Tag Archives: NAS

Anti-fluoridationists put faith in new “strong” studies to provide evidence missing in draft NTP review

The US National Academies of Science (NAS) found the National Toxicity Programme’s (NTP) conclusion in their recent draft report that fluoride is neurotoxic was not supported by the reviewed evidence (see Another embarrassment for anti-fluoride campaigners as neurotoxic claim found not to be justified). This was a huge defeat for anti-fluoride activists who had been roundly promoting the conclusion of the draft report – despite the warning on every page that it “should not be construed to represent any NTP determination or policy” and that the draft had been “distributed solely for the purpose of pre-dissemination peer review.”

So the anti-fluoridationists declared belief that the NTP draft was going to mean the end of community water fluoridation (CWF) was dashed. But that has not stopped Paul Connett, head of the main US anti-fluoride group Fluoride Action Network (FAN) from putting his own spin on the NAS peer review report. In his attempt to present this huge defeat as somehow positive he issued a press release where he claims:

“If the recommendations are adopted, they will make the final report ‘iron-clad’ against criticisms. The NAS suggestions should strengthen the draft report’s conclusion that fluoride is a presumed neurotoxin in children, which is based on 149 human studies. This finding brings into question the long-standing assurances from public health officials that water fluoridation is safe.”

The NAS peer review is very critical – and not just about the fact that the draft conclusion was not supported by the reviewed evidence. There are criticisms of biased study selection, insufficient consideration of the effect of confounders and problems with statistical analyses used. But besides playing with words to misrepresent the peer review, Paul Connett has declared a belief that the NTP will now consider new studies, published since the draft report was released, and these will provide the evidence missing in the original draft. He is hoping the revised review will include new “strong” (in his opinion) studies which will finally swing things his way:

“Multiple strong scientific studies, at exposures relevant to fluoridation, have been published after the NTP’s review. They link fluoridation in Canada to greatly lowered IQ in formula-fed infants (Till 2020) and 300% higher rates of ADHD (Ridell 2019); fluoridation in USA with sleep disturbances in adolescents (Malin 2020); and fluoride with lower IQ by thyroid disruption (Wang 2020).”

Notably, Connett actively ignores, yet again, a new study which does not fit his bias because it reports a positive relationship between maternal prenatal urinary F and child IQ – the complete opposite of what he wishes (see The anti-fluoride brigade won’t be erecting billboards about this study). But Connett has been specific so we can objectively consider just how strong or weak these new studies are and evaluate for ourselves the likelihood that they can be used to provide support for the unwarranted conclusion expressed in the draft NTP report.

I have discussed several of these studies in previous articles but briefly consider them together here.

Till et al (2020) formula-fed child study

I discussed this study in my article Anti-fluoride propagandists appear not to read the articles they promoteIt’s citation is:

Till, C., Green, R., Flora, D., Hornung, R., Martinez-mier, E. A., Blazer, M., … Lanphear, B. (2020). Fluoride exposure from infant formula and child IQ in a Canadian birth cohort. Environment International, 134(September 2019), 105315.

This has been blindly promoted by anti-fluoride propagandists as finding a decrease in IQ for children formula-fed as babies and a negative relationship of IQ for these children with drinking water F. However, the relationships are not statistically significant. It’s possible those anti-fluoride activists claiming a significant relationship had been influenced by Till’s previous conference paper where she indulged in special pleading for a non-significant relationship.

The findings reported by Till et al (2020) are summarised below:

While there are no significant relationships for IQ (FSIQ – Full-Scale IQ), the authors did report a significant negative relationship of performance IQ (PIQ) with water fluoride for children both breastfed and formula-fed as babies (and also for estimated F-intake for formula). Strangely, the anti-fluoride promoters of this paper generally don’t refer to this – perhaps because very few of them actually read the papers they promote.

Why there is a difference between IQ and PIQ is a bit of a mystery but there is a recommendation that PIQ, a subset of IQ tests, should not be used for clinical decision making because it is not consistent with current standards (see Beware of scientific paper abstracts – read the full text to avoid being fooled).

Riddell et al (2018) ADHD study

My article ADHD and fluoride – wishful thinking supported by statistical manipulation? discussed this study. Its citation is:

Riddell, J. K., Malin, A., Flora, D., McCague, H., & Till, C. (2019). Association of water fluoride and urinary fluoride concentrations with Attention Deficit Hyperactivity Disorder in Canadian Youth. Submitted to Environment International, 133(May), 105190.

