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The following three articles were originally published in and reproduced here with the permission of, Dental Digest, which is provided as a service to health professionals through an educational grant from the Sugar Bureau.

By J M ten Cate, Academic Centre for Dentistry, Amsterdam, The Netherlands

The caries-preventive effects of fluoride have been known since the 1930s. But, it has taken a considerable length of time for the mechanisms of action of fluoride to be unravelled. Our current understanding of the caries process and the way fluoride interacts with tooth decay has led to a more rational approach to fluoride use resulting in increased efficiency and improved cost effectiveness.

Dental caries is now known to result from an imbalance between the dissolution of the dental hard tissue and the reprecipitation of these tissues from the oral fluids. The former occurs when dietary sugars and starches are metabolised in dental plaque, forming cariogenic acids and yielding a pH of plaque which can dissolve dental tissue minerals. Typically this occurs at pH values below approximately 5.5. The building blocks of the hard tissues (in particular calcium and phosphate ions) are present in saliva and the aqueous phase of dental plaque. Consequently, when the pH of plaque is near neutrality (pH 7.0) these minerals present in saliva can be deposited onto the tooth surface. When this occurs at the tooth surface it leads to calculus formation. When minerals are deposited in porous dental tissues, however, remineralisation of previously formed caries lesions or the maturation of the dentition after eruption takes place.

Fluoride interferes with both of these processes mentioned above. Incorporation of fluoride into the tooth mineral reduces the potentially erosive and cariogenic effect of acids. Moreover, the presence of low concentrations of fluoride in saliva, or plaque, stimulates the precipitation of hydroxyapatite, a main component of tooth enamel. In this way, both sides of the carries pendulum are favourably affected by fluoride. The presence of fluoride in dental tissues does not completely protect teeth from cariogenic acids: dissolution is only slowed down, and this again depends on whether fluoride ions are available in the fluids in which the teeth are bathed (i.e. saliva). This explains why fluoride is only effective in caries prevention when it is provided to the oral cavity on a regular basis. Fluoride provided via drinking water, or by regular brushing with fluoride toothpaste, has been shown to be significantly more effective than applying fluoride periodically e.g. by topical applications.

Calcium fluoride.

In addition to the mechanism described above, fluoride may precipitate onto tooth surfaces as calcium fluoride (CaF2) (1). Elevated levels of fluoride, typically above 10 parts per million (ppm), are required for this to occur. Calcium fluoride forms after the topical acidic application of fluoride, for example with products containing 0.4 or 1.2% fluoride. In the past, topical applications were formulated with the addition of phosphoric acid, commonly known as Acidulated Phosphate Fluoride solutions or gels. The addition of phosphate served to limit the dissolution of enamel or dentine and thereby the formation of calcium fluoride. This approach was based on the observation that calcium fluoride dissolves quickly in water, and it was assumed that calcium fluoride would be washed away from the dentition by the oral fluids. However, it was found later that relatively stable calcium fluoride globules were formed in the mouth, protected by a protein and phosphate rich coating. Moreover, these globules have been shown to possess pH- modulated slow release properties for fluoride. In essence, this means that at low pH values the stabilising coating breaks open releasing the fluoride. Fluoride is therefore available to act against dental caries development when it is most needed.

Formulation issues.

In recent years, questions have been raised over how the protective effects of fluoridated toothpaste could be increased further. Should the fluoride content be increased, possibly beyond the current maximum level permitted, or should the type of fluoride active in toothpaste be changed? On the latter topic, there have been many changes to the formulation of toothpaste over time. The fluoride salt used experimentally in toothpaste in the 1940s (sodium fluoride) was found to be clinically inactive as a result of binding to the abrasive used at that time. This led to the formulation of mono fluorophosphate and the use of stannous fluoride, both of which were compatible with calcium-containing abrasives. In the 1980s abrasives compatible with sodium fluoride were introduced, e.g. hydrated silica. Besides mono fluorophosphate and sodium fluoride, amine fluoride is added to toothpaste and other caries-preventative products. The mode of action of all fluoride ‘actives’ is similar, in that the caries preventative effect originates from the fluoride anion (F-). In addition to this, amine and stannous, as counter-ions, have an antimicrobial effect.

