1. Why Dentrifice is Important

Why Dentrifice is Important

The oral environment is an ecosystem comprised of diverse microorganisms. Plaque biofilms provide a protective matrix in which these bacteria reside. Factors such as oral hygiene, nutrition, and host response impact the toxicity of plaque biofilms and the extent to which they have harmful consequences on hard and soft tissues. Mechanical hygiene is commonly used to remove plaque biofilms, but it is well-recognized that most patients have sub-optimal oral hygiene, largely due to not following proper brushing technique and/or insufficient brushing time (Beals et al. 2000). Poor plaque removal can lead to various oral diseases (e.g., caries, gingivitis) and conditions (e.g., tooth stain, calculus).

This is where the right dentifrice choice plays a critical role in protecting patients’ oral health and the appearance of their smile. Dentifrice is a convenient, cost-effective delivery system to provide fluoride, anti-bacterial agents and other ingredients that provide benefits beyond brushing alone. Dental professionals are in a unique position to educate patients on the best dentifrice option to address their specific oral health needs.

Stannous Fluoride: More Benefits Than Other Fluorides

There is a misconception that “all fluorides are the same”. That’s simply not true. Stannous fluoride is unique among fluoride compounds, offering multiple benefits not found with sodium fluoride or sodium monofluorophosphate. While all three compounds provide anti-caries benefits, stabilized stannous fluoride has demonstrated broader and significantly greater protection than other fluorides against plaque (Sharma et al. 2013; Garcia-Godoy et al. 2015), gingivitis (Archila et al. 2004; Mallatt et al. 2007), erosion (Hooper et al. 2007; West et al. 2017), sensitivity (Schiff et al. 2005; He et al. 2011) and halitosis (Farrell et al. 2007). (See Table 1)

Electric Brush and Toothpaste

Table 1. Stannous fluoride offers broader and greater protection relative to other fluorides.

Stannous Fluoride offers broader and greater protection.

So why isn’t stannous fluoride used in every dentifrice? Stannous fluoride has some inherent challenges to formulate, requiring skill and expertise to ensure it is delivered in a bioavailable, esthetically pleasing dentifrice (White 2013). These challenges can be overcome by including extrinsic whitening agents and ingredients to stabilize the stannous fluoride (e.g., chelants), but it’s not a simple process. The following section describes decades of innovations by Procter & Gamble resulting in the largest portfolio of stabilized stannous fluoride dentifrices available to improve patients’ oral health and provide a brushing experience that delights them. (See Figure 1)


The anti-caries benefit of fluoride was confirmed in the mid-1940s (Dean et al. 1942). However, an effective anti-caries dentifrice was not brought to market until 1955, when Procter & Gamble and collaborators at Indiana University became the first to successfully formulate stannous fluoride into a clinically proven dentifrice, with caries reductions of up to 53% (Muhler et al. 1954). The stannous fluoride in this early dentifrice had limited stability. While the product delivered an anti-caries benefit, the full therapeutic benefits of stannous fluoride were not realized. Subsequently, the stannous fluoride in daily use dentifrice was replaced with more stable fluoride products, mainly sodium monofluorophosphate and sodium fluoride. However, P&G maintained interest in stannous fluoride because of the unique potential of this compound to also provide gingival health and anti-hypersensitivity benefits.


By the early 1990s, stannous fluoride systems had been stabilized and reformulated with a new abrasive system in the formulation. During this era, there was also more focus from the dental professional community on plaque and gingivitis control. After researching a number of formulations, a new stabilized stannous dentifrice (Crest® Gum Care) was launched in the mid-1990s focused on periodontal health (White 1995). The reception was mixed. The new dentifrice was highly effective at plaque and gingivitis control as well as caries prevention. Trade-offs persisted, however, such as a lack of anti-tartar effect and some extrinsic staining. The challenge was how to provide therapeutic benefits, while concurrently providing cosmetic benefits of tooth whitening and tartar control.

