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Gazikalović E, Obrenović D, Nidzović Z, Toskić-Radojicić M. Gazikalović E, et al. Vojnosanit Pregl. 1996 Mar-Apr;53(2):117-20. Vojnosanit Pregl. 1996. PMID: 9214090 Serbian.

Calcium carbonate

Calcium carbonate, CaCO₃, is one of the most common compounds on Earth, making up about 7% of Earth ’ s crust. It occurs in a wide variety of mineral forms, including limestone, marble, travertine, and chalk. Calcium carbonate also occurs combined with magnesium as the mineral dolomite, CaMg (CO₃)₂. Stalactites and stalagmites in caves are made of calcium carbonate, as are a variety of animal products, notably coral, seashells, eggshells, and pearls. Calcium carbonate has two major crystalline forms — two different geometric arrangements of the calcium ions and carbonate ions that make up the compound — aragonite and calcite. All calcium carbonate minerals are conglomerations of various-sized crystals of these two forms, packed together in different ways and containing various impurities. The large, transparent crystals known as Iceland spar, however, are pure calcite. In its pure form, calcium carbonate is a white powder with a specific gravity of 2.71 in the calcite form or 2.93 in the aragonite form. When heated, it decomposes into calcium oxide (CaO) and carbon dioxide gas (CO₂). It also reacts vigorously with acids to release a froth of carbon dioxide bubbles. It is said that Cleopatra, to show her extravagance, dissolved pearls in vinegar (acetic acid). Every year in the United States alone, tens of millions of tons of limestone are dug, cut, or blasted out of huge deposits in Indiana and elsewhere. It is used mostly for buildings and highways and in the manufacture of steel, where it is used to remove silica (silicon dioxide, SiO₂) and other impurities in the iron ore. Calcium carbonate decomposes to calcium oxide in the heat of the furnace, and the calcium oxide reacts with the silica to form calcium silicates (slag), which float on the molten iron and can be skimmed off. Calcium carbonate deposits can be formed in sea-water when calcium ions dissolved from other minerals react with dissolved carbon dioxide (carbonic acid, H₂ CO₃). The resulting calcium carbonate is insoluble in water and sinks to the bottom. Most of the calcium carbonate deposits found today were formed by sea creatures millions of years ago when oceans covered much of what is now land. They manufactured shells and skeletons of calcium carbonate using the calcium ions and carbon dioxide in the oceans, just as clams, oysters, and corals do today. When these animals died, their shells settled on the sea floor. Now, long after the seas have gone, they have been compressed into thick deposits of limestone. England ’ s White Cliffs of Dover are chalk — a soft, white porous form of limestone made from the shells of microscopic sea creatures called Foraminifera that lived about 136 million years ago. Blackboard “ chalk, ” in contrast, is mostly gypsum, or calcium sulfate (CaSO₄). In pearls — which mollusks make when irritated by a foreign body in their flesh — and in seashells, the individual CaCO₃ crystals are invisibly small, even under a microscope. But they are laid down in such a perfect order that the result is smooth, hard, shiny, and sometimes even iridescent, as in the rainbow colors of abalone shells. In many cases, the mollusk makes its shell by laying down alternating layers: calcite, aragonite, calcite, aragonite, and so on. This gives the shell great strength, as in a sheet of plywood in which the grain of the alternating wood layers runs in crossed directions.

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Mechanism of Action

Calcium is naturally present in the body. Most of the body’s stored calcium is within the bones and teeth as hydroxyapatite. The rest of the body’s calcium is in blood, extracellular fluid, muscle, and other body tissues.[19] In the blood, 40% of calcium is bound to albumin, 13% binds to an anion, like phosphate and lactate, and the majority, 47%, is free, unbound, ionized calcium (Ca 2+ ). The amount of ionized calcium found in the blood is essential and tightly regulated by homeostatic controls because it is physiologically active and plays a vital role in the cellular processes of excitable tissues, such as blood vessels, muscles, glands, and nerves.[1]

Calcium carbonate has three separate mechanisms of action that have pharmacologic effects. Calcium affects the stomach, small intestine, and blood.[20]

As an antacid, calcium carbonate neutralizes gastric acid by acting as a buffer in the stomach’s acidic environment. When CaCO₃ enters the stomach, it dissociates into ionized calcium (Ca 2+ ) and a carbonate anion (CO₃ 2- ). The carbonate anion will then bind to the free protons (H+) found in the stomach to increase the pH by decreasing the concentration of hydrogen ions. By increasing the pH in the stomach, pepsin, bile acids, and the toxins of Helicobacter pylori become inhibited.[21]

