Calcium

Calcium is a dietary macromineral found in high amounts in dairy products, and to a lesser extent in vegetables. Used primarily to support bone health, calcium also has a role in maternal and cardiovascular health.

This page features 116 unique references to scientific papers.

Summary

All Essential Benefits/Effects/Facts & Information

In Progress


This page on Calcium is currently marked as in-progress. We are still compiling research.



Calcium is one of the 24 vitamins and minerals required for good health in the human body. It is a macromineral due to the relatively large amounts required in the diet (at times exceeding a gram a day) and is predominately found in diary products and vegetables. Similar to many other nutrients, calcium does follow the general advice of "if the diet is sufficient in calcium then supplementation is unnecessary" and excessive intakes of calcium do not promote greater benefits to health and may simply promote constipation.

The major benefit of calcium is preventative, mitigating the risk of developing osteoporosis during the aging process. Osteoporosis can be at least partially seen as a condition resulting from long-term calcium insufficiency and, while not fully preventative, maintaining adequate calcium intake throughout life is associated with significantly reduced risk.

Calcium can come from any source be it supplementation, food, or even food-derivatives such as Whey Protein. Each form does have their benefits and drawbacks, such as coral calcium technically being better absorbed than calcium carbonate, but due to calcium's ability to be absorbed at all points in the intestine the issue of calcium absorption is one that is greatly influenced by the diet. Diets high in fermentable fibers (usually found in vegetables) and high enough in bulk and fiber to slow the rate at which food passes through the intestines increase calcium absorption; simply taking a calcium supplement on top of a low fiber/low bulk diet will not be as effective as consuming the calcium through dairy or even vegetables.

for updates

Confused about supplements?

Free 5 day supplement course

Things To Know

Also Known As

Ca2+, Ca, Coral Calcium

Things to Note

  • Calcium is found in both over-the-counter products and prescription medications such as calcium carbonate, calcium citrate, calcium lactate, calcium phosphate. Use of these medications can result in increased serum calcium levels.

Is a Form Of

Goes Well With

  • Vitamin D, Vitamin K, and Magnesium (Preventative supplements for bone health)

  • Fermentable fiber sources (Inulin, vegetables; aids absorption)

Caution Notice

  • The maximum dose of elemental calcium that should be taken at one time is 500 mg, to avoid unwanted effects on absorption of calcium and parathyroid hormone.[1]

  • Reported adverse effects of calcium use include constipation, excessive abdominal cramping, bloating, severe diarrhea, and abdominal pain.[2]

  • Additionally, high serum calcium levels, also known as hypercalcemia, has been associated with an increased risk of cardiovascular events, myocardial infarction, and stroke.[3][4][5]

Examine.com Medical Disclaimer

How to Take

Recommended dosage, active amounts, other details

Supplementing calcium should be done in accordance with your overall intake of calcium from the diet, in an attempt to get as close to the recommended daily intake (RDI) as possible. This intake is:

  • 700 mg for those 1-3 years of age

  • 1,000 mg for those 4-8 years of age, as well as for adults between the ages of 19-50

  • 1,300 mg for those between the ages of 9 and 18

  • 1,200 mg for adults over the age of 71 and for females above the age of 50 (males between the ages of 50-70 only require 1,000 mg)

Calcium from all sources, including diary-derived protein supplements such as Whey Protein or Casein Protein should be included and there is no specific timing of calcium supplements required. They can be taken at any point in the day, although preferably with a meal to aid in absorption.

Confused about supplements?

Free 5 day supplement course

Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects calcium has on your body, and how strong these effects are.

Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
Pre-Eclampsia Risk Notable Very High See all 4 studies
Calcium supplementation appears to be quite potent in reducing the risk of pre-eclampsia when supplemented at 1,000mg a day, with more efficacy in those with lower dietary calcium intake.
Fecal Bile Acids - Low See 2 studies
Fecal Cholesterol - Low See study
Fecal Water Genotoxicity - Low See study
Lipid Absorption - Low See study
Blood Pressure Low See study
Bone Mineral Density - Low See study
Free Testosterone - Low See study
Testosterone - Low See study

Scientific Research

Table of Contents:

  1. 1 Sources and Structure
    1. 1.1 Sources
    2. 1.2 Biological Significance
    3. 1.3 Recommended Intake
    4. 1.4 Deficiency
    5. 1.5 Sufficiency and Excess
    6. 1.6 Formulations and Variants
  2. 2 Molecular Targets
    1. 2.1 Calcium-Sensing Receptors (CaSRs)
  3. 3 Pharmacology
    1. 3.1 Absorption
    2. 3.2 Drug-Drug Interactions
  4. 4 Cardiovascular Health
    1. 4.1 Lipid Absorption
    2. 4.2 Platelets
    3. 4.3 Atherosclerosis
  5. 5 Fat Mass and Obesity
    1. 5.1 Mechanisms
  6. 6 Skeletal and Bone Mass
    1. 6.1 Osteoporosis
    2. 6.2 Fractures
  7. 7 Interactions with Hormones
    1. 7.1 Testosterone
  8. 8 Interactions with Cancer Metabolism
    1. 8.1 Colon Cancer
  9. 9 Pregnancy and Lactation
    1. 9.1 Hypertension
    2. 9.2 Delivery
    3. 9.3 Bone Mineral Density
  10. 10 Interactions with Organ Systems
    1. 10.1 Intestines
  11. 11 Nutrient-Nutrient Interactions
    1. 11.1 Vitamin D
    2. 11.2 Absorption Modifiers
  12. 12 Safety and Toxicology
    1. 12.1 General
    2. 12.2 Human Toxicity
    3. 12.3 Side Effects with Safe Usage
    4. 12.4 Withdrawal
    5. 12.5 Case Studies

Don't Miss an Update!

