Vitamin B12 (cobalamin)

Pick Ordered or Not ordered to see the note.

Indicated when

• —At least one common symptom or sign of B12 deficiency (abnormal blood count such as anemia or macrocytosis, cognitive difficulty, eyesight or optic nerve problems, glossitis, peripheral neuropathy, balance or gait problems, or unexplained fatigue) together with at least one common risk factor [1]
• —A recognized risk factor with a symptom, using clinical judgement even if the picture is not classic: a diet low in animal-source foods (including a vegan diet), metformin, a proton pump inhibitor or H2-receptor antagonist, prior bariatric surgery, gastrectomy, or terminal ileal resection, coeliac disease or another autoimmune condition, or recreational nitrous oxide use [1]
• —Methylmalonic acid (MMA) as a second-line test when an initial B12 result is indeterminate, or plasma homocysteine is used as a less specific alternative, taking into account factors like folate deficiency that also raise homocysteine [1, 2]
• —Anti-intrinsic factor antibody testing once B12 deficiency is confirmed and autoimmune gastritis is suspected, in a person without a prior positive result or a qualifying prior surgery; anti-parietal cell antibody testing considered next if anti-intrinsic factor antibody is negative but suspicion remains [1]

Not indicated when

• —Routine population screening in a person with no symptom or sign and no recognized risk factor [1]
• —Relying on a negative anti-intrinsic factor antibody result alone to rule out autoimmune gastritis [1]

Why not

Second-line testing has real interpretive limits: plasma homocysteine is less specific than methylmalonic acid for confirming B12 deficiency and is also raised by folate deficiency, so it can point the wrong way if used alone [2, 1]. Antibody testing for cause-finding is not black-and-white either; a negative anti-intrinsic factor antibody result does not rule out autoimmune gastritis, so a reassuring antibody result can still miss the underlying cause [1].

Better first step

Use total B12 (serum cobalamin) or active B12 (serum holotranscobalamin) as the initial test when a symptom and/or risk factor is present. Reserve MMA for an indeterminate initial result, and reserve antibody testing for identifying the cause once deficiency is already confirmed [1].

Typical ND rationale

An ND may order B12, often together with MMA and antibody testing, in a patient with fatigue, brain fog, or tingling, reasoning that B12 deficiency is common, under-recognized, and has many contributing causes, diet, medications, and absorption among them, that are worth identifying together rather than one at a time.

Ontario coverage & CONO orderability

OHIP status

insured

L345 Vitamin B12 is listed in the 2026 Schedule of Benefits for Laboratory Services with no restricting condition, so it is insured whenever a physician orders it after clinically assessing the patient ([4]; Reg. 552 s.22). Methylmalonic acid and holotranscobalamin were not found by name in the 2026 Schedule during this session's search, so their coverage status is unverified rather than asserted. ND-ordered testing of any of these is patient-paid regardless of coverage status [7].

CONO orderable

Yes — CONO list #129, #21, #81

CONO list item 129, blood: 'Vitamin B (all tests),' which covers B12 testing broadly. Items 21 (Anti-Parietal Cell Antibody) and 81 (Intrinsic Factor Blocking Antibody) are separately listed, blood. Methylmalonic acid and holotranscobalamin do not appear as separate line items on the CONO list, so they are not confirmed orderable through it.

Linked conditions

• Vitamin B12 deficiency ↗
• tired ↗

Counselling script

“B12 deficiency is common and treatable, and a standard blood count can miss it, so testing makes sense when there's a symptom plus a risk factor like a vegan diet, metformin, an acid-reducing medicine, or past stomach surgery. If the first result is borderline, there's a more specific follow-up test. Without a symptom or a risk factor, B12 isn't something I'd check as routine screening.”

Revisit if

• —New symptom suggestive of B12 deficiency (fatigue, neuropathy, balance problems, cognitive change, glossitis)
• —New risk factor: dietary change, starting metformin, PPI, or H2-receptor antagonist long term, or GI/bariatric surgery
• —Confirmed B12 deficiency with suspected autoimmune gastritis, to consider antibody testing

References

1. [1]National Institute for Health and Care Excellence (NICE) (2024). Vitamin B12 deficiency in over 16s: diagnosis and management (NG239). linkTesting pathway for suspected B12 deficiency: initial test criteria, common symptoms and risk factors, second-line MMA, and antibody testing for cause once deficiency is confirmed, including that a negative anti-intrinsic factor antibody result does not rule out autoimmune gastritis
2. [2]British Committee for Standards in Haematology (2014). Guidelines for the diagnosis and treatment of cobalamin and folate disorders. linkolder guidelinePlasma homocysteine is a less specific second-line test than methylmalonic acid for confirming B12 deficiency
3. [3]Biomarkers of Nutrition for Development (BOND) Project (2018). Biomarkers of Nutrition for Development (BOND): Vitamin B-12 Review. linkHistorical B12 deficiency focus has been pernicious anemia and strict vegetarianism, with more recent recognition of insufficiency from low intake of animal-source foods
4. [4]Ontario Ministry of Health (2026). Ontario Health Insurance Plan: Schedule of Benefits for Laboratory Services (effective April 1, 2026) - L345 Vitamin B12. linkL345 Vitamin B12 is listed in the 2026 OHIP Schedule with no restricting condition
5. [5]Ontario Ministry of Health (2026). Ontario Health Insurance Plan: Schedule of Benefits for Laboratory Services (effective April 1, 2026). linkCommunity lab tests are insured only when ordered under the Schedule by an authorized prescriber
6. [6]Government of Ontario (e-Laws) (2026). Health Insurance Act, R.R.O. 1990, Reg. 552: General, s. 22 (insured laboratory services). linkA lab test is insured only when ordered by a physician, midwife, or NP who has clinically assessed the patient
7. [7]Ontario Ministry of Health (2026). Ontario Health Insurance Plan: Schedule of Benefits for Laboratory Services (effective April 1, 2026). linkTests ordered by anyone other than an authorized provider, including NDs, are not insured services