Fluoride, Neurotoxicity, Endothelial dysfunction, Endoplasmic reticulum, Neurodegenerative disease

Fluoride and Mental Decay

By John D. MacArthur

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 impact on 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: endothelial dysfunction, arterial stiffness, endoplasmic reticulum (ER) stress, and microglial activation.

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.²

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.³

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.”^4,5 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.⁶

Another fluorinated drug that increases blood levels of fluoride and causes endothelial cell dysfunction is 5-fluorouracil.^7,8

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, including hypertension, stroke, kidney dysfunction, cerebrovascular disease, dementia, and Alzheimer’s disease. Arterial stiffness is associated with the extent and progression of β-amyloid deposition in the brain. Among elderly adults, the risk of incident dementia was significantly related to higher baseline aortic stiffness, which is measured by pulse wave velocity.^9,10

In people with fluorosis, the elastic properties of the ascending aorta are impaired. 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%.^11,12

Compared with Whites, African Americans have greater arterial stiffness – and reduced microvascular endothelial function – even after adjusting for traditional cardiovascular risk factors. African American children are more vulnerable to fluoride’s toxicity. They have significantly higher rates and more severe forms of dental fluorosis than white children.^13,14

Impaired elasticity of the ascending aorta is associated with subclinical hypothyroidism. Higher TSH levels, a measure of hypothyroidism, correlate with aortic stiffness. Data from nearly 8,000 medical practices in England showed that hypothyroidism was positively associated with fluoride levels in patients’ drinking water. Those living in a fluoridated region had twice the hypothyroidism prevalence as those in a nonfluoridated one.^15,16 This British study did not include undiagnosed subclinical hypothyroidism.

The US National Research Council (2006) said, “Subclinical hypothyroidism is associated with increased cholesterol concentrations, increased incidence of depression, diminished response to standard psychiatric treatment, cognitive dysfunction, and, in pregnant women, decreased IQ of their offspring.” The more severe the maternal hypothyroidism, the lower the child’s IQ.¹⁷

Several animal studies showed that fluoride exposure increased LDL cholesterol levels. JAMA Neurology (May 2019) reported an association between elevated levels of LDL cholesterol and the risk of Alzheimer’s disease – even before age 65 (early-onset Alzheimer’s).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 neuronal degeneration in numerous human diseases whose pathology includes accumulation of misfolded proteins in the brain, a distinguishing aspect of neurodegenerative diseases. 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 apoptosis (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 diseases. Only recently is it becoming clear that brain microglia are also key regulators of brain development.^26,27

Fluoride exposure has been shown to activate microglia and increase inflammation in the central nervous system, which leads to neurodegeneration. When rats were treated for 30 days with fluoride in their drinking water, it caused an increase in microglial activation and neuroinflammation.^28,29

Microglial activation decreases levels of postsynaptic density protein-95 (PSD-95), which is concentrated in the trillions of tiny synapses that allow neurons to communicate with each other. Research demonstrates that PSD-95 orchestrates synaptic development and plays an important role in synaptic plasticity, the basis of learning and memory.³⁰

When rats were sub-chronically exposed to fluoride in their drinking water, researchers found that fluoride activated microglia and decreased PSD-95 protein levels in the brain’s hippocampus. The fluidity of synaptic membranes and the expression level of PSD-95 decreased gradually with increasing fluoride concentration – suggesting a molecular basis of central nervous system damage caused by fluoride.^31,32

Rats anesthetized for four hours with 2.5% Sevoflurane showed decreased PSD-95 expression and long-term deficits in hippocampal function. Seven weeks after exposure, they had significant spatial learning and memory impairment.³⁰

Fluoridation’s Ecological Associations

Fluoride’s multiple causative links to mental decay are reinforced by multiple ecological associations with leading causes of death and with prevalence rates of neurodevelopmental disorders.

Alzheimer’s Disease. Death rates from Alzheimer’s disease (sixth leading cause of death in 2013) 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% in 2012), Alzheimer’s death rates averaged 25% higher than in the 10 least fluoridated states (avg. 35%).

Hypertension 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 In the 10 most fluoridated states, death rates from hypertension (thirteenth leading cause of death) averaged 13% higher, and 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.³⁷

In 2019, Americans unusually susceptible to fluoride 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.³⁸

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.

Preterm Birth. A well-designed New York state public health study found that water fluoridation was independently associated with a 15% increased risk of preterm birth. No follow-up research was done, although two years earlier the US Institute of Medicine reported: “Those born preterm have an appreciable risk of long-term neurological impairment.”^39,40

Since 2009, a team of researchers at the Neurotoxicology Division of the EPA continues to find substantial evidence that fluoride is a “developmental neurotoxicant,” one of 22 gold standard chemicals “well documented to alter human neurodevelopment.” Others include aluminum, arsenic, ethanol, lead, and methylmercury.⁴¹

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).⁴²

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.^33,43

Mental Retardation/Intellectual Disability. In 1993, mental retardation prevalence rates averaged 33% higher for children (aged 6-17) in the 26 states fluoridated above the national average (62% in 1992) compared to the 24 states fluoridated below it.^44,45

By 2012, it had nearly doubled. The prevalence rates of “intellectual disability” (the new term for mental retardation) averaged 57% higher for students (aged 6-21) in the 26 states fluoridated above the national average (75% in 2012) compared to the 24 states fluoridated below it.^33,46

In the 10 most fluoridated states, intellectual disability prevalence averaged 84% higher than in the 10 least fluoridated states.

Fluoridation Must End

In 2019, a large longitudinal study found a dose-response 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.⁴⁷

It’s important to minimize fluoride consumption, but this is very difficult because fluoridation chemicals (increasingly from China) are intentionally added to about 75% of US tap water. An EPA-regulated water contaminant, fluoride now contaminates the nation’s processed food and beverage chain, essentially making the US artificially fluoride endemic. Products produced in a fluoridated city still contain fluoride even if the label says “filtered water” (unless specifically filtered by reverse osmosis).

The amount of fluoride we consume is unknown, because food and beverage labels have never included fluoride content, even though the National Research Council said they should: “To assist in estimating individual fluoride exposure from ingestion, manufacturers and producers should provide information on the fluoride content of commercial foods and beverages.”⁴⁸ (Practically every recommendation in this extremely comprehensive 2006 report has been ignored.)

The annual cost of neurological diseases and disorders to American society is approaching $1 trillion. Even if ending water fluoridation reduced mental decay by merely 10%, not only would this be incalculable benefit to millions of families but would save $100 billion a year.

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