Your e-mail is safe with us. We don’t share personal data.


1Sources and Structure

1.1. Sources

Calcium is an essential mineral.

1.2. Biological Significance

Calcium is most well known to serve as a major building block of bone in the human body, with there being anywhere from 1-2 kg of calcium in the human body that is 99% localized to bone tissue (skeleton and teeth).[1][2] The calcium tends to be stored in the form of hydroxyapatite crystals (Ca10(OH)2(PO4)6) formed by bone cells known as osteoblasts.[3]

The remaining calcium is in a soluble form, found in the bloodstream and cells across the body, where it serves a vital role in aiding cellular signalling.[2][4]

1.3. Recommended Intake

The recommended daily intake for calcium is:[5][6]

  • 700 mg for those 1-3 years of age

  • 1,000 mg for those 4-8 years of age, as well as for adults between the ages of 19-50

  • 1,300 mg for those between the ages of 9 and 18

  • 1,200 mg for adults over the age of 71 and for females above the age of 50 (males between the ages of 50-70 only require 1,000 mg)

Infants less than a year old have minor calcium requirements of 200-260 mg whereas women who are pregnant or lactating require up to 1,300 mg of calcium daily.[5][6]

1.4. Deficiency

While the condition of bone deformation known as Rickets is commonly attributed to be due to a Vitamin D deficiency,[7] calcium also plays a pivotal role as the two are intricately linked when it comes to supporting the growth of bones (alongside other nutrients such as phosphorus and Magnesium)[8] and instances of rickets in the presence of adequate Vitamin D have been reported.[9][10] While this condition affects children and youth exclusively, usually those under 18 months of age associated with lack of Vitamin D[8][11] and potentially in early adolescence with very low calcium intake,[12] adults don't experience any disease state specific to a lack of dietary calcium a lifetime of insufficient intake is one of the major risk factors in the promotion of osteoporosis.

Both Vitamin D and calcium deficiency can lead to rickets, usually with Vitamin D presenting rickets within 1-2 years of age and calcium deficiency presenting rickets in childhood to early adolescence. Adults don't have a disease state specifically associated to calcium deficiency but it plays a major role in the onset of osteoporosis

1.5. Sufficiency and Excess

The tolerable upper limit (TUL) of calcium is between 2,000-3,000 mg depending on age group, the higher TUL being for adolescents and pregnant or lactating women and the lower TUL of 2,000 mg for adults over the age of 50. Young adults and children have a TUL of 2,500 mg.[5][6]

1.6. Formulations and Variants

Calcium phosphate (pentacalcium hydroxytriphosphate) is a form of calcium that is 2/3rds calcium by weight, and is an endogenous metabolite of calcium in the body (after forming with phosphorus in the intestines).[13]

At 1,000mg (calcium equivalent) calcium phosphate supplementation is able to increase serum concentrations of calcium without affecting phosphorus levels in the postprandial state[14] although it has been noted to not influence fasting levels of calcium nor phosphorus over six weeks at 1,500mg.[15]

Calcium phosphate appears to be a viable form of calcium supplementation

Coral calcium is a dietary supplement from coral (Coral calx or Praval bhasma) that is claimed to be better absorbed when compared to other forms of calcium supplementation, referencing a small study comparing a 525 mg dose of calcium as carbonate versus the same dose of calcium from coral from the Ryukyu islands (a 2:1 calcium:Magnesium).[16] It's popularity as a supplement has at times been reported[17] to be associated with how the long lifespan of Okinawans are, in turn, associated with water intake that may have its mineral contents modified by the presence of high amounts of coral reef.[18]

Coral is also known to possess hydroxyapatite,[19] a product of calcium in the human body that is very prominent in human bones and teeth. The relevance of orally ingested hydroxyapatite from coral calcium is currently unknown. Despite this, studies in rats do confirm that coral calcium is able to improve bone mineralization in models of bone loss.[20][21]

Coral calcium is calcium derived from Coral calx. As it confers dietary calcium it appears to also work well as a bone health supplement (based on limited but coherent evidence). Whether it is better than traditional calcium supplements is unknown and there is no good evidence for any claim that cannot also be given for standard calcium supplements


2Molecular Targets

2.1. Calcium-Sensing Receptors (CaSRs)

Calcium-sensing receptors (CaSRs) are receptors that respond to changes in calcium concentrations. Expressed in the kidneys, thyroid and the parathyroid which serve as a link between fluctuating calcium concentrations and manipulating the actions of parathyroid hormone and Vitamin D to help mitigate abnormal levels of calcium.[22] These receptors can be influenced by inflammation,[22] as both IL-6[23] and IL-1β[24] are known to increase the trancription rates and, ultimately, the amount of receptors.

Calcium-sensing receptors are the receptors where changing levels of calcium in the body are 'detected', which then signal for other changes to initiate to help regulate calcium levels in the body


3Pharmacology

3.1. Absorption

Calcium is absorbed by one of two ways in the intestines; a transporter-mediated process and a paracellular process.[25][26]

The transporter-mediated process occurs primarily in the first two segments of the intestines, the duodenum and jejunum.[27][28] This is the stage of calcium absorption that has a rate-limit and can be regulated by both calcium levels in the body and Vitamin D[28] (although paracellular is still somewhat regulated[29]). It is an active transport system which starts with uptake through calcium channels (TRPV6 and TRPV5; previously known as CaT1 and CaT2 respectively) with TRPV6 being the variant favored in the intestines rather than the kidneys where TRPV5 dominates[30][31] while an L-type channel known as Cav1.3 also exists in the intestines that can also help transport calcium from the intestines.[32] The two receptors seem to have complementary roles with TRPV6 being more active in calcium reuptake during fasting and Cav1.3 being more active during feeding.[26][32]

