Severe dental fluorosis and cognitive deficits – now peer reviewed

peer-review-cartoon
Last May I raised the possibility that the much touted relationship of small IQ declines for children living in areas with naturally high fluoride in drinking water could be associated with severe dental fluorosis and not a chemical neurotoxicant (see Confirmation blindness on the fluoride-IQ issue). In November I repeated this argument because the recently published work by Choi et al (2015) provided evidence of a statistically significant relationship of cognitive deficits to severe dental fluorosis for Chinese children living in high fluoride areas  (see Severe dental fluorosis the real cause of IQ deficits?).
I am pleased to report the journal Neurotoxicology and Teratology (which published the Choi et al., 2015 paper) have now accepted a peer-reviewed letter to the Editor from me on the subject:

Perrott, K. W. (2015). Severe dental fluorosis and cognitive deficits. Neurotoxicology and Teratology.

Don’t limit possible hypotheses

My letter warns:

“cognitive deficits could have many causes or influences – genetic, environmental and/or social. Researchers need to be careful not to limit their possible hypotheses or research approaches. Unfortunately Choi et al. (2015) appear to be doing just this with their plans for a larger scale study targeted only at “fluoride’s developmental neurotoxicity.””

It points out:

Choi et al. (2012) did highlight the need for further research. Broadbent et al. (2014) showed no effect of fluoride on IQ at the optimum drinking water concentrations used in CWF [community water fluoridation]. However, most of the reports reviewed by Choi et al. (2012) considered data from areas of endemic fluorosis where drinking water fluoride concentrations are higher.”

“Choi et al. (2015) did not find a statistically significant association of drinking water fluoride concentration with any of the neuropsychological measurements. But they did find one for moderate and severe dental fluorosis with the WISC-R digit span subtest.”

This suggests a possible hypothesis involving the effects of negative physical appearance and not a chemical neurotxocant:

“Emotional problems in children have been related to physical anomalies, including obvious oral health problems like severe tooth decay (Hilsheimer and Kurko, 1979). Cognitive deficits can sometimes be related to emotional problems and subsequent learning and behavior problems. Quality of lifeparticularly oral health related quality of life – is negatively related to tooth decay and severe dental fluorosis. It is possible that negative oral health quality of life feelings in children could induce learning and behavior difficulties which are reflected in neuropsychological measurements.”

Difference between areas of endemic fluorosis and CWF

This hypothesis is applicable to children in areas of endemic fluorosis but is not relevant to areas where CWF is used:

“Sixty percent of the children in the Choi et al. (2015) pilot study had dental fluorosis graded as moderate or severe. This likely reflects the endemic fluorosis of the study area. Only a few percent of individuals in areas exposed to the optimum levels of drinking water fluoride used in CWF have dental fluorosis that severe. For example, a recent oral health survey in New Zealand found 2% of individual had moderate dental fluorosis and 0% had severe dental fluorosis (Ministry of Health, 2010). Similarly a US survey found only 2% of individuals exhibited moderate dental fluorosis and less the 1% severe dental fluorosis (Beltrán-Aguilar et al., 2010).”

“Tooth decay and other oral defects negatively impact a child’s quality of life as assessed by children and parents (Barbosa and Gavião, 2008; Nurelhuda et al., 2010; de Castro et al., 2011; Aguilar-Díaz et al., 2011; Biazevic et al., 2008; Abanto et al., 2012Krisdapong et al., 2012; Bönecker et al., 2012; Locker, 2007). Quality of life impacts have also been found for dental fluorosis, but there is a marked difference in physical appearance and quality of life assessments for children with moderate/severe dental fluorosis compared with those having none/questionable or very mild/mild forms.

The physical appearance of moderate and severe forms of dental fluorosis is generally considered undesirable so we could expect these forms to be associated with poor quality of life and this appears to be the case (Chankanka et al., 2010; Do and Spencer, 2007; Chikte et al., 2001). In contrast, most studies report no effect or a positive effect of questionable, very mild and mild forms of dental fluorosis on quality of life (Do and Spencer, 2007; Chankanka et al., 2010; Peres et al., 2009; Biazevic et al., 2008; Büchel et al., 2011; Michel-Crosato et al., 2005).

Given the different patterns of dental fluorosis severity in areas of endemic fluorosis and areas where CWF is practiced and fluoride intakes are likely to be optimal it seems reasonable to expect a difference in ways fluoride intake influences health-related quality of life and possibly cognitive factors.”

