The medical significance and importance of the interaction of fluoride with calcium and magnesium has profound implications for human health. Fluoride seeks out essential elements such as calcium and magnesium and binds with them, thereby interfering with their capacity to fulfil important
metabolic processes in the body.168 It is known that the level of fluoride
absorption depends significantly on the presence of calcium, magnesium and aluminium.169,170,171,172,173
Calcium is necessary for bone mineralization and is an important cofactor for hormonal secretion in endocrine organs. At the cellular level, calcium is an important regulator of ion transport and membrane integrity. Calcium regulation is critical for normal cell function, neural transmission, membrane stability, bone structure, blood coagulation, and intracellular signalling.174
Calcium (Ca2+) is a substantial component of bones and teeth. In addition, it plays a role in neuromuscular excitability (i.e., decreases the proper function of the conducting myocardial system, heart and muscle contractility, intracellular information transmission and the coagulability of blood). Calcium intake is important at all ages,175,176 but the need for Ca2+ is higher during childhood, fetal growth, pregnancy, and lactation.177 Epidemiological, animal and clinical studies support the existence of an inverse relation
between Ca2+ intake and the occurrence of osteoporosis.178,179
168 UK Medical Research Council Working Group Report: Water Fluoridation and Health, September 2002
169 Harrison JE, Hitchman AJW, Hasany SA, Hitchman A, Tam CS (1984). The effect of diet calcium on fluoride toxicity in growing rats. Can J Physiol Pharmacol 62: 259-265. 170 Ku hr J, Helbig J, Anders G, Mu nzenberg KJ (1987). Interactions between fluorides and magnesium. Magnesium-Bulletin 9: 110-113.
171 Cerklewski FL (1997). Fluoride bioavailability – nutritional and clinical aspects. Nutr Res 17: 907-927.
172 Spencer H, Osis D, Lender M (1981). Studies of fluoride metabolism in man. A review and report of original data. Sc Total Environ 17: 1-12.
173 McClure FJ, Mitchell HH, Hamilton TS, Kinser CA (1945). Balances of fluorine ingested from various sources in food and water by five young men. Excretion of fluorine through the skin. J Ind Hyg Toxicol 27: 159-170.
174 Suneja M, Muster H A,Batuman V,Arnold J L, Medscape Reference, Hypocalcemia, Oct 2011
175Heany RP. Nutritional factors in osteoporosis. Annu Rev Nutr. 1993;13:287–316 176Consensus Development Conference. Diagnosis, prophylaxis, and treatment of
osteoporosis. Am J Med. 1993;94:646–50.
177Garzon P, Eisenberg MJ. Variation in the mineral content of commercially
available bottled waters: implications for health and disease. Am J Med. 1998;105:125–30
178Heany RP, Gallagher JC, Johnston CC. Calcium nutrition and bone health in the
elderly. Am J Clin Nutr. 1982;36:986–1013
179Summary and recommendations. Washington, DC: DHHS (PHS); 1988. The Surgeon
A diet that is fortified in Ca2+ may reduce the rate of age-related bone loss and hip fractures, especially among adult women.180 In spite of this knowledge, nutritional surveys indicate that a significant proportion of Irish men and women consume inadequate levels of Ca2+ and particularly women may have inadequate intake of this essential mineral.181,182
Although many foods are now fortified with calcium (e.g., orange juice), naturally bio-available Ca2+ is found almost exclusively in milk, milk products, and water. Drinking water may be a significant source of Ca2+ for many consumers. It is logical therefore that one should not inject a substance into drinking water that may interact with calcium and further prevent its bio- availability for metabolism in the human body. Unfortunately this is exactly what the State is undertaking by fluoridating drinking water supplies with silicofluorides.
It is critically important therefore to note thatas far back as 1993 the U.S. Agency for Toxic Substances and Disease Registry reported183 on the toxicological profile of fluorides and stated “(b)ecause fluoride interacts with calcium ions needed for effective neurotransmission, fluoride can affect the nervous system."
It is known that fluoride not only inhibits enzymatic metabolism but that it also functions to prevent vital calcium and magnesium reactions as well as dramatically destabilising calcium binding in the body.184
Disorders in calcium metabolism give rise to many conditions including hypocalcaemia.
180McDowell LR. Minerals in animal and human nutrition. San Diego, Ca: Academic
Press; 1992. pp. 26–73.pp. 78–95.pp. 98–137.
181 SLÁN Survey of Lifestyle, Attitudes and Nutrition in Ireland Dietary Habits of the Population 2007, Department of Health and Children, 2008
182 National Adult Nutrition Survey Summary report 2011, Irish Universities Nutrition Alliance.
183Toxicological Profile for Fluorides, Hydrogen Fluoride & Fluorine, U.S.Agency for Toxic Substances & Disease, Dept Of Health & Human Services, 1993, page 125.
