The benefits of using fluoride to prevent caries have been known for many years, but a complete understanding of this mechanism is still being researched. The fluoride concentration in the apatitic structure of enamel does not have as significant an effect on reducing caries as a continuous presence of fluoride in the plaque liquid. Concentrated, topical fluoride agents (such as in toothpaste, fluoride mouth rinses, gels, or varnishes) have a different mechanism of fluoride protection than low-concentration applications (such as fluoridated water). In initial caries lesions and plaque, concentrated agents form globules of a calcium fluoride-like material on the enamel surface. This material is fairly insoluble, possibly because it is coated with phosphates or proteins. This mechanism explains how the topical application of a fluoride varnish, two or three times a year, can result in caries reduction.