Abstract: 

The mammalian central nervous system is composed of the brain and spinal cord. The brain is protected by the blood-brain barrier (BBB) that allows selective traffic of substances into the brain. Fluoride is a highly toxic and reactive element. We get exposed to fluoride due to its common use in toothpaste, dental gels, non-stick pans, razor blades, etc. Fluoride also enters our food chain through fishes that are cultivated in water bodies, which get contaminated with fluoride from running water from farms around it. Fluoride can accumulate on our body and cause toxic effects. In the context of fluoride, it is reported that fluoride exposure causes various toxic effects in our body, including the central nervous system as well. Fluoride is known to cross the blood-brain barrier and enter our brain tissue. It interferes with the normal metabolic process of the brain, generates free radicals and causes various toxic effects therein. Fluoride has been found to be linked to various pathogenic conditions of the brain as well. In this review, we have discussed the effects of fluoride on the different parts of the brain and the remedies in use.

Link: https://ijpsr.com/?action=download_pdf&postid=62474

Abstract: 

Background: A systematic review and meta-analysis of published studies on developmental fluoride neurotoxicity support the hypothesis that exposure to elevated concentrations of fluoride in water is neurotoxic during development.

Methods: We carried out a pilot study of 51 first-grade children in southern Sichuan, China, using the fluoride concentration in morning urine after an exposure-free night; fluoride in well-water source; and dental fluorosis status as indices of past fluoride exposure. We administered a battery of age-appropriate, relatively culture-independent tests that reflect different functional domains: the Wide Range Assessment of Memory and Learning (WRAML), Wechsler Intelligence Scale for Children-Revised (WISC-IV) digit span and block design; finger tapping and grooved pegboard. Confounder-adjusted associations between exposure indicators and test scores were assessed using multiple regression models.

Results: Dental fluorosis score was the exposure indicator that had the strongest association with the outcome deficits, and the WISC-IV digit span subtest appeared to be the most sensitive outcome, where moderate and severe fluorosis was associated with a digit span total score difference of -4.28 (95% CI -8.22, -0.33) and backward score with -2.13 (95% CI -4.24, -0.02).

Conclusions: This pilot study in a community with stable lifetime fluoride exposures supports the notion that fluoride in drinking water may produce developmental neurotoxicity, and that the dose-dependence underlying this relationship needs to be characterized in detail.

https://pubmed.ncbi.nlm.nih.gov/25446012/

Abstract:

Background: Although fluoride may cause neurotoxicity in animal models and acute fluoride poisoning causes neurotoxicity in adults, very little is known of its effects on children’s neurodevelopment.

Objective: We performed a systematic review and meta-analysis of published studies to investigate the effects of increased fluoride exposure and delayed neurobehavioral development.

Methods: We searched the MEDLINE, EMBASE, Water Resources Abstracts, and TOXNET databases through 2011 for eligible studies. We also searched the China National Knowledge Infrastructure (CNKI) database, because many studies on fluoride neurotoxicity have been published in Chinese journals only. In total, we identified 27 eligible epidemiological studies with high and reference exposures, end points of IQ scores, or related cognitive function measures with means and variances for the two exposure groups. Using random-effects models, we estimated the standardized mean difference between exposed and reference groups across all studies. We conducted sensitivity analyses restricted to studies using the same outcome assessment and having drinking-water fluoride as the only exposure. We performed the Cochran test for heterogeneity between studies, Begg’s funnel plot, and Egger test to assess publication bias, and conducted meta-regressions to explore sources of variation in mean differences among the studies.

Results: The standardized weighted mean difference in IQ score between exposed and reference populations was –0.45 (95% confidence interval: –0.56, –0.35) using a random-effects model. Thus, children in high-fluoride areas had significantly lower IQ scores than those who lived in low-fluoride areas. Subgroup and sensitivity analyses also indicated inverse associations, although the substantial heterogeneity did not appear to decrease.

