EAL

NSUP: Vitamin E (2014)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To describe the effect of vitamin E supplementation on coagulation in a male with history of cardiovascular disease and prescribed warfarin and clofibrate therapies.

Inclusion Criteria:

Informed consent.

Exclusion Criteria:

Description of Study Protocol:

Recruitment

Design Case Study

Blinding used (if applicable)

Intervention (if applicable)

Following stable clinical and hematological status for two months, patient was re-challenged with 800 IU over-the-counter vitamin E supplement (90% alpha tocopherol) daily for seven weeks until patient developed clinical evidence of bleeding.
Diet and medication (prescription and nonprescription including aspirin) use remained unchanged during this period.
After seven weeks of supplementation, vitamin E was stopped (other medications were continued) and patient was followed for changes in coagulation and until clinical signs of bleeding resolved.

Statistical Analysis

Data Collection Summary:

Timing of Measurements

At weekly intervals
- Platelet functon
  - Platelet count
  - Bleeding time
  - Platelet adherence to glass beads
  - Platelet aggregation
  - Clot retraction.
- Vitamin K dependent coagulation factors (II, VII, IX, X)
- Plasma warfarin level
- Clinical evidence of bleeding.

Dependent Variables

Prothrombin time
Plasma warfarin levels
Vitamin K dependent coagulation factors.

Independent Variables

800 IU vitamin E

Control Variables

Description of Actual Data Sample:

Initial N: N=1 (male)

Attrition (final N): N=1

Age: 55 years

Ethnicity: not described

Other relevant demographics:

Medical history included: arteriosclerotic heart disease, type IV hyperlipidemia, myocardial infarction
Medications included: digoxin, warfarin sodium, clofibrate, procainamide
Prothrombin time: 20.7 seconds
Coagulation factors:
- Factor II: 11%
- Factor VII: 27%
- Factor IX: 30%
- Factor X: 15%.
Clinical evidence of bleeding: none.

Anthropometrics (e.g., were groups same or different on important measures)

Location: University of Arizona Medical Center, Tucson, AZ

Summary of Results:

Key Findings

Variables	Week 7	Week 8 (1 week without Vitamin E)
Prothrombin time, seconds	29.2	22.3
Factor II, %	7	21
Factor VII, %	16	20
Factor IX, %	14	23
Factor X, %	10
Clinical evidence of bleeding	Multiple ecchymoses on both legs, ankle, arm; hematoma in pre-tibial area.

Over time, prothrombin time, coagulation factors and clinical evidence of bleeding returned to baseline values.
Plasma warfarin levels did not change during the eight week period.

Other Findings

Author Conclusion:

In patients receiving both warfarin and clofibrate therapies, addition of vitamin E reduces vitamin K-dependent coagulation factors further and increases risk of hemorrhage.

Funding Source:

University/Hospital:

University of Arizona Medical Center, Tucson, AZ

Reviewer Comments:

Supplement specifics were not identified: natural vs synthetic, acetate vs succinate.
No biomarker measured to assess vitamin E status.
Adherence to supplement not discussed.
No assessment of diet including dietary fat intake was provided; lipid levels were not measured.
Clofibrate intensifies the action of warfarin.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	???
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	N/A
	2.2.	Were criteria applied equally to all study groups?	N/A
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		N/A
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		N/A
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	Yes
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	Yes
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	No
	7.7.	Were the measurements conducted consistently across groups?	N/A
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		N/A
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	N/A
	8.2.	Were correct statistical tests used and assumptions of test not violated?	N/A
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	N/A
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	N/A
	8.6.	Was clinical significance as well as statistical significance reported?	N/A
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		No
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	No
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes