Geoff Pain
Draft 12 October 2018
Abstract
Experts in endocrinology have shown that Fluoride causes Diabetes and Obesity. This review assembles
the wealth of science that shows how Fluoride damages the organs that generate or use Insulin to control
Glucose metabolism and the crucial involvement of other hormone systems.
Keywords: Anaemia, Anovulation, Arsenic, Autophagy, Cadmium, Cataract, Comorbity, Coronary Disease,
Diabetes, Endoplasmic Reticulum Stress Fluoride, FoxO1, Ghrelin, Hypertension, Hyperinsulinemia,
Hyperkalemia, Hyperlipoproteinemia, Hormone, Insipidus, Insulin, Kidney, Lead, Low-dose endocrine
disruptor, Mellitus, Mercury, MHC 1,Obesity, Proinsulin, Secondary Hyperparathyroidism
Introduction
This review updates an earlier version summarizing the peer-reviewed literature that was easily accessible
to March 2015 [Pain 2015]. Since then there have been many publications that report advances in the
enabling technologies, such as protein and mRNA sequencing, that add sophistication to the earlier
definitive works.
The immense scale of the Diabetes problem is summarized by the World Health Organization [Bergman
2013] as follows: “The number of diabetics in the world is expected to increase from 194 million in 2003 to
330 million in 2030 with three of four affected individuals living in developing countries. The global health
expenditure on diabetes alone is expected to rise to US$ 490 billion in 2030 – 12% of all per capita health-
care expenditures [Zhang 2010]. The burden of premature death from diabetes in developing countries is
similar to that of HIV/AIDS, yet the problem is largely unrecognised in these areas.”
There has been an explosion in the incidence of diabetes in the developed countries over the last 40 years
[Bergman 2013] which matches the timescale of deliberate fluoridation of public water supplies in those
countries.
In simple terms Diabetes involves the disruption of key biochemical pathways involving hormone signalling,
enzyme production, metabolism of food and storage of sugars and fats. The key organs involved are the
Brain, which responds to hunger stimulus, Pancreas which produces the glucose controlling hormone
Insulin, the Liver which produces Glucose, the muscles which store and use Glucose. Common to all
organs damaged by Fluoride are the energy producing mitochondria [Dabrowska 2004, Maassen 2004].
Peripheral neuropathy is linked to advanced glycation products [Misur 2004, Kellow 2014]. Morbidities
associated with Diabetes include pancreatic cancer, anovulation [Dunaif 1995, Franks 1996], dyslipidemia,
cardiovascular disease, hypertension, infertility, endometrial hyperplasia, and endometrial cancer.
Figure 1. Factors in increased Blood Glucose levels [Khardori 2017]
Recent proteomic analysis of Fluoride damage to the jejunum could affect the neuronal functions of the gut
with increased expression of numerous transporter proteins [Dionizio 2018]. This provides a possible
explanation for the increased sensitivity to insulin recently reported to occur in rats with diabetes induced by
streptozotocin exposed to 10 mgF/L in the drinking water [Leite 2014, Lobo 2015].
Fluoride is an Endocrine disruptor
As seen in the following Table (Figure 2), Fluoride is well known as an Endocrine disruptor [Bergman
2013].
Figure2. Fluoride in a Table of Low Dose Endocrine Disruptors [Bergman 2013]
Furthermore Fluoride is known to cause Diabetes by simultaneously affecting multiple hormone systems
(Figure 3) [Vandenberg 2012].
Figure 3. Fluoride used as a water “additive” is stated by expert endocrinologists to inhibit Insulin
secretion and damage Parathyroid and Thyroid Hormone systems, also impacting on bone mass
and strength [Vandenberg 2012]
The reduction in Insulin expression and the messenger RNA that controls it is clearly dose-dependent
(Figure 4 ) [García-Montalvo 2009].
![Clear Dose-dependent Insulin and mRNA reduction by Fluoride [García-Montalvo 2009]](https://www.researchgate.net/profile/Geoff_Pain/publication/328249196/figure/fig2/AS:680915864911877@1539354401588/Clear-Dose-dependent-Insulin-and-mRNA-reduction-by-Fluoride-Garcia-Montalvo-2009_Q320.jpg)
Figure 4. Clear Dose-dependent Insulin and mRNA reduction by Fluoride [García-Montalvo 2009]
I have summarized some of the hormone systems known to be damaged by Fluoride (Figure 5).
Hormones and their receptors mentioned in this figure include Thyroid Stimulating Hormone, Leptin,
Ghrelin, Antidiueretic Hormone, Follicle Stimulating Hormone Receptor, Luteinizing Hormone Receptor, Tri-
iodothyronine (T#), Thyroxine (T4), Catecholamines, Insulin, Prostoglandin, Testosterone, Estradiol,
Melatonin, Parathyroid Hormone, Calcitonin, CD4(+), CD8(+), Inhibin. Damage by Fluoride often proceeds
by attack on key enzymes including Alkaline Phospahatase, Iodothyronine Deiodinase, Adenylate Cyclase,
Vassopressin.
Figure 5. Hormone systems known to be damaged by Fluoride
It has been said that there are perhaps 5 types of diabetes including Diabetes Insipidus, Type 1 Diabetes
Mellitus caused by the pancreas not producing adequate amounts of Insulin, and Type 2 Diabetes Mellitus
caused by the body’s cells becoming less responsive to insulin that is produced. Diabetes takes a terrible
toll on the quality of life and kills many Australians.
Ghrelin hormone disruption is a vital contributor to Diabetes because it enhances appetite and increases
food intake in humans [Wren 2001]. Fluoride upsets metabolism by upregulation of Ghrelin expression in
the stomach upon fasting [Toshinai 2001]. Ghrelin modulates the downstream molecules of insulin
signalling in hepatoma cells [Murata 2002]. Ghrelin disruption is also implicated in salt-induced and
maternal Hypertension [Hamada 2012].
Figure 6. Before Premature Death, Diabetes patients suffer terrible comorbidities
Diabetes Insipidus victims of water Fluoridation suffer dreadful damage to their Teeth as shown by
Australian researchers (Figure 7 ) [Seow 1994]. They drink very large volumes of water, up to 30 litres per
day [Pivonello 1998, Prystupa 2011].
Figure 7. Diabetes Insipidus causes severe Fluorosis and Tooth Decay, note Mercury fillings
[Seow 1994].
Figure 8. Far-reaching complications of Diabetes [Anon]
Epidemiology of Diabetes in relation to Fluoride
Workers in the phosphate fertilizer industry are exposed to Fluoride and experience higher incidence of
diabetes as well as skeletal fluorosis [Renke 1987].
Workers in the cryolite industry also suffer Chronic Fluoride Intoxication (CFI) and have lower insulin and
increased C-peptide serum levels [Tokar 1992]. It was shown that the incidence of diabetes increased with
years of exposure. The observed lower serum insulin levels in Fluoride intoxication might be due to
associated liver damage [Tokar 1992]. Liver damage has also been observed by Vasant and
Narasimhacharya [2013a] who state “Exposure to fluoride through drinking water not only significantly
increased plasma glucose and lipid profiles, but also elevated both hepatic and renal lipid peroxidation,
hepatic lipid profiles and G-6-Pase activity with a reduction in plasma HDL-C, hepatic glycogen content,
hexokinase activity and antioxidant status”.
Diabetes has been increasing in a number of countries since the 1940s in line with the roll out of
Fluoridation. Insulin resistance in humans caused by chronic Fluoride exposure from drinking water is well
known [Trivedi 1993, Stephen 1994, Cheoud 2008, Menoya 2008, Chiba 2010, Chiba 2012a, 2012b
Bergman 2013, Vandenberg 2012].
In chronic exposures, effects on glucose metabolism occurred when plasma fluoride concentrations
exceeded 0.1 mg/L (5 µmol/L) [Rigalli 1992, 1995], or just one 15th the concentration allowed in Australian
drinking water. The US National Research Council [2006] stated “In general, impaired glucose metabolism
appears to be associated with serum or plasma fluoride concentrations of about 0.1 mg/L or greater in both
animals and humans.”
Figure 9 USA increase in Diabetes incidence 1980-2011 [CDC]
More detailed analysis of Diabetes incidence in USA was provided (Figure 10) [Waugh]
Figure 10. More detailed analysis of Diabetes incidence in USA [Waugh 2014]
Canada displays regional variations in Type 1 Diabetes that correlate with Fluoridation status [Chafe 2018].
Diabetes Mortality has increased in the Republic of Ireland (Fluoridated) much more than in Northern
Ireland [Waugh].
Figure 11. Higher Diabetes Death rate in Fluoridated Republic of Ireland [Waugh 2014].
Diabetes in Australia
Figure 12. Prevalence of Diabetes in Australia versus Age
There is strong gender dependence with men more affected than women with increasing age.
Figure 13. Diabetes Gender difference with Age in Australia
Looking at data from New South Wales, which is almost completely Fluoridated, we see an alarming
increase if Diabetes in children from 1990 to 2002 (Figure 14).
Figure 14. Alarming increase if Diabetes in NSW children from 1990 to 2002
If Fluoridation is a factor in increased Diabetes, we would expect to see lower incidence in communities
that have not received the poison in their drinking water. Byron in New South Wales has resisted relentless
pressure from the Fluoride waste disposal industry and indeed shows lower Diabetes incidence.
Figure 15. Byron is not Fluoridated and shows lower Diabetes incidence
Townsville in the state of Queensland, Australia, fluoridated since 1964, suffers 10% higher rate of diabetes
than the rest of non-fluoridated Queensland (not poisoned with Fluoride until 2008) [PHIDU 2005].
Townsville also suffers higher rates of hospital admissions for unspecified dental conditions, as well as
asthma, congestive heart failure, convulsions and epilepsy, congestive obstructive pulmonary disease, ear
nose and throat conditions and pyelonephritis. Townsville also suffers increased death rates due to
circulatory system, ischaemic heart disease, cerebrovascular disease – Stroke, chronic lower respiratory
disease and cancer of the trachea [Queensland Hospital Data 2005-2006]. Townsville can therefore be
considered a randomised control trial centre for Fluoride toxicology.
Fluoride alteration of Insulin levels
A recent study [Rogalska 2017] found, unsurprisingly, that Plasma fluoride levels in Wistar rats after 30
days of drinking fluoridated water were significantly (p < 0.05) higher in the group exposed to NaF 50 ppm
(0.0823 ± 0.0199 μg/ml) in comparison to control (0.0541 ± 0.0135 μg/ml) and NaF 10 ppm (0.0596 ±
0.0202 μg/ml).
Plasma glucose concentration trend was up but did not significantly differ among the experimental groups
However, plasma insulin levels (Figure 16) were significantly higher as fluoride concentration increased in
drinking water, attaining significance between control (0.48 ± 0.24 μg/ml) and fluoride (50 ppm) groups
(0.72 ± 0.13 μg/ml). Hyperinsulinemia enhances myocardial calcification [Ng 1998].
Figure 16. Increased Plasma Insulin in Fluoride treated Wistar rats [Rogalska 2017]
Simultaneously, glucose uptake by the rat Brain increased with Fluoride dose, initiating an elevation in
carcinogenic malondialdehyde (the end product of lipid peroxidation) and an increase in damage to
hippocampal neurons [Rogalska 2017]. Various regions of the brain are affected by Insulin, including the
hypothalamus, ventral tegmental area, substantia nigra, and amygdala. Positive feedback of damage has
been demonstrated by the finding that diet-induced obesity induces endoplasmic reticulum stress (also
induced directly by Fluoride [Sharma 2008, Ito 2009]) and insulin resistance in the amygdala of rats [Castro
2013].
Fluoride interference with Insulin will also translate to the disruption of the adipocyte hormone Leptin, which
is involved in the regulation of food intake, energy expenditure, and body fat stores [Mueller 1998].
Diabetes from Fluorinated Drugs and Drugs used in Fluoridated areas
Many Fluorine containing drugs are metabolized to liberate free Fluoride ions. A recent study showed that
exposure to statins increased risk of Diabetes with increasing dose of statin from the hazard ratio of 1.17
(95% CI 0.84-1.65) for the lowest dose to 1.51 (95% CI 1.14-1.99) for the highest dose [Jones 2017].
Autoimmune Destruction of Pancreas Cells caused by Fluoride produces Type 1 Diabetes
A very important study that the NHMRC ignored in its 2017 Review was submitted by me as vital evidence
[Irmak 2014]. One can easily see why the NHMRC wants to bury this key paper by reading the authors’
own words (with minor edits for clarity):
“The incidence of Type 1 diabetes has increased substantially in Finland. We know that use of amoxicillin
and anti-cariogenic fluoride tablets is a common practice for children in Finland. It seems that beta-cell
destruction is initiated by modification of the proinsulin by combined effects of fluoride and amoxicillin.
Amoxicillin especially when used together with clavulanic acid results in an acid environment around the
beta-cells that promotes the conversion of Fluoride ion to hydrogen fluoride (HF).
Unlike Fluoride ion, HF can diffuse easily into the beta-cell cytosol. Because the cytosol has a neutral pH,
virtually all HF reverts to Fluoride ion in the cytosol and Fluoride ion cannot easily diffuse out of the cell.
Exposure to excess promotes proinsulin covalent dimerization and simultaneously hyperexpression of MHC
Class I molecules.
Proinsulin dimers then migrate to the cell membrane with MHC class I molecules, accumulate at the beta-
cell membrane and produces a powerful immunogenic stimulus for the cytotoxic T-cells.
Production of cytotoxic cytokines from the infiltrating Tcells initiates the destruction of beta-cells. In Finnish
children, this might be helped along by a higher beta-cell activity and by a reactive thymus-dependent
immune system induced by higher levels of thyroid hormones and calcitonin respectively. After repeated
similar attacks, more and more effector T-cells are raised and more and more beta-cells are destroyed, and
clinical diabetes occurs.” [Irmak 2014].
However the idea that Fluoride defeats the diffusion barrier by entering the cell as Hydrogen Fluoride and is
converted to Fluoride ions, allowing it to concentrate above the extracellular concentration is not new.
Experiments were performed to show that Fluoride is more toxic at lower pH [Sharma 2010].
As shown in Figure 17 there is absolutely no doubt that the above mechanism for Fluoride bioaccumulation
is occurring daily in people exposed to the toxin.
Figure 17. Bioaccumulation of Fluoride is demonstrated at all ages in Humans through use of Radioactive 18F
Autoimmune diseases represent a spectrum of disorders caused by inflammation of organs due to
production of antibodies against self-structures and cytotoxic action of T cells and such antibodies can
affect multiple organs. Type 1 Diabetes Mellitus is associated with ant- thyroid-stimulating hormone
receptor, anti- thyroid peroxidise, and anti- thyroglobulinantibodies [Fröhlich 2017].
Thyroid hormone disruption can be measured when the Fluoride concentration is just 0.5 ppm.
Hypothyroidism in people exposed to Fluoride in drinking water is closely associated with other diseases
including Diabetes (odds ratio: 3.7, 95% Confidence Interval (CI): 1.7–8), Hypertension (odds ratio: 3.2, CI
95%: 1.3–8.2), and volume of water consumption (odds ratio: 4, CI 95%: 1.2–14) [Kheradpisheh 2018].
Epidemiology of Pancreatic Cancer
Fluoridated areas suffer higher Pancreatic Cancer Death and incidence rates than non-Fluoridated areas in
the USA [Takahashi 2001] and we know Australia’s NHMRC was still discussing this fact in 2013. Ghrelin,
up-regulated by Fluoride, promotes pancreatic adenocarcinoma cellular proliferation and invasiveness
[Volante 2002, Duxbury 2003].
Figure 18. Higher Death Rates for Pancreas and Liver Cancer in Fluoridated areas
One of the key reasons that there is such a low survival rate for Pancreatic Cancer is that general
practitioners might easily ignore warning signs (Figure 19).
Figure 19. Common warning signs ignored leading to high Pancreatic Cancer Mortality
Pancreatic Cancer Deaths for men are higher than those for women in Australia (Figure 20). This is in line
with the incidence of Diabetes shown above in Figure 13.
Figure 20. Gender difference for Death and Incidence rates of Pancreatic Cancer in Australia
[AIHW].
Kidney and Diabetes patients need extra protection from Fluoride
Previous studies have emphasized the adverse impact of Fluoride on diabetic patients because they
typically consume much larger quantities of water than average humans and have impaired kidney function
leading to higher risk from the diverse toxic effects of Fluoride [see for example Prystupa 2011, Doull 2006,
Marier 1977]. It has also been shown that Fluoride toxicity is greater in diabetics [Banu Priya 1997].
Diabetics suffer impaired glucose tolerance (IGT), hypertension, hyperlipoproteinemia and coronary
disease. They have a higher risk of death from breast cancer [Youlden 2009], pancreatic cancer [Michaud
2004], uterine cancer [Purdie 2001] and colorectal cancer [Youlden 2008]. Diabetics also suffer reduced
bone mass and strength through Fluoride exposure [Dunipace 1996]. The Pancreas has been shown to
produce a bone/calcium metabolism-regulating factor which is disrupted by Fluoride [Izbicka 1996].
Diabetics have a higher incidence of chronic kidney disease which leads to impaired renal clearance of
fluoride [Hanhijarvi 1974], the “vicious cycle” that too often results in Death or the need for transplant.
The role of Diabetes in End Stage Renal Failure (ESRF) is highlighted in Figure 21 [Atkins 2005].
Figure 21. Incidence of Diabetes in ESRF Australia from 1980 to 2000 [Atkins 2005]
In 2005, 18% of adult Australians had at least one indicator of chronic kidney disease, including hematuria
(5.6%), proteinuria (2.4%), albuminuria (5.3% in males and 7.1% in females), and renal impairment, defined
by a calculated GFR of less than 60 mL/m, was 12.1% [Atkins 2005].
