MenaQ7 and OAC treatment
Oral anticoagulants (also known as coumarin-derivatives) act as antagonists of vitamin K. Obviously, 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 larger the day-to-day fluctuations are and the more difficult it is to maintain the patient in the target window.
Everyone (also non-supplemented persons) 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 subjects are subclinically 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, our 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 in which we have checked at what intake of MenaQ7 the level of oral anticoagulation is affected. 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. After stable anticoagulation was obtained, the volunteers received increasing doses of MenaQ7 10 micrograms per day during the first week, than 20 micrograms per day in the next 2 weeks etcetera. We found that about half of the volunteers responded only at 200 micrograms per day, a response being defined as a change in INR value that is regarded as clinically relevant by the supervising hematologist. However, there were also rapid responders, and one person was found who showed a measurable effect at an intake as low as 50 micrograms per day. Parts of these data are NattoPharma’s proprietary data and have not yet been published.
So if analyzed on a group level, no response was obtained at 50 micrograms per day, but the fact that we found one subject responding at 50 micrograms per day is why we say that in fortified foods that may be consumed in very irregular doses, a safe concentration will provide not more than 25 micrograms per day of MenaQ7. For food supplements we feel that 50 micrograms per capsule or tablet can be used, because a) the package insert will describe the potential interference with oral anticoagulants and b) the supplement can be taken on a more regular basis (e.g. 1 capsule per day). We want to stress here that the regular intake of supplemental vitamin K is not contra-indicated in combination with oral anticoagulants, rather the high vitamin K intake (and in this respect MK-7 is preferable over K1) in combination with the higher coumarin dose will result in more stable anticoagulation levels. Experts even recommend this approach to prevent instability of INR values.
The alleged “risk” of supplemental vitamin K during anticoagulation should also be regarded in the context of total dietary vitamin K. A dose of 45 micrograms of MenaQ7 gives a comparable amount of vitamin K2 as 100 grams of cheese, so an irregular dietary cheese intake is comparably “harmful” as irregular intake of MenaQ7 capsules. No reasonable doctor will deny a patient the consumption of 4 slices of cheese per day, even if this is not taken every day. And also, no reasonable doctor will deny a patient to eat 100 grams of broccoli once weekly. We have no data showing that such dietary habits interfere with ral anticoagulant therapy, and neither we have data showing that a daily dose of supplemental MenaQ7 between 20 and 45 micrograms per day can be a problem for the group of anticoagulated patients.
For patients on oral anticoagulants it is important to maintain a regular life style and to avoid large day-to-day variations in their dietary pattern. It benefits their INR stability if their vitamin K intake is more or less constant, with every day more or less comparable intakes 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 at high levels of vitamin K intake than at low levels.