Fluoride: A Statement of Concern
continues from part 1
26. Surely, if objective government scientists had been aware of this concern or prediction, they might have taken far more seriously the studies that followed. For example, in 1990 the National Toxicology Program (NTP) published the results of a 2-year study of rats and mice treated with fluoride in their drinking water performed by scientists at Battelle laboratories (38). Even though a peer review of this Battelle study removed some of the other cancers found (erroneously according to Dr. William Marcus at the US EPA) (39), it still showed a dose-related increase in osteosarcoma in the male but not the female rats. Rather than taking this result as a serious red flag, government scientists seemed to have done everything they could to downplay it. According to Dr. William Marcus, who was the senior scientist at US EPA’s Office of Drinking Water in 1990, the NTP studies done by Battelle
“showed that there was an increased level of bone cancer and other kinds of cancer in the animals. When I got a hold of the contractor report and reviewed it very carefully and not only was it reporting cancers in the animals, osteosarcomas, which bothered me a lot because I’ve been trying to produce osteosarcomas in animals for almost 20 years and the only luck I ever had was with an experiment in dogs and monkeys and the osteosarcomas took nearly the lifetime of the animals and we were using radium which specifically produces that in bones and here we have a compound commonly available (fluoride) that did it in rats in two years or less. That was upsetting to begin with. Secondarily, there was a study of, in that same study, there were cancers of the liver that are very rare according to the board certified veterinary pathologist at the contractor, Battelle, and those really were very upsetting because they were hepatocholangiocar-cinoma, a very rare, rare, liver cancer and when that occurs, something similar to that occurred with vinyl chloride in a far less well conducted study and it was determined that it was carcinogenic, highly carcinogenic. Then there were several other kinds of cancers found in the jaw and other places and I felt at the time that the report was very, very interesting. It showed that the levels of the fluoride that caused the cancers in the animals were actually lower than those levels seen in people who are ingesting lower amounts but for longer periods of time and that was very very worrisome. It meant that the general population could be exposed to fluoride known to cause cancer in animals and have levels near the cancer being produced in the bones… I went to a meeting that was held in Research Triangle Park in April 1990, the latter part of April, in which the NTP was presenting their review of the study and I went with several colleagues of mine one of whom was a board certified veterinary pathologist who had originally reported hepatocholangiocarcinoma as a separate entity in rats and mice and I asked him if he would have an opportunity to look at the slides to see if that really was a tumor or the pathologist at Battelle had made an error and he told me after looking at the slide that in fact it was correct and at the meeting every one of the cancers that was reported by the contractor had been down-graded by the NTP. Now I’ve been in the toxicology business looking at studies of this nature for nearly 25 years and I’ve never seen that, never ever seen where every single endpoint that was a cancer endpoint had been down-graded. I’d seen one or two endpoints argued over, usually on a definition what is a cancer in that particular tissue but I’ve never seen every one of them down-graded. I found that very suspicious and I went to see an investigator in the Congress at the suggestion of my friend Bob Carton and this gentleman and his staff investigated very thoroughly and found out that the scientists at the NTP down at Research Triangle Park had been coerced to change their findings.” (40)
Some said the results were equivocal. Others said the doses were so high that they weren’t relevant, and yet it is standard toxicological practice to treat a small group of animals to a large dose of a toxicant if you are to have a statistical chance of observing any change in the small sample size. The alternative is to treat a very large number of animals to a lower dose, which is prohibitively expensive. The National Research Council (NRC) in a 1993 report (41) described the result as follows: “The equivocal result of osteosarcoma in male rats was not supported by results in females in the same study” (page 122). This is an extraordinary statement in the context of the concerns raised by the NAS in 1977 (see paragraph 25) because it is precisely the result the authors had feared. The NRC further downplayed the result based upon a study by Proctor and Gamble (42) (hardly a disinterested party in these matters) which hadn’t found any osteosarcomas in their rat studies (they had found osteomas in mice, but they were considered not important because they were non-malignant). Dr. John Yiamouyiannis used the Freedom of Information Act to take a closer look at the P&G studies and found that they had found cancers in their rats as well as lesions which could lead to cancers (43).
