Arginine in combination with calcium bases and fluoride in toothpaste may be better than fluoride alone


Arginine is an amino acid which when metabolized leads to an increase in pH so potentially reducing the cariogenicity of oral biofilms. Research into its anticaries effects has being taking place since the early 1980s with more recent studies suggesting that it arrests and reverses caries.

The aim of this review was to assess the anti-caries effect of arginine-containing formulations in vivo on caries lesions compared with fluorides or placebo.


Searches were conducted in the Medline/PubMed, Embase, CENTRAL, Web of ScienceChinese Biological Medical, National Research Register, Open- Grey, the World Health Organization’s International Clinical Trial Registry Platform, Database of Abstracts of Reviews of Effects, Health Technology Assessment (HTA), Turning Research into Practice (TRIP) database, National Technical Information Service (NTIS), International Clinical Trials Registry Platform Search Portal, International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) Clinical Trials Portal, International Standard Randomised Controlled Trial Number Register, UK National Research Register (NRR), Eli Lilly and Company Clinical Trial Registry, OpenSIGLE, Pharmaceutical Industry Clinical Trials Database (ABPI/CMR), Current Controlled Trials and clinical study results for US-marketed pharmaceuticals databases.

Human randomized or quasi-randomized clinical trials and human in situ RCTs using arginine formulations in any modality and com- paring their effects with those of placebo or fluoride alone were considered. The primary outcomes were coronal/root caries increments or changes in the proportion of participants developing new caries.

Two reviewers independently selected studies abstracted data and assessed study quality using the Cochrane Risk of bias tool. The overall quality of evidence was assessed using GRADE.


  • 10 trials involving 15,546 patients were included.
  • Most patients were 6-14 years of age.
  • 9 studies used toothpaste containing 1.5% w/w arginine, an insoluble calcium compound and 1,450ppm fluoride.
  • 1 evaluated the effect of arginine on artificially demineralised human enamel thin sections in vivo.
  • A range of diagnostic methods were employed, visual/tactile, microradiography/electrical caries monitor/ quantitative light-induced fluorescence, QLF.
  • All of the trials concluded that the dentifrices containing 1.5% arginine, an insoluble calcium compound and 1,450 ppm fluoride provided significantly greater protection against early-stage caries or caries lesion cavitation compared with dentifrices containing fluoride alone.
  • Based on 270 and 258 carious lesions in the intervention and positive control groups, respectively, from the 2 studies related to the primary root caries, the summary risk ratio for 1.5% arginine was 1.16 (95% CI: 1.01, 1.33).
  • Based on 457 and 460 carious lesions in the intervention and positive control groups, respectively, from the 3 studies related to early buccal coronal caries, the summary mean difference for 1.5% arginine was –4.67 (95% CI: –6.34, –3.01).
  • The effects of arginine dentifrices of different calcium bases with those of positive controls on cavitated coronal caries show pooled mean differences of –0.09 (95% CI: –0.13, –0.06) and –0.09 (95% CI: –0.13, –0.05), respectively.
  • The overall quality was assessed as low.
  • All of the included trials were industry sponsored.


The authors concluded:

..evidence suggests that arginine in combination with calcium bases (either Dical or calcium carbonate) and fluoride provides a superior effect compared with fluoride alone. However, this conclusion was based on a small number of clinical trials, and potential publication bias could not be ignored.


A very wide database search was conducted to identify trials for this review. While 10 studies were included, 9 were sponsored by the same company, a point highlighted and discussed by the authors. In addition none of the studies were considered to be at low risk of bias and there was marked variation in the follow-up periods (2 weeks to 2 years) and the diagnostic methods used. Consequently, the authors considered that the overall quality of the evidence was low. This means that further research is very likely to have an important impact on confidence in the estimate of effect and is likely to change the estimate.


Primary paper

Li J, Huang Z, Mei L, Li G, Li H. Anti-Caries Effect of Arginine-Containing Formulations in vivo: A Systematic Review and Meta-Analysis. Caries Res. 2015 Nov 5;49(6):606-617. [Epub ahead of print] PubMed PMID: 26536588.

Other references

Dental Elf – 7th Feb 2014 -Study suggests that dentifrices containing 1.5% arginine, an insoluble calcium compound provides additional benefit to fluoridated toothpastes

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