Subject: The University of York Review on Fluoridation

Dear Madam / Sir

Thank you for the opportunity to comment.

Difficulty of interpreting the results as printed with only limited access to the original papers:

I have experienced some difficulty in interpreting some of the results without having access to the original papers because of uncertainty about whether the results as listed in the tables are accurate and properly represent the material in the original paper. I understand the data in the tables has gone through a triple check process for accuracy but as noted it is possible that some errors remain. After finding some errors I have had doubts about what is accurate and what is not.

Examples of errors:

In the Caries study validity assessment reference is made to Brown 1965 but in the Dental Caries Studies: Results table the reference is to Brown 1962 rather than 1965.

In the Fluorosis Study Validity Assessment Colquhoun is mispelt as Colguhoun.

In the Cancer Studies: Results Lynch (1985) prostate is mispelt repeatedly as prostrate.

In the Bone Effects Studies: Results table for Kurttio (1999) the crude risk for Males / 100 000 for Group 2 [first reference to Kurttio 1999] is given as 7140.6 and for the Control group [second reference to Kurttio 1999] the figure is given as 9166.2. However reference to the original paper indicates that the correct figures are 140.6 and 166.2 respectively.

Difficulties with interpretation:

I find the method of setting out the results in tables makes interpretation of the significance of the paper difficult.

Using the example above of the Kurttio 1999 paper in the Bone Effects Studies:Results it appears that there are two studies by Kurttio in 1999.

In the first, the results for females show the rate ratio for Group 3 [F 0.5-1.0] of 1.12 was not different from the Control Group [F 0.3-0.5] value of 1.12. The rate ratios for Group 2 [F 1.1-1.5] and Group 1 [F 1 >1.5] were 1.08 and 1.08, both less than the control group. Thus one might conclude that the rate ratios for Groups 1,2 and 3 were all less than or equal to that of the control group and therefore there was no increase in hip fractures in females related to greater exposure to fluoride.

Similarly, in the second, the rate ratio for females in Group 1 [F 0.11-0.30] of 0.93 is less than that for the Control Group [F < or = 0.10] of 1.0. One might again conclude that there is no increase in hip fractures in females related to greater exposure to fluoride.

However by reference to the original paper it is apparent that there was only one study in which six groups were compared with fluoride levels of < or = 0.10, 0.11-0.30, 0.31-0.50, 0.51-1.00, 1.10-1.50 and >1.50. The reporting of the results in the table as two studies with two controls being compared to three comparison groups and one comparison group appears not to reflect the nature of the original study. Using the original method of reporting if the lowest fluoride group, <0.10, was taken as the control group then, of the five comparison groups, four would have higher rate ratios.

Thus, depending on how the results are presented, two different conclusions might be reached of either a lower or equal rate ratio in the higher fluoride groups, or a higher rate ratio in four out of the five higher fluoride comparison groups.

This reporting of this study also raises questions about the objectivity and neutrality of the reporting of the results. As noted different conclusions might be drawn depending on how the results are reported. However the results reported refer only to the group age 50-80 years. The original study also reported the results for the age group 50-65 years. These results for females indicate that if the lowest fluoride group, < or = 0.1, is considered to be the control then all five comparison groups have a higher rate ratio with this reaching 2.09 for the group with a fluoride level of >1.5.

The conclusion of the authors of the study is that the results suggest that increase in the estimated fluoride concentrations in well water is associated with elevated risk of hip fracture among women who were age 50-64 years at the beginning of the 14 year follow-up.

As dietary fluoride is only incompletely excreted with about half being stored in the body, particularly in bones, and the amount retained is related to the level and duration of intake, this study has relevance to fluoridation. For example, the total amount of fluoride retained by using water with 1 ppm of fluoride for 21 years would approximate that retained using water with 1.5 ppm of fluoride for 14 years, if other factors were constant.

By simply omitting mention of the results for the group aged 50-65 years questions about the objectivity and neutrality of the presentation of the results are liable to arise.

