FLUORIDE toxicity and PINEAL gland


The pineal gland is a naturally calcifying endocrine organ which secretes the sleep-promoting hormone melatonin. Age-related changes of the pineal have been observed, including decreased pinealocyte numbers, increased calcification, and a reduction in melatonin production. Fluoride is attracted to calcium within the pineal gland. The study sought to examine the effects of a fluoride-free diet on the morphology of the pineal gland of aged male rats (26 months old). All animals had previously been raised on standard fluoridated food and drinking water. These control animals were compared to other animals that were placed on a fluoride-free diet (Bfluoride flush^) for 4 or 8 weeks. At 4 weeks, pineal glands from fluoride-free animals showed a 96% increase in supporting cell numbers and at 8 weeks a 73% increase in the number of pinealocytes compared to control animals. In contrast, the number of pinealocytes and supporting cells in animals given an initial 4-week fluoride flush followed by a return to fluoridated drinking water (1.2 ppm NaF) for 4 weeks were not different from control animals. Our findings therefore demonstrate that a fluoride-free diet encouraged pinealocyte proliferation and pineal gland growth in aged animals and fluoride treatment inhibited gland growth. These findings suggest that dietary fluoride may be detrimental to the pineal gland.

Fluoride exposures in early life
Fluoride is contained in natural foods such as brewed black tea, raisins, and white wine decaffeinated tea contains more fluoride than that of caffeinated tea.
The prevalence of dental fluorosis has increased in the U.S., Canada, and other nations due to the widespread ingestion of fluoride during the first three years of life. In the first few months of life, daily fluoride intake of infants may be significantly higher than the optimum.
More than 90% of the toothpastes in the U.S. contain fluoride and many children are exposed to fluoride through incidental ingestion of toothpaste. For children 1–3 years, 30–75% of the dentifrice is ingested, and for children 4–7 years, 14–48% is ingested. Each tube of toothpaste displays the warning “Keep out of reach of children under 6 years of age. If more than used for brushing is accidentally swallowed, get medical help or contact a Poison Control Center right away.” Many children accidentaly swallow toothpaste, fluoride gels for topical applications, and mouthwashes. Between 1994 and 2011, calls to Poison Control Centers due to toothpaste ingestion increased approximately seven times.
For 2013-2014, as part of ongoing National Health and Nutrition Examination Survey, the data were released in the public. According to this survey, about 30% of the children were at the risk of dental fluorosis. Younger children generally ingest a higher proportion of toothpaste than older children, ingesting over half of the toothpaste per brushing. Some children ingest more than 1 gram of dentifrice per brushing (1 mg of fluoride). Toothpastes specifically flavored for children have been linked to the use of larger quantities of toothpaste than suggested, increasing the importance of the pathway of excessive fluoride intake. Additive effects by ingesting toothpastes results in 5.56 times likely to develop fluorosis, and timing and fluorosis are closely associated.
Among children aged 12 and 24 months, the amount of fluoride ingested from toothpastes could constitute a substantial proportion of the total daily intake of fluoride and again among young children from 2 to 7 years of age. Thus, if one starts brushing teeth from a young age, it is likely that one will develop fluorosis. Boiling water doubles fluoride concentrations found in non-boiled water, suggesting that foods or infant formula prepared with boiled water may result in increased fluoride intake through diet.
Based upon the animal study and human, Chan et al. have found that plasma levels of fluoride in the presence of caffeine was significantly higher than that of fluoride alone, suggesting that the presence of fluoride would remain longer due to the ingestion of caffeine-containing beverages. They hypothesized that the increase of the fluorosis may partly explain the presence or intake of caffeine and fluoride concomitantly. Therefore, according to their hypothesis, theoretically, babies born to pregnant mothers who are heavy coffee drinkers (coffee contains caffeine on the average of approximately 100 mg/ cup of coffee and soft drinks contain caffeine approximately a little less than half of the cup of coffee) and/or habitual drinkers of caffeinated beverages must have a much greater chance of fluorosis in the future than babies of mothers who do not drink caffeinated drinks during pregnancy. According to the recent findings that higher fluorosis severity was associated with soft drink consumption as most soft drinks contain caffeine.

