EAL

NNNS: Adverse Effects (2011)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate the association between self-reported consumption of aspartame-containing beverages and incident hematopoietic and brain cancers in the prospective NIH-AARP Diet and Health study.

Inclusion Criteria:

AARP (American Association of Retired Persons) members aged 50 to 71
Residing in one of eight study areas
Responded to one of 3.5 million questionnaires mailed during 1995 and 1996.

Exclusion Criteria:

History of cancer or death reports of cancer
Proxy responders
Outliers on reported energy intake
Missing or outlier values of body mass index (BMI) and BMI less than 18.5.

Description of Study Protocol:

Recruitment: 3.5 million questionnaires mailed by authors
Design: Prospective cohort study.

Statistical Analysis

Histological confirmed incident cancers were identified from eight state cancer registries
Multi-variable-adjusted relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression that were adjusted for age, sex, ethnicity, body mass index and history of diabetes.

Data Collection Summary:

Timing of Measurements

Histologically confirmed incident cancer cases ascertained from the eight state cancer registries up to December 31, 2000.

Dependent Variables

Malignant gliomas
Hematopoietic cancer.

Independent Variables

Consumption of aspartame (divided into cohorts based on aspartame content per 100g beverage determined self-administered baseline questionnaire including a food frequency questionnaire (FFQ) calibrated against two 24-hour recalls).

Description of Actual Data Sample:

Initial N

Mailed out 3.5 million questionnaires as part of the NIH-AARP Diet and Health Study.

Attrition (Final N)

473,984 questionnaires analyzed: 285,079 men and 188,905 women
2,060,611 person years.

Age

51 to 75 years of age (includes no history of any prior cancer for up to 5.2 years; up to 75 years of age, median 67).

Ethnicity

91% non-Hispanic white
4% non-Hispanic black
5% others.

Other Relevant Demographics

One of eight study areas: California, Florida, Pennsylvania, New Jersey, North Carolina, Louisiana, Atlanta, Detroit
Education: 6%, less than 12 years; 52%, 12 to 15 years; 39%, 16+ years
Family history of cancer: 49%
Calories: 1,835 kcal per day
Caffeine: 366mg per day
Daily frequency (serving per day): Diet soda, 0.4; diet fruit drinks, 0.05; diet ice tea, 0.1; aspartame in coffee/hot tea, 0.3.

Anthropometrics

BMI: Greater than 18.5 and less than 25, 35%; greater than 25 and less than 30, 43%; greater than 30 and less than 35, 16%; greater than 35, 6%.

Location

One of eight geographic study locations: California, Florida, Pennsylvania, New Jersey, North Carolina, Louisiana, Atlanta, Detroit.

Summary of Results:

After following up 473,984 persons without history of any prior cancer for up to 5.2 years:

Hematopoietic Cancers (N=1,888)
- Adjusted RR for more than 600mg per day vs. none 0.98 (95% CI 0.76 to 1.27)
- 1,318 men and 570 women were diagnosed with incident hematopoietic cancers.
Malignant Gliomas (N=315)
- Adjusted RR for more than 400mg to less than 600mg per day vs. none 0.73 (95% CI 0.46 to 1.15); inverse linear trend, P=0.05
- 225 men and 90 women were diagnosed with malignant gliomas.

Author Conclusion:

Findings did not support the hypothesis that aspartame increases hematopoietic or brain cancer risk.

Funding Source:

Government:

NIH

Reviewer Comments:

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?		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?	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?	Yes
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?	Yes
	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?	Yes
	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?	Yes
	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?		N/A
	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.)	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	No
	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?	N/A
	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?	N/A
	6.6.	Were extra or unplanned treatments described?	No
	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?	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?	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)?	Yes
	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?	Yes
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?	No
	10.2.	Was the study free from apparent conflict of interest?	Yes