Fluoride level in toothpastes.

The optimal level of fluoride that should be added to toothpaste has also been the subject of wide discussion. A number of studies have recently investigated the use of fluoride in toothpaste at levels exceeding the maximum level allowed in the USA (1100ppm) or in Europe (1450ppm). Increasing fluoride addition to 2800ppm resulted in a 20% increase in protective effect observed (2). This additional benefit, however, is considered to be relatively small in comparison to other tooth brushing parameters (frequency of brushing, rinsing after brushing etc.). It was also argued that the additional risk of fluorosis, at least as perceived by the public, would not justify further investigation of this option. Other studies have even questioned the 1500ppm maximum level applied in Europe (3), as relatively little data illustrate increased efficacy as a result of increasing fluoride addition from 1000 to 1450ppm (4). Without question, this issue requires further investigation to determine the optimum formulation of toothpaste and obtain universal agreement on acceptable fluoride levels. Children’s toothpaste Fine-tuning the fluoride level of toothpaste, in terms of maximum benefit and minimal fluoride ingestion, is also of relevance in designing a fluoride toothpaste to be used by children. For this reason, a study was performed on the dose-response relationship of a range of fluoride concentrations in toothpaste using a laboratory-simulated dental caries model. ‘pH cycling’ experiments simulate the fluctuations in pH that occur naturally in the mouth. The effects of treatments on inhibiting demineralisation and enhancing remineralisation are differentiated by this method. The greatest net effect on enamel was observed between the 0 and 250ppm fluoride treatments. But some additional benefit was observed with increasing fluoride concentration. Remineralisation also increased gradually with increasing fluoride concentration. These findings confirm that increasing the fluoride content of toothpaste gives additional benefit, with the largest effect observed in the range 0-500ppm fluoride. A fluoride toothpaste, containing 500ppm, has been specially developed for children’s use and is now available in many European countries.

Fluoridation of drinking water.

Toothpaste is obviously not the only vehicle by which fluoride may be supplied to the dentition and products such as fluoride rinses, lacquers, gels, and tablets are still prescribed for use. Large differences exist between countries, in regard to the protocols employed. These originate to an extent from government preference, but they are also determined by regional caries prevalence data and geographical factors. Fluoridation of the drinking water, either when naturally present or when it is added, is still the preferred method of administering fluoride to a population. The reason for this is that water is drunk by consumers in high volumes and is also used for cooking. The frequency of exposure of teeth to fluoride is therefore increased. An important consideration in implementation of water fluoridation is that this method of fluoride ‘application’ does not require compliance of the individual. Toothpaste differs from the other products mentioned in terms of compliance, as tooth brushing is widely used and is generally well adhered to as part of the daily oral hygiene routine of most individuals. Fluoridation of drinking water has a long and turbulent history. The original discovery of the caries-protective effects of fluoride was made in regions where drinking water contained fluoride. A light to heavy staining of the teeth was found to be associated with low caries prevalence. Later studies by Dean revealed that the presence of around Ippm fluoride resulted in a substantial reduction in caries prevalence and no staining (fluorosis) was apparent (5). Studies and intervention programs on the addition of fluoride to drinking water have used this fluoride level. As fluoride is naturally present in drinking water in many parts of the world, it has been relatively easy to study the possible side effects resulting from long-term consumption of fluoridated water. These studies have all shown that fluoride use is safe and is very beneficial to oral health (6).

Promotion of artificial fluoridation of drinking water has proved, however, to be very difficult. Small groups of individuals, protesting against fluoride, have often been more influential than large bodies of dental practitioners or the wealth of data available from balanced scientific studies.


Fluoride is, without question, the most powerful caries preventative agent, and is probably the only one for which a substantial efficacy has been shown beyond doubt. It is also a therapeutic agent which is safe for use, as shown in many long-term studies. The current divergence in caries prevalence and incidence between various groups in society will probably lead to more individualised recommendations for oral health schemes and the development of new products specifically for high-risk groups.


