TL;DR
Canker sores are not caused by a virus. They result from a dysregulated local immune response in which T-lymphocytes attack the oral epithelium. Multiple triggers can activate this pathway in genetically susceptible individuals. The most evidence-backed triggers are: nutritional deficiencies (B12, iron, folate, zinc), SLS in toothpaste, psychological stress, oral trauma, and hormonal fluctuations. This page breaks down the mechanism behind each.
The Core Mechanism: Immune Dysregulation
Before listing triggers, it's important to understand why triggers cause ulcers — because the same trigger (e.g., stress) can affect everyone differently. In canker sore sufferers, the immune response to epithelial insults is aberrant.
Current evidence points to:
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TNF-α and IL-6 elevation: Inflammatory cytokines are significantly elevated in aphthous ulcer tissue compared to surrounding mucosa. TNF-α acts as the key mediator of epithelial destruction (Natah et al., 2004 — PMID: 14988753).
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CD8+ T-cell predominance: Early lesions show CD4+ T-cell infiltration; established ulcers show CD8+ cytotoxic T-cells as the dominant infiltrate. This pattern suggests a cell-mediated autoimmune mechanism directed at epithelial antigens.
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Reduced regulatory T-cell activity: Tregs normally suppress self-directed immune responses. Chronic RAS sufferers show reduced Treg frequency and function, failing to terminate the inflammatory cascade.
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Mast cell degranulation: Mast cells in the prodromal period degranulate and release histamine and proteases — explaining the burning/tingling sensation 1–2 days before visible ulceration.
This is not a simple infection or a straightforward autoimmune disease. It is a locally dysregulated immune response with no systemic target antigen identified.
Nutritional Deficiencies
This is the most action-actionable category — deficiencies are testable and correctable.
Vitamin B12 Deficiency
B12 deficiency is significantly overrepresented in RAS patients. One study found deficiency in 28% of RAS patients versus 3% of controls (Volkov et al., 2005 — PMID: 15705112). The mechanism likely involves B12's role in maintaining the mucosal epithelium and modulating immune function — B12 deficiency impairs DNA synthesis in rapidly dividing epithelial cells, increasing mucosal fragility.
More compelling: supplementation works. An RCT (Volkov et al., 2009 — PMID: 20012098) found that 1000mcg sublingual B12 nightly reduced ulcer frequency significantly versus placebo, regardless of baseline serum B12 levels. This is one of the stronger RCTs in this space.
Iron Deficiency
Iron deficiency disrupts mucosal integrity via impaired oxidative metabolism in epithelial cells. Studies have found serum ferritin levels significantly lower in RAS patients (Rogers & Hutton, 1986 — PMID: 3531785). Iron deficiency anemia should be screened with ferritin, not just hemoglobin — ferritin depletion precedes anemia.
Folate Deficiency
Folate (vitamin B9) is required for DNA synthesis and cell proliferation. Mucosal cells turn over rapidly; folate deficiency creates a vulnerability. Associated with RAS in several case series, particularly in patients with celiac disease (which impairs folate absorption).
Zinc Deficiency
Zinc is essential for epithelial repair and T-cell immune regulation. Zinc deficiency both weakens the mucosal barrier and dysregulates the immune response — a dual mechanism. Serum zinc has been found lower in RAS patients versus controls in multiple studies (Orbak et al., 2003 — PMID: 12756553).
See the full supplement guide: Best Supplements for Canker Sore Prevention →
Sodium Lauryl Sulfate (SLS) in Toothpaste
SLS is a detergent used in most commercial toothpastes. It disrupts the oral mucin layer — the protective protein film over the epithelium. Without this layer, the mucosa is more vulnerable to physical trauma and immune-mediated damage.
The evidence is reasonably consistent:
- Herlofson & Barkvoll (1994 — PMID: 8088761): Switching from SLS-containing to SLS-free toothpaste reduced aphthous ulcer frequency by ~50% in a double-blind crossover study.
- Multiple subsequent studies have replicated this association.
Verdict: Strong evidence. If you use SLS-containing toothpaste and suffer from RAS, switching to SLS-free is a low-risk, evidence-supported intervention. See our review: Do Home Remedies for Canker Sores Actually Work? →
Psychological Stress
Stress is consistently reported as a trigger, and the mechanism is well-characterized.
HPA axis activation → cortisol elevation → suppression of secretory IgA (sIgA) in saliva. sIgA is the primary immunological defense at mucosal surfaces. Reduced sIgA allows bacteria and immune triggers to penetrate the mucosa more effectively.
Additionally, stress-induced catecholamine release alters peripheral T-cell function, potentially exacerbating the already-dysregulated T-cell response in RAS sufferers.
The stress-RAS association is supported by multiple prospective studies, though the correlation is imperfect — stress frequency alone doesn't reliably predict outbreaks, suggesting it acts as a permissive rather than direct cause.
Oral Trauma
Minor trauma — biting the cheek, dental procedures, ill-fitting dentures, sharp food edges — is a well-established trigger, particularly in susceptible individuals. In people who don't have RAS, the same trauma heals without ulceration. In RAS sufferers, trauma can initiate the immune cascade that produces ulcers.
This likely explains why ulcers preferentially form at specific sites: the movable mucosa (inner cheeks, tongue), which is subject to more mechanical stress.
Hormonal Fluctuations
Many women report canker sores in the premenstrual phase. Progesterone fluctuations are thought to affect mucosal immune function. Studies have documented a significant association between RAS outbreaks and the luteal phase of the menstrual cycle, and some patients report remission during pregnancy — when progesterone is elevated and stable (Ship, 1965 — PMID: 14282450).
This is not universal, but the pattern is notable enough to track if you menstruate.
Genetic Predisposition
RAS has a strong familial component. If both parents have RAS, their offspring have a ~90% chance of developing it. HLA typing studies have identified several associated alleles, though no single HLA type is necessary or sufficient.
Genetics establishes the susceptibility — environmental triggers determine whether and when ulcers occur. This is why identical twins with the same HLA profile can differ in outbreak frequency.
Celiac Disease and IBD
Celiac disease and inflammatory bowel disease (Crohn's and ulcerative colitis) are both significantly associated with RAS. The association is likely multifactorial:
- Malabsorption of B12, iron, folate, and zinc → nutritional deficiency mechanism
- Systemic immune dysregulation → generalized mucosal vulnerability
- In Crohn's specifically: oral manifestations including aphthous ulcers are a recognized feature
If you have frequent, severe, or atypical RAS that doesn't respond to nutritional interventions, screening for celiac and IBD is clinically indicated.
What Does NOT Cause Canker Sores
- Herpes simplex virus: Despite the common confusion with cold sores, HSV is not involved in RAS. They are mechanistically distinct.
- Poor dental hygiene: No evidence supports this. Some antiseptic mouthwashes may actually irritate the mucosa and worsen outbreaks.
- Citrus / acidic foods: These are irritants that worsen existing ulcers, not causes of new ones.