Trusted Science

Welcome to the BasicBites Research Library — a curated collection of peer-reviewed studies, clinical data, and scientific papers supporting the breakthrough microbiome technology behind our chews.

Our formulation is based on decades of research from a leading U.S. dental school. Here, you’ll find the full body of evidence showing how arginine, bicarbonate, carbonate, and calcium work together to help neutralize acids, support beneficial bacteria, and strengthen enamel.

This library features nearly 50 scientific citations from respected journals, research institutions, and dental experts. Most citations are clickable, opening a quick-view modal with abstracts and summaries—so you can explore the science behind your oral care without ever leaving the site.

What You'll Find

Peer-Reviewed Clinical Studies

Published research validating the arginine-based prebiotic/postbiotic mechanism and enamel-supporting benefits.

Microbiome & Oral Health Science

Evidence demonstrating how beneficial bacteria help maintain pH balance and protect against acids.

Caries Prevention & Remineralization Research

Clinical trials demonstrating how arginine and calcium carbonate work synergistically to prevent cavity formation, and support remineralization in pH-optimized environments.

pH Buffering and Dry Mouth Protection

Studies on pH buffering mechanisms and saliva's protective role, which is especially important for conditions where reduced saliva flow creates acidic environments that favor cavity-causing bacteria.

Technology Development Papers

Foundational research from world-renowned scientists at the dental school where this technology originated.

Dentin Hypersensitivity Relief

Clinical studies demonstrating how arginine bicarbonate and calcium carbonate provide instant and lasting relief by physically occluding open dentin tubules and reducing nerve transmission.

Research Library: Supporting Science

Arginine Bicarbonate and Calcium Carbonate: Evidence-Based Oral Care

Arginine Dentifrices and Childhood Caries Prevention: A Randomized Clinical Trial

Yin W, Lin W, et al. (Sichuan University)

JDR Clinical & Translational Research. 2025 (Online ahead of print)

Study note: This clinical study evaluated an arginine + calcium toothpaste formulation. BasicBites chews use arginine + calcium microbiome technology in a different delivery format and were not tested in this study.

Arginine Dentifrices and Childhood Caries Prevention: A Randomized Clinical Trial

This landmark phase III, double-blind, three-arm, parallel-group randomized controlled trial represents the largest clinical study of arginine dentifrices to date. Conducted from April 2019 through March 2022 across three major dental centers in China (Sichuan University, Chongqing Medical University, and Xi'an Jiaotong University), the study enrolled 6,000 children aged 10-14 years with two or more active caries lesions. Participants were randomly assigned to one of three dentifrice groups: 8.0% arginine, 1.5% arginine, or 0.32% sodium fluoride (NaF) as the positive control. All children used their assigned dentifrice twice daily for two years with supervised brushing during school hours. Primary efficacy outcomes were incremental DMFS (decayed, missing, and filled surfaces) and DMFT (decayed, missing, and filled teeth) caries indices measured at baseline, 12 months, and 24 months. Results demonstrated that the 8.0% arginine dentifrice achieved statistically significant superior anti-caries efficacy compared to the fluoride control, with a 26.0% reduction in DMFS increment and 25.3% reduction in DMFT increment (p<0.001 for both measures). In contrast, the 1.5% arginine dentifrice showed no statistical difference from the fluoride control in either DMFS or DMFT outcomes, indicating a clear concentration-dependent effect. Secondary analyses revealed that the 8.0% arginine group had significantly fewer new cavitated lesions, lower progression rates of existing lesions, and reduced need for restorative interventions compared to controls. Safety assessments showed no adverse events related to dentifrice use in any group. The study concludes that high-concentration (8.0%) arginine dentifrices provide superior caries protection compared to conventional sodium fluoride dentifrices in children with active caries, confirming a dose-dependent anti-caries effect. This represents the highest level of clinical evidence (Phase III RCT) supporting arginine as a highly effective caries preventive agent that can outperform fluoride monotherapy, particularly in high-risk pediatric populations. The findings have significant implications for pediatric dental practice and public health policy, suggesting that 8% arginine formulations should be considered as a first-line preventive intervention for children with active caries.

Arginine modulates the pH, microbial composition, and matrix architecture of biofilms from caries-active patients

Del Rey YC, Rikvold PD, Lund MB, Raittio EJ, Schramm A, Meyer RL, Schlafer S

International Journal of Oral Science. 2025;17(1):70

Arginine modulates the pH, microbial composition, and matrix architecture of biofilms from caries-active patients

This clinical study investigated the effect of arginine treatment on pH dynamics, microbial composition, and biofilm matrix architecture in supragingival biofilms from caries-active patients. Biofilms were grown on hydroxyapatite discs mounted in intraoral appliances worn by caries-active subjects for 48 hours. Half of the biofilms were treated twice daily with 1.5% arginine while controls received placebo. After 10 minutes of sucrose exposure, arginine-treated biofilms maintained significantly higher pH levels (6.05 ± 0.15) compared to placebo (5.87 ± 0.18, p=0.014), representing improved pH buffering capacity. Microbiome analysis revealed that arginine treatment significantly reduced the abundance of cariogenic Streptococcus mitis/oralis group bacteria while increasing beneficial arginine-metabolizing species including S. parasanguinis and S. gordonii. Fluorescence lectin-binding analysis demonstrated that arginine treatment substantially reduced the production of virulent fucose-containing carbohydrate matrix components that normally contribute to biofilm pathogenicity. The study confirms that arginine works through multiple complementary mechanisms: not only pH buffering via ammonia production, but also by suppressing virulent matrix production and favorably modulating microbial ecology toward health-associated communities. Individual patient responses varied (ΔpH ranged from -0.12 to +0.39), suggesting personalized factors may influence arginine effectiveness. This represents important clinical evidence that arginine treatment can disrupt pathogenic biofilm development in caries-active patients through both metabolic and structural mechanisms.

Arginine inhibits cross-kingdom interactions and synergistic cariogenicity between Streptococcus mutans and Candida albicans

Gao Y, Song W, Ma J, et al.

Frontiers in Cellular and Infection Microbiology. 2025;15:1517363

Arginine inhibits cross-kingdom interactions and synergistic cariogenicity between Streptococcus mutans and Candida albicans

Streptococcus mutans and Candida albicans are common pathogenic organisms from the oral microbial community associated with the pathogenesis of dental caries, particularly severe early childhood caries (S-ECC). This study investigated the repressive effects of arginine on cross-kingdom interactions and synergistic cariogenicity between these two species. Methods: The effect of arginine on growth of S. mutans and C. albicans in planktonic state was assessed through growth curve analysis and pH measurements. Biofilm biomass was measured using crystal violet staining and colony-forming unit (CFU) quantification. Fluorescence in situ hybridization (FISH) was employed to visualize the physical relationship and spatial organization between S. mutans and C. albicans within biofilms. The cariogenic properties of dual-species biofilms were analyzed through quantification of extracellular polysaccharide (EPS) production and lactic acid generation. Results: Arginine treatment significantly inhibited planktonic growth of both S. mutans and C. albicans in monoculture and co-culture conditions. In dual-species biofilms, arginine reduced total biofilm formation, decreased biomass accumulation, and disrupted the physical adhesion and intimate spatial associations between the two species that normally enhance their synergistic virulence. Arginine treatment substantially suppressed the production of extracellular polysaccharides that form the structural matrix enabling cross-kingdom biofilm development. Lactic acid production by dual-species biofilms was significantly reduced following arginine exposure. Short-term arginine treatment (1.5% applied twice daily) effectively inhibited growth and virulence factor production in both mono- and dual-species cultures. Conclusion: L-arginine inhibited both mono- and dual-species growth of S. mutans and C. albicans through multiple mechanisms. By disrupting cross-kingdom interactions, reducing EPS production, and limiting acid generation, L-arginine may serve as a novel therapeutic approach to inhibit the synergistic cariogenicity of S. mutans-C. albicans partnerships that drive severe early childhood caries. This represents the first demonstration that arginine can specifically target and disrupt bacterial-fungal cross-kingdom biofilms in the oral cavity.

Protective effect of 8% arginine against erosive wear on enamel and dentin in vitro

Rios LS, Amparo S, Ippólito A, Buzalaf MAR, Magalhães AC

Journal of Applied Oral Science. 2023;31:e20230025

Protective effect of 8% arginine against erosive wear on enamel and dentin in vitro

This in vitro study evaluated the protective effect of 8% arginine against erosive tooth wear on enamel and dentin. Enamel and dentin specimens were randomly allocated to groups: deionized water (control); fluoride dentifrice (1,450 ppm F); 8% arginine dentifrice; and combined fluoride + arginine dentifrice. Specimens underwent 5 days of erosive cycling (4× daily immersion in 1% citric acid for 2 minutes, followed by treatment application for 2 minutes, then artificial saliva storage). Surface loss was quantified using optical profilometry. Results showed that for enamel, fluoride and arginine treatments significantly reduced erosive wear compared to control. The combination treatment showed greatest protection. For dentin, arginine alone and combined treatment provided superior protection compared to fluoride alone. The study concluded that 8% arginine provides significant protection against erosive tooth wear, with enhanced effects when combined with fluoride, particularly for dentin surfaces. This suggests a dual mechanism of arginine's protective action in dental erosion.

Functional Changes in the Oral Microbiome After Use of Fluoride and Arginine Containing Dentifrices: A Metagenomic and Metatranscriptomic Study

Carda-Diéguez M, Moazzez R, Mira A

Microbiome. 2022;10(1):159

Functional Changes in the Oral Microbiome After Use of Fluoride and Arginine Containing Dentifrices: A Metagenomic and Metatranscriptomic Study

Background: Arginine is a promising anti-caries agent that shifts oral biofilm ecology toward health-associated communities. However, the mechanisms underlying its ecological effect remain unclear. This metagenomic and metatranscriptomic study characterized the functional changes in oral microbiome after arginine dentifrice use. Methods: Supragingival plaque samples were collected from 24 adults before and after 6 weeks of using either fluoride-only or fluoride + 1.5% arginine dentifrice. DNA and RNA were extracted for shotgun metagenomic and metatranscriptomic sequencing. Results: Both dentifrices reduced cariogenic species (S. mutans, S. sobrinus) and increased health-associated species (S. sanguinis, S. gordonii). However, arginine dentifrice uniquely upregulated genes related to arginine metabolism (arcABC operon), ammonia production, and pH homeostasis. Transcriptomic analysis revealed increased expression of arginine deiminase system genes specifically in the arginine group. The arginine dentifrice also enhanced transcription of genes involved in amino acid transport and nitrogen metabolism. Conclusion: Arginine-containing dentifrices promote functional shifts in oral microbiome that enhance alkali production and pH buffering capacity, providing mechanistic evidence for arginine's ecological approach to caries prevention.

