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Calcium

June 10, 2008 - 7:30am
 
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Calcium

Supplement Forms/Alternate Names
  • Bonemeal, Calcium Aspartate, Calcium Carbonate, Calcium Chelate, Calcium Citrate, Calcium Citrate Malate, Calcium Gluconate, Calcium Lactate, Calcium Orotate, Dolomite, Oyster Shell Calcium, Tricalcium Phosphate
Principal Proposed Uses
  • ]]>Osteoporosis]]>, ]]>Premenstrual Syndrome (PMS)]]>

Calcium is the most abundant mineral in the body, making up nearly 2% of total body weight. More than 99% of the calcium in your body is found in your bones, but the other 1% is perhaps just as important for good health. Many enzymes depend on calcium in order to work properly, as do your nerves, heart, and blood-clotting mechanisms.

To build bone, you need to have enough calcium in your diet. But in spite of calcium-fortified orange juice and the best efforts of the dairy industry, most Americans are calcium deficient. ]]>1]]> Calcium supplements are a simple way to make sure you're getting enough of this important mineral.

One of the most important uses of calcium is to help prevent and treat osteoporosis, the progressive loss of bone mass to which ]]>menopausal]]> women are especially vulnerable. Calcium works best when combined with vitamin D.

Other meaningful evidence suggests that calcium may have an additional important use: reducing PMS symptoms.

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Requirements/Sources

Although there are some variations between recommendations issued by different groups, the official US and Canadian recommendations for daily intake of calcium are as follows:

  • Infants
    • 0-6 months: 210 mg
    • 7-12 months: 270 mg
  • Children
    • 1-3 years: 500 mg
    • 4-8 years: 800 mg
  • Males and Females
    • 9-18 years: 1,300 mg
    • 19-50 years: 1,000 mg
    • 51 years and older: 1,200 mg
  • Pregnant and Nursing Women
    • Under 19 years: 1,300 mg
    • 19 years and older: 1,000 mg

To absorb calcium, your body also needs an adequate level of vitamin D (for more information, see the article on Vitamin D]]> ).

Various medications may impair calcium absorption or metabolism, either directly or through effects on vitamin D. People who use these may benefit by taking extra calcium and vitamin D. Implicated medications include ]]>corticosteroids]]> , ]]>30-32]]>]]>heparin]]> , ]]>33-35]]>]]>isoniazid]]> , ]]>36-38]]> and ]]>anticonvulsants]]> . ]]>39-45]]>Note: Calcium carbonate might interfere with the effects of anticonvulsant drugs, and for that reason should not be taken at the same time of day. ]]>46,47]]>

Milk, cheese, and other dairy products are excellent sources of calcium. Other good sources include orange juice or soy milk fortified with calcium, fish canned with its bones (such as sardines), dark green vegetables, nuts and seeds, and calcium-processed tofu.

Many forms of calcium supplements are available on the market, each with its own advantages and disadvantages.

Naturally Derived Forms of Calcium

These forms of calcium come from bone, shells, or the earth: bonemeal, oyster shell, and dolomite. Animals concentrate calcium in their shells, and calcium is found in minerals in the earth. These forms of calcium are economical, and you can get as much as 500 mg to 600 mg in one tablet. However, there are concerns that the natural forms of calcium supplements may contain significant amounts of lead. ]]>2]]> The level of contamination has decreased in recent years, but still may present a health risk. ]]>3,4]]> Calcium supplements rarely list the lead content of their source, although they should. The lead concentration should always be less than 2 parts per million.

Refined Calcium Carbonate

This is the most common commercial calcium supplement, and it is also used as a common antacid. Calcium carbonate is one of the least expensive forms of calcium, but it can cause constipation and bloating, and it may not be well absorbed by people with reduced levels of stomach acid. Taking it with meals improves absorption because stomach acid is released to digest the food. ]]>121]]> (See the section, Chelated Calcium, below.)

