EAL

FNOA: Antioxidants (2011-2012)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate whether a relatively high habitual intake of those isoflavones and lignans commonly seen in a Western diet is associated with better cognitive performance in post-menopausal women.

Inclusion Criteria:

Subjects from the first group were healthy Dutch women, aged 60 to 75 years at baseline in 2000 and living in Utrecht or its surroundings. They had complied with the biannual call to participate in a national screening program for breast cancer in 1999 and all had a normal mammogram.
Subjects from the second group were women recruited between 1993 and 1997 through the regional breast cancer screening program.

Exclusion Criteria:

Subjects in both groups met the following exclusion criteria:

History of malignant disease, active kidney or liver disease
History of thromboembolism
Current estrogen use or estrogen use in the six months prior to enrollment
Known allergy to soy or milk protein
Endometrial thickness over 4mm.

Description of Study Protocol:

Recruitment

Women were recruited from two sources:

First group consisted of 202 women who attended screening and baseline visits for a double-blind, randomized placebo-controlled trial assessing the effect of an intervention with phytoestrogens on bone mineral density, cardiovascular disease risk factors, cognitive function, well-being and physical performance
To increase the power of the study, more women were recruited from an ongoing cohort study from which participants were selected who fulfilled the same inclusion and exclusion criteria. The ongoing cohort study is one of two Dutch contributions to the European Prospective Investigation into Nutrition and Cancer (EPIC) cohort
Recruitment from the EPIC cohort was similar to that for the trial; the women received a letter with information about the study
Women who were interested returned an answer form and were called by one of the researchers to explain further details and answer questions.

Design

Cross-sectional analysis of baseline measurements of randomized controlled trial with added measurements from cohort participants.

Statistical Analysis

Energy-adjusted dietary intake of total phytoestrogens, lignans and isoflavones was divided into quartiles
Data were analyzed using linear regression models, after adjusting for potential confounders
Results were analyzed both including and excluding depressed participants.

Data Collection Summary:

Timing of Measurements

All participants had a physical examination, completed a general and health questionnaire and completed a more detailed food frequency questionnaire for the present study.

Dependent Variables

Weight and height measured
Blood pressure and heart rate
Waist and hip circumferences
Presence of depression assessed using self-rated Geriatric Depression Scale
Cognitive function measured in three domains (memory, processing capacity and speed) and executive function
- Folstein's Mini-Mental State Examination
- Rey's Auditory Verbal Learning Test
- Doors Test
- Digit Span Test, a subset of the Wechsler Adult Intelligence Scale (WAIS)
- Boston Naming Test for Verbal Competence and Semantic Retrieval
- Digit Symbol Substitution Test
- Trail-Making Test parts A1, A2 and B
- Dutch Adult Reading Test.

Independent Variables

Dietary isoflavone and lignan intake was assessed with a food frequency questionnaire covering habitual intake in the year preceding enrollment.

Control Variables

Energy
Age
Education level
Verbal intelligence
Number of post-menopausal years
Systolic and diastolic blood pressure
BMI
Waist-hip ratio
Smoking status
Physical activity determined by the Questionnaire on Mobility in Elderly
Intake of:
- Total energy
- Alcohol
- Saturated fat
- Monounsaturated fat
- Polyunsaturated fat
- Fiber
- Folic acid
- Vitamin E
- Fruit
- Vegetables.

Description of Actual Data Sample:

Initial N: 301 women
Attrition (final N): 301 women
Age: Aged 60 to 75 years
Ethnicity: Assumed Caucasian
Location: The Netherlands.

Summary of Results:

Key Findings

Median intake of isoflavones was 0.18mg per day in the lowest intake quartile and 14.6mg per day in the highest quartile
For lignans, intake was 0.65mg per day and 2.3mg per day for the lowest and highest quartiles
Women with high isoflavone intake were somewhat younger and more physically active, consumed more vegetables and fruits but less fat and consumed slightly more alcohol
No association between dietary isoflavone intake and cognitive function was found
High lignan intake was associated with a better performance in processing capacity and speed and in executive function (P for trend over quartiles = 0.01 and 0.02, respectively), but not memory.

Cognitive Function and Quartiles of Lignan Intake

Cognitive Function Domains	Difference	P-value	95% CI	P for Trend
Memory (Z-score)				0.42
2nd quartile	0.027	0.836	-0.232, 0.286
3rd quartile	0.181	0.216	-0.106, 0.468
4th quartile	0.094	0.580	-0.240, 0.428
Processing Capacity and Speed (Z-score)				0.01
2nd quartile	0.183	0.089	-0.028, 0.394
3rd quartile	0.345	0.004	0.110, 0.580
4th quartile	0.325	0.020	0.052, 0.597
Executive Function (Z-score)				0.02
2nd quartile	0.064	0.546	-0.143, 0.270
3rd quartile	0.270	0.020	0.043, 0.498
4th quartile	0.260	0.054	-0.995, 0.524
MMSE				0.99
2nd quartile	0.284	0.420	-0.410, 0.978
3rd quartile	0.191	0.625	-0.577, 0.959
4th quartile	0.074	0.871	-0.816, 0.963

Author Conclusion:

This observational study in post-menopausal women suggests that high dietary lignan intake has a beneficial effect on cognitive function, notably on processing speed and capacity, and executive function. We found no apparent relationship between dietary isoflavone intake and cognition in the range of intake common in a Westernized population. This finding calls for further research into the role of lignans.

Funding Source:

Industry:

Solae Company

Pharmaceutical/Dietary Supplement Company:

Not-for-profit

Netherlands Organization for Scientific Research, Netherlands Organization for Health Research and Development

Other non-profit:

Reviewer Comments:

Groups recruited from two sources but new measurements completed. Authors note the following limitations:

Study population consisted of women who volunteered to take part in a trial on phytoestrogens and women participating in an ongoing cohort study into the effects of nutrition on cancer and recruited through a breast cancer screening program, which may limit how much findings can be generalized to the general population since women willing to participate in these studies are more health conscious and may adhere to a healthier diet and lifestyle
Observational studies may suffer from confounding and bias.

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)	N/A
	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)	N/A

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?	???
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		???
	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?	???
	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?	???
	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?	N/A
	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?	Yes
	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?		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?	N/A
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	N/A
	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?	N/A
	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?	Yes
	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)?	Yes
	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?	N/A
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?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes