EFFECTS OF A VITAMIN-K - DEFICIENT DIET AND ANTIBIOTICS IN NORMAL HUMAN VOLUNTEERS

  • 1 August 1987
    • journal article
    • research article
    • Vol. 110  (2) , 180-188
Abstract
Decreased concentrations of vitamin D-dependent plasma clotting factors are a well-documented response of vitamin K-deprived patients administered broad-spectrum antibotics. It has recently been claimed that antibiotics containing a N-methylthiotetrazole (NMTT) side chain cause this response through a direct effect of NMTT on the vitamin K-dependent posttranslational carboxylation of these clotting factors. To further study these relationships, 11 groups of three volunteers were fed a synthetic vitamin K-free diet for 2 weeks. Durign the last 10 days of vitamin K restriction, seven of the volunteer groups received a therapeutic dose of antibiotics not containing NMTT: ampicillin, sulfamethoxazole-trimethoprim (Bactrim), cefoxitin, cefotaxime, ceftazidime, clindamycin, and piperacillin, and three groups received NMTT-containing antbiotics: moxalactam, cefamandole, and cefoperazone. Serum phylloquinone (vitamin K1) concentrations reflected dietary intake and fell from 1.4 .+-. 0.9 ng/ml after 3 days of hospital diet to 0.4 .+-. 0.3 ng/ml after 13 days of vitamin K-free diet. Median stool excretion of phylloquinone was 19 .mu.g/day while subjects consumed the hospital diet, and fell to 3 .mu.g/day by day 6 on vitamin K-free diet. Prothrombin times remained within the normal range throughtout the study. Suppression of vitamin K-dependent clotting factor biosynthesis was evident by decreased factor VII levels in seven of the volunteers and by an increased concentration of des-.gamma.-carboxy (abnormal) prothrombin in 21 of the volunteers. The changes occurred in the control subjects and in subjects receiving all nine of the 10 antibiotics with no consistent pattern. The data indicate that restriction of dietary vitamin K can produce mild functional disorders of coagulation, but do not support the hypotheses that NMTT-containing antibiotics suppress vitamin K-dependent clotting factor biosynthesis among patients receiving NMTT-containing antibiotics must be more complex than postulated and may be dependent on a number of unidentified factors.