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The NuGOwiki Metabolite Database is a joint initiative of NuGO and HMDB
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| Calcium | |
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| Chemical Name | calcium |
| Chemical Formula | Ca |
| CAS Number | 7440-70-2 |
| Chemical Information | HMDB00464 |
| Biochemical Taxonomy |
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| Functional Taxonomy |
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| Nutritional Taxonomy |
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| Metabolic Pathways | Not Available |
| Biofluid Location |
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| Tissue Location | Not Available |
| Normal Biofluid Concentrations |
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| Normal Tissue Concentrations | Not Available |
| Diseases / Conditions Related to Nutrition |
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| Other (Monogenic Disorders) |
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| Abnormal Biofluid Concentrations |
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| Abnormal Tissue Concentrations | Not Available |
| Physiological Processes | Not Available |
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Contents |
Introduction
guidelines
Calcium is essential for the normal growth and maintenance of bones and teeth, and calcium requirements must be met throughout life. Requirements are greatest during periods of growth, such as childhood, during pregnancy and when breast-feeding. Long-term calcium deficiency can lead to osteoporosis, in which the bone deteriorates and there is an increased risk of fractures. Adults need between 1,000 and 1,300 mg of calcium in their daily diet. Calcium is essential for living organisms, particularly in cell physiology, and is the most common metal in many animals. Calcium combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Calcium is an important component of a healthy diet. A deficit can affect bone and tooth formation, while overretention can cause kidney stones. Vitamin D is needed to absorb calcium. Dairy products, such as milk and cheese, are a well-known source of calcium. However, some individuals are allergic to dairy products and even more people, particularly those of non-European descent, are lactose-intolerant, leaving them unable to consume dairy products. Fortunately, many other good sources of calcium exist. These include: seaweeds such as kelp, wakame and hijiki; nuts and seeds (like almonds and sesame); beans; amaranth; collard greens; okra; rutabaga; broccoli; kale; and fortified products such as orange juice and soy milk. Calcium has also been found to assist in the production of lymphatic fluids.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Calcium is essential for the normal growth and maintenance of bones and teeth, and calcium requirements must be met throughout life. Requirements are greatest during periods of growth, such as childhood, during pregnancy and when breast-feeding. Long-term calcium deficiency can lead to osteoporosis, in which the bone deteriorates and there is an increased risk of fractures. Adults need between 1,000 and 1,300 mg of calcium in their daily diet. Calcium is essential for living organisms, particularly in cell physiology, and is the most common metal in many animals. Calcium combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Calcium is an important component of a healthy diet. A deficit can affect bone and tooth formation, while overretention can cause kidney stones. Vitamin D is needed to absorb calcium. Dairy products, such as milk and cheese, are a well-known source of calcium. However, some individuals are allergic to dairy products and even more people, particularly those of non-European descent, are lactose-intolerant, leaving them unable to consume dairy products. Fortunately, many other good sources of calcium exist. These include: seaweeds such as kelp, wakame and hijiki; nuts and seeds (like almonds and sesame); beans; amaranth; collard greens; okra; rutabaga; broccoli; kale; and fortified products such as orange juice and soy milk. Calcium has also been found to assist in the production of lymphatic fluids.
Biological Function
guidelines
Calcium is the most common mineral in the human body. About 99% of the calcium in the body is found in bones and teeth, while the other 1% is found in the blood and soft tissue.
Calcium is essential in muscle contraction, oocyte activation, building strong bones and teeth, blood clotting, nerve impulse transmission, regulating heartbeat, signal transduction pathways and the secretion of hormones, such as insulin. Excesses of calcium within a cell may damage it or even cause it to undergo apoptosis.
In eukaryotes, Ca2+ ions are one of the most widespread second messengers used in signal transduction. They make their entrance into the cytoplasm either from outside the cell through the cell membrane via calcium channels (such as Ca-binding proteins), or from some internal calcium storages. Ca2+ entering the cell plasma causes the specific action of the cell, whatever this action is: secretory cells release vesicles with their secretion, muscle cells contract, synapses release synaptic vesicles and go into processes of synaptic plasticity, etc.
