Reduced vitamin K intake associated with greater cancer mortality
An article published online on March 24, 2010 in the American Journal of Clinical Nutrition reports the finding of researchers from the German Cancer Research Center and the German Research Centre for Environmental Health of an association between reduced vitamin K2 intake and an increased risk of dying from cancer.
The current research analyzed data from 24,340 participants in the European Prospective Investigation into Cancer and Nutrition-Heidelberg (EPIC-Heidelberg) prospective study who were aged 35 to 64 upon enrollment between 1994 and 1998. Participants, who were free of cancer at the beginning of the study, were followed through 2008. Dietary questionnaires completed upon enrollment were analyzed for phylloquinone (vitamin K1) and menaquinones (vitamin K2) intake.
Over the follow up period, there were 1,755 cases of cancer, including 458 fatalities. While the those whose intake of vitamin K2 was among the top 25 percent of participants had a 14 percent nonsignificant reduction in cancer incidence compared with those whose intake was among the lowest fourth, the group with the highest intake experienced a 28 percent lower risk of dying of the disease. Further analysis of the data determined that the reduction in cancer incidence associated with vitamin K2 occurred in men. When cancers were examined by cause, a 62 percent reduction in the risk of lung cancer and a 35 percent lower risk of prostate cancer were observed in those whose intake of vitamin K2 was among the top 25 percent. Although exclusion of prostate and lung cancer from the analysis still found an inverse association between vitamin K2 intake and metastatic cancer risk, the researchers did not consider it to be of statistical significance. No associations were found between vitamin K1 and cancer incidence or mortality.
The authors explain the difference in vitamin K2's effects on men and women by the fact that the men in the study had cancer sites (prostate, lung) that were likelier to be influenced by vitamin K2. Concerning the greater inverse association of vitamin K2 with cancer mortality compared to cancer incidence, the authors remark that "This observation is consistent with the assumption that factors affecting apoptosis and cell cycle arrest are likely to play a role later in carcinogenesis. In addition, experimental studies suggest an inhibitory role of menaquinones in angiogenesis, which is tightly linked to the development of metastasis."
"This study showed inverse associations between the dietary intake of menaquinones and both overall cancer incidence and mortality," the authors conclude. They suggest additional studies using biomarker measurements of vitamin K status.
A novel form of vitamin K that appears extremely promising in the treatment of primary liver cancer, a type notoriously resistant to chemotherapy has been discovered by scientists at the University of Pittsburgh Cancer Institute (UPCI). The research published in the Journal of Biological Chemistry described an innovative approach to treat, and possibly prevent, cancer by triggering apoptosis (Ni et al.1998).
The UPCI team found that a vitamin K analog, Compound 5 (CPD5), causes an imbalance in the normal activity of enzymes that controls the addition or removal of small molecules (phosphate groups) from proteins inside cells. Specifically, CPD5 blocks the activity of enzymes (protein-tyrosine phosphatases) that normally remove phosphate groups from selected proteins inside liver cancer cells. CPD5, however, does not interfere with another group of enzymes called protein tyrosine-kinases, which add phosphate groups to the same proteins. The result is an excess of tyrosine-phosphorylated proteins, which triggers a variety of activities within cells, including the shutting down and subsequent death of the cell.
It may be possible to remove some individuals from liver transplant waiting lists if CPD5 is as effective in humans as it is experimentally. However, the vitamin K compound is not limited to killing liver cancer; in tissue culture the compound was also effective against melanoma and breast cancers. Although the new vitamin K is not in clinical testing at this time, clients and physicians may contact the UPCI's Cancer Information and Referral Service at (800) 237-4PCI (4724) or (412) 624-1115 for periodic updates regarding the treatment. Inquirers can also visit the university's website at http://www.upci.upmc.edu.
Vitamin K compounds inhibited IL-6 production by lipopolysaccharide-stimulated fibroblasts, which are recognized as rich sources of cytokines (Reddi et al. 1995). This finding has significant anticancer implications because over-expression of IL-6 is intricately involved in the inflammatory process, bone resorption, the activation of telomerase, and cancer proliferation.
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