My purpose in this letter was to argue that other mechanisms besides chemical neurotoxicity should be considered in these studies. I hope researchers take this on board and look forward to the response of Choi and her co-workers to this suggestion.

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26 responses to “Severe dental fluorosis and cognitive deficits – now peer reviewed

  1. Ken

    Do you have any evidence that dental fluorosis results in teasing or reduced numbers of friends?

    Ron

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  2. Why do you ask, Ron?

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  3. Ken, this is nothing short of outstanding!!! Choi needed a response to her latest stab at the decades old attempts to tie fluoridation to “mind control.” You did so in excellent manner. Thank you!

    Steven D. Slott, DDS

    Liked by 1 person

  4. rather than have all those “coulds” it would be great if we could do some partial correlations on the data.

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  5. sound Hill, Choi et al did statistically analyse their data. That’s why I, and they, were able to say there was a significant association of cognitive deficit with severe dental fluorosis.

    However, a significant correlation does not remove the need for “could” and “may” as the classical example of prostitutes and ministers of religion show. Correlation is not causation.

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  6. I don’t remember partial correlations being mentioned to remove your PP trouble.

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  7. Nor do partial correlations prove causation or spuriosity but they are definitely evidence for or against.

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  8. I don’t have a PP problem. And yes I did use their statistical analysis as evidence for my suggested hypothesis. I don’t know what you are moaning about.

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  9. I have to explain so much in this group.

    Ken does not like the frequently used meaning of “your”
    “your
    adjective \yər, ˈyu̇r, ˈyȯr\

    : relating to or belonging to you : made or done by you

    —used to refer to any person or to people in general ”
    http://www.merriam-webster.com/dictionary/your
    “Your PP problem” and you don’t like ministers of region being called parsons or preachers.

    “Your PP problem” then is the causation vs correlation problem.

    Have you seen anywhere where Choi & al. explained their process?

    I had a long argument with someone who was quite sure that partial correlation in a table of variables only meant selecting the pair from a table of correlations.

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  10. I don’t know what you are burbling about Soundhill.

    Have a read of Choi et al’s paper to learn about their methodology.

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  11. Thanks, Ken,

    I’ve made some comments on the previous thread.

    I’ll see if I may interloan the paper.

    In the mean time it says it is a pilot study.

    After more consideration and comment from this group I may feed back to Choi & al. to try to look at fluoride levels at various life stages.

    Many people know that if you look after a bird and it has no contact with its natural parents at a certain stage of development it will develop thinking you are its parent.

    If Acetylcholinesterase can be inhibited by fluorine compounds at certain stages of life there may also be inhibition of the developmental processes associated with those stages.

    Here is a paper developing on such areas:

    http://omicsonline.org/a-sensitive-period-of-peer-social-learning-2161-0495.1000158.pdf

    ” Cholinergic and other neurotransmitter systems control
    chick basal ganglia. The neurotoxicology such as acetylcholine esterase
    inhibitor, Physostigmine suggests the relevancy to developmental
    disorders [27]. Thus, social affiliation development in chick suggests
    a common neural substrate, i.e., mesolimbic system which comprises
    a social brain network. In human, the network interacts with more
    complex cognitive system eventually yielding a theory of mind [28].
    Therefore, our animal model and a statistical behavior measure may
    be relevant to evaluate development of a subcortical limbic system
    comprising a common neural substrate for social affiliation acquisition
    over species [29]. ”

    And from an older paper:
    http://www.fluoridealert.org/wp-content/uploads/westendorf.pdf

    “The residual complexes, at least in the case of (SiF6)2-, inhibit AChE more strongly than fluoride. Therefore, if one postulates the existence of such complexes in the organism, the range in which inhibition still appears shifts towards physiological F concentrations’

    “According to a theory of Knappwost’s, fluoride’s protection against tooth decay relies on a vagotonic influence on saliva quantity and quality. Therefore, we looked for signs of a vagotonic mechanism for the effect of fluoride. On the basis of the inhibition of acetylcholinesterase by fluoride we could show that this inhibition increases when the pH is
    shifted towards a more acidic level (up to pH 6-6.5). Elucidating this state of affairs showed that the HF molecule is the actual inhibitory agent. From this it could be deduced that in those areas
    of the organism where such pH shifts occur, an inhibition of AChE is possible at physiological F concentrations.”

