How Chronic Fluoride Can Damage Mitochondria And The Gut Biome

The Effects Of Chronic Fluoride On The Body



Fluoride is a trace element, but it is found in our daily exposure more than a “trace”. R

In small amounts, it appears to be okay. R

The problems with fluoride appear to be in chronic use of it over long periods of time and/or being exposed to a high dose of it in a single instance. R

Apart from the effects on skeletal tissue and teeth, fluoride can cause changes in the kidneys, liver, thyroid, pituitary gland, testis, muscle tissues, stomach, brain, neurons, and immune system. R

I have mild dental fluorosis, probably from drinking too much fluoridated water, using fluoridated toothpaste, along with taking fluoride at the dentist to protect my enamel, so I will cover a little bit of fluorosis as well. 

In this post I will be discussing how fluoride works on the body and what you can do to protect yourself.


  1. Basics
  2. How Fluoride Affects The Whole Body
  3. How To Prevent Toxicity And Testing
  4. Mechanism Of Action
  5. Genetics
  6. More Research 


Fluoride is an element that is toxic to the body. R R R R

Chronic exposure to fluoride seems to be bad, whereas acute exposure once in a while probably isn’t that bad, and may have some benefits (not recommended). R

It has been added to our water to strengthen our bones and act as a microbial.

It has also been added to toothpaste to strengthen our teeth and protect against tooth decay. R R

Some believe it calcifies your “third eye” as you may see calcification of the pineal gland with age in x-rays (partially true). 

The US Department of Health and Human Services’s National Toxicology Program addresses that fluoride under the World Health Organization’s (WHO) set levels may cause neurological problems, depression, anxiety and other functional problems. R

Billions of people are exposed to fluoride daily. R R R R

How Fluoride Affects The Whole Body

1. Affects The Brain and Central Nervous System



Fluorine is toxic to the central nervous system (CNS), in both human developmental stages and adulthood (more on development below). R R R

Fluoride causes neuroinflammation (inflammation in the brain). R R R R

For example, fluoride creates oxidative stress and shrinkage of the brain, especially the cerebellum and hippocampus. R R R

One way it does this is by fluoride’s ability to crosses the blood brain barrier, accumulate in neurons, and create higher amounts of advanced glycation end products (AGEs), which cause free radicals in the brain. R

Fluoride changes the metabolism of neurotransmitters (mainly glutamate neurotransmission). R

For example, fluoride at normal drinking water levels causes changes in the secretion of serotonin, dopamine, norepinephrine, acetylcholine and epinephrine. R R

Fluoride may affect cognition as well.

For example, higher fluoride intake is associated with lower IQ. R R R

In animal models, fluoride exposure decreases spacial memory and learning capacity. R R R

Fluoride also causes improper glucose utilization in the brain. R

High fluoride intake is associated with demylination and smaller dendritic size of neurons. R R

Fluoride also changes the pH of brain cells and causes DNA damage to brain cells. R R

Fluoride may also cause paralysis. R

2. Affects Mitochondria And Inflammation

Fluoride causes mitochondria to produce less energy. R

For example, fluoride decreases the ability for cells to utilize glucose effectively. R

It also decreases ATP production in immune cells and blood cells. R R

Fluoride also increases free radicals in cells, such as reactive oxygen species (ROS), while decreasing cell’s abilities to clean it up (aka oxidative stress and inflammation). R

This degrades mitochondrial DNA and causes apoptosis (cell death). R 

This ROS may be beneficial, as in an adaptive response (called Hormesis), fluoride may upregulate some beneficial genes such as SIRT1 (good for longevity), Klotho (good for intelligence) and UCPs (good for making brown fat). R R

Fluoride also causes stress in the endoplasmic reticulum (ER). R R R

3. Affects Circadian Rhythms

Fluoride may affect circadian rhythms. 

For example, fluoride decreases a protein called Rab-10, which interacts with melatonin receptors. R R

Also, fluoride interacts with another protein called CK1ε, which is a regulator of the central clock in the suprachiasmatic nucleus. R R

4. Alters The Gut Microbiome And Is An Antimicrobial



Fluoride may make alcohol more damaging to the gut. R

It also has an effect on gut bacteria.