The Australian Institute of Health and Welfare has forecast the proportion of diabetics undergoing
transplants or dialysis would rise to 64 per cent in 2020 from 45 per cent in 2009 [Henderson 2012].
The total number of Australians being treated for end-stage kidney disease is forecast to rise by up to 80
per cent to about 4300 in the coming decade.
Comparison of people with diagnosed Kidney disease residing in Catalonia, Spain serum fluoride
concentration ranging from 28 to 185 micrograms per litre compared to the control group who ranged from
1 to 47 micrograms per litre [Torra 1998].
Hyperkalemia in dialysed patients is caused by Fluoride [Nicolay 1999]. Patients who drank Vichy St-Yorre
water had plasma Fluoride levels of 100 to 380 µg/ l, or 5.26 to 20 µmol/ l.
Anomalies in Birth Weight due to Fluoride and Diabetes
Diabetic women generally have a higher risk of premature birth and low birth weight children [Patel 1975].
Preventing gastrointestinal damage by lowering the F intake can lead to improved absorption of nutrients
and increased fetal growth [Susheela 2010].
However it has been found that in the infants of well nourished diabetic mothers, there is increased glucose
transfer to the fetus resulting in β-cell hyperplasia, increased insulin secretion, and greater fetal adiposity
[Dunger 2007]. A continuous relationship has been observed between maternal glucose levels and the
birth weight of the offspring [Sacks 2010].
These apparently anomalous results have been explained [Aghaei 2015], whereby mechanisms could be
present in which raised Fluoride intake could lead to fetal growth being either increased, via increased
maternal hyperglycaemia, or decreased, via increased damage to the microvilli with reduced nutrient
absorption and anaemia. The net effect depends on the relative strengths of the two effects.
Fluoride directly reduces insulin synthesis in rats [Lin 1976]. Microcirculatory defects, increased
capillary permeability and altered protein biosynthesis in the pancreas is associated with Fluoride exposure.
Because human hormones interact with each other, the known adverse effect of Fluoride on melatonin
production and the knock-on effect on insulin should also be considered [Rasmussen 1999]. The fact that
Fluoride causes hypothyroidism and also exacerbates the damage to diabetics through reduction of
peripheral glucose metabolism [Cettour-Rose 2005]. Hypothyroidism induces Secondary
Hyperparathyroidism which can contribute to Diabetes.
A genetically inherited condition demonstrates an association between pineal gland hyperplasia and insulin
resistance [West 1980].
Blood fluoride level of just 234 ppb after a single acute exposure caused significant impairment in glucose
metabolism, as evident by sharp rises in blood glucose and decreases in insulin [Whitford 1987]. Similar
results have been measured in rats and human volunteers [Rigalli 1990, Suketa 1985 ].
Short-term acute exposures to high levels of fluoride generated by metabolism of the fluorinated anesthetic
methoxylflurane impairs the kidney’s ability to concentrate urine and produces a diabetes insipidus-like
condition marked by excessive urination [Mazze 1977].
Directly observed toxic effects in the pancreas of albino rats caused by Fluoride includes hematological,
biochemical, DNA damage, histilogical and immunohistochemical alteration [Agha 2012].
Pancreas pathological morphometry analysis via β cells [Hu 2012] of rats exposed to Fluoride showed
increased islet size. The same rats exhibited increased alkaline phosphatise and osteocalcin, increase of
serum insulin level and a general decrease of glucagon level. The complex hormonal interplay between
insulin, osteocalcin and other hormones in relation to bone metabolism and glucose metabolism allows
Fluoride to intervene at many points in the system and involves FoxO1 [Rached 2010, Kode 2012, Guntur
2012].
Rats with Fluoride induced diabetes that were encouraged to exercise demonstrated accelerated skeletal
fluorosis [Lombarte 2013]. Diabetic rats also show enhanced contractile responses of arteries to sodium
fluoride which directly stimulates GTP-binding proteins (G-proteins) [Weber 1996].
Fluoride induced hyperglycemia has been stated to be mainly due to increased hepatic glycogenolysis
[Varadacharyulu 1997]. Rabbits fed 16 mg of Fluoride per day exhibited hyperglycemia as well as reduction
of bone strength through fluorosis [Turner 1997].
People exposed to high Fluoride levels in their drinking water suffer a high incidence of skeletal fluorosis.
As demonstrated by Xie et al. [2000] they exhibit a higher and longer lasting blood glucose level after an
oral glucose tolerance test (OGTT). Impaired glucose tolerance in humans has been reported in separate
studies at F intakes of 0.07–0.4 mg/kg/day, corresponding to serum F concentrations above about 0.1 mg/L
[Doull 2006 cited in Ahhaei 2015].
Those with diagnosed skeletal fluorosis demonstrate high levels of serum insulin.
Diabetics are exposed to an acceleration of their disease due to water fluoridation. They typically drink
much larger volumes of water [Prystupa 2011] and accumulate, or retain, more Fluoride.
According to Australia’s NHMRC, “People with kidney impairment have a lower margin of safety for fluoride
intake. Limited data indicate that their fluoride retention may be up to three times normal ” [NHMRC
Australian Drinking Water Guidelines 2004 and 2011].
The mechanisms by which Fluoride induces diabetes most likely include antagonism to calcium and
magnesium centred biochemistry [De Valk 1999, Simmons 2010]. Insulin secretion (both basal and
glucose-stimulated) by isolated islets of Langerhans in vitro is inhibited as a function of fluoride
concentrations [Rigalli 1990, 1995].
Diabetics are more susceptible to Fluoride induced arterial contraction [Hattori 2000] increasing risk of
cardiovascular disease. Cardiovascular disease death rates were about 1.7 times higher among adults
aged 18 years or older with diagnosed diabetes than among adults without diagnosed diabetes. Rates for
heart attack were 1.8 times higher among adults aged 20 years or older with diagnosed diabetes. Rates for
stroke were 1.5 times higher [CDC 2014].
Fluoride induced diabetes will also cause damage to the periodontum and tooth loss [AHMAC 2001].
Diabetics are a “Sensitive Subpopulation” or “Vulnerable Group” and no attempt has been made by
Australian health authorities to warn diabetics about Fluoride toxicity or protect them from harmful
exposure.
Breast feeding is known to have a protective role against insulin dependent diabetes [Mayer 1988]. Breast
fed children have much less exposure to Fluoride because human mothers’ milk contains very low Fluoride,
despite Australian Federal and State government attempts to increase it by Fluoridation.
Fluoride the Universal Toxin
Fluoride is a bio-accumulative toxin with no nutritional value
One of the primary mechanisms of Fluoride toxicity, in virtually all studied cell types, is disruption of
Guanine nucleotide-binding proteins (G proteins) transmit extracellular chemical signals from
transmembrane G-protein-coupled receptors to intracellular targets by activating the cascades of second
messengers. This toxic mechanism often involves Aluminium which forms FluoroAluminate ions that mimic
Phosphate ions (Figure 22) [Agalakova 2012]. The summary reads: “Fluoride is able to stimulate G-proteins
with subsequent activation of downstream signal transduction pathways such as PKA-, PKC-, PI3-kinase-,
Ca2+-, and MAPK-dependent systems. G-protein-independent routes include tyrosine phosphorylation and
protein phosphatase inhibition. Along with other toxic effects, fluoride was shown to induce oxidative stress
leading to excessive generation of ROS, lipid peroxidation, decrease in the GSH/GSSH ratio, and
alterations in activities of antioxidant enzymes, as well as to inhibit glycolysis thus causing the depletion of
cellular ATP and disturbances in cellular metabolism. Fluoride triggers the disruption of mitochondria outer
membrane and release of cytochrome c into cytosol, what activates caspases-9 and -3 (intrinsic) apoptotic
pathway. Extrinsic (death receptor) Fas/FasL-caspase-8 and -3 pathway was also described to be
implicated in fluoride-induced apoptosis. Fluoride decreases the ratio of antiapoptotic/proapoptotic Bcl-2
family proteins and upregulates the expression of p53 protein. Finally, fluoride changes the expression
profile of apoptosis-related genes and causes endoplasmic reticulum stress leading to inhibition of protein
synthesis.”
Figure 22. Mechanisms of Fluoride Toxicity with or without Aluminium [Agalakova 2012]
The Figure caption [Agalakova 2012] reads “Figure 1: A simplified scheme of intracellular molecular
mechanisms involved in fluoride toxicity and apoptosis. Nc: nucleus, ER: endoplasmic reticulum; Mt:
Mitochondria; RTK: receptor tyrosine kinase; GPCR: G protein-coupled receptor; FasR: Fas receptor; PI3K:
phosphoinositol-3 kinase; Akt: Akt kinase; PLC: phospholipase C; PKC: protein kinase C; PIP2:
phosphatidylinositol 4,5-biphosphate; IP3: inositol 1,4,5-triphosphate; DAG: diacylglycerol; CaM:
calmodulin; AC: adenylyl cyclase; PKA: protein kinase A; RhoGEF: Rho guaninenucleotide exchange
factor; RhoK: Rho kinase;MLCK: myosin light chain kinase; PERK: RNA-activated protein kinase-like ER
kinase; IRE1: inositol-requiring protein-1; eIF2α: eukaryotic translational initiation factor 2 subunit α; Xbp-1:
X-box binding protein 1; Bip/GRP78: BiP/glucose-responsible protein 78; GADD153: DNA damage-
inducible protein; PPs: protein phosphatases; K Ch: K+ channels; NKCC: Na+-K+–2Cl− cotransport; NHE:
Na+/H+ exchange.
