Tag Archives: IQ

Anti-fluoridationists rejection of IQ studies in fluoridated area.

US anti-fluoride activist Paul Connett claims studies cannot detect an IQ effect from fluoridated water because total fluoride intake is the real problem – but still campaigns against community water fluoridation. Image credit: MSoF “Activist Spouts Nonsense – The Evidence Supports Fluoridation”

This is another article in my critique of the presentation Paul Connett prepared to present to a meeting at Parliament in February.

I deal with his coverage of the studies of IQ effects where community water fluoridation (CWF) is used. There are now actually three such studies (Broadbent et al. 2015, Barberio et al. 2017  and  Aggeborn & Öhman 2016), but Connett pretends there is only one – the Broadbent et al. (2015) New Zealand study.

Maybe because it was the first one to provide evidence challenging his extrapolation of the fluoride/IQ studies (see The 52 IQ studies used by anti-fluoride campaigners) results in areas of endemic fluorosis to areas where CWF is used. It is also the study which seems to have resulted in the most hostility from anti-fluoride campaigners.

So here I will just be sticking with his criticism of the New Zealand study Broadbent et al (2015):

Slide 76 from Paul Connett’s presentation prepared for his February meeting at  parliament buildings

Broadbent’s findings do not “negate all other human studies”

Paul allows emotion to get the better of him as no one is suggesting this at all. The studies Connett refers to are all from areas of endemic fluorosis (see  The 52 IQ studies used by anti-fluoride campaigners), not from areas of CWF.

Broadbent et al (2015) simply concluded that their “findings do not support the assertion that fluoride in the context of CWF programmes is neurotoxic.”  That is a modest statement and Broadbent et al. (2015) simply do not draw any conclusions about the studies Connett relies on. But, of course, Connett is upset because this and similar studies just do not support his attempt to extrapolate results from areas of endemic fluorosis to areas of CWF.

The health problems suffered by people in areas of endemic fluorosis are real and it is right they should be studied and attempts made to alleviate them. But this has absolutely nothing to do with CWF.

“Fatally flawed” charge is itself fatally flawed

Again, Paul has allowed emotions to get the upper hand. It is possible, and necessary, to critique published papers – but critiques should be evidence-based and realistic. Paul’s “fatally flawed” charge (slides 77 & 78) simply displays how much this paper has put his nose out of joint.

But let’s look at the specific “flaws” Paul (and other critics associated with the Fluoride Action Network) claim.

The two villages mindset: Paul alleges that the Broadbent et al (2015) study “essentially compared two groups.” He is stuck in the mindset of most of his 52  studies from areas of endemic fluorosis (see  Fluoride & IQ: The 52 Studies). The mindset of simply comparing the IQ levels of children in a village suffering endemic fluorosis with the IQ levels of children in a village not suffering endemic fluorosis. This simple approach can identify statistically significant differences between the villages but provides little information on causes. For example, most of these studies used drinking water fluoride as a parameter but there could be a whole range of other causes related to health problems of fluorosis.

Professor Richie Poulton, current Director of the Dunedin Multidisciplinary Health and Development Research Unit

In contrast, Broadbent et al. (2015) used “General Linear models to assess the association between CWF and IQ in childhood and adulthood, after adjusting for potential confounders.” The statistical analysis involved includes accounting for a range of possible risk-modifying factors besides CWF., This was possible because the study was part of the Dunedin Multidisciplinary Health and Development Study. This is a highly reputable long-running cohort study of 1037 people born in 1972/1973 with information covering many areas.

The fluoride tablets argument: Connett and other critics always raise this issue – the fact that “In New Zealand during the 1970s, when the study children were young, F supplements were often prescribed to those living in unfluoridated areas.” Often they will go further to claim that all the children in the unfluoridated area of this study were receiving fluoride tablets – something they have no way of knowing.

But the fact remains that fluoride tablets were included in the statistical analysis. No statistically significant effect was seen for them.  Overlap of use of fluoride tablets with residence in fluoridated or unfluoridated areas will have occurred and their influence would be reflected in the results found. Presumably, the effect would be to increase the confidence intervals. As the critics, Menkes et al. (2014), say “comparing groups with overlapping exposure thus compromises the study’s statistical power to determine the single effect of CWF.”  I agree. But this does not negate the findings which are reported with the appropriate confidence intervals (see below).

The point is that the simplistic argument that effects of fluoride tablets were ignored is just not correct. Their effect is reflected in the results obtained.

Potential confounders: Many poor quality studies have ignored possible confounders, or considered only a few. This is a general problem with these sort of studies – and even when attempts are made to include all that the researchers consider important a critic can always claim there may be others – especially if they do not like the results. Claims of failing to consider confounders can often be simply the last resort of armchair critics.

In this case, there is no actual reported association to be confounded (unlike my identification of this problem with the Malin & Till 2015 ADHD study – see Perrott 2017). However, Osmunson et al. (2016) specifically raised possibilities of confounding by lead, manganese, mother’s IQ and rural vs urban residence. Mekes et al. (2014) also raised the rural vs urban issue as well as a possible effect from breastfeeding reducing fluoride intake by children in fluoridated areas.  In their response, Broadbent et al (2015b & 2016) reported that a check showed no significant effect of lead or distance from the city centre and pointed out that manganese levels were too low to have an effect. Broadbent et al (2015b) also reported no significant breastfeeding-fluoride interaction occurred.

Numbers involved: Connett claims the study was fatally flawed because “it had very few controls: 991 lived in the fluoridated area, and only 99 in non-fluoridated” (Slide 77). But the numbers are simply given by the longer term Dunedin study themselves – they weren’t chosen by Broadbent and his co-workers. That is the real world and is hardly a “fatal flaw.”

The 95% confidence intervals

Yes, statisticians always love to work with the large numbers but in the real world, we take what we have. Smaller numbers mean less statistical confidence in the result – but given that Broadbent et al (2015) provides the results, together with confidence intervals, it is silly to describe this as fatally flawed. These were the results given in the paper for the parameter estimate of the factors of interest:

Factor Parameter estimate 95% Confidence interval p-value
Area of residence -0.01 -3.22 to 3.20 .996
Fluoride toothpaste use 0.70 -1.03 to 2.43 .428
Fluoride tablets 1.55 -0.38 to 3.49 .116

Connett did not refer to the confidence intervals reported by Broadbent et al (2015). However, Grandjean and Choi (2015) did describe them as “wide” – probably because they were attempting to excuse the extrapolation of “fluoride as a potential neurotoxic hazard” from areas of endemic fluorosis to CWF.

The argument over confidence intervals can amount to straw clutching – a “yes but” argument which says “the effect is still there but is small and your study was not large enough to find it.” That argument can be never ending but it is worth noting that Aggeborn & Öhman (2016) made a similar comment about wide confidence intervals for all fluoride/IQ studies, including that of Broadbent et al. (2015).  Aggeborn & Öhman (2016) had a very large sample (almost 82,000 were involved in the cognitive ability comparisons) and reported confidence intervals of -0.18 to 1.03 IQ points (compared with -3.22 to 3.20 IQ points reported by Broadbent et al 2015). Based on this they commented, “we are confident to claim that we have estimated a zero-effect on cognitive ability.”

