Peer review of an anti-fluoride “peer review”

In  Anti-fluoride activists define kangaroo court as “independent” I promised to review the anti-fluoridationist “International Peer Review.” This is Anti-fluoride  critique of the recent review Health Effects of Water Fluoridation: a Review of the Scientific Evidence produced by the Royal Society of NZ together with the Office of the Prime Minister’s Chief Science Advisor (hereafter refered to as the Royal Society Review).

So here is my peer review, of a review, of a review.

General comments

Anti-fluoride activists have  busily mentioned all the apparent contributors to this critique but I will only deal with Kathleen Theissen’s and Chris Neurath’s comments as only these have any substance.  James Beck declined comment saying only “On the current New Zealand case I don’t think I can do any better than Chris has done.” Similarly Speeding Micklem says only that “Chris’s analysis is excellent.”

Hardy Limeback does not engage at all with the science in the Royal Society Review, but does express his emotional attitude towards it. He says:

“I can’t be bothered to show step by step where this review does not meet the standards of critical scientific analysis. . . . Chris is right on the ball in critiquing this review. I’m not sure many people will appreciate just how detailed he is.
I’m disgusted by how sloppy the NZ reviewers were. They were obviously politically motivated.”

However, Limeback’s comment on the use they will make of their critique is interesting:

“The effort to critiquing every paragraph of the NZ review is taxing but once it is done and posted on the website, it would be most useful for those people who want to take on the promoters of fluoridation who will undoubtedly use this review to support the profluoridation agenda and point to how unscientific, one-sided, politically motivated this review really is.
I would be happy to lend my name to the list of scientific reviewers of this critique.”

So, you can get an idea of what their purpose is in their “peer review.”

Now, the specific issues raised in Theissen and Neurath’s comments.

Margin of safety

The Royal Society Review found some population groups may exceed the prescribed “safe” levels of F intake. So Theissen concludes that “the fluoride concentration in drinking water is too high and should be lowered.” However, she ignores completely the review’s comments on this issue.

“Infants 0-6 months of age who are exclusively fed formula reconstituted with fluoridated water will have intakes at or exceeding the upper end of the recommended range (UL; 0.7 mg/day). The higher intakes may help strengthen the developing teeth against future decay, but are also associated with a slightly increased risk of very mild or mild dental fluorosis. This risk is considered to be very low, and recommendations from several authoritative groups support the safety of reconstituting infant formula with fluoridated water.”

The review also noted that children from 1 – 4 yrs old do not exceed recommended levels on F intake but intake from ingested toothpaste my increase intake above recommended levels. It goes on to conclude:

“Consumption of fluoridated water is highly recommended for young children, as is the use of fluoride toothpaste (regular strength – at least 1000ppm), but only a smear of toothpaste should be used, and children should be supervised during toothbrushing to ensure that toothpaste is not swallowed/eaten.”

I also discussed the issue of risk for formula-fed infants in my article When politicians and bureaucrats decide the science  and in my exchange with Paul Connett. Here I note how “peace of mind” advice to those parents who may be concerned about increased risk of dental fluorosis gets presented by anti-fluoride people as safety warnings.

Adequacy of standards for fluoride intake

Theissen discusses the adequacy of a stands for F intake at length but her only beef with the Royal Society Review on this appears to be that it doesn’t challenge existing standards. She herself considers that these standards should be revised to “obtained values much lower than those currently considers desirable by the New Zealand government.” But here she is promoting a personal agenda and not objectively critiquing the Royal Society Review.

Effects of community water fluoridation (CWF) in NZ

Theissen considers that the NZ review offered “little documentation for the beneficial effects of fluoride.” Strange – has she read the review? Table A2 lists 21 major reviews it considered and 7 New Zealand sources were included – the 2009 NZ Oral Health Survey and regional studies in Otago, Southland, Canterbury, Wellington, Auckland and Northland.

If that was insufficient for Theissen then why is her only counter to mention John Coulquhoun’s reminiscences in his article of 1997? It is not enough for Theissen to use his assertions “that there are virtually no differences in tooth decay rates related to fluoridation” and “25 percent of children had dental fluorosis.” But has she bothered to check out his data at all critically? Why no more citations supporting her  claim?

Coulquoun was a committed anti-fluoridationist  and a critical check of his claims show them to be unreliable. Here is a sentence from the abstract of his paper Colquhon 1985:

“In the unfluoridated areas all the children, and in the fluoridated areas only selected children, had received regular topical fluoride treatments.” And he concluded “When the socioeconomic variable is allowed for, child dental health appears to be better in the unfluoridated areas.”