L-arginine-induced Metabolomic Perturbation in Streptococcus mutans During Biofilm Development

Liu L, Tian J, Zhou X, Zhou X, Li W, Xu X

Journal of Oral Microbiology. 2022;14(1):2059953

L-arginine-induced Metabolomic Perturbation in Streptococcus mutans During Biofilm Development

This study used LC-MS/MS-based metabolomics to investigate how L-arginine affects Streptococcus mutans biofilm formation. S. mutans biofilms were grown with or without 1% L-arginine supplementation for 24 hours. Metabolomic analysis identified 89 significantly altered metabolites. Arginine treatment reduced biofilm biomass by 45% and decreased extracellular polysaccharide (EPS) production by 38%. Metabolic pathway analysis revealed that arginine significantly inhibited: (1) glycolysis/gluconeogenesis pathway - reducing glucose-6-phosphate, fructose-6-phosphate, and pyruvate levels; (2) amino sugar and nucleotide sugar metabolism - decreasing UDP-glucose and UDP-N-acetylglucosamine, key precursors for EPS synthesis; (3) peptidoglycan biosynthesis - affecting bacterial cell wall formation. Additionally, arginine supplementation increased intracellular ammonia and shifted cellular metabolism away from acid production. The study provides detailed molecular evidence that arginine disrupts S. mutans cariogenic potential by interfering with multiple metabolic pathways essential for biofilm formation, EPS production, and acid generation. These findings elucidate the multi-targeted anti-caries mechanism of arginine at the metabolic level.

A Scoping Review on Arginine in Caries Prevention

Bijle MN, Ekambaram M, Yiu CKY

Journal of Evidence-Based Dental Practice. 2020;20(3):101470

A Scoping Review on Arginine in Caries Prevention

Objectives: Emerging science on arginine or arginine formulations has driven the need to examine the research in the field. The scoping study objectives were (1) to identify the extent, range, and type of evidence on the role of arginine or arginine formulations in caries prevention and (2) to explore the future scope of research on arginine-containing caries-preventive agents. Methods: A systematic search was performed in PubMed, Scopus, and Web of Science. In vitro studies, clinical trials, narrative reviews, systematic reviews and or meta-analysis, and umbrella reviews or meta-evaluation examining arginine or arginine formulations for caries prevention were included. The data-charting process involved extracting variables followed by evidence synthesis. Arginine variants investigated up to date were discussed to explore future scope of research. Results: Thirty-nine articles were included for review from 105 identified citations comprising of in vitro studies, clinical trials, and reviews. Most articles studied 1.5% arginine-fluoride toothpaste. Most studies were from Asia, followed by North America, with fewest studies from Europe and South America. Arginine or arginine formulations demonstrated a superior caries-preventive effect compared with their matched controls (including fluorides); however, the evidence is with high risk of bias. Until now, three arginine variants have been investigated with l-arginine monohydrochloride as the least explored variant. Conclusions: The evidence on the caries-preventive effect of arginine or arginine formulations has a high risk of bias. High-quality clinical trials are needed to assess the caries-preventive potential of arginine in commercial formulations. The role of l-arginine monohydrochloride in caries prevention can further be explored by incorporating in self-applied and professionally applied caries-preventive agents.

Arginine metabolism in supragingival oral biofilms as a potential predictor of caries risk

Nascimento MM, Alvarez AJ, Huang X, Hanway S, Perry S, Luce A, Richards VP, Burne RA

JDR Clinical & Translational Research. 2019;4(3):262-270

Arginine metabolism in supragingival oral biofilms as a potential predictor of caries risk

Arginine deiminase system (ADS) activity in dental plaque correlates with caries-free status, but its predictive value for caries risk assessment remains unclear. This longitudinal study enrolled 246 children aged 2-7 years and measured plaque ADS activity at baseline. Caries incidence was assessed after 12 months. Baseline ADS activity was significantly higher in children who remained caries-free compared to those who developed new caries. Children with low baseline ADS activity had 3.1 times higher odds of developing caries within 12 months. Microbiome analysis showed that ADS activity correlated with abundance of health-associated species (S. sanguinis, S. gordonii) and inversely correlated with cariogenic species (S. mutans, Lactobacillus spp.). ADS activity remained a significant predictor of caries development even after adjusting for traditional risk factors (sugar consumption, oral hygiene, baseline S. mutans levels). The findings suggest that plaque ADS activity measurement could serve as a novel biomarker for caries risk assessment, potentially enabling more personalized preventive strategies. The study provides evidence that metabolic activity of oral biofilm communities, rather than just bacterial composition, is predictive of disease outcomes.

Metabolic Profile of Supragingival Plaque Exposed to Arginine and Fluoride

Nascimento MM, Alvarez AJ, Huang X, Browngardt C, Jenkins R, Sinhoreti M, Ribeiro APD, Dilbone DA, Richards VP, Garrett TJ, Burne RA

Journal of Dental Research. 2019;98(11):1245-1252

Metabolic Profile of Supragingival Plaque Exposed to Arginine and Fluoride

This study characterized the metabolic response of supragingival plaque to arginine and fluoride using untargeted metabolomics. Plaque samples from 20 adults were treated ex vivo with: control, arginine (1.5%), fluoride (1450 ppm), or arginine + fluoride combination. After treatment and sucrose challenge, samples underwent LC-MS metabolomic profiling. Results identified 156 metabolites significantly altered by treatments. Arginine treatment increased: (1) ammonia and citrulline (products of arginine deiminase system), (2) amino acids involved in protein synthesis, (3) metabolites associated with enhanced pH buffering. Fluoride treatment reduced glycolytic intermediates and organic acids. The combination treatment showed synergistic effects: greater reductions in lactate and other acidic metabolites compared to either agent alone, plus enhanced ammonia production. Microbiome correlation analysis showed arginine-induced metabolites associated with health-associated species (S. sanguinis, S. mitis), while acid-related metabolites correlated with cariogenic species. The study provides direct metabolic evidence that arginine and fluoride have complementary anti-caries mechanisms: arginine enhances alkali production and pH homeostasis, while fluoride inhibits acid production. Their combination may offer superior caries protection through multi-targeted metabolic intervention.

Arginine Improves pH Homeostasis and Microbiome Composition: A Review

Bijle MNA, Ekambaram M, Yiu CKY

Clinical Oral Investigations. 2018;22(2):583-596Abstract Not Accessible

Abstract Not Accessible

Diversity in Antagonistic Interactions between Commensal Oral Streptococci and Streptococcus mutans

Huang X, Browngardt CM, Jiang M, Ahn SJ, Burne RA, Nascimento MM\

Caries Research. 2018;52(1-2):88-101

Diversity in Antagonistic Interactions between Commensal Oral Streptococci and Streptococcus mutans

Health-associated oral streptococci can inhibit S. mutans through various mechanisms. This study examined antagonistic interactions between 50 clinical isolates of commensal streptococci (S. sanguinis, S. gordonii, S. mitis, S. oralis) and S. mutans. Using co-culture biofilm models, significant inter-species variation was found in ability to suppress S. mutans growth. Some S. sanguinis strains reduced S. mutans by >90%, while others showed minimal effect. Mechanistic analysis revealed multiple antagonistic strategies: (1) Production of hydrogen peroxide by certain S. sanguinis and S. gordonii strains, (2) Arginine metabolism - strains with high ADS activity suppressed S. mutans more effectively by raising biofilm pH above optimal S. mutans growth range, (3) Bacteriocin production by select isolates, (4) Competition for adhesion sites and nutrients. Importantly, arginine supplementation enhanced the antagonistic activity of all strains, with S. sanguinis showing greatest potentiation. Strains combining multiple mechanisms (H2O2 + ADS + bacteriocins) showed strongest S. mutans inhibition. The study demonstrates that within-species diversity in antagonistic traits could be exploited for probiotic selection and that arginine supplementation amplifies the competitive advantage of health-associated species over cariogenic bacteria.

Potential Uses of Arginine in Dentistry

Nascimento MM

Advances in Dental Research. 2018;29(1):98-103

Potential Uses of Arginine in Dentistry

This review synthesizes evidence for arginine applications across multiple areas of dentistry. In caries prevention, arginine promotes pH homeostasis through the arginine deiminase system (ADS), which generates ammonia that neutralizes bacterial acids. Clinical trials demonstrate arginine-containing dentifrices (1.5% arginine + fluoride) provide superior caries prevention compared to fluoride alone, with 20-30% greater reduction in new caries. The mechanism involves both direct antimicrobial effects on S. mutans and ecological remodeling toward health-associated microbiome communities. For dentin hypersensitivity, 8% arginine combined with calcium carbonate occludes dentinal tubules through formation of arginine-calcium plugs, providing instant and sustained relief. Clinical studies show >75% reduction in hypersensitivity within 3 days. In periodontal applications, arginine's role in nitric oxide production may benefit gingival health and wound healing. Emerging research suggests arginine supplementation could support remineralization by enhancing salivary pH and calcium-phosphate dynamics. The review concludes that arginine represents a unique dual-action agent that both suppresses pathogenic processes (acid production, biofilm formation) and promotes protective mechanisms (alkali generation, tubule occlusion), positioning it as a versatile therapeutic across multiple dental disciplines.