Figure 1. A timeline of stannous fluoride dentifrice innovations

Timeline of Stannous Fluoride Dentrifice Innovations


A series of inventions by P&G ultimately led to the formulation of a stabilized stannous fluoride dentifrice with an advanced anti-calculus and whitening agent, sodium hexametaphosphate (Baig & He 2005). This was the first truly multi-benefit dentifrice offering the full array of therapeutic benefits afforded by stannous fluoride, in addition to the tooth whitening and anticalculus benefits that are important to consumers. The formulation was marketed across the globe as Crest® PRO-HEALTH or Oral-B® Pro-Expert, depending on the region. The first key invention leading to this breakthrough included developing chemical approaches to protect the stannous ion from inactivation by oxidation and hydrolysis which typically occur when stannous fluoride is formulated into a dentifrice. Second, groundbreaking research on tartar control agents led to the discovery of sodium hexametaphosphate, a powerful whitening and anti-calculus ingredient. Third, developing methods to formulate a low-water dentifrice (<3% water vs. 20-70% water in typical dentifrices) allowed stannous fluoride and sodium hexametaphosphate to be combined into one dentifrice formulation that provides stability to both ingredients and allows them to co-exist in the same formulation to deliver their unique benefits.


The current decade has seen three more innovations in the Procter & Gamble stabilized stannous fluoride dentifrice portfolio to further enhance efficacy and provide esthetic alternatives to meet different patient preferences:

  • A high bioavailable version of Crest® PRO-HEALTH (Crest® PRO-HEALTH Advanced Gum Protection) was launched containing stannous chloride as a reservoir for stannous to allow even greater stannous bioavailability for enhanced gingivitis efficacy (Gerlach & Amini 2012,He et al. 2012a, He et al. 2012b).
  • A novel 2-step system was launched as Crest® PRO-HEALTH [HD]. Patients brush with stabilized stannous fluoride dentifrice for 1 minute (step 1) followed by a 1-minute brushing with hydrogen peroxide whitening gel (step 2). Separating oral hygiene into two consecutive steps optimizes gingival health benefits to a level comparable to chlorhexidine but also provides significant extrinsic whitening (Gerlach et al. 2015, Sagel et al. 2016).
  • A “smooth texture” stabilized stannous fluoride dentifrice version was introduced with zinc citrate as the anti-calculus agent to appeal to patients who don’t like the characteristic “gritty texture” of formulas with sodium hexametaphosphate (Milleman et al. 2017). This formula also includes distinct flavors and foaming to create a novel brushing experience.

Each stabilized stannous fluoride dentifrice provides multiple mechanisms of action and delivers multiple benefits. In addition to the anti-caries benefit of stannous fluoride, the actions of stannous fluoride against oral bacteria impart effectiveness against plaque, gingivitis, and halitosis (Baig & He 2005). Stannous fluoride also promotes the occlusion of open dentinal tubules associated with hypersensitivity and binds to the enamel surfaces to protect against acid erosion (Zsiska et al. 2011, Faller & Eversole 2014). Additionally, tooth whitening and calculus control are delivered by sodium hexametaphosphate or other ingredients, depending on the specific formulation (Schiff et al. 2005, Terezhalmy et al. 2007, Farrell et al. 2016, Friesen et al. 2017).

The following pages address the mechanisms of action and efficacy of the stabilized stannous fluoride dentifrice formulas for each important oral care benefit.

Periodic Table of the Elements

Anti-Plaque Activity

It is widely acknowledged that mechanical hygiene is the most common method to remove plaque, however mechanical plaque removal is not enough (Bellamy et al. 2014). Stannous fluoride hemotherapeutically inhibits plaque regrowth and metabolism to improve plaque control.

The development of supragingival plaque can be divided into several distinct phases (Marsh 2006, Liljemark & Bloomquist 1996, Hojo et al. 2009, Lovegrove 2004):

  • Formation of the acquired pellicle. The pellicle consists mainly of salivary glycoproteins that are adsorbed onto the tooth surface within minutes of exposure of the surface to saliva (e.g., after cleaning). It is acellular, membranous and appears to be unstructured.
  • Attachment of primary plaque-forming bacteria to pellicle-coated tooth surfaces. Bacterial colonization begins with Gram-positive cocci and rods which loosely adhere within an hour.
  • Bacterial growth to form micro-colonies on the pellicle. The bacteria also produce an extra-cellular matrix that facilitates the attachment and division of bacteria (co-aggregation) and protects the micro-colonies from host defenses and antimicrobial agents. Co-adhesion enables other bacteria to adhere to the earlier colonizers. By 8–12 hours, the plaque has become multi-layered.
  • Maturation of the dental plaque (dental biofilm): it is in this phase of development that the plaque may become pathogenic. At 24–48 hours, only Gram-positive cocci and rods are present and the plaque increases in thickness, however by day five Gramnegative filaments increase in number and begin to coaggregate with the Gram-positive microorganisms and form a more complex structure.

