Research ArticleDRUG MECHANISM

NPC1L1 is a key regulator of intestinal vitamin K absorption and a modulator of warfarin therapy

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Science Translational Medicine  18 Feb 2015:
Vol. 7, Issue 275, pp. 275ra23
DOI: 10.1126/scitranslmed.3010329

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A tug of war: Two drugs modulate vitamin K function

Kale was the superfood of 2014, with even soda-laden convenience stores like 7-Eleven adding kale juices to their inventories. But patients on warfarin—a commonly prescribed drug to prevent blood clotting—should avoid eating these healthy, leafy greens. Greens such as kale and spinach harbor loads of vitamin K (VK), which can interfere with the drug’s activity. The mechanism linking VK to warfarin action remains unclear; however, in a new study in rodent models, Takada et al. reveal that Niemann-Pick C1-like 1 (NPC1L1) protein, a cholesterol transporter, plays a key role in vitamin transport, too. The consequence of this interaction between VK and NPC1L1? Animals taking lipid-lowering drugs like ezetimibe, which act on NPC1L1, demonstrate heightened activity of warfarin, presumably because VK is not absorbed properly. When the animals were given oral VK supplementation, warfarin activity returned to normal, even if the animals were taking both drugs. Takada and colleagues retrospectively evaluated the medical records of patients taking warfarin alone or warfarin with ezetimibe and confirmed that the anticoagulant activity of warfarin was increased in more than 85% of patients also taking ezetimibe. This drug-drug interaction will be an important consideration when prescribing patients both warfarin and ezetimibe (or similar anticoagulant and cholesterol drugs), but lucky for those patients, this study further suggests that the interaction can be countered in part by a kale salad or, for those averse to this trendy roughage, a daily supplement of VK.