Randomized trial shows arginine treatment improves pH levels in dental biofilms — Evidence Review

A new clinical study finds that arginine, a natural amino acid, can reduce the acidity and alter the bacterial makeup of dental biofilms in people with active tooth decay, potentially lowering cavity risk. Related studies broadly support these findings, showing that arginine improves oral biofilm composition and pH balance, reinforcing its potential role in caries prevention, as seen in research from Aarhus University.

• Multiple laboratory and small human studies indicate that arginine supplementation enhances the alkali-generating activity of beneficial oral bacteria, decreases the dominance of acid-producing bacteria, and modifies the biofilm structure to be less conducive to cavities 1 2 4 5.
• Evidence from in vitro and clinical studies shows that arginine can suppress the growth and virulence of Streptococcus mutans (a key caries pathogen), while promoting more stable, health-associated bacterial communities 2 3 4.
• The new study’s observation of higher biofilm pH and shifts in bacterial composition with arginine aligns with prior findings, but provides novel, direct in-mouth human evidence using a controlled clinical model 1 2 4 5.

Study Overview and Key Findings

Dental caries remain a prevalent global health issue, driven primarily by acid production from bacterial metabolism of dietary sugars. This study is timely as it moves beyond laboratory settings, using a clinical model to examine how arginine—a substance already present in saliva and some oral care products—affects the formation and characteristics of dental biofilms in people with active tooth decay. By employing custom-fitted dentures for in situ biofilm growth and direct comparison, the researchers provide detailed insights into arginine’s effects on oral microbial communities, biofilm structure, and acidity under real-world conditions.

Property	Value
Study Year	2025
Organization	Aarhus University
Journal Name	International Journal of Oral Science
Authors	Yumi C. Del Rey, Pernille D. Rikvold, Marie B. Lund, Eero J. Raittio, Andreas Schramm, Rikke L. Meyer, Sebastian Schlafer
Population	Participants with active dental caries
Sample Size	12 participants
Methods	Randomized Controlled Trial (RCT)
Outcome	pH levels, bacterial composition, carbohydrate structure
Results	Biofilms treated with arginine had significantly higher pH levels

Literature Review: Related Studies

To understand how these findings fit into the broader scientific landscape, we searched the Consensus paper database, which covers over 200 million research papers. We used the following search queries to identify relevant studies:

1. arginine dental biofilm pH levels
2. natural amino acids teeth health
3. sugar impact on dental cavities

Literature Review Topics Table

Topic	Key Findings
How does arginine affect oral biofilm pH and caries risk?	- Arginine enhances alkali (ammonia) production in oral biofilms, raising pH and reducing caries risk 1 2 4 5. - Arginine-containing products shift microbial composition toward less cariogenic profiles 1 2 5.
What mechanisms underlie arginine’s effects on oral bacteria and biofilm structure?	- Arginine suppresses the growth and virulence of S. mutans and favors the dominance of arginolytic, health-associated streptococci 2 3 4. - Arginine reduces exopolysaccharide (EPS) and alters biofilm architecture 2 4 5.
What is the relationship between dietary sugars, amino acids, and dental caries?	- High sugar intake is strongly linked to higher dental caries risk, while amino acids (including arginine) may have anti-caries effects 9 10 11 12 13 14. - Salivary amino acid composition—including arginine—may influence caries susceptibility 7 8 9.
How might protein and amino acid intake influence oral health across the lifespan?	- Adequate dietary protein and amino acids support oral tissue health in older adults and may reduce caries and enamel hypoplasia risk 8 9. - There is a potential role for amino acids as anti-caries agents, but more human studies are needed 8 9.

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How does arginine affect oral biofilm pH and caries risk?

The literature consistently shows that arginine increases the pH of oral biofilms by enhancing alkali (ammonia) production through the arginine deiminase system (ADS), particularly in beneficial bacteria. This action counteracts the acidification caused by sugar metabolism, thus reducing caries risk. The new study confirms these effects in a clinical setting, demonstrating higher biofilm pH in arginine-treated samples from caries-active individuals.

• Arginine supplementation in toothpastes increases ADS activity and shifts microbial communities toward a healthier, less cariogenic profile 1.
• In vitro studies show that arginine stabilizes pH and reduces acidification in mixed-species biofilms 2 5.
• The new study's direct measurement of higher pH in biofilms after arginine treatment supports and extends these laboratory and small clinical findings to a controlled human model 1 2 4 5.
• These effects may be particularly beneficial for individuals with low natural alkali production in saliva or high caries risk 1 4.

