A 2025 network meta-analysis of nine randomized controlled trials and 462 patients found that trehalose, erythritol, and glycine all improve probing pocket depth, clinical attachment level, and bleeding on probing in non-surgical periodontal treatment — with no statistically significant pairwise differences. Ranked by SUCRA for probing-depth reduction, trehalose placed second (48.0) behind erythritol (84.1) and ahead of glycine (28.5). This article walks through what the data actually show, where trehalose fits in current clinical practice, and where the evidence is still thin. The primary source is Zi-le et al., Frontiers in Physiology 2025;16:1593204 (DOI: 10.3389/fphys.2025.1593204; PROSPERO CRD42022366792).
The short answer for clinicians
Clinical equivalence: trehalose, erythritol, and glycine perform similarly on PPD, CAL, and BOP in NSPT in the pooled 2025 evidence.
SUCRA ranking on PPD reduction: erythritol 84.1 > trehalose 48.0 > glycine 28.5.
Where trehalose fits today: supportive periodontal therapy with devices and powders that explicitly accept it. Implant indications and long-term outcomes are still under-studied.
What trehalose is, in one paragraph
Trehalose is a non-reducing disaccharide formed by two glucose units joined through an alpha,alpha-1,1-glycosidic bond. It occurs naturally in fungi, insects, and certain plants, and is approved as a food ingredient in the EU and US. Its dental interest is twofold. First, it is non-cariogenic — important for any powder that may be partially swallowed during a prophylaxis appointment. Second, in vitro work on human gingival fibroblasts suggests trehalose has a more favourable cellular tolerability profile than glycine and a meaningfully less cytotoxic profile than the erythritol-plus-chlorhexidine combination powder studied in earlier work. For a broader powder-property comparison, see our how to choose the right prophylaxis powder article.
The 2025 network meta-analysis in detail
Zi-le and colleagues published a systematic review with both direct and network meta-analysis in the open-access journal Frontiers in Physiology, with a PROSPERO-registered protocol (CRD42022366792). The review pooled randomized controlled trials in non-surgical periodontal treatment (NSPT) that compared subgingival air polishing using erythritol, glycine, or trehalose against scaling and root planing (SRP) alone or against each other.
How the search was conducted
Searches were run in PubMed, Embase, Web of Science, and the Cochrane Library up to August 2024. A total of 742 records were screened. Twenty-three were assessed in full text, and nine RCTs met the inclusion criteria. The pooled population, as reported in the abstract and conclusion, is 462 patients. (Note: one section of the published paper states 497 — an internal discrepancy in the source that does not affect the meta-analytic point estimates, but worth flagging.)
What the network meta-analysis showed
The primary clinical outcomes were probing pocket depth (PPD), clinical attachment level (CAL), and bleeding on probing (BOP). The network meta-analysis (NMA) compared the three powders indirectly through their shared comparator, scaling and root planing alone.
| Powder | SUCRA (PPD reduction) | NMA mean difference vs control (95% CrI) |
|---|---|---|
| Erythritol | 84.1 | 0.77 (0.47, 1.24) |
| Trehalose | 48.0 | 0.97 (0.59, 1.51) |
| Glycine | 28.5 | 1.13 (0.57, 2.18) |
None of the pairwise comparisons reached statistical significance. Erythritol versus glycine returned a mean difference of 1.46 (0.64, 3.27); erythritol versus trehalose, 1.27 (0.64, 2.34); glycine versus trehalose, 0.86 (0.38, 1.89). The direct meta-analysis on erythritol versus glycine showed essentially flat differences on all three outcomes — PPD MD 0.04 (-0.11, 0.19); CAL MD 0.12 (-0.09, 0.32); BOP MD -1.13 (-5.04, 2.79), with heterogeneity I² of 0 throughout.
The authors' bottom line
From the published conclusion, verbatim: "According to our meta-analysis, there was no statistically significant difference in the effects of glycine, trehalose, and erythritol sandblasting powder on PPD, CAL and BOP in NSPT. However, erythritol (SUCRA = 84.1) has an advantage over trehalose (SUCRA = 48.0) and glycine (SUCRA = 28.5) in reducing PPD." The recommended priority order is erythritol, trehalose, glycine — but with the explicit caveat that a limited number of RCTs makes publication-bias testing unreliable.
How trehalose has been used in earlier RCTs
The trehalose-specific evidence base predates the 2025 synthesis. Three RCTs are particularly worth knowing.