27. A suspicious person might wonder if the US government was maneuvering around the Delaney Clause, which was operating at that time. This clause introduced by Congressman Delaney required that no chemical found to cause cancer in animal studies be added to food. Thus, if a link had been found between fluoride and cancer in these animal studies it would have scuttled the whole fluoridation program then and there.
28. In 1992, a report was published by the New Jersey Department of Health (44) which indicated that in three fluoridated counties in NJ, there was a seven-fold increase in osteosarcomas in young males, compared to non-fluoridated counties. There was no increase in the females. Again, this is precisely the result feared/anticipated by the NAS commentators in 1977.
29. In an earlier national survey under the SEER program (45) increases in osteosarcomas in young males were further correlated with fluoridation in two other states. However, a study in New York, published in 1991, had not found any increase they could relate to water fluoridation (46). Three other studies have failed to find a relationship between bone cancer rates and fluoridation. These are discussed by Dr. John Yiamouyiannis in an excellent review of the osteosarcoma data for the journal Fluoride (43). Dr. Yiamouyiannis has pursued the fluoride-cancer connection more thoroughly than any other scientist alive. For some, the positive and negative results on osteosarcoma incidence in fluoridated communities neatly cancel one another out. For me this is too serious an issue to be so lightly dismissed. In an interview I had with the late Dr. John Colquhoun he posed the question: “How many cavities would have to be saved to justify the death of one young man from osteosarcoma?” (Video interview identified in paragraph 14).
Fluoride’s impact on enzymes, soft tissues, the endocrine system, and the brain.
30. Some of the earliest opponents of fluoridation were biochemists. One of those early opponents was one of the world’s leading authorities on enzyme chemistry, Nobel laureate Dr. James Sumner at Cornell University. He said:
“We ought to go slowly. Everybody knows fluorine and fluorides are very poisonous substances…We use them in enzyme chemistry to poison enzymes, those vital agents in the body. That is the reason things are poisoned; because the enzymes are poisoned and that is why animals and plants die.”
31. Dr. James Sumner was one of at least 12 Nobel Prize winners in Chemistry and Medicine, who have either opposed fluoridation or expressed reservations about it. These include Giulio Natta (1963 Nobel Prize in Chemistry), Nikolai Semenov (Chemistry, 1956), Sir Cyril Norman Hinshelwood (Chemistry, 1956), Hugo Theorell (Medicine, 1955), Walter Rudolf Hess (Medicine, 1949), Sir Robert Robinson (Chemistry, 1947), James B. Sumner (Chemistry, 1946), Artturi Virtanen (Chemistry, 1945), Adolf Butenandt (Chemistry, 1939), Corneille Jean-François Heymans (Medicine, 1938), William P. Murphy (Medicine, 1934), and Hans von Euler-Chelpin (Chemistry, 1929). This listing makes absurd the ADA’s claim that there is “no scientific debate” over this issue and that the only people who oppose it are `crackpots’.
32. It is known that many enzymes are inhibited (poisoned) in test tubes (in vitro) at the levels at which water is fluoridated (1 ppm) or less (47). One early explanation given for these observations was that many of the enzymes inhibited had magnesium ion as a co-factor, and that the fluoride ion interfered with the enzyme’s interaction with the magnesium. A second explanation from Dr. John Emsley throws more light on how the “humble” fluoride ion, which is inert from a chemical point of view, can be so active and so toxic from a biological point of view.
