Calcium

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Calcium is very well-known mineral and the most prevalent mineral in the human body. 99% of calcium in the human body is found in the bones and teeth, where it serves the role of keeping bones and teeth strong. In addition, calcium plays a role in heart, nerve, and muscle function. Notably, calcium is commonly used to help prevent the disease osteoporosis. Calcium is dependent on magnesium, phosphorous, vitamin D, and vitamin K for proper absorption and utilization. Calcium absorption can be impacted by age, health conditions, and medications. Carbohydrates are known to increase absorption, while substances like coffee and smoke can reduce absorption of calcium. Calcium can be consumed easily through the diet as many foods are fortified with calcium. Calcium supplements are also available.

Children and older adults must be especially cautious of their calcium levels as significant changes to bones occur during these periods. Populations who may require calcium supplementation include:

  • Postmenopausal women
  • People who consume a lot of caffeine, alcohol, or soda
  • Those who are on corticosteroid medications

Deficiency is common amongst those with Crohn's disease, celiac disease, and some types of intestinal surgeries.

Also known as:  Acétate de Calcium, Aspartate de Calcium, Bone Meal, Calcarea Carbonica, Calcarea Phosphorica, Calcio, Calcium Acetate, Calcium Aspartate, Calcium Carbonate, Calcium Chelate, Calcium Chloride, Calcium Citrate, Calcium D-Gluconate, Calcium Disuccinate, Calcium Glucoheptonate, Calcium Gluconate, Calcium Glycerophosphate, Calcium HVP Chelate, Calcium Hydrogen Phosphate, Calcium Hydroxyapatite, Calcium Lactate, Calcium Lactogluconate, Calcium Orotate, Calcium Oxide, Calcium Phosphate, Calcium Sulfate, Carbonate de Calcium, Chélate de Calcium, Chlorure de Calcium, Citrate de Calcium, Citrate Malate de Calcium, Coquilles d'Huîtres Moulues, Coquilles d'œuf, Di-Calcium Phosphate, Dolomite, Egg Shell Calcium, Gluconate de Calcium, Glycérophosphate de Calcium, Heated Oyster Shell-Seaweed Calcium, Hydroxyapatite, Lactate de Calcium, Lactogluconate de Calcium, MCHA, MCHC, Microcrystalline Hydroxyapatite, Orotate de Calcium, Ossein Hydroxyapatite, Oyster Shell, Oyster Shell Calcium, Phosphate de Calcium, Phosphate de Calcium Hydrogène, Phosphate de di-Calcium, Phosphate Tricalcium, Poudre d'os, Sulfate de Calcium, Tricalcium Phosphate

Diseases and Conditions

Taking calcium carbonate orally as an antacid is effective for treating dyspepsia (indigestion). Calcium carbonate has FDA approval for use as an antacid. Administering calcium gluconate intravenously can reverse electrocardiographic changes and arrhythmias induced by hyperkalemia. Intravenous calcium gluconate is FDA-approved for preventing cardiac abnormalities precipitated by hyperkalemia.

Taking calcium orally is effective for treating and preventing hypocalcemia. Intravenous calcium gluconate, acetate, gluceptate, or chloride is effective for severe hypocalcemia or hypocalcemic tetany. Taking calcium carbonate or calcium acetate orally is effective as a phosphate binder in renal failure. Calcium acetate (PhosLo) appears to control hyperphosphatemia better than sevelamer (Renagel). Calcium citrate is not recommended for this purpose because it increases aluminum absorption and does not bind phosphate as efficiently as calcium acetate or calcium carbonate.

Safety

Calcium is likely safe when consumed orally and intravenously, in the correct dosage. The Institute of Medicine has set the limit of calcium based on age as follows:

  • 0-6 months - 1000 mg
  • 6-12 months -1500 mg
  • 1-8 years - 2500 mg
  • 9-18 years - 3000 mg
  • 19-50 years - 2500 mg
  • 51+ years - 2000 mg

Consuming too much calcium can lead to constipation, may interfere with the body’s ability to absorb zinc and iron, and may increase risk for kidney stones as well as heart disease. It is likely safe for children to consume calcium orally and appropriately, but unsafe when consumption exceeds the recommended dosage. Children who consume large doses of calcium are at risk for developing milk-alkali syndrome and hypercalcemia.