Chelated Calcium

Chelated calcium is calcium bound to an organic acid (citrate, citrate malate, lactate, gluconate, aspartate, or orotate). The chelated forms of calcium offer some significant advantages and disadvantages compared with calcium carbonate.

Certain forms of chelated calcium (calcium citrate and calcium citrate malate) are widely thought to be significantly better absorbed and more effective for osteoporosis treatment than calcium carbonate. However, while some studies support this belief, ]]>6,7,9,10]]> others do not. ]]>8,122,123]]> The discrepancy may be due to the particular calcium carbonate products used; some calcium carbonate formulations may dissolve better than others.

One study found that calcium citrate malate in orange juice is markedly better absorbed than tricalcium phosphate/calcium lactate in orange juice. ]]>148]]>

A form of calcium called active absorbable algal calcium (AAACa) has also been promoted as superior to calcium carbonate, but the study upon which claims of benefit are founded actually used quite questionable statistical methods (technically, post-hoc subgroup analysis). ]]>133]]>

Chelated calcium is much more expensive and bulkier than calcium carbonate. In other words, you have to take larger pills, and more of them, to get enough calcium. It is not at all uncommon to need to take five or six large capsules daily to supply the necessary amount, a quantity some people may find troublesome.

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Therapeutic Dosages

Unlike some supplements, calcium is not taken at extra high doses for special therapeutic benefit. Rather, for all its uses, it should be taken in the amounts listed under Requirements/Sources, along with the recommended level of vitamin D. (See the article on vitamin D]]> for proper dosage amounts.)

Calcium absorption studies have found evidence that your body can't absorb more than 500 mg of calcium at one time. ]]>11]]> Therefore, it is most efficient to take your total daily calcium in two or more doses.

Use of ]]>prebiotics]]> known as "inulin fructans" may improve calcium absorption. ]]>149]]>

It isn't possible to put all the calcium you need in a single ]]>multivitamin/mineral]]> tablet, so this is one supplement that should be taken on its own. Furthermore, if taken at the same time, calcium may interfere with the absorption of ]]>chromium]]> and ]]>manganese]]> . ]]>12,13,14]]> This means that it is best to take your multivitamin and mineral pill at a separate time from your calcium supplement.

Although the calcium present in some antacids or supplements may alter the absorption of ]]>magnesium]]> , this effect apparently has no significant influence on overall magnesium status. ]]>15,16]]> Calcium may also interfere with ]]>iron]]> absorption, ]]>17-22,]]>]]>150]]> but the effect may be too slight to cause a problem. Some studies show that calcium may decrease ]]>zinc]]> absorption when the two are taken together as supplements; however, studies have found that, in the presence of meals, zinc levels may be unaffected by increases of either dietary or supplemental calcium. ]]>23-29]]>

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Therapeutic Uses

According to most, though not all studies, use of calcium (especially in the form of calcium citrate) combined with vitamin D]]> may modestly slow the bone loss that leads to ]]>osteoporosis]]> . ]]>48-55,151-153]]>

A rather surprising potential use of calcium came to light when a large, well-designed study found that calcium is an effective treatment for ]]>premenstrual syndrome]]> (PMS). ]]>56]]> Calcium supplementation reduced all major symptoms, including headache, food cravings, moodiness, and fluid retention. It is at least remotely possible that there may be a connection between these two uses of calcium: weak evidence hints that PMS might be an early sign of future osteoporosis. ]]>57,58]]>

One small but carefully conducted study suggests that getting enough calcium may help control symptoms of ]]>menstrual pain]]> . ]]>89]]>

Some, but not all, observational and intervention studies have found evidence that calcium supplementation may reduce the risk of colon ]]>cancer]]> . ]]>59,134-135,154-156]]> Risk reduction might continue for years after calcium supplements are stopped. ]]>182]]> However, calcium supplements might increase risk of prostate cancer in men, as discussed in the ]]>Safety Issues]]> section. For menopausal women, calcium supplementation, especially with vitamin D added, may reduce cancer risk in general. ]]>187]]>