Cofactor for enzymes and proteins Calcium is necessary to stabilize or allow for optimal activity of a number of proteins and enzymes. The binding of calcium ions is required for the activation of the seven "vitamin K-dependent" clotting factors in the coagulation cascade.
Regulation of calcium levels Calcium levels in the blood and fluid surrounding the cells (extracellular fluid) must be maintained within a very narrow concentration range for normal physiological functioning. When blood calcium decreases, calcium-sensing proteins in the parathyroid glands send signals resulting in the secretion of parathyroid hormone (PTH). PTH stimulates the conversion of vitamin D to its active form, calcitriol, in the kidneys. Calcitriol increases the absorption of calcium from the small intestine. Together with PTH, calcitriol stimulates the release of calcium from bone by activating osteoclasts (bone resorbing cells), and decreases the urinary excretion of calcium by increasing its reabsorption in the kidneys. When blood calcium rises to normal levels, the parathyroid glands stop secreting PTH and the kidneys begin to excrete any excess calcium in the urine. Circulating calcium is either in the free, ionized form or bound to blood proteins such as albumin.
Catabolism
guidelines
Calcium, combined with phosphate to form hydroxylapatite [Ca10(PO4)6(OH)2], the mainly mineral component of bone.
Disorders of calcium metabolism
- Hypocalcemia
- Hypercalcemia
- Pseudohypoparathyroidism
- Alzheimer's patients
- Multiple Sclerosis
Hypocalcemia is the presence of low serum calcium levels in the blood, usually taken as less than 2.2 mmol/L or 9mg/dl or an ionized calcium level of less than 1.1 mmol/L (4.5 mg/dL). It is a type of electrolyte disturbance. It mainly occurs due to a deficiency of parathyroid hormone, inefficient parathyroid hormone, or deficiency of Vitamin D.
Effects:
- Perioral tingling and parasthesia, 'pins and needles' sensation over the extremities of hands and feet. This is the earliest symptom of hypocalcemia.
- Tetany, carpopedal spasm are seen.
- Trousseau sign (eliciting carpal spasm by inflating the blood pressure cuff and maintaining the cuff pressure above systolic).
- Chvostek's sign (tapping of the inferior portion of the zygoma will produce facial spasms).
Hypercalcemia is an elevated calcium level in the blood. It can be an asymptomatic laboratory finding, but because an elevated calcium level is often a clue to other serious disease. Symptoms are more common at high calcium levels (12.0 mg/dL or 3 mmol/l). Severe hypercalcemia (above 15-16 mg/dL or 3.75-4 mmol/l) is considered a medical emergency: at these levels, coma and cardiac arrest can result.
Hypercalcemia per se can result in fatigue, depression, confusion, anorexia, nausea, vomiting, constipation, or increased urination; if it is chronic it can result in urinary calculi (renal stones or bladder stones). Abnormal heart rhythms can result, and an EKG finding of a short QT interval suggests hypercalcemia.
Hyperparathyroidism and malignancy account for ~90% of cases.
Pseudohypoparathyroidism is a condition that mimics hypoparathyroidism, but is due to a resistance to parathyroid hormone, rather than a lack of the hormone.
Related diseases
Osteoporosis
Long-term calcium deficiency can lead to osteoporosis, in which the bone deteriorates and there is an increased risk of fractures. Osteoporosis is a multifactorial disorder, and nutrition is only one factor contributing to its development and progression. Genetics play about a 60-80% role in determining whether or not one will be afflicted with this disease. The remaining 20-40% are influenced by nutritional and lifestyle factors. Men begin to lose, on average, about 0.4% of their bone mass per year beginning at about the age of 50. At age of 35, women lose, on average, about twice as much as men because of menopause (estrogen production dramatically decreases). The dramatic decrease in estrogen causes the body to absorb less calcium from nutritional sources and less calconite to be produced, which is a hormone that blunts bone resorption. The net cause of this is a high rate of bone loss.