The “yes but” argument about confidence intervals may mean one is simply expressing faith in an effect so small as to be meaningless.

Total fluoride exposure should have been used: Connett says (slide 77) “Broadbent et al did not use the proper measure of fluoride exposure. They should have used total F exposure.  Instead, they used only exposure from fluoridated water.” Osmunson et al. (2016) make a similar point, claiming that the study should not have considered drinking water fluoride concentration but total fluoride intake. They go so far as to claim “the question is not whether CWF reduces IQ, but whether or not total fluoride intake reduces IQ.”

This smacks of goalpost moving – especially as the argument has specifically been about drinking water fluoride and most of the studies they rely on from areas of endemic fluorosis specifically used that parameter.

In their response to this criticism Broadbent et al (2016) calculated estimates for total daily fluoride intake and used them in their analysis which “resulted in no meaningful change of significance, effect size, or direction in our original findings.”

It’s interesting to note that Connett and his co-workers appear to miss completely the point about “wide” confidence intervals made by Grandjean and Choi (2015). Instead, they have elevated their argument to the claim that fluoride intake is almost the same in both fluoridated and unfluoridated areas so that any study will not be able to detect a difference in IQ. Essentially they are claiming that we are all going to suffer IQ deficits whether we live in fluoridated or unfluoridated areas.

This is the central argument of their paper – Hirzy et al (2016). However, the whole argument relies on their own estimates of dietary intakes – a clear example where motivated analysts will make the assumptions that fit and support their own arguments. This argument also fails to explain why the Dunedin study found lower tooth decay in fluoridated areas.

Last time I checked the anti-fluoride campaigners, including Connett, were still focusing on CWF – fluoride in drinking water. One would think if they really believed their criticism that they would have given up that campaign and instead devoted their energies to the total fluoride intake alone.

Conclusions

All studies have limitations and of course, Broadbent et al. (2015) is no exception. However, the specific criticisms made by Connett and his fellow critics do not stand up to scrutiny. Most have been responded to and shown wrong – mind you this does not stop these critics from continuing to repeat them and disregard the responses.

I believe the relatively wide confidence intervals could be a valid criticism – although it does suggest a critic who is arguing for very small effects. A critic who may always find the confidence intervals still exclude their very small effect – no matter how large the study is.

In effect, the narrow confidence intervals reported by Aggeborn & Öhman (2016) should put that argument to rest for any rational person.

References

Aggeborn, L., & Öhman, M. (2016). The Effects of Fluoride In The Drinking Water

Barberio, A. M., Quiñonez, C., Hosein, F. S., & McLaren, L. (2017). Fluoride exposure and reported learning disability diagnosis among Canadian children: Implications for community water fluoridation. Can J Public Health, 108(3),

Broadbent, J. M., Thomson, W. M., Ramrakha, S., Moffitt, T. E., Zeng, J., Foster Page, L. A., & Poulton, R. (2015). Community Water Fluoridation and Intelligence: Prospective Study in New Zealand. American Journal of Public Health, 105(1), 72–76.

Broadbent, J. M., Thomson, W. M., Moffitt, T., Poulton, R., & Poulton, R. (2015b). Health effects of water fluoridation: a response to the letter by Menkes et al. NZMJ, 128(1410), 73–74.

Broadbent, J. M., Thomson, W. M., Moffitt, T. E., & Poulton, R. (2016). BROADBENT ET AL. RESPOND. American Journal of Public Health, 106(2), 213–214. https://doi.org/10.2105/AJPH.2015.302918

Grandjean, P., Choi, A. (2015). Letter: Community Water Fluoridation and Intelligence. Am J Pub Health, 105(4).

Hirzy, J. W., Connett, P., Xiang, Q., Spittle, B. J., & Kennedy, D. C. (2016). Developmental neurotoxicity of fluoride: a quantitative risk analysis towards establishing a safe daily dose of fluoride for children. Fluoride, 49(December), 379–400.

Malin, A. J., & Till, C. (2015). Exposure to fluoridated water and attention deficit hyperactivity disorder prevalence among children and adolescents in the United States: an ecological association. Environmental Health, 14.

Menkes, D. B., Thiessen, K., & Williams, J. (2014). Health effects of water fluoridation — how “ effectively settled ” is the science? NZ Med J, 127(1407), 84–86.

Osmunson, B., Limeback, H., & Neurath, C. (2016). Study incapable of detecting IQ loss from fluoride. American Journal of Public Health, 106(2), 212–2013.

Perrott, K. W. (2017). Fluoridation and attention deficit hyperactivity disorder – a critique of Malin and Till ( 2015 ). Br Dent J.

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A conference paper on the maternal neonatal urinary fluoride/child IQ study has problems

Image credit: Do new mothers doing a Ph.D. get enough support?

The anti-fluoride movement has certainly mobilised over the neonatal maternal urinary fluoride study which reported an association with child IQ. They see it as the best thing since sliced bread and believe it should lead to the end of fluoridation worldwide.

They also seem to be putting all their eggs in this one basket and have started a campaign aimed at stopping pregnant women from drinking fluoridated water (See Warning to Pregnant Women: Do Not Drink Fluoridated Water).

So I was not surprised to see a newsletter this morning from the Fluoride Action Network reporting another output from this study – a conference paper (most likely a poster) presented at the  3rd Early Career Researchers Conference on Environmental Epidemiology. The meeting was in Freising, Germany, on 19-20 March 2018.

I had been aware of the poster for the last week so had expected FAN to gleefully jump on it and start promoting it in their campaigns.

Here is a link to the abstract:

Thomas, D., Sanchez, B., Peterson, K., Basu, N., Angeles Martinez-Mier, E., Mercado-Garcia, A., … Tellez-Rojo, M. M. (2018). Prenatal fluoride exposure and neurobehavior among children 1-3 years of age in Mexico. Occupational and Environmental Medicine, 75(Suppl 1), A10–A10.

It’s only an abstract and it may be some time before a formal paper is published, if at all. Posters do not get much in the way of peer review and often not followed by formal papers.  So I can’t say much about the poster at this stage as I never like to make an assessment of studies on the basis of abstracts alone.

But, in this case, I have Deena Thomas’s Ph.D. thesis which was the first place the work was reported. If you are interested you can access it from this link:

Thomas, D. B. (2014). Fluoride exposure during pregnancy and its effects on childhood neurobehavior: a study among mother-child pairs from Mexico City, Mexico. University of Michigan.

I will wait for a formal paper before properly critiquing the poster, but at the moment I find a big discrepancy between the Thesis conclusions and the conclusions presented in the poster abstract.

Thesis conclusions

In her work, Deena Thomas used the Mental Development Index (MDI) which is an appropriate way of determining neurobehavioral effects in young children.

She concluded in her thesis (page 37):

“Neither maternal urinary or plasma fluoride was associated with offspring MDI scores”

And (page 38):

“This analysis suggests that maternal intake of fluoride during pregnancy does not have a strong impact on offspring cognitive development in the first three years of life.”

And further (page 48):

“Maternal intake of fluoride during pregnancy does not have any measurable effects on cognition in early life.”

So – no association found of child MDI score with maternal neonatal urinary F concentrations.

Poster conclusions

But the poster tells a different story.

