Fluoridation and child IQ – the problem of counting chickens before they hatch

Image credit: Cherry-picking data – don’t get fooled by misleading statistics

It’s easy to find studies that confirm ones own bias on health issues. But cherry-picking such studies is unscientific because one could equally cite studies showing the exact opposite. The problem is these studies often rely on poor data, do not sufficiently account for confounding factors and often use poor statistical analysis so contradictory results are inevitable. A more objective requires a meta-analysis of all the available studies.

Anti-fluoride activists do this when they cherry-pick studies to argue that science has “proved” fluoride intake by pregnant women lowers the IQ of their children. These activists rely on just a few studies from two related groups – they cite Bashash et al (2107), Green et al (2019) and Till et al (2020). But what about studies that show the exact opposite – an increase in child IQ and the low fluoride intake relevant to community water fluoridation. Studies they ignore like those of Santa-Marina et al (2019) and Ibarluzea et al (2020).

The publication this month of new extensive data from an important study will be harder to ignore. This establishes a relationship of prenatal maternal intake of fluoride with the cognitive results for children in areas of Spain where community water fluoridation is used. In contrast to the negative results found in the studies anti-fluoride activists rely on, this new study reported: “Maternal fluoride levels were associated with better cognitive scores in childhood.”

Here is the citation for the new study:

Ibarluzea, J., Gallastegi, M., Santa-Marina, L., Jiménez Zabala, A., Arranz, E., Molinuevo, A., Lopez-Espinosa, M.-J., Ballester, F., Villanueva, C. M., Riano, I., Sunyer, J., Tardon, A., & Lertxundi, A. (2021). Prenatal exposure to fluoride and neuropsychological development in early childhood: 1-to 4 years old children. Environmental Research, 112181.

The figure below summarises the results for relationships of child cognitive scores with maternal prenatal urine – a measure of fluoride intake. cognitive scores are from McCarthy Scales tests appropriate for age 4. GCI is a General Cognitive Index.

The data points are for ß coefficients of the linear regressions of cognitive score against material urinary fluoride – the slope in units of amount of cognitive change per unit of urinary F (mg/L or equivalent). The bars are the 95% confidence intervals – if they include zero in the range this indicates the score is not beta value for the score is not statistically significant.

As we can see all the cognitive scores a positive and statistically significant for boys – hence the conclusion that “Maternal fluoride levels were associated with better cognitive scores in childhood.” However, none of the changes in scores for girls was statically different from zero

Don’t get me wrong. I am certainly not arguing that maternal intake of fluid will increase the cognitive levels of offspring male children. I am not attempting to confirm a pro-fluoride bias here. Remember, I said that objective assessment requires a meta-analysis of all the available studies.

The figure below shows the results of a meta-analysis of all the available studies which considered the relationship of the cognitive score with prenatal maternal urinary F.

As we can see, some of the beta values are positive and some are negative. Many are not significantly different from zero – any effect is not statistically signficant. Over all the studies, on average the score is positive (ß = 2.1 for 1 mg/L increase in urinary fluoride, or the equivalent measure) but not statistically significant from zero (95% confidence level is -1.9 to 6.1).

So the best objective conclusion to date is that child cognitive scores are not influenced by prenatal maternal fluoride intake at the levels expected in these studies which are relevant to community water fluoridation.

Conclusion

These studies illustrate the danger of cherry-picking studies to draw conclusions. or even simply taking the data from only a few studies that have so far been published. But that is what Grandjean et al (2021) have done in the benchmark analysis of cherry-picked studies. They concluded that a safe level for maternal urinary fluoride is as low as about 0.2 mg/l.

Image credit: Cherry-Picking

At best they counted their chickens before they had hatched, given that some important studies had not been published in scientific journals. At worst the cherry-picked to confirm a bias.