It is likely safe for pregnant and breastfeeding women to consume calcium orally within the recommended dosage but there is insufficient information on intravenous use. Possible side effects of consuming calcium include:

  • Flatulence
  • Belching
  • Stomach upset
  • Diarrhea
  • Constipation
  • Increased risk of myocardial infarction
  • Increased risk of prostate cancer
  • Increased risk for dementia for elderly women who take calcium for 5 years

Medication Interactions

The following interactions have been studied between calcium and different medications:

Aluminum Salts: Calcium citrate may increase the absorption of aluminum when taken with aluminum hydroxide. The increase in aluminum levels may become toxic, particularly in individuals with kidney disease. However, the effect of calcium citrate on aluminum absorption is due to the citrate anion rather than calcium cation. Calcium acetate does not appear to increase aluminum absorption.

Bisphosphonates: Calcium supplements decrease absorption of bisphosphonates. Bisphosphonates should be taken at least 30 minutes before calcium, but preferably at a different time of day. The bisphosphonates include alendronate (Fosamax), etidronate (Didronel), ibandronate (Boniva), risedronate (Actonel), and tiludronate (Skelid).

Calcipotriene (Dovonex): Calcipotriene is a vitamin D analog used topically for psoriasis. It can be absorbed in sufficient amounts to cause systemic effects, including hypercalcemia. Theoretically, combining calcipotriene with calcium supplements might increase the risk of hypercalcemia. Calcium supplements should not be taken while taking calcipotriene.

Calcium Channel Blockers: Calcium when given intravenously may decrease the effects of calcium channel blockers. It is used in the management of calcium channel blocker overdose. Intravenous calcium gluconate has been used before intravenous verapamil (Isoptin) to prevent or reduce the hypotensive effects without affecting the antiarrhythmic effects. But there is no evidence that dietary or supplemental calcium when taken orally interacts with calcium channel blockers. The calcium channel blockers include nifedipine (Adalat, Procardia), verapamil (Calan, Isoptin, Verelan), diltiazem (Cardizem), isradipine (DynaCirc), felodipine (Plendil), amlodipine (Norvasc), and others.

Ceftriaxone (Rocephin): Case reports in neonates show that administering intravenous ceftriaxone and calcium can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys. In several cases, neonates have died as a result of this interaction. So far there are no reports in adults; however, there is still concern that this interaction might occur in adults. To be cautious, avoid administering intravenous calcium in any form, such as parenteral nutrition or Lactated Ringers, within 48 hours of intravenous ceftriaxone.

Digoxin (Lanoxin): Hypercalcemia increases the risk of fatal cardiac arrhythmias with digoxin. However, one retrospective analysis of clinical data suggests that intravenous calcium does not increase the risk of dysrhythmias or mortality in patients receiving digoxin. To be cautious, avoid administering intravenous calcium to patients taking digoxin.

Diltiazem (Cardizem, Dilacor, Tiazac): Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation.

Dolutegravir (Tivicay): Evidence from a pharmacokinetic study suggests that taking calcium carbonate 1200 mg concomitantly with dolutegravir 50 mg reduces blood levels of dolutegravir by almost 40%. Calcium appears to decrease levels of dolutegravir through chelation. Take dolutegravir either 2 hours before or 6 hours after taking calcium supplements.

Elvitegravir (Vitekta): Pharmacokinetic research suggests that taking calcium along with elvitegravir can reduce blood levels of elvitegravir through chelation (94166). Take elvitegravir either 2 hours before or 2 hours after taking calcium supplements.

Estrogens: Estrogen increases supplemental calcium absorption in postmenopausal women.

Levothyroxine (Synthroid, Levothroid, Levoxyl, and others): Calcium reduces levothyroxine absorption, probably by forming insoluble complexes. Calcium carbonate supplements reduce effectiveness of levothyroxine in patients with hypothyroid. Take levothyroxine and calcium supplements at least 4 hours apart.

Lithium: Clinical evidence suggests that long-term use of lithium may cause hypercalcemia in 10% to 60% of people. Theoretically, concomitant use of lithium and calcium supplements may further increase this risk.

Quinolone Antibiotics: Taking calcium at the same time as quinolones reduces quinolone absorption. Calcium forms insoluble complexes with quinolones. Take these drugs at least 2 hours before, or 4-6 hours after calcium supplements or calcium-fortified foods. Quinolones include ciprofloxacin (Cipro), levofloxacin (Levaquin), ofloxacin (Floxin), moxifloxacin (Avelox), gatifloxacin (Tequin), gemifloxacin (Factive), and others.