The abstract concluded:

“Our findings add to our team’s recently published report on prenatal fluoride and cognition at ages 4 and 6–12 years by suggesting that higher in utero exposure to F has an adverse impact on offspring cognitive development that can be detected earlier, in the first three years of life.”

So her conclusions reported in her thesis are exactly the opposite of the conclusions reported in her conference poster!

What the hell is going on?

The data

Obviously, I do not have access to the data and she does not provide it in her thesis. But from her descriptions of the data in her thesis and her poster perhaps we can draw some tentative conclusions.

The table below displays the data description, and a description of the best-fit line determined by statistical analysis, in her thesis and her poster.

Information on data Thomas Ph.D. Thesis Conference abstract
Number of mother/child pairs 431 401
Maternal Urinary F range (mg/L) 0.110 – 3.439 0.195 – 3.673
Mean maternal urinary F (mg/L) 0.896 0.835
Model β* -0.631 -2.40
Model p-value 0.391 – Not significant
95% CI for β -4.38 to -0.40

*β is the coefficient, or slope, of the best-fit line

Conclusions

Apparently at least 30 data pairs have been removed from her thesis data to produce the dataset used for her poster. Perhaps even some data pairs were added (the maximum urinary F value is higher in the smaller data set used for the poster).

This sort of change in the data selected for the statistical analysis could easily swing the conclusion from no effect to a statistically significant effect. So the reasons for the changes to the dataset are of special interest.

Paul Connett claims this poster “strengthens” the findings reported in the Bashash paper.  He adds:

“This finding adds strength to the rapidly accumulating evidence that a pregnant woman’s intake of fluoride similar to that from artificially fluoridated water can cause a large loss of IQ in the offspring.”

But this comes only by apparently removing the conflicting conclusions presented in Deela Thomas’s Ph.D. thesis. We are still left with the need to explain this conflict and why a significant section of the data was removed.

To be clear – I am not accusing Thomas et al. (2018) of fiddling the data to get the result they did. Just that, given the different conclusions in her thesis and the poster,  there is a responsibility to explain the changes made to the dataset.

From the limited information presented in the poster abstract, I would think the scatter in the data could be like that seen in the Bashash et al. (2017) paper. The coefficient of the best fit line (β) is relatively small and while the 95% CI indicates the fit is statistically significant its closeness to zero suggest that it is a close thing.

However, let’s look forward to getting better information on this particular study either through correspondence or formal publication of a research paper.

Other articles on the Mexican study

Fluoride, pregnancy and the IQ of offspring,
Maternal urinary fluoride/IQ study – an update,
Anti-fluoridation campaigners often use statistical significance to confirm bias,
Paul Connett “updates” NZ MPs about fluoride?
Paul Connett’s misrepresentation of maternal F exposure study debunked,
Mary Byrne’s criticism is misplaced and avoids the real issues

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The 52 IQ studies used by anti-fluoride campaigners

Slide number 30 from Paul Connett presentation prepared for a talk at NZ Parliament buildings in February 2018.

Continuing my critique of the presentation prepared by Paul Connett for his much-publicised meeting at Parliament Building in February. The meeting attracted only three MPs but his presentation is useful as it presents all the arguments anti-fluoride campaigners rely on at the moment.

My previous articles on this presentation are Anti-fluoride activist commits “Death by PowerPoint” and Paul Connett’s misrepresentation of maternal F exposure study debunked.

In this article, I deal with the argument presented in the slide above. it is an argument repeated again and again by activists. Connett has posted a more detailed list of these studies and his description of them in Fluoride & IQ: The 52 Studiesat the Fluoride Action Network website.

Studies in areas of endemic fluorosis

All the 52 studies comment refers to are from regions of endemic fluorosis in countries like India, China, Mexico and Iran where dietary fluoride intake is above the recommended maximum level. People in these areas suffer a range of health problems and studies show cognitive deficits as one of them. However, a quick survey of Google Scholar shows this concern is well down the list (See Endemic fluorosis and its health effects). Only 5% of the Google Scholar hits related to health effects of endemic fluorosis considered IQ effects.

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

In, most, but not all, cases the major source of fluoride in the diet is drinking water with high fluoride levels (above the WHO recommended 1.5 mg/L). Paul Connett’s logic is simply to extrapolate to low drinking water fluoride concentrations typical of community water fluoridation (CWF). However, we do not see the other health effects like severe dental fluorosis, skeletal fluorosis, etc., where CWF is used.

His logic also ignores the possibility that cognitive deficits may result from other health problems common in areas of endemic fluorosis. Problems such as premature births and low birth weight, skeletal fluorosis or even the psychological effect of unsightly teeth due to severe dental fluorosis.

Comparing “high” fluoride villages with “low” fluoride villages

This approach is simplistic as it simply compares a population suffering fluorosis with another population not. Yes, the underlying problem is the high dietary intake (mainly from drinking water) in the high fluoride villages – but that does not prove fluoride in drinking water is the direct cause of a problem. The examples discussed above, eg., low birth weights or premature births, could be the direct cause.

It is easy to show statistically significant differences of drinking water fluoride and a whole host of fluorosis related diseases between two villages but that, in itself, does not prove that drinking water fluoride is the direct cause. Nor does it justify extrapolating such results to other low concentrations situations typical of CWF.

Paul Connett’s logic ignores the fact that in most of these studies the “low” fluoride villages (which the studies were treating as the control or normal situations where IQ deficits did not occur) had drinking water fluoride concentrations like that used in CWF. It also ignores, or unjustly attempts to dismiss) studies which show no cognitive deficits related to CWF.

A low fluoride concentration study showing an IQ effect

After making a big thing about the large numbers of studies and being challenged by the high fluoride concentrations involved Connett normally goes into a “yes, but” mode and attempts to transfer that credibility of “large numbers” to the very few studies which report effects at low fluoride concentrations.

He usually makes a big thing of the study by Lin et al (1991):

Lin Fa-Fu, Aihaiti, Zhao Hong-Xin, Lin Jin, Jiang Ji-Yong, M. (1991). THE RELATIONSHIP OF A LOW-IODINE AND HIGH- FLUORIDE .ENVIRONMENT TO SUBCLINICAL CRETINISM lN XINJIANG. Iodine Deficiency Disorder Newsletter, 24–25.

Connett claims this study shows a lower IQ when the drinking water F concentration was 0.88 ppm, but the areas suffered from iodine deficiency which is related to cognitive deficits.

The study I reviewed recent by Bashash et al (2017) (see Paul Connett’s misrepresentation of maternal F exposure study debunked) is also on Connett’s list. He doesn’t mention, however, that while an association of child IQ with prenatal maternal urinary fluoride was reported the paper also reported there was no observed association of child IQ with child urinary fluoride concentrations.

Studies not showing an effect

Connett lists 7 studies which showed no effect on IQ. One of these was the well-known Broadbent et al., (2014) study from New Zealand, which he, of course, proceeds to debunk in an irrational and not very truthful manner.

He does not mention the studies from Canada (Barberio et al. 2017 ) and Sweden (Aggeborn & Öhman 2016) which also show no effect of CWF on IQ.

The 6 other studies listed are all Chinese, and not translated. Interesting because Connett’s Fluoride Action Network invested money and time into translating obscure Chinese papers that could support their argument of harm. They obviously did not bother translating those papers which did not confirm their bias.