A similar scheme was published by another group of leading Fluoride toxicologists in 2010 (Figure 23)
[Barbier 2010].
Figure 23. Devastation caused to mammalian cells by Fluoride [Barbier 2010]
Of specific relevance to Diabetes is the destruction of normal Pancreas function.
Optical microscopy revealed increased width of connective tissue and increased mitotic activity in
pancreases rats [Ogilvie 1953]. Fluoride-induced ultrastructural changes in exocrine pancreas cells of rats
involve disruption the export of zymogens from the rough endoplasmic reticulum [Matsuo 2000].
Dose-dependent toxic Fluoride effects involving Gαi protein have been demonstrated in the clonal RINm5F
pancreatic β-cells and rat Langerhans islets [Loweth 1996, Elliott 2001, Elliott 2002].
Fluoride inhibits tyrosine kinase activity of insulin receptors purified from rat skeletal muscles and human
placenta by direct binding to the receptors [Vinals 1993].
Reactive oxidation species induced by Fluoride are extremely effective killers of cells. Mouse pancreatic β–
cells exposed to 1.35–2.26 mM Fluoride were shown to have elevated superoxide anion resulting in
impaired glucose tolerance [García-Montalvo 2009].
Diabetes, metabolic disorders and Cataract
Metabolic cataracts include those associated with Diabetes Mellitus, Galactosaemia, Hypercholesteraemia,
Lipidemia, Endocrinological cataract associated with Hypothyroidism and Hypercalcaemia and cataracts
associated with certain skin diseases such as Atopic Dermatitis [Dawson 1981, Kador 2008].
Elevated Plasma albumin, bilirubin, calcium, cortisol, glucose, sodium and γ– glutamyl transpeptidase levels
in cataract patients were linked to liver disease [Donnelly 1995]. Fluoride is a known hepatotoxin.
Diabetes is associated with severe mitochondrial disorders such as Kearns-Sayre syndrome and
Mitochondrial Encephalomyopathy, Lactic Acidosis, and Strokelike episodes (MELAS). Mitochondrial forms
of diabetes mellitus occur in conjunction with hearing loss, myopathy, seizure disorder, strokelike episodes,
retinitis pigmentosa, external ophthalmoplegia and cataracts.
Fluoride is very effective in damaging the retina through inhibition of glycolysis [Sorsby 1960].
There is evidence of maternal inheritance [van den Ouweland 1992, Khardori 2017]. Increased glycated
haemoglobin level was associated with increased risk of nuclear and cortical cataracts in those with
diabetes [Klein 1998]. Fluoride is known to cause Diabetes [Pain 2015c].
Diabetes is associated with low birth weight and while there is a genetic component to low birth weight
[Wang 2016], Fluoride is known to cause low birth weight in exposed populations [Hart, MacArthur 2013].
Prevalence studies on diabetes complications reported up to the early 1990s gave widely variable figures.
These have been reviewed in two studies and include figures ranging from 9 to 16 percent for cataract, 7 to
52 percent for retinopathy, 6 to 47 percent for neuropathy, 6 to 30 percent for nephropathy, and 1 to 5
percent for macroangiopathy [Mbanya 2003; Rolfe 1997].
Women diabetics suffer higher rates of cataract and earlier surgery than men. Risk factors from the
Framingham heart study that were significantly associated with cataract formation included: elevated blood
sugar, elevated blood pressure, increased serum phospholipids, decreased pulmonary vital capacity, small
stature, and less than seven years of schooling [Kahn 1977].
A patient suffering diabetes, ischemic heart disease, hypertension and renal dysfunction and taking insulin
developed hydroxyapatite cataracts 4 months after implantation of an intraocular lens. Another patient,
diabetic and taking insulin developed hydroxyapatite cataracts 9 months after implantation. Another patient
in good overall health developed hydroxyapatite cataracts 15 months after implantation. All patients
received dexamethasone sodium phosphate eye drops [Yu 2001].
Prescribed Insulin increases risk of Cataracts, Odds Ratio = 3.38 (95% CI 1.61, 7.08) [Klein 2001].
In cases of suspected suicide by Insulin injection, they vitreous humour of the eye is analysed for the
presence of Insulin.
Diabetes and anaemia are comorbidities [Antwi-Bafour 2016]. Anaemia is a direct toxic effect of Fluoride
[Susheela 2010].
Laboratory animals with induced diabetes mellitus (NIDD-non insulin-dependent diabetes) demonstrated
more vulnerability to fluoride toxicity than non-diabetic animals [Singer 1976].
Vitamin D, Fluoride and Diabetes
Vitamin D deficiency is risk factor for Diabetes [Holick 2005]. A survey of Canadians living in Toronto,
Canada (Fluoridated) found that more than 93% of the total sample had concentrations of serum 25-
hydroxyvitamin D [25(OH)D], the main indicator of vitamin D status, below 75 nmol/L [Gozdzik 2008].
Fluoride interference with Vitamin D metabolism and consequent health damage will be reviewed
elsewhere.
Other Toxins impacting Diabetes incidence
Diabetes is associated with Arsenic exposure [Del Razo 2011, Gonzalez-Horta 2012, Maull 2012, Currier
2014, Chafe 2018].
Korean researchers found an association between Diabetes and exposure to Lead, Mercury and Cadmium
[Moon 2013].
References
Note: Those marked * were deliberately excluded from the NMRC 2007 Review.
Those marked ** were deliberately excluded from the NMRC 2017 Review.
Agalakova NI, Gusev GP. 2012. Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic
Fluoride. International Scholarly Research Network ISRN Cell Biology 2012, Article ID 403835
doi:10.5402/2012/403835. **
Agha FE, El-Badry MO, Hassan DAA, Elraouf AA. 2012. Role of vitamin E in combination with methionine
and L-carnosine against sodium fluoride-induced hematological, biochemical, DNA damage, histilogical and
immunohistochemical changes in pancreas of albino rats. Life Science Journal, vol. 9(2):1260-1275.
Aghaei M, Derakhshani R, Raoof M, Mohsen Dehghani M, Hossein Mahvi A. 2015. Effect of Fluoride in
Drinking Water on Birth Height and Weight: An Ecological Study in Kerman Province, Zarand County, Iran.
Fluoride 48(2):160-168.
Alavi AA, Amirhakimi E, Karami B. 2006. The prevalence of dental caries in 5-18-year-old insulin-
dependent diabetics of Fars Province, southern Iran Archives of Iranian Medicine, 9(3):254–260. *
Antwi-Bafour S, Hammond S, Kofi Adjei J, Kyeremeh R, Martin-Odoom A, Ekem I. 2016. A Case-Control
Study of Prevalence of Anemia Among Patients with Type 2 Diabetes. J Med Case Reports 10:110.
Atkins RC. 2005. The epidemiology of chronic kidney disease. Kidney International 67 Supplement 94:S14-
S18.
Australian Health Ministers’ Advisory Council (AHMAC) Steering Committee for National Planning for Oral
Health. 2001. Oral health of Australians: National planning for oral health improvement: Final report. South
Australian Department of Human Services.
Avtsyn AP, Zhavoronkov AA. Fluorosis pathology (Novosibirsk, 1981) cited in Tokar 1992.
Banu Priya CAY, Anitha K, Murali Mohan E, Pillai KS, Murthy PB. 1997. Toxicity of fluoride to diabetic rats.
Fluoride 30(1):43-50.
Barbier O, Arreola-Mendoza L, María Del Razo L. 2010. Molecular mechanisms of fluoride toxicity.
Chemico-Biological Interactions 188 (2010):319-333.
Basha MP, Saumya SM. 2013. Influence of fluoride on streptozotocin induced diabetic nephrotoxicity in
mice: Protective role of Asian ginseng (Panax ginseng) & banaba (Lagerstroemia speciosa) on
mitochondrial oxidative stress. The Indian Journal of Medical Research February 137(2):370-379.
Bergman Å, Heindel JJ, Jobling S, Kidd KA, Zoeller RT. Editors. 2013. State of the Science of Endocrine
Disrupting Chemicals – 2012. An assessment of the state of the science of endocrine disruptors prepared
by a group of experts for the United Nations Environment Programme and World Health Organization.
Birkner E, Grucka-Mamczar E, Zalejska-Fiolka J et al. 2006. Influence of sodium fluoride and caffeine on
the concentration of fluoride ions, glucose, and urea in blood serum and activity of protein metabolism
enzymes in rat liver. Biol Trace Elem Res. 112(2):169–74.
