Dietary Modification as Cause of Anticoagulation Instability

Kalra, P.A.; Cooklin, Michael; Wood, Grahame; O’Shea, Geraldine M.; Holmes, A.M.

doi:10.1016/s0140-6736(88)92461-0

Cited by 23 publications

(12 citation statements)

References 3 publications

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“…There is limited information, some based on case reports, to clarify the extent of the contribution of variations in dietary vitamin K to changes in the INR. Dietary modification resulting in a lower intake of vitamin K has been demonstrated to cause warfarin sensitivity (Colvin & Lloyd, 1977; Kalra et al , 1988; Chow et al , 1990). On the contrary, patients who increase their dietary vitamin K intake have become resistant to warfarin anticoagulation (O'Reilly & Rytand, 1980; Pedersen et al , 1991).…”

Section: Discussionmentioning

confidence: 99%

Dietary vitamin K influences intra‐individual variability in anticoagulant response to warfarin

Khan¹,

Wynne²,

Wood³

et al. 2004

Br J Haematol

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SummaryThe relationship between dietary intake of vitamin K, fat, plasma vitamin K concentrations and anticoagulation response to warfarin within individuals, as well as the contribution of dietary vitamin K to differences in warfarin dose requirements between individuals were investigated in 53 patients on warfarin therapy who had stably controlled anticoagulation. Each patient completed a dietary record of all foods consumed on a daily basis for 4 weeks. Each week a blood sample was taken for measurement of the international normalized ratio (INR), plasma vitamin K, triglycerides and warfarin enantiomer concentrations. The patients' genotype for CYP2C9 was also determined. Regression analysis of the data showed that, for each increase of 100 lg in the daily dietary intake of vitamin K averaged over 4 d, the INR was reduced by 0AE2. There was no correlation between warfarin daily dose and average daily dietary vitamin K intake when calculated over 28 d. The regression model for warfarin dose showed that, while dietary vitamin K had no effect, CYP2C9 genotype (P ¼ 2%) and age (P < 1%) significantly contributed to inter-patient variability in warfarin dose requirements. A consistent intake of vitamin K could reduce intrapatient variability in anticoagulation response and thus improve the safety of warfarin therapy.

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Section: Discussionmentioning

confidence: 99%

Dietary vitamin K influences intra‐individual variability in anticoagulant response to warfarin

Khan¹,

Wynne²,

Wood³

et al. 2004

Br J Haematol

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“…10,11 Although a dietary vitamin K-OAC interaction is empirically well established, quantitative aspects of the dose-response relationship are presently lacking. 12 Current information comes from sporadic case reports, mostly documenting a resistance to OACs from increased intakes of vitamin K-rich foods 13,14 or supplements 15,16 or from limited experimental studies in patients. 17,18 Here, we report a systematic vitamin K dose-response study in 12 young healthy adults who had been initially stabilized with acenocoumarol for 4 weeks to a target INR of 2.0.…”

