HISTORY:FLUORIDE-IODINE ANTAGONISM

SOME HISTORY: 

In 1854 Maumene feeds 10g sodiumfluoride (4.5g F-) to a dog and causes a goiter to appear. He was the first to consider fluorides as a cause of goiter.

[Burgi (1984) writes:”Not unexpectedly the dog tried and ran away and succeeded to escape from such harsh treatment.” Todays fluoride content in dog food: “low” -> 55 ppm (mg/kg) high -> 460 ppm (mg/kg)]

Pighini (1923) is also able to cause goiters in rats, dogs and chicken.

Goldemberg (1926, 1930) is the first to take advantage of the iodine-fluoride antagonism and begins to use fluorides to cure Basedow’s disease (Graves’ Disease).

May (1935, 1937) follow suit. In 1950 May publishes his findings that addition of thyroxine (T4) raised the iodine level in the blood, while the addition of fluorides lowered the iodine level in blood.

Litzka (1937) discusses the mode of action in of fluorides in treating patients with Graves’ disease: fluoride antagonizes thyroid hormone effects on liver metabolism.

Wilson and DeEds (1940) report that dental fluorosis is a result of the synergistic action of fluoride and the thyroid. Results are “strikingly clearcut”.

Wilson (1941) reports in the Lancet on his findings that mottling of teeth is prevalent in the same areas in the UK which had been previously prevalent with goitre.

1944 editorial in the Journal of the American Dental Association (JADA) states:

“We do know that the use of drinking water containing as little as 1.2 to 3ppm of fluorine will cause such developmental disturbances in bones as osteosclerosis, spondylosis and osteopetrosis, as well as goitre”. 

Steyn (1948, 1955) finds that fluoride has a thyrostatic effect. He investigates the incidence of endemic goitre (fluorine -induced) in the North Western Cape Province in South Africa and reports that his findings closely agree with the above JADA editorial.

Wespi finds mottled teeth (dental fluorosis) together with goiters in Italy. (1954)

Korrodi, Wegmann, Galetti and Held (1955) also verify a fluoride – iodine antagonism, proclaiming that the fluoride ion pushes out the iodine in the thyroid gland.

Galetti et al (1957) treats hyperthyroid patients with fluoride, and documents a significant reduction in protein-bound iodine, as well as an overall reduction of iodine and a reduction of iodine uptake by the thyroid gland.

Jentzer (1959) further shows reduced iodine levels under the influence of fluorides.

In 1960 Gordinoff and Minder describe the results of experiments with radioactive iodine (I131) which show that fluorides remove an iodine atom. Effects were dose-responsive, meaning the higher the fluoride intake the lower the iodine measurements.

Steyn writes in 1962 that drinking water containing as little as 1 to 2 ppm of fluorine can cause serious disturbances of general health and especially in normal thyroid gland function and in the normal processes of calcium-phosphate metabolism (parathyroid function).

In 1963 Gorliter von Mundy reports on the [then] current knowledge gained from experiments with I131 as to how the effects of the enzyme responsible for the T4 to T3 conversion were inhibited if a fluorine ion was absorbed before the conversion was supposed to happen.

Pastan et al (1968), Rodesch et al (1969), and Zor et al, (1969) report that fluoride mimicks TSH.

In 1969 Siddiqui show small visible goiters in persons 14 to 17 years of age in India to be connected directly to high fluoride concentrations in drinking water.

Ahn and Rosenberg (1970) report that fluoride mimicks TSH.

Willems et al (1972) document that sodium fluoride blocks thyroid hormone secretion.

Also in 1972 Day and Powell-Jackson studied 648 people in 13 mountaineous regions in Nepal where the iodine content in the water was low and found a close relationship between fluoride intake and the incidence of goiter.

Bobek and Kahl (1976) document that rats on 1.0 mg fluoride daily from drinking water had significantly lowered T4, T3, and free thyroxine index in plasma.

