FLUORIDE IN THE BODY
WHAT HAPPENS to fluoride once it has entered the human body? To answer this question one of two methods is usually used.
In one the total quantity of fluoride consumed over a given period from all food and drink is measured and compared with the amounts of fluoride eliminated through the kidneys and bowels. This approach, however, is only partially reliable because some fluoride leaves the body with sweat, saliva, and tears, all of which are difficult to collect. The procedure was first reported in 1891 by two German pharmacologists, J. Brandl and H. Tappeiner, who over the course of 21 months fed slightly more than 14 ounces (403 g) of sodium fluoride to a 28-pound dog.1 During this period the dog excreted 81 % of the fluoride through the kidneys and bowels. Of the fluoride detected in the dog when they then killed it, over 92% was present in the bones and cartilage. The rest, in decreasing amounts, was found in the skin, muscle, liver, teeth, and blood.
The second approach uses the radioactive tracer technique. Radioactive fluoride, 18F, is imbibed with water or injected into a vein, and a Geiger counter then records the amount of radiation which emanates from 18F as it passes through the body. Thus, it can be determined exactly where the radioactive fluoride localizes and how much is eliminated. In these experiments, all information must be obtained in about 8-10 hours because of the rapid disintegration of 18F, which has a half-life of 1.87 hours as it decays (by loss of a positron) to 180, a stable isotope of oxygen. Radioactive tracer studies were first reported on rats in 1954,2 on sheep in 1955,3 on rats and mice in 1958,4 and on humans in 1960.5 Many similar studies have been carried out subsequently.
In 1945 fluoride balance studies were described on five healthy young men for 28 test periods, each consisting of five eight-hour days. These findings indicated that more than 80% of the fluoride ingested in drinking water was being excreted in urine and perspiration.6 Indeed, sweat is “an important avenue for the elimination of fluoride,” the authors stated”
In a later investigation, the daily diet of nine male ambulatory patients, which averaged 4.4 mg fluoride, was supplemented by 9.1 mg of fluoride (as sodium fluoride).7 Of the total daily amount of fluoride (13.5 mg) thus consumed, 3.6 mg was retained, amounting to 115 mg during the 32-day experimental period. During the 18 days following termination of the experiment, the total amount of excess fluoride excreted in the urine and feces was 9.8 mg, which means that only about 10% of the 115 mg of fluoride retained during the experiment was subsequently eliminated.
ABSORPTION INTO THE BLOOD
Under ordinary conditions fluoride is detectable in the blood stream by 18F tracer within 10 minutes after ingestion and reaches a maximum concentration about 50 minutes later.5 About 47.5% is absorbed through the upper bowels and 25.7% through the stomach wall within one hour by simple diffusion, no active transport mechanism being involved.8 This “normal” course of the metabolic fate of fluoride, however, may be modified considerably by many factors. For instance, when accompanied by calcium, aluminum, magnesium, and phosphates present in food or water, fluoride is absorbed more slowly,9,10 although increased intake of calcium and phosphorus has only a limited effect on the amount that is absorbed.7 Similarly, simultaneous ingestion of fat considerably delays the emptying of the stomach,11 but enhances fluoride absorption into the blood stream.12
When the stomach is unduly acid, as in persons with stomach ulcers, fluoride is more rapidly and more completely absorbed than in a less acid stomach. Once fluoride has reached the lower bowels, little absorption takes place because, in contrast to the acidity of the stomach, the bowel content is alkaline, and some fluoride, instead of entering the blood stream, leaves the body with the fecal material. When fluoride is swallowed with food, tablets, or salt, less of it reaches the blood stream than when taken in water or most other liquids, as with milk, in which the calcium and protein tend to bind fluoride; the absorption is slower and less complete. In an experiment with rats, continuous feeding of fluoride caused greater retention in the body than interrupted feeding.13
In workers and in persons residing close to factories which emit fluoride, however, the respiratory tract is a major route of fluoride ingress. In its gaseous form – essentially hydrogen fluoride – the halogen readily enters the blood stream, mainly in the upper portion of the respiratory tract. The uptake of particulate fluoride compounds is governed mainly by the size of the particles: the larger ones settle in the nose, sinuses, and pharynx and are promptly removed from the body with mucus or swallowed.14 Particles with a diameter of 0.5-5μ will be impacted in the alveolar-capillary bed, the terminal areas of the lungs, where they are absorbed into the blood stream within minutes, especially if they are water soluble.15
In the blood stream between 80% and 90% of the fluoride is present in a “bound” or non diffusible form.16 Most of this fluoride appears to be attached by stable covalent bonds to organic molecules. The rest of the fluoride in blood is in a free, ionic form, the concentration of which reflects both the level of intake and the efficiency of excretion. The “normal” level of serum ionic fluoride, according to D.R. Taves of the University of Rochester, is 0.2-0.4 micromole/liter (μM) or 0.004-0.008 ppm “when the drinking water contains only traces of fluoride, and about 0.5-1 μmol (0.01-0.02 ppm) in a community with fluoridated water.17
In the most extensive studies to date, H. Hanhijärvi reported somewhat higher serum ionic fluoride levels (but in a comparable ratio) in 2200 hospital patients in a non-fluoridated and a fluoridated community in Finland.” His data showed that ionized plasma fluoride increases with age, diabetes, and renal insufficiency but decreases slightly during pregnancy. Diseases of the liver and heart also reflected higher serum fluoride levels, especially in the fluoridated community (Table 4-1, page 50).19
Mean Ionic Plasma Fluoride Levels of 2200
Patients in Two Finnish Hospitals19
Plasma Fluoride (μM)
The small “free” or dissociated fluoride ion easily penetrates the walls of tiny capillary blood vessels and thereby reaches the cells of various organs in the body, especially the bones. In these movements the fluoride ion concentration and the calcium and carbon dioxide levels in the blood, together with the composition of the tissue fluids, all play a role in determining how much and how fast fluoride reaches the tissues.