Subgingival plaque develops subsequent to supragingival plaque development. The presence of plaque at the gingival margin results in an inflammatory reaction, which affects the composition of the plaque. The structure of the plaque becomes highly organised with micro-colonies interspersed with voids and channels that allow nutrients and other agents to circulate through the plaque (Figure 2). Different bacterial species also function synergistically or antagonistically within the plaque. Three to twelve weeks after plaque begins to form, Gram-negative cocci and rods, filamentous bacteria and spirochaetes collectively become dominant in the subgingival plaque.

Dental plaque contributes to the development of gingivitis. The onset of gingivitis coincides with an increase in the bacterial load and complexity of plaque as it matures. Stannous fluoride chemotherapeutically acts against the bacteria that cause plaque.

Figure 2. The structure of dental plaque

The structure of dental plaque

Mechanism of action of stannous fluoride and anti-bacterial activity

Scientific evidence indicates the anti-bacterial activity of stannous fluoride against both Gram-positive and Gram-negative bacteria and inhibits bacterial metabolism. Bacteria exposed to stannous fluoride retain large amounts of tin, and bacterial metabolism could be affected through several different mechanisms. Exposure to stannous fluoride reduces bacterial growth, bacterial adhesion, and the production of acids and other metabolic toxins that contribute to gingivitis. Active levels of tin in plaque persist for up to twelve hours following exposure to stabilized stannous fluoride dentifrice, consistent with the plaque and gingivitis reductions observed for the dentifrice and indicative of a sustained mechanism of action with twice-daily use (Ramji et al. 2005, Otten et al. 2012).

Early studies of stannous fluoride suggest that it affects bacterial adhesion. Plaque bacteria produce extracellular polysaccharides (EPS) which are responsible for the adhesiveness of the plaque. Busscher et al. (2008) demonstrated that stabilized stannous fluoride dentifrice significantly reduced EPS production in vivo compared to a regular sodium fluoride dentifrice. This helps to prevent bacterial adhesion and cohesion, thus reducing the thickness and stickiness of plaque.

One important mechanism that has been proposed for stannous fluoride’s anti-bacterial action is the oxidation by stannous of thiol groups in the enzymes involved in bacterial glycolysis (Ellingsen et al. 1980) In vivo plaque glycolysis and regrowth models have shown that stabilized stannous fluoride dentifrice exerts strong inhibitory actions on plaque acid production and regrowth relative to a regular sodium fluoride dentifrice (Ramji et al. 2005). A minimum metabolic inhibitory concentration was determined for stannous by measuring the reduction in acid production by bacteria in human saliva samples; 99% inhibition of metabolic activity occurred as low as 20 ppm stannous.

Most recently, research has shown that stannous fluoride makes plaque less toxic, or less virulent, by neutralizing lipopolysaccharides (LPS), or bacterial endotoxins (Haught et al. 2016a, Haught et al. 2016b, Huggins et al. 2016, Klukowska et al. 2017). LPS are responsible for activating toll-like receptors, which trigger the host response and inflammatory cascade associated with periodontal disease. By blocking the reactivity of LPS with tissue receptors that trigger inflammation, stannous fluoride decreases the pathogenicity of plaque.

Stannous Fluoride inhibits plaque by killing bacteria, Inhibiting plaque metabolism/acid production/regrowth, reducing bacterial adhesion and cohesion, reducing plaque virulence, sustained activity (retained up to 12 hours)

Stannous Fluoride Research Summaries

The following study summaries represent a sample of research demonstrating the benefits of stabilized stannous fluoride dentifrice for plaque control.

A 24-Hour Dental Plaque Prevention Study with a Stannous Fluoride Dentifrice

Full text available in the Research Database at www.dentalcare.com

Reference: White DJ, Kozak KM, Gibb RD, Dunavent JM, Klukowska M, Sagel PA. J Contemp Dent Pract. 2006; 7(3):1-11


Crest® PRO-HEALTH produced a statistically significant reduction in dental plaque coverage 24 hours following last use.


To determine whether the antiplaque efficacy of Crest® PRO-HEALTH, a dentifrice containing anti-bacterial stannous fluoride (and sodium hexametaphosphate for cosmetic benefits), extended to 24 hours post use.


