מאמר של Waugh. נספח לתצהיר שלו

Waugh Submitted to Journal Environmental Health, Harvard School of Public Health, Dec 2013

Title:

The Contribution of Artificial Fluoridation to Asthma Prevalence

Worldwide- A Population-based Ecological Study of Inflammatory

Respiratory Disease:

Author Details:

D.T. WAUGH BSc. MCIWEM. MIEMA. MCIWM. CEnv.

EnviroManagement Services, Bandon, Co. Cork, Republic of Ireland.

Member of The Chartered Institution of Water and Environmental Management

Member of The Institute of Environmental Management and Assessment

Member of The Chartered Institution of Wastes Management

Chartered Environmentalist

Contact Details:

Email: [email protected]

Tel: 00353-23-8841933

mailto:[email protected]


Abstract

This review article is designed to update the known and potential association, that forms the basis of

understanding for a (causal) role for artificial fluoridation to inflammatory respiratory disease. The largest

international (case controlled, cohort, cross sectional) epidemiological studies ever conducted in both

developed and developing countries, include the International Study of Asthma and Allergies in Childhood

(ISAAC) and the European Community Respiratory Health Surveys (ECRHS). Both these studies found

pronounced, statistically significant geographic variation in the prevalence of childhood and adult asthma in

specific countries and concluded that the major differences in prevalence of asthma between populations

globally are likely to be due to environmental factors. The most significant observation from these studies is

that the countries with the highest prevalence of asthma share one common environmental exposure risk

factor that to date has not been investigated, namely exposure to elevated anthropogenic or natural sources

of fluoride. Globally the highest prevalence of asthma were to be found in the few English speaking countries

where highly soluble inorganic fluorides are used for artificially fluoridation of drinking water followed by

Latin American countries with either artificial water or salt fluoridation programmes.. In 2006, the United

States National Academies, National Research Council (NRC) noted that fluoride was a pro-inflammatory

agent that increased the inflammatory response to irritants in humans. Fluoride is also acknowledged to

increase the production of free radicals, eosinophils, cytokines and cause oxidative stress, in addition to

altering calcium and magnesium balance and homeostasis. Importantly, the NRC also reported that fluoride

affects thyroid function particularly at low doses especially where patients are iodine deficient. Perhaps the

most significant finding of the NRC was that fluoride is a cholinesterase inhibitor. Cholinesterase inhibitors

are acknowledged to increase the risk of pulmonary disorders including pneumonia, persistent cough,

bronchitis, and asthma. Finally, recent findings regarding the toxicological mode of action of colloidal silica

dispersions, compounds which are created in the process of artificially fluoridating drinking water,

demonstrate a direct causal association between lung inflammation and artificial fluoridation. All of these

factors independently play a key role in the pathogenesis of asthma and clearly suggest that artificial

fluoridation has a direct causal association with inflammatory disease. This article represents the first study,

to my knowledge, to address the effects of fluoridation on inflammatory respiratory disease, and discusses

the evidence that is gathered from many scientific studies showing strong links that help explain the

significantly higher burden of respiratory disease which is to be found in countries that practice artificial

fluoridation. The results of this study provides strong evidence that the significantly increased burdens of

inflammatory respiratory disease present in geographic regions where fluoridation exists may be directly

related to increased exposure to highly soluble inorganic fluorides.

Keywords: fluoride, fluoridation, inflammatory respiratory disease, asthma


1. Introduction

Preventable chronic inflammatory respiratory diseases include asthma and respiratory allergies, chronic

obstructive pulmonary disease (COPD), occupational lung diseases, sleep apnoea syndrome and pulmonary

hypertension. They constitute a serious public health problem in all countries throughout the world, most

especially in countries where artificial fluoridation of water and salt is a public health policy. An estimated 300

million people worldwide suffer from asthma with 250,000 premature deaths annually attributed to the

disease. Almost all of these deaths are avoidable[1].

While controversy exists over artificial fluoridation worldwide nowhere to my knowledge has the mechanism

by which fluoridation may contribute to pulmonary disease every been investigated. The objective in this

study was to examine geographic variations in the incidence of inflammatory respiratory disease, specifically

asthma worldwide, and establish if there was a possible causal association with artificial fluoridation. Previous

epidemiological studies including the International Study of Asthma and Allergies in Childhood (ISAAC) and

European Community Respiratory Health Surveys (ECRHS) found pronounced, statistically significant

geographic variation in the prevalence of childhood and adult asthma and concluded that the major

differences in prevalence of asthma between populations are likely to be due to environmental factors(2-5).

The most significant observation from these studies is that the countries with the highest prevalence of

asthma share one common environmental exposure risk factor that to date has not been investigated, namely

exposure to elevated anthropogenic or natural sources of fluoride. It is a undisputed fact that the highest

burden of inflammatory respiratory disease were to be found in English speaking countries where highly

soluble inorganic fluorides are used for artificially fluoridation of drinking water followed by Latin American

countries with either artificial water or salt fluoridation programmes, in particular, those with a high

prevalence of poor nutrition which is acknowledged to increase the toxicity of fluoride in humans.