In bones and teeth, fluoride becomes incorporated directly into the crystalline mineral phase, called hydroxyapatite, to form fluoroapatite. The cancellous part of long bones and the surface of the shaft incorporate fluoride more rapidly than does the cortex [marrow].20 Developing bones and teeth take up more fluoride than do mature ones.21 In the absence of kidney impairment adults therefore accumulate fluoride more slowly than children.
Although most of the body fluoride is stored in hard tissues – bones, teeth, and nails – we now know that the fluoride ion can penetrate into and be “stored” in virtually any tissue of the body, sometimes in rather substantial quantities.. Much fluoride is found,
for instance, in the aorta, the main artery of the heart22 – even at relatively uncalcified sites – and in ligaments. Under certain conditions, significant amounts of fluoride can also accumulate in the skin, bowels, kidneys, liver, muscles, and other organs.23 The highest level of fluoride stored in soft tissue organs, 8400 ppm, was found in the aortas of two middle-aged men.24
The elimination of fluoride from the body – through kidneys and less through feces, sweat, saliva, tears, and milk – in general is unpredictable. During a person’s growth, the clearance of fluoride through the kidneys increases, but after age 50 it begins to decline, an indication of greater storage. Of a given dose in adults, 37% to 48% is usually retained, but these values vary considerably,25 Early in my fluoride studies I administered to several patients, as a test dose, 15 mg of sodium fluoride (6.8 mg of F-), which is seven times the daily intake of fluoride recommended for prevention of tooth decay in children.26 One patient eliminated in the urine as little as 3.6% in 24 hours, another as much as 99.5%.
Fluoride excretion in excess of intake may continue for a long time after large amounts of the halogen have been ingested. For instance, 27 months after the drinking water in Bartlett, Texas, was defluoridated from 8 ppm to about 1 ppm, the average fluoride concentration in urine specimens of 116 white males, age 7 to over 70, decreased from 6-8 ppm to about 2 ppm.27 These values indicate that previously stored fluoride was metabolized and excreted in the urine.
Because there are wide variations among people in their retention and excretion of fluoride (Fig. 4-1, page 52), it is logical to conclude that there must also be great differences in the health effects of fluoride from person to person. Unfortunately, our knowledge about the behavior of fluoride in the human organism is still very imperfect. We do not know why some individuals respond so much differently to fluoride than do others. Are there predisposing – perhaps inherited – factors which explain the variations in retention of fluorine in some persons? What role do malnutrition, vitamin deficiencies, differences in food habits, functional impairment of certain organs, presence of disease, occupational exposure, and socio-economic factors play in the action of fluoride in the body? These questions indicate clearly that there are important areas of research which still need answers. At the moment, we have scarcely begun to formulate the questions, much less to grope for answers. The area to which scientists have given most attention is the action of fluoride on teeth, specifically its value in preventing tooth decay, and even here our knowledge is still incomplete.
• Living in Detroit, Mich. with 0.1 p.p.m. F- in water supply
O Living in fluoridated cities (about 1 p.p.m.)
Fig. 4.1 Unpredictable variations in 24·hour urinary fluoride excretion by age
among allergic persons living in fluoridated and non-fluoridated communities.
(From G.L. Waldbott: Fluoride in Clinical Medicine.
Internat. Arch. Allergy Appl. Immunol., Suppl. 1 to Vol. 20, 1962.)
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2. Wallace-Durbin, P.: The Metabolism of Fluorine in the Rat Using F18 as a Tracer. J. Dent. Res., 33:789·800, 1954.
3. Perkinson, J.D., Jr., Whitney,I.B., Monroe, R.A., Lotz, W.E., and Comar, C.L.: Metabolism of Fluorine 18 in Domestic Animals. Am. J. Physiol., 182:383-389,1955.
4. Ericsson, Y., and Ullberg, S.: Autoradiographic Investigations of the Distribution of F18 in Mice and Rats. Acta Odontol. Scand., 16:363-374, 1958.
5. Carlson, C.H., Armstrong, W.D., and Singer, L.: Distribution and Excretion of Radiofluoride in the Human. Proc. Soc. Exp. Biol. Med., 104:235-239, 1960.
