Synergism and Vitamin C

A number of natural compounds appear to act syner-gistically with vitamin C to produce cytotoxic effects via stimulation of free radicals. These include vitamin K3 and high-molecular-weight compounds such as PSK and lignans. Each is described briefly below. Since their clinical use would involve prooxidant mechanisms, as well as intravenous administration, such synergistic combinations are not advocated; they are mentioned only because some readers may find references to them in the literature.

Vitamin K is used medicinally as a procoagulant agent in hemorrhagic (bleeding) diseases and as an antidote to anticoagulant overdose. Vitamin K3 potentiates the cy-totoxic effects of vitamin C in vitro, the optimum ratio being approximately 1:100. This combination may be 4- to 61-fold more potent than vitamin C alone, depending on the cell line and exposure times.109,110 Vitamin K3 by itself also displays cytotoxic activity in a variety of cell lines. In addition, it augments the antitumor effect of the anticoagulant drug warfarin and the antitumor activity of a number of cytotoxic drugs when used with vitamin C.111117 Possible mechanisms of vitamin K3 antitumor activity include induction of free radical damage, inhibition of DNA synthesis, induction of apoptosis, modulation of coagulation, and inhibition of growth factor binding. The antitumor effects of a combination of vitamins C and K3 are completely prevented by the addition of catalase, suggesting that free radical production is a nec-

essary component.

High-molecular-weight substances such as the mushroom extract PSK and lignans from pine cones increase vitamin C oxidation and synergistically enhance the cy-totoxicity of vitamin C against human leukemia and brain cancer cells in vitro.119,120,121 Again, a prooxidant mechanism is at work. Optimal results in vitro are obtained when a sodium solution is used to dissolve vitamin C, the mixture is freshly made before testing, the vitamin C concentration is 300 pM or greater, and the lignin to vitamin C ratio is roughly 20 to 1 (weight to weight).

Combining vitamin K3 or high-molecular-weight substances with vitamin C is not practical for our purposes. To provide optimal results, high concentrations of vitamin C are still required, which would require intravenous administration. To achieve sufficient plasma concentrations, vitamin K3 would also need to be administered intravenously. Lastly, the required dose of PSK or other lignans would be excessive. Both vitamin K3 and PSK can, of course, be used in combination with vitamin C, but it is unlikely that using these compounds alone at oral doses applicable to humans would produce significant synergistic effects or high cell kill.

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