EAL

FNOA: Antioxidants (2011-2012)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine the effects on cognitive performance of a five-week supplementation with Enzogenol Pinus radiata bark extract containing flavonoids.

Inclusion Criteria:

Male non-smokers aged 50 to 65 years who were right-handed and did not exercise much
Had a sedentary occupation
BMI higher than 25kg/m²
Not taking any form of vitamin or herbal supplementation
Not suffering from any neurological disorder or epilepsy.

Exclusion Criteria:

Excluded if not included above.

Description of Study Protocol:

Recruitment

Participants were recruited by way of newspaper advertisements, posters and e-mails. Advertisements asked for male non-smokers aged 50 to 65 years, who were right-handed and did not exercise much. Interested participants were screened via telephone and invited to participate if they met more specific inclusion and exclusion criteria.

Design

Randomized controlled trial. Participants were randomized using a random permuted block procedure.

Blinding Used

Double-blind.

Intervention

Five-week supplementation with Enzogenol Pinus radiata bark extract containing flavonoids (960mg Enzogenol) plus vitamin C (120mg) or vitamin C only (120mg).

Statistical Analysis

For each of the eight cognitive tasks, mean accuracy and response time scores were calculated for each participant, prior to and following supplementation
Cognitive performance on the spatial working memory and immediate recognition tasks were analyzed individually using repeated measures analysis of variance
Remaining tasks were included in two multivariate analysis of variance models for accuracy and response time data.

Data Collection Summary:

Timing of Measurements

Measurements made before and after five weeks of supplementation.

Dependent Variables

Cognitive performance assessed through battery of eight computerized cognitive tests to assess the following:
- Contextual memory
- Immediate recognition
- Simple reaction time
- Choice reaction time
- Visual vigilance
- Complex visual vigilance
- Spatial working memory
- Delayed recognition memory
Cardiovascular and hematological parameters:
- Systolic and diastolic blood pressure
- Blood samples analyzed for liver function tests, urea and electrolytes, a full blood cell and differential count and blood lipid profiles.

Independent Variables

Five-week supplementation with Enzogenol Pinus radiata bark extract containing flavonoids plus vitamin C or vitamin C only.

Description of Actual Data Sample:

Initial N: 106 men responded to advertisements. 45 met the telephone screening criteria and underwent medical examination. 42 males passed the medical examination and were randomized.
Attrition (final N): 42 males, all completed the study (22 in treatment group, 20 in control group)
Age: Aged 50 to 65 years, mean age 58 in both groups
Anthropometrics: There were no significant differences between groups in terms of age, years of education, height, weight, BMI, hematological indices or cognitive tasks at baseline
Location: Australia.

Summary of Results:

Key Findings

The speed of response for the spatial working memory and immediate recognition tasks improved after supplementation with Enzogenol plus vitamin C, whereas vitamin C alone showed no improvements
For the spatial working memory task, repeated measures ANOVA indicated there was a significant group by time interaction, reflecting a decrease in response time of 64ms or 6.4% for participants in the treatment group, and this change in response time was significant in the treatment group (P=0.004) but not in the control group (P=0.95)
For the immediate recognition task, repeated measures ANOVA indicated there was a significant group by time interaction, reflecting an improvement in the response time of 60ms or 5.4% in the treatment group, compared with a small increase in the control group
Post-hoc T-test showed that the change was significant in the treatment group (P=0.016) but not in the control group (P=0.696)
A trend in reduction of systolic blood pressure was observed with Enzogenol plus vitamin C but not with vitamin C alone
Blood safety parameters were unchanged
No adverse effects were reported by participants in the study.

Author Conclusion:

This randomized, double-blind, vitamin C controlled study has demonstrated the potential to improve both cognitive and cardiovascular functions prone to decline with age after a relatively short duration of supplementation with Enzogenol plus vitamin C in a group of older men that may be at risk of cognitive decline. Larger studies in men and women of different age groups are necessary to ascertain its potential as a preventive treatment to fight age-related or neurodegenerative loss in brain function.

Funding Source:

Industry:

ENZO Bioactives Pty Ltd

Pharmaceutical/Dietary Supplement Company:

In-Kind support reported by Industry:

Yes

Reviewer Comments:

Study was sponsored by ENZO Bioactives Pty Ltd.
Small numbers of subjects in groups and only five weeks of supplementation.
Authors note that it is unclear whether the Pinus radiata bark extract alone would have demonstrated the same positive effects or whether there is a synergistic benefit when combined with vitamin C.

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)	Yes
	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?		???
	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?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	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?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	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?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	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%.)	Yes
	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?	Yes
	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?	N/A
	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?		???
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	???
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	???
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	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?	Yes
	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?	???
	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?	???
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	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)?	???
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		No
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	No