Conclusion

So, Connett’s 52 studies are rather a waste of time. Based in areas of endemic fluorosis their findings are not transferable to areas where CWF is used. The quality of most papers is low and, usually, the studies are simply a comparison of two villages, one where fluorosis is endemic and the “control” village where it isn’t but drinking water concentrations are like that used in CWF.

Connett simply is not able to properly evaluate, or in some cases even consider, studies which show no effect of fluoride on IQ or were made in areas where CWF exists and no effects are shown.

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Paul Connett “updates” NZ MPs about fluoride?

Data from Bashash et al., (2017). Despite a statistically significant relationship of child IQ with mothers prenatal urinary fluoride, this explains only about 3% of the huge scatter in the data.

I haven’t followed the latest speaking tour of Paul Connett – organised by the local Fluoride Free NZ organisation. But I watched a TV interview with him this morning and came away thinking he is skating on very thin ice – scientifically. He has put all his eggs in one basket – promoting a Mexican study as the be-all and end-all of scientific research which should lead to the immediate ceasing of community water fluoridation.

Paul is a leader of the anti-fluoride activist group the Fluoride Action Network and appears to love visiting New Zealand during our summer (and his winter). Local campaigners seem to idolise him – and rely heavily on him as a self-declared  “world expert on fluoridation.” But this idol has feet of clay (don’t they all?).

In fact, Paul has no original research on fluoride and is simply presenting a biased picture of the scientific literature on the subject., He relies heavily on his academic status and qualifications to give his biased views respectability.

But back to the Mexican study. Paul is referring to this paper:

Bashash, M., Thomas, D., Hu, H., Martinez-mier, E. A., Sanchez, B. N., Basu, N., … Hernández-avila, M. (2016). Prenatal Fluoride Exposure and Cognitive Outcomes in Children at 4 and 6 – 12 Years of Age in Mexico.Environmental Health Perspectives, 1, 1–12.

I have written about this study in some detail in my articles:

Here I will simply return to the poor explanatory power of fluoride for the children’s IQ measured in the study.

The graph above is a plot of the data from the paper – child IQ compared with the pre-natal urinary fluoride levels of the mothers.

Now, Paul describes this study as “rigorous” and relies heavily on it. But despite a statistically significant relationship, the huge scatter in the data really stands out.

In fact, this relationship explains only about 3% of this scatter! It probably only appears because the researchers did not include any proper risk-modifying factors in their regression analysis.

Well, Paul is making a big thing of speaking to New Zealand MPs tonight to “update” them on this latest research. Rather smug because it implies the research is his – when it isn’t.

But this research does not “prove” what Connett implies. It is not as rigorous as he claims. And it is certainly not an argument to stop community water fluoridation in New Zealand.


Note: Paul Connett and I had a scientific exchange on the fluoridation issue four years ago. Interested readers can download the full text from Researchgate –  The fluoride debate.

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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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Anti-fluoridation campaigners often use statistical significance to confirm bias

I was pleased to read this Nature article – Five ways to fix statistics – recently as it mirrors my concern at the way statistical analysis is sometimes used to justify or confirm a bias and not reveal a real causal relationship. Frankly these days I just get turned off by media reports of studies showing statistically significant relationships as evidence for or against the latest health or other fads.

As the Nature article says, statistical significance tests often amount “to uncertainty laundering:”

“Any study, no matter how poorly designed and conducted, can lead to statistical significance and thus a declaration of truth or falsity. NHST [null hypothesis significance testing] was supposed to protect researchers from over-interpreting noisy data. Now it has the opposite effect.”

No matter how good a relationship appears, or how significant the statistical analysis shows it to be, it is simply a relationship and may have no mechanistic or causal backing.  An example often used to illustrate this is the close relationship between the prevalence of autism and sales of organic produce.

Clearly statically significant but we don’t find those activists claiming autism is related to one thing or another ever citing this one. I am picking these activists may well have a bias towards organic produce.

Here are several examples I have discussed before which illustrates how “statistical significance” is sometimes used to confirm bias in fluoridation studies. I think these are very relevant as anti-fluoridation campaigners often cite statistical significance as if it is the final proof for their claims.

Ignoring relevant confounders

This is an easy trap for the biased researcher (and let’s face it, most of us are biased – it’s only human). Just ignore other confounders or risk-modifying factors that may be more important. Or ignore the fact that the risk-modifying factor one is interested in (in this case fluoride) may just be acting as a proxy for (and therefore is related to) something else which is more relevant.

This why all credible risk-modifying factors should be considered in correlation studies. They should be included in the statistical analyses.

It’s amazing how many researchers either ignore the possible risk-modifying factors besides their pet one – or pay lip-service to the problem by limiting their consideration to only a small range of such factors.

Examples of studies promoted by anti-fluoride campaigners where this is a problem include:

Peckham et al., (2015) hypothyroidism paper:

Peckham, S., Lowery, D., & Spencer, S. (2015). Are fluoride levels in drinking water associated with hypothyroidism prevalence in England? A large observational study of GP practice data and fluoride levels in drinking water. J Epidemiol Community Health, 1–6.

This has been widely condemned for a number of reasons – one of which is that iodine deficiency, a known factor in hypothyroidism, was not included in the statistical analysis.

(See Paper claiming water fluoridation linked to hypothyroidism slammed by experts and Anti-fluoride hypothyroidism paper slammed yet again).

The  Takahashi et al., (2001) cancer paper:

Takahashi, K., Akiniwa, K., & Narita, K. (2001). Regression Analysis of Cancer Rates and Water Fluoride in the USA based Incidence on IACR / IARC ( WHO ) Data ( 1978-1992 ). Journal of Epidemiology, 11(4), 170–179.

These authors reported an association between fluoridation and a range of cancers. Problem is, they did not consider any other risk-modifying factors. When some geographical parameters were included in the statistical analyses there were no statistically significant relationships of cancer with fluoridation.

(see Fluoridation and cancer).

The Malin & Till (2015) ADHD paper:

Malin, A. J., & Till, C. (2015). Exposure to fluoridated water and attention deficit hyperactivity disorder prevalence among children and adolescents in the United States: an ecological association. Environmental Health, 14.

This reported an association of ADHD prevalence with the extent of fluoridation in the US. Anti-fluoride campaigners have cited this paper a lot because it is the only study indicating any effect of fluoridation on cognitive ability. All other studies they rely on were from areas of endemic fluorosis where the natural levels of fluoride are higher than that used in community water fluoridation.

Malin & Till (2015) considered only household income as a possible risk-modifying factor. No consideration was given to residential elevation which other researchers had around the same time reported as associated with ADHD prevalence.

I repeated their statistical analysis but included residential elevation and a range of other risk-modifying factors. This showed there was no statically signficant association of ADHD with fluoridation when other risk-modifying factors, particularly elevation, were included. My critique of Malin and Till (20215) is now published:

Perrott, K. W. (2017). Fluoridation and attention deficit hyperactivity disorder – a critique of Malin and Till ( 2015 ). Br Dent J.

(See ADHD linked to elevation not fluoridationADHD link to fluoridation claim undermined again and Fluoridation not associated with ADHD – a myth put to rest).