In examining the prevalence of inflammatory disease it is critically important to acknowledge both the direct

and indirect influence of fluoride in the pathogenesis of inflammatory disease. Fluoride not only acts directly

to augment the inflammatory response to irritants, but accumulates in lung tissue, amplifies biological stress

in the body, increases production of chemokines and pro-inflammatory cytokines, activate G proteins,

initiates eosinophil response] and induce excessive production of oxygen free radicals. Indirectly, fluoride

interferes with calcium, magnesium and iodine metabolism, contributing to nutritional deficiencies, inhibition

of enzymes and protein synthesis as well as endocrine function, with resultant wide ranging negative health

effects. Moreover, the fact that fluoride is acknowledged as a cholinesterase inhibitor is of particular

significance, especially given that cholinesterase inhibitors have already been established in the medical

literature for their respiratory and pulmonary toxicity. All of these aspects are highlighted in the present

paper, discussion on the potential direct and indirect role of fluoride in respiratory and pulmonary toxicity is

provided along with examination of epidemiological evidence and case studies from selected countries.

2. Presentation of the Hypothesis

Asthma is defined as a chronic inflammatory disorder characterized by airway inflammation and airway

hyper-responsiveness (AR) to inhaled stimuli [6]. It has been demonstrated that exposure to a mix of allergens

and irritants can at times promote the development of the disease [7] and it has further been reported that

chronic obstructive pulmonary disease and asthma are associated with low-grade systemic inflammatory

changes [8]. Many complex mechanisms play a role in the in the pathogenesis of asthma and chronic

obstructive pulmonary disease including cytokine production, reactive oxygen species, oxidative stress,

lysosomal cathepsins, G protein activation and eosinophils [9,10]. Fluoride is known to activate alveolar


macrophages, enhance the production of chemokines and pro-inflammatory cytokines[11], activate G

proteins, [12] initiate eosinophil response [13] and induce excessive production of oxygen free radicals [14].

The U.S. National Academies National Research Council (NRC) Scientific Committee on Fluoride in Drinking

Water (2006) reported that fluoride exposure increases the inflammatory response to irritants and

hypothesized that the main route was by means of activation of G—protein complex[15]. The NRC also

observed that “there is no question that fluoride can affect the cells involved in providing immune

responses”[15]. Finn et al. (2009) reported that immune responses play a critical role in asthma

pathogenesis[16]. It is also acknowledged that increases in cytokines and eosinophils direct and modify the

inflammatory response in asthma and likely determine its severity[9]. Fluoride even at low doses, can interact

with a wide range of cellular processes including gene expression, cell cycle proliferation and migration,

respiration, metabolism, ion transport, secretion, endocytosis, apoptosis/necrosis, and oxidative stress [17].

It has also been reported that the problems associated with fluoride exposure is that it amplifies the

biochemical stress in the body by generating imbalance between reactive oxidative species and antioxidants

thereby inducing oxidative stress and inhibiting several groups of enzymes including many whose action

depends on divalent metals such as magnesium (enolase, phosphatases) or trivalent metals (catalase,

peroxidase). These effects have been observed in several soft tissues and cells, such as brain, gastrocnemius

muscle, kidney, liver, heart, nervous system, blood and osteoblasts [18]. It has been demonstrated that

epithelial cells of the lung release increasing amounts of inflammatory cytokines in response to fluoride[19]. It

is further reported that the number of eosinophils increases with increasing urinary fluoride levels [13].

Research has revealed the importance of inflammation of the airways in asthma and the need for clinical

treatment to reduce chronic inflammation. Purohit and associates (1999) demonstrated that ingested fluoride

in water at biologically relevant exposure levels results in accumulation of fluoride in lung tissue and that

prolonged fluoride ingestion damages pulmonary tissues [20]. After six months the fluoride content in lung

tissue of the fluoride treated group was 1250% higher than the control group. Histopathological changes of

alveolar haemorrhage, congestion, oedema fluid, necrosis of alveolar epithelium, distortion of alveolar

architecture and desquamation of epithelium of respiratory tract with damage to tracheal cartilage were

observed in the animal sample groups exposed to fluoride[20]. It has also been reported that epithelial lung

cells and alveolar macrophages undergo apoptosis after fluoride exposure [19,20]. Thrane et al. (2001)

demonstrated that fluorides induced apoptosis and inhibited proliferation of cell growth in epithelial lung cells

from animals and humans[21].

Additional risk factors that contribute to increased risk of fluoride toxicity as well as asthma and asthma

morbidity include poor nutrition, particularly deficiencies in calcium, magnesium and iodine metabolism,

Vitamin D. Each play a role in the the pathogenesis of the disease while deficiency increases susceptibility to

fluoride [15,22,23]. Recently, it has also been identified that enolase plays a role in autoimmune disorders and

regulating cellular inflammatory response and inflammatory in lung tissue [24,25]. These findings are major

important as it is well established that fluoride is a potent inhibitor of enolase. However, the fact the NRC

(2006) reported that fluorides inhibit cholinesterases, including acetylcholinesterase (AChE) [15] also

provides a critical role for fluoride in contributing to respiratory disease, as cholinesterase inhibitors are

associated with increased risk of pulmonary disorders including pneumonia, persistent cough, bronchitis, and

asthma [26]. Another major finding in the link between artificial fluoridation and significantly increased

burdens of respiratory disease reported for fluoridated countries, is that the addition of artificial fluoridation

chemicals to water results in the creation of either "colloidal silica" or an "oligomerosilicate"[27]. These

compounds have been found to induce lung inflammation and tissue damage [28,29,30]. A summary review

of some of these risk factors follows.


