entirely understood, calcium metabolism appears to play a role. Risk factors for PIH include first pregnancies, multiple gestations (e.g., twins or triplets), chronic high blood pressure, diabetes, and some autoimmune diseases. Data from epidemiological studies suggests an inverse relationship between calcium intake and the incidence of PIH, but the results of experimental research on calcium supplementation and PIH have been less clear. A systematic review of randomized placebo-controlled studies found that calcium supplementation reduced the incidence of high blood pressure in pregnant women at high risk of PIH, as well as in pregnant women with low dietary calcium intake. However, in women at low risk of PIH and with adequate calcium intake the benefit of calcium supplementation was judged small and unlikely to be clinically significant (26). A large multi-center clinical trial of Calcium for Preeclampsia Prevention (CPEP) in over 4,500 pregnant women, found no effect of 2,000 mg of supplemental calcium on PIH. However, women in the placebo group had a mean intake of 980 mg/day, while those in the supplemental group had a mean intake of 2,300 mg/day (27). For the general population, meeting current recommendations for calcium intake during pregnancy may also help prevent PIH. Further research is required to determine whether women at high risk for PIH would benefit from calcium supplementation above the current recommendations. 

Lead toxicity

Children who are chronically exposed to lead, even in small amounts, are more likely to develop learning disabilities, behavioral problems, and to have low IQ's. Abnormal growth and neurological development may occur in the infants of women exposed to lead during pregnancy. In adults, lead toxicity may result in kidney damage and high blood pressure. Although the use of lead paint and leaded gasoline has been discontinued in the U.S., lead toxicity continues to be a significant health problem, especially in children living in urban areas. A study of over 300 children aged 1 through 8 years in an urban neighborhood found that 49% had blood lead levels above current guidelines indicating excessive lead exposure, while only 59% of children ages 1-3 years and 41% of children ages 4-8 years had calcium intakes meeting the recommended levels (28). Adequate calcium intake appears to 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 its may remain for more than twenty years. Adequate calcium intake also prevents exposure to lead mobilized from the skeleton during bone demineralization. A recent study of blood lead levels 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 related to increased bone demineralization with the release of accumulated lead into the blood (29). 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 postmenopausal women, increased calcium intake was associated with decreased blood lead levels, along with other factors known to decrease bone demineralization, for example, estrogen replacement therapy and physical activity (30).

DISEASE TREATMENT

High blood pressure (hypertension)

The relationship between calcium intake and blood pressure has been investigated extensively over the past two decades. An analysis of 23 large observational studies 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 (31). A large systematic review of 42 randomized controlled trials examining the effect of calcium supplementation on blood pressure compared to placebo found an overall reduction of 1.44 mm Hg in systolic blood pressure and a reduction of 0.84 mm Hg in diastolic blood pressure (32). Calcium supplementation in these randomized controlled trials ranged from 500-2,000 mg/day, with 1,000-1,500 mg/day being the most common dose. 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 fruits (~5 servings/day) and vegetables (~3 servings/day), and 3) a combination diet rich in fruits and vegetables, and low-fat dairy products (~3 servings/day) (33). 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. The combination diet reduced systolic blood pressure 5.5 mm Hg and diastolic blood pressure 3.0 mm Hg more than the control diet, while the fruit/vegetable diet reduced systolic blood pressure 2.8 mm Hg and diastolic blood pressure 1.1 mm Hg more than the control diet. Among those 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 systolic and 2.8 mm Hg diastolic compared to the control diet (34). This research indicates that a calcium intake at the recommended level (1,000-1,200 mg/day) may be helpful in preventing and treating moderate hypertension (35). More information about the DASH diet is available from the National Institutes of Health (NIH).

SOURCES

Food sources

Average dietary intakes of calcium in the U.S. are well below the adequate intake (AI) recommendation for every age and gender group, especially in females. Only about 25% of boys and 10% of girls ages 9 to 17 are estimated to meet the AI recommendations. 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 (1, 3). Dairy products represent rich and absorbable sources of calcium, but certain vegetables and grains also provide calcium. However, the bioavailability of that calcium must be taken into consideration. While the calcium rich plants in the kale family (broccoli, bok choy, cabbage, mustard, and turnip greens) contain calcium that is as bioavailable as that in milk, 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 in high concentrations in spinach and rhubarb and somewhat lower concentrations in sweet potato and dried beans. Phytic acid is a less potent inhibitor of calcium absorption than oxate. Yeast possess an enzyme (phytase) which breaks down phytic acid in grains during fermentation, lowering the phytic acid content of breads and other fermented foods. Only concentrated sources of phytate such as wheat bran or dried beans substantially reduce calcium absorption (1). The table below lists a number of calcium rich foods, along with their calcium content, and the number of servings of that food required to equal the absorbable calcium from one glass of milk (8). For more information on the nutrient content of foods you eat frequently, search the USDA food composition database. 