After initial uptake into the cell, calbindins (CBs) bind to calcium to carry it through the cell from the apical membrane to the basolateral membrane[26][33] and also help support the cell they are in by acting as buffering agents.[34] After the transfer, the calbindins pass calcium off to two proteins known as PMCA (mostly PMCA1b[35]) and NCX1; a pump and a Na+/Ca2+ exchanger respectively where the former is generally responsible for 80% of the calcium efflux.[36][37]

Unlike the transport-mediated process, the paracellular (between cells) process occurs at all points in the intestines. It does occur in the ileum (segment of the large intestine that calcium transporters don't work in)[27] and also occurs throughout the entirety of the large intestine.[38] Generally speaking, this route of absorption is more relevant when chyme (digested food) travels through the intestines at a slower rate[39] and when the diet is sufficiently high in calcium.[25]

Calcium can be absorbed at any point in the intestines. Most absorption occurs quite soon after ingestion by active transports whereas there is a small concentration-dependent absorption that can occur for as long as chyme that contains calcium remains in the intestines

3.2. Drug-Drug Interactions

There have been many drug interactions reported among users of the various dosage forms of calcium. The type of interaction encountered will be different for every medication.

Taking calcium with bisphosphonate drugs for osteoporosis or thyroid hormones like levothyroxine can cause reduced drug absorption.[40]

Calcium can also reduce the efficacy of some antivirals (e.g. amprenavir and zalcitabine), aspirin, several antibiotics (e.g. several fluoroquinolones, tetracycline, and several cephalosporins), and some antifungals (e.g. ketoconazole) can cause reduced drug efficacy.[40] Efficacy is also reduced for some drugs used for gastrointestinal issues (e.g. hyoscyamine, bisacodyl, and bismuth subcitrate), the antiplatlet drug ticlopidine, the calcium channel blocker verapamil, and the beta-blocker atenolol.[40] Efficacy of Iron is also reduced by calcium.[40] Phosphate absorption is also reduced when calcium is taken concurrently.[40]

Serious interactions between calcium and the thiazide (such as hydrochlorothiazide) and thiazide-like (e.g. clopamide and chlorthalidone) can also occur. Taking these drugs together with calcium can cause milk-alkali syndrome, which is characterized by hypercalcemia, metabolic alkalosis, and renal failure.[40]

Another serious interaction between calcium and digitoxin or digoxin can occur, leading to cardiotoxicity.[40]

Calcium has many drug interactions, each of which can cause a different effect. While some interactions may be mild, calcium can cause more serious complications such as renal failure and reduced plasma concentration or efficacy of other drugs. Some of the more common drug interactions include aspirin, atenolol, bisacodyl, bismuth subcitrate, ciprofloxacin, doxycycline, tetracycline, and digoxin.


4Cardiovascular Health

4.1. Lipid Absorption

Consumption of milk products with additional calcium (10-fold higher than normal) is able to increase fecal lipids by 139% and free fatty acids by 195%.[41]

Calcium phosphate is known to be produced in the gut from calcium and phosphorus[13] where it appears able to precipitate intestinal substances such as bile acids or fatty acids.[42][43] Supplementation of 1,000mg calcium has been demonstrated to increase fecal bile acids while reducing fecal cholesterol concentrations.[43]

4.2. Platelets

Dietary calcium intake has once been noted to be inversely related to clotting activity of platelets in farmers[44] and studies in research animals have noted dietary calcium to be associated with less platelet calcium responses[45] and handling[46] in hypertensive rats; thought to indicate a protective effect.

While dietary calcium seems to have a facilitative role in platelets that reduces their overall aggregatory potential it is uncertain as to what effect high or low calcium intake in the diet or supplementation results in

4.3. Atherosclerosis

Fatty acid binding protein (FABP), specifically FABP4, is both a cytosolic and plasma protein involved in trafficking fatty acids. It appears to have an additive effect on lipids and atherosclerotic buildup due to knockout mice being resistant to these states[47][48] and its release from adipocytes (and macrophages) is known to be partially dependent on calciums action as assessed by 0.5-3µM ionomycin.[49] Increases in FABP4 levels have been detected in vitro with other agonists that stimulate calcium release such as Capsaicin.[50] There are currently no human studies assessing dietary calcium supplementation and it's relation to serum FAB4.

Calcium is involved in the release of FABP4 but an interaction with this protein and supplementation of calcium itself is not yet known

The presence of calcium in arteries (Coronary artery calcium; CAC) is known to be predictive of cardiovascular disease and coronary heart disease even in adults without cardiovascular diseases.[51][52] This is thought to be related to arterial stiffness related to calcium, related to both Vitamin D intake[53] and proteins influenced by Vitamin K intake.[54]


5Fat Mass and Obesity

5.1. Mechanisms

Calcium's role in the adipocyte is that of an intracellular messenger, being released in response to various agonists such as Capsaicin.[50]


6Skeletal and Bone Mass

6.1. Osteoporosis

Osteoporosis, a weakening of skeletal bones due to loss of bone mass, is a relatively common bone ailment in the first world with one study noting an estimated 10.3% prevalence of osteoporosis in those above the age of 50 in the USA (2010) and a further 43.9% prevalence of low bone mass without osteoporosis.[55] Calcium is investigated in its role in osteoporosis due both to its pivotal role in being a large constituent of bone mass but also due to generally low intake of calcium in populations which suffer from osteoporosis and reduced bone mass.[56][57]

6.2. Fractures

Fractured bones are known to be a large risk during advancing age due to a combination of reduced bone integrity and diminishing muscular strength,[58] largely tied in to osteoporotic pathology.[59] Beyond other preventative measures such as resistance training which is effectively preventative[60] calcium supplementation is also investigated due to aiding in bone integrity during osteoporosis.

