Non-Cochrane · DTA · PM42254999

The role of salivary lactoferrin as a potential biomarker for periodontal disease: a systematic review and meta-analysis.

Tayebi-Hillali Hoda, Leira Yago, Botelho João, et al. · Frontiers in oral health · 2026 · PubMed · doi:10.3389/froh.2026.1812772

Findings

6 findings

Population
Individuals with periodontitis vs periodontally healthy controlsPeriodontitis (exposure)Periodontally healthy controlsLactoferrin level in gingival crevicular fluid
Cross-sectional (single time point) · Gingival crevicular fluid · Chronic periodontitis (CP) studies
ROM 8.63 [2.68, 27.87]
Low
Downgraded: risk of bias, inconsistency
3 studies · 88 participants
Individuals with periodontitis vs periodontally healthy controlsPeriodontitis (exposure)Periodontally healthy controlsLactoferrin level in unstimulated saliva
Cross-sectional (single time point) · Unstimulated whole saliva · Chronic periodontitis (CP) studies
ROM 1.77 [1.40, 2.24]
Low
Downgraded: risk of bias, inconsistency
4 studies · 189 participants
Individuals with periodontitis vs periodontally healthy controlsPeriodontitis (exposure)Periodontally healthy controlsLactoferrin level in stimulated saliva
Cross-sectional (single time point) · Stimulated whole saliva · All periodontitis types (AgP + CP), overall
ROM 2.14 [1.38, 3.32]
Low
Downgraded: risk of bias, inconsistency
4 studies · 215 participants
Individuals with periodontitis vs periodontally healthy controlsPeriodontitis (exposure)Periodontally healthy controlsLactoferrin level in unstimulated saliva
Cross-sectional (single time point) · Unstimulated whole saliva · All periodontitis types (AgP + CP), overall
ROM 1.46 [0.98, 2.19]
Low
Downgraded: risk of bias, inconsistency
5 studies · 209 participants
Individuals with periodontitis vs periodontally healthy controlsPeriodontitis (exposure)Periodontally healthy controlsLactoferrin level in stimulated saliva
Cross-sectional (single time point) · Stimulated whole saliva · Chronic periodontitis (CP) studies
ROM 2.06 [1.13, 3.74]
Low
Downgraded: risk of bias, inconsistency
3 studies · 176 participants
Individuals with periodontitisMechanical periodontal treatmentLactoferrin levels before treatment (pre-post)Lactoferrin level in saliva and/or gingival crevicular fluid after treatment
2 to 4 weeks after non-surgical treatment · Not specified
A reduction in LF levels was observed across different sample types 2-4 weeks after non-surgical periodontal treatment, although the effect size could not be calculated
Low
Downgraded: risk of bias, indirectness
6 studies

