Mouth Ulcers and B12: The Trial Worked Regardless of Your Level

reason nobody expects. A randomised, double-blind, placebo-controlled trial of 58 patients
gave 1000 mcg of sublingual vitamin B12 daily for six months. Duration of outbreaks, number
of ulcers and pain level all fell significantly, and the trial’s own wording is the important part:
regardless of initial vitamin B12 levels in the blood. In the final month,
74.1% of the B12 group reached “no aphthous ulcers status” versus 32.0% on placebo
(P<0.01). Now hold that against the deficiency data: in 273 patients with recurrent mouth ulcers
compared against 273 matched controls, only 4.8% were B12 deficient. Iron deficiency was
four times commoner at 20.1%, and low haemoglobin commoner still at 20.9%. So B12 supplementation appears to
help people who were never short of B12, which means this is not deficiency correction and nobody knows what
it is. Two practical numbers before you try it: the benefit reached significance only at
months 5 and 6, and the useful form is sublingual.
Almost everything on this site so far has pointed one way: test before you supplement, because the
nutrient people search for is usually the wrong one. This page is the exception, and it is worth
understanding why.
The trial
Volkov and colleagues, published in the Journal of the American Board of Family Medicine, 2009. A
randomised, double-blind, placebo-controlled trial in primary care patients.
- 58 patients with recurrent aphthous stomatitis: 31 intervention, 27 control
- 1000 mcg sublingual B12 daily
- Six months
The results:
The duration of outbreaks, the number of ulcers, and the level of pain were reduced
significantly (P < .05) at 5 and 6 months of treatment with vitamin B12, regardless of initial
vitamin B12 levels in the blood.
And the headline outcome:
| Final month of treatment | Reached “no aphthous ulcers status” |
|---|---|
| Vitamin B12 | 74.1% |
| Placebo | 32.0% |
| P < 0.01 | |
The authors’ conclusion: B12 treatment, which is simple, inexpensive and low-risk, seems to be effective
for patients suffering from recurrent aphthous stomatitis, regardless of the serum vitamin B12
level.
Why that last clause is strange
Look at how few patients are actually deficient. A study measured haemoglobin, iron, B12, folic acid and
homocysteine in 273 patients with recurrent mouth ulcers against 273 age- and sex-matched
healthy controls:
| Deficiency | Patients affected |
|---|---|
| Haemoglobin | 57 (20.9%) |
| Iron | 55 (20.1%) |
| Vitamin B12 | 13 (4.8%) |
| Folic acid | 7 (2.6%) |
| High homocysteine | 21 (7.7%) |
All of those were significantly commoner than in the matched controls (P=0.000 for each except folic acid
at P=0.022). So deficiencies are genuinely over-represented in this condition.
But B12 specifically is the least common of them, at under one in twenty. And the trial found
benefit in everyone.
Those two facts together rule out the obvious explanation. If B12 worked by correcting a shortage, it
would work in the 4.8% and do nothing for the other 95%. That is not what happened. Whatever B12 is doing to
the oral mucosa here, it is not simply filling a gap, and a 2022 review is direct about the underlying
uncertainty: there is conflicting evidence that B12 deficiency causes recurrent aphthous
stomatitis.
The timeline is the part people get wrong
Significance appeared at months 5 and 6. Not week two.
A 2022 review of seven randomised trials reached the same shape of conclusion, finding that a higher dose
of 1000 mcg sublingually achieved a significant reduction in outbreaks, number and duration of ulcers,
especially after six months, and suggesting a daily dose of 1000 mcg sublingually for six
months.
That review adds its own caution, which belongs here rather than in a footnote: this conclusion should be
considered tentative due to the lack of high quality, large scale studies.
Two other findings from it are worth knowing before you buy something:
- Multivitamins showed no difference in new episodes or duration. This is not a
general-nutrition effect. - The route matters. Sublingual, buccal discs, ointment and injection all showed effects in different
trials; the review’s recommendation lands on sublingual 1000 mcg.
If you want to run the trial protocol on yourself
The specification is unusually precise for a supplement, which is the whole
reason this box exists: 1000 mcg, sublingual, once daily, for six months. Not a
multivitamin, which showed no difference. Not a four-week trial, because the effect did not reach
significance until month five. Buy enough to finish, because stopping at week eight tells you nothing that
the trial did not already predict.
Sublingual B12 1000 mcg
Ferritin test
As an Amazon Associate we earn from qualifying
purchases. The ferritin test is listed alongside because iron deficiency was four times commoner than B12
deficiency in these patients, and it is the one that needs measuring rather than trying.
The nutrient that actually is missing
Iron, not B12. Iron deficiency at 20.1% and low haemoglobin at 20.9%
dwarf B12’s 4.8%.