What mechanisms underlie arginine’s effects on oral bacteria and biofilm structure?

Arginine not only raises pH but also disrupts the growth and virulence of key caries-causing bacteria such as Streptococcus mutans, while promoting the dominance of less harmful, arginolytic bacteria. It also reduces the formation of exopolysaccharides (EPS), weakening the biofilm matrix and potentially making it less protective for acid-producing bacteria.

• Exposure to 1.5% arginine suppresses S. mutans and favors S. gordonii, leading to reduced EPS production and altered biofilm architecture 2 4.
• Novel strains with high arginolytic capacity (e.g., A12) can inhibit S. mutans via multiple mechanisms, including hydrogen peroxide production and interference with signaling pathways essential for virulence 3.
• Arginine destabilizes biofilm structure, enhances the efficacy of antimicrobials like cetylpyridinium chloride, and promotes the detachment of pathogenic bacteria 5.
• The new clinical study's findings of altered bacterial composition and carbohydrate structure in biofilms echo these mechanistic insights 2 3 4 5.

What is the relationship between dietary sugars, amino acids, and dental caries?

Dietary sugars are the primary driver of dental caries, providing substrate for acidogenic bacteria. Multiple reviews and meta-analyses confirm the direct, dose-dependent relationship between sugar intake and caries incidence. Amino acids, including arginine, may counteract some of this risk by buffering acids and supporting non-cariogenic bacteria, though their effect is generally secondary to the impact of sugars.

• Restricting free sugar intake to less than 10% (ideally under 5%) of energy intake is associated with lower caries risk 10 11 13 14.
• Amino acids in saliva, influenced by diet and salivary flow, may alter caries susceptibility, but their preventive effect is generally smaller than that of reducing sugar intake or using fluoride 7 8 9 12.
• The anti-caries potential of arginine and other amino acids is supported by animal and in vitro research, but human evidence is still emerging 9.
• The new study’s results fit within this context, suggesting arginine could be an adjunctive strategy, especially for those unable to fully restrict sugar consumption 1 2 9 10.

How might protein and amino acid intake influence oral health across the lifespan?

Adequate protein and amino acid intake are important for maintaining oral tissue health and resistance to caries, particularly in older adults who may be at increased risk of protein-energy malnutrition. While the relationship is complex and influenced by multiple factors, emerging evidence suggests that amino acids—including arginine—could play a protective role.

• Protein-energy malnutrition is associated with increased risk of caries, enamel hypoplasia, and salivary gland atrophy in older adults 8.
• Some studies suggest that specific amino acids, such as glycine and arginine, may have anti-caries effects, but more human research is needed to translate these findings into clinical practice 8 9.
• The new study highlights arginine’s potential as a safe, naturally occurring supplement for oral health, prompting questions about its use across different age groups 1 8 9.
• While dietary protein appears beneficial, its effects are best realized in conjunction with other preventive strategies, such as sugar reduction and oral hygiene 8 12.

Future Research Questions

Further research is needed to clarify the clinical significance, optimal delivery methods, and long-term effects of arginine supplementation for caries prevention. Key questions remain about how arginine interacts with the oral microbiome over time, its benefits for different populations, and its effectiveness compared to or in combination with other established preventive measures.

Research Question	Relevance
What are the long-term effects of regular arginine use in oral care?	Long-term, real-world studies are needed to determine if arginine continues to provide protective effects over months or years, and whether it affects the development of the oral microbiome or has any unintended consequences 1 2 4.
Does arginine supplementation benefit children and older adults differently?	Age-related differences in oral microbiota, saliva production, and caries risk may affect how well arginine works in different populations, and tailored interventions may be needed 7 8 9.
How does arginine interact with fluoride and other preventive strategies?	It is important to understand if arginine has additive, synergistic, or redundant effects when used alongside established measures like fluoride, dietary modification, or xylitol 1 2 12.
Can arginine reduce caries in high-risk populations with poor oral hygiene?	High-risk groups may benefit most from adjunctive strategies, but efficacy in less controlled, real-world settings remains to be demonstrated 1 2 5.
What are the optimal formulation and dose of arginine for oral health?	Studies vary in arginine concentrations and delivery methods; determining the most effective and practical approach for different populations is crucial for clinical adoption 2 4 5.