6. McClure, F.J., Mitchell, H.H., Hamilton, T.S., and Kinser, C.A.: Balances of Fluorine Ingested from Various Sources in Food and Water by Five Young Men. Excretion of Fluorine Through the Skin. J. Ind. Hyg. ToxicoI., 27:159- 170,1945. (Reprinted in Fluoride Drinking Waters, 1962, pp. 377-384.)
7. Spencer, H., Kramer, L., Osis, D., and Wiatrowski, E.: Excretion of Retained Fluoride in Man. J. Appl. Physiol., 38 :282-287, 1975.
8. Stookey, G.K., Dellinger, E.L., and Muhler, J.C.: In vitro Studies Concerning Fluoride Absorption. Proc. Soc. Exp. BioI. Med., 115:298-301, 1964.
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10. Weddle, D.A., and Muhler, J.C.: The Effects of Inorganic Salts on Fluorine Storage in the Rat. J. Nutr., 54:437-444,1954.
11. McGown, E.L., and Suttie, J.W.: Influence of Fat and Fluoride on Gastric Emptying of Rats. J. Nutr., 104:909-915, 1974.
12. McGown, E.L., Kolstad, D.L., and Suttie, J.W.: Effect of Dietary Fat on Fluoride Absorption and Tissue Fluoride Retention in Rats. J. Nutr., 106: 575-579, 1976.
13. Lawrenz, M., Mitchell, H.H., and Ruth, W.A.: The Comparative Assimilation of Fluoride by Growing Rats During Continuous and Intermittent Dosage. J. Nutr., 20:383-390,1940.
14. Task Group on Lung Dynamics (Bates, D.V., Fish, B.R., Hatch, T.F., Mercer, T.T., and Morrow, P.E.): Deposition and Retention Models for Internal Dosimetry of the Human Respiratory Tract. Health Phys., 12:173-207, 1966.
15. Collings, G.H.,Jr., Fleming, R.B.L., May, R., and Bianconi, W.O.: Absorption and Excretion of Inhaled Fluorides: Further Observations. Arch. Ind. Hyg. Occup. Med., 6:368-373,1952.
16. Taves, D.R.: Evidence That There Are Two Forms of Fluoride in Human Serum. Nature (Lond.), 217:1050,1968.
17. Hodge, H.C., and Taves, D.R.: Chronic Toxic Effects [of Fluoride] on the Kidneys, in Fluorides and Human Health. World Health Organization Monograph Series No. 59, Geneva, 1970, p. 254.
18. Hanhijärvi, H.: Comparison of Free Ionized Fluoride Concentrations of Plasma and Renal Clearance in Patients of Artificially Fluoridated and Non-Fluoridated Drinking Water Areas. Proc. Finn. Dent. Soc. 70: suppl. III, 1974.
19. Hanhijarvi, H.: Inorganic Plasma Fluoride Concentrations and Its Renal Excretion in Certain Physiological and Pathological Conditions in Man. Fluoride. 8:198-207,1975.
20. Weidmann, S.M., and Weatherell, J.A.: The Uptake and Distribution of Fluorine in Bones. J. Pathol. Bacteriol., 78:243-255,1959.
21. Savchuck, W.B., and Armstrong, W.D.: Metabolic Turnover of Fluoride in the Growing Skeleton. J. Dent. Res. 30:467468, 1951; J. Biol. Chem., 193:575-585,1951.
22. Waldbott, G.L.: Fluoride and Calcium Levels in the Aorta. Experientia (Basel), 22:835-837, 1966.
23. Waldbott, G.L.: Introduction to Symposium on the Non-Skeletal Phase of Chronic Fluorosis. Fluoride, 9:5-8, 1976.
24. Geever, E.F., McCann, H.G., McClure, F.J., Lee, W.A., and Schiffmann, E.: Fluoridated Water, Skeletal Structure, and Chemistry. Health Serv. Mental Health Admin. Health Rep., 86:820-828,1971.
25. Largent, E.J., and Heyroth, F.F.: The Absorption and Excretion of Fluorides. III. Further Observations on Metabolism of Fluorides at High Levels of Intake. J. Ind. Hyg. Toxicol., 31 : 134-138, 1949.
26. Waldbott, G.L.: Comments on the Symposium “The Physiologic and Hygienic Aspects of the Absorption of Inorganic Fluorides.” Arch. Environ. Health, 2:155-167,1961.
27. Likins, R.C., McClure, F.J., and Steere, A.C.: Urinary Excretion of Fluoride Following Defluoridation of a Water Supply. Public Health Rep., 71: 217-220, 1956. (Reprinted in Fluoride Drinking Waters, 1962, pp. 421-423.)Fluoride, Fluoridation,
SOURCE: Fluoridation: The Great Dilemma, George L. Waldbott, MD, Albert W. Burgstaller, PH.D, H.Lewis McKinney, PH.D, Coronado Press, 1978, pp 47-54.
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