The authors expressed disappointment that they could not find any relationship of ADHD prevalence to urinary F which they considered the best measure of F exposure. However, they were able to squeeze out some significant relationships with water F when the data was divided according to youth age. Significant for older youth but not younger. The findings of Riuddell et al (2019) are summarised in this figure.

The relationships are tenuous with large confidence intervals indicating their weakness. Manipulation of the data by age to find significant relationships reminds me of the saying that if data is tortured enough it will produce the answer you want

So, again, hardly a “strong” study and I cannot see Connett’s wish that the NTP will be able to justify its unwarranted draft conclusion with this.

Malin et al (2020) sleep “disturbances” study

I reviewed this study in my article Sleep disorders and fluoride: dredging data to confirm a bias. The paper citation is:

Malin, A. J., Bose, S., Busgang, S. A., Gennings, C., Thorpy, M., Wright, R. O., … Arora, M. (2019). Fluoride exposure and sleep patterns among older adolescents in the United States: a cross-sectional study of NHANES 2015 – 2016. Environmental Health, 1–9.

First of all, this paper has been poorly peer-reviewed. Effectively just an “in-house” review by coworkers all involved in publishing the same work (see Some fluoride-IQ researchers seem to be taking in each other’s laundry). This figure illustrates the relationships between the authors and their coworkers working with the same and similar data:

Relationships between Malin and her peer reviewers as indicated by joint publications. Links to the papers listed from the top are: Malin & Till (2015) Thomas et al (2014)Bashash et al (2017)Marlin et al (2018), Malin et al (2018)Bashash et al (2018)Thomas et al (2018), and Riddell et al (2018)

I think this sort of self-selected peer-review during journal publication is almost scientifically corrupt. In my article, I concluded that the journal was chosen for publication and the absence of genuine peer review, together with the weak findings, indicated  this is another poor quality paper on fluoride and health effects which make unwarranted claims – and which will be used by anti-fluoride activists in their campaign against community water fluoridation.”

The study used a range of parameters which facilitated dredging of the data to find apparently statistically significant relationships (see  Statistical manipulation to get publishable results). None of the relationships with blood plasma F were statistically significant (despite a bit of special pleading by the authors). They did report significant relationships with water F for sleep apnea, snoring, bedtime and waketime. An apparent reduction of snoring with an increase in water F baffled the authors. The confidence interval for sleep apnea was very large and small differences in bedtime and wake time are easily understood as connected with social differences between rural and city residents. There were no relationships with sleep duration.

So much for Connett’s description of this as a “strong scientific study” capable of reinstalling NTP confidence in their unsupported draft conclusion of a neurotoxic effect of fluoride.

Wang et al (2020) IQ study

This study is reported in:

Wang, M., Liu, L., Li, H., Li, Y., Liu, H., Hou, C., … Wang, A. (2020). Thyroid function, intelligence, and low-moderate fluoride exposure among Chinese school-age children. Environment International, 134(September 2019), 105229. https://doi.org/10.1016/j.envint.2019.105229

Although Connett claims the study was “at exposures relevant to fluoridation” this is not so. The study was aimed at measuring “low-moderate fluoride exposure affects” in the Chinese context and involved comparison of children from areas of “endemic and non-endemic fluorosis areas in Tianjin, China.” Water fluoride concentrations ranged from 0.20 to 3.90 mg/L and urinary F from 0.01 to 5.54 mg/L. Not at all comparable to the concentration where community water fluoridation (CWF) is present.

However, the study did separate results into different quartiles according to water F and urinary F concentrations and the data for the lowest quartiles are worth considering because they are for concentrations similar to that present where CWF is used.

I have extracted that data for quartile 2 of water F (0.7 to 1.00 mg/L) – a bit high compared with CWF but the data for the more relevant quartile 1 was not presented. Also the data for the second and third quartile of urinary F (UF) with the ranges 0.15 to 0.41 mg/L and 0.451 top 2.28 mg/L. Again these values are high.

Linear regression in these ranges showed no significant relationship of child IQ with either water F or Urinary F (UF) (see figure below). So much for Connett’s claim that this is a “strong scientific studies, at exposures relevant to fluoridation” that will lead to the NTP strengthening the NTP’s unsupported draft conclusion of a neurotoxic effect.