A review[61] found only two interventions using 800mg calcium (one with Vitamin D using milk[62] and the other supplementation[63]) and 50 publications assessing correlations between calcium intake and fracture rates predominately in the elderly; the authors found that, overall, there was no significant and consistent relationship between fracture rates and dietary calcium, milk intake, or intake of dairy overall.[61] Despite this, meta-analyses assessing the usage of calcium in conjunction with Vitamin D do support the preventative benefits of supplementing both to assist in reducing the risk of fractures showing a 15% reduction of total fractures (Summary relative risk estimate (SRRE) of 0.85; 95% CI 0.73-0.98) with a 30% reduction in hip fractures specifically (SRRE 0.70; 95% CI 0.56-0.87).[64]

While supplementing calcium alone does not appear to be sufficient enough to prevent the risk of fractures in the elderly, combining calcium and Vitamin D supplementation does appear to be effective


7Interactions with Hormones

7.1. Testosterone

Four week supplementation of calcium in active and sedentary males (35mg/kg calcium as gluconate) failed to increase testosterone in sedentary men relative to their own baseline, and while an increase in testosterone was seen in the active group supplemented with calcium it was not significantly different than the active group given no supplement.[65]

No significant influence on testosterone concentrations


8Interactions with Cancer Metabolism

8.1. Colon Cancer

Soluble bile acids (rather than total fecal bile acids) contributes to colonic epithelium toxicity[66][67] and are thought to underlie colonic DNA damage and genotoxicity;[68][69] due to the ability of calcium to precipitate these bile acids[70][41][71] secondary to forming amorphous calcium phosphate[72] it is thought to be protective against colon cancer.

Supplementation of 1,000mg calcium for four weeks in otherwise healthy adults has failed to alter the genotoxicity of fecal water, which may be due to barely affecting bile acids in fecal water (despite significantly reducing insoluble bile acids).[43]


9Pregnancy and Lactation

9.1. Hypertension

Hypertension has been estimated to complicate 5% of worldwide pregnencies and 11% of first time pregnancies;[73] due to this being associated with morbidity safe interventions to prevent hypertension and a related condition, pre-eclampsia, are sought after. Calcium is investigated as an inverse relationship between calcium intake and blood pressure during pregnancy is known[74] which extends to pre-eclampsia.[75] Low blood calcium also appears to be a useful predictor of both hypertension[76] and pre-eclampsia[77] during pregnancy.

A Cochrane review on the topic of calcium supplementation during pregnancy has found that, in 13 studies that assess high dose calcium supplementation (1,000mg or greater) the average risk of high blood pressure appeared to be reduced (RR 0.65; 95% CI of 0.53-0.81) alongside a significant reduction in the risk of developing pre-eclampsia (RR 0.45; 95% CI of 0.31-0.65);[78] the effect was most significant in women who were at greater risk of pre-eclampsia as assessed by other factors and women who had low dietary calcium intake.[78]

It appears that supplementation of 1,000mg calcium during pregnancy is able to reduce the risk of developing high blood pressure and pre-clampsia with particular potency in people who have a low dietary calcium intake. Increasing calcium intake from food products is also able to confer this protective effect.

It is known that the risk of pre-eclampsia is increased with high BMI during pregnancy (greater than 35) and with high blood pressure before pregnancy,[79] calcium supplementation of 2g a day for the second half of pregnancy appears to be unable of normalizing this risk.[80]

While calcium reduces the risk of pre-eclampsia related to low dietary calcium intake, it does not appear to significantly the risk of pre-eclampsia caused by other factors such as excessive body weight

Based on observational studies suggesting that increased maternal calcium intake is associated with reduced blood pressure in the child[81][82] the topic has been reviewed[83] assessing four trials using calcium supplementation[84][85][86][87] which found that, when assessing the mother's intake of calcium during pregnancy, that the child's blood pressure in youth appeared to be inversely associated with the mother's calcium intake.

This effect may only persist in women who were hypertensive during pregnancy[86] as one of these trials in women with low dietary calcium intake (West Africa) given 1,500 mg calcium during the second half of pregnancy failed to find an effect of supplementation when the mothers had normal blood pressure.[87]

Supplemental calcium during pregnancy may have a beneficial effect on the blood pressure of the offspring during youth, potentially related to alleviating the high blood pressure of the mother

9.2. Delivery

In studies assessing the delivery of the child, it was found that supplementation of calcium (1.8g) throughout the second half of pregnancy was associated with less usage of antenatal corticosteroids[88] and less complications with preterm birth (rupture of membranes and admittance for threatened preterm labour).[88]

9.3. Bone Mineral Density

In women who just gave birth (5 days postpartum) given calcium either through dairy products (932mg calcium) or via supplementation (1000mg) for six months, both groups were associated with increased bone mineral density and bone mineral content and were not significantly different.[89]


10Interactions with Organ Systems

10.1. Intestines

Past research has suggested that soluble fatty acids and secondary bile acids, which act as surfactants in the intestines, may have a role in the promotion of cancer due to stimulating colonic crypt cells[90] which may be indicative of increased risk of colon cancer.[91] Calcium has been investigated in regards to colon cancer as it has a negative correlation with the prevalence of this form of cancer[92] and has shown a suppressive effect when tested in mice subject to a combination of fatty acids and intestinal inflammation.[90] It is thought that excess calcium administration can combine with these soluble lipids and form inert calcium soaps for elimination[90] which has been noted in humans given milk with an increased calcium content (10-fold more than normal) which successfully increased elimination of fatty and bile acids in the feces.[41]

Studies in humans using supplemental calcium in various instances of intestinal inflammation have found a reduction in intestinal hyperproliferation following intestinal bypass (2,400 or 3,600mg calcium carbonate for twelve weeks)[93] and in subjects with a familial history of colon cancer given 700mg calcium carbonate supplementation (1.3-1.5g calcium daily in conjunction with diet).[94] In both cases the level of crypt cell proliferation has reduced.

