Fluoride Action Network

Fluoride & the Brain

FAN Science Watch | Feb. 22, 2004 | By Michael Connett

The goal of this newsletter will be to keep FAN members abreast of the latest studies and reports on fluoride’s toxicity. Many of the studies and reports which we will be posting – like the one below – come directly from the US National Library of Medicine’s online database PubMed. See: http://www.ncbi.nlm.nih.gov/PubMed/

One of the benefits of PubMed is that it picks up studies written in other languages that would otherwise be inaccessible to the English speaking world. This is particularly important with a subject like fluoride, since much of the key research on fluoride & health is currently being conducted in China and India – where researchers aren’t thwarted by the type of political obstacles that make intelligent research in the United States so difficult.

The recent experience of the US scientist Dr. Phyllis Mullenix is a particularly telling example of the political obstacles thwarting good, essential research in the US. Whereas Dr. Mullenix got fired for publishing results suggesting that fluoride was a neurotoxin (i.e. that it damaged the brain), researchers in China are now regularly reaching this conclusion. Instead of getting fired, however, these China scientists seem able to secure more funding for additional research.

The most recent Chinese study on fluoride & the brain was posted on PubMed just last week (see abstract below). The study looked at the effect of fluoride on the hippocampal region of rat brain, and concluded that: “Fluoride may go through the blood-brain barrier and accumulate in rat hippocampus, and inhibit the activity of cholinesterase.”

These findings are of particular interest in light of Mullenix’s own findings. According to Mullenix (1995):

“Hyperactivity and cognitive deficits are generally linked with hippocampal damage, and in fact, the hippocampus is considered to be the central processor which integrates inputs from the environment, memory, and motivational stimuli to produce behavioral decisions and modify memory… Overall, the behavioral changes from fluoride exposure are consistent with interrupted hippocampal development. Whether the hippocampus is indeed the brain region most susceptible to fluoride is a possibility deserving consideration in future studies”

Below, I have posted the full abstract of the new study. I have also posted a bibliography (in chronological order) of recent studies on fluoride & the brain.

Michael Connett
Editor, FAN Science Watch



Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2003 Apr;21(2):102-4.

[Studies on fluoride concentration and cholinesterase activity in rat hippocampus]

[Article in Chinese]

Zhai JX, Guo ZY, Hu CL, Wang QN, Zhu QX.
School of Public Health, Anhui Medical University, Hefei 230032, China.

OBJECTIVE: To study the accumulation of fluoride in rat hippocampus and its effect on cholinesterase activity. METHODS: Rats were subchronically exposed to NaF, and fluoride concentration and cholinesterase activity in rat hippocampus were determined. RESULTS: Fluoride concentration in rat hippocampus was significantly correlated with the dosage of fluoride, and there were significant differences among high dosage group [(13.03 +/- 1.79) micro g/g], low dosage group [(9.83 +/- 0.92) micro g/g] and control [(8.27 +/- 1.11) micro g/g], P < 0.01.Acetylcholinesterase activities among three groups [(0.111 +/- 0.031) micro mol/mg, (0.143 +/- 0.025) micro mol/mg, (0.183 +/- 0.027) micro mol/mg] were also significantly different (P < 0.01), which was negatively correlated with fluoride concertration in rat hippocampus (r = -0.700, P < 0.01). The activity of butylcholinesterase in high dosage group [(0.041 +/- 0.010) micro mol/mg] was different from that of control [(0.067 +/- 0.025) micro mol/mg, P < 0.05], but the activity was not significantly related with fluoride concertration in rat hippocampus (r = -0.317, P = 0.094). CONCLUSION: Fluoride may go through the blood-brain barrier and accumulate in rat hippocampus, and inhibit the activity of cholinesterase.

PMID: 14761523 [PubMed – in process]



Chen J, et al. (2003). Selective decreases of nicotinic acetylcholine receptors in PC12 cells exposed to fluoride. Toxicology 183(1-3):235-42.

Shashi A. (2003). Histopathological investigation of fluoride-induced neurotoxicity in rabbits. Fluoride 36: 95-105.

Xiang Q, et al. (2003). Effect of fluoride in drinking water on children’s intelligence. Fluoride 36: 84-94.

Zhai JX, et al. (2003). [Studies on fluoride concentration and cholinesterase activity in rat hippocampus]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 21(2):102-4.

Long YG, et al. (2002). Chronic fluoride toxicity decreases the number of nicotinic acetylcholine receptors in rat brain. Neurotoxicology and Teratology 24(6):751-7.

Bhatnagar M, et al. (2002). Neurotoxicity of fluoride: neurodegeneration in hippocampus of female mice. Indian Journal of Experimental Biology 40: 546-54.

Chen J, et al. (2002). [Studies on DNA damage and apoptosis in rat brain induced by fluoride] Zhonghua Yu Fang Yi Xue Za Zhi36(4):222-224.

