Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction of all muscle cell types, and in fertilization. Many enzymes require calcium ions as a cofactor, including several of the coagulation factors. Extracellular calcium is also important for maintaining the potential difference across excitable cell membranes, as well as proper bone formation.

Plasma calcium levels in mammals are tightly regulated, electronic-book electronic- with bone acting as the major mineral storage site. Calcium ions, Ca2+, are released from bone into the bloodstream under controlled conditions. Calcium is transported through the bloodstream as dissolved ions or bound to proteins such as serum albumin. Parathyroid hormone secreted by the parathyroid gland regulates the resorption of Ca2+ from bone, reabsorption in the kidney back into circulation, and increases in the activation of vitamin D3 to calcitriol. Calcitriol, the active form of vitamin D3, promotes absorption of calcium from the intestines and bones. Calcitriol also plays a key role in upregulating levels of intracellular calcium, and high levels of this ion appear to be protective against cancers of the breast and prostate. The suppression of calcitriol by excessive dietary calcium is believed to be the major mechanism for the potential link between dairy and cancer. However, the vitamin D present in many dairy products may help compensate for this deleterious effect of high-calcium diets by increasing serum calcitriol levels. Calcitonin secreted from the parafollicular cells of the thyroid gland also affects calcium levels by opposing parathyroid hormone; however, its physiological significance in humans is in dispute.

Intracellular calcium is stored in organelles which repetitively release and then reaccumulate Ca2+ ions in response to specific cellular events: storage sites include mitochondria and the endoplasmic reticulum.

Characteristic concentrations of calcium in model organisms are: in E. coli 3 mM (bound), 100 nM (free), in budding yeast 2 mM (bound), in mammalian cell 10–100 nM (free) and in blood plasma 2 mM.

Humans

+ Age-adjusted daily calcium recommendations (from U.S. Institute of Medicine RDAs) Age Calcium (mg/day) 1–3 years 700 4–8 years 1000 9–18 years 1300 19–50 years 1000 >51 years 1000 Pregnancy 1000 Lactation 1000

In 2022, it was the 277th most commonly prescribed medication in the United States, with more than 700,000 prescriptions.

Dietary recommendations The US Institute of Medicine (IOM) established Recommended Dietary Allowances (RDAs) for calcium in 1997 and updated those values in 2011. See table. The European Food Safety Authority (EFSA) uses the term Population Reference Intake (PRIs) instead of RDAs and sets slightly different numbers: ages 4–10 800 mg, ages 11–17 1150 mg, ages 18–24 1000 mg, and >25 years 950 mg.

Because of concerns of long-term adverse side effects such as calcification of arteries and kidney stones, the IOM and EFSA both set Tolerable Upper Intake Levels (ULs) for the combination of dietary and supplemental calcium. From the IOM, people ages 9–18 years are not supposed to exceed 3,000 mg/day; for ages 19–50 not to exceed 2,500 mg/day; for ages 51 and older, not to exceed 2,000 mg/day. The EFSA set UL at 2,500 mg/day for adults but decided the information for children and adolescents was not sufficient to determine ULs.

Labeling For US food and dietary supplement labeling purposes, the amount in a serving is expressed as a percent of Daily Value (%DV). For calcium labeling purposes, 100% of the Daily Value was 1000 mg, but as of 27 May 2016, it was revised to 1300 mg to bring it into agreement with the RDA. A table of the old and new adult daily values is provided at Reference Daily Intake.

Health claims Although as a general rule, dietary supplement labeling and marketing are not allowed to make disease prevention or treatment claims, the FDA has for some foods and dietary supplements reviewed the science, concluded that there is significant scientific agreement for a beneficial effect of dietary calcium on bone mineral density (along with vitamin D to facilitate its absorption), and published specifically worded allowed health claims. An initial ruling allowing a health claim for calcium dietary supplements and osteoporosis was later amended to include calcium and vitamin D supplements, effective 1 January 2010. Examples of allowed wording are shown below. In order to qualify for the calcium health claim, a dietary supplement must contain at least 20% of the Reference Dietary Intake, which for calcium means at least 260 mg/serving.Food Labeling: Health Claims; Calcium and Osteoporosis, and Calcium, Vitamin D, and Osteoporosis U.S. Food and Drug Administration.

"Adequate calcium throughout life, as part of a well-balanced diet, may reduce the risk of osteoporosis." "Adequate calcium as part of a healthful diet, along with physical activity, may reduce the risk of osteoporosis in later life." "Adequate calcium and vitamin D throughout life, as part of a well-balanced diet, may reduce the risk of osteoporosis." "Adequate calcium and vitamin D as part of a healthful diet, along with physical activity, may reduce the risk of osteoporosis in later life."

In 2005, the FDA approved a Qualified Health Claim for calcium and hypertension in light of the evidence available at that time, with suggested wording "Some scientific evidence suggests that calcium supplements may reduce the risk of hypertension. However, FDA has determined that the evidence is inconsistent and not conclusive." Evidence for pregnancy-induced hypertension and preeclampsia was considered inconclusive.Qualified Health Claims: Letter of Enforcement Discretion – Calcium and Hypertension; Pregnancy-Induced Hypertension; and Preeclampsia (Docket No. 2004Q-0098) U.S. Food and Drug Administration (2005). The same year, the FDA approved a QHC for calcium and colon cancer, with suggested wording "Some evidence suggests that calcium supplements may reduce the risk of colon/rectal cancer, however, FDA has determined that this evidence is limited and not conclusive." Evidence for breast cancer and prostate cancer was considered inconclusive.Qualified Health Claims: Letter Regarding Calcium and Colon/Rectal, Breast, and Prostate Cancers and Recurrent Colon Polyps (Docket No. 2004Q-0097) U.S. Food and Drug Administration (2005). Proposals for QHCs for calcium as protective against kidney stones or against menstrual disorders or pain were rejected.Qualified Health Claims: Letter of Denial – Calcium and Kidney Stones; Urinary Stones; and Kidney Stones and Urinary Stones (Docket No. 2004Q-0102) U.S. Food and Drug Administration (2005).Qualified Health Claims: Letters of Denial - Calcium and a Reduced Risk Of Menstrual Disorders (Docket No. 2004Q-0099) U.S. Food and Drug Administration (2005)