(1) Petzold M. The influence of different fluoride compounds and CaF2 precipitation and microstructure. Caries Res 2001;35:Suppl 1:45-51.
(2) Biesbrock A R et al. Relative anti- caries efficacy of 1100, 1700, 2200, and 2800 ppm fluoride ion in a sodium fluoride dentifrice over 1 year. Community Dent Oral Epidemiol 2001;29:382-9.(3) Bloch-Zupan A. Is the fluoride concentration limit of 1,500 ppm in cosmetics (EU guideline) still up-to- date? Caries Res 2001;35:Suppl 1:22-5.(4) 0′ Mullane D et al. A three-year clinical trial of a combination of tri meta phosphate and sodium fluoride in silica toothpaste. J Dent Res1997;76:1776-1781.(5) Aoba T and Fejerskov O. Dental fluorosis: chemistry and biology. Crit Rev Oral BioI Med 2002;13:155-170.(6) McDonagh MS et al. Systematic review of water fluoridation. BMJ 2000;321 :855-859.

Key points.

Fluoride is the most powerful weapon available in the fight against dental caries. The addition of fluoride to toothpaste and drinking water increases the frequency of fluoride exposure to teeth, a factor highly influential in caries prevalence.

By Dr Ralph M Duckworth, Unilever Dental Research, Bebington, Wirral, CH63 3JW

Good oral hygiene is a prerequisite to maintaining oral health. The term dentifrice was originally used to describe any mixture, or preparation used to clean teeth in conjunction with a toothbrush. Whilst this definition still applies, toothpaste and dentifrice have been almost synonymous for more than 50 years. Despite the proliferation of other product forms, the toothbrush/ toothpaste combination is the most common aid to oral hygiene practised today. The basic ingredients of a toothpaste (abrasive particles or cleaning agent, detergent and water) enable removal of food debris, plaque bacteria and, to a lesser extent, tartar. The addition of for example sorbitol, and/or glycerol, and particulate or polymeric thickeners make the final formulation into a manageable paste. Flavourings and artificial sweeteners, for example, saccharin, are added to give the paste a pleasant taste. Key components of a modern dentifrice are the therapeutic agents, which have made an increasing impact over the past 50 years.

Fluoride is the only anticaries agent with extensive clinical proof of efficacy. Following epidemiological observations of an inverse association between caries prevalence and natural levels of fluoride in drinking water, an era of artificial water fluoridation arose in the late 1940s and 1950s. The first successful fluoridated dentifrice, Crest, was introduced in the USA in 1955. Since then, over 100 clinical trials have been conducted on a variety of fluoride toothpaste formulations. On average, 3-year reductions in caries incidence of about 25% were recorded, relative to none-fluoridated control dentifrices (1).

The anticaries efficacy of fluoridated toothpaste is linked to the oral hygiene routine employed. Increased frequency of brushing has been proven to increase efficacy, whereas thorough rinsing with water can have a marked detrimental effect as the fluoride is removed from the mouth (2). Today, the most common sources of fluoride in toothpaste are sodium fluoride (NaF) and sodium mono- fluorophosphate (Na2FPO3, often abbreviated to SMFP). Although NaF is regarded by some researchers as marginally more effective, SMFP is often used because it is compatible with a wider range of formulation ingredients. As high doses of fluoride can cause fluorosis and be toxic, the fluoride content of toothpaste is regulated by legislation for safety. In Europe no more than 1500 ppm F (0.32% NaF, 1.14% SMFP) is permitted, whilst in some other countries the limit is 1000 ppm F (0.22% NaF, 0.76% SMFP). As an aid to control tooth decay, toothpaste with this level of fluoride can be assumed to be ‘safe and effective’ for the general population. Young children are at higher risk of dental fluorosis owing to their tendency to swallow paste at a time when the permanent teeth are being formed.

The British Society of Paediatric Dentistry has recommended that such children should use toothpaste containing no more than 600 ppm F and, moreover, use a small pea-sized amount of paste per brushing (3). For this reason, toothpaste with a lower fluoride content is available for children under the age of 6. A simple ‘rule of thumb’ is for adults to use a paste ribbon of one brush length per brushing and children to use a ribbon of one brush width. Given the lack of evidence of an anticaries benefit for fluoridated dentifrices below 500 ppm F, this concentration would seem to be a good compromise.