It is thought that soluble fatty acids in the intestines may damage intestinal tissue which subsequently play a role in promoting colon cancer. Calcium supplementation, or higher than normal calcium intake, seems to protect against this effect


11Nutrient-Nutrient Interactions

11.1. Vitamin D

In Japanese men who were subject to dietary analysis, low dietary calcium appeared to be associated with increased arterial stiffness (assessed by ba-PWV); while vitamin D itself has no relation it appeared that there was even less arterial stiffness in those who consumed high levels of calcium and vitamin D.[53]

11.2. Absorption Modifiers

In vitro, sugar alcohols appear to enhance the absorption of calcium in the small intestine (ileum and jejunum) as well as in the large intestine.[95] Tested sugar alcohols (Erythriol, xylitol, maltitol, lactitol, sorbitol, and palatinit) all appear to enhance absorption of calcium overall with some differences in where they affect absorption.[95]

This effect has also been noted with oligosaccharides[96][97][98] and is thought to be related to changes in the solubility of calcium;[99][100] fermentation of these molecules and production of SCFAs can alter the acidity of the lumen which is known to increase passive (paracellular) calcium absorption.[101]

Absorption of calcium appears to be increased by fermentable and partially fermentable carbohydrates, possibly related to the reduced colonic pH increasing the solubility of calcium


12Safety and Toxicology

12.1. General

The maximum dose of elemental calcium that should be taken at a time is 500 mg to prevent unwanted effects on absorption of calcium and parathyroid hormone.More specifically, absorption of calcium decreases two-fold when calcium is overused, which may lead to bone resorption and increase in parathyroid hormone levels. [102] In other words, calcium supplements might interfere with how well our bones absorb calcium. [103] Natural calcium products have also been reported to contain measurable lead content. [104] While minimum calcium intake varies by age group and pregnancy, maximum calcium intake is consistently 2500 mg per day for everyone. Calcium intake that exceeds the recommended maximum daily dose can result in adverse effects and can interfere with absorption of other minerals, such as Zinc, phosphorus, and Magnesium.[102]

12.2. Human Toxicity

In one meta-analysis, the authors claimed a possible increased risk of cardiovascular disease with calcium use, although the results of the analysis were not statistically significant.[105] In a different meta-analysis, calcium supplementation of 500 mg or greater per day without coadministered Vitamin D was linked with an increased risk of myocardial infarction.[106] Furthermore, a re-analysis of one study, where postmenopausal women were taking 1 g of calcium and 400 IU of Vitamin D daily, found that there was interaction between personal calcium use or allocated calcium and Vitamin D use and cardiovascular events. Two meta-analyses of 11 placebo controlled trials found that calcium or calcium with Vitamin D modestly increased the risk of cardiovascular events, specifically myocardial infarction and stroke.[107] Fatal prostate cancer has also been associated with calcium intakes from food or supplementation in amounts 1500 mg per day.[102]

Meta-analyses of calcium supplementation suggest that it may be linked to increased risk of cardiovascular disease.

12.3. Side Effects with Safe Usage

Calcium supplementation has been reported to cause constipation, excessive abdominal cramping, bloating, severe diarrhea, and abdominal pain.[108]

12.4. Withdrawal

There is evidence that support that the benefits from calcium supplementation disappear after consistent use is withdrawn.[109][110]

12.5. Case Studies

There have been reports of severe hypercalcemia in Williams-Beuren syndrome patients. This is caused by a deleted gene, which is responsible for regulating the intestinal absorption of calcium.[111] Calcium supplementation may be cautioned in people who suffer from this condition.

There has also been evidence that calcium supplementation is linked with the severity of pseudoxanthoma elasticum (PXE) lesions in people affected by this condition.[112]