The elephant in the room – Santa-marina et al (2019)

Of course, Connett studiously ignores this study because it reported a positive relationship between maternal prenatal urinary F and child IQ (see The anti-fluoride brigade won’t be erecting billboards about this study).

The citation for this study is:

Santa-Marina, L., Jimenez-Zabala, A., Molinuevo, A., Lopez-Espinosa, M., Villanueva, C., Riano, I., … Ibarluzea, J. (2019). Fluorinated water consumption in pregnancy and neuropsychological development of children at 14 months and 4 years of age. Environmental Epidemiology, 3.

I have summarised the findings reported by Santa Marina et al (2019) below. These are certainly not going to provide any hope to Connett that the unsupported NTP conclusion will somehow be retrieved.

Conclusions

Connett is simply attempting, in his press release, to put a brave face on the embarrassment of the NAS peer review report. He and his supporters had been actively promoting the unsupported conclusion of the draft report – even suggesting it would shortly lead to the end of CWF. So a public embarrassment and he responds by holding out hope that his position will be retrieved by new studies.

His reliance on new studies is effectively an acknowledgement that the studies considered by the NTP were not adequate for the draft conclusion presented. However, he is wrong to describe these studies as “strong.” They are actually very weak and are hardly likely to change the final NTP assessment. He has also actively ignored, and hidden, the fact that the new studies are contradictory (Santa-marina et al 2019 produced the opposite result to what Connett wants) and conflicting (the different studies rely on different measures of cognitive ability and fluoride intake as well as manipulation of the data to find significant relationships).

The revised NTP report will not be produced soon as the peer reviewers identified a range of problems which will require major changes. There may well be even newer studies reported in the interim and these may not help Connett’s case any more the ones he cited. On top of that, the NTP may well discover older studies that their biased selection process missed in their original literature search (I still hold out hope that they will this time in include Perrott (2018) which, I believe, raises important issues about the effect of confounders ignored by other studies).

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Industry-funded translation can introduce bias in selection of studies for scientific review

Image credit: Assessing and addressing bias in systematic reviews

The Fluoride Action Network (FAN), in the last decade, paid for translation of a lot of Chinese-language scientific papers linking high fluoride dietary intake to IQ deficits in children. They, of course, selected papers to fit their own ideologically-motivated bias. This is perfectly understandable for an activist group. But has this caused a bias in available English-language sources on this topic? And does this mean recent scientific reviews of this subject unintentionally suffer from selection bias?

I hadn’t considered this possibility before, but it is an issue raised in the recent US National Academies of Sciences (NAS) peer review of the US National Toxicity Program’s (NTP) review of possible neurotoxic effects of fluoride (see Another embarrassment for anti-fluoride campaigners as neurotoxic claim found not to be justified).

Use of FAN sources introduces biased study selection

The NAS peer reviewers are harshly critical of the NTP draft review. A central concern was the way the NTP evaluated the literature on the subject. The NAS peer reviewers say on page 3 of their report:

“The committee had substantive concerns regarding NTP’s evaluation of the human evidence as noted below. The strategy used for the literature search indicated that NTP used FAN as a source to identify relevant literature. The process by which FAN identified and selected studies is unclear, and that uncertainty raises the question of whether the process could have led to a biased selection of studies. Such a concern raises the need for a formal evaluation of any potential bias that might have been introduced into the literature-search process.”

OK, I am not impressed that the NTP used FAN as a source. FAN is hardly a reliable source and its “study tracker” certainly does not pick up anywhere near the full literature available (see Cherry-picking and ring-fencing the scientific literature). But, at first thought, I imagined that the FAN source simply produced a subset of anything that is picked up using a more reliable source like PubMed to do literature searches.