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  12. Soundhill, you keep referring to Westendorf’s thesis as a “paper.” It is not, it is simply an unpublished thesis and therefore not subject to normal peer review of a journal.

    Personally I find the section on the degree of decomposition of fluorosilicates extremely poor and doubt it could get published as he doesn’t provide proper scientific details. I suspect what he has measured the F- remaining in solution after precipitation of MgF2 rather than the degree of hydrolysis.

    Anti-fluoride propagandists love to cite this thesis- most without having read it of course – and ignore the higher quality work on this hydrolysis.

    Choi et al (2015) is a pilot study – my concern is that they are planning to extend the work simply to support their favourite chemical toxicity hypothesis. My point was to raise with them the importance of being open-minded and, as they were measuring severe dental fluorosis, to consider the effect of physical anomalies like this.

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  13. Ken if you are referring to “Reexamination of Hexafluorosilicate Hydrolysis by 19F NMR and pH Measurement” it is only going to 10^-5M.

    And why would that article cite Westendorf’s if it were not a proper article? I do not think Germany would have been giving out PhDs easily in 1975, and note has thesis had a principal reviewer and 4 others.

    I need to look more into Pollack and micro-effects of pH &c.

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  14. I hadn’t realised there was a classification “proper article.”

    My comments about the lack of relevant experimental detail are key to the judgments on the thesis because it prevent proper critical assessment. If I had reviewed it for a journal I would have knocked it back until the proper material had been included. In the absence of proper experimental details it seems to me that the results when Mg is present could be explained by solubility factors. There is also the question of complications with ion electrodes and I would have liked to see some sort of confirmation about what species were being detected. This would also explain why the author got results very different to others.

    Incidentally, I do not see theses as having the same sort of quality control we expect for a scientific journal. Good thesis work is alway submitted to journals and I am always suspicious of unpublished theses. Having been through the PhD process I certainly can see how the conferring of a degree does not automatically confer reliability on the research.

    The NMR research is far better quality – as are some other more recent work. The concentration was limited by the sensitivity of the method but certainly does not negate the conclusions.

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  15. Ken, it is not frequent to get 80 or more page article published in a journal. And since theses are publicly available that fulfils a similar function.
    The thesis has been translated from German 25 years after it was written and to my mind the translation is not always quite clear.

    Maybe some of the technique has not been put in by Westendorf to reduce length since cited articles have explained, as for the “fluoride specific electrode” referred to in the introduction. Could you elucidate on the “results very different?” There is a lot to go through and direction would help.

    You are a chemist, does that include biochemistry?

    “For a cholinergic neuron to receive another impulse, ACh must be released from the ACh receptor. This occurs only when the concentration of ACh in the synaptic cleft is very low. Inhibition of AChE leads to accumulation of ACh in the synaptic cleft and results in impeded neurotransmission.”
    http://en.wikipedia.org/wiki/Acetylcholinesterase

    Pollack in his book (p132) shows pH sensitive dyes indicating a strong pH gradient around charged spheres.

    I think we have a way to go to understand all the AChE matters.

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  16. Sour sill, yes chemistry covers a multitude of sins, including biochemistry. However, chemists do specialises – I did not specialise in biochemistry. My comments in this thesis are related not to biochemistry but to the hydrolysis of fluorosilicates.

    Westendorf is quoted by those anti-fluoride propagandists who argue that fluorosilicates are not completely hydrolysed on dilution. This thesis is really the only reference that can be used for that. Even Crosby, who is sometimes used, effectively reported complete hydrolysis and the propagandists rely on their silly interpretation of greater than 97%, or similar

    Westendorf does not give proper details for his hydrolysis experiments – and he should have. In particular he does not provide any evidence of remaining unhydrolysed fluorosilicate..

    One should always approach the literature, peer reviewed or not, critically and intelligently.That is all I have done and hence Westendorf’s material does not come across as reliable.i suspect if he has submitted it to a journal he would have been asked to revise drastically. Maybe this happened and he withdrew his paper. It happens.

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  17. Westenforf should have tried the journal “Fluoride”…..,they’re not too picky when it comes antifluoridationist “literature”……

    Steven D. Slott, DDS

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  18. Fluoride Alert does their best to promote this old and unreliable thesis – this is where Soundhill got it from.

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  19. Apparently they published some articles in journals before the thesis.
    http://www.ncbi.nlm.nih.gov/pubmed/4848956
    plus others on Pubmed.