Ignoring the lack of explanatory power

I think this is where the over-reliance on statistical significance, the p-value, can be really misleading. Researchers desperately wishing to confirm their bias will proudly claim  a statistically significant relationship, a p-value less than 0.05, etc., as if that is the final “proof.” These researchers will often hide the real meaning of their relationship by not making the actual data available or limiting their report of their statistical analysis to p-vlaues and, maybe, a mathematical relationship.

However, if the reported relationship actually explains only a small part of the observed variation in the data it may be meaningless. Concentration on such a relationship means that other more signficant risk-modifying factors which would explain more of the variation are ignored. Anyway, where a factor explains only a small part of the variation it is likely a more complete statistical analysis would show that its contribution was not actually statistically signficant.

Some examples:

The prenatal fluoride exposure and IQ study of Bashash et al (2017):

Bashash, M., Thomas, D., Hu, H., Martinez-mier, E. A., Sanchez, B. N., Basu, N., … Hernández-avila, M. (2016). Prenatal Fluoride Exposure and Cognitive Outcomes in Children at 4 and 6 – 12 Years of Age in Mexico.Environmental Health Perspectives, 1, 1–12.

These authors reported a statistically significant association of Child IQ with the prenatal fluoride exposure of their mothers. However, their figures showed a very wide scatter in the data indicating very little explanation of the variation in child IQ by the association with prenatal fluoride. (see below left). This must be why the Fluoride Action Network removed the data points from the figure when reproducing it for their promotion of the paper (see below right).

Bashash et al., (29017) did not give the complete statistical analysis of their data. However, I was able to digitally extract the data from their figure and my analysis showed that prenatal fluoride expose was only able to explain a little over 3% of the variation in child IQ. So, despite the statistical significance of their observed relationship prenatal fluoride exposure is unlikely to be a real factor in child IQ. In fact, concentration on this minor (even if statistically significant) factor will only inhibit the discovery of the real causes of IQ variation in these children.

Yes, anti-fluoride campaigners will protest that this study did consider some other possible risk-modifying factors. However the very low-level of explanation of the variation in the data indicates they did not consider enough.

(see Premature births a factor in cognitive deficits observed in areas of endemic fluorosis? Fluoride, pregnancy and the IQ of offspring and Maternal urinary fluoride/IQ study – an update).

The Xiang et al., (2003) water fluoride and IQ study:

Xiang, Q; Liang, Y; Chen, L; Wang, C; Chen, B; Chen, X; Zhouc, M. (2003). Effect of fluoride in drinking water on children’s intelligence. Fluoride, 36(2), 84–94.

Anti-fluoride campaigners rely a lot on this and other papers from this group.  Even though this research involved areas of endemic fluorosis it, in a sense, provides some of their best evidence because they reported a dose-dependent relationship of IQ to water F. Xiang et al., (2003) claimed a statistically signficant association of child IQ to fluoride water levels.  Other anti-fluoride campaigners, and some other researchers, have cited Xiang et al., (2003) to support such an association.

I don’t question these researchers found a significant association – but there is a problem. Nowhere do they give a statistical analysis or the data to support their claim! Very frustrating for critical readers (and we should all be critical readers).

They did, however, give some evidence from a statical analysis of the relationship of IQ with urinary fluoride. They did not give a complete statistical analysis but they included the data in a figure  (see below) – so I did my own statistical analysis of data digitally extracted from the figure.

The figure shows a high scatter of data points so this is another case of a statistically significant relationship explaining only a small part of the variability. My analysis indicates the relationship explains only about 3% of the variability in IQ value. Another case where researchers have concentrated on their own pet relationship and in the process not properly searched for more reasonable risk-modifying factors capable of explaining a larger proportion of the variation.

I have made a more detailed critique of Xiang et al.  (2015) and Hirzy et al., (2016) which relies on this data (see Does drinking water fluoride influence IQ? A critique of Hirzy et al. (2016)). A paper based on this has been submitted to a journal for publication and is currently undergoing peer review..

(see Anti-fluoride authors indulge in data manipulation and statistical porkiesDebunking a “classic” fluoride-IQ paper by leading anti-fluoride propagandists,  Connett fiddles the data on fluorideConnett & Hirzy do a shonky risk assesment for fluoride and Connett misrepresents the fluoride and IQ data yet again).

Conclusion

This  briefly outlines the statistical problems of a number of papers anti-fluoride campaigners rely on. Two common problems are:

  • Insufficient consideration of confounders or other risk-modifying factors – indicating a bias towards a “preferred” cause, and
  • Reliance on a relationship that, although statistically significant, explains only a very small fraction of the observed variation – again indicating bias towards a “preferred” cause

I don’t for a minute suggest that only those researchers publishing “anti-fluoride” research are guilty of these errors. They are probably quite common. Authors will generally responsibly warn that “correlation does not prove causation” and suggest more work needs to be done including  consideration of a wider number of confounders or risk-modifying factors. However, bias is only human so researcher advocacy for their own findings is understandable. The published research may even be of general value if readers interpret it critically and intelligently.

However, in the political world such critical consideration is very rare. Activists will use published research in the way a drunk uses a lamppost – more for support than for illumination. This makes it important that the rest of us be more objective and critically assess the claims they are making. Part of this critical assessment must include an objective consideration of the published research that is being cited.

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Endemic fluorosis and its health effects

Much of the anti-fluoridation propaganda used by activists rely on studies done in areas of endemic fluorosis. Slide from a presentation by Q. Xiang to an anti-fluoride meeting organised by Paul Connett’s Fluoride Action Network in 2014.

 

The public debate in New Zealand might convince the casual reader that all the science related to fluoride revolves around tooth decay and IQ. But that is certainly not the case on a world scale.

The World Health Organisation gives guidelines for the concentration of fluoride in drinking water recommending it should be in the range 0.5 – 1.5 mg/L. OK, above 0.5 mg/L because of the positive effect it has on oral health, in reducing dental decay. That interests us in New Zealand because our drinking water is more likely to be deficient in fluoride.

But on the world scale, many people are far more interest in the higher limit – or at least in attempting to reduce their drinking water fluoride concentration to below this limit. This is because large areas of the world suffer from the health effects of endemic fluorosis due to the excessive dietary intake of fluoride and the high concentration in their drinking water.

There are significant health effects from endemic fluorosis – effects we don’t’ have here but are important to many countries. So there is plenty of research – both on the health effects and on reducing drinking water concentrations and dietary intake.

In fact, the anti-fluoride campaigners get all the scientific reports they use in “evidence” to oppose community water fluoridation from studies in countries where fluorosis is endemic. Not only is this misrepresenting the science. It is also unbalanced because scientific studies on IQ in areas of endemic fluorosis represent only a small proportion of such health-related studies.

To illustrate this I have done a number of searches on Google Scholar using the terms “endemic fluorosis” and one other term related to a health effect. Here is the resulting table.