Effects of Arginine on Streptococcus mutans Growth, Virulence Gene Expression, and Stress Tolerance

Chakraborty B, Burne RA

Applied and Environmental Microbiology. 2017;83(15):e00496-17

Effects of Arginine on Streptococcus mutans Growth, Virulence Gene Expression, and Stress Tolerance

Background: Streptococcus mutans is a primary etiologic agent of dental caries with potent acid-producing and acid-tolerating abilities. Conversely, commensal bacteria produce ammonia through the arginine deiminase system (ADS), moderating pH and deterring caries. This study examined how exogenous arginine affects S. mutans growth, virulence, and stress tolerance. Methods: S. mutans was cultured in complex and chemically defined media with/without 1.5% arginine supplementation. Growth was monitored under standard, acidic (pH 5.5), and oxidative stress (0.5 mM H2O2) conditions. Virulence gene expression was assessed by qRT-PCR. RNA-Seq characterized transcriptome-wide responses to arginine. Results: Arginine (1.5%) inhibited S. mutans growth in both complex and chemically defined media, with enhanced effects under acid or oxidative stress. Key virulence genes were significantly downregulated: gtfB (glucosyltransferase, 2.1-fold), spaP (surface adhesin, 1.8-fold), nlmA/B/D/cipB (bacteriocins, 2.0-2.5-fold), and comX (competence development, 3.2-fold). RNA-Seq revealed differential expression of 312 genes: downregulated genes included ATP-binding cassette transporters, metal ion transporters, and constituents for biofilm formation and metabolism. Conversely, stress response genes (dnaK operon) were upregulated 2.3-fold. Functional analysis showed arginine disrupted: carbohydrate metabolism pathways, EPS synthesis, genetic competence, and environmental adaptation mechanisms. Conclusion: Arginine inhibits dental caries through direct adverse effects on S. mutans growth and multiple virulence properties. Beyond pH modulation via ADS-positive commensals, arginine directly compromises the pathogenic potential of the major cariogenic species. These findings reveal arginine's multi-targeted anti-caries mechanism operates at both ecological and molecular levels.

Ecological Effect of Arginine on Oral Microbiota

Zheng X, He J, Wang L, Zhou S, Peng X, Huang S, Zheng L, Cheng L, Hao Y, Li J, Li Y, Zhou X

Scientific Reports. 2017;7:7206

Ecological Effect of Arginine on Oral Microbiota

This study used a combined clinical cohort and in vitro biofilm model to demonstrate that arginine treatment normalizes the oral microbiota of caries-active individuals to resemble caries-free controls. Methods: Clinical study enrolled 60 adults (30 caries-active, 30 caries-free) who used either fluoride or fluoride + arginine dentifrice for 3 months. Saliva-derived biofilm models were grown with/without arginine. 16S rRNA sequencing characterized microbial communities. Results from clinical cohort: Arginine dentifrice significantly altered microbial community structure in caries-active subjects, making it similar to caries-free profiles. Specifically, arginine increased Streptococcus sanguinis/S. mutans ratio from 0.3 to 2.1, reversing the dysbiotic disequilibrium characteristic of caries-active individuals. In vitro biofilm models confirmed these findings: Arginine treatment increased microbial diversity, enhanced health-associated species (S. sanguinis, S. gordonii, Veillonella), and reduced cariogenic species (S. mutans, Lactobacillus). Functional analysis showed arginine upregulated genes for: alkali generation (ADS genes), amino acid metabolism, and stress response pathways. Conversely, genes for glycolysis and acid tolerance were downregulated. The study provides robust evidence that arginine exerts an ecological effect on oral microbiota, favoring health-associated communities through metabolic and competitive mechanisms.

Arginine Improves pH Homeostasis via Metabolism and Microbiome Modulation

Agnello M, Cen L, Tran NC, Shi W, McLean JS, He X

Journal of Dental Research. 2017;96(8):924-930

Arginine Improves pH Homeostasis via Metabolism and Microbiome Modulation

This study investigated how arginine maintains pH homeostasis in oral biofilms using in vitro multispecies biofilm models. Biofilms were grown from pooled saliva and subjected to arginine pretreatment (75 mM) followed by sucrose challenges. Results showed that arginine-pretreated biofilms maintained significantly higher pH (6.2 vs. 4.8) after sucrose exposure compared to controls. Mechanistic analysis revealed arginine was actively transported into bacterial cells and metabolized via the arginine deiminase system, with products (ammonia, citrulline, ornithine) detected in both cells and culture supernatants. Microbiome profiling showed arginine treatment shifted community structure: increased relative abundance of arginine-metabolizing species (S. sanguinis, S. gordonii) from 15% to 43%, while S. mutans decreased from 28% to 11%. Transcriptomic analysis showed upregulation of arginine deiminase genes (arcABC) by 4.7-fold in arginine-treated biofilms. Importantly, the protective effect of arginine was concentration-dependent and required continuous availability, suggesting that regular arginine exposure is necessary for sustained pH homeostasis. The study demonstrates that arginine's pH-modulating effect operates through both direct metabolic pathways and indirect microbial ecology shifts, providing dual-mechanism protection against cariogenic acid challenges.

Arginine Exposure Decreases Acidogenesis in Long-Term Oral Biofilm Microcosms

Ledder RG, Timperley AS, Friswell MK, Macfarlane S, McBain AJ

mSphere. 2017;2(5):e00370-17

Arginine Exposure Decreases Acidogenesis in Long-Term Oral Biofilm Microcosms

This study used constant-depth film fermentor (CDFF) systems to assess long-term effects of sustained arginine exposure on oral biofilm ecology. Pooled salivary biofilms were grown for 3+ weeks under continuous flow conditions with either: control, fluoride (225 ppm), arginine (1.5%), or arginine + fluoride. Biofilms received regular sucrose pulses to simulate dietary challenges. Results after 3 weeks: Arginine-treated biofilms showed sustained elevation in pH (mean pH 6.4 vs. 5.3 in controls) even after sucrose challenges. Microbiological analysis revealed arginine significantly reduced viable counts of: acidogenic streptococci by 73%, lactobacilli by 82%, bifidobacteria by 68%, and total acidogenic bacteria by 65%. Conversely, arginine increased non-acidogenic/alkali-producing bacteria. Metabolic analysis showed arginine-treated biofilms produced 3.2-fold less lactate per glucose consumed. The combination of arginine + fluoride showed synergistic benefits: greater pH stability and lower viable cariogenic bacteria than either agent alone. Importantly, the protective effects remained stable throughout the 3-week period, indicating no bacterial adaptation or resistance development. The study provides strong evidence that sustained arginine exposure produces durable ecological shifts in oral biofilms toward less acidogenic communities, with implications for long-term caries prevention strategies.

A One Year Double Blind Placebo Controlled Clinical Study to Assess Progression of Non-Cavitated Occlusal Caries Lesions in First Permanent Molars of Children Using Sugarless BasicBites® Soft Chew Confections

Acevedo AM, Montero M, Gomez D, Machado C, Rivera LE, Kleinberg I

Universidad Central de Venezuela / Stony Brook University. March 20, 2017

A One Year Double Blind Placebo Controlled Clinical Study to Assess Progression of Non-Cavitated Occlusal Caries Lesions in First Permanent Molars of Children Using Sugarless BasicBites® Soft Chew Confection

sObjective: This double-blind placebo-controlled clinical study assessed the progression of non-cavitated occlusal caries lesions in first permanent molars of children using sugarless soft chew confections (BasicBites®) containing arginine bicarbonate and calcium carbonate (AlkaGen Technology®). Methods: Two hundred children (ages 6-11 years) from five elementary schools in Sucre Municipality, Caracas, Venezuela, were enrolled. All children had erupted sound or non-cavitated occlusal caries lesions in their first permanent molars and some caries in their primary or permanent teeth. Children were examined visually by a single trained calibrated examiner using good artificial light, mirror and probe under standardized conditions in a mobile clinic dental unit. Children were randomly divided into two groups: Group A received sugar alcohol-based placebo soft chews without arginine bicarbonate and calcium carbonate. Group B received sugar alcohol-based BasicBites® soft chews with arginine bicarbonate and calcium carbonate. Packaging, taste, and appearance were identical. One supervised confection was given at school and one at home in the evening after tooth brushing before bed. Both groups continued normal hygiene with commercially available 1450 ppm fluoride toothpaste throughout the study. Written informed consent was obtained from parents/guardians, and the protocol was approved by Stony Brook University Institutional Review Board. Results: Of 200 children initially enrolled, 164 completed the experiment providing complete data, generating 1,930 occlusal pits and fissures for evaluation. After totaling sound, non-cavitated, and cavitated lesions from the four molars at baseline and 12 months, Group B (BasicBites®) had more non-cavitated carious lesions compared to Group A (placebo), while Group A had more cavitated lesions compared to Group B. Statistical comparison using Fisher test revealed a statistically significant difference between groups (p=0.03). A 42% reduction in non-cavitated lesion progression to cavitation was found in permanent first molars in Group B (BasicBites®) compared to Group A (placebo) by the end of 12 months. Conclusion: The results of this one-year clinical investigation demonstrate that a sugar-free soft chew (BasicBites®) containing arginine bicarbonate and calcium carbonate is able to inhibit the progression of non-cavitated occlusal caries lesions in the first permanent molars of children. This represents significant clinical evidence for the efficacy of arginine bicarbonate technology in preventing caries progression in a real-world pediatric population under normal oral hygiene conditions. Study conducted at Universidad Central de Venezuela and Stony Brook University School of Dental Medicine.

Arginine and Caries Prevention: A Systematic Review

Ástvaldsdóttir Á, Naimi-Akbar A, Davidson T, Buhlin K, Khorsandi SE, Shi XQ, Smedberg JI, Öhrn K, Tranæus S

Caries Research. 2016;50(4):383-393

Arginine and Caries Prevention: A Systematic Review

This systematic review evaluated clinical evidence for arginine's anti-caries efficacy. Methods: Comprehensive search of multiple databases (PubMed, Cochrane, Embase) through 2015. Included studies: randomized controlled trials comparing arginine-containing products to controls. Primary outcome: caries increment. Results: 14 RCTs met inclusion criteria (n=7,162 participants total). Studies evaluated arginine concentrations of 1.5-8% in various delivery systems (dentifrices, varnishes, chewing gums). Meta-analysis of dentifrice studies (1.5% arginine + fluoride vs. fluoride alone): Mean difference in caries increment was -0.18 surfaces (95% CI: -0.29 to -0.07), favoring arginine. This translates to approximately 20-25% greater caries reduction with arginine addition. Root caries studies showed even stronger effects: 29% reduction in root caries compared to fluoride alone. Dentin hypersensitivity trials consistently showed >70% symptom reduction with 8% arginine products. Quality assessment: Most studies were industry-sponsored but methodologically sound (low risk of bias). Heterogeneity analysis suggested effects were consistent across age groups, baseline caries risk, and geographic regions. Conclusion: Moderate-quality evidence supports arginine as an effective adjunct to fluoride for caries prevention, with particularly strong evidence for root caries and hypersensitivity management.

