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British Medical Journal
Volume 298; June 24 1998; pp. 1686-1687
Tissue response of gastric mucosa after ingestion of fluoride
Carl-Johan Spak, Svante Sjostedt, Lennart Eleborg, Bela Veress, Leif Perbeck, Jan Ekstrand.
Department of Cariology, School of Dentistry and Departments of Surgery, Anaesthesiology, and Pathology, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden.
Fluoride has been used successfully to prevent dental caries and has also been used to treat osteoporosis. Doses of sodium fluoride of about 50 mg a day have long term beneficial effects on the mineral content of bone and the incidence of fracture. (1) These doses, however, have resulted in gastric disturbances in some patients. (1, 2) We studied the response of the gastric mucosa after a single dose of fluoride.
Methods and results
Twelve healthy volunteers (age range 22-45, four men and eight women) underwent two endoscopies after overnight fasts. One endoscopy was a control and the other was performed two hours after subjects ingested 20 ml sodium fluoride solution containing 20 mg fluoride (53 mmol/l). There was at least two weeks between endoscopies to assure complete recovery of the mucosa in case of iatrogenic injuries from the gastroscope. During the endoscopy the mucosa was graded according to an arbitrary scale (0 to 4), slightly modified from that of Lanza. (3) The stomach was also videotaped and the tape later examined by another gastroenterologist. The results of both examinations were similar (p<0.01, Wilcoxon's signed rank test). Two biopsy specimens were taken from the antrum and two from the body of the stomach. The histopathological changes were assessed on an arbitrary scale from 0 to 3.
After taking fluoride all subjects had petechiae or erosions (graded 3 or 4) in the body of the stomach and six had changes (graded 1-4) in the antrum. No petechiae or erosions were recorded in the oesophagus or the duodenum. In four subjects a layer of clotted blood was found over a large part of the gastric mucosa. The table shows the results of the macroscopic and microscopic evaluations. Three components of the gastric mucosa were affected by fluoride: the surface epithelium, the gastric pits, and the superficial stroma. The damaged epithelial cells were smaller than undamaged ones, and the vacuoles containing mucus were reduced in size or had disappeared. The most severely damaged epithelium was disrupted or totally lost. The most characteristic changes in the gastric pits were irregular dilation and flattening of the epithelial cells. There was also a noticeable los of mucin.
Comment
Our study showed that one ingestion of fluoride at a dose used to treat osteoporosis affects the gastric mucosa. We do not know, however, to what extent repeated doses affect the mucosa, which might adapt after a while, as occurs with regular treatment with aspirin. (3) Our findings confirm data from experiments on animals, which showed that fairly low concentrations of fluoride can damage the surface of the gastric mucosa. (4)
The low pH of gastric juice and the formation of hydrogen fluoride probably caused the mucosal injuries. The uncharged molecule can easily penetrate the lipid cell membranes, enter the cell, and dissociate to fluoride and hydrogen ions, which may have toxic effects on enzyme systems and cause structural damage.
Symptoms like nausea and vomiting are not unusual when fluoride is used to treat osteoporosis. (2) They also occur occasionally when high doses are used for dental prophylaxis. (5) In our study only four subjects developed nausea, which suggests that using nausea as the first sign of fluoride toxicity might not be valid as all our subjects showed mucosal damage.
Finally, our results are also clinically important in dentistry because as much as 30 mg fluoride may be swallowed by children after prophylactic treatment with fluoride gel (1.23% fluoride). (5) If the risk of subsequent gastric injury is as high as our results suggest the use of such large amounts of fluoride in children should be questioned.
Part of this study was supported by grants from the Swedish Medical Research Council (No 6002) and the National Institute of Dental Research/National Institutes of Health (United States Public Health Services grant No 5Q DE07010).
1. Mamelle N, Meunier PJ, Dusan R, et al. Risk-benefit ratio of sodium fluoride treatment in primary vertebral osteoporosis. Lancet 1988; ii: 361-5.
2. Riggs BL, Hodgson SF, Hoffman DL, Kelly PJ, Johnson KA, Taves D. Treatment of primary osteoporosis with fluoride and calcium. Clinical tolerance and fracture occurrence. J.A.M.A 1980; 243: 446-9.
3. Lanza FL. Endoscopic studies of gastric and duodenal injury after the use of ibuprofen, aspirin, and other nonsteroidal anti-inflammatory agents. Am J Med 1984; 77:19-24.
4. Pashley DH, Allison NB, Easmann RP, McKinney RV, Horner JA, Whitford GM. The effects of fluoride on the gastric mucosa of the rat. J Oral Pathol 1984; 13:535-45.
5. LeComte EJ. Clinical application of topical fluoride products -- risks, benefits, and recommendations. J Dent Res 1987; 66: 1066-71.
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