When fluoride has been used (at doses of 18-34 mg/day) as an experimental treatment for osteoporosis, gastric pain is one of the two main side effects consistently encountered. To better understand how fluoride causes this effect, researchers have sought to determine how fluoride affects the tissue that lines the gastrointestinal tract.

In a study published in the British Medical Journal, the researchers gave a single dose of 20 mg/F to 12 healthy volunteers and then examined, both microscopically and macroscopically, the impact on the gastric mucosa. The examination revealed that the fluoride dose caused erosions (petechiae) in the stomach of all the subjects tested, with six of the subjects having similar effects in the antrum as well. Other findings were as follows:

“In four subjects a layer of clotted blood was found over a large part of the gastric mucosa… 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 loss of mucin.”
SOURCE: Spak CJ, et al. (1989). Tissue response of gastric mucosa after ingestion of fluoride. British Medical Journal 298:1686-87. [See study]

Despite the fact that tissue damage was found in all 12 volunteers, only 4 of the volunteers experienced nausea. Thus, “using nausea as the first sign of fluoride toxicity might not be valid as all subjects showed mucosal damage.”

In a follow-up study, published in 1990, the authors examined the impact of lower doses of fluoride to determine whether the use of self-applied topical gels could cause damage to children’s gastric system. In the study, the volunteers ingested a single dose of just 3 to 9 mg of fluoride, which is considerably lower than what some people ingest from higher-concentration professional fluoride gels. Despite using low doses, the authors again found significant damage to the gastric mucosa. They described this damage as follows:

“After F exposure, histopathological changes were found in nine out of ten patients. The surface epithelium of the gastric mucosa showed the greatest effects: In two cases, there was a slight dilation of the gastric pits and a focal loss of surface epithelium. In some cases, the mucus-containing intercellular vacuoles were reduced in size, and focal hemorrhages within the epithelium occurred.”
SOURCE: Spak CJ, et al. (1990). Studies of human gastric mucosa after application of 0.42% fluoride gel. Journal of Dental Research 69:426-9.

Interestingly, the authors note that they “could not find any correlation between the presence of mucosal injuries and the size of the ingested F dose.” Based on this, they suggest that individual variability to fluoride may be a more important predictor of fluoride-induced gastric damage when low levels of fluoride are ingested. As they note: “The various reactions of the mucosa to F exposure are most likely due to individual variations in gastric fluid volume, gastric pH, and motility and mucosal resistance.”

Such findings emphasize the difficulty of determining a uniform “safe” fluoride dose for an entire population. Indeed, if significant variability to fluoride is observed among 10 otherwise healthy humans, the variability is likely to be quite vast when studying the population as a whole, especially when including those with diseases that render one particularly susceptible to fluoride toxicity.

Dose Response Data from Spak (1990):

excerpts from studies Examining Fluoride’s Effect on Gastric Mucosa in Humans

“In a prospective case controlled study, we evaluated the adverse effects of long-term fluoride ingestion on the gastrointestinal tract. Ten patients with otosclerosis who were receiving sodium fluoride 30 mg/day for a period of 3-12 months, and 10 age- and sex-matched healthy volunteers were included… Seven subjects (70%) ingesting fluoride had abdominal pain, vomiting, and nausea. Petechiae, erosions, and erythema were seen on endoscopy in all the subjects, but not in the controls. Histological examination of the gastric antral biopsy showed chronic atrophic gastritis in all the subjects but in only one (10%) healthy volunteer. Scanning electron microscopic examination showed “cracked-clay” appearance, scanty microvilli, surface abrasions, and desquamated epithelium in the subjects ingesting fluoride, but not in the controls. We conclude that long-term fluoride ingestion is associated with a high incidence of dyspeptic symptoms as well as histological and electron microscopic abnormalities.”
SOURCE: Das TK, et al. (1994). Toxic effects of chronic fluoride ingestion on the upper gastrointestinal tract. Journal of Clinical Gastroenterology 18(3):194-9.

“In a randomized double-blind study with two parallel groups of 10 male healthy volunteers each the response of gastric mucosa after a 7 days ingestion of sodium fluoride tablets (NaF) or sodium monofluorophosphate tablets (MFP) was compared. Gastroscopic evaluations were performed before treatment, day 1 and day 7… In the MFP-group no severe gastric lesions were observed, whereas in the NaF-group in 7 of the 10 subjects significant gastric mucosal lesions including acute hemorrhages and free blood in the gastric lumen were found. The differences of the lesions scores in both groups were statistically significant (p = 0.0015)… In summary, under the experimental conditions used MFP is well tolerated by the stomach while NaF produces significant gastric mucosal lesions.”
SOURCE: Muller P, et al. (1992). Sodium fluoride-induced gastric mucosal lesions: comparison with sodium monofluorophosphate. Z Gastroenterol. 30(4):252-4.

“Dental prophylaxis with APF gels (1.23%) may cause gastric distress as a side-effect. This gastric irritation is probably due to a direct toxic effect of fluoride (F), swallowed in conjunction with the treatment, on the gastric mucosa. The aim of the present study was to investigate whether–and to what extent–a dental treatment with 3 g of a 0.42%-F gel could affect the gastric mucosa due to inadvertent swallowing of the gel. Ten subjects underwent a control gastroscopy, and two weeks later, a second gastroscopy was performed two h after a F gel treatment. During the gastroscopy, the mucosa was examined and the injuries graded according to an arbitrary scale. Four biopsies of the antral and corpus regions of the stomach were taken and evaluated histologically. The mean (+/- SD) amount of F retained after the application was 5.1 +/- 2.1 mg, i.e., 40% of the applied amount of F. Petechiae and erosions were found in the mucosa in seven of the ten patients. The histopathological evaluation revealed changes in nine of ten patients, with the surface epithelium as the most affected component of the mucosa. The present study clearly shows that a treatment with a F gel of rather low F concentration may result in injuries to the gastric mucosa. The importance of current recommended guidelines so that the amount of F swallowed during a gel application can be minimized is emphasized. From a toxicological standpoint, the use of a low-F gel instead of a 1.23%-F gel in small children is recommended for avoidance of adverse gastric effects.”
SOURCE: Spak CJ, et al. (1990). Studies of human gastric mucosa after application of 0.42% fluoride gel. Journal of Dental Research 69:426-9.

“We studied the response of the gastric mucosa after a single dose of fluoride. 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)… 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… 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 loss of mucin. Our study showed that one ingestion of fluoride at a dose used to treat osteoporosis affects the gastric mucosa… Symptoms like nausea and vomiting are not unusual when fluoride is used to treat osteoporosis. They also occur occasionally when high doses are used for dental prophylaxis. 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.”
SOURCE: Spak CJ, et al. (1989). Tissue response of gastric mucosa after ingestion of fluoride. British Medical Journal 298:1686-87.

Print PDF