In 1978 George Waldbott writes that in most cases of poisoning from fluoridated water in which he had occasion to study the action of the thyroid gland, it’s function was low. He cites a case of a 33-year-old male who exhibited typical manifestations of pre-skeletal fluorosis and a basal metabolism rate of -22, indicative of hypothyroidism. Within three months after the man ceased consuming fluoridated water, the thyroid function had returned to normal (BMR=0) In addition, Waldbott writes that “simultaneously, other symptoms associated with low grade fluoride poisoning – including excessive thirst, headaches, blurred vision, arthritis in shoulders, elbows, knees, and gastrointestinal disturbances – also disappeared.” [He did not know that the symptoms he ascribed to low-grade fluoride poisoning would be likewise considered symptoms of hypothyroidism some 20 years later. See:

COMPARISON OF SYMPTOMS:FLUORIDE POISONING/HYPOTHYROIDISM 

Hillman et al (1979) find that cattle afflicted with fluorosis developed hypothyroidism, anemia, and eosinophilia of leukocytes. [The latter two also now commonly associated with hypothyroidism.(Green and Ng, 1986; Pennec et al, 1984)]

Sidora (1983)finds iodine deficiency and adaptive amplification of the hypophyseal-thyroid system, not ensuring an absolute compensation in the citizens using drinking water with an enhanced fluorine content as compared to a “decreased” one, accompanied by an augmented incidence of functional disturbance

Bachinskii et al (1985) document how fluorides at 2.3 ppm in water cause tension of function of the pituitary-thyroid system that is expressed in TSH elevated production, a decrease in the T3 concentration [both sure-tell diagnostic signs of hypothyroidism] and more intense absorption of radioactive iodine by the thyroid. The results lead to a conclusion that excess of fluorine in drinking water was a risk factor of more rapid development of thyroid pathology.

Tokar’ and others (1989) in a study on workers exposed to fluorides write that changes in the pituitary-thyroid axis were seen without co-existing clinical manifestations of hypo- or hyperthyroidism, and that those changes were caused by disorders of the regulatory chain and fluorine impact on thyroid hormones’ metabolism at the level of target cells.  [This info especially important as it relates to behaviour disorders, for it is known that behaviour disturbances can be observed in dogs as in humans well before any clinical signs of hypothyroidism are manifest. (Aronson and Dobman, 1997)]

Lin Fa-Fuet al (1991) report that a low iodine intake coupled with “high” (0.88ppm) fluoride intake excaberates the central nervous lesions and the somatic developmental disturbance of iodine deficiency. The authors considered the possibility that “excess” fluoride ion affected normal deiodination.

Brtko et al (1993) find that fluoride inhibits binding of 125I-T3 to its receptor in rat liver nuclei.

Tezelmann et al (1994) report that fluoride, by increasing the intracellular cAMP concentration, causes desensitization of the thyroid stimulating hormone receptor (TSHR). No specific thyroid factor(s) other than increased levels of cAMP are required for desensitization.

Balabolkin et al (1995) study the thyroid and immune statuses in workers continuously exposed to fluorine. The examinees with euthyroid condition had immune disorders with an allergic tendency (increased number of B-lymphocytes, immunoglobulins A). In workers with subclinical hypothyrosis (T3 reduced in 51%), the immune alterations were more evident, T-lymphocytes count rose, but their functional activity declined, indicating impaired cooperation of immunocytes as a result of imperfect control under low concentrations of T3.

Zhao et al (1998) does an extensive study on mice receiving several fluoride-iodine combinations in addition to basal diet. He finds that iodine and fluorine do have mutually interacting effects on both goiter and fluorosis in the experimental mice.

Jooste et al (1999) show that goiter occurrence in two iodine-sufficient areas in Africa seem to be once again due to high fluoride water levels.

In 1999, as a result of research into molecular biology (“the art of cloning”) there are hundreds upon hundreds of studies available documenting the actions of fluorides upon G proteins, the “On” and “Off” switches involved in cellular signal transmission. Fluorides become known as the universal G-protein activator. Although there have been numerous studies before showing that fluorides mimick TSH, the thyroid stimulating hormone, it can now be documented in deep detail, for it is known that G proteins are normally absolutely dependent on TSH and are _inactive_ without it. Too much TSH (speak fluoride) in the system will cause hypothyroidism and other severe thyroid disorders. Because high TSH levels in the system are indicative of hypothyroidism, TSH tests at birth are implementated on a global basis, to avoid severe brain damage and stunted growth resulting from congenital hypothyroidism.

