We examined the effect of vitamin-K-rich vegetables, vitamin-K-poor vegetables and phytomenadione on the stability of warfarin-induced anticoagulation. Patients on stable anticoagulant treatment were randomized to either 1 (n = 5), 2 (n = 7) or 7 (n = 13) d with high intake of vitamin-K-rich vegetables (median daily vitamin K intake 1100 micrograms) or high intake of vitamin-K-poor vegetables (daily vitamin K intake 135 micrograms) for 6 d (n = 7), or habitual diet supplemented with 1000 micrograms of phytomenadione daily (n = 5). Nine patients (69%; 95% CI, 39-91%) who consumed vitamin-K-rich vegetables for 7 d reached activities above the therapeutic level. Two (40%; 95% CI, 5-85%) and three patients (43%; 95% CI, 10-86%) who consumed vitamin-K-rich vegetables for 1 and 2 d, respectively, exceeded the upper therapeutic limit. No changes were observed in the vitamin-K-poor group. All patients who received phytomenadione exceeded the upper therapeutic limit. Dietary vitamin K should be regarded as an important environmental factor contributing to unwanted disturbances in warfarin-induced anticoagulation.

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It has been shown that boric acid has well-defined biological effects such as stimulation of wound healing in vivo, release of growth factors and cytokines, and increase of the extracellular matrice turnover. We examined its action at the molecular level, using cell-free systems of transcription (isolated placenta nuclei) and translation (wheat germ extract). We found that 10 mM boric acid greatly increased RNA synthesis, measured by absorbance at 260 nm (x 6.4) or by [3H]-UTP uptake (x 11). Full-length functional mRNA was produced because proteins of 14-80 kDa were translated. Among these proteins, factors involved in angiogenesis and, subsequently, in wound healing (VEGF and TGFbeta) were identified by slot blot, whereas growth factors such as FGF1 and TNFalpha were not detected. These results demonstrate that boron may contribute to biological cell activities at both the transcription and translation levels. However, the mechanism of action is still not known.