The difference in how to handle them is important. B12 at 1000 mcg sublingually is water-soluble, cheap
and low-risk, which is why trying it without testing is defensible. Iron is not.
Unnecessary iron causes constipation and stomach upset, and is genuinely harmful in anyone with undiagnosed
iron overload. Iron is a test-first nutrient.
A review notes that patients with B12 or folate deficiency showed rapid improvement with replacement,
while those with iron deficiency showed a less remarkable response, which is worth knowing so that a slower
result from iron correction does not get mistaken for failure.
Know which ulcer you have
Recurrent aphthous stomatitis affects up to 25% of the worldwide population, and comes in
three forms that behave very differently.
| Type | Size and course |
|---|---|
| Minor (over 70% of cases) | Usually under 5 mm, heals within two weeks without scarring |
| Major (10%) | Over 10 mm, lasts 5 to 10 weeks, usually leaves scarring |
| Herpetiform (1–10%) | Up to 100 ulcers at once, 2 to 3 mm, one to two weeks |
Listed triggers and associations include local trauma, stress, smoking cessation,
anaemia, hematinic deficiency, Crohn’s disease, ulcerative colitis, coeliac disease, Behçet’s disease and
HIV infection.
Smoking cessation on that list surprises people and is worth flagging: a crop of mouth ulcers a few weeks
after quitting is a documented phenomenon, not a reason to start again.
When it is not just mouth ulcers
The conditions to rule out are Behçet disease, MAGIC syndrome, PFAPA syndrome, cyclic neutropenia and HIV
disease. Recurrent mouth ulcers are also a recognised presentation of coeliac disease and inflammatory bowel
disease.
The pattern that should send you to a doctor rather than a pharmacy: ulcers that appear suddenly
in adulthood when you never had them before, ulcers accompanied by genital ulcers or eye
inflammation, ulcers with fever or diarrhoea or weight loss, or any single ulcer that has not healed in
three weeks.
Frequently Asked Questions
Does B12 actually help mouth ulcers?
On the available randomised evidence, yes. A double-blind, placebo-controlled trial of 58 patients using
1000 mcg sublingual B12 daily for six months found the duration of outbreaks, the number of ulcers and the
level of pain all significantly reduced at months 5 and 6, and in the final month 74.1% of the B12 group
reached no-ulcer status against 32.0% on placebo (P<0.01). The trial was small, and a later review of
seven randomised trials calls the overall conclusion tentative due to the lack of high quality, large scale
studies. But it is far more than most supplement claims have behind them.
Do I need to be B12 deficient for it to work?
Apparently not, and this is the most interesting finding on the page. The trial explicitly reports benefit
regardless of initial vitamin B12 levels in the blood, and concludes that B12 seems effective regardless of
the serum vitamin B12 level. That matters because only 4.8% of patients with recurrent mouth ulcers were B12
deficient in a 273-patient study. If the mechanism were simple deficiency correction, the treatment could not
work in the other 95%. Nobody has established what it is doing instead.
How long before I know if it works?
Five months, on the trial data. Significance appeared at months 5 and 6, not earlier, and a review of the
wider literature similarly found the effect of 1000 mcg sublingual especially after six months. This is the
single most useful practical fact here, because it means a four-week trial is not a test. If you are going to
try it, commit to six months or do not start.
Will a multivitamin do?
No. The review of seven trials states plainly that multivitamins showed no difference in new episodes or
duration. Whatever is happening is specific to B12 at a meaningful dose and by a route that gets it absorbed,
rather than a general effect of topping up nutrition. The reviewed protocol is 1000 mcg sublingually.
Which deficiency is actually most common?
Iron and low haemoglobin, not B12. In 273 patients with recurrent mouth ulcers, 20.9% had haemoglobin
deficiency and 20.1% had iron deficiency, against 4.8% for B12 and 2.6% for folic acid, with 7.7% showing
abnormally high homocysteine. All were significantly commoner than in matched controls. So if you are getting
one blood test, ferritin is the higher-yield one, and unlike B12 it is a nutrient you should not supplement
without a measurement.
Why did I get ulcers after quitting smoking?
Because smoking cessation is a listed trigger, alongside local trauma, stress, anaemia, hematinic
deficiency and several systemic conditions. It is a well-recognised and temporary phenomenon rather than a
sign that something has gone wrong, and it is not a reason to resume smoking. If it persists well beyond the
first weeks, it is worth raising with a doctor rather than assuming it is the cessation.
How do I tell a serious ulcer from an ordinary one?