2.1 Fluoride, Calcium, Vitamin D and Asthma

Fluoride is known to induce or exacerbate calcium deficiency by decreasing calcium absorption in the gastro-

intestinal tract, thus increasing the body’s calcium requirements. Fluoride exposure can alter both thyroid and

parathyroid function contributing to subclinical hypothyroidism, subclinical hyperthyroidism and secondary

hyperparathyroidism[15]. The toxic effects of fluoride are more severe and complex in geographical areas

with low calcium in drinking water and amongst individuals with dietary calcium deficiency. High risk

subpopulation groups include growing children, adolescents, pregnant and lactating mothers, because of the

greater demands for calcium.[31-34] It is not surprising, therefore, that asthma is the most common chronic

disease of childhood [35-41] and its prevalence has substantially increased worldwide particularly in countries

with artificial fluoridation. Asthma has been also reported to affect 3.7 to 8.4 percent of pregnant women,[42]

making it potentially the most common serious medical problem to complicate pregnancy[43].

Vitamin D3 is one of the primary biological regulators of calcium homeostasis [44], low calcium absorption has

been linked to reduced vitamin D status [45,46] and low vitamin D levels are associated with increased risk of

asthma and asthma morbidity [48,49,50]. Since fluoride is known to exacerbate calcium deficiency any

potential role of fluoride contributing to Vitamin D deficiency is therefore of critical importance, not just for

respiratory disease but for overall general health of the population.

2.2 Fluoride, Magnesium and Asthma

Magnesium is a required cofactor for over 300 enzyme systems [51]. Fluoride forms magnesium-fluoride

complexes that have an inhibitory effect on many enzymes. Among its other effects, ingestion of fluoride

increases the requirement for certain nutrients. For example, the metabolic requirement for magnesium is

increased by fluoride, sequestering it into the skeleton and thereby making magnesium less biologically

available [52].There has been a gradual decline of dietary magnesium in the developed economies in recent

decades, largely due to increased consumption of processed foods which are low in magnesium[53].

Magnesium deficiency is now relatively common in many developed countries such as the USA[54]. There are

also interactions between magnesium, calcium and vitamin D[54]. During magnesium depletion, intracellular

calcium rises. Since calcium plays an important role in skeletal and smooth muscle contraction, a state of

magnesium depletion may result in muscle cramps, hypertension, and coronary and cerebral vasospasms

[54]. Fatemi et al.( 1991) reported that even mild degrees of magnesium depletion, may result in a significant

fall in the serum calcium concentration [55].Magnesium is also important in vitamin D metabolism and/or

action[54].

The magnesium ion has an inhibitory action on smooth muscle contraction[56], on histamine release from

mast cells [57] and on acetylcholine release from cholinergic nerve terminals [58]. Neuromuscular hyper-

excitability is the initial problem cited in individuals who have or are developing magnesium deficiency [59],

generalised seizures may also occur (54]. Magnesium has been shown to relax bronchial smooth muscle in

vitro by modulating calcium ion transport at the cellular level, low serum concentrations have been associated

with diminished respiratory muscle power [60]. It is also suggested that magnesium may decrease the

production of free radicals [61] which are a major contributor to inflammation. The Institute of Medicine

(1997) reported that a lower dietary magnesium intake was associated with impaired lung function, bronchial

hyper-reactivity, and an increased risk of wheezing [54]. Kazaks et al (2010) reported that magnesium

supplementation has been demonstrated to shows improvement in both objective and subjective measures

of lung function with benefits for asthma control and quality of life [62]. A particularly high risk group for

magnesium deficiency are individuals who consume excessive alcohol [54]. Excessive alcohol has been shown

to cause renal magnesium wasting, which, if a diet is marginal in magnesium content, could place an

individual at risk for magnesium depletion [54]. Nearly all chronic alcoholics have symptoms of magnesium


depletion [54] and intake of alcohol has been associated with new-onset asthma in adults [63].

Overall, there is strong evidence to suggest that magnesium plays a protective role in inflammatory

respiratory disease. Therefore, any factor that may alter magnesium homeostasis could lead to increased risk

of asthma. Marier (1980) reported that increased dietary intake of fluoride reduces intestinal magnesium

resorption, owing to high chemical affinity of both elements and production of MgF+ and MgF2 [64] Clearly,

therefore it can be ascertained that increased dietary intake of fluoride plays an inhibiting role in magnesium

bioavailability thereby increases the health risks associated with magnesium deficiency, including in a number

of diseases such as metabolic diseases, cardiovascular and neuromuscular function, hypertension,

osteoporosis, diabetes and asthma [54].

