Table 6.
Studies on a possible association of fluoride exposure from drinking water and human intelligence published since 2012
| Reference | Study location | Study type (CS/PC/L) | Fluoride resource (E/CWF) content (mg/L); location of measurement |
Comparator | Participant number [age (years)] | Statistical adjustment performed | Outcome | Results/conclusion, as stated by the authors |
|---|---|---|---|---|---|---|---|---|
| Saxena et al. (2012) | India (Madhya Pradesh State) | CS | E < 1.5 vs. 1.5–3.0 vs. 3.1–4.5 vs. > 4.5; water samples from each child’s home |
IQ and water fluoride IQ and urinary fluoride Urinary fluoride and water fluoride |
120 (12) | Yes | ↓ | Reduction in intelligence was observed with an increased water fluoride level (p 0.000). The urinary fluoride level was a significant predictor for intelligence (p 0.000). Children in endemic areas of fluorosis are at risk for impaired development of intelligence |
| Seraj et al. (2012) | Iran (Makoo) | CS | E 0.8 (± 0.3) vs. 3.1(± 0.9) vs. 5.2 (± 1.1); groundwater samples distributed over the study area | IQ and water fluoride | 293 (6–11) | Yes | ↓ | Children residing in areas with higher than normal water fluoride levels demonstrated more impaired development of intelligence. Thus, children’s intelligence may be affected by high water fluoride levels |
| Nagarajappa et al. (2013) | India (Kutch District, Gujarat) | CS | E 0.5 vs. 2.4–3.5; data obtained from Water and Sanitation Management Organization, Gujarat | IQ and water fluoride | 100 (8–10) | No | ↓ | Chronic exposure to high levels of fluoride in water was observed to be associated with lower intelligence quotient |
| Pratap et al. (2013) | India (Dausa district, Rajasthan) | CSa | E 1.03 (± 0.15) vs. 6.8 (± 1.6); water samples from each child’s home |
IQ and water fluoride Urinary/serum fluoride and water fluoride |
142 (9–12) | No | ↓ | IQ scores and serum fluoride levels was directly correlated with the concentration of serum fluoride level. The conclusion of the study is that the excessive fluoride delineates the neuronal impairment which were evident by reduced IQ score and serum acetylcholinesterase activity |
| Wei et al. (2014) | China (Bijie City, Guizhou Province) | CSa | E endemic fluorosis area (long-term treatment group vs. short-term treatment) vs. non-fluorosis areab,c | IQ and urinary fluoride | 741 (8–12) | No | ↓ | Urinary fluoride was negatively correlated with the level of IQ (r=− 0.553, p < 0.01). The intelligence development of children in coal-burning-borne endemic fluorosis area is significantly delayed |
| Karimzade et al. (2014) | Iran (West Azerbaijan) | CSa | E 0.25 vs. 3.94; water samples from drinking water supplies (wells and springs) in the two study regions | IQ and water fluoride | 39 (9–12) | No | ↓ | The study found that children residing in a region with a high drinking water fluoride level had lower IQs compared to children living in a low drinking water fluoride region (p < 0.001) |
| Broadbent et al. (2015) | New Zealand (Dunedin) | PCd |
CWF vs. E 0.7–1.0 vs. 0.0–0.3 and/or fluoride dentifrice and/or intake of 0.5 mg fluoride tablets assessed in early life; with or without CWF coded from residential address data |
IQ and water/dentifrice/tablets fluoride | 992/942 (7–13/38)e | Yes | → | No clear differences in IQ because of fluoride exposure were noted. These findings held after adjusting for potential confounding variables |
| Choi et al. (2015) | China (Southern Sichuan) | CSa | E 1.0–4.07 (GM 2.20); data measured and recorded by Mianning County Center for Disease Control obtained from well-water in the communities |
IQ and water fluoride IQ and urinary fluoride Urinary fluoride and water fluoride |
51 (6–8) | Yes | ↓ | This pilot study in a community with stable life-time fluoride exposures supports the notion that fluoride in drinking water may produce developmental neurotoxicity, and that the dose-dependence underlying this relationship needs to be characterized in detail |
| Zhang et al. (2015a) | China (Tianjin City) | CS | E 1.40 (1.23–1.57) vs. 0.63 (0.58–0.68); water samples from each child’s home |
IQ and water fluoride Urinary/serum fluoride and water fluoride IQ and urinary/serum fluoride |