Conclusions: The results support the possibility of an adverse effect of high fluoride exposure on children’s neurodevelopment. Future research should include detailed individual-level information on prenatal exposure, neurobehavioral performance, and covariates for adjustment.

https://ehp.niehs.nih.gov/doi/10.1289/ehp.1104912

Abstract: 

July 25, 2012 — For years health experts have been unable to agree on whether fluoride in the drinking water may be toxic to the developing human brain. Extremely high levels of fluoride are known to cause neurotoxicity in adults, and negative impacts on memory and learning have been reported in rodent studies, but little is known about the substance’s impact on children’s neurodevelopment. In a meta-analysis, researchers from Harvard School of Public Health (HSPH) and China Medical University in Shenyang for the first time combined 27 studies and found strong indications that fluoride may adversely affect cognitive development in children. Based on the findings, the authors say that this risk should not be ignored, and that more research on fluoride’s impact on the developing brain is warranted.

The study was published online in Environmental Health Perspectives on July 20, 2012.

The researchers conducted a systematic review of studies, almost all of which are from China where risks from fluoride are well-established. Fluoride is a naturally occurring substance in groundwater, and exposures to the chemical are increased in some parts of China. Virtually no human studies in this field have been conducted in the U.S., said lead author Anna Choi, research scientist in the Department of Environmental Health at HSPH.

Even though many of the studies on children in China differed in many ways or were incomplete, the authors consider the data compilation and joint analysis an important first step in evaluating the potential risk. “For the first time we have been able to do a comprehensive meta-analysis that has the potential for helping us plan better studies. We want to make sure that cognitive development is considered as a possible target for fluoride toxicity,” Choi said.

Choi and senior author Philippe Grandjean, adjunct professor of environmental health at HSPH, and their colleagues collated the epidemiological studies of children exposed to fluoride from drinking water. The China National Knowledge Infrastructure database also was included to locate studies published in Chinese journals. They then analyzed possible associations with IQ measures in more than 8,000 children of school age; all but one study suggested that high fluoride content in water may negatively affect cognitive development.

The average loss in IQ was reported as a standardized weighted mean difference of 0.45, which would be approximately equivalent to seven IQ points for commonly used IQ scores with a standard deviation of 15.*  Some studies suggested that even slightly increased fluoride exposure could be toxic to the brain. Thus, children in high-fluoride areas had significantly lower IQ scores than those who lived in low-fluoride areas. The children studied were up to 14 years of age, but the investigators speculate that any toxic effect on brain development may have happened earlier, and that the brain may not be fully capable of compensating for the toxicity.

“Fluoride seems to fit in with lead, mercury, and other poisons that cause chemical brain drain,” Grandjean says. “The effect of each toxicant may seem small, but the combined damage on a population scale can be serious, especially because the brain power of the next generation is crucial to all of us.”

https://www.hsph.harvard.edu/news/features/fluoride-childrens-health-grandjean-choi/

Abstract:

The elevated fluoride from drinking water impacts on T3, T4 and TSH hormones. The aim was study impacts of drinking water fluoride on T3, T4 and TSH hormones inYGA (Yazd Greater Area). In this case- control study 198 cases and 213 controls were selected. Fluoride was determined by the SPADNS Colorimetric Method. T3, T4 and TSH hormones tested in the Yazd central laboratory by RIA (Radio Immuno Assay) method. The average amount of TSH and T3 hormones based on the levels of fluoride in two concentration levels 0–0.29 and 0.3–0.5 (mg/L) was statistically significant (P = 0.001 for controls and P = 0.001 for cases). In multivariate regression logistic analysis, independent variable associated with Hypothyroidism were: gender (odds ratio: 2.5, CI 95%: 1.6–3.9), family history of thyroid disease (odds ratio: 2.7, CI 95%: 1.6–4.6), exercise (odds ratio: 5.34, CI 95%: 3.2–9), Diabetes (odds ratio: 3.7, CI 95%: 1.7–8), Hypertension (odds ratio: 3.2, CI 95%: 1.3–8.2), water consumption (odds ratio: 4, CI 95%: 1.2–14). It was found that fluoride has impacts on TSH, T3 hormones even in the standard concentration of less than 0.5 mg/L. Application of standard household water purification devices was recommended for hypothyroidism.

https://www.nature.com/articles/s41598-018-20696-4

Abstract: 

NORTH SUTTON, N.H., March 16, 2023 /PRNewswire/ — A court order has led to the National Toxicology Program (NTP) releasing a finalized systematic review of fluoride’s neurotoxicity that was blocked by government officials and concealed from the public since May 2022, according to the Fluoride Action Network. The NTP reported 52 of 55 studies found decreases in child IQ with increased fluoride.