Individuals who are deficient in calcium may be at greater risk of developing ]]>high blood pressure]]> . ]]>60,61,126]]> Among individuals who already have hypertension, increased intake of calcium might slightly decrease blood pressure, according to some, but not all, studies. ]]>62,127]]> Weak evidence hints that use of calcium by pregnant mothers might reduce risk of hypertension in their children. ]]>185]]>

Calcium supplements might slightly improve the ]]>cholesterol]]> profile. ]]>63,64,124]]>

Calcium supplementation has also been tried as a treatment to prevent ]]>preeclampsia]]> in pregnant women. While the evidence from studies is conflicting, ]]>66-68,157-15]]> calcium supplementation might offer at least a minimal benefit.

The drug ]]>metformin]]> , used for diabetes, interferes with the absorption of ]]> vitamin B 12]]> . Interestingly, calcium supplements may reverse this, allowing the B 12 to be absorbed normally. ]]>70]]>

Rapid ]]>weight loss]]> in overweight postmenopausal women appears to slightly accelerate bone loss. ]]>71,136]]> For this reason, it may make sense to take calcium and vitamin D supplements when deliberately losing weight. It has been additionally suggested that ]]>calcium]]> supplements, or high-calcium diets, may directly enhance weight loss, but current evidence is more negative than positive. ]]>72,130,137,159-165,186,188,189,191]]>

Finally, calcium is also sometimes recommended for ]]>attention deficit disorder]]> , ]]>migraine headaches]]> , and ]]>periodontal disease]]> , but there is as yet no meaningful evidence that it is effective for these conditions.

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What Is the Scientific Evidence for Calcium?

Osteoporosis

A number of double-blind, placebo-controlled studies]]> indicate that calcium supplements (especially as calcium citrate, and taken with vitamin D) are slightly helpful in preventing and slowing down bone loss in postmenopausal women. ]]>73-76,138,165-169,180]]> Contrary to some reports, milk does appear to be a useful source of calcium for this purpose. ]]>183-184]]> However, the effect of calcium supplementation in any form is relatively mild and may not be strong enough to reduce the rate of osteoporotic fractures. Note that use of calcium and vitamin D use must be continual. Any improvements in bone rapidly disappear once the supplements are stopped. ]]>77]]> Calcium carbonate may not be effective. ]]>170-171]]>

One study found benefits for male seniors using a calcium and vitamin D-fortified milk product. ]]>172]]> (See, however, possible increased risk of prostate cancer discussed in ]]>Safety Issues]]> .)

Calcium and vitamin D supplementation may help bones heal that have become fractured due to bone thinning. ]]>139]]>

Calcium supplements may do a better job of strengthening bones when people have relatively high protein intake. ]]>125]]>

Heavy ]]>exercise]]> causes increased calcium loss through sweat, and the the body does not compensate for this by reducing calcium loss in the urine. ]]>190]]> The result can be a net calcium loss great enough so that it presents health concerns for menopausal women, already at risk for osteoporosis. One study found that use of an inexpensive calcium supplement (calcium carbonate), taken at a dose of 400 mg twice daily, is sufficient to offset this loss. ]]>190]]>

Calcium supplementation could, in theory, be useful for young girls as a way to "put calcium in the bank"—building up a supply for the future in order to prevent later osteoporosis. However, surprisingly, the benefits seen in studies have been modest to nonexistent, and this approach may only produce results when exercise is also increased. ]]>79-81,140-143,173-175,181]]>

One study found that in calcium-deficient pregnant women, calcium supplements can improve the bones of their unborn children. ]]>82]]>

Evidence suggests that the use of calcium combined with vitamin D can help protect against the bone loss caused by corticosteroid drugs, such as prednisone. A review of five studies covering a total of 274 participants reported that calcium and vitamin D supplementation significantly prevented bone loss in corticosteroid-treated individuals. ]]>83]]> For example, in a 2-year, double-blind, placebo-controlled study that followed 65 individuals with rheumatoid arthritis taking low-dose corticosteroids, daily supplementation with 1,000 mg of calcium and 500 IU of vitamin D reversed steroid-induced bone loss, causing a net bone gain. ]]>84]]>

