Water Fluoridation: Safety, Effectiveness and Value in Oral Health: A Symposium at the 2014 Annual Meeting of the American and Canadian Associations for Dental Research

Correction: An incorrect version of this article was originally published in error on November 5, 2015. The correct, updated version of the article now appears, as of November 30, 2015. The JCDA.ca editorial team apologizes for this error.

Introduction

For more than 60 years, community water fluoridation (CWF) has been a cornerstone in the prevention and control of dental caries in the United States, Canada, Australia, as well as other countries in Europe, South America and Asia.^1,2 The benefits of CWF have been recognized by many professional and international health agencies, including the American and Canadian dental and medical associations, the federal governments of Canada and the United States, the World Health Organization, and grassroots organizations working on improving the oral health of their communities.^2-6 CWF is an effective way to prevent and control dental caries, one of the most prevalent chronic diseases affecting children and adults.² CWF works by maintaining a low concentration of fluoride in saliva and dental plaque (biofilm) that promotes remineralization while preventing demineralization of hard tissue in both enamel and cementum.²

Other sources of fluoride, such as toothpastes, mouthrinses, gels, and varnishes, also extend the benefits of fluorides ⁷. A major advantage of CWF over other fluoride vehicles is that people receive its benefits throughout the day without making a conscious effort to buy and use the product or visit the dental office for a topical fluoride application. Because of its role in reducing tooth decay and improving oral health, the Centers for Disease Control and Prevention (CDC) identified CWF as one of 10 great public health achievements of the 20^th Century, along with vaccination and sanitation.⁸

Despite its merits, CWF may be one of the most scrutinized public health interventions. Early allegations included increased overall mortality and occurrence of Down syndrome in fluoridated communities.¹ More recently, claims have focused on specific cancers, endocrine disorders, behavioural, cognitive and other neurological effects.²

Alleged adverse health claims have triggered governmental reviews. The National Research Council (NRC) in the U.S. reviewed the major adverse health claims of fluoride in 1993 and 2006.^9,10 The 1993 review found no adverse health effects associated with the ingestion of fluoride at the concentrations used for CWF (0.7-1.2 milligrams/liter (mg/L). The only unwanted effect at these levels, enamel fluorosis, was considered an aesthetic problem. The 2006 review focused on potential adverse effects of naturally occurring fluoride at 2–4 mg/L in drinking water, levels higher than that recommended for CWF. At these higher  levels, the 2006 NRC review found substantial evidence only for an increased risk of severe enamel fluorosis (measured by pitting of the tooth enamel) as a health effect and recommended that the U.S. Environmental Protection Agency (EPA) review its drinking water standards in order to prevent this outcome.¹⁰

Parallel to EPA's review of safety of fluoride in drinking water,^11,12 the U.S. Department of Health and Human Services initiated its review and update of the 1962 U.S. Public Health Service (PHS) Drinking Water Standards related to community water fluoridation. The PHS now recommends an optimal fluoride concentration of 0.7 mg/L.²   This updated guidance for the U.S. is based on the effectiveness of CWF in preventing caries in children and adults, the availability of other fluoride sources, the increase in dental fluorosis with access to more sources of fluoride, and current evidence showing that outdoor temperature is not an important predictor of water intake in children^{2, 13}.  As part of its review, HHS accepted the comprehensive 2006 NRC review as the summary of hazard and took into account findings of updated health and exposure assessments by EPA.^11,12  

The public discussions between opponents and supporters of CWF, whether at the ballot box or city council meetings, can be similar to other passionate public debates on health-related issues, such as global warming or vaccination. Positions may at times be shaped by personal experience or findings from studies of questionable scientific rigor to support, for example, potentially harmful effects of CWF, claims that are not based on the best available science.² As public health practitioners and scientists, it is critical that we continue to provide sound evidence-based information in response to allegations against CWF to support informed decision-making by the public.

