Observations on Possible Effects of Daily Vitamin K Replacement, Especially Upon Warfarin Therapy

Abstract

Daily parenteral vitamin K supplement is now recommended by the U.S. Food and Drug Administration (FDA) for patients receiving IV hyperalimentation. This is considered as preferable to the previous recommendations of weekly parenteral or oral supplement, or as in some cases no supplement at all. Supplemental vitamin K1 will ensure adequate supplies for hepatic saturation and thus the production of clotting factors II, VII, IX, and X, plus the anticoagulants protein C, protein S, and protein Z. But this is not the entire story. This recommended supplement will affect other physiologic systems that also use vitamin K-dependent gamma-carboxylation. Vitamin K is not 1 molecule but rather 2 natural substances, vitamin K1 and K2, and the synthetic K3's. It is not understood, what, if any, effect may occur because of the saturation or competition from the vitamin K1 upon the functioning of vitamins K2 and the derivatives of K3 in vivo upon bone mineralization, cell growth, and blood vessel health, all known to be influenced by the vitamins K. There are probably other physiologic systems yet to be studied relative to vitamins K and gamma-carboxylation. This review also considers the available research upon warfarin when given to patients receiving hyperalimentation and what effects the vitamin K supplements may have. Because studies to date have not controlled for vitamin K intake, consideration is given to whether one should expect any change in previously reported outcomes when using low-dose warfarin for prophylaxis against central vein thrombosis. Also considered are possible positive or negative effects that chronic warfarin therapy may have upon the other vitamin K-dependent systems under discussion. This review offers a platform for further discussion and derived clinical research provoked by this new FDA recommendation.

The Canadian Home Total Parenteral Nutrition (HTPN) Registry

“…The best known of the 3 bone‐related Gla proteins is OC. Even though the exact role of OC is unknown, a number of studies have shown that vitamin K insufficiency is associated with an increase in the concentration of circulating undercarboxylated OC 3 . ‐ 20 Vitamin K supplementation has been shown to improve the bone turnover profile and decrease the level of circulating undercarboxylated OC 21 as well as reduce bone loss and decrease fractures 22 .…”

“…The other forms are vitamin K2 (menAQuinone), synthesized by microflora in the gut, and the synthetic form, vitamin K3 (minadinone), which is converted to menAQuinone by bacteria in the gastrointestinal tract 2 . Vitamin K is a cofactor for several physiologic pathways, including coagulation, cell differentiation, and NAD(P)/NAD(P)H via the oxidation reduction cycle 3 …”

Micronutrient Assessment in Long‐Term Home Parenteral Nutrition Patients

“…Patients requiring warfarin therapy should have a international normalized ratio (INR) monitored when initiating or discontinuing PN because a change in PN will result in a change in the daily vitamin K intake 76 . There are injectable multivitamin preparations available without vitamin K. A review of vitamin K‐dependent systems addressed the need for more research on the impact of daily vitamin K and warfarin therapy in patients receiving both therapies long‐term 77 …”