Dental fluorosis is a fluoride‑induced disturbance in tooth formation, which results in hypomineralized enamel with increased porosity. It is caused by excessive intake of
fluoride, but only during the period of tooth development. The most important risk factor for dental fluorosis is the amount of fluoride consumed from all sources during the
critical period of tooth development.
Fluoridated supplements, fluoridated dentifrices, and infant formulas before the age of seven are the three major risk factors other than fluoridated water for dental fluorosis.
It now appears that the risk of dental fluorosis is the lowest during the secretory stage of enamel development. It is suggested that fluorosis causes subsurface hypomineralization or porosity of enamel. This subsurface porosity is most likely caused by a delay in the hydrolysis and removal of enamel proteins, particularly amelogenins, as the enamel matures. This delay could be due to the direct effect of fluoride on the ameloblasts or to an interaction of fluoride with the proteins or proteinases in the mineralizing matrix.
Early maturation stage of enamel formation appears to be particularly sensitive to fluoride exposure. The risk of enamel fluorosis is lowest when exposure takes place only
during the secretory stage of enamel formation, but highest when exposure occurs in both secretory and maturation stages of enamel formation.

Chronic fluoride toxicity may produce skeletal fluorosis characterized by stiffness in the back and various joints, deformity in hips, knees, and other joints, bony exostosis in limb bones, neurologic manifestations, difficulty in walking due to weakness, nausea, loss of
appetite, pain in the stomach, constipation, diarrhea, and allergic manifestations.

Fluorosis occurs mainly by systemic route and can be predicted from fluoride expression in biological fluids like serum, plasma, and urine. Fluoride level of serum and urine are good indicators of fluoride exposure of the patients. Fluoride level in hair and nail have also been used to evaluate the risk of dental fluorosis.

Pineal Morphology and Aging
The pineal gland is a neuroendocrine organ that secretes the sleep-regulating hormone melatonin (MEL). The most widely accepted concept is that melatonin is the recognized major product of the pineal gland. Melatonin is the derivative of tryptophan. The secretory pinealocyte cells of the rat and human pineal gland are classified as either light (type I) or dark (type II) cells based on their light microscopic staining characteristics, with the majority of pinealocytes being light cells. More recently, single-cell analysis of rat pinealocytes transcriptomes has described α- and β-pinealocytes which together contribute to the production of MEL Pinealocytes constitute approximately 95% of the gland, with the remainder consisting of interstitial and supporting cells, such as astrocytes, microglia, and capillary endothelial cells, within a network of nerve fibers. Aging is associated with morphological changes in the pineal gland and a decline in MEL production. Pineal parenchymal volume is directly proportional to both pinealocyte numbers and melatonin production. The size and weight of the human pineal declines with age and glands from aged rats and humans show increased fibrosis and elevated glial cell numbers. In both rats and humans, levels of MEL as measured in the saliva, blood serum, or urine also decline with increasing age.

The decline in MEL production with aging is due to the loss of pinealocytes. Several studies have found that the pineal glands of aged (> 22 months) rats or shrews have decreased numbers of pinealocytes. Although the total number of pinealocytes declines with age, glands from elderly animals have elevated numbers of dark pinealocytes, but these cells display several indicators of degeneration, including organelle swelling, increased numbers of cytoplasmic vacuoles and dense bodies, and increased plasma membrane permeability, suggesting that dark cells may be in the process of undergoing cell death. Pinealocyte precursor cells have the morphological features of type II pinealocytes (dark cells) and are found dispersed throughout the gland of adult rats. Observations of dying dark cells in aged animals may therefore indicate the selective loss of these precursor cells, thereby reducing the regenerative ability of the pineal.

The pineal also has naturally occurring intracellular and extracellular calcium phosphate concretions known as acervuli (corpora arenacea or brain sand). In rats, shrews, and humans, the degree of pineal calcification increases with age. An analysis of light and dark cells in the rat pineal found elevated levels of intracellular calcium and signs of cellular degeneration only in dark cells, suggesting that calcification is related to both the age-dependent loss of pinealocytes and the decline in MEL production in older humans. Decreased pineal volume and increased calcification have also been correlated with the cognitive decline of Alzheimer’s disease but not other dementias, a finding that may be related to a decline in MEL secretion and the loss of its neuroprotective antiinflammatory and anti-oxidative actions

The federally required Material Safety and Data Sheet classifies fluoride as a mutagen, and studies have suggested that dietary fluoride has the potential to cause human health problems. As an anion, fluoride tends to concentrate in calciumcontaining areas such as the pineal gland. Elevated fluoride has been found in the pineal glands of elderly humans. In these glands, fluoride was positively correlated with calcium levels and the fluoride/calcium ratio of the pineal exceeded that of bone. Similarly, ducks exposed to elevated environmental levels of fluoride show significantly higher concentrations of fluoride in their pineal gland compared to bone tissue.

Fluoridated public drinking water is widely used as a systemic treatment for dental caries, but few studies have been conducted to assess the effects of chronic dietary fluoride exposure. The objective of this study was to examine the effect of removing fluoride from the diet of aged rats (starting age 26 months) on the cellular structure of the pineal gland and compare this to pineal glands from animals exposed to dietary fluoride. Glands obtained from animals previously raised with fluoridated food and drinking water were compared to animals placed on a fluoride-free diet for 4 or 8 weeks. Additional animals were maintained fluoride-free for the initial 4-week period and then switched back to fluoridated drinking water (1.2 ppm) for the final 4 weeks. It was found that the fluoride free diet resulted in increased numbers of supporting cells and pinealocytes, suggesting growth of the pineal gland. In comparison, glands from both groups of fluoride-treated animals showed fewer pinealocytes, suggesting that dietary fluoride may have a detrimental effect on the pineal gland.

Dietary fluoride may have the potential to cause adverse human health problems. Previous animal studies have found that dietary fluoride can induce oxidative stress and cell death within the brain and other organs. Rats administered moderate levels of fluoride in their drinking water (2 or 10 ppm NaF) showed neuronal losses within the hippocampus, with remaining neurons exhibiting shrunken cell bodies, reduced nuclear diameters, and increased levels of cathepsin D, an intracellular protease that serves as a marker of cell death. Similarly, brain, heart, liver, and kidney tissues of rats given drinking water with 150 ppm NaF showed increased levels of malondialdehyde and elevated activities of the antioxidant enzymes catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase, all of which are indicators of oxidative stress.

A leading pharmaceutical company, Sepracor, disclosed that the fluoride in toothpaste activate G proteins in the cavity precipitates gingivitis, periodontitis and oral cancer.

Numerous researches have advocated that fluoride is a causative agent for precipitation of
variety of toxicities including neurological, reproductive, hepatic, immunological, cardiac,
nephrological, osseous, dental etc.

The current World Health Organization Guideline recommendation on fluoride in drinking water is 1 ppm. Excessive amounts of this element can lead to deformation of teeth as well as bones, leading to life threatening diseases such as dental and skeletal fluorosis. Other than fluorosis, neuropathic effects, impaired thyroid function, lower intelligence of children, slow growth of the brain function, increased rates of kidney stones, and carcinogenicity due to excess fluoride.

Fluoride sensitivity of cells from different organs of rats showed that kidney cells being the most sensitive type. After the pineal gland, the kidney is the most exposed to high concentrations of fluoride compared to all other soft tissues.

Therefore, exposure to higher concentrations of fluoride may contribute to kidney disease. Fluoride is removed from the kidneys by glomerular filtration, and nearly one-third of ingested fluoride discharged in the urine within 24 h. In other studies, a considerable number of investigations specifically pointed out that there is an immediate effect of excess fluoride on tubular area of the kidney. Fluoride inhibits tubular reabsorption primarily in the medullary portion of the ascending limb of Henle’s loop, and this was proven by examination of renal tubular site of action of fluoride, using clearance techniques on Fischer 344 rats.

Fluorides affect the functioning of many enzyme pathways, and this has been shown by in vivo experiments. Kidney enzymes such as lactate dehydrogenase (mice); isocitrate dehydrogenase (mice); glutathione peroxidase (rats), superoxide dismutase (rats); aspartate transaminase (rats and mice); alanine transaminase (rats and mice); alkaline phosphatase (rats); acid phosphatase (rats, mice); glucose-6- phosphatase (rats); and adenosine triphosphatase (dogs) isolated from mice, rats, and dogs are significantly deactivated by the fluoride ion, sometimes the deactivation as high as 90%.

