Dentifrices. Part 2: the evidence behind their formulation

Successful oral hygiene should rely on advice from the best, currently available evidence.¹ A dental care professional should then be able to advise each individual patient on which dentifrice is most appropriate in his/her particular situation.

All major brands sell products that are supported by a substantial body of evidence. Many scientific publications on dentifrice are published or sponsored by the dentifrice industry. A recent meta-review regarding the evidence behind dentifrices,² like most other scientific literature reviews, still does not include a recommendation for the individual consumer with respect to which specific dentifrice to choose and purchase.³ It is, therefore, debatable whether the professional has the correct scientific information from dentifrice research to offer effective advice on a dentifrice based on the patient's requirements. There are several challenges, as outlined in Table 1.

Dentifrice formulations

The complex formulations of modern dentifrices make them one of the most sophisticated pharmaceutical products on the market today. The demands of the consumer, coupled with the complexity of the oral cavity, make it a challenging development process.⁴ Insufficient concentrations of the active ingredients and/or chemical incompatibility within the dentifrice formulation may result in a lack of efficacy. Several challenges can be identified in formulating an effective fluoride dentifrice. Dentifrices of equal total fluoride concentration can significantly differ in their capacity to release bioavailable fluoride owing to differences in their formulation composition.^5,6 Therefore, the bioavailable amount released is regarded as a more appropriate parameter than total fluoride content.^6,7 Fluoride can appear in different ways in dentifrices. Soluble fluoride is the only one capable of interacting with the dental surface and causing an anti-caries effect.⁸ Fluoride is primarily known for its adherence to the tooth surface and its incorporation into the pellicle and dental plaque.⁹ Studies on the interaction of fluoride with oral soft tissues are sparse, which may be due to experimental design challenges. However, oral soft tissues are probably the main oral reservoir for fluoride.¹⁰

The most commonly used anionic surfactant ingredient in dentifrices is sodium lauryl sulphate (SLS),^11,12 which can also influence fluoride effectiveness, and may interfere with fluoride uptake by enamel.¹¹ SLS increases cleaning and foaming actions.¹² Dentifrices with strong flavour characteristics may also affect fluoride effectiveness. This may be primarily a result of excessive salivary stimulation from the strong taste and thus, an increased rate of fluoride clearance from the mouth by dilution.^10,11

Another dentifrice ingredient is calcium phosphate. A range of calcium phosphate technologies has been developed to enhance the ability of fluoride to promote remineralization.^5,6,10 Dentifrices with only fluoride remineralize the surface layer of a caries lesion predominantly.⁵ Dentifrice with added calcium phosphate technologies remineralize the body of the lesion.⁵ However, a concern with adding calcium to dentifrice formulations is the potential for unwanted reactions. Calcium, fluoride, and phosphate may interact to form poorly soluble phases in a paste. During shelf life and when in use, this can reduce the bioavailability of the fluoride and/or the calcium ions.^5,6

Findings from in vitro studies suggest that adding baking soda to a dentifrice may interfere with the reactivity of fluoride with enamel, mainly reducing the concentration of the CaF₂ formed.^13,14 This illustrates the point that adding other active ingredients to a dentifrice, such as baking soda in this instance, requires careful formulation.

Ingredients in dentifrice that aim to inhibit calcium phosphate deposits and prevent the development of calculus are mainly pyrophosphates. Theoretically, pyrophosphates may negatively affect the demineralization–remineralization equilibrium at the tooth surface. Therefore, it is remarkable that in the past 20 years, no long-term, large-scale trials have been published to provide convincing evidence that pyrophosphates do not compromise the caries protection given by fluoride dentifrice. Manufacturers do, however, clearly indicate that products with pyrophosphates are not suitable for children under 12 years of age.¹⁵

Contemporary dentifrices

Dentifrice formulations often contain more than 20 ingredients. Their chemical compositions are constantly changing because of manufacturer competition, commercial innovation and scientific development.¹⁶ To formulate a dentifrice, several ingredients are essential. Abrasive agents, modified silica abrasives or enzymes help to clean the teeth and may help to whiten teeth by removing surface stains. Examples are calcium carbonate, dehydrated silica gel, hydrated aluminium oxide, magnesium carbonate, phosphate salts and silicates.¹⁷ Detergents, such as SLS or sodium N-lauryl sarcosinate¹⁷ create a foaming action that may help to increase the solubility of plaque and accretions during brushing. SLS is also known to have a slight anti-plaque effect.¹¹

Flavouring agents and non-caloric sweeteners, such as saccharin, are used to improve the taste. Sugar or other cariogenic ingredients are not permitted in any ADA-accepted dentifrices. Humectants, such as glycerol, propylene glycol and sorbitol, are added to prevent dehydration in the dentifrice.¹⁷ Thickening agents or binders are added to stabilize the dentifrice formula. They include mineral colloids, natural gums, seaweed colloids and synthetic cellulose.¹⁷