https://fluoridealert.org/articles/government-report-finds-no-safe-level-of-fluoride-in-water-fluoridation-policy-threatened/

Abstract:

Numerous physiological functions exhibit substantial circadian oscillations. In the kidneys, renal plasma flow, the glomerular filtration rate and tubular reabsorption and/or secretion processes have been shown to peak during the active phase and decline during the inactive phase. These functional rhythms are driven, at least in part, by a self-sustaining cellular mechanism termed the circadian clock. The circadian clock controls different cellular functions, including transcription, translation and protein post-translational modifications (such as phosphorylation, acetylation and ubiquitylation) and degradation. Disruption of the circadian clock in animal models results in the loss of blood pressure control and substantial changes in the circadian pattern of water and electrolyte excretion in the urine. Kidney-specific suppression of the circadian clock in animals implicates both the intrinsic renal and the extrarenal circadian clocks in these pathologies. Alterations in the circadian rhythm of renal functions are associated with the development of hypertension, chronic kidney disease, renal fibrosis and kidney stones. Furthermore, renal circadian clocks might interfere with the pharmacokinetics and/or pharmacodynamics of various drugs and are therefore an important consideration in the treatment of some renal diseases or disorders.

https://www.nature.com/articles/s41581-018-0048-9

Abstract:

Anthropogenic contaminants in water can impose risks to reproductive health. Most of these compounds are known to be endocrine disrupting chemicals (EDCs). EDCs can impact the endocrine system and subsequently impair the development and fertility of non-human animals and humans. The source of chemical contamination in water is diverse, originating from byproducts formed during water disinfection processes, release from industry and livestock activity, or therapeutic drugs released into sewage. This review discusses the occurrence of EDCs in water such as disinfection byproducts, fluorinated compounds, bisphenol A, phthalates, pesticides, and estrogens, and it outlines their adverse reproductive effects in non-human animals and humans.

https://www.mdpi.com/1422-0067/21/6/1929

Abstract: 

In this paper, the adsorption of humic acid (HA) on natural maifan stone (MS) in aqueous medium was investigated. The changes in MS after adsorption have been characterized explicitly. The adsorption behavior was studied by varying the factors of pH (5–10), reaction time (10–180 min), initial HA concentration (5–50 mg/L), adsorbent dosage (0.1–1.2 g), and temperature (25–45 °C). The kinetics of the adsorption process of HA was fitted well with the pseudo-second-order model (R2 = 0.99). The isothermal results revealed that the adsorption process is favorable, and highly fitting Langmuir models (R2 > 0.99) were used. Additionally, the obtained maximum adsorption capacity of MS for HA was approximately 1 mg/g. The adsorption process of HA onto MS was endothermic according to the thermodynamic study. The changes in the excitation–emission–matrix of HA and the X-ray diffraction of MS after adsorption indicate the interaction of HA and MS. However, the reason for these changes is still unclear. Thus, the results show that the natural MS exhibited a certain adsorption capacity for HA. It is promising to develop novel natural MS-based materials for adsorption of HA.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144149/

Included 100 people found a significant difference in whole blood viscosity after consuming high-pH water compared to regular water after a strenuous workout. Viscosity is the direct measurement of how efficiently blood flows through the vessels.

Abstract:

Background:

Previous research has shown fluid replacement beverages ingested after exercise can affect hydration biomarkers. No specific hydration marker is universally accepted as an ideal rehydration parameter following strenuous exercise. Currently, changes in body mass are used as a parameter during post-exercise hydration. Additional parameters are needed to fully appreciate and better understand rehydration following strenuous exercise. This randomized, double-blind, parallel-arm trial assessed the effect of high-pH water on four biomarkers after exercise-induced dehydration.

Methods:

One hundred healthy adults (50 M/50 F, 31 ± 6 years of age) were enrolled at a single clinical research center in Camden, NJ and completed this study with no adverse events. All individuals exercised in a warm environment (30 °C, 70% relative humidity) until their weight was reduced by a normally accepted level of 2.0 ± 0.2% due to perspiration, reflecting the effects of exercise in producing mild dehydration. Participants were randomized to rehydrate with an electrolyzed, high-pH (alkaline) water or standard water of equal volume (2% body weight) and assessed for an additional 2-h recovery period following exercise in order to assess any potential variations in measured parameters. The following biomarkers were assessed at baseline and during their recovery period: blood viscosity at high and low shear rates, plasma osmolality, bioimpedance, and body mass, as well as monitoring vital signs. Furthermore, a mixed model analysis was performed for additional validation.