2.3 Fluoride, Iodine and Asthma

In humans, the effects on thyroid function have been associated with fluoride exposures of 0.05-0.13

mg/kg/day when iodine intake was adequate and 0.01-0.03 mg/kg/day when iodine intake was inadequate

[15]. The NRC (2006) reported that fluoride in excess may be inducing diseases that have usually been

attributed to iodine deficiency, noting in particular that the toxic effects of fluoride occur at much lower

concentrations when there is iodine deficiency and that reduced iodine intake could contribute to increased

toxicity of fluoride [15].

A number of studies have reported a link between thyroid disease and asthma [65,66,67]. Thus, is reasonable

to suggest that iodine intake and thyroid function have a protective role in the prevention of inflammatory

respiratory disease. Iodine deficiency is one of the four major deficiency diseases in the world [68]. Globally, it

is estimated that 2 billion individuals have an insufficient iodine intake [69]. It is estimated that 47.8% of

school-aged children and 46.1% of the general population in Europe are deficient in iodine[70].

It has been reported that iodine deficiency is increasing in the US population, an increase which is reported, in

part, to changes in food production [71]. Iodine deficiency is also a public health concern in Australia [72] while

up to 50% of pregnant women in the UK and Ireland may be significantly iodine deficient [73]. In New

Zealand, 28 per cent of children aged 5-14 years have been reported to be iodine deficient [74] and 31.3% of

children aged 8-10 years in Dunedin and Wellington (both fluoridated cities) were reported to be deficient in

iodine [75]. While the latter study was undertaken on apparently healthy children it is noteworthy that asthma

prevalence was reported in 18% of participants in the study. Much higher prevalence rates of childhood

asthma (> 30%) have been reported among the general population of children in both Dunedin and

Wellington. It is interesting to note also that the widespread use of phosphate fertilisers, which are high in

fluoride, have been linked to reduction in bioavailability of soil iodine levels. This would result in reduced

iodine uptake in crops and nutritional iodine deficiency within the population consuming food from regions

where large scale use of such fertilisers are practised [76].

2.4 Fluoride inhibition of Cholinesterase and Pulmonary disease

The NRC (2006) reported that fluorides inhibit cholinesterases, including acetylcholinesterase (AChE) [15].

AChE limits the duration of the activity of acetylcholine (ACh) and thus prevents its accumulation at synaptic

junctions. Inhibition of AChE results in excessive stimulation of cholinergic synapses, which leads to bronchial

constriction, laryngospasm, muscle weakness, convulsion, and ultimately death [77]. Hirshman (1992)

reported that cholinesterase inhibitors may provoke bronchospasm by increasing acetylcholine (ACh) at

parasympathetic nerve terminals[78].


Helou and Rhalimi (2010) reported that cholinesterase inhibitors are associated with increased risk of

pulmonary disorders including pneumonia, persistent cough, bronchitis, and asthma [26]. Bardal et al (2011)

reported that increased ACh would be expected to cause bronchial constriction as well as an increase in

bronchial secretions, both of which could exacerbate the symptoms of asthma and potentially promote an

asthma attack.[80] Hilmas et al. (2006) reported that ACh release causes broncho-constriction and that

excess ACh at smooth muscles surrounding airways due to AChE inhibition can produce significant increased

airway resistance that is readily characterized on inspiratory and expiratory auscultation of the lungs. The

authors noted that the effector muscles of respiration including diaphragmatic, intercostal, abdominal, and

accessory muscles of respiration are very sensitive to the toxic effects of AChE inhibitors. In addition AChE

inhibitors are toxic to accessory muscles of respiration leading to an excess of ACh, excessive stimulation of

nicotinic cholinergic synapses and eventual flaccid paralysis. Subsequent expansion of the chest wall to inflate

the lungs will not occur and respiration will cease. [81] This is the same biological effect on humans following

lethal ingestion of soluble inorganic fluoride where death is usually caused by respiratory paralysis [82].

Because of their pharmacological action, cholinesterase inhibitors may be expected to increase gastric acid

secretion due to increased cholinergic activity increasing the risk of developing peptic ulcers or

gastrointestional bleeding.. Increased cholinergic activity may also affect cardiovascular function as well as

cause anorexia in limited cases[83].

In reporting cholinesterase inhibitors it is important also to note that fluorosilicic /hexafluorosilicic acid, the

chemical used predominantly for artificial fluoridation dissociates into free fluoride ions, and silicic acid at

near neutral pH, but forms silicofluoride complexes at lower pH conditions which are typical of those found in

many common beverages, as well as representative of stomach gastric acid conditions. Finney et al. (2006)

demonstrated that the dissociation of silicofluorides resulted in the creation of either "colloidal silica" or an

"oligomerosilicate": the first is a sheet of silicate, the second a string of silica atoms, like beads [27]. Colloidal

silica is also known to act as a acetylcholinesterase inhibitor [84]. Pölloth (2012) reported that the toxicity and

biological activity of colloidal silica dispersions relate to their ability to adsorb to cellular surfaces which can

affect membrane structures and integrity. Toxicity is linked to mechanisms of interactions with outer and

inner cell membranes, signalling responses, and vesicle trafficking pathways. Interaction with membranes

may induce the release of endosomal substances, reactive oxygen species, cytokines and chemokines and

thus induce inflammatory responses [28]. Kaewamatawong et al. (2005, 2006) compared the pulmonary

toxicity of ultrafine and fine colloidal silica particles after intra-tracheal instillation in mice. The smaller

particles had a greater ability to induce lung inflammation and tissue damage. Electron microscopy showed

both particles on the bronchiolar and alveolar wall surface and in the cytoplasm of alveolar epithelial cells,

alveolar macrophages and neutrophils [29,30].

