Fluoride and Preterm Birth


by John D. MacArthur

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Preterm birth is birth prior to 37 weeks (8.5 months) of pregnancy. Not just a temporary problem dealt with during the first weeks of an infant’s life, preterm birth is the leading cause of long-term neurological disabilities in children.1 Preterm infants are more likely to have lower IQs and require significantly more educational assistance than children who were born at term.2

Many studies have documented the prevalence of a broad range of central nervous system dysfunctions and neurodevelopmental impairments in people who were born preterm, including mental retardation, ADHD, and major depression. The societal economic burden associated with preterm birth in the US is estimated to be at least $26.2 billion per year, or $51,600 per infant born preterm.3

A vibrant brain is a most precious gift of life.
It is inexcusable to promote, condone,or ignore
a policy that diminishes this birthright.

Preterm or premature birth is the most common pregnancy complication that can seriously compromise the newborn brain’s viability and normal development. The genesis and wiring of the human brain during fetal development is one of the most remarkable feats in all of biology. During the last trimester, dynamic changes occur in the two brain areas most important to cognitive processes: the cerebellum, whose surface area increases 30-fold, and the cerebral cortex, whose white matter undergoes striking changes. Damage to cerebral white matter is the most commonly recognized pathology of prematurity, say neuroscientists at the Dana Alliance for Brain Initiatives. “Babies born preterm face a range of potential neurological disruptions … The earlier the birth, the greater the risk that these disruptions will produce devastating and potentially life-long cognitive, behavioral, and socialization deficits.”4

US Preterm Birth Rate Unusually High

The misconception that preterm birth is a third-world problem was shattered in May 2012 by the first global report to compare premature birthrates in 184 countries. Three years in the making, “Born Too Soon: The Global Action Report on Preterm Birth” was produced jointly by the World Health Organization, Save the Children, the March of Dimes, and the Partnership for Maternal, Newborn and Child Health.5

America lags behind 130 other nations in preterm birth rate. “The United States is similar to developing countries in the percentage of mothers who give birth before their children are due. … It does worse than any Western European country and considerably worse than Japan or the Scandinavian countries,” reported Donald G. McNeil Jr. in the New York Times. Canada, Australia, and most European countries are in the 7% to 9% range, while the US shares the 12% range with Kenya, Turkey, Thailand, East Timor, and Honduras – meaning that 1 in 9 births is early.6

“This report offers conclusive evidence that the United States rate of preterm birth has been far too high for far too long,” says Dr. Jennifer L. Howse, president of the March of Dimes. “We have failed to do enough to prevent preterm births and help more mothers carry their babies full-term.”7 “If somebody had a simple explanation of why the UK and Europe do much better, I wouldn’t believe them,” says Dr. Gordon C. S. Smith at the University of Cambridge.6

“Residence in the US a Risk Factor for Preterm Birth” is the title of a 2012 study involving 2141 women. It revealed that duration of stay in the US is associated with increased risk of preterm birth for Hispanic women. Dr. Radek K. Bukowski, an expert on preterm birth at the University of Texas Medical Branch in Galveston, found that the longer a woman lived in this country, the greater her chances of giving birth prematurely. Presented at the Society for Maternal-Fetal Medicine’s 2012 annual meeting, “The findings support the hypothesis that preterm birth is, at least in part, related to environmental, potentially preventable, factors,” says Bukowski. “It remains unclear what specific environmental factors protect or predispose women to preterm birth.”8

The risk for preterm birth was 4% for recent immigrants, 7% for those living here less than a decade, and 10% for citizens. Even after controlling for risk factors such as age, poverty, smoking, obesity, and diabetes, “We really don’t have an explanation for what’s behind it,” Bukowski says. “But whatever it is, it’s not genetic. It’s something they acquire here.”6

‘Best-Available Science’ Will Reduce Preterm Birth by Only 5%

Although preterm birth is the leading cause of death for children younger than 5 years in high-income countries, second leading cause worldwide, and a major contributor to the global burden of disease, it wasn’t until November 2012 that the first multicountry analysis of trends in preterm birth rates was published. The international team of researchers concluded, “The current potential for preterm birth prevention is shockingly small.” If five proven interventions were implemented, it would lower the preterm rate from an average 9.6% of live births to 9.1%. Dr. Joy Lawn of Save the Children, who coordinated the research, says, “The best-available science will allow just 5 percent relative reduction in high income countries’ preterm birth rates by 2015.” Note: of the 39 countries with a “very high human development index,” the US has the third highest preterm birth rate (after Cyprus and Bahrain).9,10

Because the triggers for premature labor are not fully understood, the poor performance by the US is partly a mystery, says Dr. Alan E. Guttmacher, director of the National Institute of Child Health and Human Development. “This underscores the need for more research,” especially because as the March of Dimes points out, in up to 40% of cases, the cause of preterm birth is unknown.

It also underscores the need to give serious attention to research already available: the biological, clinical, and ecological evidence that fluoride is a significant risk factor for preterm birth.