Hydrogen and carbamide peroxides help to reduce intrinsic stains.¹⁷ Current dentifrices may also contain several active ingredients to help improve oral health. Desensitizing agents are used to reduce oral discomfort owing to hypersensitivity, with potassium nitrate and stannous fluoride commonly being used.¹⁷ Antimicrobial agents (such as stannous fluoride) are used to reduce gingivitis, and pyrophosphates and zinc citrate are included to reduce the build up of calculus.¹⁷

In an attempt to enhance the natural salivary antimicrobial defence mechanisms, enzymes and proteins have been added to dentifrices. Zendium dentifrice (Unilever, the Netherlands) contains a triple-enzyme system that includes amyloglucosidase, glucose oxidase and lactoperoxidase. This combination generates the natural antimicrobial agents of hydrogen peroxide and hypothiocyanite ions. The salivary proteins, lactoferrin and lysozyme, are also added to the dentifrice.^18–20 A recent monadic clinical study indicated that long-term use of this dentifrice was associated with better gingival health status than with the use of other dentifrices.¹⁸

Dentifrices and abrasivity

Dentifrice formulations include abrasives to improve the rheology of the dentifrice⁴ and to remove stained pellicles.^21,22 Improved surface smoothness is conductive to a feeling of oral cleanliness. An increase in lustre of the tooth surface contributes to oral aesthetics. Brushing with a dentifrice without an abrasive often results in stained teeth.²³ Highly polished enamel appears whiter than duller enamel and is less receptive to the accumulation and retention of dental plaque, calculus, and extrinsic stain. The polishing ability of a dentifrice is therefore an important physical aspect associated with the abrasive system within the composition.²⁴ Abrasive substances may alter the substantivity or the antimicrobial activity of active ingredients.^25,26

Low correlations between the abrasiveness of the dentifrices studied and their cleansing properties indicate that cleaning is not necessarily related to the abrasiveness of dentifrices.²⁷ For details on the particle size and radioactive dentine abrasion (RDA) value of dentifrices, see Table 2.

Alternative dentifrice formulations

Natural, herbal and organic dentifrices are an answer to consumer preferences and concerns about chemical ingredient safety. By emphasizing the use of plant extracts and non-synthetic substances in their branding, the idea is that these ‘natural‘ ingredients are safe. However, terms such as ‘natural’ and ‘herbal’ can be used loosely without being clear what it means, which can make it confusing for consumers.³

A modern example of a popular product framed as ‘natural’ is charcoal dentifrice. An increasing number of toothpastes with activated charcoal are commercially available.²⁸ It has been intensively promoted by influencers on social media. Internet advertisements have included unsubstantiated therapeutic claims, such as antibacterial, antifungal, antiviral and oral detoxification properties, as well as potentially misleading product assertions.²⁹ In the scientific literature, there is insufficient clinical and laboratory data to substantiate the safety and efficacy claims of charcoal and charcoal-based dentifrices.²⁹ Nevertheless, 96% of commercially available activated charcoal toothpastes claim to effectively whiten teeth in their marketing expressions.³⁰ Studies have identified other methods of whitening to be more effective.^28,30 For instance, most dentifrices that are specifically formulated for tooth whitening have a beneficial effect in reducing extrinsic tooth surface discolouration.³¹ The possible health risks associated with the use of charcoal-based dentifrices have been considered to be related to the possible inclusion of human carcinogenic polyaromatic hydrocarbons in charcoal and the use of bentonite clay in some charcoal-based dentifrices.³² Charcoal, as an ingredient, may contain high concentrations of heavy metals.^33,34 Also, charcoal has been recognized as an abrasive mineral to the teeth and gingiva.²⁹ A study that evaluated 50 charcoal-based dentifrices sold via the internet showed that only 8.0% of the products contained fluoride.²⁹ Furthermore, charcoal is a well-known absorptive agent capable of inactivating fluoride.²⁹ In effect, charcoal-based dentifrices will most likely not provide (sufficient) fluoride to the consumer. As fluoride is the main effective ingredient in dentifrice for caries prevention, this is very undesirable.^29,32,35,36

In contrast to popular ‘green’ orientated dentifrices, the well-known commercial fixed formulations of premier brands or their derivative white label dentifrices are generally well described and researched. However, recently, recognized brands have also started to sell charcoal dentifrice with fluoride added to the list of ingredients. These commercial companies are capitalizing on the popularity that began with little or no scientific support through the spread of fake news.³⁷ Such a marketing approach is not limited to just charcoal-based dentifrices.³²

Consumer mistrust of several ingredients used in the industry has led to the development of a trend for homemade dentifrice.³⁴ A recent study collected 84 homemade dentifrice recipes from 504 websites.³⁴ All studied recipes were fluoride free. The quantities of substances to be used were imprecise. The recipes were difficult to make and impossible to control. Abrasivity, purity and microbial contamination could not be predicted and verified. The importance of professionals addressing the problem and warning consumers of the dangers involved was emphasized.³⁴