2.5 Fluoride inhibition of Enolase

Enolase is the enzyme responsible for the reversible conversion of D-2-phosphoglycerate (2PGA) and

phosphoenolpyruvate (PEP) in glycolysis and gluconeogenesis, two metabolic pathways that are often vital

for cellular function [85]. New evidence has been recently presented to suggest that enolase plays an

important role in pulmonary health and disease prevention. These findings are potentially very significant as

fluoride is known to be a potent inhibitor of enolase [86-91].

Chang et al (2003) reported that enolase-α is localized in both the cytoplasm and the nucleus in various cell

types of normal lung tissue, including bronchial epithelium and that down-regulation of enolase-α play an

important role in lung tumorigenesis [92].


Pancholi (2001) reported that the role of enolase in systemic and invasive autoimmune disorders was

recognized only very recently [85]. In addition to this property, its ability to function as a heat-shock protein

and to bind cytoskeletal and chromatin structures indicate that enolase may play a crucial role in transcription

and a variety of pathophysiological processes [85].

Recently, Ramos et al. (2012) reported that recent accumulation of evidence reveals that, in addition to its

innate glycolytic function, enolase plays an important role in several biological and pathophysiological

processes in cancer, Alzheimer's disease, and rheumatoid arthritis, among others [93] In a recent study

Wygrecka et al. (2009) reported that α-enolase plays a central role in regulating cellular inflammatory

response and in inflammatory lung disease [94]. Thus, inhibition of enolase provides another potential link

between exposure to fluoride and inflammatory disease.

3. Testing of the Hypothesis

The rapid increase in asthma in countries with artificial fluoridation of water such as the USA, Brazil, Canada,

Australia, the Republic of Ireland and New Zealand, as well as in countries with salt fluoridation programmes,

such as Mexico, Jamaica, Costa Rica, Peru, and Chile, has undeniably occurred in parallel with increased

dietary exposure to fluorides, either through water or salt fluoridation.

3.1 Epidemiological Data on Asthma

The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One (1993-1997), examined the

prevalence of asthma symptoms from 156 centres in 56 countries internationally and reported marked

variations in the prevalence of asthma symptoms with up to 15-fold international differences [95]. ISAAC

noted that a striking feature of the study data was the high rates of asthma symptoms in Australia, New

Zealand, the USA, Republic of Ireland, United Kingdom and Canada. Within the European region, asthma

prevalence rates were significantly higher in the RoI and the UK than any other European country. Within

Spain, the prevalence of asthma ever was significantly higher in fluoridated Bilbao compared to other non-

fluoridated centers in Spain.

The report concluded that the major differences in prevalence of asthma between populations are likely to be

due to environmental factors, however, the report did not identify that artificial fluoridation is practised

extensively in every one of the countries where significantly higher prevalence rates of asthma were reported.

In considering possible aetiological factors that may influence the study outcomes, the authors observed that

while high rates of asthma symptoms were also found in some non-English-speaking countries particularly in

Latin America (Brazil, Peru, Argentina, Chile, Costa Rica, Jamaica and Uruguay) rates were not uniformly high

among countries sharing the same language. For example, the ISAAC reported that Peru and Costa Rica had a

much higher prevalence than Spain. Brazil had a higher prevalence than Portugal, and Hong Kong had a

higher prevalence than China. However, the ISAAC again did not report the clearly obvious fact that the one

environmental exposure common to these countries is once again consumption of artificially fluoridated

water, followed by mandatory salt fluoridation programmes.

Furthermore in Brazil and Hong Kong the majority of the population are provided with artificially fluoridated

water, while mandatory fluoridation of salt programmes are operated in Peru and Costa Rica as well as other

Latin America countries. There are no salt or water fluoridation programmes in either Portugal or China and

less than 10% of the Spanish population are provided with artificially fluoridated water.


Findings from the ISAAC Phase Three Study involving 277 centres in 98 countries were published in 2009. As

with the original study the phase three investigation reported striking variations in the prevalence of asthma

symptoms exist between different geographic areas and populations with a 13 to 9 fold difference between

countries with the highest and lowest prevalence rates [96]. Globally the international patterns as reported in

the phase one study remained with the highest prevalence of asthma to be found in English-speaking and

Latin American countries. It is clinically significant that the lowest prevalences of asthma were to be found in

countries with no artificial fluoridation programmes or low fluoride exposure of population.

The only other international surveys of asthma comparable to the ISAAC are the two European Community

Respiratory Health Surveys (ECRHS) which studied asthma prevalence among adult males and females aged

20–44 years of age. The first of these studies published in 1994, involved 11 countries in the European

Community, with five other European states and 15 centers in seven other countries internationally

participating [97]. The second study published in 1996 involved 48 centers in 22 countries including

international centres in New Zealand, Australia, India, Algeria and the USA [98].

