A Randomized Clinical Trial Shows Malva sylvestris Reduces Chemotherapy-Induced Stomatitis and Pain More Quickly
Chlorhexidine is the reference mouthwash for managing chemotherapy-induced stomatitis, also known as oral mucositis. Used routinely in oncology centers, it has a well-established safety profile backed by decades of clinical use.
However, a randomized trial published in BMC Cancer in 2025 showed that a mouthwash based on Malva sylvestris can reduce the severity of mucositis and associated pain more quickly and markedly than the conventional standard.
This head-to-head comparison with the gold standard is not a preliminary observation or a preclinical model: it is a randomized, triple-blind, controlled trial, with assessments carried out by an oncologist at predefined intervals.
Chemotherapy-induced stomatitis affects between 40% and 100% of cancer patients, depending on the treatment regimen, the type of malignancy, and age. It presents with erythema, ulceration, and intense pain that compromises the ability to eat and communicate; in some cases it leads to chemotherapy dose reductions, directly impacting the likelihood of treatment success.
Available therapeutic options are limited, and many show only partial efficacy. Against this backdrop, the data on Malva sylvestris take on significant clinical and formulation relevance.
Malva sylvestris: Phytochemical Profile and Pharmacological Rationale
Malva sylvestris, common across Europe, western Asia, and North Africa, belongs to the Malvaceae family. Phytochemical analysis of its leaves and flowers reveals a complex composition: flavonoids, mucilage, phenolic compounds, terpenoids, coumarins, tannins, saponins, and alkaloids. This variety of bioactive molecules translates into a multidirectional pharmacological profile.
Flavonoids and mucilage inhibit pro-inflammatory cytokines such as TNF-alpha and IL-1beta, the same cytokines found elevated in mucosal tissue damaged by chemotherapy. Phenolic compounds act as scavengers of reactive oxygen species, reducing the oxidative stress that accelerates the progression of ulcerations. Terpenoids and tannins help control secondary infections, which are common in open lesions.
Mucilage, finally, forms a protective film on the oral mucosa: it reduces contact between nociceptive receptors and irritant agents, dampens mechanical irritation, and prevents further damage to already compromised surfaces.
Why does this physical barrier mechanism matter clinically? Because chlorhexidine does not have it: it acts mainly as an antimicrobial, and does not address inflammation reduction or the structural protection of the mucosa.
The Clinical Trial: Design and Results Over 14 Days of Treatment
The study was conducted in 2024 on 70 cancer patients with grade I-III chemotherapy-induced stomatitis, recruited from medical centers affiliated with Rafsanjan University of Medical Sciences in Iran. Its design was a randomized, controlled, triple-blind trial: patients, researchers, and analysts were all unaware of group allocation.
The intervention group used 15 ml of Malva sylvestris-based mouthwash three times a day for 14 days, after each meal. Meanwhile, the control group received the standard mouthwash based on 0.2% chlorhexidine. To preserve blinding, both preparations were distributed in opaque bottles: the herbal formulation was developed to replicate the color, taste, and smell of chlorhexidine.
Stomatitis severity was assessed with the WHO Oral Mucositis Grading Scale, and pain with the Visual Analog Scale (VAS), at baseline and on days 3, 7, and 14. The most marked difference emerged on day 7: the mean stomatitis score in the Malva sylvestris group was 0.58 versus 1.25 in the chlorhexidine group (P < 0.001), with an effect size of -0.96. According to Cohen’s criteria, this is a large effect. Indeed, ninety-six percent of the reduction in stomatitis score observed on day 7 is directly attributable to the herbal mouthwash.
On the pain front, the data confirm the same trajectory: on day 7, the mean score in the intervention group was 0.73 versus 1.81 in the control group (P = 0.01), with an effect size of -0.65. Notably, the reduction was concentrated mainly in the first week.
By day 14, scores in the Malva group remained lower than in the chlorhexidine group, but the difference no longer reached statistical significance (P = 0.07 for stomatitis; P = 0.08 for pain). The clinically relevant difference is the speed at which the therapeutic response occurred.
Why Malva sylvestris Responds Faster: The Advantage of Multi-Target Action
Already by day 3, the Malva sylvestris group showed lower stomatitis scores than the control (P = 0.08), without yet reaching statistical significance. In the chlorhexidine group, by contrast, no significant reduction from baseline was observed. The improvement trajectory started earlier in the herbal group.
The biological rationale is consistent with this finding. Chlorhexidine acts on a single target: reducing the microbial load in the lesions. Malva sylvestris acts simultaneously on multiple pathways: anti-inflammatory, antioxidant, antimicrobial, and physical barrier formation. This complementary mode of action explains why the clinical response appears sooner, and why the effect is larger during the most critical treatment window.
The authors point out the study’s limitations: single-center design, small sample size, short follow-up. These are serious methodological considerations, which the researchers themselves identify as priorities for future multicenter trials. Current evidence, however, is robust enough to justify a formulation-oriented evaluation of this plant.
Applications in Oncology Supportive Care: A High-Value Clinical Segment
The data from this trial place Malva sylvestris in a precise application segment: supportive care for cancer patients during chemotherapy. This is not a generic positioning such as ‘antioxidant’ or ‘mucosal soothing agent’, but an indication verified in a controlled clinical setting and published in a peer-reviewed journal.
The mouthwash formulation is the one tested in the study, but the plant’s pharmacological profile also opens opportunities for topical forms of mucosal application. The choice of vehicle and extract concentration is critical: phenolic compounds and flavonoids show variable stability depending on pH, temperature, and solvent composition.
The scale of the problem is clinically significant: millions of cancer patients face stomatitis every year, with a direct impact on quality of life and treatment adherence. A herbal product backed by solid clinical data, a contained cost, and a favorable safety profile addresses a therapeutic need that conventional medicine has not yet solved satisfactorily.
If your company is interested in developing Malva sylvestris-based formulations
Source: Salmaninejad Z, Mazhari F, Pourhosseini SME, Raeiszadeh M, Sadeghi T. “The effect of Malva sylvestris mouthwash on chemotherapy-induced stomatitis and associated pain in patients with cancer: a triple-blind randomized clinical trial.” BMC Cancer. 2025;25:1695. DOI: https://doi.org/10.1186/s12885-025-15158-w