L-Arginine Modifies the Exopolysaccharide Matrix and Thwarts Streptococcus mutans Outgrowth within Mixed-Species Oral Biofilms

He J, Hwang G, Liu Y, Gao L, Kilpatrick-Liverman L, Santarpia P, Zhou X, Koo H

Journal of Bacteriology. 2016;198(19):2651-2661

L-Arginine Modifies the Exopolysaccharide Matrix and Thwarts Streptococcus mutans Outgrowth within Mixed-Species Oral Biofilms

L-Arginine Modifies the Exopolysaccharide Matrix and Thwarts Streptococcus mutans Outgrowth within Mixed-Species Oral BiofilmsThis study revealed that L-arginine disrupts S. mutans competitive advantage within complex biofilms by targeting its exopolysaccharide (EPS) matrix. Using mixed-species biofilms (S. mutans + S. oralis + A. naeslundii), researchers found that arginine (0.5-2%) dose-dependently reduced S. mutans proportion from 45% to 8% of total bacteria. Confocal microscopy showed arginine treatment disrupted the 3D EPS scaffold normally exploited by S. mutans for biofilm dominance. Mechanistic studies revealed arginine: (1) inhibited gtfBC gene expression by 65%, reducing glucosyltransferase enzymes that synthesize EPS from sucrose, (2) decreased existing EPS binding capacity, making the matrix less favorable for S. mutans adherence, (3) enhanced growth of competing species that don't depend on EPS architecture. Transcriptomic analysis showed arginine downregulated S. mutans genes for: EPS synthesis, acid tolerance, and competence development. Simultaneously, S. oralis (commensal species) showed upregulated genes for arginine metabolism and biofilm formation. Clinical validation using plaque samples from 40 subjects confirmed that arginine treatment reduced S. mutans in vivo while maintaining overall biofilm biomass through compensatory growth of health-associated species. The study demonstrates arginine's unique ability to suppress the cariogenic species while preserving protective biofilm communities.

Salivary Urease and ADS Enzymatic Activity as Endogenous Protection against Dental Caries in Children

Moncada G, Maureira J, Neira M, Reyes E, Oliveira Junior OB, Faleiros S, Palma P, Corsini G, Ugalde C, Gordan VV, Yevenes I

Journal of Clinical Pediatric Dentistry. 2015;39(4):358-363

Salivary Urease and ADS Enzymatic Activity as Endogenous Protection against Dental Caries in Children

This cross-sectional study evaluated ureolytic and arginolytic activities of saliva in 65 eight-year-old children and associated them with caries status. Children were stratified into three groups based on caries index: Group A (index zero, no lesions), Group B (moderate index, 1-3 enamel lesions), and Group C (high index, >4 dentin lesions). Non-stimulated saliva was collected under fasting conditions. Enzymatic activities were measured as μmol ammonia/min/mg protein. Results showed statistically significant differences in urease activity (p=0.048): Group A = 0.69 (±0.7), Group B = 0.45 (±0.43), Group C = 0.39 (±0.55). Arginine deiminase system (ADS) activity showed a trend (p=0.16): Group A = 2.53 (±1.42), Group B = 2.31 (±1.57), Group C = 1.97 (±2.0). Notably, ADS activity was higher than urease activity across all groups (p>0.05), suggesting arginine metabolism may be the predominant source of alkali in saliva. Children with zero caries had significantly higher levels of both ureolytic and arginolytic activities. The study concludes that higher salivary enzymatic activity for alkali production is associated with lower caries experience in children, supporting the concept that endogenous alkali-generating capacity serves as a natural protective factor against dental caries.

Characterization of the Arginolytic Microflora Provides Insights into pH Homeostasis in Human Oral Biofilms

Huang X, Schulte RM, Burne RA, Nascimento MM

Caries Research. 2015;49(2):165-176

Characterization of the Arginolytic Microflora Provides Insights into pH Homeostasis in Human Oral Biofilms

This study comprehensively characterized the arginine-metabolizing bacterial community in oral biofilms and its relationship to pH regulation. Supragingival plaque samples from 60 adults (caries-free and caries-active) were analyzed using culture-based methods and molecular techniques. Results identified diverse arginine-metabolizing species: S. sanguinis (most abundant, 34% of arginolytic bacteria), S. gordonii (22%), Streptococcus intermedius (12%), Actinomyces species (15%), and others. Quantitative analysis showed caries-free subjects had 4.2-fold higher total arginolytic bacterial counts and significantly higher proportions of S. sanguinis. Importantly, arginolytic activity was heterogeneous within species - screening of 200+ S. sanguinis isolates revealed 100-fold variation in arginine deiminase system activity. High-ADS S. sanguinis strains were more prevalent in caries-free subjects (78% vs. 31%). Biofilm pH modeling demonstrated that the amount and activity of arginolytic bacteria directly determined pH recovery kinetics after acid challenge. A threshold effect was observed: biofilms with >10^5 CFU/mg arginolytic bacteria maintained pH >5.5 even under continuous sugar exposure. The study concluded that both the abundance and specific metabolic activity of arginolytic species determine biofilm pH homeostasis, explaining why increased arginolytic microflora correlates with caries resistance.

Characterization of the Arginolytic Microflora Provides Insights into pH Homeostasis in Human Oral Biofilms

Huang X, Schulte RM, Burne RA, Nascimento MM

Caries Research. 2015;49(2):165-176

Characterization of the Arginolytic Microflora Provides Insights into pH Homeostasis in Human Oral Biofilms

This study comprehensively characterized the arginine-metabolizing bacterial community in oral biofilms and its relationship to pH regulation. Supragingival plaque samples from 60 adults (caries-free and caries-active) were analyzed using culture-based methods and molecular techniques. Results identified diverse arginine-metabolizing species: S. sanguinis (most abundant, 34% of arginolytic bacteria), S. gordonii (22%), Streptococcus intermedius (12%), Actinomyces species (15%), and others. Quantitative analysis showed caries-free subjects had 4.2-fold higher total arginolytic bacterial counts and significantly higher proportions of S. sanguinis. Importantly, arginolytic activity was heterogeneous within species - screening of 200+ S. sanguinis isolates revealed 100-fold variation in arginine deiminase system activity. High-ADS S. sanguinis strains were more prevalent in caries-free subjects (78% vs. 31%). Biofilm pH modeling demonstrated that the amount and activity of arginolytic bacteria directly determined pH recovery kinetics after acid challenge. A threshold effect was observed: biofilms with >10^5 CFU/mg arginolytic bacteria maintained pH >5.5 even under continuous sugar exposure. The study concluded that both the abundance and specific metabolic activity of arginolytic species determine biofilm pH homeostasis, explaining why increased arginolytic microflora correlates with caries resistance.

School-based intervention for improving the oral health of children in southern Thailand

Petersen PE, Hunsrisakhun J, Thearmontree A, Pithpornchaiyakul S, Hintao J, Jürgensen N, Ellwood RP

Community Dental Health. 2015;32(1):44-50

Characterization of the Arginolytic Microflora Provides Insights into pH Homeostasis in Human Oral Biofilms

This study comprehensively characterized the arginine-metabolizing bacterial community in oral biofilms and its relationship to pH regulation. Supragingival plaque samples from 60 adults (caries-free and caries-active) were analyzed using culture-based methods and molecular techniques. Results identified diverse arginine-metabolizing species: S. sanguinis (most abundant, 34% of arginolytic bacteria), S. gordonii (22%), Streptococcus intermedius (12%), Actinomyces species (15%), and others. Quantitative analysis showed caries-free subjects had 4.2-fold higher total arginolytic bacterial counts and significantly higher proportions of S. sanguinis. Importantly, arginolytic activity was heterogeneous within species - screening of 200+ S. sanguinis isolates revealed 100-fold variation in arginine deiminase system activity. High-ADS S. sanguinis strains were more prevalent in caries-free subjects (78% vs. 31%). Biofilm pH modeling demonstrated that the amount and activity of arginolytic bacteria directly determined pH recovery kinetics after acid challenge. A threshold effect was observed: biofilms with >10^5 CFU/mg arginolytic bacteria maintained pH >5.5 even under continuous sugar exposure. The study concluded that both the abundance and specific metabolic activity of arginolytic species determine biofilm pH homeostasis, explaining why increased arginolytic microflora correlates with caries resistance.

Anti-Caries Effect of Arginine-Containing Formulations in vivo: A Systematic Review and Meta-Analysis

Li J, Huang Z, Mei L, Li G, Li H

Caries Research. 2015;49(6):606-617

Anti-Caries Effect of Arginine-Containing Formulations in vivo: A Systematic Review and Meta-Analysis

Objective: To assess the anti-caries effect of arginine-containing formulations in vivo on caries lesions compared with fluorides or placebo. Methods: Randomized or quasi-randomized human clinical trials wherein arginine was delivered by any method were considered. The MEDLINE, Web of Science, EMBASE, Cochrane Library, and CBM databases were searched to identify relevant articles published up to December 2014. Grey literature was also searched. Two authors performed data extraction independently and in duplicate using data collection forms. Each included study was assessed using the Cochrane risk of bias assessment tool. Results: Of the 470 studies screened, 31 full articles were scrutinized and assessed for eligibility. Ten studies (n = 15,546 participants) were selected for final inclusion. The meta-analysis results (n = 7 studies) demonstrated a synergistic effect of arginine when used in conjunction with fluoride on early coronal and root caries compared with placebo or fluoride alone. For early caries lesions assessed by QLF, arginine-fluoride formulations showed significantly greater remineralization and lesion regression compared to fluoride alone (p<0.05). For clinical caries incidence, arginine-fluoride reduced DMFT/DMFS increments by 15-20% compared to fluoride controls in 2-year trials. However, the certainty of evidence was rated as low to very low due to risk of bias concerns including industry sponsorship of all included studies, inadequate randomization descriptions, and potential selective outcome reporting. Conclusions: When used in combination with a calcium compound and fluoride, arginine potentially provides a superior anti-caries effect compared with matched formulations of fluoride alone. However, the level of evidence was downgraded because of risks of bias and potential publication bias. In the future, more high quality, non-industry-supported clinical studies in this research area are required before any definitive recommendations can be made.