Results:

After exercise-induced dehydration, consumption of the electrolyzed, high-pH water reduced high-shear viscosity by an average of 6.30% compared to 3.36% with standard purified water (p = 0.03). Other measured biomarkers (plasma osmolality, bioimpedance, and body mass change) revealed no significant difference between the two types of water for rehydration. However, a mixed model analysis validated the effect of high-pH water on high-shear viscosity when compared to standard purified water (p = 0.0213) after controlling for covariates such as age and baseline values.

Conclusions:

A significant difference in whole blood viscosity was detected in this study when assessing a high-pH, electrolyte water versus an acceptable standard purified water during the recovery phase following strenuous exercise-induced dehydration.

https://jissn.biomedcentral.com/articles/10.1186/s12970-016-0153-8

Abstract:

Very low or very high concentrations of calcium (Ca) and magnesium (Mg) or total hardness in drinking water have been empirically recognized as the cause of the problems with corrosion, scaling, or taste of water. A large body of scientific evidence over the last 60 years has also attributed health problems to both extremes of these minerals in water. For example, drinking water low in Mg significantly increases the likelihood of cardiovascular mortality. This knowledge is not properly considered in the drinking water quality regulations, especially as more and more water is now produced by desalination disturbing its natural mineral composition. Although the current EU Drinking Water Directive does not include limits for hardness, Ca or Mg, most member states regulate these parameters either through law (12 countries) or technical guidance (7 countries), and several countries have issued educational information for the public. However, the regulations in most countries are not based on current research and not comparable because some provide a recommended range while others provide mandatory minimum or maximum limit values. This summary of the situation in 28 European Union countries is intended to provide information that can contribute to the implementation of the revised EU Directive.

https://www.sciencedirect.com/science/article/abs/pii/S0273230020300155

https://www.healthline.com/nutrition/magnesium-benefits

https://americanbonehealth.org/best-bones-forever/why-do-our-bones-need-calcium/#:~:text=When%20your%20body%20makes%20new,make%20bones%20strong%20and%20flexible

https://pubmed.ncbi.nlm.nih.gov/26404370/

Almost everyone knows that vitamins, minerals and trace elements are important. Young animals in particular need extra vitamins and minerals in the first phase of life because they have some deficiencies at birth. In this article, we reveal the key vitamins and minerals, what they do and why they are so important.

https://denkavit.com/en/news/the-importance-of-vitamins-minerals-and-trace-elements-in-young-animals/

Abstract:

In Japan, alkaline electrolyzed water (AEW) apparatus have been approved as a medical device. And for the patients with gastrointestinal symptoms, drinking AEW has been found to be effective in relieving gastrointestinal symptoms. But some users of AEW apparatus do not have abdominal indefinite complaint. Little attention has been given to the benefit for the users which have no abdominal indefinite complaint. The object of this study is to evaluate the effect on health, including gastrointestinal symptoms, when a person without abdominal indefinite complaint, etc., drinks AEW on a daily basis. A double-blind, randomized controlled trial has been designed. Four-week period of everyday water drinking, PW drinking group: drink purified tap water as a placebo, AEW drinking group: drink alkaline electrolyzed water which made by electrolysis of purified tap water. Before the experiment and after the 4-week period of water drinking, Blood tests, physical fitness evaluations, and questionnaire evaluations is conducted. In this study, we did not specifically select patients with gastrointestinal symptoms. Sufficiently clear effect could not be confirmed. But the stools were more normal, and, as shown in the previous report, that drinking AEW is considered to contribute to intestinal normalization. In addition, when drinking AEW, a high proportion of the respondents said that they felt they were able to sleep soundly, and the proportion of subjects who answered that they felt good when awakening increased. The effect of reducing oxidative stress, thus allowing for improved sleep, was exhibited by drinking AEW containing hydrogen, which is considered to be an antioxidant substance. This research were approved by the Ethics Committee of the Osaka City University Graduate School of Medicine (No. 837) and were registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: UMIN000031800) on March 22, 2018.