Bolgul BS, Celenk S, Ayna BE, Atakul F, Uysal E. 2004. Evaluation of caries risk factors and effects of a
fluoride-releasing adhesive material in children with insulin-dependent diabetes mellitus (IDDM): Initial first-
year results Acta Odontologica Scandinavica, 62(5):289-292. *
Boros I, Keszler P, Csikós G, Kalász H. 1998. Fluoride intake, distribution, and bone content in diabetic rats
consuming fluoridated drinking water. Fluoride 31(1):33–42.
Castro G, Areias MFC, Weissmann L, Quaresma PGF, Katashima CK, Saad MJA, Prada PO 2013. Diet-
induced obesity induces endoplasmic reticulum stress and insulin resistance in the amygdala of rats. FEBS
Open Bio 3:443–449.
CDC. Center for Disease Control. 2014. National Center for Chronic Disease Prevention and Health
Promotion. National Diabetes Statistics Report, 2014.
Cettour-Rose P, Theander-Carrillo C , Asensio C, Klein M, Visser TJ, Burger AG, Meier CA, Rohner-
JeanrenaudF. 2005. Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially
corrected by central leptin infusion. Diabetologia 48(4):624-633 cited in Doull 2006.
Chafe R, Aslanov R, Sarkar A, Gregory P, Comeau A, Newhook LA. 2018. Association of type 1 diabetes
and concentrations of drinking water components in Newfoundland and Labrador, Canada BMJ Open
Diabetes Research and Care 6:e000466. http://drc.bmj.com/content/6/1/e000466.
Chang CH, Tsai RK, Wu WC, Kuo SL, Yu HS. 1997. Use of dynamic capillaroscopy for studying cutaneous
microcirculation in patients with diabetes mellitus. Microvascular Research 53:121–127. *
Chehoud KA, Chiba FY, Sassaki KT, Garbin CA, Sumida DH. 2008. Effects of fluoride intake on insulin
sensitivity and insulin signal transduction Fluoride October-December 41(4):270-275.
Chiba FY, Colombo NH, Shirakashi DJ, Da Silva VC, Moimaz SAS, Garbin CAS, Antoniali C, Sumida DH.
2012. NaF treatment increases TNF-a and resistin concentrations and reduces insulin signal in rats.
Journal of Fluorine Chemistry 136:3-7.
Chiba FY, Garbin CAS, Sumida DH. 2012a. Effect of fluoride intake on carbohydrate metabolism, glucose
tolerance, and insulin signaling. Fluoride July-September 45(3 Pt 2):236-241.
Chiba FY, Colombo NH, Shirakashi DJ, Gomes WD, Moimaz SAS, Garbin CAS, Silva CA, Sumida DH.
2010. Insulin signal decrease in muscle but not in the liver of castrated male rats from chronic exposure to
fluoride. Fluoride January-March 43(1):25-30.
Chlubek D, Grucka-Mamczar E, Birkner E, Polaniak R, Stawiarska-Pieta B, Duliban H. 2003. Activity of
pancreatic antioxidative enzymes and malondialdehyde concentrations in rats with hyperglycemia caused
by fluoride intoxication. J. Trace Elem. Med. Biol. 17:57-60.
Cohen BZ, Wald KJ, Toyama K. 1997. Neodymium:YLF picosecond laser segmentation for retinal traction
associated with proliferative diabetic retinopathy. American Journal of Ophthalmology 123:(4):515-523 *
Cortet B, Berniere L, Solau-Gervais E, Hacene A, Cotten A, Delcambre B. 2000. Axial osteomalacia with
sacroiliitis and moderate phosphate diabetes: Report of a case. Clinical and Experimental Rheumatology
18(5):625-628.
Currier JM, Ishida MC, Gonzalez-Horta C, Sanchez-Ramírez B, Ballinas-Casarrubias L, Gutiérrez-Torres
DS, Cerón RH, Morales DV, Terrazas FA, del Razo LM et al. 2014. Associations between arsenic species
in exfoliated urothelial cells and prevalence of diabetes among residents of Chihuahua, Mexico. Environ.
Health Perspect. 122:1088-1094.
Dabrowska E, Balunowska M, Letko R, Szynaka B.2004. Ultrastructural study of the mitochondria in the
submandibular gland, the pancreas and the liver of young rats, exposed to NaF in drinking water. Ann.
Acad. Med. Bialost. 49:180-181.
Dawson CR, Schwab IR. 1981. Epidemiology of cataract – a major cause of preventable blindness. Bulletin
of the World Health Organization 59 (4):493-501.
de Cássia Alves Nunes R, Chiba FY, Pereira AG, Pereira RF, de Lima Coutinho Mattera MS, Ervolino E, et
al. 2016. Effect of Sodium Fluoride on Bone Biomechanical and Histomorphometric Parameters and on
Insulin Signaling and Insulin Sensitivity in Ovariectomized Rats. Biol Trace Elem Res.
de la Sota M, Puche RC, Rigalli A, Fernandez LM, Benassati S, Boland .R 1997. Modificaciones en la
masa o´sea y en la homeostasis de la glucose en residentes de la zona de Bahia Blanca con alta ingesta
esponta´nea de flu´or. [Changes in bone mass and glucose homeostasis in subjects with high spontaneous
fluoride intake] Medicina 57:417-420.
Del Razo LM, García-Vargas GG, Valenzuela OL, Hernandez-Castellanos E, Sanchez-Peña LC, Currier
JM, Drobna Z, Loomis D, Stýblo M. 2011. Exposure to arsenic in drinking water is associated with
increased prevalence of diabetes: A cross-sectional study in the Zimapan and Lagunera regions in Mexico.
Environ. Health 10, doi:10.1186/1476-069X-10-73.
Desai M, Li T, Ross MG. 2011. Hypothalamic neurosphere progenitor cells in low birth-weight rat
newborns: neurotrophic effects of leptin and insulin. Brain Res. 1378:29-42.
De Valk HW. 1999. Magnesium in diabetes mellitus. Neth J Med 54:139–46.
Dionizio AS, Melo CGS, Arias ITS, Ventura TMS, Leite AL, Souza SRG, Santos EX, Heubel AD, Souza JG,
Perles JVCM, Zanoni JN, Buzalaf MAR. 2018. Chronic treatment with fluoride affects the jejunum: insights
from proteomics and enteric innervations analysis. Nature Scientific Reports. 8:3180 DOI:10.1038/s41598-
018–21533-4.
Donnelly CA, Seth J, Clayton RM, Phillips CI, Cuthbert J, Prescott RJ. 1995. Some blood plasma
constituents correlate with human cataract. British Journal of Ophthalmology 79:1036-1041.
Doull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE,
Reed N-MR, Thiessen KM, Webster TF, Committee on Fluoride in Drinking Water, Board on Environmental
Studies and Toxicology, Division on Earth and Life Studies, National Research Council of the National
Academies. 2006. Fluoride in drinking water: A scientific review of EPA’s standards. Washington, DC:
National Academies Press; 2006.
Dunaif A. 1995. Hyperandrogenic anovulation (PCOS): a unique disorder of insulin action associated with
an increased risk of non-insulin-dependent diabetes mellitus. Am J Med. Jan 16. 98(1A):33S-39S.
Dunger DB, Petry CJ. Ong KK. Genetics of size at birth. Diabetes Care 2007;30 Suppl 2:S150-5. Available
Dunipace AJ, et al. 1996. Absence of detrimental effects of fluoride exposure in diabetic rats. Archives of
Oral Biology 41(2):191-203.
Duxbury MS, Waseem T, Ito H, et al. 2003. Ghrelin promotes pancreatic adenocarcinoma cellular
proliferation and invasiveness. Biochem Biophys Res Commun 309:464-8.
Elliott J, Scarpello JHB, Morgan NG. 2001. Effects of tyrosine kinase inhibitors on cell death induced by
sodium fluoride and pertussis toxin in the pancreatic β-cell line, RINm5F. British Journal of Pharmacology
132(1):119-126.
Elliott J, Scarpello JHB, Morgan NG. 2002. Differential effects of genistein on apoptosis induced by fluoride
and pertussis toxin in human and rat pancreatic islets and RINm5F cells. Journal of Endocrinology
172(1):137-143. *
Fluegge K. 2016. Community water fluoridation predicts increase in age-adjusted incidence and prevalence
of diabetes in 22 states from 2005 and 2010. Journal of Water and Health https://
Franks S, Robinson S, Willis DS. 1996. Nutrition, insulin and polycystic ovary syndrome. Rev Reprod.
1(1):47-53.
Fröhlich E, Wahl R. 2017. Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and extra-
Thyroidal Diseases. Frontiers in Immunology 8:521 doi: 10.3389/fimmu.2017.00521.
García-Montalvo EA, Reyes-Pérez H, Del Razo LM. 2009. Fluoride exposure impairs glucose tolerance via
decreased insulin expression and oxidative stress. Toxicology 263(2-3):75–83.