In response to these challenges, one of the co-authors (SA) proposed 3 years ago to promote scientific discussion of CWF and fluoride at the joint annual meeting of the American and Canadian Associations for Dental Research (AADR/CADR). Two prominent researchers and two public health professionals with extensive experience in fluoride, fluoridation and public health implementation were invited to present at a symposium. One of our speakers, Dr. Jay Kumar, was part of the 2006 National Research Council review on fluorides. Dr. Barbara Gooch is a public health professional with the Centers for Disease Control and Prevention and served on the HHS Federal Panel on Community Water Fluoridation that updated the recommendation based on the current science. Two leading methodologists and researchers on fluoride, Dr. Angeles Martinez-Meir and Dr. Gary Slade, provided the background needed to engage in discussion.

The objective of this symposium was to review the scientific evidence supporting CWF and consider the implications for optimizing the use of fluoride in public health and clinical practice. The following presentations were held at the symposium:

1. Effectiveness of fluorides: findings of evidence-based reviews

Dr. Martinez-Mier, Professor and Chair, Department of Cariology, Operative Dentistry and Dental Public Health, Indiana University School of Dentistry

2. The health assessment of fluoride in drinking water: Conclusions from the National Research Council and subsequent scientific assessments by EPA

Dr. Jay Kumar, State Dental Director California Department of Public Health Chronic Disease Control Branch

3. Gaps in scientific knowledge regarding water fluoridation and other fluoride modalities

Dr. Gary Slade, John W. Stamm Distinguished Professor of Dentistry, Department of Dental Ecology, University of North Carolina at Chapel Hill

4. Community water fluoridation: Translating evidence into public health practice

Dr. Barbara Gooch, Associate Director for Science, Division of Oral Health, NCCDPHP, CDC

We have edited and summarized these presentations; for reasons of brevity, we may have omitted specific issues. The symposium was designed to highlight current issues in water fluoridation and confirm its safety and effectiveness in dealing with caries. The presentations and slide decks can be found at the end of this article.

Our goal in this meeting report is to highlight the most important aspects of the presentations to those who need to provide answers to anti-fluoridation claims at the local level.

Summary

The 4 speakers at the symposium agreed that community water fluoridation (CWF) is safe, effective and adds value in oral health care.

Dr. Martinez-Mier's presentation reported that the use of fluoride has been associated with a substantial reduction in caries in children and adolescents. The presentation also highlighted evidence gaps for effectiveness of certain fluoride modalities, as well as the relationship among effectiveness, dose, and safety for the products. With the exception of enamel fluorosis, no other adverse effects are associated with community water fluoridation.

Dr. Kumar reviewed the findings and recommendations of the 2006 National Research Council report ¹⁰ that identified severe enamel fluorosis as a health effect of fluoride ingestion. Dr. Kumar also reviewed the two 2010 U.S. Environmental Protection Agency (EPA) reports^11,12 that followed the NRC recommendations. From these reports, the EPA has proposed a reference dose of 0.08 mg/kg/day for protection against severe enamel fluorosis. He reported that the Department of Health and Human Services has proposed a single fluoride value of 0.7 mg/L in drinking water for the prevention of caries instead of the range of 0.7–1.2 mg/L which has been used since 1962. This recommendation came into effect in April 2015.²

Dr. Slade emphasized the need to focus on adults. He reported the results of a nationally representative study¹⁴ of Australians adults; those with prolonged lifetime exposure to water fluoridation had less caries experience than adults with negligible exposure. The study found that fluoridated water reduces the prevalence of dental caries in adults even if they start drinking it after childhood.

Dr. Gooch reported that 2 systematic reviews by the Community Preventive Services Task Force found that community water fluoridation was cost-savings in all included studies.^15,16 The Community Preventive Services Task Force in 2013¹⁶ also found no evidence that CWF results in severe dental fluorosis, bone fractures, skeletal fluorosis or in any unwanted health effects other than milder forms of dental fluorosis.

