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Nano-hydroxyapatite

Two trials funded by a hydroxyapatite toothpaste maker found it not inferior to fluoride toothpaste for new cavities over 1 to 1.5 years, and a 2025 review found no difference from fluoride. An independent 2022 review found the evidence inconclusive. Two reviews found less tooth sensitivity than with comparison products. No serious adverse events were reported in the cavity trials.

Add to Bio HackChecked 2026-11-12
Status
Toothpaste and mouthwash ingredient. Not approved by the FDA as a drug for any use. The EU's Scientific Committee on Consumer Safety has assessed the nano form in oral care products.
Also called
n-HA, nHA, nano-HA, nano-HAP, HAP, hydroxyapatite, hydroxyapatite toothpaste, biomimetic hydroxyapatite, microcrystalline hydroxyapatite, fluoride-free toothpaste, Apagard, Karex
Taken for
cavities, tooth decay, fluoride-free toothpaste, enamel, remineralization, white spots, early enamel lesions, sensitive teeth, tooth sensitivity

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help2

Reported risks0

No risks sourced yet.

What people take it for, and what was found

Shown to help2

Moderate

Tooth sensitivity

Shown to lower tooth sensitivity more than placebo and fluoride in adults. Reviews disagree on whether it differs from other desensitizers.

The numbers and sources
Effect
Across 6 RCTs with 4 weeks of follow-up, nano-hydroxyapatite lowered sensitivity to air (SMD -1.09, 95% CI -1.24 to -0.94) and touch (SMD -0.93, 95% CI -1.42 to -0.43) more than other treatments, with no difference for cold (SMD -0.17, 95% CI -0.81 to 0.48). The overall SMD was -0.93 (95% CI -1.19 to -0.68) [7]. Across 44 clinical trials, hydroxyapatite lowered sensitivity by 39.5% more than placebo (95% CI 30.06 to 48.93) and 23% more than fluoride (95% CI 11.82 to 34.18). Against other desensitizing agents, the 10.2% difference was not significant (95% CI -19.26 to 21.76) [8].
Population
Adults with dentin hypersensitivity [7][8].
Sources
[7], [8]
Caveats
Follow-up was 4 weeks [7]. Two authors of the 44-trial review are employees of a hydroxyapatite toothpaste maker [2][8]. The reviews disagree on whether hydroxyapatite differs from other desensitizers [7][8].
Limited

Early enamel lesions and white spots

Limited evidence: mostly lab studies found nano-hydroxyapatite raised enamel hardness and mineral gain more than fluoride, with no change in white spot color.

The numbers and sources
Effect
Across 12 pooled studies, pure nano-hydroxyapatite raised enamel surface hardness (MD 9.29, 95% CI 7.74 to 10.84) and mineral gain (MD 0.09, 95% CI 0.05 to 0.13) more than fluoride alone. The color of white spot lesions did not change (MD -2.76, 95% CI -6.79 to 1.27) [9]. Under remineralizing conditions in situ, nano-hydroxyapatite and sodium fluoride remineralized enamel to the same degree [6].
Population
14 studies: 10 in vitro, 1 in situ and 3 in people [9]. In situ studies [6].
Sources
[9], [6]
Caveats
Mostly in vitro, with high risk of bias and short follow-up [9]. Evidence was very low [6].

Mixed results1

Moderate

Cavities, compared with fluoride toothpaste

Mixed results: maker-funded trials found hydroxyapatite toothpaste not inferior to fluoride for cavities, while an independent review rated the evidence very low.

The numbers and sources
Effect
In 207 children, a fluoride-free toothpaste with microcrystalline hydroxyapatite used three times a day for 336 days was not inferior to a fluoride toothpaste: enamel cavity scores rose in 72.7% of the hydroxyapatite group and 74.2% of the fluoride group [1]. In 189 adults over 18 months, 89.3% on hydroxyapatite toothpaste and 87.4% on 1,450 ppm fluoride toothpaste had no rise in decayed, missing and filled surfaces, which met the trial's non-inferiority margin [2]. A 2025 meta-analysis of 4 studies in people under 25 found no difference between hydroxyapatite and fluoride toothpaste (RR 0.98, 95% CI 0.85 to 1.12) [3]. A 2021 meta-analysis of 3 RCTs reported 17% protection against cavities with hydroxyapatite [4], and a 2024 update by the same group pooled 5 clinical and 8 in situ trials [5]. An independent 2022 review found too few and too varied clinical studies to pool. In its in situ studies, sodium fluoride hindered enamel demineralization and nano-hydroxyapatite did not differ from a fluoride-free control [6].
Population
Children with baby teeth [1]. Adults [2]. Children, adolescents and young adults in 4 trials [3]. People of all ages in clinical and in situ trials [4][5][6].
Sources
[1], [2], [3], [4], [5], [6]
Caveats
Both trials were funded by Dr. Kurt Wolff GmbH, which makes hydroxyapatite toothpaste, and three authors of the adult trial are its employees [1][2]. Two of those employees are authors of the 2021 and 2024 meta-analyses [4][5]. The children's trial used microcrystalline, not nano, hydroxyapatite, against a 500 ppm amine fluoride toothpaste [1]. The independent review rated the evidence very low, noted high risk of bias, and found 6 studies funded or published by the makers of the products tested [6].