33. In an article published in the Journal of the American Chemical Society in 1981, Emsley (48) and co-workers showed that fluoride could form a strong hydrogen bond with the amide function. This particular function appears throughout proteins and nucleic acids. The hydrogen bond is the “velcro strip” of biology. It is a weak bond compared to regular chemical bonds (ionic and covalent), but when they act in consort they are able to provide the shape of vitally important molecules and in biochemistry, shape is exquisitely tied to function. Like the velcro strip when the shape has to be changed in some important maneuver, like the opening of the two DNA chains or the interaction between an enzyme and its substrate (the chemical changed by the enzyme), these bonds can easily be broken and reformed with little energy input. Thus, fluoride’s interference with hydrogen bonds could cause all sorts of problems at the very heart of biological functioning. The counter-argument from those promoting fluoridation is that at 1 ppm fluoride in our drinking water, fluoride would not reach these concentrations in the soft tissues. Such statements are usually accompanied with a reference to the father of toxicology, Paracelsus, who said, ” ’tis the dose that makes the poison.” While this ancient observation remains valid to this day the argument that a concentration of 1 ppm for fluoride (i.e. 1,000 parts per billion) is “harmless” is extremely arrogant, and I define arrogance as ignorance backed with over-confidence. We should note that today we are concerned about very much lower levels of lead in childrens’ blood than we were in the late 1970s. Scientists and government officials were wrong about lead then, could they be wrong about what constitutes a safe level of fluoride now?
34. It is interesting to note what the Swedish Nobel Prize winner Dr. Hugo Theorell said about these concerns in 1958. He wrote:
“Even if with respect to caries fluoride may be a good prophylactic, it is in larger doses, none the less a poison. In principle this signifies nothing; in sufficiently large doses all substances are toxic for the human organism. What is important is the distance between the therapeutic and the toxic dose… it may be said that even if the risks from the viewpoint of enzyme chemistry connected with water fluoridation up to 1 ppm should not be exaggerated, yet the distance to toxic doses is none the less so short as to justify some hesitation” (49).
Recognizing that fluoride’s target in tooth protection is the “surface layer of the dental enamel” he suggests that water fluoridation is “a roundabout way” of delivering it, because “on its Odyssey through the body fluids most of the fluoride will be lost in other organs, where it will probably not do any good, but possibly do damage to enzymes” (49).
35. Recent work from Dr. Jennifer Luke (50-51) indicates that fluoride reaches one very important gland in the body–the pineal gland–at very much higher concentrations than 1 ppm. This small gland is almost at the geometrical center of the brain, between the two hemispheres. However, it is outside the blood brain barrier. It also has a very high supply of blood (a perfusion rate second only to the kidney) and it is a calcifying tissue, laying down crystals of calcium hydroxyapatite like the teeth and the bone. Because of these observations Luke argued that one would expect the pineal gland to concentrate fluoride. When she had the pineal gland from 11 human corpses analyzed she indeed found this to be the case. The levels of fluoride in the apatite crystals averaged about 9,000 ppm (and went as high as 21,000 ppm). The average level is as high as you would expect in the bones of someone afflicted with skeletal fluorosis. The average projected by Luke for the whole tissue was 300 ppm, well over the 1 ppm found to inhibit many enzymes.
36. Luke next examined the effect of dosing Mongolian gerbils (the animal of choice for studying the pineal gland) with fluoride. She found that animals fed higher doses of fluoride had a significant decrease in their excretion of melatonin metabolite in their urine. She also found that the high dose fluoride animals took a shorter time to reach puberty. This is exactly what you would expect if melatonin production was lowered. If this result is confirmed by others it would make fluoride an environmental hormone or endocrine disrupter, a topic of intense discussion (52) and review by regulatory agencies in the US and around the world.
37. Another line of evidence which indicates that fluoride is an endocrine disrupter is the number of studies that indicate the fluoride may inhibit the functioning of the thyroid gland. Andreas Schuld, president of a group called Parents of Fluoride Poisoned Children, has prepared an excellent summary of the evidence that points in this direction (53, 54). To put the matter as simply as I can, his group has been able to show that areas of endemic fluorosis are also areas designated as being endemic with iodine deficiency disorders (IDD). The group rediscovered studies and documentation from the European medical literature spanning over 30 years of research testifying to fluoride’s pharmacological effectiveness in the treatment of hyperthyroidism (the term used to describe an over-functioning thyroid gland). Thyroid hormones are absolutely essential for normal growth and development. Hyperthyroidism means that the thyroid gland is producing too much of the thyroid hormones, T3 and T4. These two hormones have 3 and 4 iodine atoms respectively. Schuld’s group has also shown that there is a remarkable similarity between the symptoms listed for hypothyroidism (underactive thyroid gland) and those reported for fluoride poisoning (55). Putting these two conditions together, it appears that fluoride decreases the production of thyroid hormones. If you are suffering from hyperthyroidism, fluoride might be of some benefit. But for a normal person if you are exposed to too much fluoride it could result in reducing thyroid hormone production below normal and necessary levels (i.e., hypothyroidism).
