The effect of thiamine supplementation on tumour proliferation - A metabolic control analysis study

Thiamine deficiency frequently occurs in patients with advanced cancer and therefore thiamine supplementation is used as nutritional support. Thiamine (vitamin B1) is metabolized to thiamine pyrophosphate, the cofactor of tra nsketolase, which is involved in ribose synthesis, necessary for cell repli cation. Thus, it is important to determine whether the benefits of thiamine supplementation outweigh the risks of tumor proliferation. Using oxythiami ne (an irreversible inhibitor of transketolase) and metabolic control analy sis (MCA) methods, we measured an in vivo tumour growth control coefficient of 0.9 for the thiamine-transketolase complex in mice with Ehrlich's ascit es tumour. Thus, transketolase enzyme and thiamine clearly determine cell p roliferation in the Ehrlich's ascites turnout model. This high control coef ficient allows us to predict that in advanced tumours, which are commonly t hiamine deficient, supplementation of thiamine could significantly increase tumour growth through transketolase activation. The effect of thiamine sup plementation on turnout proliferation was demonstrated by in vivo experimen ts in mice with the ascites tumour. Thiamine supplementation in doses betwe en 12.5 and 250 times the recommended dietary allowance (RDA) for mice were administered starting on day four of tumour inoculation. We observed a hig h stimulatory effect on tumour growth of 164% compared to controls at a thi amine dose of 25 times the RDA. This growth stimulatory effect was predicte d on the basis of correction of the pre-existing level of thiamine deficien cy (42%), as assayed by the cofactor/enzyme ratio. Interestingly, at very h igh overdoses of thiamine, approximate to 2500 times the RDA, thiamine supp lementation had the opposite effect and caused 10% inhibition of tumour gro wth. This effect was heightened, resulting in a 36% decrease, when thiamine supplementation was administered from the 7th day prior to tumour inoculat ion. Our results show that thiamine supplementation sufficient to correct e xisting thiamine deficiency stimulates tumour proliferation as predicted by MCA. The tumour inhibitory effect at high doses of thiamine is unexplained and merits further study.