Systematic Reviews on Effects of Community Water Fluoridation Released after 2014 AADR/CADR

In 2015, the Department of Health of the Republic of Ireland reported the results of a systematic review on the health effects of water fluoridation¹⁷ and concluded that in non-endemic or CWF areas, defined as < 1.5 mg F/L in the drinking water, there is "no strong evidence that CWF is definitively associated with negative health effects." The review concluded that the evidence for some health outcomes is scarce and mostly ecological studies where causality cannot be established. In the interpretation of whether a hypothesized health effect exists, the public health professional should take into account the plausibility of an effect (biological), the criteria for causality, the design and scientific rigor of the studies and, in the case of systematic reviews, the PICO questions (Population, Intervention, Comparison, Outcome) and criteria for inclusion and exclusion of studies.

In 2015, the Cochrane Oral Health Group also released findings of their systematic review on the effects of fluoride in water on preventing tooth decay and on dental fluorosis.¹⁸ Consistent with other reviews Cochrane found that water fluoridation was effective at reducing caries in children's permanent and primary teeth – resulting in up to 35% fewer teeth affected by cavities.  In addition, CWF resulted in higher percentages of children who were caries-free. The investigators noted, however, that few recent studies met their inclusion criteria of evaluating at least one population that received fluoridated water and one that did not at two points in time. Results also suggested that about 12% of persons could have dental fluorosis of aesthetic concern (e.g. "mild" or worse in Dean's Fluorosis Index) when the fluoride concentration in drinking water was 0.7 mg/L.   

THE AUTHORS

	Dr. Abrams is a general practitioner in Toronto, Ontario, and president and founder of Quantum Dental Technologies. Email: dr.abrams4cell@sympatico.ca
	Dr. Beltrán-Aguilar is currently a consultant on epidemiology and public health in Atlanta, Georgia.
	Dr. Martinez Mier is professor and chair, department of cariology, operative dentistry and dental public health, Indiana University School of Dentistry, Indianapolis, Indiana.
	Dr. Kumar is state dental director, California department of public health, chronic disease control branch, Sacramento, California.
	Dr. Slade is John W. Stamm distinguished professor of dentistry, department of dental ecology, University of North Carolina, Chapel Hill, North Carolina.
	Dr. Gooch was associate director for science, division of oral health, National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Centers for Disease Control and Prevention (CDC), Atlanta, Georgia.

Synopsis of presentation made at Session # 111, AADR/CADR Annual Meeting and Exhibition, Charlotte, NC March 21, 2014

Title "Effectiveness of Fluorides: Findings of Evidence-Based Reviews"

Author: Esperanza Angeles Martinez-Mier, DDS, MSD, PhD Professor, Indiana University School of Dentistry. .

Synopsis

In her presentation, Dr. Martinez Mier discussed the findings of selected evidence‐based reviews regarding the effectiveness of fluoride.  The presentation highlighted evidence gaps for effectiveness of certain fluoride modalities, as well as the relationship among effectiveness, dose, and safety for the products. Finally, she also discussed selected findings of a newly funded study on the relationship between fluoride exposure and neurobehavioral outcomes.

Most reviews have shown that fluoride is effective and safe the way it is currently used

In general, systematic reviews have shown that the application of fluoride gels and varnishes has been associated with a substantial reduction in caries in children and adolescents. ¹ However, most of the clinical trials conducted to assess the effectiveness of gels are more than 30 years old. On the other hand, clinical trials conducted to assess fluoride varnishes are more recent but of moderate quality due to issues with trial designs. ² Clinical recommendations for the use of these products have been developed based on the available evidence. ³

In the case of toothpastes, there is strong evidence supporting a caries-preventive effect in children and adolescents. ^4,5 Results of these studies have demonstrated that increased fluoride concentration, frequency of use, and supervised brushing provided a greater preventive effect. Furthermore, there is evidence supporting supervised fluoride mouth rinse use by children for caries prevention. However, as in the case of gels, most of the clinical trials conducted to assess the effectiveness of rinses are more than 30 years old. ⁶ Systematic reviews have also shown that using combinations of topical fluoride modalities offers additional benefits for caries prevention. ^7,8

Water fluoridation remains an effective and safe public health measure for caries prevention

Although the relative impact of water fluoridation on caries prevalence has steadily declined due to the widespread use of topical fluoride; water fluoridation remains a safe and effective public health measure for caries prevention. With the exception of enamel fluorosis, no other adverse effects have been associated to the use of water fluoridation. ^9,10  A newly funded study  is investigating the relationship between fluoride exposure and neurobehavioral outcomes and has demonstrated a wide range of fluoride concentrations in biomarkers of subjects exposed to normally fluoridated salt. 