Kidney stones
Most kidney stones are composed of calcium oxalate or calcium phosphate. Although their cause is usually unknown, abnormally elevated urinary calcium (hypercalciuria) increases the risk of developing calcium stones. Increasing dietary calcium increases urinary calcium slightly, and the rise is more pronounced in those with hypercalciuria. However, other dietary factors such as sodium and protein are also known to increase urinary calcium (Martini LA and Wood RJ,2000, Heller HJ,1999). A large prospective study that followed men over a period of twelve years found the incidence of symptomatic kidney stones to be 44% lower in men in the highest quintile (1/5) of calcium intake, averaging 1,326 mg/day, compared with men in the lowest quintile of calcium intake, averaging 516 mg/day (Curhan GC, 1993). Similar results were observed in a large prospective study of women over four years (Curhan GC, 1997). The authors of the two studies suggested that increased dietary calcium might inhibit the absorption of dietary oxalate and reduce urinary oxalate, a risk factor for calcium oxalate stones. Support for this idea comes from a study in which people ingested oxalate with or without supplemental calcium (Liebman M and Chai W, 1997). Providing 200 mg of elemental calcium along with the oxalate significantly reduced its absorption and urinary oxalate excretion. Although the risk of forming kidney stones is increased in individuals with abnormally elevated urinary calcium (hypercalciuria), this condition is not usually related to calcium intake, but rather to increased excretion of calcium by the kidneys. Overall, increased dietary calcium has been associated with a decreased risk of kidney stones. However, in a large prospective study, the risk of developing kidney stones in women taking supplemental calcium was 20% higher than in those who did not (Curhan GC, 1997). This effect may be related to the fact that calcium supplements can be taken without food, eliminating their beneficial effect of decreasing intestinal oxalate absorption.
Pregnancy-induced hypertension (preeclampsia)
Pregnancy-induced hypertension (PIH) occurs in 10% of pregnancies, and is a major health risk for pregnant women and their unborn children. PIH is a term that includes gestational hypertension, preeclampsia, and eclampsia. Although the cause of PIH is not entirely understood, calcium metabolism appears to play a role. Data from epidemiological studies suggests an inverse relationship between calcium intake and the incidence of PIH, but the results of experimental research on calcium supplementation and PIH have been less clear. A systematic review of randomized placebo-controlled studies found that calcium supplementation reduced the incidence of high blood pressure in pregnant women at high risk of PIH, as well as in pregnant women with low dietary calcium intake. However, in women at low risk of PIH and with adequate calcium intake the benefit of calcium supplementation was judged small and unlikely to be clinically significant (Kulier R, 1998). A large multi-center clinical trial of Calcium for Preeclampsia Prevention (CPEP) in over 4,500 pregnant women, found no effect of 2,000 mg of supplemental calcium on PIH. However, women in the placebo group had a mean intake of 980 mg/day, while those in the supplemental group had a mean intake of 2,300 mg/day (Levine RJ, 1997). For the general population, meeting current recommendations for calcium intake during pregnancy may also help prevent PIH. Further research is required to determine whether women at high risk for PIH would benefit from calcium supplementation above the current recommendations.
Fetal Bone Health
According to one study, for pregnant women in the second or third trimesters with low dietary calcium intake, supplementation of calcium of up to about 2 grams per day can increase the mineralization of the bones of their fetus; however, women who already have an adequate supply of calcium from their diet are not likely to cause any significant increase in the mineralization of the bones of their fetus (Koo WW, 1999).
Colon Cancer
Animal studies are strongly supportive of a protective role for calcium in preventing intestinal cancers. In humans, controlled clinical trials have found modest decreases in the recurrence of colorectal adenomas (precancerous polyps) with calcium supplementation of 1,200-2,000 mg/day (Baron JA,Bonithon-Kopp C). Wu and other authors explained that more calcium generally equals a lower risk of “distal” colon cancer; however, they also explained how there seems to be a point of calcium consumption when consuming more calcium than necessary may not reduce the risk of developing colon cancer. (Wu K, 2002). One study showed that calcium supplementation may have a more prominent effect on advanced lesions of the colon than any other type of polyp (Wallace K, 2004). Another study agrees that calcium may reduce the risk of colon cancer; in fact, the authors stated that dairy foods, which obviously contain calcium, may have this same benefit (Holt PR, 2001). However, most large prospective studies have found increased calcium intake to be only weakly associated with a decreased risk of colorectal cancer. These weak associations might be explained by the presence of groups within the population that differ in their response to calcium. A recent case-control study of 511 men found that increased calcium intake was more strongly associated with decreased colorectal cancer risk in those men with higher circulating levels of a growth factor known as IGF-1 (Ma J, 2001). There is some evidence that individuals with increased circulating levels of IGF-1 are at increased risk of colorectal cancer, and increased calcium intake may benefit this subgroup more than others.