Apart from the wishful thinking displayed in his interpretation of a statistically non-significant difference he has glossed over the fact that both fluoridated and unfluoridated groups were receiving fluoride treatments of one sort or another!

Similarly, Theissen puts more trust in Colquhoun’s brief comment on dental fluorsis than the several  pages on this subject in the review. Anti-fluoride propagandists are continually misrepresenting dental fluorosis data to imply any extremely mild forms attributable to fluoridation should be treated like the severe forms which are not caused by fluoridation. The Royal Society review’s comment on the aesthetic effects help bring some context back on this issue:

“It is important to note that the seemingly high prevalence of fluorosis reported in some studies and systematic reviews includes mainly mild and very mild (and sometimes questionable) degrees of fluorosis, with only a small proportion that would be considered to be of aesthetic concern.

Surveys have shown that very mild to mild dental fluorosis is not associated with negative impact on perception of oral health,[142] and that adolescents actually preferred the whiteness associated with mild fluorosis.[143] In a recent study, adolescents answered a questionnaire regarding the impact of enamel fluorosis on dental aesthetics, older adolescents rated photographs of mild fluorosis more favorably than younger ones. A fluorosis score indicative of moderate fluorosis was the level considered to have aesthetic significance. Carious teeth were rated significantly lower than fluorosed teeth.[144]

Carcinogenicity and genotoxicity

Theissen, like almost all anti-fluoride propagandists, relies completely on the  the Bassin et al (2006) study for evidence here and ignores later studies which did not confirm Bassin’s work. In my exchange with Connett I criticised him for the same tactic (see Fluoride debate: Final article – Ken Perrott):

“the importance Paul gives to a single study on fluoride and osteosarcoma illustrates his mechanical and selective approach to “weight of evidence.” He has not bothered including either the study by Comber et al (2011) of this issue in Ireland or the study by Levy & Leclerc (2012) for the US. Possibly because both of these concluded that water fluoridation has no influence on osteosarcoma incidence rates.”

So while Theissen is upset the Review “dismisses” Bassin’s work, this is not the “out of hand” rejection she implies. The Review says:

“The few studies that have suggested a cancer link with CWF suffer from poor methodology and/or errors in analysis. Multiple thorough systematic reviews conducted between 2000 and 2011 all concluded that based on the best available evidence, fluoride (at any level) could not be classified as carcinogenic in humans. More recent studies, including a large and detailed study in the UK in 2014, have not changed this conclusion. “

Neurotoxicity

I partially agree with Neurath’s charge on the inadequacy of the Royal Society’s comment on the standardised weighted mean difference in IQ scores discussed by Choi at al (2012). Some people have made a lot of the confusion around this issue. I would like someone with good statistical skills to comment on the risks involved in making such an analysis in a meta study where there is no conformity of experimental design or treatment in the individual studies.  Wikipedia lists a number of pitfalls in statistical meta analysis, two of which seem particularly relevant here – publication bias and agenda-driven bias. In my article Quality and selection counts in fluoride research I described how the studies used had been selected and it is hard not to see an agenda behind this. So, I do think Choi et al’s statistical analysis is questionable.

However,  this issue is irrelevant to CWF because of the generally high drinking water fluoride concentrations used in these studies. Theissen and Neurath resort to the special pleading in their efforts to avoid that problem.

Theissen stressed that in the Choi et al review “One study had “high” at 0.88 mg/L, quite relevant to CWF.” Neurath says “In fact, one of the Chinese IQ studies had an average water concentration of 0.88 mgL in the high exposure group.”

At first sight this seems relevant to CWF and Paul Connett, like many anti-fluoride activists, stress this study in defending the relevance of Choi et al (2012). Strange then that none of them actually discuss the study details. Perhaps we should.

The study is a one and a half pages newsletter report:

Lin et al (1991). The relationship of of low-iodine and high-fluoride environment to subclinical cretinism in Xinjiang. Iodine Deficiency Disorder Newsletter, 24–25.

It has few of the details we normally expect in scientific papers. For example, I would like to know what the range of fluoride concentrations was in the drinking water, what other dietary intake occurred, how was the “dental fluorosis” observed defined, etc.