180 (10–12) | Yes | ↓ | Significantly high levels of fluoride in drinking water, serum, urine, along with poor IQ scores were observed in the high fluoride exposure group compared with those in control (all p < 0.05). Levels of fluoride serum and urine were inversely related with IQ (rs = − 0.47, p < 0.01; rs = − 0.45, p = 0.002) |
| Khan et al. (2015) | India (Lucknow district) | CS | E 0.19 vs. 2.41; water samples were collected from borewells | IQ and water fluoride | 429 (6–12) | No | ↓ | Findings of this study suggest that the overall IQ of the children exposed to high fluoride levels in drinking water and hence suffering from dental fluorosis were significantly lower than those of the low fluoride area |
| Sebastian and Sunitha (2015) | India (Mysore District) | CS | E 0.4 vs. 1.2 vs. 2.2; information from Rajiv Gandhi National Rural Drinking Water Program | IQ and water fluoride | 405 (10–12) | Yes | ↓ | In bivariate analysis, significant relationships were found between water fluoride levels and IQ of school children (p < 0.05) School children residing in area with higher than normal water fluoride level demonstrated more impaired development of intelligence when compared to school children residing in areas with normal and low water fluoride levels |
| Kundu et al. (2015) | India (Delhi) | CS | E high vs. low fluoride areaf; water samples were collected from borewell | IQ and water fluoride | 200 (8–12) | Yes | ↓ | Fluoride in the drinking water was significantly related with the IQ of children. Along with fluoride, mother’s diet during pregnancy was also found to be significantly related with IQ of children. |
| Aravind et al. (2016) | India (Virajpet, Banavara, Mastihalli) | CS | E < 1.2 vs. 1.2–2 vs. > 2g; drinking water samples from, e.g., open well/bore well/tube well | IQ and water fluoride | 288 (10–12) | No | ↓ | It is concluded that IQ level was negatively correlated with fluoride level in drinking water |
| Das and Mondal (2016) | India (West Bengal) | CS | E 0.25–9.40 (M 2.11); water samples from tube wells of study areas |
IQ and exposure doseh Urinary fluoride and exposure dose IQ and urinary fluoride |
149 (6–18) | Yes | ↓ | The results also reveal that exposure dose has a positive correlation with dental fluorosis (r = 0.299, p < 0.01) and urinary fluoride concentration (r = 0.513, p < 0.01) and a negative correlation with IQ (r = − 0.343, p < 0.01) along with BMI (r = 0.083, non-significant) |
| Mondal et al. (2016) | India (West Bengal) | CS | E 0.33–18.08; groundwater samples pre-monsoon and post-monsoon from borewells |
IQ and water fluoride Urinary/serum fluoride and water fluoride |
40 (10–14) (subpopulation of 235) | No | ↓ | IQ test also signifies that fluoride has a bearing on the intelligence development of the study area school children |
| Sharma et al. (2016)i | India (District Una, Himachal Pradesh) | CSa | E 0.40–0.68; water sample from selected schools |
Fluorosis level and water fluoride IQ and fluorosis level |
270 (10–14) | No | ↓ | As the fluorosis level increased, the proportion of children with lower intelligence increased. Based on the findings, the chronic exposure to high levels of fluoride can be one of the factors that influence intellectual development |
| Bashash et al. (2017) | Mexico (Mexico City) | L | Ek | Child´s cognitive functionl and MUFm | 287/211 (4/6–12) | Yes | ↓ | Higher prenatal fluoride exposure, in the general range of exposures reported for other general population samples of pregnant women and non-pregnant adults, was associated with lower scores on tests of cognitive function in the offspring at age 4 and 6–12 years |
| Razdan et al. (2017)n | India (Mathura district) | CS | E 0.60 vs. 1.70 vs. 4.99; water samples from different villages surrounding Mathura District from the hand pumps noted to be the source of consumed water for the inhabitant | IQ and water fluoride | 219 (12–14) | No | ↓ | Concentration of fluoride in the ingested water was significantly associated with the IQ of children. It has also coined the proportional variability in mental output in accordance to the ingested fluoride level |