Gozdzik A, Barta JL, Wu H, Wagner D, Cole DE, Vieth R, Whiting S, Parra EJ. 2008. Low wintertime
vitamin D levels in a sample of healthy young adults of diverse ancestry living in the Toronto area:
associations with vitamin D intake and skin pigmentation. BMC Public Health 8:336
Gonzalez-Horta C, Sanchez-Ramirez B, Ballinas-Casarrubias L, Ishida-Gutierrez C, del Razo LM, García-
Vargas G, Loomis D, Drobna Z, Stýblo M. July 2012. Chronic exposure to arsenic and prevalence of
diabetes in Mexico. In Proceedings of the 4th International Congress on Arsenic in the Environment,
Cairns, Australia, 22–27:169-171.
Greenberg LW, Nelsen CE, Kramer N. 1974. Nephrogenic diabetes insipidus with fluorosis. Pediatrics
54:320-322.
Grucka-Mamczar E, et al. 2004. Activities of some enzymes and concentration of ammonia in serum of rats
with fluoride hyperglycemia Ann Acad Med Stetin. 50 Suppl 1:36–41.
Grucka-Mamczar E, Birkner E, Zalejska-Fiolka J, Machoy Z, Kasperczyk S, Blaszczyk I. 2007. Influence of
extended exposure to sodium fluoride and caffeine on the activity of carbohydrate metabolism enzymes in
rat blood serum and liver. Fluoride 40:62-66.
Guntur AR, Rosen CJ. 2012. Bone as an Endocrine Organ Endocr Pract. 18(5):758-762.
Gutowska I, Baranowska-Bosiacka I, Rybicka M, Dudzinska W, Marchlewicz M, Nocen I, Sawinski G,
Wiszniewska B, Chlubek D. 2009. Changes in the concentration of fluoride in the serum and bones of
female rats with streptozotocin induced diabetes. Fluoride January-March 42(1):9–16.
Haddad N, Howland R, Baroody G, Daher C. 2006. The modulatory effect of leptin on the overall insulin
production in ex-vivo normal rat pancreas. Can J Physiol Pharmacol 84:157-162.
Hamada N, Nishi Y, Tajiri, Y, Setoyama K, Kamimura Y, Miyahara K, Nuruki N, Hosoda H, Kangawa K,
Kojima M, Mifune H. 2012. Disrupted Regulation of Ghrelin Production under Antihypertensive Treatment in
Spontaneously Hypertensive Rats. Circulation Journal. 76:1423-1429.
Hanhijarvi H, Penttila I, Pekkarinen A, Hakulinen A. 1974. The effect of age on free ionized plasma fluoride
concentrations in patients from Artificially Fluoridated and Non-fluoridated Drinking Water Communities.
Proc Finn Dent Soc. 3:25-34.
Hart R, et al. Relationship between municipal water fluoridation and preterm birth in Upstate New York.
American Public Health Association 137th Annual Meeting.
Hattori Y, Matsuda N, Sato A, Watanuki S, Tomioka H, Kawasaki H, Kanno M. 2000. Predominant
contribution of the G protein-mediated mechanism to NaF-induced vascular contractions in diabetic rats:
association with an increased level of G(qalpha) expression. J Pharmacol Exp Ther. 292(2):761–8.
Henderson, Michelle. 28 May 2012 AAP online news http://www.news.com.au/breaking-news/m-have-
undiagnosed-kidney-disease/story-e6frfku0-1226368819679.
Holick MF. 2005. Vitamin D: Important for prevention of osteoporosis, cardiovascular heart disease, type 1
diabetes, autoimmune diseases, and some cancers. South Med J 98(10):1024-1027.
Hu CY, Ren LQ, Li XN, WuN, Li GS, Liu QY, Xu H. December 2012. Effect of fluoride on insulin level of rats
and insulin receptor expression in the MC3T3-E1 cells. Biological Trace Element Research 150(1-3):297–
305.
Irmak MK, Ozcelik IS, Kaya A. 2014. Fluoride toxicity and new-onset diabetes in Finland: a hypothesis
Journal of Experimental and Integrative Medicine 4(1):3-8. **
Ito M, Nakagawa H, Okada T, Miyazaki S, Matsuo S. 2009. ER-stress caused by accumulated intracistanal
granules activates autophagy through a different signal pathway from unfolded protein response in exocrine
pancreas cells of rats exposed to fluoride. Archives of Toxicology 83(2):151-159.
Izbicka E, Yoneda T, Takaoka Y, Horn D, Williams P, Mundy GR. 1996. Identification of a novel
bone/calcium metabolism-regulating factor in porcine pancreas. Journal of Biological Chemistry
271(38):23230-23234. *
Jiang C, Zhang S, Liu H, Guan Z, Zeng Q, Zhang C, Lei R, Xia T, Wang Z, Yang L, Chen Y, Wu X, Zhang
X, Cui Y, Yu L, Wang A. 2014. Low glucose utilization and neurodegenerative changes caused by sodium
fluoride exposure in rat’s developmental brain. Neruomol Med 16:94-105.
Jones M, Tett S, Peeters GMEE, Mishra GD, Dobson A. 2017. New-Onset Diabetes After Statin Exposure
in Elderly Women: The Australian Longitudinal Study on Womenʼs Health. 34(3):203-209.
Kador PF, Wyman M. 2008. Asteroid hyalosis: pathogenesis and prospects for prevention. Eye 22:1278-85.
Kahn HA et al. 1977. The Framingham Eye Study. II. Association of ophthalmic pathology with single
variables previously measured in the Framingham Heart Study. American Journal of Epidemiology 106:33-
41.
Kathpalia A, Susheela AK. 1978. Effect of sodium fluoride on tissue protein in rabbits Fluoride 12:125-129.
Cited in Tokar 1992.
Kellow NJ, Coughlan MT, Savige GS, Reid CM. 2014. Effect of Dietary Prebiotic Supplementation on
Advanced Glycation, Insulin Resistance and Inflammatory Biomarkers in Adults With Prediabetes. A Study
Protocol for a Double-Blind Placebo-Controlled Randomised Crossover Clinical Trial. BMC Endocr Disord
14:55.
Khardori R, Griffing GT, Bessen HA, Brenner BE, Isley WL, Ligaray KPL, Peters AL, Schade DS, Schalch
DS, Schraga ED, Talavera F, Votey SR. 2017. Type 2 Diabetes Mellitus. Medline.
Kheradpisheh Z, Mirzaei M, Hossein Mahvi A, Mokhtari M, Azizi R, Fallahzadeh H, Hassan Ehrampoush M.
2018. Impact of Drinking Water Fluoride on Human Thyroid Hormones: A Case-Control Study. Nature
Scientific Reports. 8:2674 DOI:10.1038/s41598-018-20696-4.
Klein BE, Klein R, Lee KE. 1998. Diabetes, cardiovascular disease, selected cardiovascular disease risk
factors, and the 5-year incidence of age-related cataract and progression of lens opacities: the Beaver Dam
Eye Study. Am J Ophthalmol 126:782-790.
Klein B. 2001. Drug use and five-year incidence of age-related cataracts: The Beaver Dam Eye Study.
Ophthalmology 108:1670-1674.
Klein H. 1975. Dental fluorosis associated with hereditary diabetes insipidus. Oral Surg. Oral
Med. Oral Pathol. 40(6):736–741.
Kode A, Mosialou I, Silva BC, et al. 2012. FoxO1 protein cooperates with ATF4 protein in osteoblasts to
control glucose homeostasis. J Biol Chem. 287:8757-8768.
LauKHW, Goodwin C, Arias M, Mohan S, Baylink DJ. 2002. Bone cell mitogenic action of fluoroaluminate
and aluminum fluoride but not that of sodium fluoride involves upregulation of the insulin-like growth factor
system. Bone 30:705-711.
Lima Leite A.Lobo GV, Pereira HA, Fernandes MS, Martini T, Zucki F, Sumida DH, Rigalli A, Buzalaf MA.
2014. Proteomic Analysis of Gastrocnemius Muscle in Rats with Streptozotocin- Induced Diabetes and
Chronically Exposed to Fluoride. Plos One.
Lin BJ, Henderson MJ, Levine BB, Nagy BR, Nagy EM. 1976. Effects of iodoacetate and fluoride on islate
respiration and insulin biosynthesis. Horm. Metabo. Res. 8:353-358 cited in Tokar 1992.
Lobo JG, Leite AL, Pereira HA, Fernandes MS, Peres-Buzalaf C, Sumida DH, Rigalli A, Buzalaf MA. 2015.
Low-Level Fluoride Exposure Increases Insulin Sensitivity in Experimental Diabetes. J Dent Res.
94(7):990-7.
Lombarte MF, Lupo BL, Buzalaf, Marı´lia A, Rigalli Alfredo. 2013. Physical exercise ameliorates the toxic
effect of fluoride on the insulin–glucose system Journal of Endocrinology 218(1):99–103.