184 Alexander J. Murphy and Richard J. Coll. Fluoride Binding to the Calcium ATPase of Sarcoplasmic Reticulum Converts Its Transport Sites to a Low Affinity, Lumen-facing Form. The Journal of Biological Chemistry by the American Society for Biochemistry and Molecular Biology, Vol. 267, no. 24, issue of august 25, pp. 16990-16994, 1992
5.1
Hypocalcaemia
It is worth noting that the link between fluoride and hypocalcaemia was first reported by Simpson et al.185 in 1980 and by the UK Expert Group on Vitamins and Minerals in 2001.186
The presentations of patients with hypocalcaemia vary widely, from asymptomatic to life-threatening situations. Hypocalcaemia is frequently encountered in patients who are hospitalized. Depending on the cause, unrecognized or poorly treated hypocalcaemic emergencies can lead to significant morbidity or death. Hypocalcaemia is an electrolyte imbalance and is indicated by a low level of calcium in the blood.
The hallmark of acute hypocalcaemia is neuromuscular irritability. Patients often complain of numbness and tingling in their fingertips, toes, and the perioral region. Paraesthesia of the extremities may occur, along with fatigue and anxiety.
Muscle cramps can be very painful and progress to carpal spasm or tetany. In extreme cases of hypocalcaemia, bronchospasm and laryngospasm with stridor may occur. Muscle symptoms can be as severe as to present as polymyositis with associated elevated muscle-associated isoenzymes. These symptoms are corrected by calcium replacement. Acute hypocalcaemia may also have cardiovascular manifestations.187
Patients with idiopathic hypoparathyroidism or pseudohypoparathyroidism may develop neurological complications, including calcifications of the basal ganglia and other areas of the brain, and extrapyramidal neurologic symptoms. If the patient has pre-existing subclinical epilepsy, hypocalcaemia may lower the excitation threshold for seizures. Epidermal changes are frequently found in patients with chronic hypocalcaemia. These include dry skin, coarse hair and brittle nails.
If hypocalcaemia has occurred prior to the age of 5, dental abnormalities may be present. Dental abnormalities include enamel hypoplasia, defects in dentin, shortened premolar roots, thickened lamina dura, delayed tooth eruption, and an increase in the number of dental caries.
Changes in smooth muscle function with low serum levels of calcium may cause irritability of the autonomic ganglia and can result in dysphagia,
185 Simpson E, Shankara Rao LG, Evans RM, Wilkie W, Rodger JC, Lakhani A (1980) Calcium metabolism in a fatal case of sodium fluoride poisoning. Ann Clin Biochem 17: 10-14.
186 UK Expert Group on Vitamins and Minerals, Review of Fluoride, May 2001, EVM/01/03/, Page 34.
187 Suneja M, Muster H A,Batuman V,Arnold J L, Medscape Reference, Hypocalcemia, Oct 2011
abdominal pain, biliary colic, wheezing, and dyspnea. In the elderly population, disorientation or confusion may be manifestations of hypocalcaemia.188
Hypocalcaemia is strongly associated with chronic kidney disease, inadequate PTH production and magnesium depletion; each of these conditions is regarded as a risks factor for developing hypocalcaemia. It is also known that fluoride toxicity and its interaction in the body specifically targets each of these conditions.
Therefore it is reasonable to suggest that fluoride may be a significant causative factor of hypocalcaemia. Hypocalcaemia is a common metabolic complication of malignant disease often requiring emergency intervention. Although it is more frequently associated with solid tumours, malignancy- associated hypocalcaemia (MAH) is seen in a significant number of patients with blood diseases.189
Of particular interest to Ireland are the studies by Christensson et al.190,191 who in a screen of apparently healthy adults in Sweden found an extraordinarily high incidence of 1.12% with hypocalcaemia among the wider population.
A further 2% of the apparently normal adults who harboured malignant disease were found to be hypocalcaemic during this health-screening programme. Depending on the cause, unrecognized or poorly treated hypocalcaemic emergencies can lead to significant morbidity or death..192 It is also known that disorders of calcium metabolism such as hypocalcaemia are common in sarcoidosis.193
188 Schafer A L., Fitzpatrick L A.. Shoback D M, Hypocalcemia: Diagnosis and Treatment - Diseases of Bone and Mineral Metabolism
189 Sargent, Jeremy T S, Smith, Owen P, Haematological emergencies managing hypercalcaemia in adults and children with haematological disorders. Br J Haematol. 2010 May;149(4):465-77. Epub 2010 Apr 4.