Shivarajashankara YM , et al. (2002). Brain lipid peroxidation and antioxidant systems of young rats in chronic fluoride intoxication.Fluoride 35: 197-203.

Shivarajashankara YM , et al. (2002). Histological changes in the brain of young fluoride-intoxicated rats. Fluoride 35(1): 12-21.

Ekambaram P, Paul V. (2001). Calcium preventing locomotor behavioral and dental toxicities of fluoride by decreasing serum fluoride level in rats. Environmental Toxicology and Pharmacology 9(4):141-146.

Zhang Z, et al. (2001). [Effects of selenium on the damage of learning-memory ability of mice induced by fluoride]. Wei Sheng Yan Jiu. 30(3):144-6.

Calderon J, et al. (2000). Influence of fluoride exposure on reaction time and visuospatial organization in children. Epidemiology11(4): S153.

Lakshmi Vani M, Pratap Reddy K. (2000). Effects of fluoride accumulation on some enzymes of brain and gastrocnemius muscle of mice. Fluoride 33: 17-26.

Lu XH, et al. (2000). Study of the mechanism of neurone apoptosis in rats from the chronic fluorosis. Chinese Journal of Epidemiology19: 96-98.

Lu Y, et al (2000). Effect of high-fluoride water on intelligence of children. Fluoride 33:74-78.

Shao Q, et al. (2000). [Influence of free radical inducer on the level of oxidative stress in brain of rats with fluorosis]. Zhonghua Yu Fang Yi Xue Za Zhi 34(6):330-2.

Sun ZR, et al. (2000). Effects of high fluoride drinking water on the cerebral functions of mice. Chinese Journal of Epidemiology 19: 262-263.

Sarri E, Claro E. (1999). Fluoride-induced depletion of polyphosphoinositides in rat brain cortical slices: a rationale for the inhibitory effects on phospholipase C. International Journal of Developmental Neuroscience 17(4):357-67.

van der Voet GB, et al. (1999). Fluoride enhances the effect of aluminium chloride on interconnections between aggregates of hippocampal neurons. Archives of Physiology and Biochemistry 107(1):15-21.

Zhang Z, et al. (1999). [Effect of fluoride exposure on synaptic structure of brain areas related to learning-memory in mice] [Article in Chinese]. Wei Sheng Yan Jiu 28(4):210-2.

Calvert GM, et al. (1998). Health effects associated with sulfuryl fluoride and methyl bromide exposure among structural fumigation workers. American Journal of Public Health 88(12):1774-80.

Guan ZZ, et al (1998). Influence of chronic fluorosis on membrane lipids in rat brain. Neurotoxicology and Teratology 20: 537-542.

Paul V, et al. (1998). Effects of sodium fluoride on locomotor behavior and a few biochemical parameters in rats. Environmental Toxicology and Pharmacology 6: 187–191.

Varner JA, et al. (1998). Chronic administration of aluminum-fluoride and sodium-fluoride to rats in drinking water: Alterations in neuronal and cerebrovascular integrity. Brain Research 784: 284-298.

Zhao XL, Wu JH. (1998). Actions of sodium fluoride on acetylcholinesterase activities in rats. Biomedical and Environmental Sciences 11(1):1-6

Issacson R, et al. (1997). Toxin-induced blood vessel inclusions caused by the chronic administration of aluminum and sodium fluoride and their implications for dementia. Annals of the New York Academy of Science 825: 152-166.

Wang Y, et al. (1997). [Changes of coenzyme Q content in brain tissues of rats with fluorosis]. Zhonghua Yu Fang Yi Xue Za Zhi. 31: 330-3.

Zhao LB, et al (1996). Effect of high-fluoride water supply on children’s intelligence. Fluoride 29: 190-192.

Li XS. (1995). Effect of Fluoride Exposure on Intelligence in Children. Fluoride 28(4):189-192.

Mullenix P, et al. (1995). Neurotoxicity of Sodium Fluoride in Rats. Neurotoxicology and Teratology 17:169-177.

Li Y, et al. (1994). [Effect of excessive fluoride intake on mental work capacity of children and a preliminary study of its mechanism]Hua Hsi I Ko Ta Hsueh Hsueh Pao. 25(2):188-91.

Shashi A, et al. (1994). Effect of long-term administration of fluoride on levels of protein, free amino acids and RNA in rabbit brain.Fluoride 27: 155-159.

Yang Y, et al. (1994). [Effects of high iodine and high fluorine on children’s intelligence and the metabolism of iodine and fluorine].Zhonghua Liu Xing Bing Xue Za Zhi.15(5):296-8.

Du L. (1992). [The effect of fluorine on the developing human brain]. Chung-hua Ping Li Hsueh Tsa Chih. 21(4):218-20.

Lin Fa-Fu; et al (1991). The relationship of a low-iodine and high-fluoride environment to subclinical cretinism in Xinjiang. Iodine Deficiency Disorder Newsletter Vol. 7. No. 3.