“A long habit of not thinking a thing wrong, gives it a superficial appearance of being right.”
 – Thomas Paine, Introduction to Common Sense, 1776

Fluoride: Ancient Enemy of Biological Systems

Many Americans think that there’s nothing wrong with fluoride, a chemical added to nearly three-fourths of US public water supplies, a chemical that now permeates the nation’s food-and-beverage chain. Even a National Academy of Sciences award-winning molecular biologist with a doctorate in biochemistry “did not know that biology cared much about this ion.” Ronald R. Breaker, PhD, and his team of experts in microbiology and bioinformatics at Yale University’s Howard Hughes Medical Institute study a type of noncoding RNA called a riboswitch that helps turn genes on and off. In 2011, they discovered a new riboswitch but could not figure out its function, until a chemistry graduate student “overcame any biases” and quickly demonstrated that pure fluoride indeed triggers riboswitch function that helps cells fight fluoride’s “antimicrobial properties.”11,12

“Despite this evidence, we were still unwilling to accept that fluoride was the natural target,” admits Breaker. “It is very likely no one would have solved the mystery of fluoride riboswitches for several more decades, if we had not been lucky enough to receive a contaminated chemical sample spiked with fluoride.” Genes associated with fluoride-sensitive riboswitches are very widespread in biology. In fact, this new riboswitch is “one of the only noncoding RNAs we’ve ever found that’s present in both bacteria and archaea,” Breaker says. This suggests an ancient biological system that cells have evolved to deal with fluoride’s toxicity.12,13

In a 2010 scientific review (“Molecular Mechanisms of Fluoride Toxicity”), the authors note that until the 1990s, the toxicity of fluoride was largely ignored due to its “good reputation” for preventing caries via topical application and in dental toothpastes. However, in the last decade, interest in its undesirable effects has resurfaced due to the awareness that “this element interacts with cellular systems even at low doses.”14

Even though some studies report no clear evidence on the potential negative effects of fluoride exposure at permissible concentrations (e.g., studies that support water fluoridation), others have shown evidence of fluoride’s effects on cellular processes at biologically relevant concentrations. When discussing these controversial results, it is important to highlight that fluoride must be actively considered as a potent toxic compound in the field of toxicology. … Fluoride can interact with a wide range of cellular processes such as gene expression, cell cycle, proliferation and migration, respiration, metabolism, ion transport, secretion, endocytosis, apoptosis/ necrosis, and oxidative stress, and that these mechanisms are involved in a wide variety of signaling pathways.14

“Although the toxicity of fluoride is well known, it has been ignored for a long time. … As a result, the consumption of fluoride by humans became uncontrolled and unpredictable, often exceeding its therapeutic window,” say the authors of “Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride,” a scientific review published in 2012. The Russian researchers detail the many ways fluoride harms life. One mechanism: “Fluoride is a well-known inhibitor of enzymes of the glycolytic pathway, first of all enolase.”15

Fluoride, Enolase, and Red Blood Cells Dental cavities are “the leading cause of chronic infections in children,” notes Marguerite DiMarco at Case Western Reserve University. “Many people do not realize that dental caries is an infectious disease that can be transmitted from the primary caregiver and siblings to other children.”16 Tooth decay is considered an infectious disease, because bacteria are involved. The bacterium that inhabits the human mouth, Streptococcus mutans, causes dental caries by converting dietary sugars into enamel-corroding lactic acid. It is well established that fluoride can inhibit the action of this bacterium.

“Fluoride’s antibacterial effect should be common knowledge amongst dental practitioners,” reported Canada’s leading dental journal, Oral Health, in 2003. “Fluoride interferes with the complete breakdown of glucose to pyruvic acid by inhibiting enolase, an intermediary enzyme in the cascade.” This results in a reduction in the synthesis of lactic acid and in a significant reduction in the metabolic activity of the saccharolytic microorganisms.17

Fluoride’s antibacterial effects, however, are not limited just to teeth. “Exposure of red blood cells (erythrocytes) to fluoride produces a variety of metabolic alterations, most of which are based upon the secondary effects of enolase inhibition.”18 Via its effect on enolase in human red blood cells, fluoride inhibits active sodium transport, aerobic glucose utilization, and lactate formation.19,20 In rat erythrocytes, fluoride leads to “impairment of the cellular antioxidant system and severe energy depletion.”21

Erythrocytes develop from bone marrow and are used in a reliable test for carcinogens that cause genetic damage. Data obtained from a 2012 study on the bone marrow cells of mice clearly documented that at low concentrations, sodium fluoride exhibits genotoxic activity and enhanced oxidative damage.22 In another in vitro study, “Exposure of the rat erythrocytes to sodium fluoride triggers rapid progression of their death in a dose- and time-dependent manner.”23

Fluoride, Anemia, and Preterm Birth:
A. K. Susheela’s Research

Anemia is a condition marked by a deficiency of red blood cells or of hemoglobin, the red protein in blood cells responsible for transporting oxygen in the blood. Anemia is common in pregnancy, because a woman needs to have enough red blood cells to carry oxygen around her body and to her baby.

The leading expert on the connection between fluoride, anemia, and preterm birth is A. K. Susheela, PhD, who has spent more than 25 years researching fluoride toxicity and has over 80 scientific publications in Western and Indian journals. She is executive director of the Fluorosis Research and Rural Development Foundation in India (FluorideAndFluorosis.com), winner of the 2013 Spirit of Humanity Award in Women’s Health presented by AmeriCares India.