For example, fluoride can inhibit biofilms of certain bacteria. R R R

It may also alter the gut microbiome by increasing Escherichia coli and Enterococcus spp while decreasing Lactobacillus spp. and Bifidobacterium spp. R

Fluoride can also fight some pathogens (bacteria and fungi): R

  • Candida albicans R
  • Pseudomonas aeruginosa R
  • Staphylococcus aureus R
  • Streptococcus mutans R R

5. Alters Development

Exposure to fluoride in the womb changes the brain and metabolism, causing problems with memory and learning later on in life. R R R R R

After birth, fluoride can be transferred from the mother to the child via breast milk. R

Mothers who chronically consume fluoride may have children with lower abilities to produce antioxidants. R

In geographical areas where the amounts of fluoride are higher, children are correlated to having significantly lower intelligence (may be influenced by COMT, see below). R R R R

There is also a higher prevalence of attention deficit disorder in children exposed to higher levels of fluoride in their drinking water. R

6. Affects The Immune System

In animal studies, fluoride causes toxic effects to the development of the spleen. R

In humans, fluoride causes immune cells to self destruct. R

Fluoride also causes a decreased function of the immune system in:

  • Spleen R R
  • Thymus R R

Having dental fluorosis my increase levels of sIgA and sIgG. R

By causing cell death, fluoride may have a protective effect against cancer. R

7. Affects Hormone Status

Chronic use of fluoride may decrease leptin levels. R R

It may also decrease estrogen levels and gonadotropin-releasing hormone (GNRH). R

Vitamin D may prevent fluorosis. R

8. Affects The Sex Organs



Fluoride may damage sex organs and reproduction.

For example, female rats exposed to chronic fluoride had less children. R

In multiple studies with male rats, fluoride consumption could damage the testicles. R R R R

Fluoride may also decrease sperm count. R R

Vitamin E and calcium may protect the testicles from fluoride damage. R

9. Affects The Thyroid

Fluoride prevalence in water may predict hypothyroidism. R

Excess fluoride can cause damage to the thyroid. R

For example, fluoride can increase parathyroid hormone (PTH), but reduce total T3 (TT3), total T4 (TT4) free T3 (FT3), and free T4 (FT4). R R R

Taurine may stabilize some of these hormonal changes to the thyroid. R

10. Affects Fat Cells and Pancreas

Fluoride can cause insulin levels to rise without the presence of sugar. R

Fluoride may also cause decreased insulin sensitivity. R R R

11. Affects The Lungs

Chronic exposure to fluoride may build up in the lungs and cause lung damage. R R

12. Affects The Heart

Fluoride may increase blood pressure. R

Fluoride can also increase lactate in the heart. R

Fluoride intake may also increase triglyceride levels and increase the risk for atherosclerosis. R R

Fluoride may also inhibit the formation of blood clots. R 

13. Affects The Liver

Excessive and chronic fluoride intake may reduce antioxidants in the liver of adults and children. R R R

In animal models, consuming fluoride during pregnancy reduces antioxidants in the offsprings liver. R

Also in animal models, chronic fluoride consumption causes DNA damage to liver cells and for those cells to die. R R R R

Some of the toxic effects to the liver can be mitigated by calcium, Vitamin EVitamin C, and resveratrol. R R

Fluoride may also reduce phosphatidylethanolamine (PE), phosphatidylcholine (PC) and phosphatidylserine (PS) levels in the liver. R

14. Affects The Kidneys



Fluoride consumption may cause damage to the kidneys. R

Fluoride’s synergistic effect with heavy metals may make kidney damage worse. R

Vitamin Ccurcumin, and taurine may protect the kidneys from fluoride exposure. R R

15. Affects Our Bones And Teeth

Fluoride stores itself in bones and in teeth. R R

Chronic use of fluoride may cause bone cells to die, while small amounts may cause them to grow. R R R

For example, dental fluorosis happens when there is too much stress on bone cells. R R R R

One way it does this is by fluoride’s ability to damage enamel cells. R R R

Another way by fluoride’s ability to demineralize teeth. R R

For example, fluoride changes calcium homeostasis in bones. R R R R

It can also disturb the collagen levels in bone. R R

Fluoride can also cause skeletal fluorosis by disrupting proper bone turnover. R R

Fluoride has also been implicated to cause spinal canal stenosis (narrowing of the spinal canal). R

It also may inhibit bone growth and development by decreasing IGF1 expression. R R

Fluoride in water, toothpaste, and mouthwash may help against tooth decay since it’s small amounts. R R