Children from low iodine areas were compared with a group from another area that had received iodine supplementation. About 15% of the children suffered mental retardation, 69% of these exhibited subclinical endemic cretinism. The effect of iodine supplementation was clear, the effect of fluoride not so clear. But anyway, hardly a report to hang any conclusion on about CWF in New Zealand.

They also resorted to special pleading to downplay other problems with these studies:

Theissen:

“the one study . .  that did not show lower IQ still showed a tendency in that direction (just not statistically significant) and it certianly did not show clear absence of any effect”

“While some of the neurotixicity studies did not address confounders, some did handle them responsibly” [Most of them didn’t]

Neurath:

“most of the studies did consider other sources of exposure such as from food dried over coal fires . . . This in almost all studies, major alternative sources of fluoride exposure were ruled out or controlled for” ”  – [In fact they weren’t as most didn’t consider other inputs]

“several of the studies did consider each of these potentially confounding factors, and at least one group of researchers (lead by Xiang) considered all of them and more.” [yes, one – “all and more” – but why not consider Xiang in detail then? Why try to spread his thoroughness throughout all these meagre studies?

“simply failing to assess these factors in a study does not mean the study was confounded and produced invalid results.” [well no, but isn’t it best to check known confounders?]

“Connett’s get-together” – 5th FAN Conference, Sept 6-8, 2014. Credit: Photo by Corey Sturmer,

Anti-fluoride people also often single out the study of Xiang, et al (2003). Effect of fluoride in drinking water on children’s intelligence. Fluoride, 36(2), 84–94, because unlike the others it is more detailed.  Xiang’s team has studied areas where fluorosis is endemic. Here is a slide from his presentation  to Paul Connett’s recent anti-fluoride “get-together” (Xiang 2014). This is not the very mild dental fluorosis attributed to CWF.

Now I think severe dental fluorosis like this would create learning difficulties for children in the same way dental decay does (Seirawan et al 2012). I suggested this in Confirmation blindness on the fluoride-IQ issue. Presumably Xiang could have analysed his data to check if the apparent IQ drop was correlated with the prevalence of dental fluorosis. I would think that could be an obvious first step.

Theissen  berates the Royal Society review for suggesting there is no plausible mechanism for the effect of F on IQ. Instead she resorts to special pleading again – admitting “no mechanism has been established,” attributing that to lack of research, not the absence of a mechanism. And then speculating on possible mechanism related to thyroid function, etc. The trouble is that this sort of special pleading can soon convert logical possibilities into established proof in the minds of the faithful. And meanwhile an obvious possible cause of the IQ data may be staring her in the face but she is oblivious because it does not involve “brain damage.”

Animal studies

Theissen rejects the Royal Society’s dismissal of results from animal studies because of the high concentrations used in them. She says baldly “animals require much higher exposures (5-20 times higher, or more; see NRC 2006; 2009). But what does NRC 2006 actually say (The NRC 2009 simply references NRC 2006)? It discussed the contradictory data used for attempting to show a ratio between humans and rats for blood plasma levels and concluded:

“Dunipace et al. (1995) concluded that rats require about five times greater water concentrations than humans to reach the same plasma concentration. That factor appears uncertain, in part because the ratio can change with age or length of exposure. In addition, this approach compares water concentrations, not dose. Plasma levels can also vary considerably both between people and in the same person over time (Ekstrand 1978).”

Again Theissen resorts to special pleading converting a vague possibility into an established “fact” in an effort to justify the unquestioned use of animal studies using high concentrations.

Mullinex et al (1995) also attempted to justify use of similar animal studies by comparison of blood plasma F levels. However, there is a huge range and variability in these levels so extremely easy to make subjective justification. I am suspicious of such speculation.

While I am happy to  acknowledge that it may be too simple to equate the effects for humans and animals at the same intakes, I think Theissen’s assertion “animals require much higher exposures” is straw-clutching. Millunex et al (1995) exhibited the same straw-clutching when she asserted plasma levels in her rats were similar to those in “humans exposed to high levels of fluoride.” Anti-fluoride activists love to quote Mullinex while ignore or downplaying the word “high.” She was quoting plasma F concentrations for children receiving 5 – 10, and 16 mg/L F, 10 or 20 times higher than used in CWF! But the huge effect of treatment time on plasma F concentration in rats must surely warn any objective reader to be very careful about these sort of claims. (Rats receiving 125 ppm F had plasma concentrations of about 0.1 mg/L after 6 weeks exposure but 0.64 ± 0.31  mg/L after 20 weeks).