Raltegravir (Isentress): Pharmacokinetic research shows that taking a single dose of calcium carbonate 3000 mg along with raltegravir 400 mg twice daily modestly decreases the mean area under the curve of raltegravir, but the decrease does not necessitate a dose adjustment of raltegravir. However, a case of elevated HIV-1 RNA levels and documented resistance to raltegravir has been reported for someone taking calcium carbonate 1 gram three times daily plus vitamin D3 (cholecalciferol) 400 IU three times daily in combination with raltegravir 400 mg twice daily for 11 months. It is thought that calcium reduced raltegravir levels by chelation, leading to treatment failure. Until more is known, use caution when taking raltegravir along with repeated doses of calcium.

Sotalol (Betapace): Calcium appears to reduce the absorption of sotalol, probably by forming insoluble complexes. Separate doses by at least 2 hours before or 4-6 hours after calcium.

Tetracycline Antibiotics: Calcium decreases the absorption of tetracyclines by forming insoluble complexes. Take these drugs at least 2 hours before or 4-6 hours after calcium supplements. Tetracyclines include demeclocycline (Declomycin), doxycycline (Vibramycin), and minocycline (Minocin).

Thiazide Diuretics: Thiazides reduce calcium excretion by the kidneys. Using thiazides along with moderately large amounts of calcium carbonate increases the risk of milk-alkali syndrome (hypercalcemia, metabolic alkalosis, renal failure). Advise patients to consult their physician about appropriate calcium doses, and to have their serum calcium levels and/or parathyroid function monitored regularly. These diuretics include chlorothiazide (Diuril), hydrochlorothiazide (HydroDIURIL, Esidrix), indapamide (Lozol), metolazone (Zaroxolyn), chlorthalidone (Hygroton).

Verapamil (Calan, Covera, Isoptin, Verelan): Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation.

Supplement and Food Interactions

Taking calcium from supplements or via food sources can decrease iron absorption from foods. Calcium supplements can decrease the absorption of dietary magnesium, but only at very high, supra-therapeutic doses. Individuals taking iron supplements should take them two hours apart from calcium-rich food or supplements to maximize iron absorption. Although high calcium intakes have not been associated with reduced zinc absorption or zinc nutritional status, an early study in 10 men and women found that 600 mg of calcium consumed with a meal halved the absorption of zinc from that meal. Supplemental calcium (500 mg calcium carbonate) has been found to prevent the absorption of lycopene (a non-provitamin A carotenoid) from tomato paste in 10 healthy adults randomized into a cross-over study.

Clinical evidence suggests that taking prebiotics or probiotics may increase the absorption of calcium. Concomitant administration of calcium with vitamin D increases active absorption of calcium in the small intestine.

Most experts recommend obtaining as much calcium as possible from food because calcium in food 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 food. No multivitamin/mineral tablet contains 100% of the recommended daily value (DV) of calcium because it is too bulky, and the resulting pill would be too large to swallow. The "Supplement Facts" label, required on all supplements marketed in the US, lists the calcium content of the supplement as elemental calcium. Calcium preparations used as supplements include calcium carbonate, calcium citrate, calcium citrate malate, calcium lactate, and calcium gluconate. To determine which calcium preparation is in your supplement, you may have to look at the ingredient list. Calcium carbonate is generally the most economical calcium supplement. To maximize absorption, take no more than 500 mg of elemental calcium at one time. Most calcium supplements should be taken with meals, although calcium citrate and calcium citrate malate can be taken anytime. Calcium citrate is the preferred calcium formulation for individuals who lack stomach acids (achlorhydria) or those treated with drugs that limit stomach acid production (H2blockers and proton-pump inhibitors).