One way it does this is by decreasing the loss of dentin. R R

16. Alters Hair Growth

By increasing oxidative stress in hair follicles, fluoride may cause slow hair growth and hair loss. R

For example, mice exposed to chronic fluoride had alopecia and less fur. R

17. May Cause Death

High levels of fluoride is deadly. R

Fluoride may cause a potassium imbalance in the heart and cause death. R

Also in animal studies, mice exposed to chronic fluoride died faster than control groups. R

How To Prevent Toxicity And Testing



Supplements and Actions 


Protective Supplements:

Fluoride Causes These Deficiencies:


  • 4-phenylbutyrate (4PBA) R
  • Teriperatide R


  • Activating AQP5 R
  • Activate FOXO1 R
  • Activate NRF2 R
  • Activate SIRT1 R

Foods/Liquids To Watch Out For

Although naturally occurring, fluoride can be found in various foods, teas, and supplements indirectly. R

Here are a few examples:

  • Beer R R
  • Coffee R
  • Krill Oil R
  • Infant Formula R
  • Prepackaged Foods (if made using fluorinated water) R
  • Rice R
  • Table Salt
  • Tea (although the polyphenols in tea may protect against fluoride’s effect on bones) R R R R
  • Wine R

Water Alternatives



First of all, stay away from unfiltered tap water. R R R R

I use glass spring water and will also use a berkey filter

Toothpaste Alternatives



The benefits to teeth do not outweigh the negatives of our body so it’s probably best to stay away from conventional toothpastes and mouthwashes. R R

For example (if you couldn’t already feel this when using mouthwash yourself), fluoride causes oxidative stress on salivary glands. R

Alternative mouthwashes:

Recommended toothpastes (also watch out for brands with sodium lauryl sulfate): R


You can test your water with this water test.

Here are other possible biomarkers:

  • Calcification of the pineal gland (other contributing factors to this) R R
  • Fluoride in blood or urine R
  • γH2AX R
  • p-ATM R
  • 8-oxoguanine R

What Makes Fluoride Exposure Worse?

  • Aging R
  • Alcohol R
  • Aluminum R R
  • Arsenic R
  • Cadmium R
  • Coal burning – fluorine in coal can be easily released into the atmosphere by burning and can then be taken in by breathing R
  • Lead R

Mechanism Of Action


  • Decreases Acetylcholine R
  • Decreases α3 nAChR R
  • Decreases α4 nAChR R
  • Decreases α7 nAChR R
  • Decreases CK1ε R
  • Decreases CORO1A R
  • Decreases DA R R R
  • Decreases FEZ1 R
  • Decreases Glutamate (when chornically exposed, will increase glutamate when ingested acutely) R R R
  • Decreases Glutathione R
  • Decreases GLUT1 R
  • Decreases GPD1R
  • Decreases GPx R
  • Decreases GSTP1 R
  • Decreases IGF1 R
  • Decreases IL-2 R
  • Decreases IL-10 (increased in spleen) R R
  • Decreases MAPK R
  • Decreases Mfn1 R
  • Decreases mGluR5 R
  • Decreases MMP2 R
  • Decreases MMP9 R R
  • Decreases MMP-20 R
  • Decreases M1 mAChR R
  • Decreases M3 mAChR R
  • Decreases NE R
  • Decreases PDI R
  • Decreases PEBP1 R
  • Decreases Pleiotrophin R
  • Decreases RACK1 R
  • Decreases Rab-1A, Rab-1B, Rab-3A, Rab5b, Rab5c, Rab-8B, Rab-10, Rab-14, and Rab-26 R
  • Decreases SOD R
  • Decreases TGFB-1 R R R
  • Increases α-Klotho R
  • Increases Casr R
  • Increases AGEs R
  • Increases BDNF R
  • Increases CAT R
  • Increases Cbfa1 R
  • Increases CGRP (with high exposure it decreases) R
  • Increases CK-MB R
  • Increases Drp1 R
  • Increases Epinephrine R
  • Increases Fgf1rc R
  • Increases Fis1 R
  • Increases GFAP R
  • Increases Histamine R
  • Increases ICAM1 R
  • Increases IL-1b R
  • Increases IL-6 R
  • Increases IL-8 R
  • Increases LDH R
  • Increases MCP1 R
  • Increases MDA R
  • Increases NRF2 R
  • Increases NO R
  • Increases NOX2 R
  • Increases OCN R
  • Increases P-sel R
  • Increases PTH R
  • Increases RAGE R
  • Increases ROS R
  • Increases Serotonin R
  • Increases SIRT1 R
  • Increases SP R
  • Increases TIPM1 R
  • Increases TNF-alpha (decreased in the spleen) R R
  • Increases UCP1 R
  • Increases UCP2 R
  • Increases VCAM1 R
  • Increases VDR R
  • Increases VIP R