Scientific Support & Reference Citations

References

  1. Booth A, Camacho P A Closer look at calcium absorption and the benefits and risks of dietary versus supplemental calcium . Postgrad Med. (2013)
  2. Lanham-New SA Importance of calcium, vitamin D and vitamin K for osteoporosis prevention and treatment . Proc Nutr Soc. (2008)
  3. Prakasam M et al. Fabrication, Properties and Applications of Dense Hydroxyapatite: A Review . J Funct Biomater. (2015)
  4. Jacobson J, Duchen MR Interplay between mitochondria and cellular calcium signalling . Mol Cell Biochem. (2004)
  5. Dietary Reference Intakes for Calcium and Vitamin D
  6. Ross AC et al. The 2011 Dietary Reference Intakes for Calcium and Vitamin D: what dietetics practitioners need to know . J Am Diet Assoc. (2011)
  7. Rajakumar K Vitamin D, cod-liver oil, sunlight, and rickets: a historical perspective . Pediatrics. (2003)
  8. Pettifor JM Nutritional rickets: deficiency of vitamin D, calcium, or both? . Am J Clin Nutr. (2004)
  9. Kooh SW et al. Rickets due to calcium deficiency . N Engl J Med. (1977)
  10. Legius E et al. Rickets due to dietary calcium deficiency . Eur J Pediatr. (1989)
  11. Majid Molla A et al. Risk factors for nutritional rickets among children in Kuwait . Pediatr Int. (2000)
  12. Pettifor JM et al. Rickets in children of rural origin in South Africa: is low dietary calcium a factor? . J Pediatr. (1978)
  13. Effects of dietary calcium and phosphate on the intestinal interactions between calcium, phosphate, fatty acids, and bile acids
  14. Trautvetter U, Kiehntopf M, Jahreis G Postprandial effects of calcium phosphate supplementation on plasma concentration-double-blind, placebo-controlled cross-over human study . Nutr J. (2013)
  15. Grimm M, et al High phosphorus intake only slightly affects serum minerals, urinary pyridinium crosslinks and renal function in young women . Eur J Clin Nutr. (2001)
  16. Ishitani K et al. Calcium absorption from the ingestion of coral-derived calcium by humans . J Nutr Sci Vitaminol (Tokyo). (1999)
  17. Kim SK, Ravichandran YD, Kong CS Applications of calcium and its supplement derived from marine organism . Crit Rev Food Sci Nutr. (2012)
  18. Ramos AA, Inoue Y, Ohde S Metal contents in Porites corals: Anthropogenic input of river run-off into a coral reef from an urbanized area, Okinawa . Mar Pollut Bull. (2004)
  19. J. Hu et al. Production and analysis of hydroxyapatite from Australian corals via hydrothermal process . Journal of Materials Science Letters. (2001)
  20. Reddy PN, Lakshmana M, Udupa UV Effect of Praval bhasma (Coral calx), a natural source of rich calcium on bone mineralization in rats . Pharmacol Res. (2003)
  21. Banu J et al. Dietary coral calcium and zeolite protects bone in a mouse model for postmenopausal bone loss . Nutr Res. (2012)
  22. Hendy GN, Canaff L Calcium-sensing receptor, proinflammatory cytokines and calcium homeostasis . Semin Cell Dev Biol. (2016)
  23. Canaff L, Zhou X, Hendy GN The proinflammatory cytokine, interleukin-6, up-regulates calcium-sensing receptor gene transcription via Stat1/3 and Sp1/3 . J Biol Chem. (2008)
  24. Canaff L, Hendy GN Calcium-sensing receptor gene transcription is up-regulated by the proinflammatory cytokine, interleukin-1beta. Role of the NF-kappaB PATHWAY and kappaB elements . J Biol Chem. (2005)
  25. Bronner F Mechanisms of intestinal calcium absorption . J Cell Biochem. (2003)
  26. Diaz de Barboza G, Guizzardi S, Tolosa de Talamoni N Molecular aspects of intestinal calcium absorption . World J Gastroenterol. (2015)
  27. Bronner F, Pansu D, Stein WD An analysis of intestinal calcium transport across the rat intestine . Am J Physiol. (1986)
  28. Bronner F, Buckley M Calcium-binding protein biosynthesis in the rat: Regulation by calcium and 1,25-dihydroxyvitamin D3 . Arch Biochem and Biophys. (1980)
  29. Alexander RT, Rievaj J, Dimke H Paracellular calcium transport across renal and intestinal epithelia . Biochem Cell Biol. (2014)
  30. Peng JB et al Molecular cloning and characterization of a channel-like transporter mediating intestinal calcium absorption . J Biol Chem. (1999)
  31. Nijenhuis T et al. Localization and regulation of the epithelial Ca2+ channel TRPV6 in the kidney . J Am Soc Nephrol. (2003)
  32. Kellett GL Alternative perspective on intestinal calcium absorption: proposed complementary actions of Ca(v)1.3 and TRPV6 . Nutr Rev. (2011)
  33. Nägerl UV et al. Binding kinetics of calbindin-D(28k) determined by flash photolysis of caged Ca(2+) . Biophys J. (2000)
  34. Schwaller B Cytosolic Ca2+ buffers . Cold Spring Harb Perspect Biol. (2010)
  35. Centeno VA et al. Dietary calcium deficiency increases Ca2+ uptake and Ca2+ extrusion mechanisms in chick enterocytes . Comp Biochem Physiol A Mol Integr Physiol. (2004)
  36. Ghijsen WE, De Jong MD, Van Os CH Kinetic properties of Na+/Ca2+ exchange in basolateral plasma membranes of rat small intestine . Biochim Biophys Acta. (1983)
  37. Freeman TC et al. Cellular and regional expression of transcripts of the plasma membrane calcium pump PMCA1 in rabbit intestine . Am J Physiol. (1995)
  38. Favus MJ Factors that influence absorption and secretion of calcium in the small intestine and colon . Am J Physiol. (1985)
  39. Pansu D et al Solubility and intestinal transit time limit calcium absorption in rats . J Nutr. (1993)
  40. Yetley EA1 Multivitamin and multimineral dietary supplements: definitions, characterization, bioavailability, and drug interactions . Am J Clin Nutr. (2007)
  41. Govers MJ, et al Calcium in milk products precipitates intestinal fatty acids and secondary bile acids and thus inhibits colonic cytotoxicity in humans . Cancer Res. (1996)
