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From the Townsend Letter
October 2019

Fluoride and Mental Decay: Causation & Correlation
by John D. MacArthur
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Back in the stone age of neuroscience, a controversial public health intervention was implemented. In 1945, because of its ecological association with decreased dental decay, fluoride was added to US drinking water. Now, fluoridation must end because of its many causative biochemical links to increased mental decay.

Well-established molecular mechanisms of fluoride toxicity are oxidative stress and inflammation, whose involvement in the initiation and pathogenesis of Alzheimer's disease is now being recognized.1

More recently, increasing scientific evidence reveals fluoride's pathological role in major neurodegenerative pathways: arterial stiffness, endothelial dysfunction, ER stress, and microglial activation.

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Arterial Stiffness
The biological aging process is always associated with arterial stiffness, which is emerging as an important risk factor underlying the effect of blood pressure on the brain. Arterial stiffness correlates with the pathogenesis of a large spectrum of vascular disorders: hypertension, stroke, kidney dysfunction, cerebrovascular disease, dementia, and Alzheimer's disease. The extent and progression of β-amyloid deposition in the brain is associated with arterial stiffness.2

When arteries lose their elasticity, it impairs their ability to absorb the increased pressure generated as the heart ejects blood into them. This arterial-pressure pulsatility is instead transmitted to smaller blood vessels. The brain's hippocampus is particularly vulnerable, because its capillaries are located close to large vessels. Swedish researchers have outlined a sequence of vascular events, connecting arterial stiffness to damaged hippocampal capillaries and impaired memory in older adults.3

TransferFactorIn people with fluorosis, the elastic properties of the ascending aorta are impaired.4 Fluoride accelerates arterial calcification and stiffening that lead to hypertension. When fluoride levels in drinking water increased from 0.84 to 1.55 mg/L, hypertension prevalence increased 22%.5

Population studies have found statistically significant positive correlations between fluoride levels in drinking water and increased hypertension, as well as a significant relationship with increased blood pressure.6

Impaired elasticity of the ascending aorta is associated with subclinical hypothyroidism. Higher TSH levels, a measure of hypothyroidism, correlate with aortic stiffness.7 Data from nearly 8,000 medical practices in England revealed a positive association between patients diagnosed with hypothyroidism and fluoride levels in their drinking water. Those living in a fluoridated region had twice the hypothyroidism prevalence as those in a nonfluoridated one.8

This study did not include undiagnosed subclinical hypothyroidism, which the US National Research Council (2006) said is associated with "cognitive dysfunction," as well as with "increased cholesterol concentrations."9 In May 2019, JAMA Neurology reported a link between high LDL cholesterol levels and early-onset Alzheimer's disease.10 Several animal studies have shown that fluoride exposure increases LDL cholesterol levels.

Endothelial Dysfunction
Endothelial cells line the inside of blood vessels from the aorta to microvessels, where they form a selective blood-tissue barrier that protects every organ system. Microvascular endothelial cells play a critical role in brain development, maturation, and homeostasis. Endothelial cell dysfunction in the blood-brain barrier is the first pathological change in the development of small vessel disease (SVD), the leading cause of vascular dementia. SVD contributes to and worsens the symptoms of Alzheimer's disease, triples the risk of stroke, and is responsible for up to 45% of dementias.11

Researchers at Johns Hopkins University School of Medicine demonstrated that sodium fluoride causes "dramatic" endothelial barrier dysfunction, as evidenced by marked increases in macromolecule endothelial cell permeability.12

Sevoflurane is a general anesthetic that significantly increases blood fluoride levels. After exposure to sevoflurane, the blood-brain barrier is compromised due to "flattening of endothelial cell surfaces."13,14

Sevoflurane is associated with high rates of post-operative delirium, a common and often fatal disorder affecting as many as 50% of older people during surgery or hospitalization. The severity of this delirium correlates directly to the severity of later cognitive impairment and decline.15

Another fluorinated drug that increases blood levels of fluoride and causes endothelial cell dysfunction is 5-fluorouracil.16,17

African Americans have reduced endothelial function – and greater arterial stiffness – compared with whites, even after adjusting for traditional cardiovascular risk factors.18

ER Stress
Within a cell, the endoplasmic reticulum (ER) is the site where proteins are synthesized and folded. ER function is highly sensitive to toxins that can overwhelm the cell's folding capacity and cause misfolded proteins to accumulate, a condition known as ER stress.