The European Food Safety Authority (EFSA) concluded that "Calcium contributes to the normal development of bones."Calcium and contribution to the normal development of bones: evaluation of a health claim European Food Safety Authority (2016). The EFSA rejected a claim that a cause-and-effect relationship existed between the dietary intake of calcium and potassium and maintenance of normal acid-base balance.Scientific Opinion on the substantiation of health claims related to calcium and potassium and maintenance of normal acid-base balance European Food Safety Authority (2011). The EFSA also rejected claims for calcium and nails, hair, blood lipids, premenstrual syndrome and body weight maintenance.Scientific Opinion on the substantiation of health claims related to calcium and maintenance of normal bone and teeth (ID 2731, 3155, 4311, 4312, 4703), maintenance of normal hair and nails (ID 399, 3155), maintenance of normal blood LDL-cholesterol concentrations (ID 349, 1893), maintenance of normal blood HDL-cholesterol concentrations (ID 349, 1893), reduction in the severity of symptoms related to the premenstrual syndrome (ID 348, 1892), "cell membrane permeability" (ID 363), reduction of tiredness and fatigue (ID 232), contribution to normal psychological functions (ID 233), contribution to the maintenance or achievement of a normal body weight (ID 228, 229) and regulation of normal cell division and differentiation EFSA Journal 2010;8(10):1725.

Food sources The United States Department of Agriculture (USDA) web site has a very complete searchable table of calcium content (in milligrams) in foods, per common measures such as per 100 grams or per a normal serving. Food, calcium per 100 gramsparmesan (cheese) = 1140 mgmilk powder = 909 mggoat hard cheese = 895 mgCheddar cheese = 720 mgtahini paste = 427 mgmolasses = 273 mgsardines = 240 mgalmonds = 234 mgcollard greens = 232 mgkale = 150 mggoat milk = 134 mgsesame seeds (unhulled) = 125 mgnonfat cow milk = 122 mgplain whole-milk yogurt = 121 mg Food, calcium per 100 gramshazelnuts = 114 mgtofu, soft = 114 mgbeet greens = 114 mgspinach = 99 mgricottas (skimmed milk cheese) = 90 mglentils = 79 mgchickpeas = 53 mgrolled oats = 52 mgeggs, boiled = 50 mgorange = 40 mghuman milk = 33 mgrice, white, long-grain = 19 mgbeef = 12 mgcod = 11 mg

Measurement in blood The amount of calcium in blood (more specifically, in blood plasma) can be measured as total calcium, which includes both protein-bound and free calcium. In contrast, ionized calcium is a measure of free calcium. An abnormally high level of calcium in plasma is termed hypercalcemia and an abnormally low level is termed hypocalcemia, with "abnormal" generally referring to levels outside the reference range.

+ Reference ranges for blood tests for calcium Target Lower limitUpper limitUnit Ionized calcium 1.03, 1.10Reference range list from Uppsala University Hospital ("Laborationslista"). Artnr 40284 Sj74a. Issued on 22 April 2008 1.23, 1.30 mmol/L 4.1,Derived from molar values using molar mass of 40.08  g•mol−1 4.4 4.9, 5.2 mg/dL Total calcium 2.1,Last page of Derived from mass values using molar mass of 40.08  g•mol−1 2.2 2.5, 2.6, 2.8 mmol/L 8.4, 8.5Blood Test Results – Normal Ranges Bloodbook.Com 10.2, 10.5 mg/dL

The main methods to measure serum calcium are:Clin Chem. 1992 Jun;38(6):904–08. Single stable reagent (Arsenazo III) for optically robust measurement of calcium in serum and plasma. Leary NO, Pembroke A, Duggan PF. O-Cresolphalein Complexone Method; A disadvantage of this method is that the volatile nature of the 2-amino-2-methyl-1-propanol used in this method makes it necessary to calibrate the method every few hours in a clinical laboratory setup. Arsenazo III Method; This method is more robust, but the arsenic in the reagent is a health hazard.

The total amount of Ca2+ present in a tissue may be measured using Atomic absorption spectroscopy, in which the tissue is vaporized and combusted. To measure Ca2+ concentration or spatial distribution within the cell cytoplasm in vivo or in vitro, a range of fluorescent reporters may be used. These include cell permeable, calcium-binding fluorescent dyes such as Fura-2 or genetically engineered variant of green fluorescent protein (GFP) named Cameleon.

Corrected calcium As access to an ionized calcium is not always available a corrected calcium may be used instead. To calculate a corrected calcium in mmol/L one takes the total calcium in mmol/L and adds it to ((40 minus the serum albumin in g/L) multiplied by 0.02). There is, however, controversy around the usefulness of corrected calcium as it may be no better than total calcium. It may be more useful to correct total calcium for both albumin and the anion gap.

Other animals

Vertebrates