June 23, 1998 COLUMBUS, Ohio -- Vitamin B1, which is usually given in excess to many cancer patients, should be carefully regulated in people undergoing cancer therapy, new research shows.
The findings reveal a long overlooked link between vitamin B1 -- also known as thiamine -- and tumor-cell growth. The results suggest that too much thiamine may actually help tumors grow. They also suggest that rational use of dietary thiamine may help slow tumor growth.
Thiamine supplementation is commonly recommended to cancer patients to counteract vitamin B1 deficiencies that can occur with leukemias, gastrointestinal tumors, and other faster-growing malignancies. Thiamine deficiency is also a side effect of some kinds of chemotherapy.
Severe thiamine deficiencies can lead to nervous system and memory impairment, and the build-up of lactic acid in the blood.
Thiamine supplementation is therefore often essential for cancer patients. However, total thiamine levels in a patient’s diet can be 250 to 20,000 percent of the normal daily recommended allowance. The government recommends that men consume 1.4 mg and women 1.0 mg of thiamine per day, amounts that are easily obtained from a typical American diet. Medical texts recommend 3 mg of thiamine daily for cancer patients, a dose that needs to be re-evaluated in light of this new research.
Physicians normally don’t worry about excess thiamine because the vitamin is water-soluble, and the body eliminates what it doesn’t need. This study indicates, however, that excess thiamine may contribute to tumor-cell proliferation and to the development of chemotherapy resistance by tumors.
“Cancer patients should be evaluated for their thiamine status, and supplementation should be administered only to meet the patient’s needs,” said Laszlo Boros, a research scientist in the Department of Surgery at Ohio State University.
The study by Boros and an interdisciplinary research team appears in a recent issue of Anticancer Research.
The link between thiamine and cancer was first discovered by Laszlo and the research team last year. That study (published in Cancer Research) revealed that rapidly dividing cancer cells produce a sugar known as ribose that forms the backbone of DNA and RNA using a chemical pathway that is more intensively used by cancer cells than by healthy cells.
Normally, cells produce ribose using a pathway that requires oxygen. Consequently, it is known as the oxidative pathway.
Cancer cells appear to produce ribose using a second pathway, one that doesn’t require oxygen. It is known as the transketolase, or TK, pathway. Transketolase is an enzyme that allows this chemical reaction to happen rapidly and without need of oxygen.
“The majority -- over 70 percent -- of ribose for DNA/RNA synthesis in tumor cells that have been studied comes from the TK pathway,” said Boros. “Nobody expected this pathway to be involved in this process so intensively.”
Furthermore, thiamine is key to that process: the vitamin is a co-factor that is necessary for the transketolase enzyme to work, said Boros. “It’s a thiamine-dependent reaction.”
The discovery led the research team to search the medical literature for other reports of a link between the TK pathway and cancer. They found only one: a 1958 paper that first described the pathway in tumor cells.
“This early observation seems to have been overlooked,” said Boros. “There is no follow-up data in the medical literature describing this pathway in cancer cells and the role of thiamine in the tumor-cell proliferation process.”
Cancer cells favor the TK pathway because it produces ribose molecules faster than the oxidative pathway -- and ribose molecules are in constant demand by rapidly dividing cancer cells for the production of new DNA and RNA.
“When it comes to tumor-cell growth, virus infections, and other conditions that require rapid DNA/RNA synthesis, cells will use the transketolase pathway.”
The ideal solution is to provide thiamine to the patient but deny it to the tumor.
“This could represent a new strategy to control tumor growth,” said W. Scott Melvin, assistant professor of surgery and senior author on the study. “It might be done in the future perhaps through a combination of thiamine restriction and the use of drugs that inhibit the TK pathway.” Such drugs are not yet available for use in humans, however.
“Right now, we’re trying to lay down guidelines to prevent oversupplying thiamine, without letting patients slip into thiamine deficiency,” said Boros, “and we want to emphasize the need to develop TK inhibitors for the treatment of cancer.”
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