  • The study design comprised 3 phases:
    1. An initial 1-week treatment period with a regimen that included toothbrushing with standard sodium fluoride dentifrice (Cavity Protection Regular) in conventional b.i.d. brushing;
    2. A second 1-week treatment period regimen where a modified hygiene regimen was applied using - Cavity Protection Regular. A non-brushing period of 24 hours was included.
    3. A third 1-week treatment period which was identical to the second treatment period except subjects used Crest® PRO-HEALTH instead of Crest® Cavity Protection Regular.
  • A digital plaque image analysis (DPIA) technique was used to quantify in situ plaque formation. Plaque formation was assessed in morning measurements following either standard evening hygiene (treatment period 1) or 24 hours since brushing (treatment periods 2 and 3). Post-brushing plaque measurements were also taken in each treatment regimen.
  • Study subjects were adults with sufficient plaque levels in pilot pre-screening to warrant participation.

Imaging System

Imaging Systems


  • Sixteen subjects completed all three treatment regimens with no side effects or oral complaints.
  • Treatment period 1:
  • Morning plaque coverage was 13.3%.

  • Treatment period 2:
  • Plaque coverage significantly increased when pre-bedtime brushing was discontinued, with 24-hour growth covering 18.4% of the dentition.

  • Treatment period 3:
  • Intervention of the antimicrobial stannous fluoride dentifrice provided significant inhibition of plaque regrowth over 24 hours (15.2% coverage, a 17.4% reduction vs. sodium fluoride dentifrice control).

  • These results support the strong retention and lasting antimicrobial efficacy of Crest® PRO-HEALTH dentifrice.

Morning Pre-Brushing Treatment Comparisons

* Two-sided P-values from a paired-difference t-test.

Plaque Control Evaluation of a Stabilized Stannous Fluoride Dentifrice Compared to a Triclosan Dentifrice in a Six-Week Trial

Reference: Sharma N, He T, Barker ML, Biesbrock AR. J Clin Dent 2013;24:31-36


Both the stannous fluoride dentifrice and the triclosan dentifrice produced a statistically significant reduction from baseline in mean plaque values for whole mouth, gingival margin, and interproximal plaque at Weeks 3 and 6 (P < 0.02 for all comparisons).

The stannous fluoride dentifrice showed a statistically significantly (P < 0.0001) lower adjusted mean plaque level compared to the triclosan group for all three tooth areas at both Weeks 3 and 6. Whole mouth plaque scores for the stannous fluoride dentifrice were 29.7% lower at Week 3 and 44.9% lower at Week 6 than the triclosan dentifrice (Figure 1).

Figure 1. Whole mouth plaque levels at Baseline, Week 3 and Week 6 per group.

Whole mouth plaque levels at Baseline


  • This was a 6-week, randomized, double-blind, two-treatment, parallel-group clinical trial.
  • Generally healthy adults with baseline plaque levels ≥ 0.5 as assessed by Rustogi, et al. Modified Navy PIaque Index (RMNPI) were randomized to one of the following treatments:
  • - 0.454% stannous fluoride dentifrice (Crest® PRO-HEALTH Advanced Deep Clean, Procter & Gamble)


    - 0.3% triclosan/0.24% sodium fluoride dentifrice (Colgate Total, Colgate-Palmolive)

    Subjects brushed their teeth with a soft manual toothbrush (Oral-B® Indicator, Procter & Gamble) using their assigned treatment dentifrice according to the manufacturer’s instructions.

  • Overnight plaque accumulation was evaluated by an experienced examiner using the RMNPI at baseline, Week 3 and Week 6. Groups were compared using analysis of covariance separately for Weeks 3 and 6, and by repeated measures for Weeks 3 and 6 combined.

A Clinical Trial to Assess Plaque Prevention with Use of a Daily Two-Step Dentifrice and Gel System

Reference: García-Godoy C, Duque N, Rothrock JA. J Dent Res 2016; 95 (Spec Iss A): Abstract 1708.


The two-step dentifrice and gel system group had significantly (P≤0.011) less overnight (prebrush) percent plaque area than the control group at Week 1 (52.9%) and Week 2 (45%). See Figures 1 & 2. Step 1 is a 0.454% stannous fluoride dentifrice and Step 2 is a 3% hydrogen peroxide whitening gel.

