A new systematic review finds promising signals for lactoferrin and probiotics—but the evidence is still too limited to call either an established treatment.
Black stain can be one of those frustrating paediatric dental findings that looks far more dramatic than the underlying clinical problem. The dark pigmentation is usually seen as a series of black lines or dots along the cervical margins of teeth, and although it is generally an extrinsic chromogenic stain rather than conventional caries, it can be persistent, recurrent and cosmetically concerning.
For clinicians, the bigger question is often what happens after the stain is professionally removed.
Could something be done to reduce its recurrence?
A 2026 systematic review published in the Oral Health Journal has looked specifically at two proposed approaches—lactoferrin and probiotics. The findings are interesting, but they also illustrate how easily a promising biological mechanism can get ahead of the clinical evidence.
Why lactoferrin?
Lactoferrin is a naturally occurring glycoprotein found in milk and other biological fluids. One of its important biological properties is its ability to bind iron.
That is relevant because iron availability has been implicated in the formation of black stain. By sequestering iron, lactoferrin may make the oral environment less favourable for microorganisms associated with chromogenic staining.
The review describes lactoferrin as having several additional biological properties, including antimicrobial, anti-biofilm, anti-adhesive and anti-inflammatory effects.
But does that translate into less black stain clinically?
The evidence is still thin.
One of the studies included in the review was an observational study in which patients received lactoferrin tablets containing 50 mg lactoferrin and 50 mg D-biotin, twice daily for 90 days after oral hygiene treatment. The authors reported that lactoferrin could help counteract black stain, supporting the hypothesis that salivary iron availability may be involved in its formation.
That is biologically plausible, but an observational study cannot establish that lactoferrin itself caused the improvement.
What about probiotics?
The probiotic argument is somewhat different.
Rather than targeting iron availability, probiotics aim to influence the oral microbial environment. The review examined evidence involving strains including Streptococcus salivarius M18 and Lactobacillus reuteri Prodentis.
An in-vitro study found that both probiotics could inhibit microorganisms associated with black stain, with S. salivarius M18 showing greater antimicrobial activity than L. reuteri in the tested conditions. The effect was also dose-dependent.
But in-vitro antimicrobial activity is not the same as clinical stain prevention.
The more clinically interesting evidence came from a randomized study involving 58 children aged 4–10 years with black stain.
Twenty-eight children received an oral preparation containing Streptococcus salivarius M18 once daily for three months, while 26 children served as an untreated comparison group. Black stain was assessed at three and six months.
After three months, black stain was present in:
6 of 28 children receiving the probiotic 13 of 26 children in the control group
At six months, stain was found in:
9 of 28 children in the probiotic group 14 of 26 children in the control group.
The findings therefore suggest that S. salivarius M18 may slow the recurrence or growth of black stain in children.
The study does not establish that the probiotic eliminates the underlying cause of black stain, nor does it establish that probiotics should replace professional stain removal and routine oral-hygiene measures.
And could lactoferrin + probiotics work better together?
This is where the review becomes particularly interesting.
The two approaches theoretically target different parts of the problem.
Lactoferrin → reduces available iron.
Probiotics → modify the microbial environment.
It is therefore tempting to imagine that combining the two could produce a stronger effect than either approach alone.
The systematic review searched PubMed/MEDLINE, Embase and Cochrane using a PRISMA-based methodology. The search was completed in October 2024. Although the searches initially identified 100 records, only four studies ultimately met the review's inclusion criteria.
The search specifically looking for studies combining chromogenic bacteria, black stain, probiotics and lactoferrin produced no eligible results.
So, despite the attractive biological rationale, there is currently no clinical evidence showing that a lactoferrin–probiotic combination works better than either intervention alone.
The review describes both lactoferrin and probiotics as promising approaches, but its own conclusion acknowledges that the available information remains limited. The authors call for controlled clinical trials to determine appropriate protocols, doses, safety and efficacy.
For a child with recurrent black stain, the immediate clinical priorities therefore remain assessment of the stain, professional removal when indicated, oral-hygiene reinforcement and evaluation of factors that may be contributing to recurrence.
Lactoferrin and probiotics are better viewed at present as emerging adjunctive possibilities—not proven standard treatments for black stain.
The evidence gives us something worth watching: the possibility that controlling iron availability and modifying the oral microbiome could influence recurrence.