FLUORIDE TOXICITY AND ITS

ANTI-CAVITY PROPERTIES

Deanna Lopez, Yancey Aquino, Johann Pacheco, and Cynthia Schleck

WHY WE CHOSE FLUORIDE

Some people say the government puts fluoride in the water as a type of population control. Most believe it is added to our water sources as an added benefit to our pearly whites. Many are worried about that fluoride is contributing to the rise in autism and other brain deficits in children. We will go through the research on fluoride, hopeful to see if it really is effective for protecting our teeth, what the toxic effects of it is, and if it can lead to autism of neurological deficits in children. First we will cover some history on fluoride and its uses. Then go over the toxicology of it including the mechanism of action. Based on the research we will share results followed up with a discussion of them. Finally we will end with a summary and conclusion. References will be found at the end of the presentation.

WHERE IS FLUORIDE FOUND?

• Fluoride is found in: • Common Toothpaste (sodium

monofluorophosphate) • Vitamins and dietary supplements (sodium

fluoride) • Insecticides and rodenticides (sodium fluoride) • Glass-etching or chrome-cleaning agents

(ammonium bifluoride) (Shin, 2014)

FLUORIDE CONTROVERSY • According to Dwyer (2012), there has been an

ongoing argument on whether or not fluoride in our drinking water is in fact toxic to children’s developing brain.

• It is commonly used to help with dental care therefore put in toothpaste too.

• Lewis and Milgrom (2003) note that in the past 30 years the availability of fluoride has played a huge part in the decline of dental caries based on studies started in the 1900s and followed up in 1940s.

MECHANISMS OF ACTIONS

1. Demineralization and mineralization

2. Inhibition of acid-producing bacteria responsible for caries

3. Effects of ion channels on the body

4. Fluoride in the pineal gland

MECHANSM OF ACTION #1DEMINERALIZATION AND REMINERALIZATION

• This mechanism is the constant tug of war between decay formation and cavity repair.

• Tooth decay is the demineralization due to an acidic environment which releases some of the mineral content out of the tooth’s tissue.

• The acidic substance are waste products of bacteria within the mouth

• The ideal pH for this acid is 4 or less

MECHANISM OF ACTION #1 (CONTINUED)DEMINERALIZATION AND REMINERALIZATION

• The demineralization process is constantly happening. To counteract this process and keep teeth healthy, teeth undergo a process call remineralization.

• Remineralization is the recovery of minerals through the dissolving of ions in the saliva.

• These ions include Fluoride, Calcium, and Phosphate.

• Fluoride is the most effective way to prevent cavities and promote remineralization.

• Fluoride is adsorbed by the surface of the tooth which is damaged. This aspect leads to the speed up of the remineralization rate and then causes the new surface to be stronger than the original surface.

MECHANISM OF ACTION #1 (CONTINUED) DEMINERALIZATION AND REMINERALIZATION

• During remineralization, the basic components of the tooth (hydroxyapatite and carbonated hydroxyapatite) are transformed to fluorapatite

• This process only happens when conditions are favorable such as having the correct minerals present and having the pH higher than 5.5

• Once the pH in the oral cavity reaches below 5.5, bacteria starts to dissolve the inner surface of the tooth, a process called demineralization.

• However, when Fluoride is present, the pH rises and demineralization is prevented.

MECHANISM OF ACTION #2 FLUORIDE ANTIMICROBIAL PROPERTIES

• Fluoride contains antimicrobial properties

• These properties result from Fluoride becoming a weak acid when it becomes HF (Marquis RE, 1995).

• Fluoride becomes HF outside of the cell, which then it is able to diffuse across the cytoplasm ,dissociates into F- (Marquis RE, 1995).

• Fluoride can also interfere with cytoplasmic activity due to its weak acidic properties.

Fig.1 Shows the proportion of [F] and [Hf] needed to induce damage to glycolysis events (Marquis RE, 1995).

MECHANISM OF ACTION #2 FLUORIDE ANTIMICROBIAL PROPERTIES (CONT.)•The main course of action is through affecting bacterial metabolism and interfering with critical pathways (Nouri et. al , 2003).

•It can act as an enzyme inhibitor by inhibiting proton-translocation F-ATPases, due to interfering with the cell attempting to maintain its intracellular pH (Marquis RE, 1995).

•Similarly, fluoride also interfered with other ATPases, such as those that aid in proton and cation transport.

•Fluoride can also interfere with glycolysis and the importation of glucose.(Nouri et. al , 2003)

•The interference with glycolysis causes a build-up of intermediate compounds of glycolysis, which ends up interfering with the importation of glucose.

•Fluoride can also inhibit some peroxidase activity which causes a build up of H2O2 in the cell and cause oxidative damage (Marquis, RE 1995).

MECHANISM OF ACTION #3FLUORIDE AND THE BODY

• According to the Shin’s article Fluoride Toxicity there are several mechanisms of toxicity explained in the pathophysiology section (Shin, 2014).

