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It is apparent that fluorides have the ability to interfere with the functions of the brain and the body by direct and indirect means.
– National Research Council (2006)
Increasing evidence reveals that prenatal exposures to some widely used chemicals are implicated in the growing pandemic of developmental neurotoxicity.1,2 Fluoride is the most controversial of these chemicals, because it is the only one intentionally added to the drinking water of more than 200 million men, women, and children in the US.
Topical fluoride in toothpaste has been used since the 1950s to reduce tooth decay. A primary mechanism of fluoride's ability to prevent dental caries is its strong antimicrobial effects. It is well established that fluoride can inhibit the growth of bacteria, says Robert Breaker, PhD, a National Academy of Sciences award-winning molecular biologist. He admits, however, "There has been little understanding of its precise effects on cells."3
Fluoride Weakens Bacterial Adhesion Forces
In 2013, a key antimicrobial mechanism of fluoride was identified by researchers in experimental physics at Saarland University in Germany. Using artificial tooth surfaces (hydroxyapatite pellets), they tested fluoride's effect on the adhesion forces of cariogenic bacteria (Streptococcus mutans and Streptococcus oralis) and a nonpathogenic bacterium (Staphylococcus carnosus).
After they were exposed to fluoride, atomic force microscopy revealed that all three bacteria species exhibited lower adhesion forces. Because fluoride makes bacteria less able to stick to teeth, decay-causing microorganisms are more easily washed away by saliva or brushing. The researchers said, "Fluoride appears to weaken bacterial adhesion forces in general."4,5
This raises the question, how do weakened bacterial adhesion forces affect the developing gastrointestinal tract, whose vast and complex ecosystem – collectively called the gut microbiota or microbiome – plays an essential role in neurological and immunological development and health?
Adhesion Forces and Bacterial Colonization of the GI Tract
The process of surface adhesion is a survival strategy employed by virtually all bacteria and refined over millions of years.6 Adhesion of bacteria to intestinal mucosa is often recognized as a prerequisite for microbial colonization of the human gastrointestinal (GI) tract.7 Emerging research shows that this colonization begins in the womb.8,9
Distinct microbial populations have recently been discovered at maternal sites that were previously thought to be sterile, including the amniotic cavity and meconium (first feces of a newborn infant). Our understanding of the impact of fetal microbial contact on health outcomes is still rudimentary.10
Of the many potential sources for a prenatal microbiome, amniotic fluid flora accounted for greater relative abundance of bacteria found in meconium than either the oral or vaginal cavities of pregnant women.11,12 When pregnant women consumed specific probiotics, microbial DNA in their amniotic fluid was associated with changes in gene expression in the fetal intestine.13
Fluoridated Amniotic Fluid
Amniotic fluid is arguably our most precious bodily fluid. Early in the second trimester, a fetus begins swallowing amniotic fluid, which passes through its digestive system and kidneys, is excreted as urine, then swallowed again – recycling the full volume of amniotic fluid every few hours. By the time the child is born, up to 15 ounces of amniotic fluid are consumed per day.
Fetal swallowing contributes importantly to gastrointestinal development as a result of the large volume of ingested fluid. Nutrients, hormones, and growth factors in amniotic fluid bathing the fetal intestine during the third trimester are needed to produce a profound maturational effect on the intestine's ability to appropriately respond to colonizing bacteria.14
Fluoride concentrations in human amniotic fluid are about 50% of maternal serum levels and are considerably higher at term than earlier in pregnancy.15,16 Women who consumed 1.25 mg of fluoride per day had a significantly higher fluoride concentration in their amniotic fluid than women who consumed 0.25 to 1.0 mg per day.17 Note: the US Institute of Medicine says that the recommended "adequate intake" level of fluoride for pregnant women is 3 mg per day.18
Ron et al. (1986) found that the fluoride concentration in women's amniotic fluid was 0.017 mg/l, when their drinking water contained <0.5 mg/l of fluoride.16 A similar fluoride concentration is secreted by salivary glands into the ductal saliva of children who drink fluoridated water.19 This very low level of fluoride provides the "systemic" benefit, the primary rationale for swallowing fluoride in water.