The inhibition of pepsin, an enzyme that can degrade tissue protein, and inhibition of bile acid helps reduce damage to and promote the healing of ulcers in the mucosal lining of the stomach and duodenum and injury to the esophagus caused by GERD.[21] There is still some criticism regarding the ulcer-healing effects of calcium carbonate solely being due to its acid-neutralizing mechanism because calcium carbonate can cause acid rebound by increasing plasma gastrin levels and has been shown to increase prostaglandins PGE2 and PGF2 after long-term use that may explain an alternative mechanism to ulcer healing.[22][23][24]

As an antacid, calcium carbonate also increases gastrointestinal motility and initiates peristalsis.[14][25] When the calcium carbonate is chewed and partially digested, the free calcium stimulates peristalsis in the esophagus to move the acid into the stomach and decrease heartburn symptoms.[25]

Calcium carbonate works in the small intestines as a phosphate binder and drug chelator. In individuals with hyperphosphatemia or overdose, calcium will bind to form an insoluble compound blocking dietary phosphate or excess drug absorption and excreting it in feces. Additionally, calcium carbonate, used as a calcium supplement, also acts in the small intestine by chelating with oxalate to prevent absorption and renal calculi formation.[1]

Lastly, calcium carbonate also works in the blood to treat or prevent negative calcium balance seen in low serum calcium conditions.[1] After being absorbed in the small intestines actively with the help of vitamin D and passively vi-a diffusion, ionized calcium circulates in the blood.

Pharmacokinetics

Absorption: After ingesting calcium carbonate tablets, they are broken down in the stomach to form soluble calcium salts. As a result, calcium becomes available for absorption in the body. Calcium absorption occurs in the small intestine by active transport dependent on Vitamin D and diffusion. Fractional calcium absorption, the amount of calcium absorbed over the amount ingested, changes throughout life and is highest in infancy, early puberty, and the last two trimesters of pregnancy for women. It steadily declines as an individual progresses into old age, with a marked decrease starting after menopause for women and late ’50s for men.[19] Besides age and the form of calcium carbonate, calcium absorption can be affected by the dose given, stomach pH, estrogen status, vitamin D level, and genetic polymorphisms.[11]

The fractional absorption is highest at 500 mg when taken with food, and the stomach is acidic. Fractional absorption also increases when the person has sufficient vitamin D, does not have an absorption disorder, is young, has more estrogen, and has a larger body size.[26] Absorption of calcium carbonate decreases if an individual has a mucosal lining disorder or achlorhydria.[27]

Distribution: As previously mentioned, calcium storage in the body is primarily in bones and teeth. However, most of the calcium is found in the ionized, physiologically active form in the blood.

Elimination: Calcium carbonate is excreted in the feces as unabsorbed calcium carbonate, in the urine depending on glomerular filtration and renal tubule reabsorption controlled by parathyroid hormone (PTH) and Vitamin D, and as carbon dioxide from the lungs.[1]

Cited by

Hossain M, Islam R, Rahman MN, Ibna Sabit Khan M, Ahmed F, Al-Amin M, Rabbi MA. Hossain M, et al. Heliyon. 2024 Aug 13;10(16):e36160. doi: 10.1016/j.heliyon.2024.e36160. eCollection 2024 Aug 30. Heliyon. 2024. PMID: 39247315 Free PMC article.

Donnelly FC, Purcell-Milton F, Caffrey E, Branzi L, Stafford S, Alhammad FA, Cleary O, Ghariani M, Kuznetsova V, Gun’ko YK. Donnelly FC, et al. Nanomaterials (Basel). 2023 Dec 31;14(1):100. doi: 10.3390/nano14010100. Nanomaterials (Basel). 2023. PMID: 38202555 Free PMC article.

Svenskaya Y, Pallaeva T. Svenskaya Y, et al. Pharmaceutics. 2023 Nov 2;15(11):2574. doi: 10.3390/pharmaceutics15112574. Pharmaceutics. 2023. PMID: 38004553 Free PMC article. Review.

Chavan PP, Tanwade PD, Sapner VS, Sathe BR. Chavan PP, et al. RSC Adv. 2023 Sep 8;13(38):26940-26947. doi: 10.1039/d3ra04286c. eCollection 2023 Sep 4. RSC Adv. 2023. PMID: 37692351 Free PMC article.

Munyemana JC, He H, Fu C, Fan Y, Sun X, Xiao J. Munyemana JC, et al. ACS Omega. 2023 Aug 16;8(34):30879-30887. doi: 10.1021/acsomega.3c01467. eCollection 2023 Aug 29. ACS Omega. 2023. PMID: 37663506 Free PMC article.

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