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.
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. 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.
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. 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.
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.
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 glands send signals resulting in the secretion of parathyroid hormone (PTH). 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.
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.
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. 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.
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. 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 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.
Osteoporosis is a multifactorial disorder, and nutrition is only one factor contributing to its development and progression. 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.
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. 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. 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). 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. 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. Similar results were observed in a large prospective study of women over four years. 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. 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. 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. 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.
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. 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. 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. 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.
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. 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.
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. 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. 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). 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. 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. More information about the DASH diet is available from the National Institutes of Health (NIH).
Calcium is one of the most important minerals for the growth, maintenance, and reproduction of the human body. The bones in the human body incorporate calcium into their structure. Bones, like other tissues in the body, are continually being reabsorbed and re-formed. Teeth arealso calcified tissues. They incorporate calcium in their structure in a manner similar to bones. Calcium is essential for the formation of andmaintenance of healthy teeth.
Calcium has other functions in addition to maintaining healthy teeth and bones. Blood coagulation, transmission of nerve impulses, muscle contraction and relaxation, normal heart beat, stimulation of hormone secretion, activation of enzyme reactions, as well as other functions all require small amounts of calcium.
1. Lin YC, Lyle RM, McCabe LD, McCabe GP, Weaver CM, Teegarden D. Dairy Calcium is Related to Changes in Body Composition During a Two-year Exercise Intervention in Young Women. J Am Coll Nutr. 2000 Nov-Dec;19(6):754-60.
Objective: Relationships between micronutrients and dairy product intake and changes in body weight and composition over two years were investigated. DESIGN: Two year prospective non-concurrent analysis of the effect of calcium intake on changes in body composition during a two year exercise intervention. SUBJECTS: 54 normal weight young women, 18 to 31 years of age.
Measures of Outcome: Mean intakes of nutrients of interest were determined from three-day diet records completed at baseline and every six months for two years. The change in total body weight and body composition (assessed by dual x-ray absorptiometry) from baseline to two years was also determined. RESULTS: Total calcium/kilocalories and vitamin A together predicted (negatively and positively, respectively) changes in body weight (R2 = 0.19) and body fat (R2 = 0.27). Further, there was an interaction of calcium and energy intake in predicting changes in body weight, such that, only at lower energy intakes, calcium intake (not adjusted for energy) predicted changes in body weight.
Conclusions: Regardless of exercise group assignment, calcium adjusted for energy intake had a negative relationship and vitamin A intake a positive relationship with two year changes in total body weight and body fat in young women aged 18 to 31 years. Thus, subjects with high calcium intake, corrected by total energy intake, and lower vitamin A intake gained less weight and body fat over two years in this randomized exercise intervention trial.
2. Davies KM, Heaney RP, Recker RR, Lappe JM, Barger-Lux MJ, Rafferty K, Hinders S. Calcium Intake and Body Weight. J Clin Endocrinol Metab. 2000 Dec;85(12):4635-8.
Five clinical studies of calcium intake, designed with a primary skeletal end point, were reevaluated to explore associations between calcium intake and body weight. All subjects were women, clustered in three main age groups: 3rd, 5th, and 8th decades. Total sample size was 780. Four of the studies were observational; two were cross-sectional, in which body mass index was regressed against entry level calcium intake; and two were longitudinal, in which change in weight over time was regressed against calcium intake. One study was a double-blind, placebo-controlled, randomized trial of calcium supplementation, in which change in weight during the course of study was evaluated as a function of treatment status. Significant negative associations between calcium intake and weight were found for all three age groups, and the odds ratio for being overweight (body mass index, >26) was 2.25 for young women in the lower half of the calcium intakes of their respective study groups (P: < 0.02). Relative to placebo, the calcium-treated subjects in the controlled trial exhibited a significant weight loss across nearly 4 yr of observation. Estimates of the relationship indicate that a 1000-mg calcium intake difference is associated with an 8-kg difference in mean body weight and that calcium intake explains approximately 3% of the variance in body weight.
3. Heaney RP. Calcium, Dairy Products and Osteoporosis. J Am Coll Nutr. 2000 Apr;19(2 Suppl):83S-99S.
Osteoporosis is a multifactorial disorder in which nutrition plays a role but does not account for the totality of the problem. 139 papers published since 1975 and describing studies of the relationship of calcium intake and bone health are briefly analyzed. Of 52 investigator-controlled calcium intervention studies, all but two showed better bone balance at high intakes, or greater bone gain during growth, or reduced bone loss in the elderly, or reduced fracture risk. This evidence firmly establishes that high calcium intakes promote bone health. Additionally, three-fourths of 86 observational studies were also positive, indicating that the causal link established in investigator-controlled trials can be found in free-living subjects as well. The principal reason for failure to find an association in observational studies is the weakness of the methods available for estimating long-term calcium intake. While most of the investigator-controlled studies used calcium supplements, six used dairy sources of calcium; all were positive. Most of the observational studies were based on dairy calcium also, since at the time the studies were done, higher calcium intakes meant higher dairy intakes. All studies evaluating the issue reported substantial augmentation of the osteoprotective effect of estrogen by high calcium intakes. Discussion is provided in regard to the multifactorial complexity of osteoporotic response to interventions and to the perturbing effect in controlled trials of the bone remodeling transient, as well as about how inferences can validly be drawn from the various study types represented in this compilation.