“There is now ample scientific evidence to support the fact that ingestion of fluoride prevents biosynthesis of hemoglobin, leading to anaemia in human beings,” Susheela says.24 “Fluoride decreases production of erythrocytes (red blood cells) by the bone marrow and other hemopoietic tissues and increases erythrocyte abnormalities resulting in premature death of red blood cells.”25

In 2010, Susheela conducted a clinical “program emphasizing a greatly reduced intake of fluoride and the inclusion of essential nutrients in the daily diet during pregnancy.” Published in Current Science (May 25, 2010), this study (“Effective Interventional Approach to Control Anaemia in Pregnant Women”) is “the first report dealing with fluoride, pregnancy, anemia, low birthweight babies and the linkages to act upon for the benefit of maternal and reproductive child health programs.”26

The 205 pregnant women in the study were all anemic. Their hemoglobin levels were less than 9 g/dl, and their urinary fluoride levels were more than 1 mg/l. Ninety pregnant women formed the sample group, and 115 formed the control group. “The major focus of the investigation of the sample group was to eliminate ingestion of fluoride as much as possible,” says Susheela. “The sample group was counseled to avoid consumption of fluoride-containing food, water, and other substances.” They even changed their toothpaste to a low fluoride paste. The women were also counseled to ensure an adequate intake of essential nutrients: calcium, vitamins, and antioxidants from dairy products, fruits, and vegetables. The women in the control group were not counseled, but both groups received the standard iron and folic acid tablets.25,26

By the time of delivery, improvements in the women’s body mass index were considerably better in the sample group than in the control group, suggesting that the sample group was absorbing nutrients more efficiently than the controls. Also, hemoglobin increased by an average of 78% in the sample group compared with 57% in the controls. “A striking impact of these interventions for improving the gestation period was also noted.”25 In the sample group, 32% of the women delivered before 37 weeks – compared with 50% in the control group.26

At the Global Maternal Health Conference convened in New Delhi in September 2010, Susheela presented results of a similar but larger study involving a total of 481 pregnant women, further confirming that anemia in pregnancy is mainly due to nonabsorption of nutrients caused by
adverse reactions of fluoride, rather than to undernutrition/malnutrition.

In June 2013, Susheela and her team submitted to the Indian Council of Medical Research results of a three-year study to correct anemia in more than 2500 adolescent schoolchildren, ages 10 to 17. When fluoride was withdrawn and nutritious food promoted, the children’s anemia was corrected. In contrast, anemia continued in the control group that consumed fluoride, even though they ate a nutritious diet.

Susheela concludes it is evident from her research: “Maternal and child under-nutrition and anemia is not necessarily due to insufficient food intake, but because of the derangement of nutrient absorption due to damage caused to GI mucosa by ingestion of an undesirable chemical substance, namely fluoride through food, water and other sources.”26

Iron-Deficiency Anemia Iron is the main constituent of the hemoglobin molecule, hence a deficiency in iron is a major cause of anemia. Pregnant women need about twice as much iron as usual, therefore they have a higher risk of iron-deficiency anemia, which can increase the risk of preterm delivery and low birth weight. About half of all pregnant women don’t have enough iron in their bodies.

As with most mineral nutrients, iron from digested food is absorbed in the intestinal lining by epithelial cells whose microvilli provide the huge surface area needed to efficiently absorb nutrients. “Fluoride not only decreases production of red blood cells by the bone marrow but also destroys microvilli – the microscopic protrusions lining the intestine,” notes Susheela.27 “Fluoride diminishes beneficial microbial growth in the gut … resulting in poor absorption of nutrients critical for the biosynthesis of hemoglobin.”25

In an August 2013 interview, Susheela explained why India’s Iron and Folic Acid Supplementation Program has failed to prevent anemia. As long as fluoride consumption is high, “No amount of tablets is going to solve anything. Withdrawal of fluoride on the other hand permits the regeneration of microvilli in the gut which improves the absorption of nutrients from the diet and hemoglobin levels improve. The evidence is there for the scientific community, bureaucrats, and policymakers, but no one has reproduced it nationally or globally. They’re simply not willing to accept the truth.”27

The Gut Microbiota

The lining of the gastrointestinal tract is the largest vulnerable surface that faces the external environment, note researchers at the University of Melbourne. Just as the other large external surface, the skin, is regarded as a sensory organ, so too should be the intestinal mucosa.28 The human gut is the natural habitat for a large and dynamic bacterial community. In June 2012, Science magazine included a special section, “The Gut Microbiota,” noting, “We are on the threshold of making profound discoveries about the microorganisms with which we share
our bodies, indeed whose cell count vastly outnumbers our own.” Major functions of the gut microflora include metabolic activities that result in salvage of energy and absorbable nutrients. Colonic microorganisms also play a part in vitamin synthesis and in absorption of calcium, magnesium, and iron.29

Lactobacillus acidophilus belongs to a group of bacteria that live in the human small intestine. These beneficial microorganisms aid digestion, help maintain a healthy intestinal tract, and prevent harmful bacteria from congregating there. Lactobacillus acidophilus supplements have been shown to increase iron bioavailability in studies with animals and with children.30 When children were fed an iron-fortified probiotic milk beverage, they “exhibited higher red blood cell status and a positive correlation between iron intake and hemoglobin” – evidence to support the use of Lactobacillus acidophilus to prevent anemias in children.31

