Why aluminum phosphate is less toxic than aluminum hydroxide

Initially characterized in uremic patients undergoing hemodialysis, toxic effects due to high aluminum (Al) body loads were subsequently observed in a number of conditions, in particular following ingestion of Al-containing antacids. Among compounds of this class, aluminum phosphate (AlPO4) was recognized as safer than aluminum hydroxide (Al(OH)3), which was thought to result from its lower solubility and thus absorption in the gastrointestinal (gi) tract. However, while virtually insoluble at acid pH, AlPO4 is more soluble than Al(OH)3 under alkaline conditions, leading to the hypothesis that Al is predominantly absorbed in the acidic region of the gi tract. Our present results suggest otherwise. Al bioavailability depends on the solubility of the salt ingested as well as on the physicochemical properties of the Al soluble complexes formed in the gi fluid. Anions of dietary acids may indeed dissolve significant fractions of Al salts and form absorbable Al complexes. It is in these terms that the well documented increase of Al gi absorption by citrate has been interpreted from computer-based speciation studies. Using similar calculations, we now demonstrate that a series of dietary acids (namely malic, oxalic, tartaric, succinic, aspartic and glutamic acids) can also dissolve significant amounts of Al(OH)3 and form Al neutral complexes available to the gi membrane. In contrast, both effects are far less apparent when Al is administered as AlPO4. We conclude from this observation that the lower toxicity of AlPO4 vs Al(OH)3 stems from its better capacity to resist dissolution and neutral complex formation in the presence of acids commonly present in food.