Section: Introductionmentioning

confidence: 99%

Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects

Schurgers

Shearer

Hamulyák

et al. 2004

Blood

122

103

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Oral anticoagulants exert their effect by blocking the utilization of vitamin K, yet little is known about competitive aspects of their interaction with dietary vitamin K. We carried out systematic dose-response studies in healthy volunteers who had been stably anticoagulated and maintained on their individualized doses for 13 weeks. First, we studied the response to weekly incremental doses (50 g-500 g) of vitamin K 1 supplements (K 1 ) taken daily for 7 days. The threshold K 1 dose causing a statistically significant lowering of the INR was 150 g/day. In 25% of the participants the INR change was regarded as clinically relevant at a vitamin K intake of 150 g/day. Circulating undercarboxylated osteocalcin did not decrease until 300 g K 1 /day compared with 100 g K 1 /day for undercarboxylated FII, suggesting differential antidotal effects on bone and hepatic ␥-carboxylation. Next, we tested the response to vitamin K-rich food items. The short-lived response after meals of spinach and broccoli suggested an inefficient bioavailability from these 2 sources. We conclude that shortterm variability in intake of K 1 is less important to fluctuations in the international normalized ratio (INR) than has been commonly assumed and that food supplements providing 100 g/day of vitamin K 1 do not significantly interfere with oral anticoagulant therapy. IntroductionOral anticoagulants (OACs) are antagonists of vitamin K that are widely used for the treatment and prophylaxis of thromboembolic disease. 1 Vitamin K is an essential micronutrient that, as the reduced hydroquinone (vitamin KH 2 ), serves as a cofactor for the transformation of selective glutamic acid (Glu) residues into ␥-carboxyglutamic acid (Gla) during the biosynthesis of vitamin K-dependent proteins, also called Gla proteins. The Gla residues confer metal binding properties and, in the case of the coagulation factors, facilitate a calcium-ion-dependent structural transition essential for the interaction of these proteins with phospholipid membranes. 2 The clinical effectiveness of OACs derives from their ability to block posttranslational ␥-carboxylation of the 4 vitamin K-dependent procoagulants (II, VII, IX, and X). Hence treatment with OACs results in the production of dysfunctional, undercarboxylated species of coagulation factors (also known as PIVKAs). OAC treatment also affects the synthesis and functional activity of a number of other Gla proteins including the anticoagulant protein C 3 and noncoagulation proteins such as osteocalcin in bone 4 and matrix Gla protein (MGP) in cartilage and the vasculature. 5 The cellular target receptor for OAC that best explains their mode of action is the enzyme vitamin K epoxide reductase. [6][7][8] In the absence of OACs, this microsomal, dithiol-dependent enzyme is responsible for the recycling of the vitamin K epoxide metabolite (produced during ␥-glutamyl carboxylation) by successively reducing vitamin K epoxide to vitamin K and then to vitamin KH 2 . In blocking the reutilization of the epoxide metabolite, OACs ...

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“…Case reports have been published on the instability of anticoagulation due to the in take of large amounts of vegetables [10,11], or due to the use of liquid-nutrition prepara tion [ 12,13], or even due to changes in dietary habits [14], However, these reports are lim ited only to a few foodstuffs and the authors have concluded that patients treated with an- (2) the improvement obtained with the diet may be related to the fact that the patients might have felt monitored more carefully. On the other hand, the patients themselves required advice on their dietary behavior especially because, their TT values fluctuating highly, they had to be controlled more frequently; (3) finally this study consid ered a minimum vitamin K requirement diet, but we believe that it is more important to administer a constant intake of vitamin K. This should be achieved by employing as many aliments as possible.…”

Section: Discussionmentioning

confidence: 99%

Controlled Vitamin K Content Diet for Improving the Management of Poorly Controlled Anticoagulated Patients: A Clinical Practice Proposal

Sorano

Biondi²,

Conti³

et al. 1993

Pathophysiol Haemos Thromb

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The aim of our study was to investigate the effect of a diet with a known vitamin K content on the monitor test for oral anticoagulant therapy. We studied 10 poorly controlled patients (7 women and 3 men, mean age 48+15 years) in therapy with acenocoumarol for at least 1 year. Another group of 10 poorly controlled patients was considered as a control group. After a baseline period, during which a free diet was allowed, patients were administered a diet with a controlled vitamin K content; in the same period, control subjects were not subjected to any dietary restriction. Thrombotest (Nyegaard, Oslo) was employed for monitoring oral anticoagulant therapy, with a therapeutic range between 2.3 and 4.8 INR. We found a significant difference by thrombotest between the percentages within the therapeutic range obtained before and during dietary treatment (p = 0.0001). The difference in percentages was -0.31 and the 95% CI, of the difference ranged from -0.45 to -0.17. No significant difference was shown in the control group in the same periods. Our data suggest that a diet with a controlled vitamin K content is effective in increasing the percentage of tests within the therapeutic range in patients with poorly controlled anticoagulation.

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Dietary Modification as Cause of Anticoagulation Instability

Cited by 23 publications

References 3 publications

Dietary vitamin K influences intra‐individual variability in anticoagulant response to warfarin

Dietary vitamin K influences intra‐individual variability in anticoagulant response to warfarin

Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects

Controlled Vitamin K Content Diet for Improving the Management of Poorly Controlled Anticoagulated Patients: A Clinical Practice Proposal

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