When fluoride comes in contact with Lactobacillus acidophilus, it inhibits this beneficial bacterium that aids in the absorption of iron. Fluoride-containing resin-based dental sealants have proved “capable of contact inhibition of L. acidophilus and S. mutans growth.”32 A statistically significant 49% reduction in Lactobacillus counts was obtained 24 hours following mouth rinsing by Egyptian children with 0.05% sodium fluoride solution.33

Maternal Fluoride Linked to Low Birth Weight and Preterm Birth

Recent evidence indicates that the gut microbiota plays a role in obesity associated diseases, such as diabetes and cardiovascular diseases. Managing gut bacteria may be an important and effective way to control weight, because these microorganisms play a far more significant role in weight loss than ever imagined. A healthy ratio of beneficial gut bacteria in infancy is protective against overweight and obesity later in life.34-36

Studies have found that a small size at birth – followed by accelerated “catch-up” growth – is associated with an increased risk of adult cardiovascular disease, diabetes, hypertension, osteoporosis, and obesity. Research at the Los Angeles Biomedical Research Institute suggests that when the mother has poor or inadequate nutrition, overeating is programmed in the fetus before birth. An animal model suggests a mechanism: low birth weight offspring exhibit reduced hypothalamic neural satiety pathways and dysregulated signaling leading to programmed hyperphagia (excessive hunger or increased appetite) and adult obesity.37,38

Many preterm infants are also low birth weight. In 2010, infants born preterm accounted for two-thirds of all low birth weight infants, and over 40% of preterm births were low birth weight.39 In Susheela’s clinical study, the number of low birth weight babies was reduced to 22% in the sample group of mothers who avoided fluoride, as opposed to 52% in the control group.26

In a 2011 study (“Association of Higher Maternal Serum Fluoride with Adverse Fetal Outcomes”) involving 108 pregnant women (17–36 years old), “A significant negative correlation was found for maternal serum fluoride vs. birth weight, gestational age, and APGAR score.” (APGAR score evaluates a newborn baby on five simple criteria: Appearance, Pulse, Grimace, Activity, Respiration.) The researchers concluded, “With increased serum fluoride in the mother, there is an inclination towards preterm delivery, low birth weight, and poor APGAR count.”40

A 2012 study (“Pregnant Women Living in Areas of Endemic Fluorosis in Senegal and Low Birthweight Newborns: Case-control Study”) found a significant association between fluoride levels in the drinking water, dental fluorosis in mothers, and low birth weight of newborns. “The water consumed and the modal score of Dean’s Index were significantly associated with the occurrence of low birth weight adjusted for gender, consanguinity, anemia and hypertension.”41 (Dean’s Index scores the severity of enamel fluorosis on a scale of 0-5, based on specific criteria.)

Lifelong Consequences of Low Birth Weight

Links between low birth weight and a range of motor and cognitive problems have been well known for some time. In 2011 researchers at the University of Pennsylvania established that the rate of autism spectrum disorder (ASD) is highly elevated in children and adults who were born at low birth weight. For 21 years, researchers followed a regional birth cohort of 1105 children who weighed less than 2000 grams (4 pounds, 6 ounces) at birth – finding that 5% of the low birth weight children were diagnosed with autism, compared with 1% of the general population.42

The 2007 National Summit on America’s Children presented an analysis of 35 years of data on more than 12,000 individuals: “Compared to their normal birth weight siblings, low birth weight children are 30 percent less likely to be in excellent or very good health in childhood. They also score significantly lower on reading, passage comprehension, and math achievement tests. … Low birth weight children are nearly twice as likely as their normal birth weight siblings to be in problematic health by ages 37-52.” These findings are the first to link birth weight with adult health and socioeconomic success using a full, nationally representative sample of the US population.43

Obesity, Sleep, and Preterm Birth

A dangerous cycle: low birth weight premature infants have an increased risk for developing adult obesity, and obesity increases the risk of preterm delivery.38 A 2013 study of 1.5 million deliveries in Sweden found that women with the highest body mass index also had the highest statistical risk of giving preterm birth – especially extremely preterm birth. Researchers at Karolinska Institutet say that maternal overweight and obesity have replaced smoking as the most important preventable risk factor for adverse pregnancy outcomes in many countries. In the US, where preterm delivery rates are twice as high as in Sweden, 53% of pregnant women are either overweight or obese compared with 34% of pregnant women in Sweden.44,45 (Sweden has prohibited artificial water fluoridation since 1971.)