Dosage

  • For preventing hypocalcemia, 1 gram of elemental calcium daily is typically used. Calcium replacement requirements in people with hypocalcemia can be estimated by clinical condition or serum calcium determinations, but a typical starting dose is 1-2 grams daily.
  • For heartburn, calcium carbonate as an antacid is usually 0.5-1.5 grams as needed.
  • For hyperphosphatemia in adults with chronic renal failure, the initial dose of calcium acetate is 1.334 grams (338 mg elemental calcium) with each meal, increasing to 2-2.67 grams (500-680 mg elemental calcium) with each meal if necessary.
  • For osteoporosis prevention, 1000-1600 mg of elemental calcium daily from supplements and food sources has been used. There is some debate over the most appropriate calcium dose for reducing bone fracture risk. Osteoporosis treatment guidelines in North America currently recommend 1200 mg daily of elemental calcium. However, a population study found that intake of elemental calcium 750 mg daily significantly reduced the risk for fractures. Doses over this amount did not provide any added benefit. Until more is known, most experts recommend sticking with 1000-1200 mg daily for osteoporosis and fracture prevention.
  • For pregnant women with low dietary calcium intake, the dose for increasing fetal bone density ranges from 300-1300 mg/day beginning at gestation week 20-22. A dose of 1-1.2 grams calcium per day as calcium carbonate has reduced symptoms of premenstrual syndrome (PMS).
  • For treatment of secondary hyperparathyroidism in people with chronic renal failure, doses of 2-21 grams calcium carbonate daily have been used.
  • For treatment of secondary hyperparathyroidism in elderly women, elemental calcium 1200 mg daily, combined with 800 IU vitamin D daily, has been used.
  • To prevent bone loss associated with chronic corticosteroid therapy, divided daily doses of 1 gram of elemental calcium daily is used.
  • For preventing colorectal cancer and recurrent colorectal adenomas, calcium 1200-1600 mg/day has been used.
  • For preventing all cancer types, calcium 1400-1500 mg/day plus vitamin D3 (cholecalciferol) 1100 IU/day in postmenopausal women has been used.
  • For hypertension, 1-1.5 grams calcium daily has been used. For preventing pre-eclampsia, 1-2 grams elemental calcium daily as calcium carbonate has been used.
  • For pregnancy-related leg cramps, 1 gram twice daily has been used.
  • For treating diarrhea and rectal epithelial hyperproliferation due to intestinal bypass, a dose of 2.4-3.6 grams daily calcium as calcium carbonate has been used.
  • For hypercholesterolemia, 1200 mg daily with or without vitamin D 400 IU daily has been used in conjunction with a low-fat or calorie-restricted diet.
  • High serum fluoride levels and symptoms of fluorosis in children have been reduced with calcium 125 mg twice daily, in combination with ascorbic acid and vitamin D.
  • For weight loss, increasing calcium consumption from dairy products to a total intake of 500-2400 mg/day in combination with a calorie-restricted diet has been used.

Calcium carbonate and calcium citrate are the two most commonly used forms of calcium. Calcium supplements are usually divided into two doses daily in order to increase absorption. It is usually recommended that calcium be administered in doses of 500 mg or less. Calcium carbonate contains 400 mg calcium/gram and calcium citrate contains 211 mg calcium/gram (1000 mg elemental calcium = 2500 mg calcium carbonate = 4700 mg calcium citrate). Absorption of calcium from supplements is greatest when taken with food in doses of 500 mg or less since the active transport system for calcium in the small bowel is easily saturated.

The Institute of Medicine publishes a recommended daily allowance (RDA) for calcium which is an estimate of the intake level necessary to meet the requirements of nearly all healthy individuals in the population. The current RDA was set in 2010. The RDA varies based on age as follows:

  • 1-3 years - 700 mg
  • 4-8 years - 1000 mg
  • 9-18 years - 1300 mg
  • 19-50 years - 1000 mg
  • Men 51-70 years - 1000 mg
  • Women 51-70 years - 1200 mg
  • 70+ years - 1200 mg;
  • Pregnant or Lactating (under 19 years) - 1300 mg
  • Pregnant or Lactating (19-50 years) - 1000 mg

For emergency management of hypocalcemia, 100-200 mg of elemental calcium can be given intravenously as a bolus, and a central vein should be used whenever possible. One milliliter of calcium chloride provides 27 mg of elemental calcium, and 1 mL of calcium gluconate provides 9 mg. For management of hyperkalemia, 20 mL of 10% calcium gluconate administered over 5-10 minutes in adults (0.5mL/kg in children), and as a slow infusion over 20-30 minutes for patients taking digoxin.

Foods

The bioavailability of calcium must be taken into consideration. The calcium content in calcium-rich plants in the kale family (broccoli, bok choy, cabbage, mustard, and turnip greens) is as bioavailable as that in milk; however, other plant-based foods contain components that 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 potatoes and dried beans. Phytic acid (phytate) is a less potent inhibitor of calcium absorption than oxalate. Yeast possess an enzyme (phytase) that breaks down phytate in grains during fermentation, lowering the phytate content of breads and other fermented foods. Only concentrated sources of phytate, such as wheat bran or dried beans, substantially reduce calcium absorption.

Foods high in calcium include:

  • Milk
  • Dairy products (yogurt, cheese)
  • Kale
  • Broccoli
  • Calcium-enriched citrus juices
  • Mineral water
  • Canned fish with bones (sardines)
  • Soy products processed with calcium (tofu)
  • White Beans, Pinto Beans, Red Beans (cooked)
  • Chinese Cabbage (bok choy)

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References

  1. https://ods.od.nih.gov/factsheets/Calcium-Consumer/
  2. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=781
  3. http://www.umm.edu/health/medical/altmed/supplement/calcium
  4. http://lpi.oregonstate.edu/mic/minerals/calcium#references

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