Injection of study bias into English-language scientific literature

But the NAS peer reviewers raise an important problem with reliance on FAN as a source and its effect on the available English-language scientific literature. On page 24 of their report they say:

“. . the process by which FAN identified and selected studies is not clear. FAN identified a number of studies published in Chinese language journals—some of which are not in PubMed or other commonly used databases—and translated them into English. That process might have led to a biased selection of studies and raises the question of whether it is possible that there are a number of other articles in the Chinese literature that FAN did not translate and about which NTP is unaware. NTP should evaluate the potential for any bias that it might have introduced into the literature search process. Possible ways of doing so could include conducting its own searches of the Chinese or other non–English-language literature and conducting subgroup analyses of study quality and results based on the resource used to identify the study (for example, PubMed vs non-PubMed articles). As an initial step in such evaluations, NTP should consider providing empirical information on the pathway by which each of the references was identified. That information would also improve understanding of the sources that NTP used for evidence integration and the conclusions drawn in the monograph.”

In a nutshell, FAN arranged and paid for translation of quite a large number of Chinese papers on this issue (fluoride intake and child IQ deficits). Naturally, they have selected papers supporting their political cause (the abolition of community water fluoridation) and ignored papers which they could not use to that end. It is therefore likely they have introduced into English-language scientific literature a biased selection of Chinese papers because FAN effectively “republished” the translated papers in the journal “Fluoride” – a well-known repository of anti-fluoride material.

Maybe I was wrong to assume anything from FAN would simply be a subset of what is available through more respectable searching sources. But, according to the peer reviewers, some of the translated papers may be picked up when FAN is used as a source of studies but not when PubMed or similar respected sources are used. A warning, though – many of the FAN-promoted translated studies have only been partly translated, maybe only the abstract is available. This is not sufficient for a proper scientific review (see Beware of scientific paper abstracts – read the full text to avoid being fooled).

I am not saying this bias introduction into the English-language scientific literature was intentional, but it is a likely end-result of their actions. Importantly, it is also a likely end-result of funding from big money sources (the “natural”/alternative health industry which funds FAN and similar anti-fluoride and anti-vaccination groups – see Big business funding of anti-science propaganda on health).

So, is this a way that big industry can inject their bias into the available scientific literature? A way to ensure that reviewers will, maybe unintentionally, convey this industry bais into their own summary of scientific findings?

Reviewers should make a critical assessment of studies

The FAN-promoted Chinese studies really do not contribute to any rational discussion of issues with CWF because they were all made in areas of endemic fluorosis. Ironically they often compare child IQ in villages where fluoride intake is high, with that in villages where the fluoride intake is low. It is the low -fluoride villages which are relevant to areas of CWF because their drinking water F concentrations are comparable.

In reality, these Chinese studies could be used to support the idea that CWF is harmless. Even if that is an inherent assumption for low fluoride intake in these studies.

So, perhaps the bias introduced to the literature by translation of the FAN-promoted studies really is of no consequence to the evaluation of CWF. However, consideration of reviews like the recent one by Grandjean (2019) indicates there is a tendency to simply extrapolate from high concentration studies to make unwarranted conclusions about CWF. In this case, the tendency is understandable as Grandjean is well known for his opposition to CWF and is often used by FAN to make press statements raising doubts about this health policy (see Special pleading by Philippe Grandjean on fluorideSome fluoride-IQ researchers seem to be taking in each other’s laundry, and Fluoridation not associated with ADHD – a myth put to rest).

This was also a problem with the draft NTP review which produced the (unwarranted) conclusion “that fluoride is presumed to be a cognitive neurodevelopmental hazard to humans.” The draft did actually mention that the conclusion “is based primarily on higher levels of fluoride exposure (i.e., >1.5 ppm in drinking water” and “effects on cognitive neurodevelopment are inconsistent, and therefore unclear”  for “studies with exposures in ranges typically found in the water distribution systems in the United States (i.e., approximately 0.03 to 1.5 ppm according to NHANES data).” But, of course, it is the unwarranted conclusion that gets promoted.

Conclusions

Reviewers need to be aware of this and other ways activist groups and big business can inject bias into the scientific literature.

This problem underlines the responsibility reviewers have of recognising all possible ways that biased selection of studies they consider can occur. It also means they should make every effort to include negative studies (not supporting the effect they may personally prefer) as well as positive studies. They also need to include all the findings (positive and negative) included in the individual studies they review.

In cases like the FAN-promoted Chinese studies, there is an obligation to at least note the possibility of bias introduced by activists and industry-funded translations. Even better, to ensure that the reviewer undertakes to independently search for all studies on the subject and arrange for translations where necessary.

Above all, reviewers should critically consider the quality of the studies they include in their reviews and not simply rely on their own confirmation bias.

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