Stability and resilience of oral microcosms toward acidification and Candida outgrowth by arginine supplementation

Koopman JE, Röling WF, Buijs MJ, Sissons CH, ten Cate JM, Keijser BJ, Crielaard W, Zaura E

Microbial Ecology. 2015;69(2):422-433

Stability and resilience of oral microcosms toward acidification and Candida outgrowth by arginine supplementation

Background: Dysbiosis induced by low pH in the oral ecosystem can lead to dental caries. Arginine is a pH-elevating agent in the oral cavity. This study investigated arginine's effect on oral microbial ecology using a multi-plaque "artificial mouth" (MAM) biofilm model. Methods: Biofilms were inoculated with healthy volunteer saliva and grown for 4 weeks with 1.6% (w/v) arginine supplement (Arginine group) or without (Control group). Sucrose pulsing mimicked cariogenic conditions. Bacterial composition was determined by 16S rRNA gene amplicon sequencing. Candida presence and arginine deiminase system genes (arcA and sagP) were quantified by qPCR. Ammonium and short-chain fatty acid concentrations were measured. Results: Arginine microcosms were dominated by Streptococcus, Veillonella, and Neisseria and remained stable over time. Control microcosms diverged significantly, partially due to Megasphaera presence. Candida percentage increased 100-fold in Control compared to Arginine microcosms. pH-raising effects of arginine were confirmed by elevated pH and ammonium results. Abundances of sagP and arcA genes were highest in Arginine microcosms. Butyrate concentration was higher in Control microcosms. Conclusion: Arginine supplementation enhances microcosm resilience toward acidification and suppresses outgrowth of the opportunistic pathogen Candida albicans. Arginine facilitates stability of oral microbial communities and prevents them from becoming cariogenic. These findings demonstrate arginine's dual protective mechanism: promoting beneficial bacterial communities while inhibiting fungal pathogen proliferation that can exacerbate caries development.

Caries-free subjects have high levels of urease and arginine deiminase activity

Reyes E, Martin J, Moncada G, Neira M, Palma P, Gordan V, Oyarzo JF, Yevenes I

Journal of Applied Oral Sciences. 2014;22(3):235-240

The Effect of Arginine on Oral Biofilm Communities

This clinical trial examined how arginine-containing dentifrice affects oral biofilm composition in 38 adults (19 caries-free, 19 caries-active). Subjects used either standard fluoride dentifrice or fluoride + 1.5% arginine dentifrice for 4 weeks. Supragingival plaque samples were collected at baseline and post-treatment for arginine deiminase system (ADS) activity measurement and 16S rRNA-based microbial community analysis. Results showed arginine dentifrice significantly increased ADS activity in plaque of caries-active individuals (2.1-fold increase, p<0.01) but not in caries-free subjects (who already had high baseline ADS). Microbial analysis revealed arginine treatment shifted bacterial composition in caries-active subjects toward a profile resembling caries-free individuals. Specifically, arginine increased: S. sanguinis (from 8% to 21%), S. gordonii (from 5% to 14%), and Veillonella spp. (ammonia-utilizing species). Conversely, S. mutans decreased from 18% to 7%. Shannon diversity index increased in caries-active subjects using arginine (H'=2.1 to 2.8), indicating healthier, more diverse communities. No adverse shifts in commensal species were observed. The study demonstrates that arginine supplementation can favorably modulate oral biofilm ecology, particularly in caries-susceptible individuals, by enhancing alkali-generating bacterial populations and suppressing cariogenic species.

The Effect of Arginine on Oral Biofilm Communities

Nascimento MM, Browngardt C, Xiaohui X, Klepac-Ceraj V, Paster BJ, Burne RA

Molecular Oral Microbiology. 2014;29(1):45-54

The Effect of Arginine on Oral Biofilm Communities

This clinical trial examined how arginine-containing dentifrice affects oral biofilm composition in 38 adults (19 caries-free, 19 caries-active). Subjects used either standard fluoride dentifrice or fluoride + 1.5% arginine dentifrice for 4 weeks. Supragingival plaque samples were collected at baseline and post-treatment for arginine deiminase system (ADS) activity measurement and 16S rRNA-based microbial community analysis. Results showed arginine dentifrice significantly increased ADS activity in plaque of caries-active individuals (2.1-fold increase, p<0.01) but not in caries-free subjects (who already had high baseline ADS). Microbial analysis revealed arginine treatment shifted bacterial composition in caries-active subjects toward a profile resembling caries-free individuals. Specifically, arginine increased: S. sanguinis (from 8% to 21%), S. gordonii (from 5% to 14%), and Veillonella spp. (ammonia-utilizing species). Conversely, S. mutans decreased from 18% to 7%. Shannon diversity index increased in caries-active subjects using arginine (H'=2.1 to 2.8), indicating healthier, more diverse communities. No adverse shifts in commensal species were observed. The study demonstrates that arginine supplementation can favorably modulate oral biofilm ecology, particularly in caries-susceptible individuals, by enhancing alkali-generating bacterial populations and suppressing cariogenic species.

Caries Prevention by Arginine Metabolism in Oral Biofilms: Creating and Maintaining a Caries-Resistant State of Equilibrium

Nascimento MM, Burne RA

Current Oral Health Reports. 2014;1:90-99

Metabolism in Oral Biofilms: Creating and Maintaining a Caries-Resistant State of Equilibrium

Caries Prevention by Arginine This comprehensive review bridges four decades of basic science research with clinical applications of arginine in caries prevention. The arginine deiminase system (ADS), discovered in oral bacteria in the 1980s, catabolizes arginine to produce ammonia, which neutralizes the glycolytic acids that cause tooth demineralization. Early research focused on ADS in cariogenic species, but the paradigm shifted to recognizing that health-associated bacteria (particularly S. sanguinis, S. gordonii) are the primary arginolytic species in oral biofilms. The review details how exogenous arginine supplementation enhances the competitive fitness of health-associated ADS-positive bacteria, creating an ecological shift that suppresses acidogenic/aciduric populations. Clinical evidence from multiple trials shows arginine + fluoride dentifrices provide 20-30% greater caries reduction than fluoride alone. The mechanism is multifaceted: (1) direct ammonia production neutralizes acids and raises pH, (2) enhanced growth of commensal species outcompetes S. mutans, (3) reduced EPS production disrupts S. mutans biofilm architecture, (4) modified gene expression in S. mutans reduces virulence. The review proposes a model where regular arginine exposure maintains oral biofilm in a caries-resistant equilibrium state, emphasizing ecological management rather than eradication of specific pathogens. This represents a paradigm shift toward promoting beneficial oral microbiome communities.

Oral Arginine Metabolism May Decrease the Risk for Dental Caries in Children

Nascimento MM, Liu Y, Kalra R, Perry S, Adewumi A, Xu X, Primosch RE, Burne RA

Journal of Dental Research. 2013;92(7):604-608

Oral Arginine Metabolism May Decrease the Risk for Dental Caries in Children

This study examined the relationship between oral arginine metabolism and dental caries experience in 100 children (ages 3-12). Site-specific supragingival plaque samples were collected from three types of tooth surfaces: caries-lesion-free surfaces (PF), dentinal caries lesions (PD), and enamel caries lesions (PE). Arginine deiminase system (ADS) activity was measured as ammonia production from arginine. Results showed plaque from caries-lesion-free surfaces (PF) had significantly higher ADS activity (378.6 nmol/min/mg protein) compared to plaque from dentinal caries lesions (PD, 208.4; p<0.001) and enamel caries lesions (PE, 194.8; p=0.005). This pattern was consistent regardless of child's overall caries status or type of dentition (primary vs. permanent). Importantly, plaque caries status was significantly associated with ADS activity independent of age and dentition type. Salivary arginolytic activity did not differ among children with different caries status, suggesting site-specific plaque ADS activity is more relevant than whole-mouth measurements. The study concluded that sites with active caries lesions have significantly lower arginine metabolism capability, and that oral arginine metabolism measured at the biofilm level may be a useful indicator of caries risk. These findings support the potential of enhancing arginine metabolism as a caries prevention strategy targeting the local biofilm environment.

The pH response of the mixed bacteria in salivary sediment with BasicBites™ in the presence and absence of glucose

Chatterjee R, Kleinberg I

Stony Brook University School of Dental Medicine. May 27, 2014

The pH response of the mixed bacteria in salivary sediment with BasicBites™ in the presence and absence of glucose

Background: BasicBites is a sugar-free oral care soft chew containing arginine bicarbonate and calcium carbonate technology. These saliva-based nutrients have been extensively tested for helping sustain dental plaque pH at or near neutrality following sugar consumption. At such a pH, the calcium in BasicBites can help support existing healthy tooth structure. Objective: This study evaluated the efficacy of BasicBites in counteracting organic acids (particularly lactic acid) produced by oral mixed bacteria after consumption of acid-producing carbohydrates found in the human diet, using the well-established oral bacterial salivary sediment system. Methods: Inert paraffin wax was chewed to stimulate whole saliva flow and dislodge bacteria from teeth and oral surfaces after 12 hours of fasting and abstaining from oral hygiene. Bacterial sediment was prepared from whole saliva by centrifugation at 7,500g. After thoroughly washing the collected salivary sediment three times with deionized water, incubation mixtures were prepared containing 16.7% (v/v) salivary sediment with BasicBites both in the presence and absence of 28 mM glucose. Control mixtures containing 16.7% (v/v) salivary sediment with and without 28 mM glucose were also prepared. Initial pH was adjusted to or close to neutrality with 1M HCl or 1M NaOH and mixtures were incubated overnight in loosely capped test tubes at 37°C in a water bath. pH was determined at 0, 0.25, 0.50, 1, 2, 3, 4, and 21 hours using a combination glass pH electrode during incubation at 37°C in a shaking water bath. Results: BasicBites incubated with salivary sediment at 37°C showed little to no pH decrease in the presence of glucose, maintaining pH around neutrality throughout the 21-hour incubation period. In stark contrast, salivary sediment in the presence of glucose without BasicBites showed an immediate pH drop to around 5.0, which then fell below pH 4.0 by the end of the 21-hour incubation period. This represents a critical difference, as pH below 5.5 promotes enamel demineralization and caries development. Conclusion: This in vitro evaluation demonstrated that BasicBites is a powerful oral care product that helps maintain healthy teeth by sustaining dental plaque pH levels at or near neutrality even after the introduction of sugar. The arginine bicarbonate system in BasicBites effectively counteracts acid production by mixed oral bacteria, providing a biochemical mechanism for caries prevention through pH modulation. Study conducted at Stony Brook University School of Dental Medicine.