• Multiple organs can be affected by fluoride. The first of course is the gastrointestinal tract due to fluoride being changed into hydrofluoric acid in the stomach.

• “Once absorbed, fluoride binds calcium ions and may lead to hypocalcemia. Fluoride also has direct cytotoxic effects and interferes with a number of enzyme systems: it disrupts oxidative phosphorylation, glycolysis, coagulation, and neurotransmission.”

• “Severe fluoride toxicity will result in multi-organ failure. Central vasomotor depression, as well as direct cardiotoxicity, also may occur. Death usually results from respiratory paralysis, dysrhythmia, or cardiac failure” (Shin 2014).

MECHANISM OF ACTION #3 (CONTINUED)

• Not only may hypocalcemia occur but hyperkalemia can occur secondary to extracellular release of potassium.

• Fluoride inhibits the sodium-potassium ATPase that allows for the excess potassium to flow out.

• Further more fluoride "inhibits acetylcholinesterase, which may be partly responsible for hyper salivation, vomiting, and diarrhea (cholinergic signs). Seizures may result from both hypomagnesemia and hypocalcemia (Connet, 2012)."

MECHANISM OF ACTION #4PINEAL GLAND

• Research in gerbils showed that high amounts of fluoride (H-F) groups in the pituitary gland resulted in a decreased rate of excretion of urinary aMTE6s secondary to fluoride affecting the pineal glands ability to synthesize melatonin (and other products like serotonin, etc) during the puberty stage of gerbils (Luke, 1997).

• It is hypothesized that the slowed rate of urinary aMTE6s is secondary to Fluoride directly affecting enzymatic conversion. For example, the formation of melatonin from tryptophan.

• Other enzymes presumed to be affected by fluoride are mitochondrial (ie. tryptophan-5-hydrolase) and pinealocyte enzymes.

• For unknown reasoning, pineal calcification starts intracellularly. A possible mechanism may be an increase of calcium demonstrated in pinealocyte mitochondria.

• Interestingly more research is being done where pineal gland calcification is starting to be linked to Alzheimer's and some cancers (Luke, 1997).

RESULTS: FLUORIDE AND TEETH

• Bacteria exist on the surface of teeth and create a layer of plaque. Not only do bacteria produce plaque, but some bacteria can also produce acids that break down tooth enamel and lead to carious lesions.

• Fluoride however, helps to reduce the amount of caries in teeth and may reverse or stop current lesions. There are four mechanisms in which this can occur.

• One method is through the prevention and reversal of tooth demineralization. • Another method is to help remineralize the enamel of the tooth by positively impacting the

addition of calcium and phosphate ions into the enamel (Lewis & Milgrom 2003). • A third method helps to inhibit the acid producing bacteria. Most of the inhibition of acid

production from the bacteria occurs in vitro. • However, too much fluoride can result in fluorosis, or discoloration of the teeth. Younger

children are more susceptible to fluorosis.

RESULTS: FLUORIDE AND TEETH (CONTINUED)

• Although toxic to the human body, fluoride still is necessary for humans to survive; it is mainly needed for teeth. Given this, fluoride has both benefits and risks when it comes to exposure.

• There has been some evidence from The Task Force on Community Preventive Services that shows a reduction of tooth decay in children by 50% in populations that are known to consume fluoridated water (Lewis & Milgrom 2003).

• Furthermore, it has been shown that fluoride can decrease the risk of coronal and root caries in adults by 30%.

• Another benefit from fluorine has to do with the economical aspect of it. According to the CDC, it cost 50 cents to fluoridate the water for a single person, but that the savings could be up to $38 dollars. This, in the long run, can have up to $39 billion dollars in dental treatments for the US population (Lewis & Milgrom 2003). This does not mean that there are no risks.

RESULTS: FLUORIDE AND TEETH (CONTINUED)

• Risks from the overexposure to fluoride ranges from dental to physical diseases. Although the usage of fluoride can help with the decaying of teeth, it can also do the opposite.

• Due to enamel abnormalities, fluorine can increase the risk of the development of fluorosis. Fluorosis is a bone disease resulting from the damage of the enamel.

• The degree of fluorosis depends on many factors including dosage and duration of exposure. It mainly affects toddlers and infants, but it is not a concern during the primary dentition development (due because fluorine does not cross the utero easily)(Lewis & Milgrom 2003). This risk can occur with only 0.44mg of fluoride consumption.

FLUOROSIS

RESULTS: FLUORIDE TOXICITY

• As of 2011, there were over 22,000 cases of fluoride toxicity reported to the American Association of Poison Control Centers across the nation (Shin, 2014).

• From these exposures, only 1096 cases were due to contamination from another source other than from toothpaste. However there were no deaths in 2011 (Shin 2014).

• Fluoride toxicity symptoms can start showing up with intake as low as 3 to 5 mg/kg

• Death can occur as early as after the intake of 2g of fluoride. Furthermore, the calculated lethal dose for fluoride has been found to be 32-64 mg/kg (Shin 2014).