Size and duration. Minor ulcers, over 70% of cases, are usually under 5 mm and heal within two weeks
without scarring. Major ulcers are over 10 mm, last 5 to 10 weeks and usually scar. Any single ulcer that has
not healed within three weeks needs looking at, because duration is the feature that separates a recurrent
aphthous ulcer from things that need a diagnosis.
When should I see a doctor?
If ulcers begin suddenly in adulthood having never occurred before; if they come with genital ulcers or
eye inflammation, which raises Behçet disease; if they come with fever, diarrhoea or weight loss, which
raises coeliac or inflammatory bowel disease; or if one has not healed in three weeks. Recurrent mouth ulcers
are also listed as a possible manifestation of HIV infection and cyclic neutropenia, which is why a new adult
onset is treated differently from a lifelong pattern.
Sources
- Volkov I, Rudoy I, Freud T, Sardal G, Naimer S, Peleg R, Press Y. Effectiveness of vitamin B12 in
treating recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled trial. J Am Board Fam
Med. 2009;22(1):9-16. PMID 19124628. Frequency of recurrent aphthous stomatitis up to 25% in the general
population; 58 patients, 31 intervention and 27 control; sublingual dose of 1000 mcg vitamin B12 for 6
months. The duration of outbreaks, the number of ulcers, and the level of pain were reduced significantly
(P<.05) at 5 and 6 months of treatment with vitamin B12, regardless of initial vitamin B12 levels in the
blood. During the last month of treatment a significant number of participants in the intervention group
reached “no aphthous ulcers status” (74.1% vs 32.0%; P<.01). Conclusion: vitamin B12 treatment, which is
simple, inexpensive, and low-risk, seems to be effective for patients suffering from RAS, regardless of the
serum vitamin B12 level. Checked August 2026 —
PubMed 19124628 - Sun A, Chen HM, Cheng SJ, Wang YP, Chang JY, Wu YC, Chiang CP. Significant association of deficiencies of
hemoglobin, iron, vitamin B12, and folic acid and high homocysteine level with recurrent aphthous stomatitis.
J Oral Pathol Med. 2015;44(4):300-5. PMID 25048341. Blood levels measured in 273 RAS patients and compared
with 273 age- and sex-matched healthy controls. 57 (20.9%) had haemoglobin deficiency (men <13 g/dl, women
<12 g/dl), 55 (20.1%) iron deficiency (<60 mcg/dl), 13 (4.8%) vitamin B12 deficiency (<200 pg/ml)
and 7 (2.6%) folic acid deficiency (<4 ng/ml); 21 (7.7%) had abnormally high blood homocysteine. RAS
patients had a significantly higher frequency of each than healthy controls (all P-values = 0.000 except
folic acid P = 0.022). Checked August 2026 —
PubMed 25048341 - Taleb R, Hafez B, El Kassir N, El Achkar H, Mourad M. Role of vitamin B12 in treating recurrent aphthous
stomatitis: A review. Int J Vitam Nutr Res. 2022;92(5-6):423-430. PMID 33103958. There is conflicting
evidence that B12 deficiency causes RAS. Seven randomised controlled trials reviewed. Three studies
administered vitamin B12 sublingually at different dosages, revealing that the higher dose (1000 mcg)
achieved a significant reduction in outbreaks, number, and duration of ulcers, especially after six months.
Multivitamins showed no difference in new RAS episodes and duration. The authors suggest a daily dose of 1000
mcg of vitamin B12 sublingually for six months can be used to treat RAS, but state this conclusion should be
considered tentative due to the lack of high quality, large scale studies. Checked August 2026 —
PubMed 33103958 - Recurrent Aphthous Stomatitis, StatPearls. Affects up to 25% of the worldwide population. Minor aphthous
ulcers are most common at over 70% of cases, usually less than 5 mm in diameter, healing within two weeks
without scarring; major aphthous ulcers occur in 10% of patients, are larger than 10 mm, last 5 to 10 weeks
and usually leave scarring; herpetiform ulcers are least common at 1 to 10% of cases, with up to 100 ulcers
simultaneously measuring 2 to 3 mm and lasting one to two weeks. Triggers and associated conditions include
local trauma, stress, smoking cessation, anaemia, hematinic deficiency, Crohn’s disease, ulcerative colitis,
coeliac disease, Behçet’s disease and HIV infection. Systemic diseases to rule out include Behçet disease,
MAGIC syndrome, PFAPA syndrome, cyclic neutropenia and HIV disease. Checked August 2026 —
StatPearls NBK431059
All figures on this page are quoted from the named studies and were
checked against them in August 2026. The B12 trial had 58 participants and the review it sits in describes
the evidence base as lacking high quality, large scale studies; both facts are reported here rather than
only the favourable one. This page summarises published research, cannot examine your mouth, and is not a
diagnosis.


