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been verified in later studies that expressed the degree of exposure as a percentage of lifetime living in places fluoridated at around 1 mg/ L F ( see Section 2 . 3 . 3 ) 6 . Experiment: studies of natural variation that plausibly imitate conditions of a randomized experiment. This criterion was addressed most convincingly in the five " twin - cities " trials ( Section 2 . 3 . 2 ) where intervention and control cities were studied in parallel , over multiple years, making them equivalent to experimental trials in many aspects, although not with respect to random allocation . Subsequent studies with comparable , non - randomized designs were reviewed and given the highest quality ratings in systematic reviews reported this century . 7 . Coherence, plausibility and analogy: a proposed causal relationship should not violate known scientific principles. The causal interpretation is biologically plausible, with good evidence that dental caries prevention is due to a combination of pre - eruptive mechanisms ( i . e . , incorporation of fluoride into developing enamel which becomes more resistant to subsequent acid attacks ) and post- eruptive mechanisms ( i . e . , concentration of intra - oral fluoride in dental biofilm , inhibiting demineralization and enhancing remineralization ) .