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Calcium citrate: from biochemistry and physiology to clinical applications

Palermo A1Naciu AM2Tabacco G2Manfrini S2Trimboli P3Vescini F4Falchetti A5,6.

Rev Endocr Metab Disord. 2019 Oct 23. doi: 10.1007/s11154-019-09520-0. [Epub ahead of print]




Adequate daily calcium intake should normally be achieved by dietary sources. Since low calcium diets are quite common in subjects that do not reach the recommended intake and particularly those at risk of fractures, calcium supplements may become necessary. Different forms of calcium salts are available, but products containing calcium citrate and calcium carbonate complexes are the most frequently used. Although only limited evidence on the efficacy and long-term safety of calcium citrate is available, these supplements may represent a valuable product for the management of different chronic pathological conditions. The aim of this review was to evaluate the current and potential clinical applications of calcium citrate. In particular, we focused on the use of calcium citrate supplementation in subjects with osteoporosis or in bariatric patients. Other pathological conditions that could benefit calcium citrate supplementation may include achloridria, chronic hypoparathyroidism and hypocitraturic subjects with moderate/high risk of nephrolithiasis. Indeed, citrate salts are widely used in the treatment of nephrolithiasis, since they have shown an inhibitory effect on kidney stone formation and recurrence.


Although we have only few available evidence, in comparison with calcium carbonate, calcium citrate demonstrated: a) higher bioavailability, with related broader area under the curve; b) higher solubility; c) higher absorption rate, both with full or empty stomach, being less influenced by gastric pH; c) lesser dependency on estrogenic and vitamin D status; d) a stronger ability in normalizing serum PTH e) optimal absorption in hypo-achloridria, without increasing cardiovascular risks; f) a reduced risk of kidney stones formation (Table 2). Calcium citrate lacks of important information about the

fracture risk behavior when given in association with antifracturative agents, in subjects at risk of fragility fractures. Although theoretically conceivable, there is no clinical evidence on whether or not calcium citrate can effectively improve the clinical management of subjects affected by hypoparathyroidism compared to calcium carbonate, currently used as supplementation and head to head RCTs should be conducted.

Finally, in hypochlroridric/achloridric subjects or individuals undergone chronic therapy with proton pump inhibitors calcium citrate should be the first-line calcium supplementation when needed and in consideration of its safety and potential efficacy, calcium citrate would be proposed to be used at all ages, as calcium integration, in individuals who fail tomeet daily requirements through food sources, although more robust data from RCTs are desirable.