Calcium

• How It Works

  Adequate calcium intake may help prevent osteoporosis, bone fracture, and colorectal cancer. However, higher calcium intake may increase the risk of cardiovascular events and prostate cancer.

  Calcium plays several essential roles in the human body. It is a main structural element in bone, which acts as a reservoir for calcium so that stable blood calcium levels are maintained. This is necessary for the many roles calcium plays in cells including muscle contraction, nerve transmission, blood clotting, and enzyme reactions. When calcium intake and bodily estrogen levels are low, the body takes calcium from bones and uses it for other processes, resulting in osteoporosis.

  Inadequate blood calcium levels are linked to high blood pressure. Whether the use of calcium supplements can increase the risk for heart disease or cardiac events is still unclear. Adequate calcium intake may help prevent osteoporosis, bone fracture, and colorectal cancer. The links of calcium supplements to increased prostate cancer risk may occur for reasons other than the supplements themselves.

  Calcium is available from a number of foods, and can be found in some antacids as well. Because the risks and benefits of calcium supplements are still unclear and calcium can interact with the absorption of a number of drugs, patients should check with their healthcare provider about whether supplementation is warranted.

• Purported Uses
  • To prevent cancer
    Many clinical studies have been performed in humans, but the consistent effects of dietary and supplemental calcium on cancer have not been determined. There does appear to be an increased risk for prostate cancer, but a decreased risk for colorectal cancer with calcium supplements. Additional studies are warranted.
  • To reduce cardiovascular disease risk
    Studies are mixed on whether calcium supplementation protects against cardiovascular disease or increases risk for this disease. Additional studies are needed to clarify under what circumstances calcium may confer benefits or risks.
  • To lower high blood pressure
    Most clinical trials have found that calcium from the diet and from supplements can have a small effect on lowering both systolic and diastolic blood pressure.
  • To prevent the progression of osteoporosis
    Some, but not all, large clinical trials have found that calcium supplementation prevents bone loss, especially in older women. Reduced bone loss may also prevent fractures.
• Do Not Take If
  • You have hypothyroidism, high blood calcium levels, or low blood phosphate levels: Consult your doctor before starting calcium supplements.
  • You are taking cardiac glycosides such as digoxin: Calcium may increase the risk of irregular heartbeat.
  • You are being treated with tamoxifen: Calcium may increase the risk of abnormally high levels of calcium in the blood. This can increase the risk of kidney stones.
  • You are taking fluoroquinolone or tetracycline antibiotics: Calcium may reduce the absorption of these antibiotics into the bloodstream. Calcium should be taken 2 hours before or 1 hour after taking these medicines.
  • You are taking drugs to treat an underactive thyroid: Taking calcium carbonate within 4 hours of this drug may decrease its absorption by almost 33%.
  • You are taking iron, zinc, or magnesium: Calcium can interfere with their absorption.
• Side Effects
  • Constipation, flatulence, chalky taste, and dry mouth; higher calcium levels in blood or urine in older women
  • Modest increased risk of urinary stones with long-term use
  • Nausea occurs rarely
  • Intake of high-dose calcium supplements (>1 g/day) can increase the risk of stroke
• Special Point
  • Increasing dietary calcium from a variety of foods including non-dairy sources instead of taking supplements has been associated with a lower risk of kidney stones.
  • For those requiring calcium supplementation, increasing fluid intake may reduce the risk of kidney stones.
  • Some medications such as those for gastric reflux may reduce calcium absorption.
  • Calcium may be an ingredient in some antacids.
• Brand Name

  Oscal®, Tums®, Caltrate®, Citracal®

• Clinical Summary

  Calcium is an essential mineral responsible for many physiological functions in the body. It is stored in the bones and helps maintain bone structure. Calcium also plays an important role in cell signaling and muscle contraction. Dietary calcium can be found in dairy products, dark greens, legumes, nuts and fish. Natural supplements are derived from minerals, oyster shells and occasionally corals. Calcium can be found in some antacids as well.

  The effects of calcium have been studied across a range of conditions including cardiovascular disease ^{(1) (2) (3) (4) (5)}, osteoporosis ⁽⁶⁾, bone density loss ⁽⁷⁾, fracture prevention ⁽⁸⁾, premenstrual syndrome ⁽⁹⁾, pre-eclampsia ^{(10) (11) (87)}, lead poisoning ⁽¹²⁾, and various cancers ^{(13) (14) (15)}.