  • Fluoride is the ionic form of fluorine, a halogen with the most electronegative elements on the periodic table. R
  • When combined with hydrogen, it forms the acid hydrogen fluoride, which is easily absorbed into tissue in the body. R
  • For example, in the gut, 50% of ingested fluoride is absorbed within 30 minutes and 80% is absorbed if there are no cations or calcium being digested. R
  • 99% of the body’s fluoride is found in calcified tissues, which it is strongly bound, but not irreversibly. 
  • Fluoride is excreted through the kidneys, which takes about 30-40min per ml, and 75mintues per ml when filtereing serum fluoride. R
  • In bacteria, fluoride inhibits bacteria’s ability to uptake glucose, thus helping protect against bacterial growth in the mouth and plaque fluid, although this same action is damaging to the gut microbiome as well. R
  • In the hippocampus, fluoride can decrease in the expression of tubulins forming the heterodimers (Tuba1 and TubB2a). R
  • Also in the hippocampus, fluorine causes a increase in the outflow of cholride ions from the cells by changing the activity of mitogen-activated protein kinases (MAPK), which is necessary for volume and activity of neurons. R
  • Fluoride also causes lowers amounts of  neural cell adhesion molecules (NCAM), glial fibrillary acidic protein (GFAP), and increased brain-derived neurotrophic factor (BDNF). R
  • Fluorine, via Ras, can change the activity of ERK-JNK and p58, leading to less growth and differentiation of cells, as well as problems with apoptosis and gene expression. R
  • In grey matter, fluorine decreases the content of Nissl bodies (which makes brain matter gray), which are concentrations of ribosomes and RNA in neurons. R
  • In the cell, fluorine changes the flow of ions and water from the cytoplasm to the extracellular space. R
  • Fluorine decreases the ability for mitochondria to use glucose properly, decreasing the expression of GLUT1. R
  • Fluroine also increases the activity of ATP5h (creating a disbalance between ATP and ADP), as well as decreasing NADH-ubichinon oxidorecductase, and a decrease in the activity of complexes I, II, III, and IV. R
  • Thus fluorine creates more ROS in the mitochondria and degrades mitocnohdrial DNA, leading to cell death. R
  • Apart from more ROS, there is more malondialdehyde (MDA), catalyase (CAT), hydroxide (OH), and nitric oxide (NO), as well as decreased superoxide dismutase (SOD),  glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione. R
  • This change in antioxidants causes a shorter lifespan of cells, growth problems, and cell death. R
  • Fluorine increases the activity of AGE receptors (RAGE) and NADPH oxidase 2 (NOX2), initiating NF-kB and causing increased ROS and demyelination of dendrites and degeneration of neurons. R R
  • Prolonged exposure to fluorine decreases the concentration of glutatmate in the brain (serum, hippocampus, and cerebral cortex), which is a downregulation mechanism to protect the brain as bergmann gilal cells (BGC) die. R 
  • This lowers aspartate transaminase (AST) and alanine aminotransferase (ALT) and decreased plasticity and “spacial learning” in the brain from decreased ability of mGluR1 and mGluR5. R
  • Fluorine also changes the secretion of serotonin, dopamin
    e, histamine, norepinephrine, acetylcholine, and epinephrine, at normal concentrations in drinking water, for example drinking water at 100mg/L caused increase in hippocampla, striatal and cerebral cortex noradrenalin and serotonin. R R
  • Fluorine influences the activity of complexes of the respiratory chain and of enzymes of the citric acid cycle as seen with a decrease in the activity of complexes I, II, III and IV; isocitrate dehydrogenase and succinate dehydrogenase was observed in the cerebral cortex, cerebellum and hippocampus of mice exposed to high concentrations of fluorine. R
  • Fluoride may decrease learning by decreasing α3, α4,  and α7 nicotinic acetylcholine receptors (nAChRs) as well as M1 and M3 muscarinic acetylcholine receptors (mAChRs). R R R
  • In duodenum, fluoride exposure increases wall thickness as well as vasoactive intestinal polypeptide (VIP), calcitonin gene related peptide (CGRP) and substance P (SP). R
  • Fluoride also downregulates Pleiotrophin and its respected proteins, protein disulfide-isomerase (PDI), guanine nucleotide-binding protein subunit beta-2-like 1 (RACK1), glycerol-3-phosphate dehydrogenase [NAD(+)]-cytoplasmic (GPD1), and Glutathione S-transferase P (GSTP1). R
  • Fluoride decreases Ras-related protein Rab-1A, Rab-1B, Rab-3A, Rab5b, Rab5c, Rab-8B, Rab-10, Rab-14, and Rab-26. R
  • Rab-10 interacts with Melatonin receptor type 1A, which mediates circadian actions of melatonin. R 
  • Fluoride also interacts with Casein kinase 1 epsilon (CK1ε), a Ser-Thr protein kinase that acts as a key regulator of the central clock in the suprachiasmatic nucleus and that is also involved in circadian regulation of gene expression. R R R
  • Fluoride also downregulates Phosphatidylethanolamine-binding protein 1 (PEBP1, a synaptic signaling protein which helps neuronal survival), Fasciculation and elongation protein zeta-1 (FEZ-1, affects mitochondrial motility and neuronal morphology), and Coronin-1A (CORO1A, involved in cytoskeleton organization and rearrangement in neuronal cells). R R R R
  • In the heart and kidneys, fluoride can increase myeloperoxidase, xanthine oxidase, blood urea nitrogen, creatinine, Lactate dehydrogenase (LDH), Creatinine kinase myocardial band (CK-MB), P-selectin (P-sel), vascular cell adhesion molecule-1(VCAM-1), and IL-8. R R
  • In the kidneys fluoride causes a significant increase in the levels of thiobarbituric acid reactive substances and reduced the GSH concentration and the activities of SOD and catalase. R
  • Fluoride also increases the levels of urea, uric acid, blood urea nitrogen, creatinine, and phosphate and decreasing the levels of calcium. R
  • In the spleen, fluoride causes an increase in Interleukin 10 (IL-10), with a decrease in TNF-a, interleukin 2 (IL-2), transforming growth factor beta (TGF-beta), interferon gamma (IFN-gamma) and cyclin (E/D and CDK2/4). R
  • Fluoride causes ameloblasts (enamel tooth cells) to decrease ameloblastin and to go into apoptosis. R
  • Fluoride activates the Rho/ROCK pathway in ameloblasts,  inducing endoplasmic reticulum (ER) stress, leading to protein misfolding. R R