38. It is not clear just how fluoride reduces thyroid hormone production. It may be that fluoride competes with iodine uptake into this gland. Alternatively, fluoride might inhibit the enzymes inside the gland which assemble the hormones from its chemical precursor, the amino acid tyrosine.
39. Schuld also points to research that fluoride can also stimulate the thyroid glands, which seems contradictory to the discussion above. However, stimulation may not lead to production of the hormones if iodide is in short supply. Such a situation (overstimulation coupled with iodide shortage) might explain the condition known as goiter. Here the gland grows and grows producing a swelling in the neck. The gland grows because it is being stimulated, but because there are no thyroid hormones produced, there is nothing to switch off the stimulating signal. In other words, the normal feedback mechanism is not working. This signal is the hormone (thyrotropin or thyroid stimulating hormone) which is produced by the pituitary gland–the master gland as far as hormonal control is concerned.
40. Now this is where the story gets very disturbing. It appears that fluoride forms a complex with the aluminum ion, in which 4 fluoride ions tightly surround an aluminum ion [AlF4]- and that this complex looks to the body just like the phosphate ion (PO43-). Moreover, this [AlF4]- complex is able to bind to G-proteins, which are part of the signaling mechanism of all water soluble hormones and many neurotransmitters.
41. To appreciate the significance of this we need first to understand what hormones are and how they function. Hormones are messengers that regulate body chemistry. They are produced at specific times and in specific glands, for example the adrenal glands produce adrenaline when we experience a sudden shock. Once they are produced they are injected into the bloodstream where they circulate the body until they find their target tissue: i.e. the tissue which they will regulate. At this point in our discussion we need to divide hormones into two groups: those which are soluble in fat and those which are soluble in water. The fat soluble ones like the steroid hormones (e.g. estrogen and testosterone) can freely enter the cells of the tissues they regulate, because the membranes of the cell are made of fat and these hormones can pass straight through. Once inside the cell they bind with a protein receptor and change the cell’s activity in a very fundamental way. Water-soluble hormones, on the other hand, cannot cross the cell membrane and their effect has to be instigated outside the cell, and this is where the G-proteins play their important intermediary role. The hormone first combines with a receptor protein on the outside membrane of the cell. When this event has taken place, it triggers a response from the G-proteins. The G-proteins have to take the signal, delivered by the hormone or neurotransmitter, the so-called “first messenger”, across the membrane (transduction), and excite (or release) a “second messenger”, on the internal surface of the membrane. Once excited (or released) this second messenger can excite various target molecules like enzymes inside the cell. Examples of these “second or intracellular messengers” are cyclic AMP (cAMP) and the Ca2+ion.
42. We will now concentrate on the action of water soluble hormones and the important role played by the G-proteins in the transduction process (getting the signal from outside the cell to the inside). The mechanism of action of the G-proteins is complicated but fully described in the literature (56,57). For our purposes we need only examine the key moment when [AlF4]- interferes with the sequence of events.
43. When the water soluble hormone attaches to its receptor it triggers a change in the G-protein which allows a phosphate group to bind to a molecule called guanosine diphosphate (GDP) which sits in a crevice of the surface of the G-protein. This incoming phosphate changes the GDP to guanosine triphosphate (GTP). If we envisage the G-protein as a switch when GDP occupies the crevice the switch is off, but when the GTP sits in the crevice the switch is on. In the on position the signal is sent to activate the cell. [AlF4]- not only performs exactly the same function as the phosphate but it also does it without the participation of the hormone. Thus in the absence of the hormone, [AlF4]- is capable of switching on the signaling mechanism which activates the cell.
44. The possible interference of [AlF4]- is, in my view, one of the most important developments in fluoride research for many years. Indications are that the aluminum levels needed for the formation of [AlF4]- are almost certainly present in our `industrial’ diets, however it may also be that high calcium (Ca2+) and magnesium (Mg2+) levels may prevent its formation. If this is the case it underlines the fear that those suffering malnutrition may be especially vulnerable to fluoride. This point needs urgent recognition by those who advocate fluoridation to provide dental care for the poor, because it is the poor who are most likely to be malnourished.