  Long-term calcium supplement use is associated with an increased risk of coronary artery calcification ⁽⁷⁷⁾. Some studies suggest that supplementation could lead to cardiovascular disease (CVD) or events ^{(1) (2) (3) (5)}, but these findings remain debatable ^{(16) (17) (18)}. In a Women’s Health Initiative sub-study, calcium plus vitamin D supplementation and hormone therapy yielded greater reductions in LDL-C than either intervention alone or placebo ⁽⁸¹⁾; but supplementation did not always modify the effects of hormonal therapy on CVD events ⁽⁸⁸⁾. Calcium and vitamin D supplementation may also benefit postmenopausal women who do not have pre-existing risk factors such as coronary heart disease, diabetes, or hypertension ⁽¹⁹⁾ and large long-term studies in women did not find adverse cardiovascular associations with calcium supplementation ^(4) (20). However, high intake of calcium supplements did increase cardiovascular mortality in men ⁽²¹⁾. Another study found supplement intake to be associated with dementia in women following stroke ⁽⁷⁵⁾.

  There is also conflicting evidence on calcium intake or calcium plus vitamin D supplementation on bone density and fractures ^{(22) (23) (24) (42) (53) (82)}. Recent US Preventive Services Task Force reports did not find any associations between calcium plus vitamin D supplementation and reduced falls or fracture incidence for community-dwelling older adults without known deficiencies, osteoporosis, or history of fracture ^(83) (84). In postmenopausal women, neither dietary calcium ⁽²⁵⁾ nor calcium plus vitamin D supplementation ⁽²⁶⁾ reduced hip fracture risk, although the latter study found significant reductions at 7 years ⁽²⁷⁾. Subgroup analysis further suggested that supplementation along with estrogen therapy conferred additive protection against hip fractures ⁽²⁸⁾. However, there appears to be no prevention benefits with calcium and vitamin D supplementation for bone mineral density loss in breast cancer patients ⁽⁷⁾ or for older adults to help prevent fractures ⁽⁷⁸⁾. Calcium plus vitamin D mitigated bone density loss associated with antiretroviral therapy ⁽⁷²⁾. In men, bone mineral density and bone loss rates were not related to dietary calcium intake ⁽⁷⁹⁾.

  Both dietary and supplemental calcium are linked with lower risk of colorectal cancer ^(13) (29), but had no effect on colorectal adenomas ⁽⁷⁴⁾. For men, calcium intake is associated with increased risk for prostate cancer ^(30) (31); a genetic disposition for high intestinal absorption of calcium among African-American men has also been noted ^(32) (33). Long-term studies suggest risks associated with calcium in prostate cancers are less strong when phosphorus intake is also considered ^(34) (35).

  For women, studies on calcium plus vitamin D supplementation for reduced risk yielded conflicting data for colorectal cancers ^(38) (85), all cancer types ^(36) (86), and mortality ^(26) (37). Other trials suggest benefits against hematologic ⁽⁸⁰⁾ but not invasive cancers ⁽³⁹⁾.

  In general, the evidence is insufficient to assess benefits of calcium plus vitamin D supplementation for those receiving androgen deprivation therapy, aromatase inhibitors, or undergoing chemotherapy-induced menopause ^{(7) (43) (44)}. Patients should consult with their oncologists or oncology healthcare teams, especially since calcium supplements can interact with a number of drugs.

  A proper diet to achieve a balance among nutrients including sodium, potassium, magnesium, calcium and vitamin D is important to affect risks for hypertension as well as cardiovascular and cerebrovascular events ⁽⁴⁰⁾. The risk–benefit ratio of supplementation is likely to vary, depending on dietary calcium intake, sex, age, ethnicity, and individual risks for cardiovascular disease and osteoporosis ^(41) (73). In individuals with normal calcium levels, genetic predisposition to higher serum levels does not affect bone mineral density nor protect against fractures ⁽⁸⁹⁾. Intake of high-dose calcium supplements (>1 g/day) can also increase the risk of ischemic stroke ⁽⁷⁶⁾. Calcium and vitamin D supplementation may increase the risk for kidney stones ^{(42) (48) (53) (84)}.

• Food Sources

  Milk, yogurt, cheese, egg, bread, salmon, prawns, sardines, shrimp, broccoli, spinach, kale, collards, spring greens, baked beans, chickpeas, lentils, kidney beans, soya beans, tofu, orange, almonds, sesame seeds and fortified cereals, orange juice and soy milk

• Purported Uses
  • Cancer prevention
  • Cardiovascular disease
  • Osteoporosis
  • Hypertension
• Mechanism of Action

  Calcium plays an important role in a variety of muscular, vascular, neurological, hormonal, and enzymatic reactions throughout the body. Calcium reserves are found mostly in the bones, helping to maintain skeletal structure.

