Calcium is the most abundant cation in the human body.
Calcium accounts for approximately 1 kg in a 70 kg male.
Calcium is a major mineral in bones and teeth and regulates muscle contraction and relaxation. It activates enzymes in various metabolic pathways and aids in blood clotting.
Research has shown that about 25-35 % of calcium in the diet is actually absorbed. Absorption declines with age and inadequate vitamin D intake. Absorption of calcium varies among individuals: the average absorption being more efficient in males than females.
Deficiency can result from a low dietary intake of calcium, reduction of stomach acid, high protein intake, low vitamin D status and increased GI motility.
The skeleton provides structural support for organs and muscles. It also stores essential minerals such as phosphorus and magnesium. The skeleton accounts for 99% of the body's calcium.
Teeth and bones contain about 99% of the body's calcium and are dependent upon calcium for strength and structure; the remaining 1% circulated in blood.
Calcium as food or dietary supplements is ingested in the form of relatively insoluble salts. The mineral is absorbed in the ionized form and must be released from these salts.
Both an active and passive transport mechanisms are responsible for absorption of calcium in the small intestine. The active mechanism depends on the action of activated form of vitamin D, 1-25-dihydroxycholecalciferol or 1,25-(OH)2D3. In vitamin D-induced calcium transport, synthesis of calbindin, a calcium-binding protein, is involved. This serves as a translocator, and as a cytosolic calcium buffer. During digestion, calcium is freed from calcium complexes into a soluble form, which can be ionized for absorption.
Calcium carbonate is more difficult to absorb on an empty stomach, it needs an acidic environment to enhance absorption. The percent of calcium absorbed decreases as the calcium load increases; therefore calcium carbonate absorption is greatest in doses of 500 mg or less, with food.
Since calcium citrate is highly soluble in acid, it is better absorbed on an empty stomach. The citrate form does not need gastric acid for absorption
Calcium lactate can be absorbed at various pHs and does not need to be taken with food for absorption for these reasons.
Elemental calcium refers to the amount of calcium found in a product because calcium alone is unstable.
Calcium phosphate is insoluble and is poorly absorbed.
Young infants and approximately 30% of elderly have low secretion of hydrochloric acid by gastric parietal cells. It has been established that low hydrochloric acid secretion can lead to decreased absorption of some minerals. Conflicting results have been reported in clinical studies on the effects of intraluminal gastric pH values on calcium absorption.
Calcium absorption can be decreased by high intake of foods that contain oxalic acid (spinach, chard, beet greens), phytic acid in unleavened whole grains, large intake of phosphorus-containing foods (meat or soda), stress, lack of movement, diazide diuretics, laxatives or aluminum -containing medications.
Osteoporosis is a disease that results in reduction in mass of bone per unit of volume due to inadequate calcium intake. Calcium exists in bone in the form of hydroxyapatite, which comprises approximately 40% of the weight of bone. Osteomalacia results from deficiency or loss of calcium salts due to vitamin D deficiency. It is softening of the bone in adults, usually caused by a failure of normal bone calcification. Osteopenia is reduction of bone mass due to an imbalance between bone breakdown and bone formation. Resorption rates are higher than bone formation rates, resulting in demineralization and ultimately osteoporosis.
Hypocalcemia is frequently asymptomatic and is often seen with underlying disorders (e.g., cataracts, basal ganglia calcification, and chronic candidiasis in some patients with idiopathic hypoparathyroidism).
Clinical manifestations are primarily neurologic. Slowly developing insidious hypocalcemia may produce mild encephalopathy.
The most characteristic syndrome of hypocalcemia is tetany, resulting from severe hypocalcemia. Tetany is characterized by sensory symptoms consisting of paresthesia of the lip, tongue, fingers and feet. Other symptoms include carpopedal spasm, generalized muscle aching, and spasm of facial musculature.
Vitamin D deficiency may be due to inadequate intake, a decreased exposure to sunlight, hepatobiliary disease or intestinal malabsorption. It is associated with rickets in children and osteomalacia in adults.
A diet lacking calcium, vitamins D, C, K, magnesium, zinc and phosphorus may all increase the risk of osteoporosis. This can cause skeletal weakness and increased bone resorption resulting in bone fractures.
Deficiency or absence of parathyroid hormone (hypoparathyroidism), a hormone deficiency characterized by low serum calcium and high serum phosphorus concentrations, is commonly seen with chronic tetany.