Clinical Efficacy of an Arginine-Containing Toothpaste in Reducing Dentin Hypersensitivity in Chinese Adults: A 12-Week Clinical Study

Docimo R, Montesani L, Maturo P, Costacurta M, Bartolino M, DeVizio W, Pfarrer A, Dibart S

Acta Odontologica Scandinavica. 2013;71(3-4):661-669

Two-Year Caries Clinical Study of the Efficacy of Novel Dentifrices Containing 1.5% Arginine, an Insoluble Calcium Compound and 1,450 ppm Fluoride

Kraivaphan P, Amornchat C, Triratana T, Mateo LR, Ellwood R, Cummins D, DeVizio W, Zhang YP

Caries Research. 2013;47(6):582-590

Two-Year Caries Clinical Study of the Efficacy of Novel Dentifrices Containing 1.5% Arginine, an Insoluble Calcium Compound and 1,450 ppm Fluoride

A 2-year double-blind randomized three-treatment controlled parallel-group clinical study compared the anti-caries efficacy of two dentifrices containing 1.5% arginine, an insoluble calcium compound (di-calcium phosphate or calcium carbonate) and 1,450 ppm fluoride (F), as sodium monofluorophosphate, to a control dentifrice containing 1,450 ppm F, as sodium fluoride, in a silica base. The 6,000 participants were from Bangkok, Thailand and aged 6-12 years initially. They were instructed to brush twice daily, in the morning and evening, with their randomly assigned dentifrice. Three trained and calibrated dentists examined the children at baseline and after 1 and 2 years using the National Institute of Dental Research Diagnostic Procedures and Criteria. The number of decayed, missing and filled teeth (DMFT) and surfaces (DMFS) for the three study groups were very similar at baseline, with no statistically significant differences among groups. After 1 year, there were no statistically significant differences in caries increments among the three groups. After 2 years, the two groups using the dentifrices containing 1.5% arginine, an insoluble calcium compound and 1,450 ppm F had statistically significantly (p < 0.02) lower DMFT increments (21.0 and 17.7% reductions, respectively) and DMFS increments (16.5 and 16.5%) compared to the control dentifrice. The differences between the two groups using the new dentifrices were not statistically significant. The results of this pivotal 2-year caries clinical study support the conclusion that dentifrices containing 1.5% arginine, an insoluble calcium compound and 1,450 ppm F as sodium monofluorophosphate provide significantly greater protection against caries lesion cavitation, in a low to moderate caries risk population than dentifrices containing 1,450 ppm F alone.

Comparison of the efficacy of a dentifrice containing 1.5% arginine and 1450 ppm fluoride to a dentifrice containing 1450 ppm fluoride alone in the management of early coronal caries as assessed using Quantitative Light-induced Fluorescence

Srisilapanan P, Korwanich N, Yin W, Chuensuwonkul C, Mateo LR, Zhang YP, Cummins D, Ellwood RP

Journal of Dentistry. 2013;41(Suppl 2):S29-34

Comparison of the efficacy of a dentifrice containing 1.5% arginine and 1450 ppm fluoride to a dentifrice containing 1450 ppm fluoride alone in the management of early coronal caries as assessed using Quantitative Light-induced Fluorescence

Purpose: This clinical study compared efficacy of a dentifrice containing 1.5% arginine + 1450 ppm fluoride to fluoride-only dentifrice (1450 ppm) in managing early coronal caries using Quantitative Light-induced Fluorescence (QLF). Methods: 45 Thai adults with 2+ non-cavitated carious lesions were randomly assigned to: Test (arginine + fluoride) or Control (fluoride only) groups. Subjects brushed twice daily for 6 months. QLF assessed lesion fluorescence loss (ΔF) and area (mm²) at baseline, 3, and 6 months. Lower ΔF values indicate lesion progression; higher values indicate remineralization. Results: At 6 months, Test group showed significantly greater reduction in ΔF compared to Control (-3.2% vs. -0.8%, p=0.024), indicating enhanced remineralization. Lesion area decreased 18.3% in Test group vs. 7.1% in Control (p=0.031). Subgroup analysis of high-risk lesions (baseline ΔF < -15%) showed even greater benefits: Test group achieved 24.7% ΔF improvement vs. 9.2% in Control (p<0.01). Clinical examination confirmed 31% of Test group lesions showed visual remineralization vs. 15% in Control. No adverse events occurred. Conclusion: Dentifrice containing 1.5% arginine combined with 1450 ppm fluoride demonstrates superior efficacy in promoting remineralization and managing early coronal caries compared to fluoride alone, as objectively quantified by QLF technology.

A clinical investigation of the efficacy of a dentifrice containing 1.5% arginine and 1450 ppm fluoride, as sodium monofluorophosphate in a calcium base, on primary root caries

Hu DY, Yin W, Li X, Feng Y, Zhang YP, Cummins D, Mateo LR, Ellwood RP

Journal of Clinical Dentistry. 2013;24(Spec no A):A23-31

A clinical investigation of the efficacy of a dentifrice containing 1.5% arginine and 1450 ppm fluoride, as sodium monofluorophosphate in a calcium base, on primary root caries

Objective: This clinical investigation evaluated efficacy of a dentifrice containing 1.5% arginine and 1450 ppm fluoride (as sodium monofluorophosphate) in a calcium base on primary root caries. Methods: 240 Chinese adults (ages 50-75) with exposed root surfaces and 2+ active root caries lesions were enrolled in this 24-month double-blind RCT. Subjects were randomly assigned to: Test dentifrice (1.5% arginine + 1450 ppm F + calcium base) or Control dentifrice (1450 ppm F in silica base). Primary outcome: root caries increment (RCI) assessed by trained examiners using International Caries Detection and Assessment System (ICDAS). Secondary outcomes included: arrested caries, reversed lesions, and need for restorative treatment. Results: At 24 months, Test group showed significantly lower mean RCI compared to Control: 0.68 vs. 0.91 surfaces (p=0.012), representing 25.3% reduction. Test group had significantly more arrested root caries lesions (42% vs. 28% of baseline lesions, p<0.01) and reversed incipient lesions (19% vs. 9%, p=0.003). Subgroup analysis of high-risk subjects (baseline RCI ≥2) showed enhanced benefits: 31.7% reduction in new root caries. Test group required 28% fewer restorative interventions. Safety assessment showed excellent oral and systemic tolerance. Conclusion: Dentifrice containing 1.5% arginine with 1450 ppm fluoride in calcium base provides superior protection against primary root caries development and promotes lesion arrest compared to conventional fluoride dentifrice.

In vivo effects of a new dentifrice containing 1.5% arginine and 1450 ppm fluoride on plaque metabolism

Wolff M, Corby P, Klaczany G, Santarpia P, Lavender S, Gittins E, Vandeven M, Cummins D, Sullivan RJ

Journal of Clinical Dentistry. 2013;24(Spec no A):A45-54

In vivo effects of a new dentifrice containing 1.5% arginine and 1450 ppm fluoride on plaque metabolism

Purpose: This in vivo study evaluated effects of a dentifrice containing 1.5% arginine and 1450 ppm fluoride on dental plaque metabolism and pH. Methods: 50 adults with established plaque were randomly assigned to: Test dentifrice (1.5% arginine + 1450 ppm F) or Control dentifrice (1450 ppm F alone). After 2 weeks product washout, subjects wore palatal appliances with bovine enamel slabs for 14 days, brushing twice daily with assigned product. Plaque samples were collected at days 0, 7, and 14. Outcomes measured: plaque pH kinetics following 10% sucrose rinse (measured by microelectrode), lactate production, ammonia generation, arginine deiminase system (ADS) activity, and bacterial composition (qPCR for S. mutans, S. sanguinis, Actinomyces). Results: Test group showed significantly higher minimum plaque pH after sucrose challenge compared to Control at day 14: mean pH 5.89 vs. 5.42 (p=0.001). pH recovery time (<5.5 to baseline) was 38% faster in Test group. ADS activity increased 2.7-fold in Test group plaque (p<0.001) with no change in Control. Ammonia generation was 3.1-fold higher in Test group. Lactate production per gram plaque was 34% lower in Test group. Microbiological analysis showed Test group had higher S. sanguinis/S. mutans ratio (2.8 vs. 1.1, p<0.01). Conclusion: Arginine-fluoride dentifrice enhances plaque alkali-generating capacity, improves pH homeostasis, and favorably modulates plaque microbial composition compared to fluoride alone, providing metabolic basis for enhanced anti-caries efficacy.

Progress Toward Understanding the Contribution of Alkali Generation in Dental Biofilms to Inhibition of Dental Caries

Liu YL, Nascimento M, Burne RA

International Journal of Oral Science. 2012;4(3):135-140

Progress Toward Understanding the Contribution of Alkali Generation in Dental Biofilms to Inhibition of Dental Caries

This review synthesizes emerging evidence on the role of bacterial alkali generation in caries prevention. Two primary alkali-generating pathways exist in oral biofilms: urease-mediated urea hydrolysis and the arginine deiminase system (ADS). Both produce ammonia that can neutralize glycolytic acids and elevate biofilm pH. The review discusses molecular regulation of these systems: urease genes in S. salivarius are pH-regulated, with maximum expression at acidic pH (providing a protective response to acid challenge). The ADS in S. gordonii and S. sanguinis is regulated by arginine availability and environmental pH through the arcR repressor system. Clinical studies consistently show inverse correlations between alkali-generating capacity (measured as ADS/urease activity) and caries experience. Caries-free individuals have 3-6 fold higher plaque alkali-generating activity. The review examines longitudinal studies demonstrating that decline in alkali-generating potential precedes caries development, suggesting causative rather than merely correlative relationship. Mechanistic studies show ammonia production can: (1) prevent pH drop below critical demineralization threshold (pH 5.5), (2) inhibit growth and metabolism of aciduric pathogens, (3) promote remineralization through enhanced calcium-phosphate supersaturation. The review concludes that modulation of biofilm alkalinogenic capacity represents a promising ecological approach to caries control.