- Hägi et al. 2018 compared trehalose subgingival air polishing with sonic debridement in residual periodontal pockets during maintenance therapy (PMID 30311948). Clinical outcomes were comparable; patient-reported discomfort was lower in the air-polishing arm.
- Park et al. 2020 reported a randomized-controlled pilot on trehalose effects on the subgingival biofilm during maintenance, with a more pronounced reduction of Gram-negative aerobic rods at three months in the air-polishing arm (PMID 32321490; PMC7178568).
- Müller et al. 2022 evaluated a conical-shaped subgingival tip for trehalose air polishing in supportive periodontal therapy (BMC Oral Health 2022; PMC8918077). PPD and CAL improved comparably between trehalose air polishing and sonic scaling, with non-inferiority demonstrated in deeper pockets.
Earlier in vitro work also informs the picture. A subgingival biofilm-model study on antimicrobial impact of different air-polishing powders compared trehalose, erythritol, and glycine against bacterial counts and viability (PMC8698523), and a separate cellular study on human gingival fibroblasts found trehalose to have a less negative effect on cell viability and proliferation than glycine (Springer, 2021).
Where trehalose fits in 2026 practice
Clear fits
Supportive periodontal therapy on residual pockets — particularly where patient-reported discomfort is a clinical priority — is the indication where trehalose has the most direct trial support. The 2025 NMA reinforces, rather than overturns, this positioning: the powder is clinically equivalent to its more widely used peers on hard endpoints. Our subgingival air polishing guide covers the nozzle and pressure-control details that apply regardless of powder choice.
Where the evidence is still thin
Two indications remain under-evidenced. The first is peri-implant maintenance, where the trehalose literature is sparse and dedicated comparisons are limited. A randomized controlled trial (ClinicalTrials.gov NCT07140146) is actively comparing trehalose to glycine air polishing for peri-implant mucositis, with completion estimated mid-2026. Until those results publish, the powder of choice for implant indications remains glycine — well documented in the broader implant literature, summarised in our air polishing on implants review — and, where the device supports it, erythritol on the basis of Delucchi 2025.
The second open question is long-term outcomes. Most trehalose studies report 3–12 month follow-up. How repeated trehalose air-polishing cycles influence soft-tissue health and biofilm composition over multi-year supportive therapy is not well mapped.
Device and powder availability in Europe
A practical constraint: a powder's evidence base only matters if the clinic's device accepts it. Air polishers from Acteon, Dentsply, EMS, Henry Schein, Hu-Friedy, Mectron, NSK, Ultradent, W&H, and Woodpecker each specify which powders are validated for use. Trehalose is not universally available across the EU consumables market the way glycine and (on EMS systems) erythritol are. Before substituting trehalose into an existing protocol, clinicians should confirm device compatibility with the manufacturer's technical documentation and check that the powder grade used in published RCTs matches what's available on their consumables order form. The broader powder-selection logic — particle size, hardness, abrasivity, indication — is laid out in our erythritol vs glycine clinical evidence piece and the erythritol powder brand comparison.
Conflict-of-interest and limitations
The 2025 Zi-le network meta-analysis was funded by Chinese provincial and municipal research grants; the authors declared no commercial or financial conflicts. That is a meaningfully cleaner sponsorship profile than industry-funded comparative work in this area. The authors' own stated limitations are that the number of RCTs is small enough to make formal publication-bias testing unreliable, and that head-to-head trehalose-versus-erythritol or trehalose-versus-glycine trials remain few. Anyone citing the SUCRA ranking as a hard hierarchy is over-reading the data; the more defensible reading is clinical equivalence on hard endpoints, with a numerical lean toward erythritol that the studies pooled here were under-powered to confirm.
Conclusion
Trehalose has earned its place in the modern subgingival air-polishing toolkit. The 2025 network meta-analysis pooling nine RCTs and 462 patients shows it performs on a par with both glycine and erythritol for the clinical endpoints that matter in non-surgical periodontal treatment, with a favourable patient-comfort profile in earlier RCTs and a less cytotoxic in vitro signal than glycine on gingival fibroblasts. Where the evidence is still thin — peri-implant indications, long-term outcomes — is precisely where the next round of trials, including NCT07140146, is now collecting data. For a deeper look at how the underlying clinical context shapes powder choice across an appointment, see our prophylaxis protocols compared overview and our glossary entries on the alternative powders.
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