RESULTS: FLUORIDE AND THE BRAIN

• Fluoride also impacts the brain and is comparative to other metals such as lead and mercury (Dwyer, 2012). A study showed that there were decrease in IQ in children between 8-13 years old in China due to too much intake of fluoride (Huff, 2010).

• In another study, the sample size was ~8,000 school aged children. Average IQ loss had a mean of 0.45 which was about 7 points of IQ.

• Studies have been conducted on animals to see the effects of fluoride on the brain. Most of the adverse effects are displayed in the brain. There are numerous accounts of neuronal damage and protein production and expression (Connet 2012). Results also showed that fluoride directly effects the pineal glands ability to efficiently excrete hormones, especially during the puberty stages of animals tested (Luke, 1997).

• Another result that showed up in various studies was that there was alterations in neurotransmitter activity. Fluoride also has effects on oxidative processes, perhaps due to its reactivity, and also reduces antioxidant levels in response to these oxidative processes (Connet 2012).

DISCUSSION

• Based off the results from Lewis and Milgrom (2003) we can see that over the decades fluoride use has improved the health of our teeth. Going off more of the results we found through our research there is an indication that fluoride is causing possible brain damage in other species, like animals, and impacting neurological development in children.

• We also have the result of Fluoride toxicity, when too high a dosage has been consumed. Lets think about what can be toxic to us, everything right. Things are great in moderation but too much of one thing, or too high a dose, can be toxic. Fluoride is beneficial and can be very toxic.

• Over the decades the use of fluoride has indeed improved dental care, it is in nearly all toothpastes and put in our water sources. Now with that said too much of it can be leading to severe complications such as neurological effects of multi-organ shut down.

SUMMARY & CONCLUSION• In summary fluoride is good for our teeth with its mechanisms of action that

inhibit bacteria from forming caries in out teeth. Also, fluoride does impact neurological development in children, damages the brain in other species, and can lead to multiple organ failure.

• The main knowledge we hope you gain from this is there are risks and benefits. Again, everything can be toxic depending on the dosage. Like medicine, there is still a lot more work to be done in the area of deciding appropriate dosing and how to minimize the associated risks in order to reap full benefits. Hopefully future studies will recognize what works for one species may not for another, for example on dosing due to different bodily mechanisms of action. Maybe in the future the perfect calculation based off of physical, mental, environmental, etc. will be able to specify specific doses tailed to ear individual. No free lunch.

INTERESTING THEORIES• The pineal gland has been called

the" third eye" or the "seat of the soul". It has been found been found in Egyptian symbols, where people recognized the pineal gland to resemble an eye?!

• There has been a movement of removing fluoride from the body and using un-fluorinated toothpastes and such.

• Conspiracy theories say it is an attempts to limit population size and gain control of "The People".

• (Bancarz, 2014)

REFERENCESBancarz, S. (2014, January 18). Proof That The Pineal Gland Is Literally A 3rd Eye. Retrieved April 20, 2015, from http://www.spiritscienceandmetaphysics.com/proof-that-the-pineal-gland-is-a-3rd-eye/

Connet, M. (2012, August 30). Fluoride's direct effect on brain: Animal studies. Retrieved March 23, 2015, from http://fluoridealert.org/studies/brain04/

Dwyer, M. (2012, July 25). Impact of fluoride on neurological development in children. Retrieved March 23, 2015, from http://www.hsph.harvard.edu/news/features/fluoride-childrens-health-grandjean-choi/

Huff, E. (2010, December 23). Study: Fluoridated water causes brain damage in children. Retrieved March 23, 2015, from http://www.naturalnews.com/030819_fluoride_brain_damage.html

Lewis, C., & Milgrom, P. (2003). Fluoride. Pediatrics in Review, 24(10), 327-336. Retrieved March 23, 2015, from http://pedsinreview.aappublications.org/content/24/10/327.full

Liu, H., Hung, H., Hsiao, S., Chen, H., Yen, Y., Huang, S., ... Lu, Y. (2013). Impact of 24-month fluoride tablet program on children with disabilities in a non-fluoridated country. Research in Developmental Disabilities, 34(9), 2598-2605. Retrieved March 24, 2015, from http://www.sciencedirect.com/science/article/pii/S089142221300190X

REFERENCES

Luke J. (1997). The Effect of Fluoride on the Physiology of the Pineal Gland. Ph.D. Thesis. University of Surrey, Guildford. p. 172-173.

Marquis, Rober E (1995) Antimicrobial Actions of Fluoride For Oral Bacteria, Can J Microbiol , 41.11 (1995) pg 955-964. Retrieved April 22, 2015.

Nouri R M, Titley K C. ( 2003, January 1 ) Paediatrics: A Review of the Antibacterial Effect of Fluoride. Retrieved April 22, 2015 from http://www.oralhealthgroup.com/news/paediatrics-a-review-of-the-antibacterial-effect-of-fluoride/1000118049/?&er=NA

Shin, R. (2014, January 21). Fluoride Toxicity . Retrieved March 24, 2015, from http://emedicine.medscape.com/article/814774-overview\