 

Food	Serving	Calcium (mg)	Servings needed to equal the absorbable calcium in 8 oz of milk
Milk	8 ounces	300	1.0
Yogurt	8 ounces	300	1.0
Cheddar cheese	1.5 ounces	303	1.0
Cheese food	1.5 ounces	241	1.2
Pinto beans	1/2 cup, cooked	45	8.1
Red beans	1/2 cup, cooked	41	9.7
White beans	1/2 cup, cooked	113	3.9
Tofu, calcium set	1/2 cup	258	1.2
Bok choy	1/2 cup, cooked	79	2.3
Kale	1/2 cup, cooked	61	3.2
Chinese cabbage	1/2 cup, cooked	239	1.0
Broccoli	1/2 cup, cooked	35	4.5
Spinach	1/2 cup, cooked	115	16.3
Rhubarb	1/2 cup, cooked	174	9.5
Fruit punch with calcium citrate malate	8 ounces	300	0.62

 

Supplements

Most experts recommend obtaining as much calcium as possible from foods because calcium in foods 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 foods. No multivitamin/multimineral 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, now required on all supplements marketed in the U.S., lists the calcium content of the supplement as elemental calcium. Calcium preparations used as supplements include calcium carbonate, calcium lactate, calcium gluconate, calcium citrate, and calcium citrate malate. 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 (36).

Lead in calcium supplements: Several years ago concern was raised regarding the lead levels in calcium supplements obtained from natural sources (oyster shell, bone meal, dolomite). In 1993, investigators found measurable quantities of lead in most of the 70 different preparations they tested (37). Since then, manufacturers have made an effort to reduce the amount of lead in calcium supplements to less than 0.5 micrograms (mcg)/1,000 mg of elemental calcium. The federal limit is 7.5 mcg/1,000 mg elemental calcium. Because lead is so widespread and long lasting on earth, no one can guarantee entirely lead-free food or supplements. A recent study found measurable lead in 8 out of 21 supplements, in amounts averaging between 1 and 2 mcg/1,000 mg of elemental calcium (38). 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, looking for supplements that are labeled "lead-free," and avoiding large doses of supplemental calcium (more than 1,500 mg/day) are ways to avoid incidental lead exposure.

SAFETY

Toxicity

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

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

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

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

Do high calcium intakes increase the risk of prostate cancer?

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

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

Drug Interactions

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

Nutrient Interactions

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

RECENT RESEARCH

Calcium and weight loss

Diets with higher calcium density (calcium per total calories) have been associated with a reduced incidence of being overweight or obese in several studies. These studies were not designed to examine the effect of calcium on obesity or body fat, and their significance was unclear until recent studies in cell culture and animal models indicated that low calcium intakes could result in hormonal and metabolic changes that increase the tendency of fat cells to accumulate fat (46). In a two-year exercise trial, higher dietary calcium intakes were associated with weight loss whether participants were in the exercise group or the control group (47). A placebo-controlled calcium supplementation trial found significantly greater weight loss in elderly women supplemented with 1,200 mg of calcium/day compared to a control group (48). While more research is needed to understand the relationships between calcium intake and body fat, these findings emphasize the importance of maintaining an adequate calcium intake while attempting to diet or lose weight.

THE LINUS PAULING INSTITUTE RECOMMENDATION

The Linus Pauling Institute supports the adequate intake levels (AI) recommended 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)

In order 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 (ages 19-50 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 men and women, 50 years of age and younger, should consume a total (diet plus supplements) of 1,000 mg/day of calcium. 

Older adults (51 years and older)

To minimize bone loss, older men and postmenopausal women should consume a total (diet plus supplements) of 1,200 mg/day of calcium. Taking a multivitamin/multimineral supplement containing at least 10 mcg (400) IU/day of vitamin D will help to ensure adequate calcium absorption (see Vitamin D). 

Pregnant and breastfeeding women 

Pregnant and breastfeeding adolescents (under 19 years of age) should consume a total of 1,300 mg/day of calcium, while pregnant and breastfeeding adults (19 and older) should consume a total of 1,000 mg/day of calcium.

REFERENCES

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Written by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed by:
Connie M. Weaver, Ph.D.
Distinguished Professor and Head of Foods and Nutrition
Purdue University

Does a high calcium intake increase the risk of prostate cancer?
Reviewed by:
June Chan, Sc.D.
Assistant Professor
Departments of Epidemiology & Biostatistics and Urology
University of California, San Francisco

Last updated 04/08/2003    Copyright 2001-2003 The Linus Pauling Institute

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The Linus Pauling Institute Micronutrient Information Center provides scientific information on health aspects of micronutrients and phytochemicals for the general public. The information is made available with the understanding that the author and publisher are not providing medical, psychological, or nutritional counseling services on this site. The information should not be used in place of a consultation with a competent health care or nutrition professional.

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