“endemic fluorosis” and “?” Hits in Google Scholar
Alone 8810
And “dental fluorosis” 3570
And “bone” 3570
And “skeletal fluorosis” 2910
And “cancer” 1690
And “death” 1180
And “birth” 1170
And “osteoporosis” 1130
And “body weight” 936
And “gastrointestinal” 808
And “Osteoclerosis 697
And “diabetes” 642
And “cardiovascular” 633
And “reproduction” 592
And “IQ” 480
And “cognitive” 331
And “heart disease” 327
And “hypothyroidism” 297
And “Renal failure” 292
And “obesity” 230
And “infertility” 216
And “non-skeletal fluorosis” 183
And “muscoskeletal” 178
And “birth weight” 135
And “birth defects” 86
And “premature birth” 29

40% of the hits related to “dental fluorosis” and another 40% to “bone” while 33% related to “skeletal “fluorosis.” Obviously, these are of big concern in areas of endemic fluorosis so receive a lot of research attention. In fact, the prevalence of these is used to define an area as endemic.

But only 5% of hits related to IQ – clearly of much less concern to researchers. Yet it seems to be all we hear about here and this illustrates how unbalanced most of the media reports we get here are.

To start with, these health effects do not occur in countries like New Zealand using community water fluoridation. They occur in regions where drinking water contains excessive fluoride and where the dietary intake of fluoride is excessive.

But the other fact is that IQ effects receive relatively little attention in health studies from those areas compared with the more obvious, and more crippling, effects like dental and skeletal fluorosis.

Mind you, that doesn’t stop activists making sporadic claims of all sorts of health effects from fluoridation and relying on studies from areas of endemic fluorosis. But the most frequent claims made by activists at the moment relate to IQ. Perhaps this is because it is harder to hide the fact that we don’t see cases fo skeletal fluorosis or severe dental fluorosis in New Zealand. IQ changes are not so obvious and this might make them a more useful tool for anti-fluoride campaigners to use in their scaremongering.

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Maternal urinary fluoride/IQ study – an update

Model of a fetus in the womb. Photo credit: CP PHOTO/ Alliance Atlantis/ HO) 

The maternal urinary fluoride/IQ study  (Bashash et al., 2017) continues to get attention – but mainly from anti-fluoride organisations. The scientific community will evaluate the published report after giving it due consideration and there have already been criticisms. But anti-fluoride campaigners consider it the best thing since sliced bread. The Fluoride Action Network (FAN) describes it as “a cannon shot across the bow of the 80 year old practice of artificial fluoridation” and Fluoride Free NZ insist that it “must spell an end to fluoridation in New Zealand.”

We expect confirmation bias from the anti-fluoride organisations. But the misrepresentations in the propaganda from these organisations are of more concern because they are blatantly meant to scaremonger.

Misrepresentation by anti-fluoride organisations

These people have worked hard to stress the respectability of the authors of the Bashash et al., (2017) paper and claim the study is impeccable. They are not interested in a critical analysis of the data and the conclusions. And they are completely silent about the evidence from the study showing no association of children’s urinary fluoride levels and IQ – normally they are quick to criticise authors reporting such a lack of association.

But this time as well as their normal misrepresentations they have actually manipulated a figure from the paper. I wonder what copyright law would say about this.

I provided the relevant figures from the paper my earlier article (see   Fluoride, pregnancy and the IQ of offspring) and commented on the large amount of scatter in the data.  This scatter should be a warning to any sensible reader – so FAN simply overcomes that problem by deleting the data points in their presentation of the figure.

Here is the original Figure 2 and the FAN misrepresentation of it:

Notice 2 things:

  1. The original figure showed the data for GCI – general cognitive index. It is not IQ and not presented as IQ in the original paper. But it is a measure  of “verbal, perceptual performance, quantitative, memory, and motor abilities of preschool-aged children.” Perhaps a fine point and FAN may be excused for inserting the more popularly understood term IQ. Or perhaps they decided not to use the real figure for IQ (Figure 3A) because it implied no effect at normal urinary fluoride levels (see figure 3A in Fluoride, pregnancy and the IQ of offspring);
  2. FAN removed all the data points in their presentation of the figure. I am sure FAN would argue this was to “simplify” the figure. But in doing so they have removed what is the most important information in Figure 2 – the wide scatter of the data points. That scatter suggests that even though the reported association is “statistically significant” it explains very little of the observed variation and is therefore not important (and may not even be real).

Association of maternal urinary F with child IQ poor and probably misleading

In Fluoride, pregnancy and the IQ of offspring I estimated that “the reported relationships with maternal urinary fluoride could explain no more than a few percent of the variation in the data.” Purely an estimation because I did not have the data to analyse myself and the authors did not give the relevant statistical information.

I have since used a plot digitiser programme to extract the data for these figures and performed my own statistical analysis.

These are the results:

For Figure 2:

Bashash-fig2

Yes, a “statistically significant” relationship (p = 0.002) but it explains only 3.3% of the variation in GCI (R-squared = 0.033)

For Figure 3A:

Bashash-figs3A

Again, “statistically significant” (p = 0.006) but explaining only 3.6% of the variation in IQ (R-squared = 0.0357).

So my estimate was pretty good. And my evaluation is valid:

“In this case, I would expect that other risk-modifying factors that explain the variation more completely could be found. And if these were included in the multiple regressions there may not be any observable relationship with urinary fluoride.”

Considering that this work was unable to explain about 97% of the variation in CGI and IQ I really question its publication. Certainly, scientific evaluations will conclude that this paper should not have any influence on policymakers.

It’s a pity that with all the data the authors had they did not seek out, or properly evaluate, other possible risk-modifying factors.

Other work by group showing no association ignored

Strangely, the Bashash et al., (2017) paper did not include relevant IQ information from the PhD thesis of one of their team Deena B. Thomas. This is her thesis citation:

Thomas, D. B. (2014). Fluoride exposure during pregnancy and its effects on childhood neurobehavior: a study among mother-child pairs from Mexico City, Mexico. PhD thesis, University of Michigan.

It can be downloaded from the full-text link.

The data in chapter 2 of this thesis – Urinary and Plasma Fluoride Levels During Pregnancy and Determinants of Exposure Among Pregnant Women from Mexico City, Mexico – was published. The citation is:

Thomas, D. B., Basu, N., Martinez-Mier, E. A., Sánchez, B. N., Zhang, Z., Liu, Y., … Téllez-Rojo, M. M. (2016). Urinary and plasma fluoride levels in pregnant women from Mexico City. Environmental Research, 150, 489–495.

Bashash et al., (2017) did reference this paper – after all, it dealt with the data they used for estimating fluoride exposure. But they did not reference the thesis itself – and two other chapters in that thesis are directly relevant to the relationship of fluoride exposure to child IQ.

Chapter 3 – Prenatal fluoride exposure and neurobehavior: a prospective study – is directly relevant except that where Bashash et al., (2017) reported data for the children when 4 years old and 6-12 years old Thomas reported data for child neurobehavioral outcomes at ages 1, 2 and 3.

She concluded:

“that maternal intake of fluoride during pregnancy does not have a strong impact on offspring cognitive development in the first three years of life.”

OK – perhaps the difference is purely due to age. But surely it is part of the picture and should at least been mention in the Bashash et al., (2017) discussion.

Chapter 4 – Concurrent Fluoride and Total WASI in 6-15 year old children from Mexico City, Mexico – is also directly relevant because Bashash et al., (2017) did include that data in their paper. They concluded that:

“there was not a clear, statistically significant association between contemporaneous children’s urinary fluoride (CUFsg) and IQ either unadjusted
or adjusting for MUFcr.”