| Mustafa et al. (2018) | Sudan (Khartoum State) | CSa | E 0.14–2.07 (dry season), 0.01–1.34 (rainy season), 0.08–1.17 (average of seasons); groundwater samples (dry and rainy season) from different rural areas in Khartoum state | Schooling performanceo and water fluoride | 775 (6–14) | No | ↓ | There may be an inverse relationship between fluoride levels in drinking water and schooling performance |
| Yu et al. (2018) | China (Tianjin) | CS | E M: 0.50 (± 0.27) vs. 2.00 (± 0.75); water samples from the public water supplies in each village |
IQ and water fluoride Urinary fluoride and water fluoride |
2886 (7–13) | Yes | ↓ | The study suggests threshold and saturation effects of moderately excessive fluoride exposure on dental fluorosis and intelligence loss in children, and a potential association between dental fluorosis and the loss of excellent intelligence |
| Sharma et al. (2018c) | India (District Una, Himachal Pradesh) | CS | E 0.31–0.68; water samples were collected from the selected schools | IQ and water fluoride | 600 (10–14) | No | → | Risk of dental caries and DAIp were more prevalent in areas with high fluoride level in water. Low intelligence level of adolescents was not significantly associated with high fluoride level hence indicating towards multifactorial causation of disease |
| Naik et al. (2018) | India (Mysore district) | CS | E < 1.2 vs. 1.2–2 vs. >2; water samples from different villages surrounding Mysore District from the hand pumps noted to be the source of consumed water for the inhabitant | IQ and water fluoride | 264 (12–15) | No | ↓ | Fluoride concentration in drinking water was negatively correlated with IQ level of school children |
| Green et al. (2019) | Canada (Vancouver, Montreal, Kingston, Toronto, Hamilton, Halifax) | PC |
CWF vs. E fluoride intake level in mg/day, M: 0.30 vs. 0.93; water fluoride concentration in mg/L, M: 0.13 vs. 0.59; data measured automatically in the water treatment plant zone matched with participants´ postal code |
IQ and maternal urinary fluoride IQ and self-reported maternal daily fluoride intake from water and beverages Maternal urinary fluoride and water fluoride/fluoride intake |
512q 400r (3–4) |
Yes | ↓ | Maternal exposure to higher levels of fluoride during pregnancy was associated with lower IQ scores in children aged 3 to 4 years |
Search criteria were: PubMed database for epidemiological studies published between January 2012 and August 2019 with the key words in the title/abstract including ‘fluoride’ and ‘IQ’ or ‘intelligence quotient’. In addition to the PubMed search, the reference lists of included studies were checked for further trials. Publications where the full text was not available in English or not published in a journal (master thesis, dissertations etc.) were excluded (see Online Resource 2)
BMI body mass index, CS cross-sectional, CWF community water fluoridation: water fluoridation in areas where water is artificially fluoridated with a precise dose of fluoride as a public health prevention measure, E endemic fluoride occurrence originating naturally in drinking water, (G)M (geometric) mean, IQ intelligence quotient, L longitudinal study, MUF maternal urinary fluoride, r(s) (partial) correlation coefficient, PC prospective cohort, ↓ increasing fluoride exposure adversely affected human intelligence, → no association between fluoride exposure and human intelligence
aSince in this observational study data obtained at one specific point in time was analyzed, this study was categorized as a cross-sectional study, although this was not specifically designated by the authors
bNo specific fluoride concentration was given in the publication. The authors stated that data of children from endemic fluorosis areas were compared to that of non-fluorosis areas. Children aged 8–12 who lived in coal-burning endemic fluorosis area in Bijie City of Guizhou Province were selected and divided into two groups according to the duration of comprehensive treatments given: long-term treatment group (Xiaba Village and Qianxixiang Zhongtun Village, furnace stove was changed and comprehensive control measure of health education was carried out for more than 3 years) and short-term treatment group (Chadi Village and Maoliping Village, stoves were improved and health education time < 1 year). The children who lived in a non-fluorosis area were selected as controls in 2012