Conclusions

Results of systematic reviews have shown that the use of fluoride in multiple modalities has been associated with a substantial reduction in caries in children and adolescents. Water fluoridation remains a safe and effective vehicle for caries prevention. With the exception of enamel fluorosis, no other adverse effects have been associated to the use of water fluoridation.

Synopsis of presentation made at Session #111, AADR/CADR Annual Meeting, Charlotte, NC March 21, 2014.

Title: The Health Assessment of Fluoride in Drinking Water: Conclusions from the National Research Council and the EPA Reports

Author: Jayanth V. Kumar, DDS, MPH, Director, Bureau of Dental Health, New York State Department of Health and Associate Professor, School of Public Health, University at Albany.

Synopsis

The presenter reviewed the drinking water fluoride standards in the U.S. and the key findings and recommendations of the 2006 National Research Council report titled Fluoride in Drinking Water. A Scientific Review of EPA's Standards. In addition, the presentation highlighted the dose response analysis conducted by EPA's Office water and their conclusions regarding the occurrence of severe enamel fluorosis associated with current fluoride intake in the U.S.  

Safety of drinking water in the United States

Fluoride occurs naturally at concentrations well above the recommended level for dental caries prevention in several communities in the U.S. Because fluoride can occur at toxic levels, the U.S. Environmental Protection Agency (EPA) regulates the naturally occurring fluoride levels in drinking water and sets standards. The Maximum Contaminant Level Goal (MCLG) is the ideal standard set to protect all. The Maximum Contaminant Level (MCL) is the enforceable standard and takes into consideration other aspects such as technological feasibility and cost.  In 1986, EPA established a maximum allowable concentration for fluoride in drinking water of 4 milligrams per liter (mg/L), a guideline designed to prevent the public from being exposed to harmful levels of fluoride. Stage III skeletal fluorosis was selected as the clinical endpoint. An advisory level called the Secondary Maximum Contaminant Level (SMCL) of 2 mg/L was set to protect the public from moderate and severe enamel fluorosis.

Findings and recommendations of the Subcommittee

In 2006, the National Research Council undertook a comprehensive review of health effects of fluoride in drinking water. After a review of all available evidence, the committee considered three toxicity end points for which there were sufficient relevant data for assessing the adequacy of the MCLG for fluoride to protect public health. These clinical end points were severe enamel fluorosis, skeletal fluorosis, and bone fractures. This report concluded that the EPA standard is not protective of health because fluoride exposure at 4 mg/L puts children at risk of developing severe enamel fluorosis that can compromise tooth enamel function and appearance. Lifetime exposure at 4mg/L of fluoride under certain circumstances could also weaken bone and increase the risk of fractures, especially among those who are prone to accumulate fluoride into their bones (e.g., people with renal disease). The basis for the conclusions is explained below.

Severe enamel fluorosis

The committee examined plots of 94 prevalence estimates of severe fluorosis from studies conducted in the U.S. and found a clear trend. The prevalence of severe enamel fluorosis is close to zero in communities at all water fluoride concentrations below 2 mg/L. Above 2 mg/L, the prevalence increases such that it occurs at an appreciable frequency, approximately 10% on average, among children in U.S. communities with water fluoride concentrations at or near the current allowable concentration of 4 mg/L.  The committee found strong evidence of an approximate population threshold in the U.S. such that the prevalence of severe enamel fluorosis would be reduced to nearly zero by bringing the water fluoride levels in these communities down to below 2 mg/L.