This differs a little from the findings in Thomas’s thesis:

“In the overall population, urinary fluoride appears to have no significant impact on total WASI scores (β =1.32, p=0.33), but this association changes once the models are separated by male and female children. Male children showed a significantly positive trend (β=3.81, p=0.05), and females showing a negative trend that was not significant (β= -1.57, p=0.39).” [WASI score is a measure of IQ]

And she wrote:

“analysis suggests concurrent urinary fluoride exposure has a strong positive impact on cognitive development among males aged 6-15 years.”

She concludes:

“These results were surprising in that they show opposite trends to what has been reported in the literature so, more studies with similar reliable methodology, which account for plasma fluoride, diurnal variations in urinary fluoride and children’s SES, are needed. If these results are substantiated, different fluoride interventions may be needed for male children versus female
children.”

I would have thought these findings and conclusions were worthy of discussion by Bashash et al., (2017). It’s not as if the authors were unaware of their colleague’s findings.

Maybe internal politics are involved. but that does not justify the omission.

Conclusion

The anti-fluoride people, and particularly FAN, are misrepresenting the study and have manipulated a figure to hide information in an unethical way. The data presented in the Bashash et al., (2017) study shows maternal urinary fluoride can only explain 3 – 4 % of the variation in General Cognitive Index and IQ of the children. The inclusion of a more viable risk-modifying factor would probably remove even that small amount explanation.  Bashash et al., (2017) also neglected to discuss relevant information from a colleague which contradicted their conclusions.

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Fluoride, pregnancy and the IQ of offspring

Anti-fluoride campaigners don’t agree. Image credit:Dental Care Tips for Mom and Baby” presentation

What’s the story about this new IQ-fluoride study? The one that claims fluoride intake by pregnant women could endanger their children’s IQ?

Whatever the truth, it has certainly got the anti-fluoride activists going. Mary O’Brien Byrne, leader of the local anti-fluoride group is even suggesting people check if their mothers lived in fluoridated areas. And they are busy promoting the newspaper articles on this. For example Fluoride exposure in utero linked to lower IQ in kids, study saysChildren’s IQ could be lowered by mothers drinking tap water while pregnant, and Higher levels of fluoride in urine linked to lower IQ scores in children.

Best not rely on those media reports, though – you know how unreliable they can be. The original paper is available – this is the citation:

Bashash, M., Thomas, D., Hu, H., Martinez-mier, E. A., Sanchez, B. N., Basu, N., … Hernández-avila, M. (2016). Prenatal Fluoride Exposure and Cognitive Outcomes in Children at 4 and 6 – 12 Years of Age in Mexico. Environmental Health Perspectives, 1, 1–12.

And here is a link to the full text. Download it and see what sense you make of it. I warn you it is a difficult paper to read.  A lot of information is lacking and the information that is included is hard to find. The statistical analysis is incomplete.

A new twist on the tired old fluoride/IQ story

Basically, it is the old drinking water fluoride causes lowering of IQ story. This time it relates to a supposed association of fluoride intake by pregnant mothers with cognitive deficits in their children. Interesting, only one other similar study (involving fluoride exposure while pregnant) has been reported – in January this year, and also in Mexico. I wrote about that study of Valdez Jiménez et al., (2017), In utero exposure to fluoride and cognitive development delay in infants,  in the article Premature births a factor in cognitive deficits observed in areas of endemic fluorosis?

Briefly, the Valdez Jiménez et al., (2017) study was from Mexican areas of endemic fluorosis with very high fluoride concentrations in drinking water so the results are not applicable to areas where community water fluoridation is used. However, the high incidence of premature births, and low birthweights for the children, for mothers with high urinary fluoride levels does suggest that problems of birth in areas of endemic fluorosis could provide a biological mechanism to explain the IQ deficits. Rather than a direct chemical toxicity mechanism.

What about the Bashash, et al. (2017) paper?

Generally, the paper concludes that “higher prenatal fluoride exposure . . . .was associated with lower scores on tests of cognitive function in the offspring.”

So here are some concerns I have about the paper

1: An association is not evidence of, or proof for, causation. Yes, that is the normal and obvious qualification for such studies and authors tend to repeat it – even if they might still attempt to argue the case that it is evidence. A lot of confirmation bias goes on with these sort of correlational studies.

2: The information about the mothers is scant. My first question, given it was Mexico, was did they come from areas of endemic fluorosis? The women were recruited from three hospitals in Mexico city but this says nothing about their current or former residential areas. No information on drinking water fluoride is presented nor any biological assessment, such as dental fluorosis, given which could help estimate the role of endemic fluorosis.

3: Assessment of fluoride exposure relied completely on urine fluoride concentration measurements. With between one and three samples for each mother-child pair! (Of the total sampled there was only one sample for 217, two for 224 and three for 71 mothers). I believe that is completely inadequate for estimating exposure – especially as fluoride levels in urine vary markedly during the day and with diet. Besides the extremely low sample numbers,  the World Health Organisation has warned that while urinary fluoride can be useful for monitoring populations “Urinary fluoride excretion is not suitable for predicting fluoride intake for individuals.”  (see Contemporary biological markers of exposure to fluoride). They further warn that 24 hr collection is preferred to the spot sampling used in this study.

4: The statistical information presented is confusing – and insufficient to estimate how relevant the reported statistically significant associations are. I believe the best idea of the data can be gleaned from the following figures presented in the paper.

Figure 2 displays the data and association of maternal urinary fluoride (MUFcr) with a general cognitive index (CGI) for the 4 yr old offspring.

Figure 3A displays the data and association of maternal urinary fluoride (MUFcr) with IQ of the offspring at age 6 -12.

While linear regression analysis showed statistically significant associations of the CGI and IQ of offspring’s with maternal urinary fluoride levels the large scatter indicates these associations will explain only a small part of the variations observed. In such situations, reliance on p values can be misleading. As a reader, I would be more interested in the R2 values which indicate the amount of variation explained by the association.

I estimate the reported relationships with maternal urinary fluoride could explain no more than a few percent of the variation in the data. In this case, I would expect that other risk-modifying factors that explain the variation more completely could be found. And if these were included in the multiple regressions there may not be any observable relationship with urinary fluoride.

I discussed this issue more fully in my article Fluoridation not associated with ADHD – a myth put to rest which showed that a published relationship of ADHD with fluoridation extent disappeared completely when altitude was included as a risk-modifying factor. And that relationship showed less scatter of the data points than in the figures above.

5: The absence of any association of child IQ to child urine fluoride was also reported in this paper. This conflicts with other researchers working in areas of endemic fluorosis who have reported such associations. It could be that the urine fluoride measurements used in the present study were not suitable. But I am picking that the anti-fluoride campaigners will be very silent about that information, given the importance they give to other studies showing a relationship in their propaganda.

Conclusions

it is a very unsatisfying paper. I couldn’t determine if areas of endemic fluorosis were implicated – as they were for the Valdez Jiménez et al., (2017) study. Urinary fluoride is an inadequate measure of fluoride exposure – especially for individuals and spot samples – and its variability does not allow comparison with other studies and other regions. I couldn’t evaluate if the reported results were relevant to New Zealand which does not have any endemic fluorosis.