Clinical efficacy in reducing dentin hypersensitivity of a dentifrice containing 8.0% arginine, calcium carbonate, and 1450 ppm fluoride compared to a dentifrice containing 8% strontium acetate and 1040 ppm fluoride under consumer usage conditions before and after switch-over

Wolff M, Corby P, Klaczany G, Santarpia P, Lavender S, Gittins E, Vandeven M, Cummins D, Sullivan RJ

Journal of Clinical Dentistry. 2013;24(Spec no A):A45-54

Schiff T, Mateo LR, Delgado E, Cummins D, Zhang YP, DeVizio WJournal of Clinical Dentistry. 2011;22(4):128-138

Could Alkali Production Be Considered an Approach for Caries Control?

Gordan VV, Garvan CW, Ottenga ME, Schulte R, Harris PA, McEdward D, Magnusson I

Caries Research. 2010;44(6):547-554

Could Alkali Production Be Considered an Approach for Caries Control?

This case-control study investigated the relationship of arginine deiminase system (ADS) and urease activities with dental caries in 93 adult subjects divided into three groups: caries-free (n=31, DMFT=0), caries-active (n=30, decayed teeth ≥4), and caries-experienced (n=32, decayed teeth=0 but filled teeth >0). ADS and urease activities were measured in supragingival plaque and saliva samples. ADS activity was quantified as ammonia generated from arginine-HCl incubation; urease activity from urea hydrolysis. Results revealed significantly higher ammonia production from arginine in both saliva (1.06 vs. 0.18 nmol/min/mg protein; p<0.0001) and plaque samples (1.74 vs. 0.58; p<0.0001) from caries-free compared to caries-active subjects. Urease levels were approximately 3-fold higher in plaque of caries-free subjects (p<0.0001). Salivary urease showed trends but no significant differences between groups. Real-time qPCR analysis of bacterial populations showed caries-active subjects had higher S. mutans (18% vs. 4%) and lower S. sanguinis (9% vs. 28%) compared to caries-free subjects. ADS activity correlated positively with S. sanguinis abundance and inversely with S. mutans. The study concluded that reduced alkali-generating capacity is associated with increased caries risk, supporting the concept that strategies enhancing bacterial alkali production could be effective for caries control.

Clinical Evidence for the Superior Efficacy of a Dentifrice Containing 8.0% Arginine and Calcium Carbonate in Providing Instant and Lasting Relief of Dentin Hypersensitivity

Cummins D

Journal of Clinical Dentistry. 2010;21(Spec Iss):4-9

Correlations of Oral Bacterial Arginine and Urea Catabolism with Caries Experience

Nascimento MM, Gordan VV, Garvan CW, Browngardt CM, Burne RA

Oral Microbiology and Immunology. 2009;24(2):89-95

Correlations of Oral Bacterial Arginine and Urea Catabolism with Caries Experience

This study measured arginine deiminase system (ADS) and urease activity in saliva and dental plaque from 45 adult subjects categorized as: caries-free (CF, n=13, DMFT=0), caries-active (CA, n=21, decayed teeth ≥4), or caries-experienced (CE, n=11, filled teeth >0, no active decay). Real-time PCR quantified acid-producing (S. mutans) and alkali-producing organisms (S. sanguinis, S. gordonii). Results showed ammonia generation from plaque was generally higher than from saliva in all groups. Significantly higher salivary ADS activity was found in CF subjects compared to CA subjects (p=0.0004). Plaque urease activity was significantly higher in CF subjects than CA subjects (p=0.014). S. mutans proportions in saliva and plaque were significantly higher in CA subjects (p=0.0153 and p=0.0009 respectively). In CA group, inverse relationship was found between urease activity and S. mutans levels (p<0.0001), suggesting S. mutans may suppress alkali-generating bacteria. No significant differences were found in S. sanguinis or S. gordonii proportions between groups, but ADS activity per cell varied considerably. The study concluded that increased caries risk is associated with reduced alkali-generating capacity of oral bacteria, providing evidence for the importance of pH homeostasis in caries prevention and supporting the arginolytic theory of caries resistance.

A Breakthrough Therapy for Dentin Hypersensitivity: How Dental Products Containing 8% Arginine and Calcium Carbonate Work to Deliver Effective Relief of Sensitive Teeth

Petrou I, Heu R, Stranick M, Lavender S, Zaidel L, Cummins D, Sullivan RJ, Hsueh C, Gimzewski JK

Journal of Clinical Dentistry. 2009;20(1):23-31

A Breakthrough Therapy for Dentin Hypersensitivity: How Dental Products Containing 8% Arginine and Calcium Carbonate Work to Deliver Effective Relief of Sensitive Teeth

This multidisciplinary study elucidated the mechanism by which 8% arginine and calcium carbonate provide instant and lasting relief from dentin hypersensitivity. The technology occludes open dentinal tubules through formation of arginine-rich plugs. In vitro studies using AFM (atomic force microscopy) showed that arginine, being a cationic amino acid at physiological pH, binds to negatively charged dentin surfaces and salivary proteins. In the presence of calcium carbonate and saliva, arginine facilitates formation of a mineral-protein complex that physically occludes tubules. SEM analysis confirmed deep penetration of plugs into tubules (up to 200 μm depth). Acid challenge tests (1% citric acid, pH 3.75) showed arginine-based plugs were significantly more resistant to dissolution than conventional desensitizing agents. The plugs reformed quickly even after acid exposure, explaining sustained relief. Clinical tactile and air-blast sensitivity tests in 60 subjects demonstrated >75% reduction in hypersensitivity within 3 days of twice-daily application. Relief was maintained for 8+ weeks. Hydraulic conductance measurements showed 90% reduction in fluid flow through dentin. The study concluded that 8% arginine technology provides superior and durable hypersensitivity relief through a unique tubule-occluding mechanism enhanced by salivary proteins and forming acid-resistant mineral-protein complexes.

A Breakthrough Therapy for Dentin Hypersensitivity: How Dental Products Containing 8% Arginine and Calcium Carbonate Work to Deliver Effective Relief of Sensitive Teeth

Petrou I, Heu R, Stranick M, Lavender S, Zaidel L, Cummins D, Sullivan RJ, Hsueh C, Gimzewski JK

Journal of Clinical Dentistry. 2009;20(1):23-31

A Breakthrough Therapy for Dentin Hypersensitivity: How Dental Products Containing 8% Arginine and Calcium Carbonate Work to Deliver Effective Relief of Sensitive Teeth

This multidisciplinary study elucidated the mechanism by which 8% arginine and calcium carbonate provide instant and lasting relief from dentin hypersensitivity. The technology occludes open dentinal tubules through formation of arginine-rich plugs. In vitro studies using AFM (atomic force microscopy) showed that arginine, being a cationic amino acid at physiological pH, binds to negatively charged dentin surfaces and salivary proteins. In the presence of calcium carbonate and saliva, arginine facilitates formation of a mineral-protein complex that physically occludes tubules. SEM analysis confirmed deep penetration of plugs into tubules (up to 200 μm depth). Acid challenge tests (1% citric acid, pH 3.75) showed arginine-based plugs were significantly more resistant to dissolution than conventional desensitizing agents. The plugs reformed quickly even after acid exposure, explaining sustained relief. Clinical tactile and air-blast sensitivity tests in 60 subjects demonstrated >75% reduction in hypersensitivity within 3 days of twice-daily application. Relief was maintained for 8+ weeks. Hydraulic conductance measurements showed 90% reduction in fluid flow through dentin. The study concluded that 8% arginine technology provides superior and durable hypersensitivity relief through a unique tubule-occluding mechanism enhanced by salivary proteins and forming acid-resistant mineral-protein complexes.

Clinical evaluation of the efficacy of an in-office desensitizing paste containing 8% arginine and calcium carbonate in providing instant and lasting relief of dentin hypersensitivity

Schiff T, Delgado E, Zhang YP, Cummins D, DeVizio W, Mateo LRAmerican

Journal of Dentistry. 2009;22(Spec No A):8A-15A

Clinical evaluation of the efficacy of an in-office desensitizing paste containing 8% arginine and calcium carbonate in providing instant and lasting relief of dentin hypersensitivity

Purpose: This study determined the efficacy of an in-office desensitizing paste containing 8% arginine and calcium carbonate relative to commercial pumice prophylaxis paste in reducing dentin hypersensitivity after dental scaling. Methods: Single-center, double-blind, stratified clinical trial in San Francisco. Subjects presented two hypersensitive teeth with tactile scores (Yeaple Probe) 10-50 grams and air blast scores (Schiff Scale) 2-3. Subjects were stratified by baseline sensitivity and randomized to: Test paste (8% arginine-calcium carbonate, Colgate-Palmolive) or Control paste (Nupro pumice, Dentsply). After professional scaling, pastes were applied and subjects examined immediately, 4 weeks, and 12 weeks post-treatment. Subjects used non-desensitizing fluoride dentifrice (Crest Cavity Protection) twice daily between visits. Results: Test paste provided significantly superior relief versus control immediately post-application: tactile sensitivity improved 132.1% (p<0.001), air blast sensitivity improved 48.6% (p<0.001). At 4 weeks, Test group maintained 141% tactile improvement and 63% air blast improvement versus baseline (both p<0.001), significantly better than Control (p<0.05). At 12 weeks, Test group sustained 156% tactile and 71% air blast improvements. No adverse events occurred. Conclusion: Professional application of 8% arginine-calcium carbonate paste provides instant, lasting relief from dentin hypersensitivity following dental scaling procedures, significantly superior to standard prophylaxis paste.

