The objectives of this review are to (a) explain the mechanism by which
thiamine (
vitamin B1) promotes
nucleic acid ribose synthesis and
tumor cell proliferation via the nonoxidative
transketolase (TK) pathway; (b) estimate the
thiamine intake of
cancer patients and (c) provide background information and to develop guidelines for alternative treatments with antithiamine
transketolase inhibitors in the clinical setting. Clinical and experimental data demonstrate increased
thiamine utilization of human
tumors and its interference with experimental
chemotherapy. Analysis of
RNA ribose indicates that
glucose carbons contribute to over 90% of
ribose synthesis in cultured cervix und
pancreatic carcinoma cells and that
ribose is synthesized primarily through the
thiamine dependent TK pathway (> 70%). Antithiamine compounds significantly inhibit
nucleic acid synthesis and
tumor cell proliferation in vitro and in vivo in several
tumor models. The medical literature reveals little information regarding the role of the
thiamine dependent TK reaction in
tumor cell
ribose production which is a central process in de novo
nucleic acid synthesis and the salvage pathways for
purines. Consequently, current
thiamine administration protocols oversupply
thiamine by 200% to 20,000% of the recommended dietary allowance, because it is considered harmless and needed by
cancer patients. The
thiamine dependent TK pathway is the central avenue which supplies
ribose phosphate for
nucleic acids in
tumors and excessive
thiamine supplementation maybe responsible for failed therapeutic attempts to terminate
cancer cell proliferation. Limited administration of
thiamine and concomitant treatment with
transketolase inhibitors is a more rational approach to treat
cancer.