Correspondence

Fiddleheads and the International Normalized Ratio

N Engl J Med 1998; 338:1550May 21, 1998

Article

To the Editor:

Many drugs and foods affect the response to oral anticoagulants.1 We describe a change in the international normalized ratio (INR) that was caused by the consumption of fiddleheads.

A 73-year-old man with atrial fibrillation had an INR of 1.71 on June 5, 1997. The previous four readings going back to February of 1997 had been in the therapeutic range of 2 to 3, and overall, 70 percent of the values from mid-1996 to the end of 1997 were considered to be within the therapeutic range. On extensive questioning about his food consumption during the week preceding the INR of 1.71, the patient stated that he had eaten fiddleheads for dinner on the previous two evenings. He was instructed to take an extra 5-mg dose of warfarin on the day of examination but otherwise to maintain his normal regimen. INRs measured over the next several months were in the therapeutic range.

Fiddleheads, the crosiers of ferns, are eaten as a delicacy by many people in northeastern North America, but also in other parts of the world, especially in the spring when they are fresh. More than 600,000 lb a year are exported from New Brunswick alone (Dykeman B, New Brunswick Department of Agriculture and Rural Development: personal communication). Given the subtle green, leafy nature of fiddleheads and their ingestion by our patient before the low INR reading, we measured the vitamin K₁ (phylloquinone) content in a sample.2

Six separate homogenized aliquots of the fiddlehead sample had a vitamin K₁ content of 170.9 μg per 100 g (range, 146.3 to 191.3); this is almost equivalent to the concentrations in broccoli (205 μg per 100 g; range, 147 to 230).3 Our patient ingested between 300 and 600 g of fiddleheads during the two meals, or approximately 510 to 1020 μg of vitamin K₁ — a sufficient amount to lower his INR. Interestingly, he had also had two INRs in the subtherapeutic range in late May and early June of 1996, coinciding with the fiddlehead season.

Fiddlehead consumption, usually restricted to the late spring in North America, may transiently lower the INR.

W.R. Bartle, Pharm.D.
Sunnybrook Health Science Center, Toronto, ON M4N 3M5, Canada

Guylaine Ferland, Ph.D.
University of Montreal, Montreal, QC H3C 3J7, Canada

3 References

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   Wells PS, Holbrook AM, Crowther NR, Hirsh J. Interactions of warfarin with drugs and food. Ann Intern Med 1994;121:676-683
   Web of Science | Medline

2. 2

   Ferland G, Sadowski JA. Vitamin K₁ (phylloquinone) content of green vegetables: effects of plant maturation and geographical growth location. J Agric Food Chem 1992;40:1874-1877
   CrossRef | Web of Science

3. 3

   Booth SL, Weibrauch JL, et al. Vitamin K₁ (phylloquinone) content of foods: a provisional table. J Food Comp Anal 1993;6:109-120
   CrossRef

Citing Articles (3)

Citing Articles

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   Vipin D.P. Nair, Brian C. Foster, J. Thor Arnason, Edward J. Mills, Isadore Kanfer. (2007) In vitro evaluation of human cytochrome P450 and P-glycoprotein-mediated metabolism of some phytochemicals in extracts and formulations of African potato. Phytomedicine 14:7-8, 498-507
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   B.C. Foster, S. Vandenhoek, J. Hana, A. Krantis, M.H. Akhtar, M. Bryan, J.W. Budzinski, A. Ramputh, J.T. Arnason. (2003) In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 10:4, 334-342
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3. 3

   J.W. Budzinski, B.C. Foster, S. Vandenhoek, J.T. Arnason. (2000) An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 7:4, 273-282
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