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Recent letters call attention to the tendency of metformin to interfere with vitamin B₁₂ function.^1-2 Perhaps metformin antagonizes other vitamins as well. Phenformin, the relatively toxic predecessor of the metformin, exhibited antithiamine activity in laboratory animals.^3-5 Because thiamine vitally participates in the entrance of glycolytic pyruvate into the mitochondrial Krebs cycle, I hypothesize that an antithiamine effect of metformin contributes to some cases of metformin-associated lactic acidosis. Perhaps, as in beriberi, thiamine should be administered in a large dose to patients who develop metformin-associated acidosis.^{4, 6-7} Metformin and thiamine have little molecular structure in common, but both are cationic molecules.

Theodore A. Alston, MD, PhD
Boston, Mass

1. Andrès E, Noel E, Goichot B. Metformin-associated vitamin B₁₂ deficiency. Arch Intern Med. 2002;162:2251-2252. FREE FULL TEXT 2. Gilligan MA. Metformin and vitamin B₁₂ deficiency. Arch Intern Med. 2002;162:484-485. FREE FULL TEXT 3. Loubatieres AL, Loubatieres-Mariani MM, Alric R, Blayac JP, Valette G. Effects of thiamine pyrophosphate and sodium dichloroacetate on the increase of lactate and insulin outputs induced by phenformin on the isolated and perfused rat pancreas. C R Seances Soc Biol Fil. 1977;171:155-160. PUBMED 4. Valette G, Ribes G, Rondot AM, Loubatieres-Mariani MM, Loubatieres AL. Effect of cocarboxylase on hyperlactatemia and hyperpyruvicemia induced by phenformin in dogs. C R Seances Soc Biol Fil. 1975;169:121-125. PUBMED 5. Valette G, Ribes G, Loubatieres-Mariani MM, Loubatieres AL. Consequences of the chronic administration of phenformine on the blood thiamine level in the dog. C R Seances Soc Biol Fil. 1975;169:1562-1567. PUBMED 6. Calabrese AT, Coley KC, DaPos SV, Swanson D, Rao RH. Evaluation of prescribing practices: risk of lactic acidosis with metformin therapy. Arch Intern Med. 2002;162:434-437. FREE FULL TEXT 7. Gan SC, Barr J, Arieff AI, Pearl RG. Biguanide-associated lactic acidosis: case report and review of the literature. Arch Intern Med. 1992;152:2333-2336. ABSTRACT

Arch Intern Med. 2003;163:983.

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