45. The role of G-proteins as intermediaries in signaling by water soluble hormones (eg insulin, adrenalin, glucogon, thyroid stimulating hormone, and many others) as well as neurotransmitters is so fundamental to the proper growth and functioning of mammals that any interference by aluminum fluoride complexes would be extremely serious indeed. Interference here would go a long way to explain health problems associated with fluoride not explained by fluoride’s direct inhibition of enzymes. Anna Strunecká & Jirí Patocka have produced an excellent review of the potential pathological consequences of human exposure to [AlF4]- (58).
46. Schuld points out that since the 1994 Nobel Prize in Physiology or Medicine was awarded to Alfred Gilman and Martin Rodbell for the discovery of G-proteins and their role in cellular signal transduction, much attention has been focused on the manifold functions of these ubiquitous molecules and on the ways in which they can become disordered in human diseases. Entire data banks have now been established listing G-protein-coupled receptor mutations or gene rearrangements, and human diseases caused by such (precocious puberty, neonatal severe hyperparathyroidism, etc.). The effects of fluorides on these can be witnessed in hundreds of studies available on Medline and elsewhere. Schuld’s group is providing the key links to these studies via their website (54).
47. Returning to the pineal gland, Luke postulates a mechanism which doesn’t involve the functioning of the hormone, but its production. In the production of melatonin in this gland there are four chemical changes between the amino acid tryptophan (a nutrient) and melatonin. All four steps are catalyzed by enzymes. The first two steps yield serotonin, a neurotransmitter, and the next two convert serotonin into melatonin. Luke argues that one or more of these enzymes which catalyze these four steps are inhibited by fluoride (51). Interfering with either the production of serotonin or melatonin is of extreme significance. A huge amount of research is ongoing in the attempt to elucidate all the subtle influences that melatonin has on regulatory mechanisms throughout the body, including the timing of puberty.
48. Of particular interest, is the knowledge that in the US there is an earlier onset of puberty, especially in girls, and no one knows what is causing this (59). There are many possible candidates, but based upon Luke’s work on the pineal gland, fluoride should be added to the list.
49. Also of interest is the fact that when children were examined in the Newburgh-Kingston study (already cited) in 1955 (ten years after fluoridation was begun) they found that the girls in fluoridated Newburgh reached menstruation five months earlier, on average, than the girls in non-fluoridated Kingston (36).
50. Our discussion now moves from the pineal gland, which is outside the blood brain barrier, to the inside of the brain. There have been several studies which indicate that fluoride can impact mental behavior. In the 1940s, US scientists working on the Manhattan Project (the making of the Atomic bomb) were concerned that exposure to fluoride could threaten the behavior and concentration of the workers in nuclear plants which were using huge quantities of fluoride in the separation of uranium isotopes. A request was made by Harold Hodge, the chief toxicologist of the project, to do a study on the impact of fluoride on rat behavior. His request was first accepted and later canceled (60). While discovering this information from formerly classified documents, researchers Cliff Honicker, Joel Griffiths and Chris Bryson, also unearthed the fact that one of the earliest and most important trials of fluoridation, the 1945-55 Newburgh-Kingston study (discussed above), was partially organized by, and closely watched by, scientists from the Manhattan Project. Apparently, there was a concern that the government would be facing lawsuits from communities impacted by fluoride emissions from the facilities which had manufactured the atomic bomb (60). Among those concerned was Harold Hodge and in one memo with respect to how to deal with impacted citizens and farmers, he asked, “Would there be any use in attempts to counteract the local fear of fluoride… through lectures on F toxicology and perhaps the usefulness of F in tooth health?” (60). While the impact of fluoride on teeth was studied early, Hodge had to wait nearly 50 years before he saw the rat-behavior experiment performed by Dr. Phyllis Mullenix at the Forsyth Dental Center in Boston.
Continue to part 3: Fluoride: A Worldwide Campaign to End Exposure