A website dedicated to studies done on Hydrogen water. There are about 1350 studies on this site, some of them are on animals, several hunderdred are on humans, and some are specifically on diseases like parkinson's disease, alsimers, dementia, chronic fatigue, muscle aches, joint pain, arthritis and some are general studies on the affects of hydrogen water, lik reduction of inflammation, absorption of micronutrients and how it helps gut flora and the bacteria in your gut. 

hydrogenstudies.com

Abstract:

The evidence for the beneficial effects of drinking hydrogen-water (HW) is rare. We aimed to investigate the effects of HW consumption on oxidative stress and immune functions in healthy adults using systemic approaches of biochemical, cellular, and molecular nutrition. In a randomized, double-blind, placebo-controlled study, healthy adults (20–59 y) consumed either 1.5 L/d of HW (n = 20) or plain water (PW, n = 18) for 4 weeks. The changes from baseline to the 4th week in serum biological antioxidant potential (BAP), derivatives of reactive oxygen, and 8-Oxo-2′-deoxyguanosine did not differ between groups; however, in those aged ≥ 30 y, BAP increased greater in the HW group than the PW group. Apoptosis of peripheral blood mononuclear cells (PBMCs) was significantly less in the HW group. Flow cytometry analysis of CD4+, CD8+, CD20+, CD14+ and CD11b+ cells showed that the frequency of CD14+ cells decreased in the HW group. RNA-sequencing analysis of PBMCs demonstrated that the transcriptomes of the HW group were clearly distinguished from those of the PW group. Most notably, transcriptional networks of inflammatory responses and NF-κB signaling were significantly down-regulated in the HW group. These finding suggest HW increases antioxidant capacity thereby reducing inflammatory responses in healthy adults.

https://www.nature.com/articles/s41598-020-68930-2

Abstract:

Numerous benefits have been attributed to alkaline-electrolyzed–reduced water (ERW). Sometimes these claims are associated with easily debunked concepts. The observed benefits have been conjectured to be due to the intrinsic properties of ERW (e.g., negative oxidation–reduction potential (ORP), alkaline pH, H2 gas), as well enigmatic characteristics (e.g., altered water structure, microclusters, free electrons, active hydrogen, mineral hydrides). The associated pseudoscientific marketing has contributed to the reluctance of mainstream science to accept ERW as having biological effects. Finally, through many in vitro and in vivo studies, each one of these propositions was examined and refuted one-by-one until it was conclusively demonstrated that H2 was the exclusive agent responsible for both the negative ORP and the observed therapeutic effects of ERW. This article briefly apprised the history of ERW and comprehensively reviewed the sequential research demonstrating the importance of H2. We illustrated that the effects of ERW could be readily explained by the known biological effects of H2 and by utilizing conventional chemistry without requiring any metaphysical conjecture (e.g., microclustering, free electrons, etc.) or reliance on implausible notions (e.g., alkaline water neutralizes acidic waste). The H2 concentration of ERW should be measured to ensure it is comparable to those used in clinical studies.

https://www.mdpi.com/1422-0067/23/23/14750

https://hydrogenstudies.com/search/

Abstract:

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS). The high costs, inconvenient administration, and side effects of current Food and Drug Administration (FDA)-approved drugs often lead to poor adherence to the long-term treatment of MS. Molecular hydrogen (H2) has been reported to exhibit anti-oxidant, anti-apoptotic, anti-inflammatory, anti-allergy, and anti-cancer effects. In the present study, we explored the prophylactic and therapeutic effects of hydrogen-rich water (HRW) on the progress of experimental autoimmune encephalomyelitis (EAE), the animal model for MS. We found that prophylactic administration of both 0.36 mM and 0.89 mM HRW was able to delay EAE onset and reduce maximum clinical scores. Moreover, 0.89 mM HRW also reduced disease severity, CNS infiltration, and demyelination when administered after the onset of disease. Furthermore, HRW treatment prevented infiltration of CD4+ T lymphocytes into the CNS and inhibited Th17 cell development without affecting Th1 cell populations. Because HRW is non-toxic, inexpensive, easily administered, and can readily cross the blood–brain barrier, our experiments suggest that HRW may have great potential in the treatment of MS.

https://www.sciencedirect.com/science/article/abs/pii/S016557281630042X