title: The contribution of vitamin K2 (menaquinones) produced by the intestinal microflora to human nutritional requirements for vitamin K.
abstract: BACKGROUND
  Coagulopathy manifest by elevation of the prothrombin time (PT) in patients receiving broad spectrum antimicrobials indirectly suggests a role for intestinal microflora synthesized menaquinone (MK) in the maintenance of normal coagulation. Nonetheless, no direct evidence is available to support this contention.
  
  
  OBJECTIVE
  Our objective was therefore to provide evidence that bacterially produced MK may be absorbed by the distal small bowel of humans.
  
  
  METHODS
  Using a cell harvester, Staphylococcus aureus (ATCC 29213) was grown in 12-L batches, harvested, and extracted by high performance liquid chromatography (HPLC) to obtain 8 mg of pure MK. Four normal volunteers were placed on a diet severely restricted in vitamin K1 (median 32-40 U/day), and were given warfarin to maintain an International Normalized Ratio of approximately 2.0. On the 10th day of warfarin administration, naso-ileal intubation was performed and 1.5 mg of MK was delivered into the ileum. PT, factor VII, II and serum vitamin K1 levels were monitored throughout the study.
  
  
  RESULTS
  Mean serum vitamin K1 levels were reduced to 30% of the pre-diet value at the time of MK administration. Within 24 h of ileal MK administration, there was a significant (p < 0.05) increase in the factor VII level of 0.28 +/- 0.10 U/ml (mean +/- SEM) and a significant decrease of 2.5 (+/- 0.1) s in the PT, whereas in the control phase (during which no MK was administered), there were no significant changes in the PT or factor VII at corresponding time intervals.
  
  
  CONCLUSIONS
  These data provide direct evidence for the absorption of vitamin K2 from the distal small bowel, supporting a definite role for bacterially synthesized vitamin K2 in contributing to the human nutritional requirements of this vitamin.
authors.affiliation: Department of Medicine, University of Saskatchewan, Saskatoon.
authors.forename: J M
authors.initials: JM
authors.lastname: Conly
authors.forename: K
authors.initials: K
authors.lastname: Stein
authors.forename: L
authors.initials: L
authors.lastname: Worobetz
authors.forename: S
authors.initials: S
authors.lastname: Rutledge-Harding
mesh_terms: D000328:Adult; D001419:Bacteria / Q000378:metabolism*; D005167:Factor VII / Q000032:analysis; D006801:Humans; D007082:Ileum / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D009751:Nutritional Requirements; D011516:Prothrombin / Q000032:analysis; D011517:Prothrombin Time; D013211:Staphylococcus aureus / Q000378:metabolism; D014812:Vitamin K / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D010837:Vitamin K 1 / Q000097:blood; D024482:Vitamin K 2 / Q000031:analogs & derivatives
chemical_list: D024482:Vitamin K 2; D014812:Vitamin K; C030814:menatetrenone; D010837:Vitamin K 1; D005167:Factor VII; D011516:Prothrombin