Other incidences of hypocalcemia, due to the result of:
Calcium supplemental doses up to 2,500 mg/day are usually well tolerated. Doses that exceed this amount may increase the risk for kidney stones and soft tissue calcification. Neither of these conditions is solely linked to calcium supplements.
Individuals that suffer from hyperparathyroidism should not take calcium without physician's supervision.
Dairy products are a good source of calcium. Eight ounces of whole milk contains 291 mg of calcium and skim milk contains 302
mg of calcium. Other milk products, such as yogurt, ice cream and ice milk, all
contain various amounts of calcium. A half-cup to 1 oz of ricotta cheese,
cottage cheese, cheddar and mozzarella all contain anywhere from 155 to 337 mg
of calcium. One cup or 8 oz of fruits and vegetables like broccoli, turnip
greens mustard greens, legumes and dried fruits contain anywhere from 56 to 300
mg of calcium. Fish, shellfish and raw tofu are also good sources of calcium.
Fortified foods such as apple juice, orange juice, and cottage cheese provide
extra calcium.
Approximately 25 million American women suffer from osteoporosis and it's potential pain and disfigurement. Another one-third to one-half of postmenopausal women are at risk for osteoporosis. Eighty percent of those who have osteoporosis are women. One out of every two women is at risk of developing fractures caused by osteoporosis.
One-third to one-half of postmenopausal women are at risk for osteoporosis because absorption of calcium in postmenopausal women declines an average of 0.21% yearly. Age of menopause can also be a factor. If menopause occurs at a younger age, estrogen concentrations decline sooner and the protective effect of estrogen is lost.
Lactose intolerant women may be at higher risk and should be especially careful to obtain adequate calcium through other non-dairy sources.
Heredity or thin, small petite women may have a higher incidence of osteoporosis.
Cigarette smoking has been shown to lower serum concentrations of estrogen and decrease calcium absorption.
Alcohol consumption may be linked with an increased incidence for falls and improper nutrition leading to deficiencies in calcium and vitamin D.
Long term use of certain medications can increase parathyroid hormone secretion, block vitamin D, and interfere with calcium absorption.
Calcium supplementation has shown to reverse the blood
pressure-lowering effect of verapamil, an anti-arrhythmic agent. It remains
unclear whether people taking the drug to treat blood pressure should avoid
calcium supplementation. However, patients taking verapamil to treat angina or
heart arrhythmias are to take reduced amounts of calcium supplementation, to
prevent possible excessive blood pressure-lowering actions caused by
verapamil.
Calcium complexes interact with tetracycline antibiotics, rendering them inactive. These should not be taken concurrently.
Thiazide diuretics, such as hydrochlorothiazide (HCTZ), are used to treat hypertension. They decrease calcium loss in the urine due to action on the kidneys. As a result, it may be less important for some people taking the drug to supplement calcium than for other people. Hypercalcemia, resulting from renal tubular reabsorption of calcium or bone release of calcium by thiazides, may be amplified by exogenous calcium.
Mean peak plasma concentrations and bioavailability of atenolol [Tenorminâ], a beta-blocker used for myocardial infarction, may be decreased by supplemental calcium, resulting in decreased beta blockage.
GI absorption of iron may be decreased when taken with calcium supplementation.
Bioavailability of norfloxacin [Noroxinâ], an antibiotic agent, is reduced by minerals, including calcium. It is advisable to take the drug 2 hours before or 4 hours after consuming dairy products such as milk, cheese, yogurt, ice cream, antacids, and mineral-containing supplements.
Steroidal anti-inflammatory drugs used for more than 2 weeks reduce the body's ability to activate vitamin D, increasing the risk of bone loss. Supplementation of vitamin D with calcium is recommended.
Calcium supplements may decrease absorption of Alendronateâ, an antiosteoporosis agent. The drug should be taken 2 hours before or after calcium supplements.
Many minerals, including calcium, can decrease absorption of tetracycline, an antibiotic, thereby, reducing effectiveness of the drug.
Information on the relationship between substances and disease is provided for general information, in order to convey a balanced review of the scientific literature. In many cases the relationship between a substance and a disease is tentative and additional research is needed to confirm such a relationship.