Chronic ER stress is responsible for neurodegeneration in numerous human diseases whose pathology includes accumulation of misfolded proteins in the brain. In Alzheimer's disease, the ER is "drastically affected."19,20 In addition, mounting proof indicates that ER stress is incriminated in psychiatric diseases like major depressive disorder, bipolar disorder, and schizophrenia.21

Fluoride exposure induces excessive ER stress and associated cell death in the hippocampus of rats, resulting in histological and ultrastructural abnormalities that impair learning and memory capabilities.22

Damaged tooth enamel is called dental fluorosis, because it is caused by fluoride, which initiates an ER stress response during tooth development. Beginning with the lowest dose tested, researchers at the Forsyth Institute observed an increase in the magnitude of ER stress with increasing doses of fluoride.23

In skeletal fluorosis, fluoride causes ER stress during osteoblast maturation. The severity of osteofluorosis is associated with accumulation of fluoride in bone in a dose-dependent manner.24,25

Microglial Activation
Microglia are a type of immune cell that account for about 10% of all brain cells. An essential function of microglia is to defend the brain against toxins. When activated, microglia produce neuroinflammation that can damage and kill neurons. Microglial activation is involved in the development and progression of a variety of neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, and Lou Gehrig's.26 Only recently is it becoming clear that brain microglia are also key regulators of the developing brain.27

Fluoride is able to cross the blood-brain barrier and accumulate in neurons, affecting many biochemical mechanisms. Fluoride exposure has been shown to activate microglia and increase inflammation in the central nervous system which leads to neurodegeneration.28

Postsynaptic density protein-95 (PSD-95) is concentrated in the trillions of tiny synapses that allow neurons to communicate with each other. PSD-95 orchestrates synaptic development and plays an important role in synaptic plasticity, the basis of learning and memory.

When rats were sub-chronically exposed to fluoride in their drinking water, researchers found that fluoride activated microglia and decreased levels of PSD-95 in the brain's hippocampus. They concluded that "the role of fluoride on synaptic plasticity may be associated with neuroinflammation induced by microglia."29

Another study found that the fluidity of synaptic membranes and the expression level of PSD-95 decreased gradually with increasing fluoride concentration, indicating that "decrease of synaptic membrane fluidity and PSD-95 expression level may be the molecular basis of central nervous system damage caused by fluoride intoxication."30

Rats anesthetized for 4 hours with 2.5% sevoflurane showed decreased PSD-95 expression and longterm deficits in hippocampal function. Seven weeks after exposure, they had significant spatial learning and memory impairment, suggesting that "sevoflurane causes neurotoxicity in the developing brain, which may be attributed to decreased PSD-95 in the hippocampus."31 In humans, exposure to 2.4% sevoflurane significantly increases serum fluoride levels.13

Fluoridation's Ecological Correlations
Fluoride's multiple causative biochemical links to mental decay are reinforced by numerous ecological associations with leading causes of death and with prevalence rates of neurodevelopmental disorders.

Alzheimer's Disease
In 2019, a large longitudinal study found a dose-response pattern of association between dementia in women and men who consumed relatively low drinking-water levels of fluoride. The dementia risk more than doubled in the highest quartile compared with the lowest.32

US death rates in 2013 from Alzheimer's disease (sixth leading cause of death) averaged 9% higher in the 20 states whose public water supplies were more than 80% fluoridated (avg. 93% in 2012), compared to the 30 states fluoridated below 80% (avg. 58%).33,34

In the 10 most fluoridated states (avg. 97%), Alzheimer's death rates averaged 25% higher than in the 10 least fluoridated states (avg. 35%).

Researched NutritionalsHypertension and Stroke
Hypertension is a major cause of vascular cognitive impairment and is the single most important modifiable risk factor for adult stroke (cerebral vascular disease). Stroke doubles the chances of developing dementia.35,36

The rate of chronic hypertension among pregnant women over age 34 increased more than 75% from 1970 to 2010. (During the same 40 years, the percentage of US population receiving fluoridated water increased 51%.) The rate of persistent high blood pressure in black women was more than twice the rate of white women.37

In the 10 most fluoridated states, death rates from hypertension (thirteenth leading cause) averaged 13% higher. Death rates from stroke (fifth leading cause of death) averaged 6% higher than in the 10 least fluoridated states.33,34

Kidney Disease
The US Public Health Service has long known: "Subsets of the population may be unusually susceptible to the toxic effects of fluoride and its compounds. These populations include the elderly, people with osteoporosis, people with deficiencies of calcium, magnesium, vitamin C, and/or protein, and people with kidney problems."38 The number of Americans unusually susceptible to fluoride's toxicity now far outnumber children with developing dentition, the claimed beneficiaries of fluoridation.

Cognitive decline is one of many manifestations of brain damage that clearly accompany the decline of kidney function, even in early stages.39

Kidney disease death rates (ninth leading cause) averaged 13% higher in the 20 states more than 80% fluoridated, compared to the 30 states fluoridated below 80%.33,34

In the 10 most fluoridated states, death rates from kidney disease averaged 26% higher than in the 10 least fluoridated states.

Attention-Deficit Hyperactivity Disorder (ADHD)
The most common neurodevelopmental disorder of childhood is ADHD. Each one-percent increase in artificial fluoridation prevalence in the US was associated with 67,000 to 131,000 additional ADHD diagnoses (2003 to 2011).40

In 2011, rates for youth (aged 4-17) currently diagnosed with ADHD averaged 25% higher in the states fluoridated at 80% or more, compared to those below 80% in 2010.33,41

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