  42. Van der Meer R, et al Mechanisms of the intestinal effects of dietary fats and milk products on colon carcinogenesis . Cancer Lett. (1997)
  43. Ditscheid B, Keller S, Jahreis G Faecal steroid excretion in humans is affected by calcium supplementation and shows gender-specific differences . Eur J Nutr. (2009)
  44. Renaud S, et al Nutrients, platelet function and composition in nine groups of French and British farmers . Atherosclerosis. (1986)
  45. Rao RM, Yan Y, Wu Y Dietary calcium reduces blood pressure, parathyroid hormone, and platelet cytosolic calcium responses in spontaneously hypertensive rats . Am J Hypertens. (1944)
  46. Oshima T, et al Modification of platelet and lymphocyte calcium handling and blood pressure by dietary sodium and calcium in genetically hypertensive rats . J Lab Clin Med. (1992)
  47. Uysal KT, et al Improved glucose and lipid metabolism in genetically obese mice lacking aP2 . Endocrinology. (2000)
  48. Makowski L, et al Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis . Nat Med. (2001)
  49. Schlottmann I, et al Calcium-dependent release of adipocyte fatty acid binding protein from human adipocytes . Int J Obes (Lond). (2014)
  50. Kida R, et al Direct action of capsaicin in brown adipogenesis and activation of brown adipocytes . Cell Biochem Funct. (20016)
  51. Gepner AD, et al Comparison of coronary artery calcium presence, carotid plaque presence, and carotid intima-media thickness for cardiovascular disease prediction in the Multi-Ethnic Study of Atherosclerosis . Circ Cardiovasc Imaging. (2015)
  52. Folsom AR, et al Coronary artery calcification compared with carotid intima-media thickness in the prediction of cardiovascular disease incidence: the Multi-Ethnic Study of Atherosclerosis (MESA) . Arch Intern Med. (2008)
  53. Uemura H, et al Association between dietary calcium intake and arterial stiffness according to dietary vitamin D intake in men . Br J Nutr. (2014)
  54. Pivin E, et al Inactive Matrix Gla-Protein Is Associated With Arterial Stiffness in an Adult Population-Based Study . Hypertension. (2015)
  55. Wright NC et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine . J Bone Miner Res. (2014)
  56. Bailey RL et al. Estimation of total usual calcium and vitamin D intakes in the United States . J Nutr. (2010)
  57. Wallace TC et al. Calcium and vitamin D disparities are related to gender, age, race, household income level, and weight classification but not vegetarian status in the United States: Analysis of the NHANES 2001-2008 data set . J Am Coll Nutr. (2013)
  58. Ensrud KE Epidemiology of fracture risk with advancing age . J Gerontol A Biol Sci Med Sci. (2013)
  59. Cummings SR, Melton LJ Epidemiology and outcomes of osteoporotic fractures . Lancet. (2002)
  60. Karinkanta S et al. Combined resistance and balance-jumping exercise reduces older women's injurious falls and fractures: 5-year follow-up study . Age Ageing. (2015)
  61. Bolland MJ et al Calcium intake and risk of fracture: systematic review . BMJ. (2015)
  62. Lau EM, et al Milk supplementation of the diet of postmenopausal Chinese women on a low calcium intake retards bone loss . J Bone Miner Res. (2001)
  63. Chevalley T et al. Effects of calcium supplements on femoral bone mineral density and vertebral fracture rate in vitamin-D-replete elderly patients . Osteoporos Int. (1994)
  64. Weaver CM et al. Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation . Osteoporos Int. (2016)
  65. Cinar V, et al Testosterone levels in athletes at rest and exhaustion: effects of calcium supplementation . Biol Trace Elem Res. (2009)
  66. Nagengast FM, Grubben MJ, van Munster IP Role of bile acids in colorectal carcinogenesis . Eur J Cancer. (1995)
  67. Roberton AM Roles of endogenous substances and bacteria in colorectal cancer . Mutat Res. (1993)
  68. Glinghammar B, Inoue H, Rafter JJ Deoxycholic acid causes DNA damage in colonic cells with subsequent induction of caspases, COX-2 promoter activity and the transcription factors NF-kB and AP-1 . Carcinogenesis. (2002)
  69. Powolny A, Xu J, Loo G Deoxycholate induces DNA damage and apoptosis in human colon epithelial cells expressing either mutant or wild-type p53 . Int J Biochem Cell Biol. (2001)
  70. Differential binding of glycine- and taurine-conjugated bile acids to insoluble calcium phosphate
  71. Govers MJ, et al Characterization of the adsorption of conjugated and unconjugated bile acids to insoluble, amorphous calcium phosphate . J Lipid Res. (1994)
  72. Termine JD, Posner AS Calcium phosphate formation in vitro. I. Factors affecting initial phase separation . Arch Biochem Biophys. (1970)
  73. Villar J, et al Strategies to prevent and treat preeclampsia: evidence from randomized controlled trials . Semin Nephrol. (2004)
  74. Belizán JM, Villar J, Repke J The relationship between calcium intake and pregnancy-induced hypertension: up-to-date evidence . Am J Obstet Gynecol. (1988)
  75. Segovia BL, et al Hypocalciuria during pregnancy as a risk factor of preeclampsia . Ginecol Obstet Mex. (2004)
  76. Kumru S, et al Comparison of serum copper, zinc, calcium, and magnesium levels in preeclamptic and healthy pregnant women . Biol Trace Elem Res. (2003)
  77. Isezuo SA, Ekele BA Eclampsia and abnormal QTc . West Afr J Med. (2004)
  78. Hofmeyr GJ, et al Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems . Cochrane Database Syst Rev. (2014)
  79. Duckitt K, Harrington D Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies . BMJ. (2005)
  80. Sibai BM, et al Risk factors associated with preeclampsia in healthy nulliparous women. The Calcium for Preeclampsia Prevention (CPEP) Study Group . Am J Obstet Gynecol. (1997)
  81. Gillman MW et al. Maternal calcium intake and offspring blood pressure . Circulation. (2004)