Obesity is much more deadly than previously thought. A major 2013 study analyzed deaths in the US from 1976–2006 and found that obesity accounted for 18% of deaths among black and white Americans. Women had a significantly higher risk than men of dying from being overweight or obese.46

A 2012 study found that obese mothers were 1.7 times more likely to have a child with autism as normal weight mothers without diabetes or hypertension, and were more than twice as likely to have a child with another developmental disorder. 47

Thyroid dysfunction is also involved in obesity, and pregnant women who have thyroid disorders face greater risk of preterm birth.48 Fluoride has been linked to thyroid problems.49 It was even used as a drug to treat hyperthyroidism, because it reduces thyroid activity quite effectively. When there is excess of fluoride in the body it can interfere with the function of the thyroid gland.50

In her 2012 Chicago Tribune article (“New Triggers Found for Weight Gain”), Julie Deardorff reported that antibiotics in infancy or too much fructose affect gut bacteria in ways that increase body mass. Another trigger, sleep deprivation, can alter the circulating levels of the hormones that control hunger.51-53 “For example, after a short sleep, ghrelin, which stimulates appetite, is higher, and leptin, which signals satiety or fullness, is lower.”54 Fluoride may be a factor in reduced leptin levels. In a rat study, sodium fluoride produced concentration dependent inhibition of leptin secretion.55

“We do not know how much of the obesity epidemic we’re seeing in this country is in fact due to restricted sleep in the population nowadays,” says Robert Stickgold, a leading sleep researcher at Harvard Medical School.56

Poor sleep quality, in both early and late pregnancy, is associated with an increased risk of delivering preterm.57 Sleep quality and duration depend on the hormone melatonin produced by the brain’s pineal gland, the central structure in the circadian system whose rhythms govern most aspects of physiology and behavior in mammals, including sleep-wake cycles. Fluoride has been shown to accumulate in the human pineal gland.58 In 2006, the National Research Council concluded, “Fluoride is likely to cause decreased melatonin production and to have other effects on normal pineal function, which in turn could contribute to a variety of effects in humans.”59

Poor sleep and disrupted circadian rhythms are also a risk factor for Alzheimer’s disease, therefore the degree of pineal fluorosis may be a biomarker for dementia.60 Another fluoride-related risk factor for dementia is anemia. A 2013 study that followed 2552 adults (aged 70–79) for 11 years found that people who had anemia at the start of the study had a nearly 41% higher risk of developing dementia than those who were not anemic.61

Prematurity and Infant Mortality

The main cause of the high US infant mortality rate – when compared with Europe – is the very high percentage of preterm births in the United States. After identifying the top 20 leading causes of infant death, the CDC determined “preterm birth is the most frequent cause of infant death in the US,” accounting for 36% of infant deaths in 2007.62,63 Prematurity is the #1 cause of death in the first month of life. In 2008, nearly 10,000 babies in the US died from preterm birth-related causes.

Infant mortality is defined as death of an infant before his or her first birthday. Fluoride therefore may also be a factor in postneonatal infant mortality, because “ingested fluoride is transformed in the stomach to hydrofluoric acid, which has a corrosive effect on the epithelial lining of the gastrointestinal tract,”64 where most of our immune system is located.

Paul Connett, PhD, professor of chemistry and director of the Fluoride Action Network (FluorideAlert.org), notes that concentrations of fluoride in mother’s milk are very low: in the range of 4 to 40 parts per billion. Even when a mother’s fluoride intake is high, levels in her breast milk remain low. As a result of this natural protection, the breastfed infant receives the lowest fluoride exposure (mg/kg) of all age groups. However, when infant formula is mixed with fluoridated water, the bottle-fed baby gets the highest exposure.65

Breast milk feedings are associated with a decrease in “necrotizing enterocolitis” (NEC), a serious disease of the intestine common in premature babies. In a study on 926 preterm infants, NEC was 6 to 10 times more likely in exclusively formula-fed babies than in those who received exclusive human milk. The risk for NEC is inversely proportional to gestational age and weight at birth (but rare in term infants). Risk factors for NEC include low APGAR scores and delayed or altered bacterial colonization in the gut of the premature infant. Compared with healthy, full-term infants, the intestinal microbiota in preterm infants features a low number of bacterial species. The rate of NEC-associated acute mortality is generally reported to be greater than 10% overall; however, probiotic therapy has been shown to reduce morbidity and mortality of NEC in premature infants in several international studies using various probiotic agents.66,67

Preterm birth doesn’t just affect the mortality of infants. A study of 674,820 individuals born in Sweden (from 1973 through 1979 who survived to age 1 year) found that “low gestational age at birth was independently associated with increased mortality in early childhood and young adulthood.”68

Water Fluoridation and Preterm Birth Rates

A 2009 study was undertaken because: “Current literature suggests an association between periodontal disease and preterm birth. Domestic water fluoridation is thought to have lessened the burden of dental disease. Theoretically, one would expect water fluoridation to be protective against preterm birth.” What was found, however, surprised the researchers (mostly) from the Department of Epidemiology & Biostatistics at the State University of New York (SUNY). They didn’t expect fluoridation to be positively associated with preterm birth rates, yet they had to conclude otherwise: “Domestic water fluoridation was independently associated with an increased risk of preterm birth in logistic regression, after controlling for age, race/ethnicity, neighborhood poverty level, hypertension, and diabetes.”69

This study (“Relationship Between Municipal Water Fluoridation and Preterm Birth in Upstate New York”) was presented at the 2009 American Public Health Association Meeting and Expo, but the research was never published. (One can’t help but wonder how much other fluoride research goes unpublished, when the results don’t support researchers’ expectations.) A logical next step would have been to look at available data for ecological associations elsewhere in the US.