Osteoporosis Osteoporosis affects about 10 million people in the United States. An additional 18 million have osteopenia (low bone mass), a condition that increases the risk of osteoporosis. 10
It has been reported that the incidence of osteopenia and osteoporosis is much greater among white women compared with African American women, with little data available on Native American women. 1112
According to the NIH Consensus Statement, women between the ages of 25 and 50 should maintain a calcium intake of 1,000 mg/day. At the onset of menopause and for years thereafter, a decline in circulating 17-beta-estradiol is the predominant factor in accelerated bone loss. Therefore, it has been suggested that postmenopausal women who do not receive estrogen replacement take in 1,500mg of calcium/day, to limit the loss of bone mass. Postmenopausal women up to 65 years of age who are receiving hormone replacement therapy should receive at least 1,000 mg/day of calcium.
For women and men over age 65, an insufficient intake of calcium due to low calcium intake and reduced absorption of the mineral can lead to accelerated age-related bone loss in older individuals. Homebound elderly and long-term care residents offer suffer from a vitamin D insufficiency, which exacerbates the problem of decreased calcium absorption. Thus, a calcium intake of 1,500 mg/day for women and men over 65 is suggested. 13
Pregnancy and Lactation: During pregnancy there is a significant physiological stress on maternal skeletal homeostasis. A term infant will obtain about 30 grams of calcium during gestation with most being accumulated during the third trimester. There are no data that show a permanent decline in body calcium if recommended levels of calcium are achieved. Lactating women lose 160-300 mg a day of maternal calcium through breast-feeding.
Studies in healthy women demonstrated that acute bone loss can occur during lactation which is followed by a rapid onset of bone mass with recurrence of menses and weaning.14
Premenstrual syndrome (PMS): There is some evidence that calcium supplementation may help treat some symptoms of premenstrual syndrome.
A study giving 1200 mg of calcium carbonate or placebo to 720 women with PMS showed decreased symptoms of PMS after 3 months. After the 3 months, women who took the calcium supplements noted a 48% drop in overall PMS symptoms, compared with a 30% drop in the placebo group. Women in the calcium group reported a 45% reduction in mood swings and depression, compared with a 28% in the placebo group.15
Abnormalities in calcium and vitamin D regulation may contribute to the causation of PMS. Premenstrual syndrome could be linked to other disorders associated with inadequate calcium intake, such as osteoporosis. There is convincing evidence that calcium supplementation at a dose of 1,000-1,200 mg/day substantially decreased many of the symptoms associated with PMS.16
Menopause: At time of menopause, estrogen declines, which protects women's bodies from bone loss. Early menopause or surgical removal of ovaries can increase chances of women to develop osteoporosis. Declines in estrogen production in younger women will increase the risk for osteoporosis. Anorexia or bulimia and excessive exercise can be associated with pre-menopausal estrogen deficiency, abnormal menstruation and finally bone loss. After menopause, women are at high risk for developing osteoporosis. Studies indicated that women lose calcium from their bones at a high rate in the first 3 years of menopause.
In a review of 7 published clinical trials measuring bone mass of postmenopausal women, 6 trials used calcium supplementation (total 1466 mg/day), with 200 IU of calcitonin, whereas one used calcitonin alone (total 627 mg/day). Bone mass of the lumbar spine increased 2.1% with calcitonin plus calcium supplementation compared with -0.2%/year with calcitonin alone. In conclusion, there appears to be a synergistic relation between a high calcium intake and estrogen and calcitonin treatment for osteoporosis. 17
A study on early and mid-postmenopausal women gave 25 women 400 mg of calcium citrate two times a day and 31 women placebo for one to two years. In the calcium citrate group, radial bone shaft density did not change, and there was a protective effect on L2-L4 bone density three years after postmenopause. In some calcium citrate treatment periods, serum bone-specific alkaline phosphatase, osteocalcin and urinary hydroxyproline and N-telopeptide concentration decreased. It was concluded that 400 mg twice a day averted bone loss, stabilized bone density (at spine, femoral neck and radial shaft) in women after menopause.18
In another study, 31 healthy women over age 70 years were given either 0.5 mg/day of estradiol or 1500 mg of elemental calcium (given as calcium carbonate) plus 800 IU of vitamin D for 12 weeks. After the initial 12 weeks, both groups received calcium, vitamin D and estradiol for another 12 weeks. All markers of bone resorption decreased with initial treatment and decreased further with combination therapy. Bone formation markers decreased with the calcium and vitamin D treatment, but not with the estradiol alone. There was no additional effect of combination therapy on bone formation markers compared to the calcium and vitamin D alone. The results indicated in older women, that there is an additive effect of low dose estrogen and calcium on bone resorption, but not on bone formation. 19
Weight reduction (This section addresses the effects of weight reduction/dieting on bone mass and also body weight/fat mass).