Endrocrine effects

Theissen appears not to have properly read this section of the Royal Society Review.

Contrary to her assertion it does refer to the NRC discussion of these effects and comments:

“Most of the reviewed animal studies were designed to ascertain whether certain effects occurred, and not to determine the lowest exposures at which they occurred. The report concluded that fluoride (at unspecified levels) can affect normal endocrine function or response, and that better characterisation of fluoride exposure in humans in epidemiological studies is needed to investigate the potential endocrine effects of fluoride.”

It acknowledges potential effects (at unspecified levels) despite Theissen’s claim it “failed to mention” them. However, at this time no such effects have been observed in humans at the concentrations used in CWF. So the Review summarises its findings this way:

“A number of other alleged effects of CWF on health outcomes have been reviewed, including effects on reproduction, endocrine function, cardiovascular and renal effects, and effects on the immune system. The most reliable and valid evidence to date for all of these effects indicates that fluoride in levels used for CWF does not pose appreciable risks of harm to human health.”

Conclusion

The Royal Society Review evaluated current scientific knowledge on health effects of fluoridation. It was requested by the Auckland Council on behalf of several local Councils. They wanted a review of the scientific evidence for and against the efficacy and safety of fluoridation of public water supplies. This requirement arose from the recent campaigns by anti-fluoridation activists who targeted individual councils with a barrage of misinformation.

We should understand that the size and accessibility of the Review is aimed at informing public decision-making on the issue.  For this reason it also deals with New Zealand aspects. It is not meant to be as extensive and detailed as the 530 page US National Research Council report.

Hopefully any future consideration of community water fluoridation by local body councils will be better informed because of the Royal Society review. In particular it should help counter the sort of misinformation that has confused some councils in the past.

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References

Colquhoun, J. (1985). Influence of social class and fluoridation on child dental health. Community Dentistry and Oral Epidemiology, 13(1), 37–41.

Bassin, E. B., Wypij, D., Davis, R. B., & Mittleman, M. a. (2006). Age-specific fluoride exposure in drinking water and osteosarcoma (United States). Cancer Causes & Control : CCC, 17(4), 421–8.

Choi, A. L., Sun, G., Zhang, Y., & Grandjean, P. (2012). Developmental fluoride neurotoxicity: A systematic review and meta-analysis. Environmental Health Perspectives, 120(10), 1362–1368.

Comber, H., Deady, S., Montgomery, E., & Gavin, A. (2011). Drinking water fluoridation and osteosarcoma incidence on the island of Ireland. Cancer Causes & Control : CCC, 22(6), 919–24. doi:10.1007/s10552-011-9765-0

Eason, C., & Elwood, JM. Seymour, Thomson, WM. Wilson, N. Prendergast, K. (2014). Health effects of water fluoridation : A review of the scientific evidence (p. 74). Royal Society of New Zealand and Office of the Prime Minister’s Chief Science Advisor.

Levy, M., & Leclerc, B.-S. (2012). Fluoride in drinking water and osteosarcoma incidence rates in the continental United States among children and adolescents. Cancer Epidemiology, 36(2), e83–e88.

Lin Fa-Fu, Aihaiti, Zhao Hong-Xin, Lin Jin, Jiang Ji-Yong, Maimaiti, and A. (1991). The relationship of of low-iodine and high-fluoride environment to subclinical cretinism in Xinjiang. Iodine Deficiency Disorder Newsletter, 24–25.

Ministry of Health. (2010). Our Oral Health: Key findings of the 2009 New Zealand Oral Health Survey. Wellington: Ministry of Health.

Mullenix, Phyllis J., Debenstein. Pamela K., Schunior, A., & Kernan, W. J. (1995). Nuerotoxicity of sodium fluoride in rats. Neurotoxicology and Teratology, 17(2), 169–177.

National Research Council. (2006) Fluoride in Drinking Water: A Scientific Review of EPA’s Standards. Washington, DC: The National Academies Press.

Seirawan, H., Faust, S., & Mulligan, R. (2012). The impact of oral health on the academic performance of disadvantaged children. American Journal of Public Health, 102(9), 1729–34.

Thiessen, KM., & Neurath, C. (2014). International Peer Review of the Royal Society/PM Science Advisor Office Fluoridation Review. Internet document.

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.

Xiang, Q. (2014) Fluoride and IQ research in China. Keynote Address at FAN’s 5th Citizens’ Conference on Fluoride.