Therefore, especially people with kidney disorders should avoid consumption of excess amounts of fluorides either through drinking water or other sources such as food, drugs, or toothpaste.

Fluoride exposure disrupt the synthesis of collagen and leads to the breakdown of collagen in bone, tendon, muscle, skin, cartilage, lung, kidney and trachea. Therefore, the breakdown of collagen in the kidneys due to excess fluoride should certainly be damaging the kidneys leading to dysfunction of kidneys, paving the way to (chronic kidney disease) CKD. A number of prominent scientists including Nobel Prize winners to have warned about inhibition and poisonous activity of fluoride on the kidney and other enzymes, based on their chemical and enzymological research. Hence, functions of kidney enzymes are at a greater risk due to excess fluoride, leading to kidney dysfunction.
As in the case of animal experiments, mostly the tubular area of the human kidneys damaged due to excess fluoride, and mitochondrion is found to be the target of fluoride toxicity.

Though it has been indicated that fluoride is essential for proper structural growth and functions of bones, teeth and collagen biosynthesis, high exposure leads to dental and skeletal fluorosis via altering ameloblast activity, osteocyte activity, matrix formation and calcium homeostasis.

Once in bones, the fluoride replaces hydroxyl ion in hydroxy-apatite to make fluoroapatite which gets deposited in bones. Increase in bone and enamel fluoride content progressively increases bone strength up to an extent, after which they become weak. At this stage bones and teeth start showing characteristics of fluorosis. Fluoride peak in blood is reached in 20 min of absorption and the level falls in 3–6 h after deposition in bones. Around 50% of absorbed fluoride is retained in the bones, rest is excreted in the urine.

Toxicity of fluoride can manifest as Dental fluorosis, Skeletal fluorosis and Non skeletal fluorosis.

There is a direct link between CKD and consumption of excess amount of fluorides. Excess fluoride is toxic to human and animal kidneys, and the tubular areas of the kidneys are the most vulnerable. Excess fluoride disrupts the collagen synthesis in the body, leading to kidney and other organ damages. In addition, excess fluoride inhibits some kidney and other enzyme pathways, leading to dysfunction of kidneys and other organs. Children are vulnerable to fluoride as low as 2 ppm in drinking water, due to their ability to retain absorbed fluoride as higher as 80% in the body/kidney. Therefore, if continue to consume water from the same source, could result in the child becoming an adult with a sick kidney, prone to ending up as a CKD patient.

Author Artūras Bartašius

Further reading on Pineal gland defluoridation follow this link: https://scottjeffrey.com/decalcify-your-pineal-gland/

SOURCES:

  1. Mrvelj, A., & Womble, M. D. (2019). Fluoride-Free Diet Stimulates Pineal Growth in Aged Male Rats. Biological Trace Element Research. doi:10.1007/s12011-019-01964-4 
  2. Dharmaratne, R. (2018). Exploring the role of excess fluoride in chronic kidney disease: A review. Human & Experimental Toxicology, 096032711881416. doi:10.1177/0960327118814161 
  3. Nakamoto, T., & Rawls, H. R. (2018). Fluoride Exposure in Early Life as the Possible Root Cause of Disease In Later Life. Journal of Clinical Pediatric Dentistry. doi:10.17796/1053-4625-42.5.1
  4. J Nat Sci Biol Med. 2013 Jan-Jun; 4(1): 138–144.doi: 10.4103/0976-9668.107278 Reversal of dental fluorosis: A clinical study
  5. Molecules 2018, 23, 301; doi:10.3390/molecules23020301 Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland
  6. Sharma, Divya, Singh, Aarti, Verma, Kanika, Paliwal, Sarvesh, Sharma, Swapnil, Dwivedi, Jaya, Fluoride: A Review of Pre-clinical and Clinical Studies.Environmental Toxicology and Pharmacology https://doi.org/10.1016/j.etap.2017.10.008
  7. Patil, M. M., Lakhkar, B. B., & Patil, S. S. (2018). Curse of Fluorosis. The Indian Journal of Pediatrics, 85(5), 375–383. doi:10.1007/s12098-017-2574-z 

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