I suspect the latter because the important Spanish data had been published as conference papers so they should have been aware of them. The authors of the benchmark paper are all associated with the limited number of studies they considered (particularly those of Bashash et al (2107), Green et al (2019) and Till et al (2020)) and were members of just two groups obviously coordinating their work. Authors from this group have been very active in promoting their own findings, studiously ignoring the findings of voters and also using their work to promote the arguments of anti-fluoride activists against community water fluoridation.

Just imagine if some pro-fluoride activists chose to claim that fluoridation will actually increase child IQ and cherry-picked the Spanish studies to support their claim. I can’t actually see that happening, but if it did it would be as bad as the approach used by the authors of  Grandjean et al (2021).

This tactic of cherry-picking studies may be used to provide a scientific basis for activist arguments – but that is not true science.

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Yet another fluoride-IQ study

As with most of these fluoride-IQ studies this one is only relevant to areas of endemic fluorosis (This is from a UNESCO paper and has been corrected for New Zealand. Identification of fluorosis in a country does not imply the whole country is high fluoride).

Yes, it’s a bit like groundhog day. Another fluoride-IQ study – and we expect this to be followed by another round of claims by anti-fluoride propagandists that this is the death knell to community water fluoridation. That this study provides the “irrefutable proof” that fluoride is a “neurotoxin.”

But that interpretation is completely wrong. This new study does nothing of the sort – in fact, quite the opposite.

The new study is:

Duan, Q., Jiao, J., Chen, X., & Wang, X. (2017). Association between water fluoride and the level of children’s intelligence: a dose-response meta-analysis.  https://doi.org/10.1016/j.puhe.2017.08.013

Now, why is this study absolutely useless for those opposing community water fluoridation?

It is not relevant to community water fluoridation

Because it is about a problem in areas of endemic fluorosis – where fluoride dietary intakes are much higher than where community water fluoridation exists.

From its first sentence it concentrates on fluorosis:

“Fluorosis is a progressive degenerative disease that causes skeletal fluorosis and dental fluorosis.”

And

“Currently, about 500 million people are exposed to environments high in fluoride content, while the incidence of fluorosis has already reached 200 million people worldwide.”

It’s not new research – it’s a meta-analysis of existing studies. Only studies dealing with areas of endemic fluorosis are considered in the meta-analysis. For example, the New Zealand (Broadbent et al., 2014) and Canadian (Barberio et a., 2017) papers which actually studied effects on IQ of community water fluoridation are not included. Nor is the Swedish study (Aggeborn & Öhman, 2016) which considered drinking water fluoride concentrations similar to that used in community water fluoridation.  So far these are the only reliable studies which considered low fluoride concentrations and they all show no effect of fluoride on IQ.

It is concerned with health effects in areas of endemic fluorosis

The meta-analysis includes 26 published studies in the meta-analysis. Most of the papers refer to “high fluoride water,” “fluorosis areas,” “endemic fluorosis” or similar terms in their titles. Low fluoride areas were only considered in the studies as “controls” and studies from areas of community water fluoridation were excluded.

Most of the considered studies simply compared IQ levels in “low fluoride” areas and “high fluoride” areas.  The mean drinking water fluoride concentration in the low fluoride levels of these studies was 0.6 mg/L (0.25 – 1.03 mg/L) and in the high fluoride areas, the mean drinking water concentration was  3.7 mg/L (0.8 – 11 mg/L).

As you can see the control or low fluoride areas, where the studies assumed there were no effects on IQ, have drinking water concentrations similar to that used in community water fluoridation (usually about 0.7 or 0.8 mg/L).

Yes, these studies did show statistically significant differences in IQ levels between the low and high fluoride areas. This is something for health authorities in areas of endemic fluorosis to be concerned about. And this, together with a range of other known health effects of excessive dietary fluoride intake, is the reason why attempts are made to reduce the fluoride levels in drinking water supplies in those areas.

People in high fluoride areas where fluorosis is endemic suffer a range of health problems. Credit: Xiang (2014)

Duan et al (2018) were able to present an overall estimate of the IQ difference between high and low fluoride areas – see figure. This is expressed as a standardised mean difference (SMD) – a necessary measure for a meta-analysis of a range of studies with different variability. The SMD = (difference in mean outcome between groups/standard deviation of outcome among participants) (see Cochrane Handbook).