High blood pressure
An analysis of 23 large observational studies found a reduction in systolic blood pressure of 0.34 millimeters of mercury (mm Hg) per 100 mg of calcium consumed daily and a reduction in diastolic blood pressure of 0.15 mm Hg per 100 mg calcium (Birkett NF, 1998). A large systematic review of 42 randomized controlled trials examining the effect of calcium supplementation on blood pressure compared to placebo found an overall reduction of 1.44 mm Hg in systolic blood pressure and a reduction of 0.84 mm Hg in diastolic blood pressure (Griffith LE, 1999). Calcium supplementation in these randomized controlled trials ranged from 500-2,000 mg/day, with 1,000-1,500 mg/day being the most common dose. In the DASH (Dietary Approaches to Stop Hypertension) study, 549 people were randomized to one of three diets for eight weeks: 1) a control diet that was low in fruit, vegetables, and dairy products, 2) a diet rich in fruits (~5 servings/day) and vegetables (~3 servings/day), and 3) a combination diet rich in fruits and vegetables, and low-fat dairy products (~3 servings/day) (Appel LJ, 1997). The combination diet represented an increase of about 800 mg of calcium/day over the control and fruit/vegetable rich diets for a total of about 1,200 mg of calcium/day. The combination diet reduced systolic blood pressure 5.5 mm Hg and diastolic blood pressure 3.0 mm Hg more than the control diet, while the fruit/vegetable diet reduced systolic blood pressure 2.8 mm Hg and diastolic blood pressure 1.1 mm Hg more than the control diet. Among those participants diagnosed with hypertension, the combination diet reduced systolic blood pressure by 11.4 mm Hg and diastolic pressure by 5.5 mm Hg more than the control diet, while the reduction for the fruit/vegetable diet was 7.2 mm Hg systolic and 2.8 mm Hg diastolic compared to the control diet (Conlin PR, 2000). This research indicates that a calcium intake at the recommended level (1,000-1,200 mg/day) may be helpful in preventing and treating moderate hypertension (Miller GD 2000).
Calcium and weight loss
Diets with higher calcium density (calcium per total calories) have been associated with a reduced incidence of being overweight or obese in several studies. Recent studies in cell culture and animal models indicated that low calcium intakes could result in hormonal and metabolic changes that increase the tendency of fat cells to accumulate fat (Zemel MB, 2000). In a two-year exercise trial, higher dietary calcium intakes were associated with weight loss whether participants were in the exercise group or the control group (Lin YC, 2000). A placebo-controlled calcium supplementation trial found significantly greater weight loss in elderly women supplemented with 1,200 mg of calcium/day compared to a control group (Davies KM,2000). However, one study that investigated this found that calcium supplementation of 1 gram per day failed to produce any significant changes in body weight, and its blood pressure lowering effect produced little benefit in most women (Reid IR, 2005).
Other (Monogenic) Disorders
- Chondrocalcinosis 2 OMIM: 118600
Nutritional Information
guidelines
Recommended Calcium IntakesDietary Reference Intakes for Calcium, Phosphorous, Magnesium, Vitamin D, and Fluoride (1997)[1]
Food sources Dairy products represent rich and absorbable sources of calcium, but certain vegetables and grains also provide calcium. However, the bioavailability of that calcium must be taken into consideration. While the calcium rich plants in the kale family (broccoli, bok choy, cabbage, mustard, and turnip greens) contain calcium that is as bioavailable as that in milk, some food components have been found to 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 potato and dried beans. Phytic acid is a less potent inhibitor of calcium absorption than oxalate.
Detailed table with calcium rich foods (Weaver CM,1999)
Toxicity
The Food and Nutrition Board of the Institute of Medicine set the tolerable upper level (UL) of intake for calcium in adults at 2,500 milligrams (mg) of calcium/day ([2]).
Vulnerable groups
Other resources
guidelines
1.- Schrager S. Dietary calcium intake and obesity. J Am Board Fam Pract. 2005;18(3):205-10.