According to CDC data for 2010, in the 25 least fluoridated states (average fluoridation rate = 52%), the preterm birth rate averaged 116 per 1000 births. In the 25 most fluoridated states (average fluoridation rate = 90%), the preterm birth rate averaged 122 per 1000 births.70 If that difference of 6 births per 1000 were extrapolated to the US, where 4 million births occurred in 2010 (when 74% of the nation was fluoridated), then higher levels of water fluoridation would be associated that year with 17,760 more preterm births – each one with an annual societal economic burden of of more than $50,000.

Although this nationwide statistical association is not adjusted for age, race, poverty, and maternal disease (as the SUNY study was), nevertheless it is the best large-scale population data we have – a snapshot that supports laboratory and clinical studies showing an association between fluoride consumption and preterm birth. It should not be dismissed. Since the SUNY study, however, no further research has been conducted – or if it has, it also was not published.

Similar statistical snapshots reveal that compared with the 25 least fluoridated states, the infant mortality rate averaged 10% higher and the low birth weight rate averaged 5% higher in the 25 most fluoridated states.71,72

The HPA Axis – Link Between Preterm Birth and Adult Disorders

In 2012, researchers at the University of Adelaide discovered a possible mechanistic link between the altered brain physiology of preterm birth and the subsequent neurological deficits. Their research provides the first physiological

evidence that human adolescents born preterm have a “significantly reduced capacity for cortical neuroplasticity.”73 Plasticity in the brain is vital for learning and memory throughout life, says Dr. Julia Pitcher of the Robinson Institute. “It enables the brain to reorganize itself, responding to changes in environment, behavior and stimuli by modifying the number and strength of connections between neurons and different brain areas.”

In response to a noninvasive magnetic brain stimulation technique, teenagers born preterm clearly showed reduced neuroplasticity. “The growth of the brain is rapid between 20 and 37 weeks gestation,” explains Pitcher. “Being born even mildly preterm appears to subtly but significantly alter brain microstructure, neural connectivity, and neurochemistry.” On the other hand, the brains of term-born teenagers were highly plastic.73

This study’s findings also suggested that altered hypothalamicpituitary-adrenal (HPA) axis function due to preterm birth may be “a significant modulator of this altered neuroplasticity.” The HPA axis is a complex neurohormone mechanism, an intricate system of stimulation and feedback interactions – among the hypothalamus, the pituitary gland, and the adrenal glands – that regulates metabolic and behavioral reactions to physiological and environmental stress.

The HPA axis is highly susceptible to programming during fetal and neonatal development. Animal and human studies have demonstrated that the stress associated with preterm birth provokes adaptive changes in endocrine and metabolic processes that become permanently programmed via the HPA axis – affecting later health, memory, learning, executive function, and associated behavior throughout life.74-77

Premature birth is a stressful event, not only due to a shortened gestation period, but also because of medical interventions during the first weeks of life (painful procedures, handling, mechanical ventilation, maternal separation). This adverse perinatal environment programs HPA function, essentially setting the thermostat regulating later responses to stress.

Abnormal regulation of the HPA axis is commonly associated with a range of affective and stress related disorders: panic disorder, chronic fatigue syndrome, obsessive compulsive disorder, fibromyalgia, generalized anxiety disorder, and bipolar disorder. Stressful life events have been implicated in the onset of each of these disorders.78 In a study of boys with ADHD and disruptive behavior symptoms, those scoring high on callous unemotional traits showed a blunted HPA axis reactivity to the experimentally induced stress.79

A 2012 Swedish study found that adults who were born late preterm (32- 36 weeks’ gestation) were 2.7 times more likely to have bipolar affective disorder. Functional MRI imaging of young adults born very preterm showed disruptions in brain networks similar to those found in psychiatric patients – strong evidence for a causative relationship rather than simply an association between preterm birth and psychiatric disorders in young adult life.80,81

The severity of all the problems associated with being born early depends on the degree of prematurity, but also there are often marked differences in the health of infants born full term.82 A 2012 study of 128,000 New York children found that “each week of increased gestation from 37 to 41 weeks showed an added benefit in both reading and math scores.”83

Hippocampus, Hyperactivity, and Fluoride

The hippocampus is the central processor in the brain that integrates inputs from the environment, memory, and motivational stimuli to produce behavioral decisions. It is one of the brain areas most sensitive to fluoride’s neurotoxicity. Electron microscopy revealed that rats treated with 20 ppm sodium fluoride in drinking water showed neurodegeneration in the hippocampus, neocortex, cerebellum, spinal cord, and sciatic nerve. The hippocampus had vacuolated myelinated fibers with breaks in continuity.84

Note: rodents more efficiently clear fluoride from their bodies compared with humans. Research shows that when rats consumed 75–125 ppm and humans 5-10 ppm fluoride in their respective drinking waters, the result was equivalent ranges of plasma fluoride levels.85

Fluoride enhances aluminum absorption from the gastrointestinal mucosa.86 Aluminum and fluoride have a close association in drinking water sources, the environment, and cooking utensils, where they form aluminum-fluoride complexes that “activate guanine nucleotide-binding proteins (G-proteins) that are coupled with the receptors for neurotransmitters and hormones,” says Phyllis Mullenix, PhD. “G-protein coupled receptors are found throughout the hypothalamicpituitary-axis, and their activation by aluminum-fluoride complex triggers cell signaling systems that are normally triggered by hormones. … In short, aluminum-fluoride complexes can send false biochemical information throughout the body.”87,88 Note: like the pineal gland, the pituitary gland and the hypothalamus are not protected by the blood–brain barrier and are thus exposed to serum fluoride.