There is some evidence that essential fatty acids may enhance the effectiveness of calcium. In one study, 65 postmenopausal women were given calcium along with either placebo or a combination of omega-6 fatty acids (from ]]>evening primrose oil]]> ) and omega-3 fatty acids (from ]]>fish oil]]> ) for a period of 18 months. At the end of the study period, the group receiving essential fatty acids had higher bone density and fewer fractures than the placebo group. ]]>85]]> However, a 12-month, double-blind trial of 42 postmenopausal women found no benefit. ]]>86]]> The explanation for the discrepancy may lie in the differences between the women studied. The first study involved women living in nursing homes, while the second studied healthier women living on their own. The latter group of women may have been better nourished and already received enough essential fatty acids in their diet.

Premenstrual Syndrome (PMS)

According to a large and well-designed study published in a 1998 issue of American Journal of Obstetrics and Gynecology, calcium supplements are a simple and effective treatment for a wide variety of ]]>PMS]]> symptoms. ]]>87]]> In a double-blind, placebo-controlled study of 497 women, 1,200 mg daily of calcium as calcium carbonate reduced PMS symptoms by half over a period of three menstrual cycles. These symptoms included mood swings, headaches, food cravings, and bloating. These results corroborate earlier, smaller studies. ]]>88,89]]>

High Cholesterol

In a 12-month study of 223 postmenopausal women, use of calcium citrate at a dose of 1 g daily improved the ratio of HDL (“good”) ]]>cholesterol]]> levels to LDL (“bad”) cholesterol levels. ]]>124]]> The extent of this improvement was ]]>statistically significant]]> (as compared to the placebo group), but not very large in practical terms. Similarly modest benefits were seen in a previous, smaller double-blind, placebo-controlled study. ]]>63]]> A third double-blind, placebo-controlled study failed to find any statistically significant effects. ]]>64]]>

Colon Cancer

Evidence from ]]>observational studies]]> showed that a high calcium intake is associated with a reduced incidence of ]]>colon cancer]]> , ]]>91]]> but not all studies have found this association. ]]>92]]>

Some but not all evidence from ]]>intervention trials]]> supports these findings. ]]>90,176-178]]>

A 4-year, double-blind, placebo-controlled study followed 832 individuals with a history of colon polyps. ]]>90]]> Participants received either 3 g daily of calcium carbonate or placebo. The calcium group experienced 24% fewer polyps overall than the placebo group. Since colon polyps are the precursor of most colon cancer, this finding strongly suggests benefit. Combing the results for two trials, involving a total of 1,346 subjects also with a history of polyps, researchers found that 1,200 mg or 2,000 mg of daily elemental calcium led to a significant reduction in polyp recurrence compared to placebo over a 3-4 year period.]]>193]]> Another, large-sized study found that calcium carbonate at a dose of 1,200 mg daily may have a more pronounced effect on dangerous polyps than on benign ones. ]]>144]]>

However, a gigantic (36,282 participant), very long-term (average 7 years) study of postmenopausal women failed to find that calcium carbonate supplements at a dose of 1,000 mg daily had any effect on the incidence of colon cancer. ]]>178]]> Given these conflicting results, if calcium supplementation does have an effect on colon cancer risk, it is probably small.

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Safety Issues

In general, it's safe to take up to 2,500 mg of calcium daily, although this is more than you need. 93,119]]> Greatly excessive intake of calcium can cause numerous side effects, including dangerous or painful deposits of calcium within the body.

Note: If you have cancer, hyperparathyroidism, or sarcoidosis, you should take calcium only under a physician's supervision.

