Is it possible to combine the herbal remedy Avosol, which contains soybean oil and avocado, with wa

Fråga: Is it possible to combine the herbal remedy Avosol, which contains soybean oil and avocado, with warfarin (Waran)? The question concerns a patient who is taking Avosol due to arthralgia.

Sammanfattning: There are a few case reports suggesting that both soy milk and avocado could affect warfarin treatment and required warfarin doses, either by their content of vitamin K, or by other active substances, such as isoflavones. Judging from the amounts of herbal extracts in Avosol, an interaction with warfarin seems unlikely, but cannot be totally ruled out. However, a regular ingestion of a product suspected to alter the effectiveness of warfarin can be acceptable. Once a therapeutic INR has been reached it is not recommended to change the amount, on a day-to-day basis, of the affecting product.

Svar: According to the product information, Avosol contains, in a daily dose, 200 mg of soy extract and 100 mg of avocado extract (1). Both soya and avocado contain vitamin K, in high (>100 ug/100g) and moderate (20-100 ug/100g) amounts, respectively (2). Given these facts, the amounts of vitamin K deriving from Avosol are very low.

Vitamin K is essential for the complete synthesis of blood coagulation factors II, VII, IX and X in the liver. Actual clotting factors are formed by carboxylation of their precursor proteins during which vitamin K is oxidized to vitamin K 2,3-epoxide (3). Oral anticoagulants prevent the reduction of this epoxide back to vitamin K. There is a resultant accumulation of the epoxide, a depletion of vitamin K, and a reduced rate of formation of complete clotting factors. By providing vitamin K through soya and avocado, you may antagonise the anticoagulant effect of warfarin, even if relatively high amounts seems to be required. The exact amounts has not been established.

A few case-reports suggest, even though not otherwise well documented, that avocado may affect microsomal liver enzymes, leading to increased degradation of warfarin, and also that it may interfere with intestinal warfarin absorption (4).

A speculative mechanism of soy milk induced loss of effectiveness from warfarin treatment has been brought up by a case report concerning INR decline after ingestion of soy milk. Soy protein (in soy milk) is a product derived from soybeans containing the isoflavones genistein and daidzein. It has been suggested, amongst other theories, that these isoflavones could alter drug absorption, metabolism and biliary excretion by interacting with the P-gp efflux system and OATP drug transporter and thus, highly speculatively, affect warfarin metabolism (5).

Even though none of these possible interactions is very well documented, they demonstrate that some foods and drinks can affect the response to oral anticoagulants. The general recommendation is to avoid a day-to-day alteration of ingestion of vitamin K rich food, drink or herbal remedies. If there is a regular intake of the herbal remedy Avosol, alterations in warfarin doses should not be necessary after a therapeutic INR has been reached.