The contribution of vitamin K2 (menaquinones) produced by the intestinal microflora to human nutritional requirements for vitamin K

Am J Gastroenterol. 1994 Jun;89(6):915-23.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bacteria / metabolism*
  • Factor VII / analysis
  • Humans
  • Ileum / metabolism
  • Ileum / microbiology*
  • Male
  • Nutritional Requirements
  • Prothrombin / analysis
  • Prothrombin Time
  • Staphylococcus aureus / metabolism
  • Vitamin K / administration & dosage
  • Vitamin K / analogs & derivatives*
  • Vitamin K / biosynthesis
  • Vitamin K / metabolism
  • Vitamin K / pharmacology
  • Vitamin K 1 / blood
  • Vitamin K 2 / analogs & derivatives


  • Vitamin K 2
  • Vitamin K
  • menatetrenone
  • Vitamin K 1
  • Factor VII
  • Prothrombin