Some evidence hints that use of calcium supplements might slightly increase ]]>kidney stone]]> risk. ]]>96,132,178]]> However, increased intake of calcium from food does not seem to have this effect and could even help prevent stones. ]]>94,95,97,132]]> One study found that if calcium supplements are taken with food, there is no increased risk. ]]>146]]> Calcium citrate supplements may be particularly safe regarding kidney stones because the citrate portion of this supplement is used to treat kidney stones. ]]>147]]>

There is weak, preliminary evidence that calcium supplementation in healthy, post-menopausal women may slightly increase the risk of cardiovascular events, such as myocardial infarction. However, it remains far from clear whether this possible risk outweighs the benefits of calcium supplementation in this population.]]>192]]>

Large observational studies have found that, in men, higher intakes of calcium are associated with an increased risk of prostate cancer. ]]>98,99,100,179]]> This seems to be the case whether the calcium comes from milk or from calcium supplements.

Calcium supplements combined with high doses of vitamin D might interfere with some of the effects of drugs in the calcium channel blocker family. ]]>101]]> It is very important that you consult your physician before trying this combination.

Concerns have been raised that the aluminum in some antacids may not be good for you. ]]>102]]> There is some evidence that calcium citrate supplements might increase the absorption of aluminum; ]]>103-107]]> for this reason, it might not be a good idea to take calcium citrate at the same time of day as aluminum-containing antacids. Another option is to use different forms of calcium, or to avoid antacids containing aluminum.

When taken over the long term, thiazide diuretics tend to increase levels of calcium in the body by decreasing the amount excreted by the body. ]]>108-111]]> It's not likely that this will cause a problem. Nonetheless, if you are using thiazide diuretics, you should consult with your physician on the proper doses of calcium and vitamin D for you.

Finally, calcium may interfere with the absorption of antibiotics in the tetracycline and fluoroquinolone families as well as thyroid hormone. ]]>112-118]]> If you are taking any of these drugs, you should take your calcium supplements at least 2 hours before or after your medication dose.

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Interactions You Should Know About

  • You may need more calcium if you are taking:
  • If you are taking ]]>aluminum hydroxide]]> , you should take calcium citrate at least 2 hours apart to avoid increasing aluminum absorption.
  • You may need more calcium if you are taking the following anticonvulsants:
  • If you are taking the following medications, you should take your calcium supplement at least 2 hours before or after your dose of medication because calcium interferes with the absorption (and vice versa):
  • Do not take extra calcium except on the advice of a physician if you are taking ]]>Thiazide diuretics]]> .
  • Do not take calcium together with high-dose vitamin D except on the advice of a physician if you are taking ]]>calcium channel blockers]]> .
  • You may need extra calcium if you are taking:
    • ]]>Iron]]>
    • ]]>Manganese]]>
    • ]]>Zinc]]>
    • ]]>Chromium]]>
    • Ideally, you should take calcium at a different time of day from these other minerals because it may interfere with their absorption.
  • It may be advisable to wait 2 hours after taking calcium supplements to eat soy (or vice versa). A constituent of ]]>soy]]> called phytic acid can interfere with the absorption of calcium.
  • Taking supplemental calcium may be helpful if you are taking ]]>metformin]]> .

References

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2.   Bourgoin BP, Evans DR, Cornett JR, et al. Lead content in 70 brands of dietary calcium supplements. Am J Public Health. 1993;83:1155-1160.

3.   Ross EA, Szabo NJ, Tebbett IR. Lead content of calcium supplements. JAMA. 2000;284:1425-1429.

4.   Heaney RP. Lead in calcium supplements: cause for alarm or celebration? JAMA. 2000;284:1432-1433.

5.   Heller HJ, Greer LG, Haynes SD, et al. Pharmacokinetic and pharmacodynamic comparison of two calcium supplements in postmenopausal women. J Clin Pharmacol. 2000;40:1237-1244.

6.   Heller HJ, Stewart A, Haynes S, et al. Pharmacokinetics of calcium absorption from two commercial calcium supplements. J Clin Pharmacol. 1999;39:1151-1154.

7.   Dawson-Hughes B, Dallal GE, Krall EA, et al. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. N Engl J Med. 1990;323:878-883.

8.   Sheikh MS, Santa Ana CA, Nicar MJ, et al. Gastrointestinal absorption of calcium from milk and calcium salts. N Engl J Med. 1987;317:532-536.