cThe authors did not state on what basis they initially divided into “endemic fluorosis areas” and “non-fluorosis areas” (for controls), but the dental fluorosis examination of study participants revealed that the incidence rate for dental fluorosis was 0/104 in the “non-fluorosis areas” group and 505/637 in the “endemic fluorosis areas” group
dThis cohort study revealed a 38-year follow-up of participants
eThe IQ scores of the study participants were assessed in childhood (992 participants) and adulthood (942 participants). The childhood IQ for each study member was assessed at ages 7, 9, 11, and 13 years by means of the conducted IQ test. The IQs determined at these four ages were averaged into one measure and standardized. Adult IQ was individually assessed at age 38 years by means of the conducted IQ test
fAlthough water samples were taken from the high (Najafgarh) and low fluoride area (Defence Colony), the results were not given in the publication. The authors stated regarding the fluoride levels that there are various high fluoride areas in Delhi which include Palam village (1.2–32.5 mg/L), Nangloi (1.7–13.6 mg/L), Sagarpur (3.4–24.6 mg/L) and Najafgarh, where except for the control part the whole block is polluted
gAlthough water samples were taken, ranges of fluoride concentrations instead of specific results of the analysis were given in the publication
hThe fluoride exposure dose was calculated by fluoride concentration (mg/L) × amount water intake per day (L/day)/body weight (kg)
iThe authors stated that this is an interim analysis of an ongoing project
jNotably, this interim study statistically examined exclusively a relationship between fluorosis level and water fluoride and IQ and fluorosis level. However, the authors drew conclusions regarding the relationship between fluoride exposure and human intelligence
kNo specific fluoride concentration was given. The authors stated that by virtue of living in Mexico, individuals participating in the study have been exposed to fluoridated salt (at 250 mg/L) and to varying degrees of naturally occurring fluoride in drinking water. Previous reports, based on samples taken from different urban and rural areas, indicate that natural water fluoride levels in Mexico City may range from 0.15 to 1.38 mg/L. Mean fluoride content for Mexico City’s water supply is not available, because fluoride is not reported as part of water quality control programs in Mexico
lChild intelligence was measured by the General Cognitive Index (GCI) of the McCarthy Scales of Children’s Abilities at age 4 years and full scale intelligence quotient (IQ) from the Wechsler Abbreviated Scale of Intelligence (WASI) at age 6–12 years
mIn this study, child´s cognitive function is compared to each’s woman average of all her available creatinine-adjusted urinary fluoride concentrations during pregnancy (MUCcr). Creatinine-adjusted urinary fluoride concentrations were obtained for each maternally derived sample by dividing the fluoride concentration (MUF) in the sample by the sample’s creatinine concentration (MUC), and multiplying by the average creatinine concentration of samples available at each trimester (MUCaverage) using the formula: (MUF/MUC) × MUCaverage. For each woman, an average of all her available creatinine-adjusted urinary fluoride concentrations during pregnancy was computed and used as the exposure measure (MUFcr)
nThe authors stated that this is a pilot study that included 10% of the total sample and was utilized to check for the feasibility of the study. However, a follow-up study that refers to this pilot study could not be identified
oThe schooling performances were measured as the average score (%) [(100 × average mark)/total mark] and the high score prevalence (%) [(100 × no. of students scoring > 70%)/total no. of students] for each of eight subjects (Islamic studies I and II, Arabic, English, mathematics, sciences, history, and technology) and the overall score
pThe abbreviation DAI is not specified in the publication
qMeasurement of maternal urinary fluoride levels
rSelf-reported maternal daily fluoride intake from water and beverage consumption