Earlier research by Mullenix found that rats who experienced prenatal exposure to fluoride exhibited higher levels of hyperactivity. “Overall, the behavioral changes from fluoride exposure are consistent with interrupted hippocampal development.”89

Attention-Deficit/Hyperactivity Disorder

Brain imaging studies support the notion of developmental origin of ADHD, and low birth weight has been associated with features of hyperactivity and reduced attention in preschoolers.76 Premature infants have significantly more severe symptoms of ADHD at school age and they were highly correlated.90

In the US, ADHD is the most common neurodevelopmental disorder of childhood, affecting about 7% of all children. In 2013, the results of a long-running study – 5718 children in Rochester, Minnesota, born from 1976 through 1982 – reported that 29% of the children with ADHD still had ADHD as adults. Of the children who still had ADHD as adults, 81% had at least one other psychiatric disorder, as compared with 47% of those who no longer had ADHD and 35% of controls. Lead investigator William Barbaresi, MD, says, “We suffer from the misconception that ADHD is just an annoying childhood disorder that’s overtreated. This couldn’t be further from the truth.”91 (Rochester’s drinking water has been artificially fluoridated since 1960.)

Other statistical snapshots of America reveal that compared to the 25 least-fluoridated states, ADHD rates for children (4–17 years old) averaged 14% higher and mental retardation rates for children (6–17 years old) averaged 38% higher in the 25 most fluoridated states.92,93

Fetal and Infant Microbiota and the HPA Axis

“The gut microbiota contributes to developmental programming; a process whereby an environmental factor acting during a developmental ‘window of vulnerability’ can have a potentially life-long impact on physiological function,” say researchers at the Brain-Body Institute at McMaster University in Ontario, Canada.”94 Other researchers there note that “the presence of gut microbiota regulates the set point for HPA axis activity.”95 Findings from a 2004 study “suggest that exposure to indigenous microbiota at an early developmental stage, when brain plasticity may still be preserved, is required for the HPA system to become fully susceptible to inhibitory neural regulation.”96

It’s long been assumed that the fetal GI tract contains no gut flora, but recent advances in understanding early host-microbe interactions indicate that this early microbial programming begins in utero.97 “During pregnancy, immune and metabolic functions of the fetus are dependent on the mother; moreover, the refinement of these functions seems to commence inside the uterus and to be diet sensitive,” Spanish researchers reported in 2011. “Observational and interventional studies suggest that diet and exposure to microbes during pregnancy may influence the metabolic and immunologic profiles of the pregnant uterus and the risk of disease developing in offspring later in life.”98

Because altered bacterial colonization in the fetal gut is a risk factor for necrotizing enterocolitis (NEC), the intestinal disease associated with preterm birth (discussed above), fluoride is certainly a risk factor.66 No studies, however, have looked at fluoride levels in mothers and their premature infants with NEC.

Mechanisms of Contraction that Need Research

Science knows more about the dark side of the moon than the inside of the fetal gut. Does maternal fluoride make its way there? We know fluoride gets into cord blood. Medical science does not yet recognize fetal fluorosis.

The process of birth begins with stimulation of the uterus by various substances, including corticotropin releasing hormone (CRH), which leads to increased uterine contractility. In full-term birth, CRH activation is largely driven by the fetal HPA axis; however, in preterm birth, it may be the maternal HPA axis that drives CRH expression. Women delivering preterm had significantly elevated CRH levels compared with those in women delivering at term.99 By inhibiting gut bacteria, perhaps fluoride could alter the fetal HPA axis and cause a premature release of CRH that triggers birth. Or perhaps fluoride could activate G-protein coupled receptors to trigger false hormonal signals in the maternal or fetal HPA axis.

Another mechanism involves the hormone progesterone. During more than 95% of gestation, uterine contractility is inhibited by a variety of biochemicals, including progesterone. At term, however, progesterone withdrawal leads to a biological cascade that promotes uterine contractility and birth.99 Progesterone supplementation is a proven (and expensive) intervention to lower preterm birth rates.

Progesterone treatment involves proteins (XIAP, BID, Bcl-2) that prevent preterm birth by hindering cell death (apoptosis) in the fetal membranes.100 Whereas progesterone helps inhibit apoptosis, fluoride can induce it. “An implication of Bcl-2 proteins in the regulation of fluoride-induced apoptosis was convincingly proved in the cells of different types,” Russian researchers reported in 2012. “Fluoride-induced apoptosis is mediated by its direct effects on the expression of Bcl-2 family members resulting in decrease in the antiapoptotic/proapoptotic proteins ratio.”15

In another mechanism, contraction is triggered by the coupling of myosin and actin, which is regulated by orchestrated waves of phosphorylation/dephosphorylation of the myosin regulatory light chain. The dephosphorylation step is mediated by myosin phosphatase, the primary effector of smooth muscle relaxation.99,101,102 A phosphatase inhibitor, sodium fluoride has been shown to inhibit myosin-specific phosphatase activity and cause “significant time-dependent increases in myosin light chain phosphorylation.”103