9.   Miller JZ, Smith DL, Flora L, et al. Calcium absorption from calcium carbonate and a new form of calcium (CCM) in healthy male and female adolescents. Am J Clin Nutr. 1988;48:1291-1294.

10.   Heller HJ, Greer LG, Haynes SD, et al. Pharmacokinetic and pharmacodynamic comparison of two calcium supplements in postmenopausal women. J Clin Pharmacol. 2000;40:1237-1244.

11.   Harvey JA, Zobitz MM, Pak CY. Dose dependency of calcium absorption: a comparison of calcium carbonate and calcium citrate. J Bone Miner Res. 1988;3:253-258.

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13.   Freeland-Graves JH, Lin PH. Plasma uptake of manganese as affected by oral loads of manganese, calcium, milk, phosphorus, copper, and zinc. J Am Coll Nutr. 1991;10:38-43.

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16.   Andon MB, Ilich JZ, Tzagournis MA, et al. Magnesium balance in adolescent females consuming a low- or high-calcium diet. Am J Clin Nutr. 1996;63:950-953.

17.   Hallberg L. Does calcium interfere with iron absorption? Am J Clin Nutr. 1998;68:3-4.

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31.   Reid IR, Ibbertson HK. Calcium supplements in the prevention of steroid-induced osteoporosis. Am J Clin Nutr. 1986;44:287-290.

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33.   Aarskog D, Aksnes L, Markestad T, et al. Heparin-induced inhibition of 1,25-dihydroxyvitamin D formation. Am J Obstet Gynecol. 1984;148:1141-1142.

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36.   Brodie MJ, Boobis AR, Dollery CT, et al. Rifampicin and vitamin D metabolism. Clin Pharmacol Ther. 1980;27:810-814.

37.   Brodie MJ, Boobis AR, Hillyard CJ, et al. Effect of isoniazid on vitamin D metabolism and hepatic monooxygenase activity. Clin Pharmacol Ther. 1981;30:363-367.

38.   Williams SE, Wardman AG, Taylor GA, et al. Long term study of the effect of rifampicin and isoniazid on vitamin D metabolism. Tubercle. 1985;66:49-54.

39.   Wahl TO, Gobuty AH, Lukert BP. Long-term anticonvulsant therapy and intestinal calcium absorption. Clin Pharmacol Ther. 1981;30:506-512.

40.   Weinstein RS, Bryce GF, Sappington LJ, et al. Decreased serum ionized calcium and normal vitamin D metabolite levels with anticonvulsant drug treatment. J Clin Endocrinol Metab. 1984;58:1003-1009.

41.   Hahn TJ, Hendin BA, Scharp CR. Effect of chronic anticonvulsant therapy on serum 25-hydroxycalciferol levels in adults. N Engl J Med. 1972;287:900-904.

42.   Jubiz W, Haussler MR, McCain TA, et al. Plasma 1,25-dihydroxyvitamin D levels in patients receiving anticonvulsant drugs. J Clin Endocrinol Metab. 1977;44:617-621.

43.   Williams C, Netzloff M, Folkerts L, et al. Vitamin D metabolism and anticonvulsant therapy: effect of sunshine on incidence of osteomalacia. South Med J. 1984;77:834-836.

44.   Brodie MJ, Boobis AR, Dollery CT, et al. Rifampicin and vitamin D metabolism. Clin Pharmacol Ther. 1980;27:810-814.

45.   Tomita S, Ohnishi J, Nakano M, et al. The effects of anticonvulsant drugs on vitamin D 3 -activating cytochrome P -450-linked monooxygenase systems. J Steroid Biochem Mol Biol. 1991;39:479-485.

46.   Carter BL, Garnett WR, Pellock JM, et al. Effect of antacids on phenytoin bioavailability. Ther Drug Monit. 1981;3:333-340.

47.   McElnay JC, Uprichard G, Collier PS. The effect of activated dimethicone and a proprietary antacid preparation containing this agent on the absorption of phenytoin. Br J Clin Pharmacol. 1982;13:501-505.

