• Increase Font Size
  • Decrease Font Size
  • View as PDF

FL: Fluoride and the Brain (2010)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To explore the influence of both fluoride (F2) and arsenic (As) on Intelligence Quotient (IQ) in children living in three rural areas with contrasting levels of fluoride and arsenic.

Inclusion Criteria:
  • All children in first through third grade of public schools in three rural areas of Mexico (Moctezuma, Salitral and 5 de Febrero) were screened
  • Children were eligible if they lived in the area since birth and were six to 10 years old at time of study.
Exclusion Criteria:

Children who did not meet the location, age or residence requirements, as listed in the inclusion criteria.

Description of Study Protocol:

Recruitment

Children in public school Grades One through Three, in selected rural towns of Mexico were screened. These locations were selected based on the levels of fluoride and arsenic measured in the drinking water.

Design

  1. IQ tested by a trained neuropsychologist (masked to exposure status)
  2. Tap water (from the home) and urine samples assessed for each participant
  3. Lead exposure assessed by venous blood samples
  4. Height, weight, age, iron status and socioeconomic factors also reviewed. 

Blinding Used

IQ testing was blinded. Most tests were laboratory values and thus not applicable.

Statistical Analysis

  • Bivariate analysis between communities
  • Linear regression and regression modeling
  • SPSS version 12.0 (SPSS Inc., Chicago, United States).
Data Collection Summary:

Timing of Measurements

  • One-time assessments
  • Tap water and urine sampling was done on the same day as IQ testing
  • Other assessments and questionnaires were not specified for timing (blood lead, socioeconomic, height, weight, age, iron status).

Dependent Variable

  • Intelligence Quotient (IQ): Performance, verbal and full
  • Blood lead level.

Independent Variables

  • Fluoride concentration in water and urine
  • Arsenic concentration in water and urine
  • Mother's education
  • Socioeconomic status
  • Height for age
  • Transferrin saturation.

Control Variables

Cross-sectional comparative study.

Description of Actual Data Sample:
  • Initial N: 308 eligible, 155 randomly selected
  • Attrition (final N): 132 (85% response rate)
  • Age: Six to 10 years
  • Ethnicity: All subjects were born in the studied communities of Mexico.

Other Relevant Demographics

  Moctezuma (N=52) Salitral (N=20) 5 de Febrero (N=60)
Water Fluoride (mg/L)
0.8±1.4
5.3±0.9 (P<0.001)
9.4±0.9 (P<0.001)
Water Arsenic (mcg/L)
5.8±1.3
169±0.9 (P<0.001)
194±1.3 (P<0.001)
Age (Years)
8.3±1.1
7.7±1.0
8.3±1.1
Socioeconomic Status
7.0±1.3
6.3±0.9
5.9±1.4
Mother's Education (Years)
6.1±1.7
4.7±2.0
5.6±1.7
Boys (Percentage)
54
50
48
Transferrin Saturation (Percentage <20)
29 (P<0.001)
53 (P<0.001)
10
Weight for Age Index (Percentage <2SD)
4
0
0
Height for Age Index (Percentage <2SD)
0
0
1.7

Location

Mexico, rural towns with measured drinking water levels of fluoride and arsenic

  • Moctezuma: Fluoride, 0.8±1.4mg per L; arsenic, 5.8±1.3mcg per L
  • Salitral: Fluoride, 5.3±0.9 mg per L; arsenic, 169±0.9mcg per L
  • 5 de Febrero: Fluoride, 9.4±0.9 mg per L ; arsenic, 194±1.3mcg per L

[Note: World Health Organization guideline values for fluoride up to 1.5mg per L and arsenic up to 10mcg per L.]

