The Review manager –indicating that in each study

The effects of Vitamin K supplements.



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Vitamin K antagonists (VKA) such as warfarin and
phenprocoumon are used to reduce and prevent clotting factors which without treatment
increase the risk of AF, stroke and heart attack in susceptible patients. It is
believed low doses of Vitamin K can improve anticoagulation control and
clinical output. INR is the time taken for a blood clot to form and is a
measurement used to monitor the effect of VKA and its anticoagulant action. Vitamin
K single dose (1 to 2.5mg) can lower the INR if needed to reduce bleeding. Systematic
review and meta-analysis were conducted to assess the effect of the daily
supplement of Vitamin K to stabilise INR, major bleeds and thromboembolic
events. This study was carried out using already available data from various
studies to investigate this and an overall conclusion was made



When data was obtained from appropriate studies it was set
to a standardised form which included factors such as; method of information,
patient number, VKA type, indication for anticoagulant use, Vitamin K use and
outcomes. Overall, 624 articles were found however only 3 studies (626
patients) are included within the meta-analysis due to the suitability needed
and the articles found.  Random effects
models were used which found statistical analysis such as an absolute
difference with the TTR results due to effects of treatment. Pool analysis was
carried out using Review manager –indicating that in each study the effect was different
(p<0.10) so random error not likely for the difference. The 3 studies were extracted using the methods below.


Phase 1 – Search Strategy;

Ovid Medline database

Embase database

International pharmaceutical abstracts

Cochrane central register of controlled trails

National institutes of health clinical trials

Review articles


Phase 2 – Eligibility Criteria;

Randomised Controlled Trails (RCT)

Patients over 18 years old

Patients receiving VKA therapy

Studies in English (language)

Compare vitamin K supplement to placebo


Phase 3 – Study outcomes include;

haemorrhagic rate

thromboembolic events

time in therapeutic range (TTR)





Study descriptions


Study 1;

200 patients taking long term (>1 year)

received vitamin k capsule or placebo for 24
weeks with VKA Therapy

mean TTR 79-80% as stable on phenprocoumon


Study 2;

70 patients with AF taking warfarin for stroke

Vitamin K oral solution or placebo

INR unstable (Standard deviation of more than
0.5 and changes of dose within 6 months)

Outcome studies TTR, INR and number of changes
in dose

Study 3;

400 patients

Vitamin K capsules or placebo after starting
phenprocoumon or acenocoumarol

Looking at the anticoagulation control, INR





Three patients had a haemorrhagic event in the vitamin K group
and none had experienced this within the placebo group. Also, two had a
thromboembolic event whilst taking Vitamin K rather than in the placebo group. It
was found that a significantly higher TTR was a result of all the studies taken
with patients on a vitamin K than in patients taking a placebo.




Overall, the systematic review did not suggest that taking
daily low dose of Vitamin K improved the INR control with patients receiving
Vitamin K antagonists in the three studies.

Also, the TTR portrayed modest improvement (3.5% absolute
difference) this however is not likely to be of clinical importance.






The quality of the overall evidence was assessed using the Grade
of recommendations assessment, development and evaluation system (GRADE.)
Within this, unclear and irregular results as well as biased risks were taken
into account. However, the overall quality was still low due to being a biased
risk and imprecision. Also;

Small number of trails

Little study in patients with inadequate INR

Big range of rates of haemorrhage and
thromboembolic events

Only used studies in that are in English

Patients from specialised clinics – not generalised.