Thiamine (Vitamin B-1) supplementation and cancer
Lee Smith: IBC patient, Ottawa, Ontario, Canada
“We have all probably heard about cancer patients not taking a B complex vitamin because it contains vitamin B1 which is thiamine. Thiamine has been one of Dr. Boros’ recent studies. I take B6 and B12 to help the peripheral neuropathy but won’t touch B1 after reading his articles.”
Abstract: “Population Thiamine Status and Varying Cancer Rates Between Western, Asian and African Countries” “The role of food supplements in the form of vitamins has not been extensively investigated in relation to varying cancer rates between populations of different geographical regions. New data indicate that thiamine (vitamin B1), a common food supplement in Western food products, is directly involved in nucleic acid ribose synthesis of tumor cells in its biologically activated form through the non-oxidative transketolase catalyzed pentose cycle reaction.”
Abstract: “Role of thiamin (vitamin B-1) and transketolase in tumor cell proliferation” “Metabolic control analysis predicts that stimulators of transketolase enzyme synthesis such as thiamin (vitamin B-1) support a high rate of nucleic acid ribose synthesis necessary for tumor cell survival, chemotherapy resistance, and proliferation.”
Abstract: “Thiamine supplementation to cancer patients: a double edged sword” “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.”
Abstract: “Nonoxidative pentose phosphate pathways and their direct role in ribose synthesis in tumors: is cancer a disease of cellular glucose metabolism?” “PPP are substantially involved in the proliferation of human tumors, which raises the prospect of new treatment strategies targeting specific biochemical reactions of PPP by hormones related to glucose metabolism, controlling thiamine intake, the cofactor of the nonoxidative transketolase PPP reaction, or treating cancer patients with antithiamine analogues.”
The Linus Pauling Institute was established at Oregon State University in August 1996 under an agreement reached between OSU and its antecedent organization, the Linus Pauling Institute of Science and Medicine (located in California from 1973 to 1996). The Institute functions from the basic premise that an optimum diet is the key to optimum health. Our mission is to understand the molecular mechanisms and physiological effects of nutritional factors; to determine the function and role of micronutrients, vitamins and phytochemicals in maintaining health and preventing and treating disease; and to continue the pioneering efforts of Dr. Pauling in nutrition research.
Major areas of research in the Institute encompass heart disease, cancer, aging, neurodegenerative diseases, immune dysfunction and disease caused by exposure to toxins. Specific laboratories address antioxidants and vascular biology; vitamin E metabolism and biological activity; colon cancer and cancer chemoprevention by phytochemicals; and the role of oxdiative stress and mitochondrial dysfunction in the aging process.
The Institute has a report on Thiamine on their web site. “Thiamin deficiency has been observed in some cancer patients with rapidly growing tumors. Recent research in cell culture and animal models indicates that rapidly dividing cancer cells have a high requirement for thiamin.”
Research of the Role of Thiamine also Includes the Following:
TGF-b2 promotes glucose carbon incorporation into nucleic acid ribose through the non-oxidative pentose cycle in lung epithelial carcinoma cells. Cancer Res 60: 1183-1195, 2000. Boros, L.G., Torday, J.S., Lim, S., Bassilian, S., Cascante, M., Lee, W-N.P.
“Recent characterization of the overall metabolic effect of TGF-b on lung epithelial carcinoma cells found that TGF-b induces invasive transformation primarily through increasing nucleic acid ribose synthesis by the transketolase-thiamine complex. Surprisingly, H441 and A549 lung epithelial carcinoma cells synthesize nucleic acid ribose entirely through transketolase and the non-oxidative reactions of the pentose cycle in culture.”
Over-expression of transketolase: a mechanism by which thiamine supplementation promotes cancer growth. Boros, L.G., Comin, B., Boren, J., Martinez, S., Moro, C., Centelles, J.J., Lee, W.N.P., and M. Cascante.
Proceedings of the American Association for Cancer Research, 41:666, 2000 (abstr#4234)
“Thiamine (vitamin B1), a common vitamin supplement and food additive, is the co-factor of transketolase (TK) which is the predominating enzyme in the synthesis of nucleic acid ribose in the nonoxidative pentose cycle. Our present study provides evidence of the importance of nonoxidative pentose synthesis in tumor cells by determining the control coefficient of transketolase on tumor cell proliferation. This was accomplished using Metabolic Control Analysis (MCA) calculations which provide the quantitative tool to determine enzyme control characteristics on various system parameters. For the present study, tumor cell TK activity and final tumor cell number were determined as the system parameters. Ehrlich’s ascites tumor cells hosted in mice were treated with daily i.p. injections of 500 g/kg/day thiamine or with 200 mg/kg/day oxythiamine which is the chemically modified inactive form of thiamine for 4 days after tumor implantation. When thiamine was administered, final tumor cell number increased by 244% as compared to untreated control tumors. In response to OT treatment, rumor tissue transketolase activity decreased by 92.7% and final tumor cell number decreased by 82.1%. Based on these values, the control coefficient of transketolase in Ehrlich’s tumor cell proliferation is very high (0.89). These results demonstrate that thiamine is a strong tumor growth promoter as the co-factor of TK in the nonoxidative pentose synthesis process and that oxythiamine treatment reduces the effective concentration of the TK-thiamine pyrophosphate complex and decreases tumor growth. In conclusion, the transketolase-thiamine pyrophosphate complex conformably determines cell proliferation in the Ehrlich’s ascites tumor model based on its high control coefficient promoting tumor growth.”
Metabolism of Genistein
WESTPORT, May 09 (Reuters Health) - The soybean isoflavonoid genistein decreases lymphatic vessel invasion and metastasis of intestinal adenocarcinomas in rats. However, it does not affect the growth of the primary cancer, Japanese researchers report in the May 1, 2000 issue of the International Journal of Cancer. The abstract of this research may be found at Genistein attenuates peritoneal metastasis of azoxymethane-induced intestinal adenocarcinomas in Wistar rats.
Genistein inhibits nonoxidative ribose synthesis in MIA pancreatic adenocarcinoma cells: a new mechanism of controlling tumor growth. Boros LG, Bassilian S, Lim S, Lee WN. Pancreas 2001 Jan;22(1):1-7 “Genistein is a plant isoflavonoid bearing potent tumor growth-regulating characteristics….It can be concluded from these studies that genistein controls tumor growth primarily through the regulation of glucose metabolism, specifically targeting glucose carbon incorporation into nucleic acid ribose through the nonoxidative steps of the pentose cycle, which represents a new paradigm for the antiproliferative action of a plant phytochemical.“