Loweth AC, Williams GT, Scarpello JHB, Morgan NG. 1996.Heterotrimeric G-proteins are implicated in the
regulation of apoptosis in pancreatic β-cells. Experimental Cell Research 229(1):69-76.
Lupo M, Buzalaf MA, Rigalli A. 2011. Effect of fluoridated water on plasma insulin levels and glucose
homeostasis in rats with renal deficiency. Biological Trace Element Research 140:198-207.
Marier JR. 1977. Some current aspects of environmental fluoride. Sci . Tot. Environ. 8:253–265.
Maassen JA, T Hart LM, Van Essen E, et al. 2004. Mitochondrial diabetes: molecular mechanisms and
clinical presentation. Diabetes 53:S103-S109.
Matsuo S, Nakagawa H, Kiyomiya K, Kurebe M. 2000. Fluoride-induced ultrastructural changes in exocrine
pancreas cells of rats: fluoride disrupts the export of zymogens from the rough endoplasmic reticulum
(rER). Arch Toxicol 73:611-617.
Matsuoka TA, Zhao L, Stein R. 2001. The DNA Binding Activity of the RIPE3b1 Transcription Factor of
Insulin Appears to Be Influenced by Tyrosine Phosphorylation Journal of Biological Chemistry
276(25):22071–22076. *
Maull EA, Ahsan H, Edwards J, Longnecker MP, Navas-Acien A, Pi J, Silbergeld EK, Styblo M, Tseng CH,
Thayer KA et al. 2012. Evaluation of the association between arsenic and diabetes: A national toxicology
program workshop review. Environ. Health Perspect. 120:1658–1670.
Mayer EJ, Hamman RF, Gay EC, et al. Reduced risk of IDDM among breast fed children. The Colorado
IDDM Registry. Diabetes 37(12):1625-1632.
Mazze RI, Calverley RK, Smith NT. 1977. Inorganic fluoride nephrotoxicity: prolonged enflurane and
halothane anesthesia in volunteers. Anesthesiology. 46(4):265–71.
Mbanya JC, Sobngwi E. 2003. Diabetes Microvascular and Macrovascular Disease in Africa. Journal of
Cardiovascular Risk 10: 97-102.
Mehta MN, Raghavan K, Gharpure VP, Shenoy R. 1998. Fluorosis: a rare complication of diabetes
insipidus. Indian Pediatr 35:463-467.
Menoyo I, Puche RC, Rigalli A. 2008. Fluoride-induced resistance to insulin in the rat. Fluoride 41:260-269.
Menoyo I, Rigalli A, Puche RC.2005. Effect of fluoride on the secretion of insulin in the rat. Arznei-mittel
Forschung (Drug Res) 55(5):455-60.
Michaud DS. 2004. Epidemiology of pancreatic cancer. Minerva Chir 59(2):99–111.
Misur I, Zarkovic K, Barada A, Batelja L, Milicević Z, Turk Z. 2004. Advanced glycation end products in
peripheral nerve in type 2 diabetes with neuropathy. Acta Diabetol 41(4):158-166.
Moon SS. 2013. Association of lead, mercury and cadmium with diabetes in the Korean population: the
Korea National Health and Nutrition Examination Survey (KNHANES) 2009-2010. Diabet Med. 30:e143-8.
Mueller WM, Gregoire FM, Stanhope KL, Mobbs CV, Mizuno TM, Warden CH, Stern JS, Havel PJ. 1998.
Endocrinology 139(2):551-558.
Murata M,Okimura Y, Iida K, et al. 2002. Ghrelin modulates the downstream molecules of insulin signaling
in hepatoma cells. JBiol Chem 277:5667-74.
Nagakawa T, Kayahara M, Ohta T, Kitagawa H, Mikami K, Kurata T, Otsuji S. 2000. Dihydropyrimidine
dehydrogenase activity in human pancreatic tumor tissues. Cancer Investigation 18(6):516-520 *
National Health and Medical Research Council (NHMRC). 2007. A systematic review of the efficacy and
safety of fluoridation PART B: EXCLUDED STUDIES
Ng CK, Soufer R, McNulty PH. 1998. Effect of hyperinsulinemia on myocardial fluorine-18-FDG uptake
Journal of Nuclear Medicine, 39(3):379-383 *
Nicolay A, Bertocchio P, Bargas E, Coudore F, Al Chahin G, Reynier J-P. 1999. Hyperkalemia risks in
hemodialysed patients consuming fluoride-rich water. Clinica Chimica Acta 281:29-36.
Ogilvie AL.1953. Histologic findings in the kidney, liver, pancreas, adrenal, and thyroid glands of the rat
following sodium fluoride administration. J. Dent. Res. 32(3):386-397.
Pain GN. 2015. Fluoride Causes Diabetes.
Pallett AL, Morton NM, Cawthorne MA, Emilsson V. 1997. Leptin inhibits insulin secretion and reduces
insulin mRNA levels in rat isolated pancreatic islets. Biochem Biophys Res Commun 238:267-270.
Patel D, Kalhan S. 1975. Glycerol metabolism and triglyceride-fatty acid cycling in the human newborn:
effect of maternal diabetes and intrauterine growth retardation. Pediatr Res 31:52-58
PHIDU. 2005. Population health profile of the Townsville Division of General Practice. Population Profile
Series: No. 78. Public Health Information Development Unit (PHIDU), Adelaide.
Pivonello R, Colao A, Di Somma C, Facciolli G, Klain M, Faggiano A, Salvatore M, Lombardi G. 1998.
Impairment of bone status in patients with central diabetes insipidus. J Clin Endocrinol Metab 83:2275-
2280.
Prystupa J. 2011. Fluorine – A current literature review. An NRC and ATSDR based review of safety
standards for exposure to fluorine and fluorides Toxicology Mechanisms and Methods, 21(2):103-170.
Pujary UR, Rao P, Mohanthy S, Krishna R, Reddy D. Correlation between serum fluoride and
hyperglycemia in endemic fluorosis area. Indian Journal of Clinical Biochemistry December 2007
22(Suppl):383.
Purdie DM, Green AC. 2001. Epidemiology of endometrial cancer. Best Pract Res Clin Obstet Gynaecol,
15(3):341-354.
Queensland Hospital Admitted Patient Data Collection 2005-2006 prepared by Health Surveillance,
Tropical Population Health Network
Rached MT, Kode A, Silva BC, et al. 2010. FoxO1 expression in osteoblasts regulates glucose
homeostasis through regulation of osteocalcin in mice. J Clin Invest 120:357-368.
Rasmussen DD, Boldt BM, Wilkinson CW, Yellon SM, Matsumoto AM. 1999. Daily melatonin administration
at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels.
Endocrinology 140:1009-1012.
Renke W, Winnicka, A and Graczyck M. 1987. Estimation of occupational hazards of the employees of a
phosphate fertilizers plant. Bull. Inst. Mar. Trop. Med. Gdynia 38:5-16.
Rigalli A, et al. 1995. Comparative study of the effect of sodium fluoride and sodium monofluorophosphate
on glucose homeostasis in the rat. Drug Res 45(3):289–92.
Rigalli A, Ballina JC, Puche RC. 1992. Bone mass increase and glucose tolerance in rats chronically
treated with sodium fluoride. Bone and Mineral 16:101-108.
Rigalli A. 1990. Inhibitory effect of fluoride on the secretion of insulin. Calcif. Tissue Int. 46:333–338.
Rogalska A, Kuter K, Żelazko A, Głogowska-Gruszka A, Świętochowska E, Nowak P. 2017. Fluoride
Alteration of [3H] Glucose Uptake in Wistar Rat Brain and Peripheral Tissues. Neurotox Res DOI
10.1007/s12640-017-9709-x.
Rolfe M. 1997. Chronic Complications of Diabetes in Africa. In Diabetes in Africa. Gill GV, Mbanya JC,
Alberti KGMM (eds) 43-50. Cambridge: FSG Communications.
Schneider S, Feilen PJ, Schreckenberger M, Schwanstecher M, Schwanstecher C, Buchholz HG, Thews
O, Oberholzer K, Korobeynikov A, Bauman A, Comagic S, Piel M, Schirrmacher E, Shiue CY, Alavi AA,
Bartenstein P, Rosch F, Weber MM, Klein HH, Schirrmacher R. 2005. In vitro and in vivo evaluation of
novel glibenclamide derivatives as imaging agents for the non-invasive assessment of the pancreatic islet
cell mass in animals and humans. Experimental and Clinical Endocrinology and Diabetes, 113(7):388-395.
*
Seow WK, Thomsett MJ. 1994. Dental fluorosis as a complication of hereditary diabetes insipidus: studies
of six affected patients. Pediatr Dent 16:128-132.
Shahed AR, et al. 1986 Effect of F on rat serum insulin levels in vivo. Journal of Dental Research 65:756.
Sharma R, Tsuchiya M, Bartlett JD. 2008. Fluoride Induces Endoplasmic Reticulum Stress and Inhibits
Protein Synthesis and Secretion Environmental Health Perspectives 116(9):1142-1146.