The ECRHS study noted that the large differences in asthma prevalence reported between countries were far

too rapid and large to be interpreted as genetic changes, and must be related to some environmental risk

[98]. This supports the findings in the ISAAC studies [95,96]. It is ecologically significant that of the 48

international centres that participated in the ECRHS survey, the highest prevalence of adult asthma

symptoms was reported in the RoI. Notably, the RoI is the only European country with a 50 year mandatory

national drinking water fluoridation programme. (Fig 1)

3.2 Case Studies of Selected Countries

One of the most pertinent countries internationally is the Republic of Ireland (RoI) as it is the only European

country with a national legislative policy of artificially fluoridating all public water supplies. In the RoI diseases

of the respiratory system are the cause of one in five deaths, one third of deaths from respiratory disease are

due to pneumonia, which is the leading respiratory killer, with COPD the third largest cause of respiratory

deaths [99]. In the context of what has been presented in this study, it is noteworthy that data from the World

Health Organisation shows that death rates from diseases of the respiratory system in Ireland are almost

double the EU average [100]. In the Republic of Ireland (RoI) asthma prevalence has increased fivefold since

the period when fluoridation of drinking water commenced [101]. Asthma is the most common and fastest

growing chronic disease in the RoI with one in five children now diagnosed with asthma. The ISAAC protocol

Study (1995–2007) reported that between 1995 and 2007, the symptoms of severe asthma in children living in

RoI increased significantly by 39% [102]. This increase occurred following the dramatic improvement in urban

air quality following the banning bituminous coal initially in Dublin and other urban centres, the introduction

of the comprehensive workplace smoke-free policy in Ireland in March 2004 and a significant decline in

current smoking status of Irish children aged 13–14 years between 1995 and 2007 [103]. Currently, despite

some of the best ambient air quality in the world, the prevalence of childhood and adult asthma in Ireland is

now amongst the worst in the world, and far greater than any other European country. According to ISAAC

data for the period 1999–2004, asthma prevalence in children across the European study centers varied from

less than 5% to over 25%. The highest prevalences of asthma symptoms in children aged 6–7 years (>20%)

and 13–14 years (>25%) were found in Ireland, followed by the UK .For the RoI asthma prevalence rates were

more than 300% above some member states [103]. The RoI also has the highest hospitalization of 0-14 yrs.’

olds for asthma among European counties [104].


According to ECRHS data, the RoI also has the highest prevalence of adult asthma in Europe, twice the

European average [105] Critically, Balanda and Wilde (2001) in a cross sectorial study on all Ireland mortality

data by the Institute of Public Health in Ireland, reported that incidence of mortality from asthma and chronic

lower respiratory disease were significantly higher in RoI (fluoridated) compared to non-fluoridated Northern

Ireland or the EU 15 countries [106]. In examining the information for the RoI and the role of artificial

fluoridation in increased burdens of inflammatory disease it is also important to note that the effects of

fluoridation in the RoI would be compounded by the low prevalence of breast feeding and high prevalence of

bottle feeding of infants, where fluoridated tap water is used to reconstitute the infant formula, in addition to

the often excessive dietary exposure of the adult population to fluoride from consumption of tea. The RoI has

the one of the lowest prevalence’s of breast feeding in the world and the highest per capita tea consumption

in the world. Tea is a significant dietary source of fluoride, even more so when made with fluoridated water.

Next to the RoI, the UK has the second highest prevalence rates of asthma in Europe. As with the RoI, there

has been a marked increase in the incidence of asthma attacks diagnosed by general practitioners over the

last few decades, such that it is now about five times higher than it was 25 years ago [107]. In England, the

National Study of Health and Growth has shown an increasing the prevalence of "persistent wheeze" in a

representative sample of English school children since the start of the study in the early 1970s [108]. The

ISAAC Phase III study reported that the incidence of asthma symptoms had risen in 6- to 7-year-olds in the

UK, from 18.4% to 20.9% over a period of approximately 5 years [96]. In the UK, a higher prevalence of

asthma children aged between 5–11 years has been documented in England than Scotland [109]. In England, 1

in 9 adults has been diagnosed with asthma 110] Northern Ireland (1 in 10), Scotland (1 in 14) and Wales (1 in

10) receiving treatment for asthma [111]. Fluoridation of drinking water only occurs in parts of England.

Between 2001-2005 the lifetime prevalence rate of asthma for adults in England increased (15-44 years:

23.3%; 45-64 years: 27.7%; >65 years: 21.5%) with an estimated 5,658,900 (95% CI 5,639,700-5,678,200) or

approximately one person in nine having being diagnosed with asthma [110]. As with the RoI, the effects of

artificial fluoridation in England would be compounded by the high dietary exposure of the population to

fluoride from consumption of tea. The UK has the second highest per capita consumption of tea in the world

next to the RoI.

In Spain, the highest prevalence of asthma and respiratory disease are also to be found in fluoridated

communities, in particular within the Basque province in northern Spain, which is the most heavily fluoridated

region of the country. The ISAAC (1998) reported the prevalence of ‘asthma ever’ among those 13-14 years

old in the Basque city of Bilbao at 16.3%, compared to a national average of 10.5% [95]. High levels,

significantly above the national average are also reported for adults in Seville [96] the largest city in southern

Spain that is fluoridated.

