Vitamin K and anticoagulants

Oral anticoagulants (also known as coumarin-derivatives) act as antagonists of vitamin K. Therefore, dietary vitamin K counteracts the activity of these coumarins, which is the reason why patients on oral anticoagulant therapy need to be kept in a delicate balance: their natural vitamin K intake should be counteracted partly by a carefully calculated dose of coumarin. The problem is that the therapeutic window is narrow: if the dose of coumarin is too high the patient will bleed, if it is too low there is risk of thrombosis. This problem is encountered at all levels of vitamin K intake, but in general we see that the lower the dietary vitamin K intake, the wider the day-to-day fluctuations are and the more difficult it is to maintain the patient in the target window.

Everyone ingests vitamin K all the time. It is very hard to find food items completely devoid of vitamin K and yet our total vitamin K intake is so low that most non-supplemented individuals are sub-clinically vitamin K deficient. Only few foods contain relatively high concentrations of vitamin K: green vegetables like spinach, broccoli or Brussels sprouts provide 100 micrograms of K1 per 100 grams of product. Cheese, curd cheese, eel and flatfish provide between 30 and 60 micrograms K2 per 100 grams of product. Because of the very limited number of foods rich in vitamin K, typical daily vitamin K intake shows considerable variation. For patients on coumarin treatment this means that their level of anticoagulation (INR-value) shows substantial day-to-day variation, and frequent control of the anticoagulant level is needed.

VitaK has conducted studies that have attempted to identify how MenaQ7 consumption levels affect oral anticoagulation. In these studies we have used healthy volunteers who received a vitamin K-restricted diet combined with a low dose of acenocoumarol with a target INR value of 2.0. This is the most sensitive human model that can be designed, and very prone to fluctuating vitamin K intake.

The results presented below showed that, for patients receiving oral anticoagulant treatment, it should be recommended that they do not take MK-7 supplements without consulting their medical doctor. For patients with unstable INR values it may be helpful, on the other hand, to combine a high dose of oral anticoagulant medication with a fixed daily dose of MK-7 (Stafford et al, Blood 2007;109:3607).

Studies confirming the influence of Vitamin K on anticoagulant treatment:

  • In an early dose-response study among anticoagulated human volunteers, it was found that the daily intake of 150 μg/day of vitamin K1 significantly affected the INR value (Schurgers et al, Blood 2004;104:2682-2689).
  • In a subsequent study comparing the potencies of K1 and MK-7 it was found that MK-7 was at least three-fold more potent than K1, which led to the following conclusion: Hematologists need to be aware that relatively low doses of MK-7 may have a larger impact on the stability of oral anticoagulation than vitamin K1. Obviously, a large study in patients on oral anticoagulant treatment is needed to demonstrate the safety of even low doses of MK-7 in this population. Until that time, it was proposed to use an upper safety limit for intake of 50 μg/d for long-chain menaquinones (including MK-7) in patients on oral
  • anticoagulant treatment (Schurgers et al, Blood 2007;109:3279-3283).
  • In May 2013, a larger study was published, showing that if measured at group level, a daily intake of 45 μg/day of MK-7 does not lead to a statistically significant decrease of the INR value, but that 10-20% of the population belongs to the “quick responders,” i.e. that they even show effects on their INR value at 10 μg/day (Theuwissen et al, J. Thromb. Haemostas 2013, epub).

 

For patients on oral anticoagulants it is important to maintain a regular lifestyle and to avoid wide day-to-day variations in their dietary pattern. It benefits their INR stability if their vitamin K intake is relatively constant, with daily consumption of the same (or routine) amounts of green vegetables, cheese and other vitamin K-containing products, including supplements and fortified foods. (NB: also other factors like alcohol consumption and other medication should be kept constant since they influence the rate at which the coumarins are metabolized in the liver). The present insights are that the target window for anticoagulation can be maintained with greater accuracy from high levels of vitamin K intake than from low levels.