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49.   Dawson-Hughes B, Dallal GE, Krall EA, et al. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. N Engl J Med. 1990;323:878-883.

50.   Peacock M, Liu G, Carey M, et al. Effect of calcium or 25OH vitamin D 3 dietary supplementation on bone loss at the hip in men and women over the age of 60. J Clin Endocrinol Metab. 2000;85:3011-3019.

51.   Prince RL. Diet and the prevention of osteoporotic fractures [editorial]. N Engl J Med. 1997;337:701-702.

52.   Nieves JW, Komar L, Cosman F, et al. Calcium potentiates the effect of estrogen and calcitonin on bone mass: review and analysis. Am J Clin Nutr. 1998;67:18-24.

53.   Lloyd T, Andon MB, Rollings N, et al. Calcium supplementation and bone mineral density in adolescent girls. JAMA. 1993;270:841-844.

54.   Dawson-Hughes B, Harris SS, Krall EA, et al. Effect of withdrawal of calcium and vitamin D supplements on bone mass in elderly men and women. Am J Clin Nutr. 2000;72:745-750.

55.   Barr SI, Petit MA, Vigna YM, et al. Eating attitudes and habitual calcium intake in peripubertal girls are associated with initial bone mineral content and its change over 2 years. J Bone Miner Res. 2001;16:940-947.

56.   Thys-Jacobs S, Starkey P, Bernstein D, et al. Calcium carbonate and the premenstrual syndrome: effects on premenstrual and menstrual symptoms. Premenstrual Syndrome Study Group. Am J Obstet Gynecol. 1998;179:444-452.

57.   Thys-Jacobs S, Silverton M, Alvir J, et al. Reduced bone mass in women with premenstrual syndrome. J Women's Health. 1995;4:161-168.

58.   Lee SJ, Kanis JA. An association between osteoporosis and premenstrual symptoms and postmenopausal symptoms. Bone Miner. 1994;24:127-134.

59.   Baron JA, Beach M, Mandel JS, et al. Calcium supplements for the prevention of colorectal adenomas. Calcium Polyp Prevention Study Group. N Engl J Med. 1999;340:101-107.

60.   Cappuccio FP, Elliot P, Allender PS, et al. Epidemiologic association between dietary calcium intake and blood pressure: a meta-analysis of published data. Am J Epidemiol. 1995;142:935-945.

61.   Van Leer EM, Seidell JC, Kromhout D. Dietary calcium, potassium, magnesium and blood pressure in the Netherlands. Int J Epidemiol. 1995;24:1117-1123.

62.   Bostick RM, Fosdick L, Grandits GA, et al. Effect of calcium supplementation on serum cholesterol and blood pressure: a randomized, double-blind, placebo-controlled, clinical trial. Arch Fam Med. 2000;9:31-39.

63.   Bell L, Halstenson CE, Halstenson CJ, et al. Cholesterol-lowering effects of calcium carbonate in patients with mild to moderate hypercholesterolemia. Arch Intern Med. 1992;152:2441-2444.

64.   Bostick RM, Fosdick L, Grandits GA, et al. Effect of calcium supplementation on serum cholesterol and blood pressure: a randomized, double-blind, placebo-controlled, clinical trial. Arch Fam Med. 2000;9:31-39.

65.   Thys-Jacobs S, Donovan D, Papadopoulos A, et al. Vitamin D and calcium dysregulation in the polycystic ovarian syndrome. Steroids. 1999;64:430-435.

66.   Levine RJ, Hauth JC, Curet LB, et al. Trial of calcium to prevent preeclampsia. N Engl J Med. 1997;337:69-76.

67.   Villar J, Belizan JM. Same nutrient, different hypotheses: disparities in trials of calcium supplementation during pregnancy. Am J Clin Nutr. 2000;71(suppl):1375S-1379S.

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Last reviewed February 2008 by EBSCO CAM Medical Review Board]]>

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