  The association of supplemental but not dietary calcium with increased cardiovascular risk could be related to their differing, acute effects on serum calcium ⁽⁴⁵⁾. Calcium supplementation may fail to compensate for renal calcium loss, resulting in increased circulatory calcium that could lead to coronary artery deposits ⁽⁴⁶⁾. Reduced dietary calcium may cause calcium depletion in membrane storage sites resulting in less stability of vascular smooth muscle cell membranes, as optimal concentrations stabilize these membranes, inhibit calcium entry into cells, and reduce vasoconstriction ⁽⁴⁷⁾. Other researchers suggest that gastrointestinal events associated with calcium supplements may account for an increase in self-reported cardiovascular events ⁽¹⁸⁾.

  Observed associations of dairy with overall prostate cancer risk may be related to the modulation of vitamin D metabolism by calcium and phosphorus ^(15) (31). Saturated fat in whole dairy correlating with higher C-peptide concentrations, along with obesity and hyperinsulinemia are proposed for associations of whole milk with fatal prostate cancer ⁽³¹⁾. Other suggested mechanisms include increasing levels of ionized calcium in the blood, as prostate cancer cells express both calcium-sensing receptors and calcium-dependent voltage-gated channels, the stimulation of which by extracellular calcium increases prostate cancer cell growth ^(44) (35). In African American men, positive associations between calcium and aggressive prostate cancer have been linked to single-nucleotide polymorphisms in the CDX-2 binding site of the VDR gene ⁽³²⁾.

• Warnings
  • Calcium may interfere with the absorption of iron, magnesium, and zinc ^(48) (49).
  • High consumption of calcium has been associated with an increased risk of prostate cancer ^{(30) (31) (32) (34) (49) (50)} and milk-alkali syndrome ⁽⁵¹⁾.
  • For those with chronic kidney disease, there is an increased risk of cardiovascular disease associated with calcium supplements ⁽⁵²⁾.
  • Calcium and vitamin D supplementation may increase the risk for kidney stones ^{(42) (48) (53) (84)}. Increasing calcium via diet rather than supplements may lower the risk ⁽⁵⁴⁾. For those who must take calcium in supplement form, adequate fluid intake is important to help reduce this risk ⁽⁵⁵⁾
• Contraindications

  Patients who have hypothyroidism ⁽⁵⁶⁾, low serum phosphate levels ⁽⁵⁷⁾, or high serum calcium levels associated with sarcoidosis, hyperparathyroidism, hypervitaminosis D, and certain cancers ⁽⁴⁹⁾ should consult their physicians before taking calcium supplements.

• Adverse Reactions

  Common: Constipation, flatulence, chalky taste and dry mouth; hypercalciuria and hypercalcemia in older women ⁽⁵⁸⁾

  Rare: Nausea ⁽¹⁴⁾; modest elevation in urinary tract stone formation with long-term use ^{(27) (58) (59)}

  Excessive intake: Constipation, vascular and soft-tissue calcification, nephrolithiasis, hypercalciuria, hypercalcemia, increased risk for prostate cancer ^{(48) (32) (34)}. Intake of high dose calcium supplements (>1 g/day) can increase the risk of ischemic stroke ⁽⁷⁶⁾.

  Case reports

  • Life-threatening hypercalcemia/milk-alkali syndrome: Confusion, nausea, vomiting, and weakness in a 64-year-old cancer survivor who took calcium-containing antacid tablets for chronic epigastric pain ⁽⁶⁰⁾.
  • Hypercalcemia-induced pancreatitis: Due to oral calcium supplementation in a 42-year-old female ⁽⁶¹⁾.
• Herb-Drug Interactions
  • Proton Pump Inhibitors: May significantly reduce calcium absorption ⁽⁶²⁾.
  • Cardiac glycosides: Calcium may increase risk of cardiac arrhythmia, although this is based on intravenous calcium, early case reports, and animal models ⁽⁶⁴⁾.
  • Quinolones: Calcium may reduce absorption of quinolones ⁽⁶⁵⁾.
  • Tamoxifen: Calcium may increase the risk of hypercalcemia ⁽⁶⁶⁾.
  • Tetracyclines: Calcium may reduce absorption of tetracyclines ⁽⁶⁷⁾.
  • Levothyroxine (to treat hypothyroidism): Taking calcium carbonate within 4 hours of this drug may decrease its absorption by nearly one-third ⁽⁶⁸⁾.
  • Estrogen therapy (for osteoporosis; positive interaction): Supplemental calcium and vitamin D may have additive benefits on bone health ⁽²⁸⁾.
  • Iron, zinc, or magnesium: Calcium can compete or interfere with their absorption ^(48) (49).
• Herb Lab Interactions

  Decreased blood pressure ^(70) (71)

• References

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