milk and milk products [27] and/or to individuals who suffer from celiac disease who often have inadequate calcium intake [28]. The effects on raising intra-oral calcium concentrations have not been studied yet but are likely to be more pronounced from these foods than from supplements, which in most cases are in tablet form with little to no contact with the oral cavity when administered (with the exception of calcium-containing gummy candies). In this context, the importance of biofilm-contained calcium, which in turn determines the concentration of retained fluoride, must be noted [29]. Several studies [e.g., 30, 31] have shown that it is possible to enhance intra-oral fluoride retention through prior application of ionic calcium (as lactate) in a rinse format. Somewhat similar effects can be expected if a fluoride application immediately follows the consumption of calcium-fortified foods (e.g., orange juice with calcium at breakfast followed by tooth brushing with fluoride toothpaste). However, calcium bioavailability and concentration, but not total dose, are lower in the case of orange juice with calcium versus a 150 mM calcium lactate rinse [30] (350 mg Ca in an 8 oz serving correspond to 36 mM Ca vs. 150 mM in a 20 mL rinse corresponding to 120 mg Ca).
Perhaps a more important aspect of calcium supplementation is that related to pregnancy, as decreased salivary calcium and phosphate concentrations have been reported during late pregnancy [32], thereby leading to increased caries risk [33]. A recent review by the Cochrane Group considered the current evidence for calcium supplementation in preventing hypertensive disorders and related problems, including caries [34]. However, only one caries-related study could be retrieved which, nonetheless, demonstrated a caries reduction in the 12-year-old offspring of those mothers receiving calcium supplements during pregnancy [35]. A somewhat related study was able to demonstrate that a high intake of cheese during pregnancy, but not milk, was able to reduce caries risk during childhood [36].
Calcium supplementation of erosive foods and in particular acidic beverages has attracted attention over the last decades. Here, calcium addition increases the degree of saturation of the solution (beverage) with respect to tooth minerals, thereby lessening the erosive potential of the contained acids. A range of commercial and experimental products have been found to reduce erosion otherwise caused by the same beverage without calcium supplementation, although sometimes at the expense of organoleptic properties. Likewise, linear chain polyphosphates, added to some beverages as a preservative (and dog food for the control of tartar [37]), have also been investigated for their ability to reduce erosion (for review of research thus far on these topics, see [38]). Lastly, the consumption of beverages containing phosphoric acid has been linked with increased risk of osteoporosis in some populations [39], although this was postulated to be due to replacement of milk with such beverages [40]. Nonetheless, there appears to be no conclusive evidence thus far as to the role of excess dietary phosphorus and bone health [41].
A considerable body of evidence, derived from animal studies, exists on the role of phosphate supplemented diets in caries prevention [42]. A subsequent multi-year study in 2,262 children in Sweden [43], with dicalcium phosphate being added to flour used for baked goods and to table sugar, was able to demonstrate that a calcium and phosphate supplemented diet can reduce the incidence of caries. However, the dicalcium phosphate used was contaminated in that it contained fluoride during the first year of the study, and caries was determined on only 4 proximal surfaces. Subsequent studies in the US (1,672 and 969 children, respectively; same dicalcium phosphate administration), however, failed to demonstrate anti-caries benefits of added calcium and phosphate [44, 45].
An animal caries study to determine the effect of phosphate structure to reduce caries incidence compared sodium ortho-, pyro-, tripoly-, trimeta-, and hexametaphosphate when present in the diet [46]. Sodium trimetaphosphate (TMP), a compound with a ring structure, was found to be most efficient, followed by hexametaphosphate (chain structure). TMP was later unsuccessfully evaluated as an anti-caries agent when formulated in a fluoride toothpaste [47]; however, TMP is still being researched to this day [48]. Sodium hexameta-, pyro-, and tripolyphosphate are nowadays used primarily for the purpose of tartar prevention and chemical stain removal in oral care products [1], although recent research on nano-sized sodium hexametaphosphate has shown promise for its ability to enhance caries lesion remineralization [49].
Sodium phytate, the sodium salt of the hexaphosphate ester of inositol and present in unrefined sugars and whole grains, legumes, nuts and seeds, has been shown to retard demineralization in vitro [50] and in animal caries studies [51]. However, a later study was unable to replicate earlier findings [52]. It has also been postulated that the effect of phytate (and presumably other compounds naturally present in foods) is restricted to its isolated application in the absence of the food matrix [53]. Similar to phytate, calcium glycerophosphate has attracted attention in the past, although less as a dietary constituent than it being formulated into oral care products alongside fluoride (for review, see [54]). Nonetheless, the present animal caries data on calcium glycerophosphate, when administered as part of the diet, is encouraging [e.g., 55]. In the context of animal caries studies, it must be noted that the salivary phosphate content in rats is approximately one tenth that in humans [56], which suggests that the anti-caries effects of dietary phosphate is likely to be more pronounced in rats than in humans. This explains earlier mentioned discrepancies for anti-caries effects of calcium phosphate enriched diets in animals versus humans.
More recently, phosphoryl oligosaccharides of calcium (POs-Ca) have been evaluated for their anti-caries and erosion prevention properties when added to foods. Three studies on chewing gums fortified with POs-Ca were able to demonstrate enhanced enamel caries lesion remineralization in vivo [57] and in situ [58, 59]. Similar erosion prevention effects were observed when POs-Ca were added to an apple juice drink [