190 Christensson, T., Hellstrom, K., Wengle, B., Alveryd, A. & Wikland, B. Prevalence of hypercalcaemia in a health screening in Stockholm. Acta MedScand 1976,200:131- 137.
191 Christensson, T., Hellstrom, K. & Wengle, B. Clinical and laboratory findings in patients with hypercalcaemia. Acta Med Scand 1976, 200: 355-360.
192 Bikha Ram Devrajani, Syed Zulfiquar Ali Shah, Hypocalcemia in Acute
Gastroenteritis(A Case-Control Study at Department of Internal Medicine) World Applied Sciences Journal 7 (6): 777-780,, 2009
Source: Fitzpatrick, L.A.: The hypocalcemic states. Disorders of Bone and Mineral Metabolism., PA, pp. 568-588, 2002.
5.2
Sarcoidosis
Ireland has one of the highest incidences of sarcoidosis disease in the world.194,195
This disease is a multi-system disorder, initially affecting young people in their 20s and 30s, which adversely affects quality of life. A number of spatial clusters of sarcoidosis have been indentified in Ireland which shows an incidence rate of this disease at rates up to twice or more than that of the European average. Interestingly, the incidence rate is Northern Ireland, where they do not fluoridate their drinking water, is less than half of the total national average for the Republic of Ireland and one quarter the incidence rate recorded in the highest incidence spatial locations found in Ireland.196
The geographic locations identified by Nicholson et al. of known spatial clusters for sarcoidosis mirror the geographic locations identifying vulnerable populations exposed to low calcium and magnesium in drinking water in this report. To my knowledge no study has ever been undertaken examining the potential link between drinking water quality, fluoridation and incidence of this disease in Ireland. This may explain why Northern Ireland, where drinking water is not fluoridated, has a much lower incidence rate of this disease compared to the ROI. It is noteworthy that the most at risk group of individuals to this disease are African Americans.197,198
This racial group are also the most at-risk group from certain cancers199 associated
with lack of calcium bio-availability and potentially therefore, also the most at-risk from exposure to fluoride as noted elsewhere in this report. While sarcoidosis does not feature prominently in the media in Ireland, more Irish people suffer from sarcoidosis than they do from cystic fibrosis or cervical cancer. Extrathoracic sarcoidosis is generally associated with chronic progressive disease, particularly central nervous system, bone and skin involvement (e.g. lupus pernio). There may also be cardiac disease, renal disease or eye disease.200
While the specific cause for sarcoidosis is not known, one may observe from the pattern of disease progression that calcium bio-availability and fluoride
194 A. Saeed, M. Khan, S. Irwin and A. Fraser, Sarcoidosis presenting with severe
hypocalcaemia. Irish Journal of Medical Science, Volume 180, Number 2, 575-577, DOI: 10.1007/s11845-009-0277-9
195 Nicholson T. T., Plant, B.J.,Henry M.T., Bredin C.P., Sarcoidosis in Ireland: Regional differences in prevalence and mortality from 1996-2005. Sarcoidosis Vasculitis And Diffuse Lung Diseases 2010; 27; 111-120
196 Nicholson T. T., Plant, B.J.,Henry M.T., Bredin C.P., Sarcoidosis in Ireland: Regional differences in prevalence and mortality from 1996-2005. Sarcoidosis Vasculitis And Diffuse Lung Diseases 2010; 27; 111-120
197 Bresnitz EA, Strom BL. Epidemiology of Sarcoidosis. Epidemiol Rev 1983; 5: 1224-34. 198 James DG, Hosoda Y. Epidemiology. In: James DG, Ed. Sarcoidosis and Other Granulomatous Disorders. Marcel Dekker, New York, 1994; 729-43.
199 Merrill RM, Sloan A, Anderson AE, Ryker K. Unstaged cancer in the United States: a population-based study. BMC Cancer. 2011 Sep 21;11:402.
200 A. Saeed, M. Khan, S. Irwin and A. Fraser, Sarcoidosis presenting with severe
hypocalcaemia. Irish Journal of Medical Science, Volume 180, Number 2, 575-577, DOI: 10.1007/s11845-009-0277-9
exposure may have a vital role to play in its development, especially as it is now known that fluoride exposure is associated with each of the latter conditions. The geographic location identifying high clusters in this disease mirror the vulnerable populations identified in Figure 3 who may be exposed to low calcium and magnesium in drinking water. Death due to sarcoidosis occurs in 1 to 5% of patients with the disease201 and mortality rates increase with age of patient. The association of fluoride or low calcium intake to sarcoidosis has to our knowledge never been tested. Perhaps the highest incidence of this disease recorded in the world was observed in a Galway/Mayo cluster where a prevalence of 96.55 per 100,000 was recorded.202