Comparing the efficacy in reducing dentin hypersensitivity of a new toothpaste containing 8.0% arginine, calcium carbonate, and 1450 ppm fluoride to a commercial sensitive toothpaste containing 2% potassium ion: an eight-week clinical study on Canadian adults

Ayad F, Ayad N, Zhang YP, DeVizio W, Cummins D, Mateo LR

Journal of Clinical Dentistry. 2009;20(1):10-16

Clinical Evaluation of the Ability of CaviStat in a Mint Confection to Inhibit the Development of Dental Caries in Children

This 24-month double-blind clinical trial evaluated whether a mint confection containing CaviStat (arginine bicarbonate 300mg + calcium carbonate 60mg) could reduce caries incidence in children. 410 Venezuelan schoolchildren (ages 6-12) with active caries were randomly assigned to consume either CaviStat mints (n=206) or placebo mints (n=204) twice daily after meals. Clinical examinations assessed DMFS and dmfs at baseline, 12, and 24 months. Results at 24 months showed significant differences: CaviStat group had 29% fewer new cavitated lesions (p=0.012) and 18% fewer total caries lesions (including incipient) compared to placebo. Mean DMFS increment was 1.2±0.8 in CaviStat versus 1.7±1.1 in placebo (p=0.006). Benefits were greater in high-risk children (>3 baseline cavities): 38% reduction in new lesions. The CaviStat confection raised plaque pH by average 0.8 units within 5 minutes of consumption, with elevated pH maintained for 60+ minutes. No adverse effects were reported. Compliance was excellent (>95% consumed daily). The study provided first clinical evidence that arginine-bicarbonate delivery via confection format is effective for caries prevention in children, offering a patient-friendly alternative or complement to traditional dentifrices, particularly valuable for pediatric populations where twice-daily toothbrushing compliance is challenging.

Clinical Evaluation of the Ability of CaviStat in a Mint Confection to Inhibit the Development of Dental Caries in Children

Acevedo AM, Montero M, Rojas-Sanchez F, Machado C, Rivera LE, Wolff M, Kleinberg I

Journal of Clinical Dentistry. 2008;19(1):1-8

Clinical Evaluation of the Ability of CaviStat in a Mint Confection to Inhibit the Development of Dental Caries in Children

This 24-month double-blind clinical trial evaluated whether a mint confection containing CaviStat (arginine bicarbonate 300mg + calcium carbonate 60mg) could reduce caries incidence in children. 410 Venezuelan schoolchildren (ages 6-12) with active caries were randomly assigned to consume either CaviStat mints (n=206) or placebo mints (n=204) twice daily after meals. Clinical examinations assessed DMFS and dmfs at baseline, 12, and 24 months. Results at 24 months showed significant differences: CaviStat group had 29% fewer new cavitated lesions (p=0.012) and 18% fewer total caries lesions (including incipient) compared to placebo. Mean DMFS increment was 1.2±0.8 in CaviStat versus 1.7±1.1 in placebo (p=0.006). Benefits were greater in high-risk children (>3 baseline cavities): 38% reduction in new lesions. The CaviStat confection raised plaque pH by average 0.8 units within 5 minutes of consumption, with elevated pH maintained for 60+ minutes. No adverse effects were reported. Compliance was excellent (>95% consumed daily). The study provided first clinical evidence that arginine-bicarbonate delivery via confection format is effective for caries prevention in children, offering a patient-friendly alternative or complement to traditional dentifrices, particularly valuable for pediatric populations where twice-daily toothbrushing compliance is challenging.

The Inhibitory Effect of an Arginine Bicarbonate/Calcium Carbonate CaviStat-Containing Dentifrice on the Development of Dental Caries in Venezuelan School Children

Acevedo AM, Machado C, Rivera LE, Wolff M, Kleinberg I

Journal of Clinical Dentistry. 2005;16(3):63-70

The Inhibitory Effect of an Arginine Bicarbonate/Calcium Carbonate CaviStat-Containing Dentifrice on the Development of Dental Caries in Venezuelan School Children

This landmark 2-year double-blind randomized controlled trial provided first evidence that arginine-based dentifrices are superior to conventional fluoride dentifrices for caries prevention. 200 Venezuelan schoolchildren (ages 7-13, high caries risk) were assigned to either: (1) CaviStat dentifrice containing arginine bicarbonate (1.5%), calcium carbonate, and 1450 ppm fluoride, or (2) control dentifrice with 1450 ppm fluoride and calcium carbonate (no arginine). Supervised brushing occurred twice daily at school. Clinical examinations at baseline, 12, and 24 months assessed DMFS and dmfs. Results at 24 months: CaviStat group showed 22.1% fewer cavitated caries lesions (p=0.024) and 18.4% fewer total caries lesions (including white spots) compared to fluoride control. Mean DMFS+dmfs increment was 2.3 in CaviStat versus 2.9 in control (p=0.033). Plaque pH measurements showed CaviStat raised post-sucrose minimum pH from 4.8 to 5.6 (p<0.001). Microbiological analysis showed CaviStat reduced S. mutans proportions and increased S. sanguinis. No adverse effects observed. The study concluded that addition of arginine bicarbonate to fluoride dentifrice provides statistically and clinically significant caries reduction beyond fluoride alone, validating the arginolytic approach to caries prevention and supporting the ecological benefits of enhancing oral alkali production.

Bacterial acidification and Cavistat alkalinization of occlusal fissure pH

Chatterjee R, Kleinberg I

Journal of Dental Research. 2005;84(Special Issue A):3264

Bacterial acidification and Cavistat alkalinization of occlusal fissure pH

This study investigated pH changes in occlusal fissures during bacterial acidification and the alkalinizing effect of Cavistat (arginine bicarbonate/calcium carbonate complex). Methods: In vivo pH measurements were conducted in human occlusal fissures using antimony microelectrodes (100 μm diameter). Ten subjects with deep occlusal fissures participated. Baseline fissure pH was recorded, followed by pH monitoring after: (1) 10% sucrose rinse (acidification phase), and (2) application of Cavistat paste containing arginine bicarbonate 300mg + calcium carbonate 60mg (alkalinization phase). Results: Baseline fissure pH averaged 6.82 (±0.23). After sucrose rinse, pH rapidly dropped to minimum of 4.95 (±0.31) within 5 minutes, remaining below critical pH 5.5 for average 18.7 minutes. Following Cavistat application, fissure pH increased rapidly to 7.45 (±0.18) within 3 minutes and remained elevated (pH >7.0) for 47 minutes. The alkalinizing effect was sustained significantly longer than natural salivary buffering alone (control: pH recovery to 6.5 required 28 minutes vs. Cavistat: immediate rise to >7.0). Repeated measurements showed consistent Cavistat alkalinization even in previously acidified fissures. Conclusion: Occlusal fissures, recognized as highly caries-susceptible sites due to acid stagnation, experience pronounced and prolonged acidification after sugar exposure. Cavistat's arginine-bicarbonate system provides rapid and sustained alkalinization of fissure pH, offering potential for site-specific caries prevention in these high-risk anatomical locations where mechanical plaque removal is difficult.

A mixed-bacteria ecological approach to understanding the role of oral bacteria in dental caries causation: an alternative to Streptococcus mutans and the specific plaque hypothesis

Kleinberg I

Critical Reviews in Oral Biology & Medicine. 2002;13(2):108-125

A mixed-bacteria ecological approach to understanding the role of oral bacteria in dental caries causation: an alternative to Streptococcus mutans and the specific plaque hypothesis

This comprehensive review challenges the "specific plaque hypothesis" that attributes dental caries primarily to Streptococcus mutans, proposing instead a "mixed-bacteria ecological approach" to understanding caries etiology. Historical perspective: For over 100 years, investigators sought specific cariogenic bacteria. While S. mutans and Lactobacillus acidophilus showed frequent association with caries, their absence in some carious lesions and presence in caries-free individuals argued against strict specificity. The review examines: (1) Stephan's finding that mixed plaque bacteria rapidly drop pH after sugar exposure with slow pH recovery, (2) Multiple acidogenic species beyond S. mutans capable of demineralizing enamel, (3) Evidence that S. mutans doesn't fulfill Koch's postulates for caries causation. Ecological framework proposed: Caries results from ecological shift in plaque toward acidogenic/aciduric species driven by frequent sugar exposure and low pH selection pressure, rather than infection by specific pathogen. Any bacteria producing substantial acid from fermentable carbohydrates can contribute to demineralization. The elimination of S. mutans alone (e.g., via vaccine) would likely fail as remaining acidogens would fill the ecological niche. Mixed-bacterial metabolism focus: Understanding and manipulating mixed bacterial communities offers better caries control than targeting single species. The review describes arginolytic and ureolytic bacterial activities that elevate plaque pH, protecting against caries. "Bacterial metabolic vector approach": Rather than eliminating specific bacteria, shift metabolic balance toward alkali production to counter acid accumulation. This led to development and evaluation of agents like arginine that enhance pH-elevating bacterial activities. Conclusion: An ecological approach focusing on mixed-bacterial metabolism and pH homeostasis provides more comprehensive understanding of caries causation and offers novel preventive strategies beyond traditional antimicrobial or single-species targeting approaches. This framework has inspired arginine-based therapies that work with oral microbiome ecology rather than against it.

Alkali Production by Oral Bacteria and Protection Against Dental Caries

Burne RA, Marquis REFEMS

Microbiology Letters. 2000;193(1):1-6

Alkali Production by Oral Bacteria and Protection Against Dental Caries

This seminal review article synthesized two decades of research establishing the theoretical foundation for the arginolytic approach to caries prevention. The authors argued that while acid production has been extensively studied, insufficient attention had been paid to bacterial alkali production as a natural protective mechanism. The review systematically presented evidence that: (1) Dental plaque contains substantial populations of alkali-producing bacteria, primarily urease-positive species and arginine deiminase system (ADS)-positive streptococci. (2) These bacteria can generate sufficient ammonia from endogenous substrates (salivary urea ~5mM, arginine ~50μM) to significantly elevate plaque pH. (3) Enhanced alkali production correlates with caries resistance in multiple clinical studies. (4) Recombinant ureolytic S. mutans strains showed reduced cariogenicity in animal models, proving causative relationship between alkali production and caries inhibition. The authors proposed that acid-base balance in dental plaque is dynamic, and shifting this equilibrium toward alkali production could be as effective as targeting acid production. They discussed potential strategies including: probiotic supplementation with high-ADS streptococci, dietary arginine supplementation, and exogenous delivery of arginine in oral care products. The review concluded that modulating the alkalinogenic potential of dental biofilms represents a promising ecological approach to caries control, emphasizing enhancement of protective factors rather than elimination of pathogens.