Sharma R, Tsuchiya M, Skobe Z, Tannous BA, Bartlett JD. 2010. The Acid Test of Fluoride: How pH
Modulates Toxicity. PLoS ONE 5(5):e10895.
Simmons D, Joshi S, Shaw J. 2010. Hypomagnesaemia is associated with diabetes: Not pre-diabetes,
obesity or the metabolic syndrome. Diabetes Res Clin Pract 87(2):261-6.
Singer I, Forrest JN. 1976. Drug-induced states of nephrogenic Diabetes Insipidus. Kidney Internal. 10:82-
95.
Sorsby A, Harding R. 1960. Experimental Degeneration of The Retina* V. Fasting and Metabolic
Accelerators in Degeneration Produced by Sodium Fluoride. Brit. J. Ophthal. 44:213-
Stephen KW. 1994. Fluoride toothpastes, rinses, and tablets. Advances in Dental Research 8:185-189.
Susheela AK. 2010. Anemia in pregnancy: an easily rectifiable problem [editorial]. Fluoride 43(2):104-7.
Suketa Y, Asao Y, Kanamoto Y, et al. 1985. Changes in adrenal function as a possible mechanism for
elevation of serum glucose by a single large dose of fluoride. Tox Appl Pharm 80:199–205.
Takahashi K, Akinawa K, Narita K. 2001. Regression Analysis of Cancer Incidence Rates and Water
Fluoride in the U.S.A. based on IACR/IARC (WHO) Data (1978-1992). J Epidemiol 11(4):170-179.
Tokar VI, Zyryanova VV, Shcherbakov SV. 1992. Chronic Fluorides Impact on Pancreas Islet Cells in
Workers Gigiena i Sanitariia November-December 42-44.
Torra M, Rodamilans M, Corbella J. 1998. The Science of the Total Environment
Toshinai K,Mondal MS,Nakazato M, Date Y,Murakami N,Kojima M et al. 2001. Upregulation of Ghrelin
expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration. Biochem
Biophys Res Commun 281:1220-5.
Trivedi N, Mithal A, Gupta SK, Godbole, MM. 1993. Reversible impairment of glucose tolerance in patients
with endemic fluorosis. Diabetologia 36:826-828.
Turner CH,Garetto LP, Dunipace A J, Zhang W, Wilson ME,Grynpas MD, Chachra D, McClintock R,
Peacock M, Stookey GK. 1997. Fluoride Treatment Increased Serum IGF-1, Bone Turnover, and Bone
Mass, but Not Bone Strength, in Rabbits Calcified Tissue International 61(1):77–83.
Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR, Lee DH, Shioda T, Soto AM, von Saal FS,
Welshons WV, Zoeller RT, Myers JP. 2012. Hormones and endocrine-disrupting chemicals: Low dose
effects and nonmonotonic dose responses. Endocrine Reviews 33(3):378-455.
van den Ouweland JM, Lemkes HH, Ruitenbeek W, Sandkuijl LA, de Vijlder MF, Struyvenberg PA, et al.
1992. Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type
II diabetes mellitus and deafness. Nat Genet. 1(5):368-71.
Varadacharyulu NC, Rao PR. 1997. Gluconeogenesis and glycogenolysis in fluoride-treated rats. Indian
Journal of Experimental Biology 35(8):906-8.
Vasant RA, Kotadiya DR, Bhole KL, Narasimhacharya AVRL. 201 Therapeutic benefits of glibenclamide in
fluoride intoxicated diabetic rats. Fluoride April-June 43(2):141–149.
Vasant RA, Narasimhacharya AV. 2013a. A multigrain protein enriched diet mitigates fluoride toxicity.
Journal of Food Science Technology 50(3):528-34.
Vasant RA, Narasimhacharya AV. 2013. Limonia fruit as a food supplement to regulate fluoride-induced
hyperglycaemia and hyperlipidaemia. Journal of the Science of Food and Agriculture January 93(2):422-6.
Vasant RA, Narasimhacharya AV. 2012. Ameliorative effect of tamarind leaf on fluoride-induced metabolic
alterations Environmental Health and Preventive Medicine November 17(6):484–93.
Vinals F, Testar X, Palacin M, Zorzano A. 1993. Inhibitory effect of fluoride on insulin receptor
autophosphorylation and tyrosine kinase activity. Biochemical Journal vol. 291(2):615-622.
Volante M, Allia E, Gugliotta P, et al. 2002. Expression of ghrelin and of GHS receptor by pancreatic islet
cells and related endocrine tumors. JClin Endocrinol Metab 87:1300-8.
Vogeser M, Parhofer KG. 2005. Limited preanalytical requirements for insulin measurement Clinical
Biochemistry 38(6):572–575. *
Wang Z, Yang X, YangS, Ren G, Ferreri M, Su Y, Chen L, Han B. 2011. Sodium fluoride suppress
proliferation and induce apoptosis through decreased insulin-like growth factor-I expression and oxidative
stress in primary cultured mouse osteoblasts. Archives of Toxicology November 85(11):1407–17.
Wang T, Huang T, Li Y, Zheng Y, Manson JE, Hu FB, et al. 2016. Low birthweight and risk of type 2
diabetes: a Mendelian randomisation study. Diabetologia. Jun 23.
Weber LP, Chow W L, Abebe W, MacLeod K M. 1996 Enhanced contractile responses of arteries from
streptozotocin diabetic rats to sodium fluoride. Br J Pharmacol. May 118(1) 115–22
West RJ, Leonard JV. 1980 Familial insulin resistance with pineal hyperplasia: metabolic studies and effect
of hypophysectomy. Arch Dis Child 55:619–21.
Whitford GM, Allman DW, Shahed AR. 1987. Topical fluorides: effects on physiologic and biochemical
processes. J Dent Res. 66(5):1072-8.
Wojtaszewski JF, Richter EA. 2006. Effects of acute exercise and training on insulin action and sensitivity:
focus on molecular mechanisms in muscle. Essays in Biochemistry 42:31–34.
Wren AM, Seal LJ, Cohen MA, et al. 2001. Ghrelin enhances appetite and increases food intake in
humans. J Clin EndocrinolMetab 86:5992.
Wuster C, Heilmann P, Ziegler R. 1997. Problems of fluoride treatment of patients with osteoporosis in
general practice. Experimental and Clinical Endocrinology and Diabetes 105(4):A57-A58.
Xie Yong‐ping, Ge Xiang‐jin, Jiang Yu‐ting, Feng Ming‐ying, Fan Ying‐yi, Wang Fu‐lun, Wei Zeng-fu, Zhao
Gui‐lu, QinAi‐qiong.2000. Clinical Study of Effect of High Fluoride on the Function of the Pancreas Islet B
Cells.Chinese Journal of Endemiology 19(2):84–85.
Youlden DR, Cramb SM, Baade PD. 2009. Current status of female breast cancer in Queensland: 1982 to
2006. Viertel Centre for Research in Cancer Control, Cancer Council Queensland. Brisbane, Queensland.
Youlden DR, Cramb SM, Baade PD. 2008. Current status of colorectal cancer in Queensland: 1982 to
2005. Viertel Centre for Research in Cancer Control, Cancer Council Queensland: Brisbane. Retrieved 13
Oct 2010
Yu AKF, Shek TWH. 2001. Hydroxyapatite Formation on Implanted Hydrogel Intraocular Lenses. Arch
Opthalmol 611-613.
Zhang P, Zhang X, Brown J, Vistisen D, Sicree R, Shaw J, Nichols G. 2010. Global healthcare expenditure
on diabetes for 2010 and 2030. Diabetes Research and Clinical Practice, 87(3):293–301.
Comment
Recommendations
This brief literature review and bibliography presents evidence that Fluoride, through fluoridation of public drinking water, causes Diabetes as well as injury to existing diabetics.
Technical Report
Full-text available
Australia’s National Health and Medical Research Council states that the only harm arising from water Fluoridation and total dietary Fluoride intake is Dental Fluorosis. This guide provides a quick reference to harms known by toxicologists to be caused by Fluoride, including those still under intensive research and recognized by other administrations.
Technical Report
Full-text available
Acute and chronic poisoning of the gastrointestinal tract by ingested Fluoride has been studied for over 130 years with the measurable damage documented from the oral cavity through to the intestines.
Technical Report
Full-text available
Fluoride causes excess suffering and death by initiating and exacerbating kidney disease, which in turn causes a cascade of secondary, often fatal, diseases. This review demonstrates that proponents of water Fluoridation have attempted to suppress evidence of harm to the population at large and especially vulnerable groups with impaired renal function.
(PDF) Fluoride Causes Diabetes 2018 Update. Available from: https://www.researchgate.net/publication/328249196_Fluoride_Causes_Diabetes_2018_Update?fbclid=IwAR3TqOJYBRqNL6-y17OYFEOtLKtiWoC9q5SVc48n0YkK2m2W11_O4ApWphc [accessed Oct 28 2018].
conspiracyoz 
Leave a comment
Comments 0