Nonskeletal Fluorosis

In addition to dental and skeletal fluorosis, Sucheela says, a third form, nonskeletal fluorosis, is important to recognize because health complaints associated with it denote the early onset of the disease, when prevention is still possible. Symptoms of nonskeletal fluorosis include gastrointestinal discomfort and irritable bowel syndrome, weakness and loss of energy, anemia and depression, abnormal sperm production, and low testosterone levels. Sucheela has shown that withdrawal of fluoride, combined with dietary interventions, can reverse these complaints to normal.104

Based on her extensive experience with fluorosis in India, Sucheela says it’s evident that only 40% of patients with fluorosis consume fluoride contaminated water. Another 40% of patients are ingesting high fluoride through food and food products. In the remaining 20%, the fluoride levels are high due to use of fluoride-containing dental products, drugs, and inhaling industrial emissions. What concerns her is “the additive effect from different sources.”104

No Threshold

One shouldn’t dismiss studies from India because of that country’s higher fluoride levels in drinking water. A major 2011 European review of fluoride’s health effects concluded: “Systemic exposure to fluoride through drinking water is associated with an increased risk of dental and bone fluorosis in a dose-response manner without a detectable threshold.”105

For half a century, fluoridation proponents have claimed that a fluoride concentration of 0.7 to 1.2 ppm in drinking water is harmless, because it’s well below the danger threshold established at 4.0 ppm. However, that’s like saying you can get drunk on hard liquor, but not on beer or wine. Obviously, it’s the dose that matters – how much alcohol you drink – not the percentage of alcohol in the beverage.

One cup of water fluoridated at 1.0 ppm contains about 0.25 mg of fluoride, the same amount that’s in the pea-sized dab of fluoride toothpaste whose poison-warning label says children should not swallow.

The archaic “one-size-fits-all” delivery of fluoride via public water supplies is obviously out of touch with modern medical reality, especially for infants and children, because fluoride is a “developmental neurotoxicant,” the EPA determined in 2009. Based on human and animal studies, the EPA’s Neurotoxicology Division found “substantial evidence” that fluoride is a chemical “toxic to the developing mammalian nervous system.”106

“No national primary drinking water regulation may require addition of any substance for preventive health care purposes unrelated to contamination of drinking water.”
– U.S. Safe Drinking Water Act, 2002107

This common-sense federal law not only recognizes the inappropriateness of using public drinking water to deliver chemicals intended to treat people, as opposed to treating water, it also recognizes that the decision to consume fluoride in drinking water should be made at the local level. Common sense tells us the decision to swallow fluoride should be made at the individual level, based on one’s amount of water consumption and fluoride intake from all sources. (The problem is, fluoride content is conspicuously missing from all food ingredient labels, including pet foods, whose very high fluoride content has been implicated in canine bone cancer.)108,109

Genetic Factor

Not only are Americans consuming uncontrolled and unknown doses of fluoride, a person’s individual susceptibility to this toxin is not taken into consideration. Animal studies show there is a genetic component in the pathogenesis of dental fluorosis and in bone response to fluoride exposure. Different strains of inbred mice demonstrate differential physiological responses to ingested fluoride.110,111

We really don’t know the genetic factors that determine an individual’s resistance to developing fluorosis and susceptibility to fluoride’s multiple mechanisms of toxicity in the body and brain.

The Elephant in the Water Supply

Water is the predominant source of fluoride in the US; however, a historically unprecedented array of other sources are responsible for a significant amount of exposure to fluoride: processed foods and beverages; toothpaste; other dental products and treatments; fluoride supplements; fluorinated pharmaceuticals, pesticides, and post-harvest fumigants. The additive effect can be substantial.

Twenty years ago, the National Research Council realized, “It is no longer feasible to estimate with reasonable accuracy the level of fluoride exposure simply on the basis of concentration in drinking water supply.”112 Therefore, even where fluoride levels in drinking water are claimed to be safe, a woman who is pregnant (or wants to be) should take steps to minimize her consumption of fluoride if she wants to reduce her risk for giving birth prematurely.

Residence in the US is a risk factor for preterm birth, and more people drink artificially fluoridated water in America alone than in the rest of the world combined.113 It is high time that we change our long habit of not thinking fluoride consumption wrong and realize that this toxin is a significant risk factor for preterm birth, low birth weight, infant mortality, and long-term neurological disabilities.

A vibrant brain is a most precious gift of life. It is inexcusable to promote, condone, or ignore a policy that diminishes this birthright.

Notes

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John D. MacArthur writes about neuroscience. His
previous contributions to the Townsend Letter were
two reports in October 2013: “Overdosed: Fluoride,
Copper, and Alzheimer’s Disease” and “Too Much
Copper, Too Little Zinc, and Cognitive Deterioration
in Alzheimer’s Disease” (with George J. Brewer,
MD). John researched and wrote “The Human Brain”
section for the Franklin Institute Science Museum
website. This summer, all his neuroscience reports
were published in a single volume, Mind Over
Gray Matter: Practical Neuroscience for the Best
Performance of Your Life.