Nutritional Deficiencies That Cause Canker Sores
The most common nutritional deficiencies causing canker sores (recurrent aphthous stomatitis) are vitamin B12, folate, iron, and zinc, with B-complex vitamins (B1, B2, B6) also playing a significant role.
Primary Deficiencies to Screen For
B-Complex Vitamins
- Vitamin B12 deficiency is strongly associated with recurrent aphthous ulceration, with patients showing significantly lower dietary intake compared to controls 1, 2
- Folate deficiency demonstrates significantly reduced dietary intake in RAS patients (P < 0.0001), supporting a clear link between low folate and canker sore development 1
- Riboflavin (B2), thiamine (B1), and pyridoxine (B6) deficiencies were found in 28.2% of patients with recurrent mouth ulcers, and replacement therapy resulted in sustained clinical improvement only in those with documented deficiencies 3
- Riboflavin deficiency specifically manifests with angular stomatitis, cheilosis, and lip inflammation, often occurring alongside other B vitamin deficiencies 4
Minerals
- Iron deficiency is a well-established cause of oral ulceration and can present with glossitis, angular cheilitis, and recurrent oral ulcers before systemic anemia symptoms develop 5
- Zinc deficiency should be actively investigated as a causative factor, with one study showing complete resolution of RAS in all 48 patients after zinc replacement therapy (mean follow-up 12 months) 6
Clinical Context and Mechanisms
Risk Factors for These Deficiencies
- Inflammatory bowel disease, particularly Crohn's disease with small bowel involvement, predisposes to vitamin B12 and folate deficiencies 4, 7
- Malabsorption conditions including short bowel syndrome and celiac disease increase risk for multiple vitamin deficiencies including riboflavin 4
- The most common nutritional deficiencies in IBD patients include vitamin B12, folate, iron, calcium, magnesium, selenium, and zinc 8
Diagnostic Approach
- Measure serum vitamin B12, folate (both serum and red blood cell folate), iron studies (ferritin, transferrin saturation), and zinc levels in all patients with recurrent aphthous ulceration 3, 1, 6
- For riboflavin assessment, use the erythrocyte glutathione reductase activity test to evaluate tissue saturation and long-term status 4
- Critical caveat: Never treat folate deficiency without first checking B12 status, as folate supplementation can improve blood parameters while worsening neurological manifestations of B12 deficiency 9
Treatment Considerations
Replacement Therapy
- Patients with documented B-complex deficiencies (B1, B2, B6) showed significant sustained clinical improvement after one month of replacement therapy, with benefits maintained at 3-month follow-up 3
- For zinc deficiency, three-monthly replacement treatment achieved complete resolution with no recurrences when taken correctly (not with milk, which impairs absorption) 6
- The daily recommended dose of riboflavin is 1.3 mg for males and 1.1 mg for females, though higher doses may be required for chronic malabsorption 4
Important Clinical Pitfalls
- Oral iron supplementation should not exceed 100 mg elemental iron daily in inactive disease and should be avoided during active inflammation due to impaired absorption 7
- Many micronutrients are acute phase reactants, making interpretation unreliable during active inflammation 7
- Two patients in the zinc deficiency study initially reported no relief due to incorrect intake with milk; proper administration instructions are essential 6
Evidence Quality Note
The strongest evidence comes from prospective studies showing that only patients with documented deficiencies benefit from replacement therapy 3, and that dietary intake of B12 and folate is significantly lower in RAS patients compared to matched controls 1. The zinc deficiency study demonstrated 100% resolution with appropriate replacement 6, making it a particularly important deficiency to screen for despite being less commonly discussed.