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Ahn CS, Rosenberg, IN – “Iodine metabolism in thyroid slices – effects of TSH, dibutyril cyclic 3′,5′-AMP, NaF and prostaglandin E1” Endocrinology 86:396-405 (1970)

Aronson, LP, Dodman NH – “Thyroid Dysfunction as a Cause of Aggression in Dogs and Cats.” Presented at the 43. Jahrestagung der Deutschen Veterinarmedizinischen Gesellschaft Fachgruppe Kleintierkrankheiten 29-31 August 1997 in HCC Hannover, Germany

Bachinskii PP, Gutsalenko OA, Naryzhniuk ND, Sidora VD, Shliakhta AI -“Action of the body fluorine of healthy persons and thyroidopathy patients on the function of hypophyseal-thyroid the system” Probl Endokrinol 31(6):25-9 (1985)

Balabolkin MI, Mikhailets ND, Lobovskaia RN, Chernousova NV – “The interrelationship of the thyroid and immune statuses of workers with long-term fluorine exposure” Ter Arkh 67(1):41-2 (1995)

Bobek S, Kahl S,Ewy Z -“Effect of Long Term Fluoride Administration on Thyroid Hormone Levels in Rats” Endocrinol Exp (Bratisl)10:289-295 (1976)

Bockmann J, Winter C, Wittkowski W, Kreutz MR, Bockers TM -“Cloning and expression of a brain-derived TSH receptor” Biochem Biophys Res Commun 238(1):173-8 (1997)

Brtko J, Knopp J, Baker ME – “Inhibition of 3,5,3′-triiodothyronine binding to its receptor in rat liver by protease inhibitors and substrates.” Mol Cell Endocrinol 93(1):81-6 (1993)

Day, TK;Powell-Jackson,PR -“Fluoride, Water Hardness, and Endemic Goitre” Lancet 1:1135-1138 (1972) [A study on 648 people in 13 mountaineous regions in Nepal where the iodine content in the water was low found a close relationship between fluoride intake and the incidence of goiter.]

Editorial:JADA, 1360 (1944)

Eisenberg AD, Curzon ME, Izaguirre-Fernandez EJ – “Interactions of selenium and fluoride on growth, glycolysis and survival of Streptococcus mutans GS-5.” Caries Res 24(5):306-11 (1990)

 

Fujisawa Y, Kato T, Ohki S, Ishikawa A, Kitano H, Sasaki T, Asahi T, Iwasaki Y “Suppression of the heterotrimeric G protein causes abnormal morphology, including dwarfism, in rice” Proc Natl Acad Sci U S A 96(13):7575-7580 (1999)

Galletti PM, Joyet G, Jallut O- “Effets du fluorore de sodium sur la fontion thyrodienne dans la maladie de Basedow” Helv Med Acta 24:209-215(1957)

Galletti PM, Joyet G – “Effect of fluoride on thyroidal iodine metabolosim in hyperthyroidism” J Clin Endocrinol 18:1102-1110 (1958)

Goldemberg L -“Action physiologique des fluorures” Compt Rend Soc Physiol (Paris)95:1169 (1926)

Goldemberg L:Compt Rend Soc Biol (Paris) 104:1031 (1930)

Gordonoff, T. – Fluor und die Schilddrse, Toxikology des Fluors Basel/Stuttgart, pp.111-123 (1964)

Gordonoff T, Minder W – “Fluoride and the thyroid gland” in “World Review of Nutrition and Dietetics” Pitman Medical Co., Vol 2:234-247 (1960)

Gorlitzer von Mundy, V – Einfluss von Fluor und Jod auf den Stoffwechsel, insbesondere auf die Schilddrse” Mnch Med Wochensschr 105:182-186 (1963)

Green ST, Ng JP-“Hypothyroidism and anaemia” Biomed Pharmacother 40(9):326-31(1986)

Guan ZZ, Wang YN, Xiao KQ, Dai DY, Chen YH, Liu JL, P. Sindelar and G. Dallner – “Influence of chronic fluorosis on membrane lipids in rat brain.” Neurotoxicology and Teratology 20 537-542 (1998).