Summary of Results:

Key Findings

  • Locations with higher levels of fluoride and arsenic in the water had significantly lower socioeconomic status (P<0.001) than those with less fluoride or arsenic, despite similar participant age, mother's education, gender, weight for age or height for age assessments
  • There was increased incidence of elevated blood lead levels (over 10mcg per dL) in areas where participants had higher levels of arsenic in urine
  • Fluoride in urine and in water had a statistically significant (P<0.001) inverse relationship on all IQ scores
  • Arsenic in urine had a statistically significant (P=0.003) inverse association with full IQ scores (inverse relationship with performance and verbal IQ found, but not significant)
  • Arsenic in water showed a statistically significant (P<0.001) inverse relationship with all IQ scores.

Table of Concentrations of Fluoride and Arsenic in Urine and Lead in Blood of Children Living in Three Rural Areas in Mexico (Moctezuma, Salitral, 5 de Febrero)

  Minimum-Maximum Reference Value Percentage Above Mean, Reference Value or CDC Limit
Fluoride in Urine (mg F/gr crt) Moctezuma
1.8±1.5
0.6-4.9
38.5
Salitral
6.0±1.6*
2.9-10.6
100
5 de Febrero
5.5±3.3*
1.2-25.0
98
Arsenic in Urine (mcg As/g crt) Moctezuma
12.6±2.0
2.0-7.0
3.8
Salitral
116 ±2.2*
26.0-285.0
80
5 de Febrero
52.5± 2.2*
10.0-325.0
52
Lead in Blood (mcg/dL) Moctezuma
7.1±2.2
3.0-13.0
10
Salitral
6.7±2.1
2.0-10.5
4.5
5 de Febrero
4.8±3.4*
0.2-16.0
10

*P<0.001, compared with Moctezuma.

Table of Multi-Variable Model Results for Performance, Verbal and Full Intelligence Quotient (IQ) by Fluoride (F2) and Arsenic (As) in Urine and Water Levels, Adjusted for Confounding Variables (N=132).

  Performance IQ Verbal IQ Full IQ
Water Urine Water Urine Water Urine
Log Fluoride
-7.78*
-13.0*
-11.5*
-16.4*
-10.9*
-17.1*
Arsenic
-5.17**
-5.3***
-7.19**
-6.9**
-7.09**
-7.1**
R2 (Percentage) Fluoride
11.1
13.4
14.7
12.9
16.7
17.4
Arsenic
10.9
, 4.8
12.8
5.0
15.3
6.5
Adjusted Models (F) Log F2
-6.7*
-13.0*
-11.2*
-15.6*
-10.2
-16.9*
Pb blood
-0.45
-0.52
-1.0***
-0.94***
-10.2*
-16.9*
Mother's education
0.62
0.37
0.35
0.11
0.64
0.34
Socioeconomic status
0.60
0.13
1.23
0.92
0.94
0.47
Height for age Z-score
0.74
0.74
2.9***
3.06***
2.1
2.17***
Transferrin saturation
-0.05
-0.10
0.01
-0.07
-0.02
0.09
Total R2 percentage (F)
14
17
26
23
25
25
Adjusted Models (As) Log As
-4.30**
-4.19
-6.40**
-5.50
-6.15**
-5.72***
Pb blood
-0.37
-0.25
-0.84***
-0.63
-0.68
-0.49
Mother's education
0.51
0.64
0.20
0.42
0.49
0.69
Socioeconomic status
0.68
0.63
1.43
1.46
1.01
1.07
Height for age Z-score
0.70
0.91
2.90***
3.26***
2.08
2.39***
Transferrin saturation
-0.06
-0.11
-0.005
-0.75
-0.03
0.10
Total R2 percentage (As)
13.5
9.5
23.5
17.2
22.8
16

*P<0.001
**P<0.01
***P<0.05.

Author Conclusion:

Fluoride and arsenic in drinking water have a potential neurotoxic effect in children.

Funding Source:
Government: Consejo Nacional de Clencia y Tecnologia
Other:
Reviewer Comments:
  • Environmental exposure levels were very high
  • Assessment of urine beneficial to see actual exposure since author's note some areas used bottled water to decrease exposure.
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? 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? 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? 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")? Yes
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? Yes
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? 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? 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? Yes
  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? Yes
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? N/A
  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)? 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? 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