Similar difficulties with interpretation arise with the Hillier 2000 study. As presented in the results, the odds ratio of 1 for both those with exposure to an average drinking water concentration of fluoride of <0.9 and > or = 0.9 indicates that there is no evidence to relate higher fluoride levels to increased hip fractures. However no mention is made in the results table that the Hartlepool water which was high is fluoride was also hard and high in calcium. Although the authors saw this as being unlikely to influence the bioavailability of the fluoride and thus affect the ability to generalise the results, this view is not held by all. Lee [http://www.cadvision.com/fluoride/leelance.htm] considers that fluoride complexed with silica or sodium is readily ionized to free fluoride ions that are quickly absorbed in the gastrointestinal tract, whereas, when chemically bound to calcium, less of it ionizes and less is absorbed. Calcium is said, by Lee, to inhibit fluoride absorption and to be, in fact, the treatment of choice for fluoride ingestion overdoses.

Whitford, 1996, notes that when a readily soluble compound, such as sodium fluoride, is ingested with water, nearly 100% of the fluoride is absorbed. If the fluoride is taken with milk or baby formula or with foods, especially those containing appreciable amounts of divalent or trivalent cations, then the degree of absorption is reduced because insoluble complexes or precipitates are formed. The ability of calcium to reduce the absorption of fluoride is the basis for treating acute fluoride toxicity with gastric lavages of calcium-containing solutions. (Whitford GM. The metabolism and toxicity of fluoride. 2^nd revised edition. Basel: Karger, 1996:12.)

Thus simply looking at the results of the Hillier (2000) study in Bone Effects Studies: Results 2 Case-Control Studies does not give enough information to make a proper assessment. As shown in the paper the interpretation might be the fluoridation has no effect on femoral neck fractures according to this study. However by referring to the original paper one might reach different conclusions such as those of Lee:

1. Calcium-rich drinking water protects against absorption of the fluoride from the mineral/fluoride complexes it might also contain.
2. Since the study did not include any subjects drinking artificially fluoridated water, no conclusion can be made about the bone effects of artificial fluoridation.

The study by Sowers 1991 in Bone Effect Studies: Results reports that the two groups (1 & 3 ) with fluoride levels of 4 mg/L had a hip fracture incidence of 1492.5 and 3067.5 respectively whereas the control group and group 2 with fluoride levels of 1 mg/L had hip fracture incidences of 0. No units for the incidence rates are given. Insufficient information is given in this table to make a proper interpretation. Reference to the original paper indicates that the 5-year relative risk for a fracture of the hip, wrist or spine was 2.70 (0.16-8.28) for women aged 20-35 years at baseline and 2.20 (1.07-4.69) for women aged 55-80 years at baseline. This confidence interval for the younger women included 1 but the result for the older women was significant. In discussion the authors comment that in an earlier report of a cross-sectional study in these communities, they described more fractures were observed in participants from the higher-fluoride community. The prospective observation that there was a greater fracture incidence in a 5-year period suggests that the observation of increased fractures was not an artifact. The increased incidence of fractures in young adults, though not statistically significant, suggests that the observation among older women is also not an artifact or the function of a specific age cohort.

From these examples I have concerns about the validity of making comments based on the information in the tables. To do justice to the papers involved I feel that there would need to be access to each of the original papers so that a check could be made that what was presented in the table fitted the information in the full paper.

I have concerns that the criteria for the inclusion of papers were so narrow as to exclude papers such as 148. Colquhoun J. Child health differences in New Zealand. Community Health Studies 1987; 11:85-90 and that others such as Yiamouyiannis JA. Water fluoridation and tooth decay: results from the 1986-87 National Survey of US Schoolchildren. Fluoride, 23, 55-67 did not even make the first list of papers to consider. Both these studies involved large groups and would have been of value in indicating a lack of benefit on dental decay from fluoridation.

I have concerns that the detailed analyses by Phillip Sutton on the various fluoridation trials may not be reflected in the results presented in the tables (Sutton PRN. The greatest fraud: fluoridation. Lorne, Australia, Kurunda).

Summary

In the time available I have not been able to make a detailed analysis of all the papers. I have indicated that commenting on the results as presented in the tables is not appropriate for reaching valid conclusions. I have not had access to all the original papers referred to in the tables. From my study of the papers I have seen my conclusion is that fluoridation is ineffective in reducing dental decay, fluoridation is associated with toxicity in the form of dental fluorosis and other toxic effects are supported by sufficient evidence that the Precautionary Principle should apply and fluoridation of water supplies should cease. The toxic effects causing concern to me include increased rates of hip fractures, impairment of cerebral functioning, changes to pineal functioning, effects on thyroid functioning, and the occurrence of oral cancer and osteosarcoma. I consider that fluoridation as a public health intervention can no longer be supported.

Thank you again for the opportunity to comment.

