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Trace Metal-Citric Acid Complexes as Inhibitors of Calcification and Crystal Formation 1

Abstract At high citrate:metal ratios the small polyvalent metals Fe3+, Be2+, Al3+, and Cr3+ interact with citrate to form potent inhibitors of both calcium uptake by a calcifiable matrix and crystal formation from a metastable solution of calcium phosphate. These unique metal-citrate complexes are effective inhibitors at 0.2-30 × 10−6 M, with iron (III) citrate being the most potent. The inhibitor effects of mixtures of the metal-citrate complexes are additive. These observations define a new role for citrate and indicate how certain trace elements may, by interaction with citrate, be important determinants in the control of calcium salt deposition in vivo. The possible pertinence of these observations to the deposition of calcium salts within the kidney and to the prevalence of idiopathic calculi in various geographic areas is now under investigation.