Aluminum-succinate complex equilibria and their potential implications for aluminum metabolism

Apparent contradictory results have been reported about the effect of succinate on aluminum toxicity, distribution and excretion in mice. Investigating the influence of this ligand on aluminum speciation in the main biofluids may help understand the above observations at the molecular level. In the absence of experimental access to ultrafiltrable aluminum speciation, computer simulations have been used in the gastrointestinal fluid and blood plasma, based on Al-succinate complex formation constants determined under physiological conditions. Calculations run for gastrointestinal conditions show that Al-succinate soluble complexes are formed in the 2 to 6 pH range--especially the neutral M2L(OH)4--which may enhance aluminum absorption. This influence, however, should be limited by dietary phosphate. In blood plasma, there is no possibility for succinate to mobilize a significant aluminum fraction, which confirms a recent suggestion that the possible protective effect of succinate against aluminum toxicity in mice may not be due to aluminum complexation.