Figure 1. Mean Overnight (Pre-Brush) Percent Plaque Area

Mean Overnight (Pre-Brush) Percent Plaque Area

Figure 2. Representative response of overnight plaque coverage at Week 1

Representative response of overnight plaque coverage at Week 1


To assess plaque area following a dental prophylaxis and twice daily use of a 2-step dentifrice and gel system versus a standard oral hygiene control.


  • This was a randomized, controlled, examiner-blind, 2-treatment parallel group plaque prevention study among healthy adult volunteers with plaque.
  • Following a whole-mouth dental prophylaxis, subjects were randomized to one of two groups:
  • - Standard oral hygiene control group: 0.76% sodium monofluorophosphate dentifrice (Colgate® Cavity Protection, Colgate-Palmolive) and a soft, regular manual toothbrush (Oral-B® Indicator, Procter & Gamble)


    - 2-step dentifrice and gel system (Crest® PRO-HEALTH [HD]™, Procter & Gamble): Step 1, 0.454% stannous fluoride dentifrice; Step 2, 3% hydrogen peroxide whitening gel. The system was used with a soft, regular manual toothbrush (Oral-B® Indicator).


  • Overnight percent plaque area was assessed after 1 and 2 weeks of treatment by digital image analysis of fluorescein-disclosed plaque.


Reference: Friesen L, Goyal CR, Qaqish J, et al. J Dent Res 2017; 96 (Spec Iss A): Abstract 0214.


  • After 4 weeks of use, the stabilized stannous fluoride (SnF2) dentifrice group had 23.1% lower whole mouth plaque scores and 43.5% lower interproximal plaque scores than the triclosan positive control dentifrice group (P <0.0001). See Figures 1 and 2.
  • Both the triclosan and SnF2 dentifrice groups demonstrated statistically significant (P<0.0001) reductions in plaque levels at Week 4 versus Baseline.
  • Both treatments were well tolerated.

Figure 1. Whole mouth plaque scores at Baseline and Week 4.

Whole mouth plaque scores at Baseline and Week 4.

N=118. *Statistically significant difference between groups, P<0.0001. **Week 4 values are adjusted means.

Figure 2. Interproximal plaque scores at Baseline and Week 4.

Interproximal plaque scores at Baseline and Week 4.


To compare the effect of a SnF2 dentifrice versus triclosan dentifrice on reduction of plaque over a 4-week period.


  • This was a randomized, parallel, double-blind, 4-week clinical trial including subjects with evidence of plaque.
  • Subjects were randomized to one of two treatment groups:
  • - Experimental 0.454% stabilized SnF2 dentifrice (Crest® PRO-HEALTH Clean Mint [Smooth Formula], Procter & Gamble)


    - Triclosan positive control dentifrice with 0.24% sodium fluoride (Colgate® Total®, Colgate-Palmolive). Both groups used a soft, regular manual toothbrush (American Dental Association) and brushed with their respective product according to manufacturer’s instructions at-home.


  • Plaque was evaluated using the Rustogi Modification of the Navy Plaque Index (RMNPI) at Baseline and after 4 weeks of product use.
  • Statistical analyses utilized analysis of covariance with baseline value as covariate.


Chemotherapeutic antimicrobial dentifrices play an important role in the control of plaqueinduced oral diseases, such as gingivitis. Both SnF2 and triclosan dentifrices have been shown to provide significant inhibition of plaque.1,2 This study showed the new smooth formula SnF2 dentifrice provided significantly greater plaque control than the triclosan dentifrice. These findings are consistent with other studies in the literature showing superior plaque protection for SnF2 versus triclosan dentifrice.3,4

1White DJ, et al. J Contemp Dent Pract. 2006;July (7)3:001-011.
2Rover JA, et al. Am J Dent. 2014 Jun;27(3):167-70.
3He T, et al. Am J Dent. 2013;26: 303-306.
4Sharma NC et al. J Clin Dent. 2013;24:31-36.

Clinical Significance

Stannous Fluoride Clinical Significance

  • These results demonstrate stabilized stannous fluoride dentifrice is an effective antiplaque agent.
  • The comparative studies demonstrate stabilized stannous fluoride dentifrice provides greater plaque reductions compared to 0.3% triclosan/copolymer dentifrice at three and six weeks.


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