Very significant increases have also been reported in Switzerland, where asthma prevalence has increased

fivefold since a national salt fluoridation programme commenced [112]. Currently approximately 8% of the

Swiss population suffers from asthma, as against only 2% some 25-30 years ago [112]. In a study on severe

asthma across Europe (2005) the highest admission rates per 100,000 adults aged 15-44 for males and

females were reported for Switzerland [107]. During this period the most intensive and successful salt

fluoridation programme of any European state was commenced in Switzerland where currently the market

share of consumption of fluoridated salt is over 80% .

In France, the market share of fluoridated salt has declined dramatically from over 60% of all salt sold to less

than 8% in recent years. In the region of France with the highest use of fluoridated salt, Montpellier, where

fluoridated salt is 70% of market share, and where FS is also used in public school canteens, the prevalence of

childhood asthma is more than 50% above the national mean [96].


Since commencement of fluoridation of salt in Germany, recent epidemiological data also demonstrates a

significant increase in asthma prevalence [113].

In North America, the prevalence of asthma in the U.S. and Canada has a marked geographic variation, with

the highest prevalence’s are to be found in the regions with the greatest penetration of fluoridation of

drinking water supplies. In the United States this includes the District of Colombia, the States of Kentucky and

Maryland. The District of Columbia (Washington DC) is the only US state that has 100% fluoridated water

followed by Kentucky (99.9%) and Maryland (99.8%) [114]. Adult lifetime asthma prevalence for the District

of Columbia are 16.2%, Kentucky (14,7%) and Maryland (14.3%) compared to U.S rates of 13.3%. The

childhood lifetime asthma prevalence was 18.4% for the District of Colombia, 13.8% for Kentucky and 14.1%

for Maryland, compared to U.S rates of 13.3% [115]. Asthma prevalence in the United States is now at its

highest level [116], prevalences rates have increased from approximately 3% in 1970to higher than 8.5% in

children, 8.1% in females and 6.2% in males in 2003 [117]. In 2010, one person in twelve (about 25.7 million

people) had asthma compared to one in 14 (about 20 million) in 2001. In 2009, one in ten children had asthma

with the greatest rise in asthma rates recorded among black children (almost 50% increase) [118].

In Canada, the lowest prevalence of childhood asthma has been recorded in non-fluoridated provinces such as

British Colombia (14.4%) compared to much higher disease burdens in fluoridated provinces such as Nova

Scotia, Newfoundland, New Brunswick and Prince Edward Island, where rates are significantly higher at 21.7%

[119].

In South America, Brazil with 73 million people in over 3350 communities provided with artificially fluoridated

water represents one of most extensively fluoridated countries in the world. Brazil also has one of the highest

levels of asthma globally [96]. Among the general population, the prevalence of clinical asthma is reported at

11.4%. The ISAAC (1998) reported the mean prevalence of asthma ever among 13-14yrs olds at 14.9% with a

much higher prevalence in Porto Allegro (21.9%) and Recife (20.9%) [95]. The Porto Allegro region in

Southern Brazil has a natural fluoride level in water of up to 6.13mg/L [120], while Recife is the fifth largest

metropolitan area in Brazil and its drinking water is artificially fluoridated. The lowest prevalence of ‘asthma

ever’ recorded among the participating cities in the ISAAC study was Curitiba at 8.6%[96]. Notably, Curitiba is

non-fluoridated.

Jamaica along with Costa Rica were the first countries in to implement a national salt fluoridation programme

[121]. Marthaler (2005) reported that in the period 2004-2005 100% of the population of Jamaica was

consuming fluoridated salt and 95% of the population of Costa Rica.[123] A recent study by Kahwa et al

(2012) reported that almost a fifth (19.6%) of Jamaican children aged 2–17years had current wheeze, while

16.7% had self-reported doctor-diagnosed asthma [124]. Lai et al (2008) reporting on the ISAAC Phase three

study reported that the prevalence of wheeze in the past 12 month in 13-14 year olds Costa Rican 6-7 year

olds was 37.6%. The prevalence of severe asthma was 16% for 13–14 year olds and 20.3% in 6–7 year olds [96].

Perhaps the best evidence to support fluoride’s contribution to respiratory diseases comes from Mexico and

Israel, due to their relatively recent commencement of fluoridation programmes and the availability of

medical records pre fluoridation on respiratory prevalence. Mexico commenced mandatory national salt

fluoridation in 1995, while Israel commenced water fluoridation in 1981. Official Mexican Department of

Health figures recorded that immediately after commencement of their national salt fluoridation programme

the number of new cases of asthma increased fivefold within a year, and the incidence of acute respiratory

infections doubled [125].

Likewise in Israel, following commencement of water fluoridation, asthma prevalence rates increased

significantly. Sacher and associates reported that between 1980 and 1991, asthma prevalence among 17±18


year olds increased by 85% among men and 115% among women [126].