Included primary studies 33

Open in Studies
StudyYearAlso included byOutcomes it informs hereTrial data
Glimvall 2012
Elevated levels of salivary lactoferrin, a marker for chronic periodontitis?
PMID:22471324
20121 other reviewnot statednot extracted yet
Ramenzoni 2021 (1)
Origin of MMP-8 and Lactoferrin levels from gingival crevicular fluid, salivary glands and whole saliva.
PMID:34353321
20211 other reviewnot statednot extracted yet
Ramenzoni 2021 (saliva, ref 57)
Oral Diagnostic Methods for the Detection of Periodontal Disease.
PMID:33810094
20211 other reviewLactoferrin level in unstimulated saliva; Lactoferrin level in stimulated salivanot extracted yet
Tsai 1998
Gingival crevicular fluid lactoferrin levels in adult periodontitis patients.
PMID:9583225
19981 other reviewnot statednot extracted yet
Wei 2004
The investigation of glutathione peroxidase, lactoferrin, myeloperoxidase and interleukin-1beta in gingival crevicular fluid: implications…
PMID:15324348
20041 other reviewnot statednot extracted yet
Wu 2009
Initial comparison of proteomic profiles of whole unstimulated saliva obtained from generalized aggressive periodontitis patients and…
PMID:19453860
20091 other reviewnot statednot extracted yet
Yadav 2014
Effect of periodontal therapy on lactoferrin levels in gingival crevicular fluid.
PMID:24913177
20141 other reviewnot statednot extracted yet
Arab 2024
Association between the concentration of salivary lactoferrin, smoking, and periodontal disease parameters: A randomized observational study
DOI:10.4103/sjoralsci.sjoralsci_35_24
2024this review onlynot statednot extracted yet
Ayettey-Adamafio 2025
Determination of Salivary Lactoferrin Levels Before and After Non-Surgical Periodontal Treatment in Patients with Aggressive Periodontitis
DOI:10.60014/pmjg.v14i1.390
2025this review onlynot statednot extracted yet
Fine 2013
Can salivary activity predict periodontal breakdown in A. actinomycetemcomitans infected adolescents?
DOI:10.1016/j.archoralbio.2012.10.009
2013this review onlynot statednot extracted yet
Fine 2013
Can salivary activity predict periodontal breakdown in A. actinomycetemcomitans infected adolescents?
PMID:23219180
2013this review onlynot statednot extracted yet
Friedman 1983
Lysozyme and Lactoferrin Quantitation in the Crevicular Fluid
DOI:10.1902/jop.1983.54.6.347
1983this review onlynot statednot extracted yet
Friedman 1983
Lysozyme and lactoferrin quantitation in the crevicular fluid.
PMID:6348246
1983this review onlynot statednot extracted yet
Glimvall 2012
Elevated levels of salivary lactoferrin, a marker for chronic periodontitis?
DOI:10.1111/j.1600-0765.2012.01479.x
2012this review onlyLactoferrin level in stimulated salivanot extracted yet
Groenink 1999
Salivary lactoferrin and low‐<i>M</i><sub>r</sub> mucin MG2 in <i>Actinobacillus actinomycetemcomitans</i>‐associated periodontitis
DOI:10.1034/j.1600-051x.1999.260501.x
1999this review onlyLactoferrin level in stimulated salivanot extracted yet
Groenink 1999
Salivary lactoferrin and low-Mr mucin MG2 in Actinobacillus actinomycetemcomitans-associated periodontitis.
PMID:10355615
1999this review onlynot statednot extracted yet
Jentsch 2004
Lactoferrin and other markers from gingival crevicular fluid and saliva before and after periodontal treatment
DOI:10.1111/j.1600-051x.2004.00512.x
2004this review onlynot statednot extracted yet
Jentsch 2004
Lactoferrin and other markers from gingival crevicular fluid and saliva before and after periodontal treatment.
PMID:15191585
2004this review onlynot statednot extracted yet
Kivadasannavar 2014
Estimation of lactoferrin levels in gingival crevicular fluid before and after periodontal therapy in patients with chronic periodontitis.
PMID:24808691
2014this review onlynot statednot extracted yet
Lee 2018
The potential of salivary biomarkers for predicting the sensitivity and monitoring the response to nonsurgical periodontal therapy: A…
DOI:10.1111/jre.12544
2018this review onlyLactoferrin level in unstimulated salivanot extracted yet
Lee 2018
The potential of salivary biomarkers for predicting the sensitivity and monitoring the response to nonsurgical periodontal therapy: A…
PMID:29882262
2018this review onlynot statednot extracted yet
Lourenco 2013
Lactoferrin, A Marker for Periodontal Disease
DOI:10.2174/1570162x11311030006
2013this review onlyLactoferrin level in unstimulated salivanot extracted yet
Lourenco 2013
Lactoferrin, a marker for periodontal disease.
PMID:23432422
2013this review onlynot statednot extracted yet
Orhue 2022
Salivary Lactoferrin Levels, Disease Severity and Correlates in Patients with Chronic Periodontitis Presenting to a Tertiary Health…
DOI:10.4314/njdr.v7i1.8
2022this review onlyLactoferrin level in stimulated salivanot extracted yet
Ramenzoni 2021 (GCF, ref 56)
Origin of MMP-8 and Lactoferrin levels from gingival crevicular fluid, salivary glands and whole saliva
DOI:10.1186/s12903-021-01743-5
2021this review onlyLactoferrin level in gingival crevicular fluidnot extracted yet
Suomalainen 1996
Peroxidases, Iactoferrin and lysozyme in peripheral blood neutrophils, gingival crevicular fluid and whole saliva of patients with…
DOI:10.1111/j.1601-0825.1996.tb00213.x
1996this review onlynot statednot extracted yet
Suomalainen 1996
Peroxidases, lactoferrin and lysozyme in peripheral blood neutrophils, gingival crevicular fluid and whole saliva of patients with…
PMID:8957925
1996this review onlynot statednot extracted yet
Tsai 1998
Gingival crevicular fluid lactoferrin levels in adult per iodontitis patients
DOI:10.1111/j.1834-7819.1998.tb00151.x
1998this review onlyLactoferrin level in gingival crevicular fluidnot extracted yet
Wei 2004
The investigation of glutathione peroxidase, lactoferrin, myeloperoxidase and interleukin‐1β in gingival crevicular fluid: implications…
DOI:10.1111/j.1600-0765.2004.00744.x
2004this review onlynot statednot extracted yet
Wu 2009
Initial comparison of proteomic profiles of whole unstimulated saliva obtained from generalized aggressive periodontitis patients and…
DOI:10.1111/j.1600-0765.2008.01172.x
2009this review onlyLactoferrin level in unstimulated salivanot extracted yet
Wu 2018
Salivary biomarker combination prediction model for the diagnosis of periodontitis in a Taiwanese population
DOI:10.1016/j.jfma.2017.10.004
2018this review onlyLactoferrin level in unstimulated salivanot extracted yet
Wu 2018
Salivary biomarker combination prediction model for the diagnosis of periodontitis in a Taiwanese population.
PMID:29129647
2018this review onlynot statednot extracted yet
Yadav 2014
Effect of periodontal therapy on lactoferrin levels in gingival crevicular fluid
DOI:10.1111/adj.12203
2014this review onlyLactoferrin level in gingival crevicular fluidnot extracted yet

Overlap with other reviews

Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match). Only the non-Cochrane dental reviews have study lists, so overlap with Cochrane reviews is not counted yet.

Review question

ElementPlanned (methods)Found (results)
PopulationHumans with clinically diagnosed periodontal disease and periodontally healthy controls (case-control); humans with periodontal disease before and after mechanical periodontal treatment. Gingivitis excluded.Periodontitis cases (373 CP and 79 AgP/JLP in case-control studies) and healthy controls; patients with CP, LJP or AgP treated mechanically (n=19 studies)
InterventionPeriodontitis (exposure); mechanical periodontal treatmentPeriodontitis (16 case-control studies); non-surgical mechanical periodontal therapy including scaling and root planing, with surgery in one study (6 studies)
ComparisonPeriodontally healthy controls; pre-treatment lactoferrin levelsPeriodontally healthy controls; pre-treatment baseline
OutcomesLactoferrin levels in saliva (unstimulated, stimulated) and/or gingival crevicular fluidLactoferrin in unstimulated saliva (7 studies), stimulated saliva (7 studies), GCF (6 studies); 11 studies in meta-analysis (ratio of means)
Study designsCase-control studies; longitudinal pre-post intervention studies; no date restriction19 studies: 16 case-control (14 ELISA) and 6 non-randomized pre-post intervention studies (3 overlap)
TimingNot specifiedPost-treatment sampling 2 to 4 weeks after therapy