Doses studied

The children's trial used hydroxyapatite toothpaste three times a day for 336 days [1], and the adult trial for 18 months [2]. The abstracts read for this page do not report hydroxyapatite concentrations. The EU assessment covered up to 29.5% in toothpaste and 10% in mouthwash [10].

Risks

Checked, no increase found2

Limited

Adverse events in trials

Small trials, both maker-funded, found no serious adverse events in children or adults using hydroxyapatite toothpaste.

The numbers and sources
Effect
Neither the children's nor the adult cavity trial reported serious or severe adverse events. In the adult trial, the causes and outcomes of adverse events did not differ between the hydroxyapatite and fluoride groups [1][2].
Population
207 children and 189 adults [1][2].
Sources
[1], [2]
Caveats
Both trials were funded by the toothpaste maker [1][2].
Moderate

EU nanoparticle assessments

The EU safety committee concluded in 2025 that rod-shaped, uncoated nano-hydroxyapatite raised no safety concern up to 29.5% in toothpaste. It excluded needle-shaped particles.

The numbers and sources
Effect
In 2021 the EU Scientific Committee on Consumer Safety could not conclude on the safety of rod-shaped nano-hydroxyapatite in oral care products, because the data were not sufficient to exclude concern over genotoxicity. It noted that needle-shaped nanoparticles, which some manufacturing produces, are of concern [11]. In 2025 it concluded that rod-shaped, uncoated nano-hydroxyapatite meeting set particle specifications raised no safety concern at up to 29.5% in toothpaste and 10% in mouthwash. It found no mutagenic, cytotoxic or inflammatory effects in a mouth lining cell model, negligible uptake through the mouth lining and rapid dissolution of swallowed particles in stomach acid. The opinion does not apply to needle-shaped particles [10].
Population
Laboratory and other data submitted to the EU regulator [11][10].
Sources
[11], [10]
Caveats
These are assessments of submitted laboratory data, not studies of people.

Claims tested and not found

  1. That nano-hydroxyapatite stops enamel losing mineral the way fluoride does. In in situ studies under demineralizing conditions, sodium fluoride hindered demineralization and nano-hydroxyapatite did not differ from a fluoride-free control [6].
  2. That nano-hydroxyapatite fades white spot lesions. Lesion color did not change [9].

Sources

  1. Paszynska E, Pawinska M, Gawriolek M, et al. Impact of a toothpaste with microcrystalline hydroxyapatite on the occurrence of early childhood caries: a 1-year randomized clinical trial. Scientific Reports. 2021. https://doi.org/10.1038/s41598-021-81112-y
  2. Paszynska E, Pawinska M, Enax J, et al. Caries-preventing effect of a hydroxyapatite-toothpaste in adults: a 18-month double-blinded randomized clinical trial. Frontiers in Public Health. 2023. https://doi.org/10.3389/fpubh.2023.1199728
  3. Chatzidimitriou K, Theodorou K, Seremidi K, et al. The role of hydroxyapatite-based, fluoride-free toothpastes on the prevention and the remineralization of initial caries lesions: A systematic review and meta-analysis. Journal of Dentistry. 2025. https://doi.org/10.1016/j.jdent.2025.105691
  4. Limeback H, Enax J, Meyer F. Biomimetic hydroxyapatite and caries prevention: a systematic review and meta-analysis. Canadian Journal of Dental Hygiene. 2021. https://pubmed.ncbi.nlm.nih.gov/34925515/
  5. Pawinska M, Paszynska E, Amaechi BT, et al. Clinical evidence of caries prevention by hydroxyapatite: An updated systematic review and meta-analysis. Journal of Dentistry. 2024. https://doi.org/10.1016/j.jdent.2024.105429
  6. Wierichs RJ, Wolf TG, Campus G, Carvalho TS. Efficacy of nano-hydroxyapatite on caries prevention: a systematic review and meta-analysis. Clinical Oral Investigations. 2022. https://doi.org/10.1007/s00784-022-04390-4
  7. de Melo Alencar C, de Paula BLF, Guanipa Ortiz MI, et al. Clinical efficacy of nano-hydroxyapatite in dentin hypersensitivity: A systematic review and meta-analysis. Journal of Dentistry. 2019. https://doi.org/10.1016/j.jdent.2018.12.014
  8. Limeback H, Enax J, Meyer F. Clinical Evidence of Biomimetic Hydroxyapatite in Oral Care Products for Reducing Dentin Hypersensitivity: An Updated Systematic Review and Meta-Analysis. Biomimetics. 2023. https://doi.org/10.3390/biomimetics8010023
  9. Alajlan S, et al. The effect of nano-hydroxyapatite on white spot lesions: A systematic review and meta-analysis. Journal of Dentistry. 2024. https://doi.org/10.1016/j.jdent.2024.105402
  10. Scientific Committee on Consumer Safety. Scientific Opinion on Hydroxyapatite (nano), Submission IV, SCCS/1677/25. European Commission. 2025. https://health.ec.europa.eu/publications/sccs-scientific-opinion-hydroxyapatite-nano-submission-iv_en
  11. Scientific Committee on Consumer Safety. Opinion on Hydroxyapatite (nano), SCCS/1624/20. European Commission. 2021. https://health.ec.europa.eu/publications/hydroxyapatite-nano_en

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