Yours sincerely,

Bruce Spittle MB ChB DPM FRANZCP
17 Pioneer Crescent 
Dunedin   
New Zealand 

Date: 27 May 2000

Subject: York Review on Fluoridation

Thank you for the opportunity to comment further.

Inclusion criteria for the review

In my view the review will lack credibility as an authoritative document concerning the safety of fluoridation because of overly restrictive criteria about what has been able to be included. In some ways the situation is reminiscent of the old joke about the intoxicated person who lost his money in a dark alley but went around the corner to look for it under a street lamp because the light was better there. The review has excluded animal studies on the effects of fluoride and biochemical studies looking at mechanisms of action of fluoride such as the effects on G proteins. I do not see in the review an adequate discussion of the concerns raised by the work of Isaacon, Varner and Jensen; Varner, Jensen, Horvath and Isaacson; or Mullenix, Denbesten, Schunior and Kernan on neurotoxicity (references in Fluoride 1998 31:59-60. Similarly the major concerns felt about fluoride effects on G proteins as reviewed by Strunecka and Potocka are not addressed (Fluoride 1999 32:204-14). The considerable literature that has been identified as showing evidence that fluoride leads to iodine deficiency disorders and that this may underlie problems of neurological development is not discussed with the appropriate level of detail. Examining the effects of fluoride from other sources than water has been seen to be an additional basic feature to provide a credible foundation for a review of the safety aspects of fluoriation. With the present review, studies such as those of Li, Zhi and Gao on neural toxicity are omitted because the fluoride came from contaminated food rather than water although the work is clearly relevant (Reference in Fluoride 1998 31: 59-60). Adequate discussion in turn of this would require consideration of the work of Lin Fa-Fu, Aihaiti, Zhao Hong-Xin, Lin Jin, Jiang Ji-Yong, Maimaiti, and Aiken on “The relationship of a low-iodine and high-fluoride environment to subclinical cretinism in Xinjiang” IDD newsletter, Vol 7, No 3, August 1991. The literature relevant to fluoride having the effect of inducing hypothyroidism is extensive and requires detailed consideration in order for a review to have appropriate standing.

The clinical experience of a group of general practitioners in Holland led them to conduct a double blind experiment to study the effects of drinking water with additional fluoride. Their paper was seen to meet the relevance criteria for the review but not to meet the inclusion criteria and was thus excluded (Grimbergen GW. A double blind test for determination of intolerance to fluoridated water [preliminary report] Fluoride 1974 7:146-52). However to many the problem will be seen to lie with the narrowness of the York Review inclusion criteria rather than with the quality or relevance of the Grimbergen paper.

Thus I have major reservations about the credibility of the review because of the narrowness of the inclusion criteria and the associated difficulties at looking at the effects of fluoride irrespective of its source using the full range of information available including biochemical and animal studies.

Accuracy of the material presented in the report

I have not been able within the time I have had available to properly comment on all of the material that has been put forward in the report but from what I have looked at I have concerns about the level of care and accuracy displayed in the production of the review. For example on page 46 of the draft in paragraph three it notes that in Table 4.20 the direction of the association found by the study is simplified into positive (increasing risk of fracture) and negative (reducing risk of fracture). In Table 4.20 the paper by Kurttio (1999) is marked by “-“ for females for the effect of fluoridation meaning according the explanation a reducing risk of fracture. However the original article found the adjusted rate ration was 2.09 for women age 50-65 years. This was an increased risk for fracture.

Thus in order to be satisfied that appropriate conclusions were being drawn I would find it necessary to be able to check that the material in the tables accurately reflected the content of the original papers. For this I would prefer to have access to the original papers rather than having to rely on the material presented in abbreviated form in the tables.

Time frame available for commenting

I am grateful for the additional time available for comment. However a time comparable to that taken by the team to produce the draft report would be necessary if a comparable amount of effort was to be put in to similarly independently reading the original papers and drawing conclusions about what had been done and its relevance. I feel it would be appropriate to consider supplying copies of the papers accepted for inclusion to the peer reviewers and allowing adequate time for them to be independently reviewed. The review panel in Bristol have not been seen to be neutral regarding the safety or effectiveness of fluoridation and my experience of the accuracy and objectivity in the way the results have been expressed has not allowed me to have absolute confidence in the material they have presented.

Thank you again for the opportunity to comment.

Yours sincerely

Bruce Spittle