Skeletal fluorosis

The current MCLG and MCL of 4 mg/L of fluoride are set to protect against stage III skeletal fluorosis, a bone and joint condition associated with prolonged exposure to high concentrations of fluoride. In general, daily intake of 10 mg fluoride for over 10 years causes changes in the bone that lead to joint stiffness and pain, sometimes classified as stage II skeletal fluorosis. There are very few known clinical cases of skeletal fluorosis in the United States, and none has been linked solely to fluoride intake from drinking water at current acceptable levels.

Bone fractures

Overall, there was consensus among the committee members that there is scientific evidence that under certain conditions fluoride can weaken bone and increase the risk of fractures. The majority of the committee found that lifetime exposure to fluoride at drinking water concentrations of 4 mg/L or higher is likely to increase fracture rates in the population, particularly in some demographic subgroups that are prone to accumulate fluoride into their bones (e.g., people with renal disease). This increase was when compared to fluoride levels of 1 mg/L. However, other committee members didn't find increased frequency of bone fractures in the US populations exposed to fluoride at 4 mg/L. The NRC committee found one study that suggested an increase in the risk for bone fractures at 2 mg/L fluoride exposure relative to 1 mg/L but that the data were inadequate to draw firm conclusions concerning this observation.  The committee observed an interesting phenomenon in a study conducted by Li et al. in China that the lowest fracture rate observed was in the 1.0 to 1.06 mg/L fluoride category.

Recommendations

The NRC committee concluded that EPA's drinking water standard of 4 mg/L is not adequately protective of health. Further, the committee suggested that, in order to develop an MCLG that is protective against severe enamel fluorosis, clinical stage II skeletal fluorosis and bone fractures, EPA should:

• Apply current approaches for quantifying dose-response where feasible,
• Consider susceptible populations,
• Characterize uncertainties and variability, and
• Provide better estimates of total exposure for individuals.

EPA assessment

In 2010, EPA's Office of Water published two reports 1) Fluoride: Dose-Response Analysis

For Non-cancer Effects; 2) Fluoride: Exposure and Relative Source Contribution Analysis. The Office of Water (OW) accepted the NRC (2006) findings as the summary of hazard for inorganic fluoride and focused on the dose-response analysis. The first report examined the human dose-response data on enamel fluorosis, skeletal fluorosis, and skeletal fractures. The second report quantified fluoride exposures from drinking water, tooth paste, diet, beverages, and soils and dust for children and adults in the United States.  

These risk assessments considered health effects data on skeletal and dental fluorosis. According to EPA, the maximum dose that is protective of severe enamel fluorosis in children will also protect adults from long-term effects on bone. EPA has proposed a reference dose (RfD) of 0.08 mg/kg/day for protection against severe enamel fluorosis compared to the generally recommended dose of 0.05 mg/kg/day for caries protection. The reference dose is the estimate of the daily exposure that is likely to be without harmful effect during a lifetime. OW's risk assessment compared exposure estimates to the fluoride dose associated with severe enamel fluorosis. A drinking water fluoride concentration of 0.87 mg/L is considered representative of the country as a whole. Based on this analysis, EPA concluded that some children drinking water at the 90th percentile intake level up to about age 7 are being exposed to fluoride on a daily basis at levels at or higher than estimated acceptable intake levels.  Several factors led to this conclusion: 1) exposure to fluoride has increased from multiple sources of fluoride. For example, the average fluoride contribution from tooth paste was calculated to be 0.34 mg/day for 1 to <4 year old children; 2) the RfD is based on protecting 99.5% of children from severe enamel fluorosis using Dean's 1942 study that showed the point of departure for severe enamel fluorosis to be 1.87 mg/L. 3). OW assumed that 0.5% of children developed severe enamel fluorosis even when consuming average amount of water at 1.87 mg/L. 