  82. McGarvey ST et al. Maternal prenatal dietary potassium, calcium, magnesium, and infant blood pressure . Hypertension. (1991)
  83. Jamshidi F, Kelishadi R A systematic review on the effects of maternal calcium supplementation on offspring's blood pressure . J Res Med Sci. (2015)
  84. Hatton DC, et al Gestational calcium supplementation and blood pressure in the offspring . Am J Hypertens. (2003)
  85. Belizán JM et al. Long-term effect of calcium supplementation during pregnancy on the blood pressure of offspring: follow up of a randomised controlled trial . BMJ. (1997)
  86. Hiller JE et al. Calcium supplementation in pregnancy and its impact on blood pressure in children and women: follow up of a randomised controlled trial . Aust N Z J Obstet Gynaecol. (2007)
  87. Hawkesworth S et al. Effect of maternal calcium supplementation on offspring blood pressure in 5- to 10-y-old rural Gambian children . Am J Clin Nutr. (2010)
  88. Crowther CA, et al Calcium supplementation in nulliparous women for the prevention of pregnancy-induced hypertension, preeclampsia and preterm birth: an Australian randomized trial. FRACOG and the ACT Study Group . Aust N Z J Obstet Gynaecol. (1999)
  89. Malpeli A, et al Calcium supplementation, bone mineral density and bone mineral content. Predictors of bone mass changes in adolescent mothers during the 6-month postpartum period . Arch Latinoam Nutr. (2012)
  90. Wargovich MJ, Eng VW, Newmark HL Calcium inhibits the damaging and compensatory proliferative effects of fatty acids on mouse colon epithelium . Cancer Lett. (1984)
  91. Lipkin M Biomarkers of increased susceptibility to gastrointestinal cancer: new application to studies of cancer prevention in human subjects . Cancer Res. (1988)
  92. Sorenson AW, Slattery ML, Ford MH Calcium and colon cancer: a review . Nutr Cancer. (1988)
  93. Steinbach G, et al Effect of calcium supplementation on rectal epithelial hyperproliferation in intestinal bypass subjects . Gastroenterology. (1994)
  94. Lipkin M1, et al Colonic epithelial cell proliferation in responders and nonresponders to supplemental dietary calcium . Cancer Res. (1989)
  95. Mineo H, Hara H, Tomita F Sugar alcohols enhance calcium transport from rat small and large intestine epithelium in vitro . Dig Dis Sci. (2002)
  96. Mineo H et al. Two-week feeding of difructose anhydride III enhances calcium absorptive activity with epithelial cell proliferation in isolated rat cecal mucosa . Nutrition. (2006)
  97. Saito K et al. Effects of DFA IV in rats: calcium absorption and metabolism of DFA IV by intestinal microorganisms . Biosci Biotechnol Biochem. (1999)
  98. Hara H, Suzuki T, Aoyama Y Ingestion of the soluble dietary fibre, polydextrose, increases calcium absorption and bone mineralization in normal and total-gastrectomized rats . Br J Nutr. (2000)
  99. Levrat MA, Rémésy C, Demigné C High propionic acid fermentations and mineral accumulation in the cecum of rats adapted to different levels of inulin . J Nutr. (1991)
  100. Younes H, Demigné C, Rémésy C Acidic fermentation in the caecum increases absorption of calcium and magnesium in the large intestine of the rat . Br J Nutr. (1996)
  101. Duflos C, et al Calcium solubility, intestinal sojourn time and paracellular permeability codetermine passive calcium absorption in rats . J Nutr. (1995)
  102. Straub DA1 Calcium supplementation in clinical practice: a review of forms, doses, and indications . Nutr Clin Pract. (2007)
  103. Reid IR1, et al Calcium supplements: benefits and risks . J Intern Med. (2015)
  104. Edward RA, Szabo NJ, Tebbett IR Lead Content of Calcium Supplements . JAMA. (2000)
  105. Mao PJ1, et al Effect of calcium or vitamin D supplementation on vascular outcomes: a meta-analysis of randomized controlled trials . Int J Cardiol. (2013)
  106. Bolland MJ1, et al Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis . BMJ. (2010)
  107. Bolland MJ1, et al Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women's Health Initiative limited access dataset and meta-analysis . BMJ. (2011)
  108. Lewis JR1, Zhu K, Prince RL Adverse events from calcium supplementation: relationship to errors in myocardial infarction self-reporting in randomized controlled trials of calcium supplementation . J Bone Miner Res. (2012)
  109. Lee WT1, et al A follow-up study on the effects of calcium-supplement withdrawal and puberty on bone acquisition of children . Am J Clin Nutr. (1996)
  110. Lambert HL1, et al Calcium supplementation and bone mineral accretion in adolescent girls: an 18-mo randomized controlled trial with 2-y follow-up . Am J Clin Nutr. (2008)
  111. Lameris AL, et al Importance of dietary calcium and vitamin D in the treatment of hypercalcaemia in Williams-Beuren syndrome . J Pediatr Endocrinol Metab. (2014)
  112. Renie WA, et al Pseudoxanthoma elasticum: high calcium intake in early life correlates with severity . Am J Med Genet. (1984)
  113. Villar J1, et al World Health Organization randomized trial of calcium supplementation among low calcium intake pregnant women . Am J Obstet Gynecol. (2006)
  114. Belizán JM1, et al Long-term effect of calcium supplementation during pregnancy on the blood pressure of offspring: follow up of a randomised controlled trial . BMJ. (1997)
  115. Hiller JE1, et al Calcium supplementation in pregnancy and its impact on blood pressure in children and women: follow up of a randomised controlled trial . Aust N Z J Obstet Gynaecol. (2007)
  116. Hawkesworth S1, et al Effect of maternal calcium supplementation on offspring blood pressure in 5- to 10-y-old rural Gambian children . Am J Clin Nutr. (2010)

(Editors who contributed to this page include )