Condition category
Circulatory System
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status

Plain English Summary

Background and study aims
Low intake of vitamin K in the diet has been linked to a higher risk of heart attacks and strokes. This may be because vitamin K is important in keeping blood vessels in good health; low levels of vitamin K are associated with stiffer blood vessels and deposits of calcium in the blood vessel wall. Vitamin K may also be important in keeping nerves working well which are important in maintaining balance and avoiding falls. It is not known whether taking extra vitamin K (as a tablet) can improve balance or blood vessel health, so the aim of this study is to test whether taking a vitamin K tablet for 6 months improves blood vessel health and improves balance in older people who have had (or are at risk of) a heart attack or stroke.

Who can participate?
Older people aged 70 and over who have had (or are at risk of) a heart attack or stroke

What does the study involve?
Participants are randomly allocated to take either vitamin K or a matching placebo (dummy) tablet once a day for 6 months. They are then followed up to assess their blood vessel health and balance.

What are the possible benefits and risks of participating?
If vitamin K improves blood vessel health, it might reduce the risk of heart attacks and strokes, but this study is too small to show this directly. Vitamin K is safe with no known side effects. It can interfere with the action of the drug warfarin, which is why patients on warfarin are excluded from the study.

Where is the study run from?
Ninewells Hospital (UK)

When is the study starting and how long is it expected to run for?
August 2011 to March 2013

Who is funding the study?
Chest Heart and Stroke Scotland (UK)

Who is the main contact?
Dr Miles Witham

Trial website

Contact information



Primary contact

Dr Miles Witham


Contact details

Ageing and Health
Ninewells Hospital
United Kingdom
+44 (0)13 8263 2436

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Vitamin K to improve markers of vascular health and physical function in older people with vascular disease: a randomised controlled trial



Study hypothesis

To test whether vitamin K supplementation improves markers of vascular health in older people with vascular disease.

Ethics approval

East of Scotland NHS Research Ethics Committee, 12/09/2011, ref: 11/ES/0009

Study design

Parallel-group double-blind placebo-controlled randomised trial

Primary study design


Secondary study design

Randomised parallel trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet


Vascular disease


Vitamin K2 (MK7 subtype) 100 mcg per day or placebo.

Added 18/08/2017:
Participants are randomised to take either:
1. Vitamin K2 (MK7 subtype) given as 100 mcg oral tablet once a day for 6 months
2. Matching placebo tablet, given once a day for 6 months
Treatment in both arms given for 6 months, which is also the length of follow up.

Intervention type



Not Applicable

Drug names

Vitamin K

Primary outcome measure

Flow-mediated dilatation of the brachial artery measured at baseline and 6 months

Secondary outcome measures

Measured at baseline, 3 months and 6 months:
1. Markers of vascular function:
1.1. Arterial stiffness and reflectivity, measured using pulse wave velocity and augmentation index
1.2. Carotid intima-media thickness and compliance
2. Markers of vascular prognosis: brain natriuretic peptide (BNP), office blood pressure (BP) (lying and standing), total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol
3. Markers of inflammation: high-sensitivity C-reactive protein
4. Serum MK7 levels, measured by high-performance liquid chromatography (HPLC)
5. Markers of physical function:
5.1. Short Physical Performance Battery; predicts disability, falls and death
5.2. Balance, measured using force plate analysis
5.3. Grip strength as a test of maximal muscle strength; predicts institutionalisation and death

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Aged 70 and over
2. At least one of the conditions:
2.1. Hypertension (based on recorded diagnosis from primary or secondary care)
2.2. Diabetes mellitus (based on recorded diagnosis from primary or secondary care)
3. Established vascular disease: myocardial infarction [based on symptoms of ischaemia or electrocardiogram (ECG) changes, plus rise in cardiac enzymes]
4. Percutaneous transluminal coronary angioplasty
5. Coronary artery bypass grafting
6. Stroke/transient ischaemic attack (TIA) (diagnosis established in secondary care)
7. Peripheral vascular disease (symptoms of peripheral ischaemia and either a previous ankle/brachial pressure index < 0.7 or previous evidence of arterial stenosis on angiography or ultrasound)

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Atrial fibrillation
2. Taking warfarin
3. Unable to give written informed consent
4. Unable to walk without human assistance (walking aids are permitted)

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Ninewells Hospital
United Kingdom

Sponsor information


Tayside Academic Sciences Collaboration (UK)

Sponsor details

Level 3 Residences
Geroge Pirie Way
Ninewells Hospital
United Kingdom
+44 (0)13 8274 0489

Sponsor type




Funder type


Funder name

Chest Heart and Stroke Scotland (ref: R11/A137)

Alternative name(s)


Funding Body Type

private sector organisation

Funding Body Subtype

Associations and societies (private and public)


United Kingdom

Results and Publications

Publication and dissemination plan

Manuscript accepted for publication.

IPD sharing statement
The datasets generated during and/or analysed during the current study are available upon request from Dr Miles Witham ( Anonymised individual participant data on all those randomised will be made available to bona fide researchers for non-commercial use, subject to sight of an analysis plan and subject to appropriate data sharing agreements and approval from the trial Sponsor.

Intention to publish date


Participant level data

Available on request

Basic results (scientific)

See additional file ISRCTN93213492_BasicResults_04Aug2017.pdf

Publication list

2016 results in:

Publication citations

Additional files

Editorial Notes

22/08/2017: The basic results of this trial have been uploaded as an additional file. 18/08/2017: Interventions details and plain English summary added. 09/08/2017: Ethics approval details added. 04/08/2017: Recruitment dates confirmed, IPD sharing statement added. 16/11/2016: Publication reference added.