(Effect on bone density)
It has been reported that weight loss induces bone resorption and calcium supplementation can help attenuate bone loss while dieting. One study found that a diet high in calcium and protein would minimize bone resorption during weight loss compared to a diet lower in calcium and protein. Subjects were either randomly assigned to isoenergetic diets wither high in dairy protein (DP, 2400 mg Ca/D)) or mixed protein sources (MP, 500 mg Ca/D). Effects of these diets on calcium excretion and bone metabolism in 50 overweight adults were examined during 12 weeks of energy restriction, followed by 4 weeks of energy balance. During the energy restriction phase, weight loss was 10%, and 24-hour urinary calcium excretion decreased independently of diet. The MP diet showed a much greater increase in bone resorption than the DP diet group by week 16. Bone formation increased from week 0 to 16 in only the MP diet group. Results showed that the DP diet group minimized overall bone turnover more than the MP diet group, and suggest that a high dairy protein, high calcium diet may protect against bone loss during weight reduction. 20
(Effect on body weight/fat )
Randomized trials with calcium supplementation were selected through a Medline search to assess the effect on body weight/composition in humans. With calcium supplementation, one study found greater weight loss in the calcium supplemented group, however the remaining studies found no changes in body weight and/or body fat. Studies on dairy product supplementation noted no significant differences in changes in body weight/composition between dairy supplement and control groups. Results from this paper suggest that more well-designed studies are needed to examine the effect of dairy product or calcium supplementation on reducing body weight or fat mass in humans. 21
Analysis of data from six observational studies and three clinical trials on the effect of calcium intake on body weight and body fat revealed a higher calcium intake reduced body weight/fat, and reduced weight gain at mid-life. Each 300 mg increment in regular calcium intake, was associated with 1 kg less body fat in children and 2.5-3.0 kg lower body weight in adults. These data suggest increasing calcium intake to the equivalent of two dairy servings per day (~600 mg) to reduce risk of becoming overweight by as much as 70%.22
Dr. Zemel from the department of nutrition at the University of Tennessee, has been a leader in research on calcium intake and adiposity. Using the agouti gene transgenic mouse, Dr. Zemel’s research has shown a key role of intracellular calcium in regulating fat cell metabolism and storage. Increasing dietary calcium suppresses calcitriol, which is produced when low calcium intakes are consumed and promotes adiposity. Suppressing calcitriol is, therefore, a target intervention for combating obesity. Transgenic mice have demonstrated that low calcium diets are marked by accelerated weight gain/fat, whereas high calcium diets inhibit lipogenesis, accelerate lipolysis, increase thermogenesis, and suppress fat accretion and weight gain in animals maintained at identical caloric intakes. His research, along with some epidemiological and clinical data, suggests that calcium from dairy sources exert greater effects than calcium supplementation, which may be due to bioactive compounds in dairy products that act synergistically with calcium to attenuate adiposity. The effects of dairy products on body weight/fat loss are greater when secondary to caloric restriction. These data indicate the important role of calcium and dairy in prevention/treatment of obesity. 23
Breast Cancer
The hypothesized effect of calcium on breast cancer is reducing fat-induced cell proliferation by maintaining intracellular calcium concentrations. 24, 25
Data from the Nurses’ Health Study cohort was analyzed to evaluate whether a high intake of dairy products, calcium, or vitamin D is associated with reduced risk of breast cancer. From the 88,691 women followed from 1980 until 1996, 3,482 women were identified with incident invasive breast cancer. Of these women, 827 were premenopausal, 2,345 were postmenopausal and 310 were of uncertain menopausal status. Results of statistical analyses showed that high intakes of dairy products, especially low-fat dairy and skim/low-fat milk, may be associated with a modest reduction in risk of breast cancer in premenopausal women, but not in postmenopausal women. Supplemental calcium and vitamin D intake was accounted for in the study. The association with calcium was due mainly to dairy sources, whereas vitamin D may be independent of dairy intake. Inverse associations were seen with calcium and vitamin D and breast cancer. However, independent associations with other constituents of dairy foods (i.e. lactose, phosphorus, conjugated linoleic acid) including calcium and total vitamin D and risk of breast cancer were difficult to distinguish. 26
Prostate Cancer
There is a body of evidence that supports an increased risk of prostate cancer in men with a high calcium intake.