Another therapeutic ingredient commonly found in dentifrices is the antimicrobial agent triclosan. Dentifrices containing triclosan, in combination with either a copolymer, zinc citrate or pyrophosphate, have demonstrated significant benefits against plaque, gingivitis and tartar (4). Products targeted at sensitive teeth (dentine hypersensitivity) are also, quite common. These dentifrices usually contain either strontium salts, which may block dentine tubules or potassium salts, which may affect tooth nerves, as the active ingredients.

Recently, dentifrices to combat stains and promote tooth whitening have increased in popularity. Such products often contain specially formulated particles that provide improved physical cleaning or an enzyme to remove stains by chemical means. Clinical support for the performance of these formulations is limited compared to the anticaries and anti-plaque toothpaste described earlier but research by the leading manufacturers is providing more evidence each year.

Brushing the teeth with a dentifrice has formed part of oral hygiene routines for centuries. William Addis made some of the first bristle brushes in the UK in the late 1700s, whilst dentifrices and toothpicks have been recorded since ancient times.

The traditional dentifrice was formulated simply to aid removal of food debris from the teeth. Modern formulations, however, also deliver therapeutic ingredients such as fluoride, to control tooth decay, antimicrobials to control plaque and gingivitis, and other components to reduce tartar, bad breath, and improve whitening.


(1) Murray JJ. Rugg-Gunn AJ, Jenkins GN. Fluorides in Caries Prevention. Oxford: Wright, 1991.
(2) Chestnutt IG, Schafer F, Jacobson APM, Stephen KW. The influence of toothbrushing frequency and rinsing on caries experience in a caries clinical trial. Community Dent Oral Epidemiol 1998 26:406-411.
(3) Holt RD, Nunn JH, Rock WP, Page J. British Society of Paediatric Dentistry: A policy document on fluoride dietary supplements and fluoride toothpaste for children. Int J Paediatric Dent 1996;6:139-142.
(4) Duckworth RM. Science and caries prevention. Int Dent J 1993;43:529-539.


Research into dental decay causation has focused primarily on establishing the relationship between plaque bacteria and foods, and the role fluoride plays in this system. Recently, however, interest in the potential protective effects of foods has grown, with the realisation that foods such as milk and cheese can neutralise cariogenic acids, in addition to aiding restoration of enamel lost during eating. Milk is known to be harmful in baby bottle tooth decay, a condition in which rampant caries develops as a result of a baby repeatedly falling asleep with a bottle of milk, juice, or other fermentable carbohydrate-containing drink still in its mouth. The milk is retained in the mouth for a prolonged period, allowing plaque micro-organisms to ferment milk lactose into cariogenic acid.

Under more normal conditions of consumption, however, milk has been shown to have minimal effect on plaque acidity and appears to protect enamel from dissolution. Cheese consumption also does not result in a reduction in plaque pH. Indeed, studies have shown that eating cheese after eating a carbohydrate-containing food returns plaque pH towards neutrality. Enamel demineralisation is a reversible process, although re-mineralisation is relatively slow. Re-mineralisation occurs naturally in the mouth because saliva contains super-saturated concentrations of calcium and phosphate ions (ions also found in abundance in milk and cheese). Thus consumption of milk or cheese might be expected to lead to enhanced re- mineralisation. Indeed, there is evidence that both exhibit some anti-cariogenic activity.

The available evidence suggests potential dental health benefits may result from consumption of milk or cheese, especially at the end of a meal. Further investigation into the precise molecular basis of such anti- cariogenic effects may help to improve our understanding of the effects of a wide range of foods on the caries process.

Kashket S. et al. Cheese consumption and the development and progression of dental caries. Nutrition Reviews 2002;60(4):97-103.

Key point

Eating a piece of cheese at the end of a carbohydrate- containing meal helps to neutralise cariogenic acids, reducing the risk of dental caries development.

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