All of the studies show a lower IQ in high fluoride areas than in low fluoride areas with the overall SMD being 0.52 (-0.62, -0.42 95% confidence interval).

To be clear – this is not 0.52 IQ points but can be interpreted as 0.52 x the standard deviation of IQ  in a population. Unfortunately, the authors do nothing to explain this, leaving readers to make the same mistake many did with a previous IQ meta-study (see Did the Royal Society get it wrong about fluoridation?).

Attempt to derive a dose-response relationship

The authors went on to attempt to derive an overall response curve relating SMD to drinking water fluoride concentration. Unfortunately, their results as presented in their  Fig 4 are confusing and the figure is not properly explained. Also, the modeling methods used to derive the response curve is not well explained.

However, the linear relationship they derived was not statistically significant. (They were able to derive a significant non-linear relationship, but again their methods and reason for doing this were not explained.)

I got the relationship shown in the figure below using the data provided in the paper without further modeling. This relationship is also not statistically significant (p=0.77).

The authors do suggest the possibility that lower intelligence may be associated with medium fluoride concentrations and “that very high fluoride concentration in water was associated with higher intelligence level than
medium fluoride.” However, although the figure above implies that IQ increases at higher fluoride concentrations, I do not think such conclusions are warranted with this data and its variability.

What causes the cognitive deficits?

Authors of these studies often seem to assume a direct chemical fluoride toxicity cause for the cognitive deficit. That also appears to be an assumption behind the desire to produce a dose-response relationship. Of course, anti-fluoride propagandists also prefer this mechanism because it enables them to argue that the effects also occur at low concentrations – they just haven’t been measured yet.

Although a dose-response relationship would be expected for a chemical toxicity mechanism this study did not produce a reasonable dose-response relationship. Some individual studies have claimed such a relationship but these claims are often not supported or the reported relationship is of only minor significance (see my discussion of Xiang et al., 2003 in Perrott, 2018).

The poor or non-existent relationship of cognitive deficits to drinking water fluoride concentration makes me suspect that there is not a direct effect. Rather the real causes of the cognitive deficits observed are dental or skeletal fluorosis or other health effects common in areas of endemic fluorosis. I suggested this in comments on Choi et al.,(2015) who observed a relationship with severe dental fluorosis but not water concentration (see Perrott 2015 – Severe dental fluorosis and cognitive deficits).

There I suggested consideration of the effects of severe dental fluorosis on quality of life and learning difficulties on cognitive deficits.  Another factor could be premature births and low birth weights which are known to influence cognitive development (see Premature births a factor in cognitive deficits observed in areas of endemic fluorosis?)

Duan et al., (2018) in their paper also allude to such possible mechanisms:

“Skeletal fluorosis is another very common and very serious side-effect of high fluoride intake, characterized by changes in the bone density, skeletal deformation, rickets, paralysis, disability, and even death. Patients with skeletal fluorosis have been reported to show neuronal nuclear vacuoles formations, cell loss in the spinal cord, and loss or solidification of Nissl bodies. Moreover, patients experience fatigue, sleepiness, headache, dizziness, and other symptoms related to the nervous system.”

Conclusions

The meta-analysis does confirm that there may be a problem with reduced of intelligence in children in areas of endemic fluorosis. This difference in IQ levels between high and low water fluoride levels is statistically significant.

However, this finding is of absolutely no relevance to community water fluoridation where the drinking water levels are similar to that in the low fluoride areas in the studies used for the meta-analysis.

The summarised data does not appear to be of sufficient quality to determine a reliable dose-response relationship. At least, the derived relationships are not statistically significant. An alternative explanation is that the observed reduced intelligence may not be directly related to drinking water concentration and instead related to dental or skeletal fluorosis, or other health effects common in areas of endemic fluorosis.

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