Aluminum speciation studies in biological fluids. Part 7. A quantitative investigation of aluminum(III)-malate complex equilibria and their potential implications for aluminum metabolism and toxicity.
As a nonessential element, aluminum may be toxic at both environmental and therapeutic levels, depending on ligand interactions. Dietary acids that normally occur in fruits and vegetables and commonly serve as taste enhancers are good ligands of the Al(3+) ion. Malic acid is one of these and also one of the most predominant in food and beverages. The present paper reports an examination of its potential influence on aluminum bioavailability through speciation calculations based on Al(III)-malate complex formation constants especially determined for physiological conditions. According to the results obtained, malate appears to be extremely effective in maintaining Al(OH)(3) soluble over the whole pH range of the small intestine under normal dietary conditions. In addition, two neutral Al(III)--malate complexes are formed whose percentages are maximum from very low malate levels. When aluminum is administered therapeutically as its trihydroxide, the amount of metal neutralized by malate peaks as its solubility pH range regresses to its original limits in the absence of malate. The enhancing effect of malate towards aluminum absorption is therefore virtually independent of the aluminum level in the gastrointestinal tract. The presence of phosphate in the gastrointestinal juice is expected to limit the potential influence of malate on aluminum absorption. Under normal dietary conditions, phosphate effectively reduces the fraction of aluminum neutralized by malate but without nullifying it. Aluminum phosphate is predicted to precipitate when aluminum levels are raised as with the administration of aluminum hydroxide, but a significant amount of neutral aluminum malate still remains in solution. Even therapeutic aluminum phosphate is not totally safe in the presence of malate, even at low malate concentrations. As plasma simulations predict that no compensatory effect in favor of aluminum excretion may be expected from malate, simultaneous ingestion of malic acid with any therapeutic aluminum salt should preferably be avoided.
Venturini-Soriano
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Equipe de Chimie Bioinorganique Médicale, ICMPS-CNRS FR1744, Université Paul Sabatier, 118 route de Narbonne (Bât. 3SC), 31062 Toulouse, France.
Berthon
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D000535:Aluminum / Q000737:chemistry* / Q000378:metabolism / Q000506:poisoning; D000818:Animals; D001769:Blood; D001826:Body Fluids / Q000737:chemistry*; D004064:Digestive System; D004355:Drug Stability; D064420:Drug-Related Side Effects and Adverse Reactions; D015386:Hazardous Substances / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008293:Malates / Q000737:chemistry* / Q000378:metabolism; D008954:Models, Biological; D010710:Phosphates / Q000494:pharmacology; D017186:Titrimetry
D015386:Hazardous Substances; D008293:Malates; D010710:Phosphates; C030298:malic acid; D000535:Aluminum