NSUP: Vitamin E (2014)
Citation:
Corrigan JJ Jr, Marcus FI. Coagulopathy associated with vitamin E ingestion. JAMA. 1974;230:1300-1301.
PubMed ID: 4479598Study Design:
Case Study or Case Series
Class:
D - 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.
- Platelet functon
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
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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 | |