CARIES-INHIBITING AGENTS
Authors: James H. Shaw
Journal: Pharmacological Reviews (1959)

From this survey of the literature pertaining to the etiology of dental caries, the procedures for the estimation of caries-inhibiting properties of potentially effective agents and the results attained from these procedures, three major conclusions can be drawn.

1. There is an unfortunate paucity of well-designed, carefully controlled and conducted investigations, especially in the clinical area. Possibly the single greatest need in future studies on caries-inhibiting agents is the development of a dependable chain of sequence from screening procedures in vitro, through laboratory animals to full-scale clinical trials where the incidence of dental caries is the measured parameter. Although this course seems difficult to attain on the basis of the present frustrations with poor correlations between the three stages, the ultimate gain to be attained more than merits the intermediate tribulations.

2. Unquestionably, the consumption of foods and confections with a low rate of oral clearance which contain readily fermentable carbohydrates is one of the primary causes of dental caries in caries-susceptible populations. Major restrictions in the consumption of these materials with the maintenance of ideal oral hygiene can lead to major reductions in dental caries among the most caries-susceptible populations. Unfortunately numerous obstacles stand in the way of the widespread achievement of this goal, among which are individual preferences and biases, economic status of the family, the greater productivity of carbohydrate foods per unit of land, and last but not least, the difficulty in maintaining the interest of the individual in the faithful continuation of prolonged procedures.

3. On the basis of presently available information, the most effective and best substantiated caries-inhibiting agent is the fluoride ion when ingested continuously throughout tooth development and the posteruptive life of the teeth in order that optimal levels of fluoride may be incorporated into the hydroxyapatite lattice. Fluoridation of public water supplies at optimal and carefully controlled levels offers the best available method for the partial prevention of dental caries at minimum cost for the maximum number of the population. Clearly inferior with respect to effectiveness is the topical application of fluorides to the tooth surfaces after eruption, which process is capable of producing modest reductions in the incidence of dental caries.

Clearly subsidiary at present to the above conclusions are several more obscure areas for which much additional data are needed.

1. Although animal studies indicated a high potential for control of dental caries through the use of penicillin and other antibiotics in the diet, dentifrices containing penicillin have in general proven to be disappointing, especially when used without careful supervision. The benefits to be derived appear to be less than the potential hazards of the development of penicillin-resistant strains of microorganisms and of sensitization on the part of the subjects. Tyrothricin, the only other antibiotic known to have been tested in a dentifrice, after indifferent results in the hamster was reported to be moderately effective in one small clinical study.

2. Dentifrices containing low levels of urea and dibasic ammonium phosphate have had little or no influence on caries incidence. On the basis of present data, which are clearly inadequate for a final appraisal, high levels of urea and dibasic ammonium phosphate in dentifrices appear to have been modestly effective in inhibiting carious lesions. Present preliminary studies with sodium N-lauroyl sarcosinate likewise suggest modest reductions in dental caries incidence.

3. Certain nutritional studies after the teeth are developed and fully erupted offer interesting leads. Lysine deficiency in rats results in a high incidence of smooth surface carious lesions but does not appear to have any significant influence on lesions in the occlusal sulci. Provision of L-lysine in the diet, in the drinking water or by intubation caused major reductions in the incidence of dental caries through what appeared to be a systemic pathway rather than through direct oral contact with the tooth surfaces. Likewise supplements

of soluble inorganic phosphates in the lysine-deficient diet of rats caused major reductions in the incidence of smooth surface lesions. Pyridoxine has also been reported in cursory studies to result in reductions in the incidence of dental caries in the hamster and the rhesus monkey. Vitamin D supplementation has been shown to cause modest postdevelopmental reductions in the incidence of dental caries in children. With the exception of the latter studies on vitamin D, the other three trials have been conducted with experimental animals without application to human populations. In addition, the three nutrients studied are not known to be deficient or borderline by current standards in human populations where the incidence of dental caries is high.

4. Observations on the ability of various dietary manipulations, such as natural versus purified diets and varied calcium-phosphorus ratios during tooth development to alter caries-susceptibility suggest that there are other areas of interest than fluoride ingestion that need to be extended in the laboratory and tested in clinical trials.