New Zealand has one of the highest reported prevalences of asthma in the world [127]. Asher et al (2001)

reported that 25% of children aged 6-7 years and 30% of 13-14yr olds with asthma symptoms [128]. In the

fluoridated city of Dunedin an astonishing 35% of the children and young adults have been diagnosed with

asthma [129]. It is also significant that the ISAAC study reported that the highest prevalence rates of 12

month wheeze, among 13-14 year olds was in Wellington New Zealand at 32.6%. Similarly the highest

prevalence of ‘asthma ever’ was also reported in Wellington at 30.8%[130]. It is noteworthy that a recent

report by the Medical Research Institute of New Zealand and University of Southampton reported that when

people from Southeast Asia and the Pacific Islands immigrate to New Zealand and Australia there is a marked

increase in the prevalence of asthma within one generation. For example, the report highlighted that the rate

of asthma doubles when people emigrate from the Pacific Islands to New Zealand [101].

In Australia, the hospitalisation rates for asthma have more than doubled over the last 30 years [101].

Currently one child in six under the age of 16years is diagnosed with asthma in Australia [131]. Notably,

children born in Australia have up to a twofold greater rate of asthma than those living in Australia but born

outside the country [101, 132,133,]

4. Implications of the Hypothesis

This paper critically examines the key scientific evidence used to support the hypothesis that artificial

fluoridation contributes to inflammatory respiratory and pulmonary toxicity. Overall it is clearly evident that

the preponderance of epidemiological data published worldwide demonstrates, without exception, that the

countries with the highest prevalence of asthma share one common environmental risk factor that can easily

be identified as increased dietary exposure to fluoride through artificial fluoridation of drinking water

supplies, salt fluoridation or high natural fluoride levels in drinking water. The countries with the highest

burden of inflammatory respiratory disease, at prevalence rates significantly above the global average,

include the Republic of Ireland, the Unites States of America, Australia, New Zealand, Canada, and Brazil, all

countries with advanced artificial water fluoridation schemes providing more than 50% of their populations

with artificially fluoridated water. Slightly lower prevalences are recorded for and Peru and Costa Rica, where

there are mandatory national salt fluoridation programmes. This strongly indicates that the increased

exposure of the population to fluoride has had a direct causal relationship to the recent "epidemic" of

pulmonary diseases including asthma, COPD in addition to other chronic inflammatory diseases which are

also higher than the global mean prevalence in these respective countries. It is also evident that this

relationship appears more aggressive among populations exposed to artificially fluoridated water, reflecting

the nature and toxicity of fluorosilicates in comparison to naturally occurring fluorides in the environment.

This supports the findings of the World Health Authority [134], the European Food Safety Authority [135] and

the United States Agency for Toxic substances and Disease Registry [136] that the toxicity of fluoride is

dependent upon the type or species of the compound ingested, and therefore, the more soluble salts of

inorganic fluorides are the most toxic.

In regard to prevalence rates of childhood asthma, it is clearly evident that the burden of this chronic disease

in fluoridated countries is simply extraordinary. It is reported that most childhood asthma begins during the

first 3 years of life [137] and the greatest prevalence of asthma is in preschool children [138]. This is extremely

pertinent to countries where fluoridation exists, particularly where public water supplies are fluoridated and

tap water may be used by caregivers to reconstitute formula milk for infants. The concentration of fluoride in

formula milk made with fluoridated tap water is approximately 20,000 per cent (200 times) that found


naturally in breast milk (0.8ppm versus 0.004ppm) and importantly no safe tolerable dietary reference levels

currently exist for infants. It is surprising therefore that to my knowledge, no study, has examined the effect

of increased dietary exposure to fluoride from fluoridated formula milk, fluoridated drinking water or salt, and

its contribution to inflammatory respiratory diseases in either children or adults. Studies have confirmed

however that bottle feeding significantly increases the incidence and duration of respiratory illness during the

first 6 months of life [139] as well as the prevalence and subsequent morbidity from respiratory illness and

infection in infancy [140,141].

The results of this analysis indicate a strong causal relationship between artificial fluoridation and

inflammatory respiratory disease. Given the established role of inflammation in the pathogenesis of chronic

disease including cardiovascular [142,143,144], cancer [145-149], diabetes [150], multiple sclerosis [151]

dementia [151, 152], Parkinson’s disease [153, 154], depression [151,155], obesity [156], inflammatory bowel

disease and arthritis it is evident that the findings of this study are of enormous public health significance.

This is especially so given the overwhelming burden of chronic inflammatory disease in countries where

artificial fluoridation of water is currently implemented.

The precautionary principle, endorsed by international treaties, states that if an action or policy has a

suspected risk of causing harm to the public, in the absence of scientific consensus that the action or policy is

harmful, the burden of proof that it is not harmful falls on those taking the action. It is clearly evident that

public health authorities must therefore take immediate and appropriate action to reduce the risk of exposure

to toxins that contribute to chronic inflammatory disease. A new approach to oral health and oral care is

urgently needed which will not involve mass fluoridation of populations with highly toxic soluble inorganic

fluorides that are known to contribute to inflammation in humans.

Acknowledgements:

I would like to thank the International Study of Asthma and Allergies in Childhood (ISAAC) and the European

Community Respiratory Health Surveys (ECRHS) for collecting the data on asthma prevalence worldwide.

The author would also like to thank Dr. Michael Godfrey for his assistance in editing this paper.

Conflict of Interest: None Declared. This work was undertaken voluntarily, funded entirely by the author

without any financial support from third parties. © The Author 2013


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