Finally, I believe aspects of the statistical analysis were inadequate. But on the positive side, I am pleased the authors did display the actual data in their figures. The information in those figures forced me to conclude that maternal urinary fluoride may not have the influence the authors suggest. If it does have an influence its contribution can only be minor and other more important risk-modifying factors will be involved.

Mind you – I am sure anti-fluoride campaigners will see it differently. They are currently heavily promoting the study and anti-fluoride guru Paul Connett sees it as the best thing since sliced bread. He has gone on record to say this means the end of community water fluoridation!

Update

I think the anti-fluoride people are aware of weaknesses in this study. The local Fluyodie Free NZ has put out a press release including a figure which they have doctored to remove the data points which show how little variation is explained. Compare their figure with the Fiugure 2 above.

Fluoride Free NZ doctors figure from paper to hide the scatter in data points showing how little of the variability the relationship explains

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Debunking a “classic” fluoride-IQ paper by leading anti-fluoride propagandists

epa-meeting-sept5-2014

Three of the paper’s authors – Quanyong Xiang (1st Left), Paul Connett (2nd Left) and Bill Hirzy (far right) – preparing to bother the EPA.

Anti-fluoride groups and “natural”/alternative health groups and websites are currently promoting a new paper by several leading anti-fluoride propagandists. For two reasons:

  1. It’s about fluoride and IQ. The anti-fluoride movement recently decided to give priority to this issue in an attempt to get recognition of possible cognitive deficits, rather than dental fluorosis,  as the main negative health effect of community water fluoridation. They want to use the shonky sort of risk analysis presented in this paper to argue that harmful effects occur at much lower concentrations than currently accepted scientifically. Anti-fluoride guru, Paul Connett, has confidently predicted that this tactic will cause the end of community water fluoridation very soon!
  2. The authors are anti-fluoride luminaries – often described (by anti-fluoride activists) as world experts on community water fluoridation and world-class scientists. However, the scientific publication record for most of them is sparse and this often self-declared expertise is not actually recognised in the scientific community.

This is the paper – it is available to download as a pdf:

Hirzy, J. W., Connett, P., Xiang, Q., Spittle, B. J., & Kennedy, D. C. (2016). Developmental neurotoxicity of fluoride: a quantitative risk analysis towards establishing a safe daily dose of fluoride for children. Fluoride, 49(December), 379–400.

bruce-spittle

Co-author Bruce Spittle – Chief Editor of Fluoride – the journal of the International Society for Fluoride Research

I have been expecting publication of this paper for some time – Paul Connett indicated he was writing this paper during our debate in 2013/2014. FAN newsletters have from time to time lamented at the difficulty he and Bill Hirzy were having getting a journal to accept the paper. Connett felt reviewers’ feedback from these journals was biased. In the end, he has lumped for publication in Fluoride – which has a poor reputation because of its anti-fluoride bias and poor peer review. But, at last Connett and Hirzy have got their paper published and we can do our own evaluation of it.

The authors are:

david-c-kennedy

Co-author David C. Kennedy – past president of the International Academy of Oral Medicine and Toxicology – an alternative dentist’s group.

Bill Hirzy, Paul Connett and Bruce Spittle are involved with the Fluoride Action Network (FAN), a political activist group which receives financial backing from the “natural”/alternative health industry. Bruce Spittle is also the  Chief Editor of Fluoride – the journal of the International Society for Fluoride Research Inc. (ISFR). David Kennedy is a Past President of the International Academy of Oral Medicine and Toxicology which is opposed to community water fluoridation.

Quanyong Xiang is a Chinese researcher who has published a number of papers on endemic fluorosis in China. He participated in the 2014 FAN conference where he spoke on endemic fluorosis in China.

xiang-Endemic fluorosis

Much of the anti-fluoridation propaganda used by activists relies on studies done in areas of endemic fluorosis. Slide from a presentation by Q. Xiang to an anti-fluoride meeting organised by Paul Connett’s Fluoride Action Network in 2014.

Critique of the paper

I have submitted a critique of this paper to the journal involved. Publication obviously takes some time (and, of course, it may be rejected).

However, if you want to read a draft of my submitted critique you can download a copy from Researchgate – Critique of a risk analysis aimed at establishing a safe dose of fluoride for children.  I am always interested in feedback – even (or especially) negative feedback – and you can give that in the comments section here or at Researchgate.

(Please note – uploading a document to Researchgate does not mean publication. It is simply an online place where documents can be stored. I try to keep copies of my documents there – unpublished as well as published. It is very convenient).

In my critique I deal with the following issues:

The authors have not established that fluoride is a cause of the cognitive deficits reported. What is the point in doing this sort of risk analysis if you don’t actually show that drinking water F is the major cause of cognitive deficits? Such an analysis is meaningless – even dangerous, as it diverts attention away from the real causes we should be concerned about.

All the reports of cognitive deficits cited by the authors are from areas of endemic fluorosis where drinking water fluoride concentrations are higher than where community water fluoridation is used. There are a whole range of health problems associated with dental and skeletal fluorosis of the severity found in areas of endemic fluorosis. These authors are simply extrapolating data from endemic areas without any justification.

The only report of negative health effects they cite from an area of community water fluoridation relates to attention deficit hyperactivity disorder (ADHD) and that paper does not consider important confounders. When these are considered the paper’s conclusions are found to be wrong – see ADHD linked to elevation not fluoridation, and ADHD link to fluoridation claim undermined again.

The data used by the Hirzy et al. (2016) are very poor. Although they claim that a single study from an area of endemic fluorosis shows a statistically significant correlation between IQ and drinking water fluoride that is not supported by any statistical analysis.

The statistically significant correlation of IQ with urinary fluoride they cite from that study explains only a very small fraction of the variability in IQ values (about 3%) suggesting that fluoride is not the major, or maybe not even a significant, factor for IQ. It is very likely that the correlation between IQ and water F would be any better.

Confounders like iodine, arsenic, lead, child age, parental income and parental education have not been properly considered – despite the claims made by Hirzy et al. (2016)

The authors base their analysis on manipulated data which disguises the poor relations of IQ to water fluoride. I have discussed this further in Connett fiddles the data on fluorideConnett & Hirzy do a shonky risk assessment for fluoride, and Connett misrepresents the fluoride and IQ data yet again.

Hirzy et al. (2016) devote a large part of their paper to critiquing Broadbent et al (2014) which showed no evidence of fluoride causing a decrease in IQ  using data from the Dunedin Multidisciplinary Health and Development Study. They obviously see it as a key obstacle to their analysis. Hirzy et al (2016) argue that dietary fluoride intake differences between the fluoridated and unfluoridated areas were too small to show an IQ effect. However, Hirzy et al (2016) rely on a motivated and speculative estimate of dietary intakes for their argument. And they ignore the fact the differences were large enough to show a beneficial effect of fluoride on oral health.

Conclusion

I conclude the authors did not provide sufficient evidence to warrant their calculation of a “safe dose.” They relied on manipulated data which disguised the poor relationship between drinking water fluoride and IQ. Their arguments for their “safe dose,” and against a major study showing no effect of community water fluoridation on IQ, are highly speculative and motivated.

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