Guadano-Ferraz A, Escamez MJ, Rausell E, Bernal J -“Expression of type 2 iodothyronine deiodinase in hypothyroid rat brain indicates an important role of thyroid hormone in the development of specific primary sensory systems” J Neurosci 19(9):3430-9 (1999)

Hernandez A, Lyon GJ, Schneider MJ, St Germain DL-“Isolation and characterization of the mouse gene for the type 3 iodothyronine deiodinase” Endocrinology 140(1):124-30 (1999)

Hillman D, Bolenbaugh DL, Convey EM – “Hypothyroidism and anemia related to fluoride in dairy cattle” J Dairy Sci62(3):416-23 (1979)

Jentzer, A – “Effet du fluor et du fluor-iod sur la teneur en iode de la thyroide de lapin” Bull Schweiz Akad Med Wiss 15:412 (1959)

Jooste PL, Weight MJ, Kriek JA, Louw AJ- “Endemic goitre in the absence of iodine deficiency in schoolchildren of the Northern Cape Province of South Africa” Eur J Clin Nutr 53(1):8-12 (1999) National Research Programme for Nutritional Intervention, Medical Research Council, Tygerberg, South Africa.  J

Jope RS, Song L, Powers R -“Agonist-induced, GTP-dependent phosphoinositide hydrolysis in postmortem human brain membranes” J Neurochem 62(1):180-6 (1994) Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham 35294-0017.

Kahl S, Bobek, S -“Effect of fluoride administration on radiothyroxine turnover in rats” Endocrynol Pol 26:391-398 (1975)

Karlsson FA, Dahlberg PA, Ritzen EM- “Thyroid blocking antibodies in thyroiditis.” Acta Med Scand 215(5):461-6 (1984)

Korrodi H, Wegman T, Galletti P, Held HR- “Sind bei der Cariesprophylaxe mit Fluor Rckwirkungen auf die Schilddrse zu erwarten?” Schweiz Med Wochenschr 85:1016 (1955)

Korrodi H, Wegman T, Galletti P, Held HR – “Fluor und Schilddrse” Z Praeventivmed 1:285-296 (1956)

Lin Fa-Fu, et al – “The Relationship of a Low-Iodine and High-Fluoride Environment to Subclinical Cretinism in Xinjiang” IDD Newsletter, Volume 7 Number 3 August 1991
http://www.idrc.ca/mi/idddocs/idd891.htm:

Litzka G – “Die experimentellen Grundlagen der Behandlung des M.Basedow und der Hyperthyreose mittels Fluortyrosin” Dtsch Med Wochenschr 63:1037-1040 (1937)

Maumene, E- “Exprience pour dterminer l’action des florures sur l’conomie animale” Compt Rend Akad Sci Paris 39:538 (1854)

May W _ Antagonismus zwischen Jod und Fluor im Organismus” Klin Wochenschr 14:790-792 (1935)

May W – “Behandlung the Hyperthyreosen einschliesslich des schweren genuinen Morbus Basedow mit Fluor” Klin Wochenschr 16:562-564 (1937)

May W – “Die Basedowsche Krankheit” Aulendorf (1950)

Minder W, Gordonoff T- “An antagonism between iodine and fluorine” Arch Intern Pharmacodyn 107:374-381 (1956)

Pastan I, Macchia V, Katzen R – “Effect of fluoride on metabolic activity of thyroid slices” Endocrinology 83:157-160 (1968)

Pennec Y, Youinou P, Le Menn G – “Hypothryoidism and eosinophilic fasciitis” J Rheumatol 11(1):110-1 (1984)

Pighini – Ist Sieroterap Milano. 41 (1923)

Rodesch F, Neve, P, Willems C, Dumont JE – “Stimulation of thyroid metabolism by thyrotropin, cyclic 3′,5′-AMP, dibutyryl cyclic 3′,5′-AMP and prostaglandin E1” Eur J Biochem 8:26-32 (1969)

Siddiqui, A.H. – “Incidence of Simple Goiter in Areas of Endemic Fluorosis in Nalgonda District, Andra Pradesh, India” Fluoride 2:200-205 (1969) In India, small visible goiters have been connected directly to high fluoride concentrations in drinking water in persons 14 to 17 years of age.