    And how about taking Ken’s advice?:
    “Don’t limit possible hypotheses”

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  20. “And why would that article cite Westendorf’s if it were not a proper article? I do not think Germany would have been giving out PhDs easily in 1975, and note has thesis had a principal reviewer and 4 others.”

    There is a difference between ‘reviewing’ (in NZ we would say ‘examining’) a thesis & peer-reviewing a paper or papers from that thesis.

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  21. Thanks, Alison, I see a terminology thing. Professor means something different here from USA I think.

    But anyway I see the work was published in 1974 in (New name:The Science of Nature) – Naturwissenschaften – Springer’s flagship multidisciplinary science journal.

    Have to think about use of the word, “should,” though I suppose it’s fairly plain:
    “According to McClure(7), the F-content of saliva, independent of the intake level, should never exceed 0.1 mg/l.”

    which goes on and explains itself:
    “More recent experiments by K.Yao and P. Groen (8), which were carried out with the help of an F-specific electrode, confirm these results. The F-content of the saliva secreted by the parotid gland, which for test subjects drinking water with < 0.1ppm of F was 0.007ppm, rose to 0.009ppm upon transition to concentrations of 1ppm of F in the water."

    I think we should suggest to Choi & al, to measure saliva, too, but not straight after drinking water as it may be a lot greater?

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  22. So tell us, Soundhill, did the Naturwissenschaften paper (where I see Westendorf is a junior author so the work probably predates his thesis work) include anything on fluorosilicate analysis? If so, did if provide information on the methodology used? Particularly did it show data for fluorosilicate remaining after hydrolysis?

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  23. Ken, I’ve been thinking of getting a UOC library card to read it and a few others. They seem to have this journal in the communal store. With the help of a translator. But I won’t be able to get a login in for the online databases. Anyone?

    If there aren’t Si complexes hanging around what else might be happening?

    The body may have mechanisms to hold chlorides at the level it wants. Though I am confused about that. I suppose it would, in association with sodium. It does have a way to balance sodium and potassium. It may even get rid of body fluid to keep up a salinity concentration of blood. Some people’s kidneys/adrenals may not be so good at making the aldosterone which is required to keep up a sufficient sodium level. They may have to supplement sodium.

    So what about fluorides? Why is saliva held so constant? Will thwe body make a compromise to other homeostasis to hold salivary fluoride at the correct level?

    Excess lead we may store in our bones. And with fluoride youths may excrete less than adults since it is going to the bones as they build them.

    Lot of things to understand about.

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  24. Soundhill, you are rabbiting on again.

    >

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  25. Ken wrote: “Choi et al (2015) is a pilot study – my concern is that they are planning to extend the work simply to support their favourite chemical toxicity hypothesis. My point was to raise with them the importance of being open-minded and, as they were measuring severe dental fluorosis, to consider the effect of physical anomalies like this. ”

    Sometimes I think it is unfortunate that more research grants can’t go to exploratory as opposed to hypothesis-based research.

    I think a lot of incidental findings may be wasted with hypothesis-based research. If you come up with an interesting correlation you have to be careful you are not just cherry picking. But at 5% there ought to be a philosophy to follow up some stuff.

    Where would Choi & al get if they did not have to stick to a hypothesis?

    You, Ken, developed the physical disability- social disability maybe affecting IQ hypothesis. I can think of an opposite one: those school kids who get laughed at for being “four eyes” i.e. wearing glasses on average may show higher IQ.

    Much arguing on this group goes to back up or attack a hypothesis or theory and I feel chances for new discovery or being wasted.

    The author of this thesis remarks that it is hypothesis-based. Presumably more could have been found if he were allowed to do a table of correlations and choose, applying some sort of protective philosophy.

    http://ir.uiowa.edu/cgi/viewcontent.cgi?article=1467&context=etd

    I have mentioned the idea previously of “balanced polymorphism,” I think on openparachute, or maybe kiwiblog.

    Let’s try to explore how nature is adjusting to challenges as well as following the old hypothesis-based protocol. Let’s try to give individuals a chance, too, as well as populations.

    I suppose I am rabbiting on. My cats bring me rabbits. Don’t know if they are poisoned.

    http://www.sciencedaily.com/releases/2013/09/130927105138.htm
    vaguely related:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597341/

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  26. Ken: “There is also the question of complications with ion electrodes”

    It seems they may not measure fluoride in colloids, so fluoride could be higher than they say:

    http://www.sciencedirect.com/science/article/pii/0011747170900835

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