Calcium

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 (1). 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.

FUNCTION

Structure: Calcium is a major structural element in bones and teeth. The mineral component of bone consists mainly of hydroxyapatite crystals, which contain large amounts of calcium and phosphorus (about 40% calcium and 60% phosphorus) (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).

Intracellular messenger: 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 asinsulin. (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.  The term, “coagulation cascade,” refers to a series of events, each dependent on the other that stops bleeding through clot formation (see Vitamin K)(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. When blood calcium decreases (e.g., in the case of inadequate calcium intake), calcium-sensing proteins in the parathyroid glandssend 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).  See diagram.

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 ofosteoclasts to PTH (see Function: regulation of calcium levels). 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 ofosteoporosis (see Disease Treatment and Prevention) (1).

Nutrient interactions: Vitamin D is required for optimal calcium absorption (see Function and Vitamin D). Several other nutrients (and non-nutrients) influence the retention of calcium by the body and may affect calcium nutritionalstatus.

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 decreasedbone 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 U.S.RDA for protein is 46-50 grams/day for adult women and 58-63 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 per 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 (see Function), 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 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 per day and reported that they drank 2-3 cups of coffee per 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 Level (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).

Adequate Intake Level (AI) for Calcium
Age and life stage group Calcium (mg/day)
0-6 months 210
7-12 months 270
1-3 years 500
4-8 years 800
9-18 years 1,300
19-50 years 1,000
51 years and older 1,200
Pregnancy: 18 years and younger 1,300
Pregnancy: 19 years and older 1,000
Breastfeeding: 18 years and younger 1,300
Breast feeding: 19 years and older 1,000

DISEASE PREVENTION

Colorectal Cancer: Colorectal cancer is the most common gastrointestinalcancer 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 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.

DISEASE PREVENTION AND TREATMENT

Calcium may play a role in both the prevention and the treatment of the health problems discussed below.

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 andanticonvulsants). 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 on osteoporosis visit the National Osteoporosis Foundation website.

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 (see Nutrient Interactions) (18,19). A large prospectiveepidemiologic 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 1326 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 epidemiologic 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 oxalic acid with or without supplemental calcium. Providing 200 mg of elemental calcium along with the oxalic acid significantly reduced its absorption and urinary oxalate excretion (22).

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 recent 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.  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 (24). At present, the only dietary change proven effective in reducing kidney stone recurrence is increasing fluid intake, though no controlled clinical trials of calcium supplementation or restriction have been reported in the literature (1,18).

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 (25).  A large systematic review of 42 randomizedclinical 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 (26).  Calcium supplementation in these randomized clinical trials ranged from 500 mg to 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).  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 (27,28).  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 (29). More information about the DASH diet is available from the National Institutes of Health (NIH) Web site.

Pregnancy-induced hypertension:  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 (30). 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 epidemiologic 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 ofrandomized 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 (31). 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 2300 mg/day (32).  For the general population, meeting current recommendations for calcium intake during pregnancy may also help prevent PIH (See the RDA).  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 recent 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 (33). 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 (34). 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 (35).

FOOD SOURCES

Average dietary intakes of calcium in the U.S. are well below the levels recommended by the FNB 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 FNB recommendations (15). 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).

Bioavailability of calcium in foods: While dairy products represent a rich and absorbable source of calcium, 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 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 acidis a less potent inhibitor of calcium absorption than oxalic acid. 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, the percent of that calcium that is generally absorbed, the estimated absorbable calcium from that food, and the number of servings of that food required to equal the absorbable calcium from one glass of milk (8).

 

Food Serving Elemental Calcium (mg) % Calcium
Absorbed
Estimated Absorbable Calcium (mg) Servings needed to equal 8 oz of milk
Milk 8 ounces 300 32 96 1.0
Yogurt 8 ounces 300 32 96 1.0
Cheddar cheese 1.5 ounces 303 32 97 1.0
Cheese food 1.5 ounces 241 32 77 1.2
Pinto beans 1/2 cup, cooked 45 27 12 8.1
Red beans 1/2 cup, cooked 41 24 10 9.7
White beans 1/2 cup, cooked 113 22 25 3.9
Tofu, calcium set 1/2 cup 258 31 80 1.2
Bok choy 1/2 cup, cooked 79 54 43 2.3
Kale 1/2 cup, cooked 61 49 30 3.2
Chinese cabbage 1/2 cup, cooked 239 40 95 1.0
Broccoli 1/2 cup, cooked 35 61 22 4.5
Spinach 1/2 cup, cooked 115 5 6 16.3
Rhubarb 1/2 cup, cooked 174 9 10 9.5
Fruit punch with calcium citrate malate 8 ounces 300 52 156 0.62

For more information on the nutrient content of foods you eat frequently, search the USDA food composition database. In this database, only the total calcium content of the food is listed.

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 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, though calcium citrate and calcium citrate malate can be taken anytime.

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 (36). 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 (37).  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 (see Disease Prevention and Treatment). 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 (see Disease Prevention and Treatment).

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 upper level (UL) of intake for calcium at 2,500 milligrams (mg) of calcium/day (3).

Drug Interactions: Taking calcium supplements in combination with thiazidediuretics (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 the cardiovascular and blood pressure medications verapamil and atenolol, and the antibiotic Norfloxacin. Calcium may decrease the absorption of antibiotics in the tetracycline class and tiludronate (used to treat Paget’s disease of the bone), so it is advisable to separate doses of these medications and calcium rich foods or supplements by two hours (38,39).

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% (40).

RECENT RESEARCH

Does a high calcium intake increase the risk of prostate cancer?

Recent epidemiologic studies have raised concern that high calcium intakes are associated with increased risk of prostate cancer. A large prospectivecohort 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 (41). 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 (42). 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 (43). Although this study did not examine supplement use, each 500 mg/day increase in calcium from dairy foods was associated with a 16% increase in the risk of prostate cancer (advanced and non-advanced).

The physiologic mechanisms underlying the relationship between calcium intake and prostate cancer are not yet clear. High levels of dietary calcium may lead to decreased circulating levels of calcitriol, the active form of vitamin D. In experimental studies conducted in prostate cancer cell lines and animal models, calcitriol has been found to have protective effects. However, the findings of studies conducted in humans on serum calcitriol levels and prostate cancer risk have been much less consistent.

Not all epidemiologic studies have demonstrated an association between calcium intake and prostate cancer. In total, 7 out of 14 case-control studies and 5 out of 9 prospective cohort studies have reported statistically significant positive associations between prostate cancer and some measure of dairy product consumption. Of those studies that have examined calcium intake, 3 out of 6 case-control studies and 2 out of 4 cohort studies reported statistically significant associations between prostate cancer and calcium intake (44). One Serbian case-control study found increased calcium intake to be associated with a decreased risk of prostate cancer (45). 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 intake level recommended by the Food and Nutrition Board of the Institute of Medicine.

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.

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 intake level recommended by the Food and Nutrition Board of the Institute of Medicine (see Recent Research).

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