Summary and conclusions:

EPA concluded that a comparison of the age-specific total estimated exposure for the 90th percentile drinking water consumer to the daily reference dose suggested that some children at ages less than seven years old may be at risk for severe dental fluorosis. The reference dose (RfD) may be a conservative estimate as it is derived from the average intake and not the 90^th percentile estimate. Furthermore, EPA's fluoride dose response analysis did not consider a key study conducted in Texas. Butler et al., reported severe enamel fluorosis in only one child in a community in Texas where the fluoride concentration was 3.3 mg/L, substantially less than that expected on the basis of the critical study selected by EPA for dose response analysis. In Dean's study, a fluoride drinking water concentration of 2.2 mg/L in Clovis, NM, was the lowest concentration associated with severe enamel fluorosis (0.7%).

The Department of Health and Human Services has proposed a single fluoride value of 0.7 mg/L in drinking water for the prevention of dental caries. Lowering of fluoride concentration in drinking water may decrease the prevalence of enamel fluorosis but its effect on dental caries is not known. Therefore, the impact of the proposed recommendation to revise the fluoride concentration from a range of 0.7 to 1.2 mg/L to a single value of 0.7 mg/L should be monitored.

Synopsis of presentation made at Session # 111, AADR/CADR Annual Meeting and Exhibition, Charlotte, NC March 21, 2014

Title "Dental caries preventive effects of community water fluoridation in adults"

Author: Gary D. Slade, BDSc, DDPH, PhD, John W. Stamm Distinguished Professor of Dentistry, University of North Carolina School of Dentistry. gary_slade@dentistry.unc.edu

Synopsis

The author undertook a narrative review of published reports from epidemiological studies investigating relationships between dental caries in adults and their exposure to fluoridated drinking water. The presentation also highlighted findings from the author's recent publication1 that investigated relationship.

Most reviews of dental-caries-preventive effects of water fluoridation have excluded studies of adults.

Systematic reviews evaluating caries-preventive effects of water fluoridation generally have excluded findings from adults. For example, the "York review"2 found there was insufficient evidence to reach conclusions about any such effects in adults, explaining that the review included studies only if they used a prospective study design that assessed caries at two points in time (among other criteria).

Exclusion of studies in adults is due to a misunderstanding of epidemiologic study design principles.

A prospective cohort study design is adequately approximated with data collected at one point in time when two conditions are satisfied:

1. The exposure of interest is lifetime exposure to fluoridation. This can be determined retrospectively by determining the places in which study cohort members have lived throughout their lifetime, and by consulting records of fluoride concentration in drinking water at those places.
2. The outcome of interest is lifetime caries experience. This can be determined when examiners measure caries experience of cohort members using the DMF index.

These two principals have been established for a long time. In 1948, Frederick McKay reported3 findings from a study of lifetime residents of Colorado Springs, CO, which had excessive fluoride content in the drinking water and compared the results to Madison, WI, which had negligible fluoride in the water. McKay reported a three-fold difference in lifetime caries experience of adults who had lived all their lives in the respective cities.

The exclusion of studies done in adults creates a serious bias.

A 2007 systematic review4 included nine studies of community water fluoridation in adults. The inclusion criteria "included cross-sectional studies if their participants lived most of their lives in fluoridated/nonfluoridated communities..." In their meta-analysis, they found that lifetime exposure to fluoridation was associated with a 35% reduction in dental caries in adults.

Recent evidence from Australia demonstrates caries-preventive benefits of water fluoridation in adults.

In our study of a nationally-representative sample of Australians,1 adults with prolonged lifetime exposure to water fluoridation had less caries experience than adults with negligible exposure. ~10% fewer teeth and

~25% fewer tooth surfaces were affected. There was an approximate inverse, dose-response gradient in DF- Surfaces across successively greater levels of exposure. The relationships remained consistent after adjustment for potential confounders. Caries-preventive effects of water fluoridation were at least as great in adults born before widespread implementation of fluoridation as after its widespread implementation.

Conclusions

Fluoridated water reduces tooth decay in adults, even if they start drinking it after childhood. Communities that implement fluoridation can expect benefits to accrue for both future and current generations. More people in the population benefit from water fluoridation than previously was thought. The greater benefit has a significant impact on calculations of population cost-effectiveness. Recent findings from Australia add to six decades of evidence showing that community water fluoridation prevents dental caries in adults. The evidence should be considered when formulating health policies and public health programs.

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