Data from the Cancer Prevention Study II Nutrition Cohort, found total calcium intake from diet and supplements, was associated with modestly increased risk of prostate cancer in men [RR = 1.2, 95% confidence interval (CI) = 1.0-1.6 for >or=2000 versus <700 mg/day, P trend = 0.02). Risk was higher with a high dietary calcium intake (2000 mg/day or more versus <700 mg/day), however, a moderate level of dietary calcium was not associated with an increased risk for prostate cancer. A very high calcium intake may modestly increase risk for prostate cancer in men.27
The Baltimore Longitudinal Study of Aging on men age 46 to 92 years old investigated the association between calcium intake and prostate cancer risk. Median calcium intake was 788 mg/day. Results from multiple logistic regression analysis indicated the adjusted odds ratio of prostate cancer from the highest tertile compared to the lowest tertile of calcium intake was 0.92. The adjusted odds ratio of prostate cancer for men with high dairy calcium intakes compared to those with low dairy intakes was 1.2. Overall, a moderate intake of calcium is not associated with a significant increase in prostate cancer risk.28
Colorectal Cancer
A systematic review of randomized controlled trials was conducted to assess the effect of dietary calcium on the incidence of colorectal cancer and the incidence or recurrence of adenomatous polyps. Two double-blind, placebo-controlled trials involving 1346 subjects met inclusion criteria. Doses of supplemental elemental calcium used were 1200 mg/daily for a mean of four years and 2000 mg/day for three years. Combined results from both trials found a reduction in recurrent colorectal adenoma. Reviewer’s concluded that calcium supplementation may have a modest effect on prevention of colorectal adenomatous polyps, however, more research is needed to support this hypothesis.29
One randomized trial examined the association between calcium intake and colon cancer risk from two prospective cohorts, the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). The study population included 87,998 women in NHS and 47,344 men in HPFS. At baseline (1980 for NHS, 1986 for HPFS), subjects provided information on medical history, lifestyle, and completed a food frequency questionnaire. Dietary information was updated at least every four years. During follow-up (1980 to May 1996 for NHS; 1986 to January 1996 For the HPFS), over 600 colon cancer cases were identified for women; approximately 400 cases were identified for men. Results for both men and women indicated an inverse association between higher total calcium intake (>1250 mg/day of calcium versus < or = 500 mg/day of calcium) and distal colon cancer. A moderate intake of calcium is suggested to be associated with a reduced risk for colon cancer. Additional benefit from high calcium intakes (> 700 mg/day) appear to be minimal. Future research is warranted to investigate the association of calcium intakes on specific cancer subsites and on dose-response relationship.30
Calcium Stones
The most common form of kidney stones are calcium stones (calcium oxalate or calcium phosphorus). Conventional wisdom has recommended individuals to limit calcium intake to prevent calcium stones, however, there is a body of evidence that actually suggests the opposite. Research shows that a normal calcium intake, along with a diet reduced in salt and protein can reduce risk for developing calcium stones.31
Some large prospective studies have shown that dietary calcium intake is inversely related to the risk of developing kidney stones for both men and women. It has been hypothesized that if enough calcium is not consumed, less calcium is available to bind to dietary oxalate. Therefore, more oxalate reaches the colon where absorption into the bloodstream takes place. It is then excreted as calcium oxalate by kidney, which allows for calcium stone formation. In comparing dietary calcium with supplemental calcium, it was found that calcium supplementation may increase risk for stones. This may be because supplements are often ingested without food or after a meal low in oxalate. Therefore, calcium supplements should be taken with a meal containing oxalate (i.e. vegetables, fruits, grains, nuts/seeds, legumes, chocolate, etc.)32,33
The dietary supplement information contained on this site has been compiled from published sources thought to be reliable, but it cannot be guaranteed. Efforts have been made to assure this information is accurate and current. However, some of this information may be purported or outdated due to ongoing research or discoveries. The authors, editors and publishers cannot accept responsibility for errors or omissions or for any consequences from applications of the information in this site and make no warranty, expressed or implied, with respect to the contents herein.
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