Sidora VD, Shliakhta AI, Iugov VK, Kas’ianenko AS, Piatenko VG – “Indices of the pituitary-thyroid system in residents of cities with various fluorine concentrations in drinking water” Probl Endokrinol (Mosk) 29(4):32-5 (1983)

Strunecka, A; Patocka, J – “Aluminofluoride complexes: new phosphate analogues for laboratory investigations and potential danger for living organisms” Cesk Fysiol 48(1):9-15 (1999) Charles University, Faculty of Sciences, Department of Physiology and Developmental Physiology, Prague/Department of Toxicology, Purkyn Military Medical Academy, Hradec Krlov, Czech Republic On-line at: http://www.cadvision.com/fluoride/brain3.htm

Susa M, Standke GJ, Jeschke M, Rohner D – “Fluoroaluminate induces pertussis toxin-sensitive protein phosphorylation: differences in MC3T3-E1 osteoblastic and NIH3T3 fibroblastic cells” Biochem Biophys Res Commun 235(3):680-4 (1997)

Susa M – “Heterotrimeric G proteins as fluoride targets in bone (Review).” Int J Mol Med 3(2):115-126 (1999)  Steyn DG – S Afr Med J 22:525 (1948)

Steyn DG, et al- “Endemic goitre in the Union of South Africa and some neighbouring territories” Union of South Africa, Department of Nutrition (March 1955)

Steyn DG – “Chronic fluorine poisoning caused by the drinking of subterranean waters containing excessive quantities of fluorine” in: Gordonoff, T. – “Fluor und die Schilddrse, Toxikology des Fluors” Basel/Stuttgart (1964)

Tezelman S, Shaver JK, Grossman RF, Liang W, Siperstein AE, Duh QY, Clark OH – “Desensitization of adenylate cyclase in Chinese hamster ovary cells transfected with human thyroid-stimulating hormone receptor.” Endocrinology 134(3):1561-9 (1994)

Tokar’ VI, Savchenko ON – “Effect of inorganic fluorine compounds on the functional state of the pituitary-testis system” Probl Endokrinol (Mosk) 23(4):104-7 (1977)

Tokar’ VI, Voroshnin VV, Sherbakov SV -“Chronic effects of fluorides on the pituitary-thyroid system in industrial workers” Gig Tr Prof Zabol 9:19-22 (1989)

Waldbott, GL; Burgstahler, AW; McKinney, HL – “Fluoridation:The Great Dilemma” Coronado Press (1978)  Wespi, HJ – “Besteht ein Antagonismus zwischen Fluor und Jod?” Praxis 43:616 (1954)

Willems, C; Berberhof-Van Sande, J;Dumont, JE- “Inhibition Of Thyroid Secretion By Sodium Fluoride (In Vitro)” Biochimica Et Biophysica Acta 264:197-204 (1972)

Williams RH, Jaffe H, Solomon B – “Effect of halides on on the antithyroid action of thiouracil and propylthiouracil” Am J Med Sci 219:197-204 (1950)

Zhao WY – “A preliminary study of the interaction of iodide and fluoride in experimental iodide-goiter and fluorosis” Chung Hua Yu Fang I Hsueh Tsa Chih 1988 May;22(3):146-8 (1988)

Zhao W, Zhu H, Yu Z, Aoki K, Misumi J, Zhang X -“Long-term Effects of Various Iodine and Fluorine Doses on the Thyroid and Fluorosis in Mice” Endocr Regul 32(2):63-70 (1998)

Zor U, Kaneko T, Lowe IP, Bloom G, Field JB – “Effect of thyroid-stimulating hormone and prostaglandins on thyroid adenyl cyclase activation and cyclic adenosin 3′-5′-monophosphate.” J Biol Chem 244;5189-5195 (1969)

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