  • rs923911 (CA or CG) + rs1996315 (CA or CG) has have a protective effect against caries R


  • PvuII – PP (carrying two dominant) alleles had a significantly increased risk of dental fluorosis compared with
    those bearing 2 copies of the p (minor) allele R


  • rs4680 – Val/Val homozygote showed lower IQ scores in children than those with Met/Met homozygote or Met/Val heterozygote R


  • C1377T – CC had higher prevalence of fluorosis followed by TT R
  • Unknown SNP – TC & TT alleles had higher prevalence of F bone injury risk than the CC genotype R




  • rs2615487 – CC allele protective effect against carries R


  • rs3798577 – CG heterozygote had lower GNRH than women were carrying C/C, C/T or T/T R


  • rs1394205 – AA allele had lower serum E2 level in those chronically exposed to fluoride R 


  • rs2235091 – GC allele have protective effect against carries vs risk haplotype GG R
  • rs198969 – GC allele have protective effect against carries vs risk haplotype GG R


  • rs1695 – GG allele had a significantly decreased risk of skeletal fluorosis vs AA R


  • rs2287074 – AA alleles had about 80 percent lower probability of developing skeletal fluorosis than GG genotype in Tibetans R


  • rs2333227 – AA allele might increase the risk of fluorosis R
  • rs61007103 -TT allele might increase the risk of fluorosis R
  • rs12601419 – AA allele might increase the risk of fluorosis R
  • rs34721594 – TT allele might increase the risk of fluorosis R


  • rs1341239 – T allele decreases the risk of brick tea SF R



  • rs2228570 – CT/TT allele  had a significantly decreased risk of skeletal fluorosis compared to CC R
    – CC allele has higher risk of male factor infertility R

More Research

  • Fluoride is toxic to worms. R
  • In zebrafish, fluoride activates NRF2. R
  • 50 Reasons To Oppose Fluoridation R