4. Baron JA, Beach M, Mandel JS, van Stolk RU, Haile RW, Sandler RS, Rothstein R, Summers RW. Calcium Supplements and Colorectal Adenomas. Ann N Y Acad Sci. 1999;889:138-45.
Experimental and observational findings suggest that calcium intake may protect against colorectal neoplasia. To investigate this hypothesis, we conducted a randomized, double-blind trial of colorectal adenoma recurrence. Nine hundred thirty patients with a recent history of colorectal adenomas were randomly given calcium carbonate (3 gm daily; 1200 mg elemental calcium) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The main analysis focused on new adenomas found after the first follow-up endoscopy, up to (and including) the second follow-up examination. Risk ratios of at least one recurrent adenoma and ratios of the average numbers of adenomas were calculated as measures of calcium effect. There was a lower risk of recurrent adenomas in subjects assigned calcium. Eight hundred thirty-two patients had two follow-up examinations and were included in the main analysis; the adjusted risk ratio of one or more adenomas was 0.81 (95% CI 0.67 to 0.99); the adjusted ratio of the average numbers of adenomas was 0.76 (95% CI 0.60 to 0.96). Among subjects who had at least one follow-up colonoscopy, the adjusted risk ratio of one or more recurrent adenomas was 0.85 (95% CI 0.74 to 0.98). The effect of calcium seemed independent of initial dietary fat and calcium intake. No toxicity was associated with supplementation. These findings indicate that calcium supplementation has a modest protective effect against colorectal adenomas, precursors of most colorectal cancers.
5. Kamel HK. Male Osteoporosis: New Trends in Diagnosis and Therapy. Drugs Aging. 2005;22(9):741-8.
Osteoporosis is a common condition in men affecting approximately 2 million males in the US. Compared with women, osteoporosis develops later in life and the incidence of osteoporosis-related fractures is lower in men. The morbidity and mortality associated with osteoporotic fractures are much greater in men compared with women, and secondary causes of osteoporosis are more frequently (in approximately 50% of cases) identified in men compared with women with osteoporosis. Excessive alcohol consumption, glucocorticoid excess and hypogonadism are the most commonly identified causes. Primary osteoporosis in men has been linked to changes in sex steroid secretion, the growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis and the vitamin D-parathyroid hormone (PTH) 25-hydroxyvitamin D [25(OH)D]-PTH system. Diagnosing osteoporosis in men is complicated by an ongoing debate on whether to use sex-specific reference values for bone mineral density (BMD) or female reference values. The International Society for Clinical Densitometry recommended using a T score of -2.5 or less of male reference values to diagnose osteoporosis in men who are > or =65 years of age. However, this definition is yet to be validated in terms of fracture incidence and prevalence. Ensuring adequate calcium and vitamin D intake is the cornerstone of any regimen aimed at preventing or treating osteoporosis in men. Bisphosphonates are currently the therapy of choice for treatment of male osteoporosis. A short course of parathyroid hormone (1-34) [teriparatide] may be indicated for men with very low BMD or in those in whom bisphosphonate therapy is unsuccessful. The use of testosterone-replacement therapy for the prevention and treatment of male osteoporosis remains controversial but likely to benefit osteoporotic men with evident hypogonadism.
6. Hildebolt CF. J Periodontol. Effect of vitamin D and calcium on periodontitis. 2005 Sep;76(9):1576-87.
The anthropological record indicates that we are exposed to considerably less ultraviolet radiation (required for the synthesis of vitamin D) and consume considerably less calcium than did our early ancestors. Most U.S.citizens have calcium intakes and serum levels of vitamin D far below recommended values. This is despite there having been extensive evidence that optimal calcium and vitamin D intakes not only benefit our postcranial bone health but also have many other health benefits. Numerous articles indicate that vitamin D and calcium deficiencies result in bone loss and increased inflammation, which are well recognized symptoms of periodontal disease. For more than 40 years, investigators have suggested that calcium intake may be associated with alveolar bone resorption, and more recently there have been a number of studies in which investigators have suggested that calcium and vitamin D may benefit periodontal health, and it has been suggested that calcium deficiency may be a risk factor for periodontal disease. There has not, however, been a vitamin-D-calcium-periodontitis clinical trial in which randomization and masking were carefully controlled, the periodontal disease status of patients known, periodontal disease measures were the primary outcomes, and levels of intake optimized to produce maximal effects. Such research might demonstrate that calcium and vitamin D are important adjuncts to standard treatments for preventing and treating periodontal disease.
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