A low concentration of fluoride – continually swallowed and recycled in amniotic fluid – must also be bioactive in the fetal GI tract. In fact, a primary reason why pregnant women are encouraged to consume fluoridated water is to help "delay colonization of the infant oral cavity by cariogenic bacteria."20
Gut Bacteria and Autism
Antimicrobials, including low-dose antimicrobials in food and water supplies, indiscriminately affect all members of the gut microbial ecosystem, especially decreasing the levels of beneficial bifidobacteria and increasing the levels of potentially harmful clostridia, as seen in the microbiota of autistic children.21,22
Autism is closely associated with a distinct gut microflora that can be characterized by reduced richness and diversity as well as by altered composition and structure of the microbial community; specifically, lower levels of important groups of carbohydrate-degrading or fermenting microbes.22-26
In a rodent model for autism spectrum disorder, autism-like behavior is associated with altered microbial colonization and activity.27 These mice have abnormally low levels of Bacteroides fragilis, a bacterium that modulates levels of several metabolites and is one of the earliest-colonizing and most abundant microbes in a healthy human intestinal tract.28 Feeding B. fragilis to these mice ameliorates defects in communicative, repetitive, and anxiety-like behaviors.29
Gut Bacteria, Immune System, Autism, and Fluoride
Increasing evidence indicates that gut microbiota also influences the immune systems and vice versa.30Microbial contact in utero is associated with changes in fetal intestinal innate immune gene expression profile.13
The GI tract has 70% to 80% of the body's immune cells and is the primary site of interaction between the immune system and microorganisms, both symbiotic and pathogenic.31 Proper microbial colonization and composition of the GI tract are essential for the maturation of the immune system.8,21,32,33 Different bacteria have clearly defined adherence sites and immunological effects.34
Immune system dysregulation in autism spectrum disorders has been reported in several studies.35
During colonization of the gut with B. fragilis, the cellular and physical maturation of the developing immune system is directed by a bacterial polysaccharide.28 Ochoa-Repáraz et al. (2010) found that a polysaccharide of B. fragilis can protect against central nervous system demyelinating disease.36 Human and animal studies implicate impairments of myelination in autism spectrum disorder.37,38
Sodium fluoride has been shown to reduce bacterial polysaccharide production by inhibiting bacterial attachment.39
A mechanism of action for fluoride's ability to reduce bacterial adhesion forces is its inhibitory effect on the activity of glucan-binding proteins.40 In the GI tract, glucans represent a significant potential in the suppression or treatment of several gastrointestinal problems.41
Adhesion Molecules, Autism, and Fluoride
In its comprehensive 2006 report Fluoride in Drinking Water: A Scientific Review of EPA's Standards, the US National Research Council concluded, "It is apparent that fluorides have the ability to interfere with the functions of the brain and the body by direct and indirect means."42
Fluoride's indirect effects on neurodevelopment via the fetal microbiome have yet to be researched. There is, however, growing evidence of fluoride's direct effects on the fetal brain, which is exposed to the fluoride circulating in maternal blood.43
Autism involves early brain overgrowth and dysfunction, an excess of neurons in the prefrontal cortex caused by a prenatal disruption of developing brain architecture as early as the second trimester.44 Research by Lahiri et al. (2013) suggests that brain enlargement in autism is likely due to cell adhesion dysfunction.45
Neural cell adhesion molecules (NCAM) are widely expressed in the nervous system, where they are involved in axon growth and guidance – fundamental processes that underlie formation of the synaptic connections and myelinated nerve structure crucial to brain development.
Significantly lower serum levels of several types of adhesion molecules, including NCAM, have been found in persons with autism.46,47 Neural pathways involving synaptic cell adhesion are disrupted in some people with autism, including alterations in the structure and expression of NCAM.48,49
Fluoride exposure has been shown to cause a dose-dependent decrease in NCAM expression levels in rat hippocampal neurons. In particular, the NCAM-140 protein expression level was significantly lower in response to the lowest dose of fluoride used.50,51 NCAM-140 is found in migrating growth cones that are crucial to the formation of synaptic connections.52
Fluoride Adversely Affects Synaptic Development
Diseases such as autism and Alzheimer's are increasingly linked to defects in the organization and number of synapses, the tens of trillions of tiny yet complex structures that link neurons so they can communicate with each other. A molecule that helps create and maintain the scaffolding around which a synapse is built is postsynaptic density protein-95 (PSD-95). Neuronal synapses with less PSD-95 are likely to be weakened or lost.53
PSD-95 is a membrane-associated kinase concentrated at glutamatergic synapses. It regulates adhesion and enhances maturation of the presynaptic terminal. Research demonstrates that PSD-95 orchestrates synaptic development and plays an important role in synapse stabilization and plasticity.54
In rats that drank water with added fluoride for several months, the fluidity of brain synaptic membranes and the expression level of PSD-95 decreased in a dose-dependent manner.55,56
Rats anesthetized for 4 hours with 2.5% sevoflurane, a fluoride-based anesthetic, showed long-term deficits in hippocampal function and decreased hippocampal PSD-95 expression. Seven weeks after exposure, they had significant spatial learning and memory impairment.54
In humans, exposure to 2.4% sevoflurane significantly increases serum fluoride levels.57 (Sevoflurane is the most prevalent volatile anesthetic in pediatric anesthesia.)
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