Vitamin B12#

Vitamin B12 (also called cobalamin) is needed to:

• Make healthy red blood cells
• Keep nerves working properly
• Produce DNA in dividing cells

Severe long-standing B12 deficiency can cause anemia, nerve damage (numbness, tingling, balance problems), and cognitive changes. Nerve damage from B12 deficiency can become permanent if left untreated for many months.

The most common test measures total B12 (cobalamin) in the blood. It is reported in pmol/L (picomoles per litre) in Canada.

Total B12 measures all the B12 in your blood, but only a small portion is actually available to your cells. That can make borderline results harder to interpret, which is why follow-up tests (methylmalonic acid and homocysteine) are sometimes used when the picture is unclear.

MMA is a chemical that accumulates in the blood and urine when B12 is functionally low. An elevated MMA confirms that B12 is functionally deficient at the cell level, even when the blood B12 number is borderline. MMA is the most reliable second-line test when B12 is borderline.

Homocysteine is an amino acid that rises when B12 or folate is deficient. It is less specific than MMA (folate deficiency, kidney disease, and genetic factors can also raise it), but it sometimes adds useful information when B12 and folate are both being investigated.

Holotranscobalamin (sometimes called "active B12") measures the portion of B12 that is bound to a transport protein and available for use by cells. Some labs offer it as an alternative or follow-up to total B12. It is not yet routinely available across all Canadian labs, and most provinces consider it an uninsured test.

Testing is reasonable if you have:

• Symptoms of B12 deficiency (numbness, tingling, balance problems, memory or concentration issues, fatigue, glossitis, mood changes)
• Macrocytic anemia (large red blood cells on a CBC) of unknown cause
• A strict vegan diet without regular B12 supplementation
• A history of bariatric surgery or other bowel surgery
• A diagnosis of autoimmune pernicious anemia or a family history of it
• Age over 65 with vague cognitive or balance complaints
• Long-term use of medications that interfere with B12 absorption (see below)

• Age over 65 (stomach acid declines with age, which reduces B12 absorption)
• Vegan or strict vegetarian diet without B12 supplementation - B12 is mostly found in animal foods
• Prior gastric or small-bowel surgery (including bariatric surgery)
• Autoimmune pernicious anemia (immune attack on the cells that absorb B12)
• Conditions that affect absorption (celiac disease, Crohn's disease)
• Heavy alcohol use
• Long-term use of medications that reduce B12 absorption:
  • Acid-suppression medications (proton pump inhibitors, H2 blockers)
  • Type 2 diabetes medication that reduces B12 absorption (commonly used first-line oral diabetes medication)
• HIV
• Long-term use of nitrous oxide (recreational or medical)

Symptoms develop slowly and can be subtle at first:

• Numbness or tingling in the hands or feet
• Difficulty with balance, unsteady walking
• Memory or concentration problems, brain fog
• Sore, smooth, red tongue ("glossitis")
• Sores at the corners of the mouth
• Fatigue
• Pale skin
• Shortness of breath on exertion
• Low mood, irritability

No fasting is required for total B12. If MMA or homocysteine is being added on, no fasting is needed either. Homocysteine results are slightly more accurate if you fast for 8 hours, but it is not strictly required.

If you are taking a B12 supplement or recently received an injection, the blood level will look normal whether or not you are truly deficient. To get a meaningful baseline, stop oral B12 supplements for at least 1 to 2 weeks before testing (your clinician may suggest longer). After a B12 injection, wait at least 4 to 6 weeks.

If you have known deficiency and are being monitored on treatment, testing on your usual routine is fine.

• High-dose biotin (vitamin B7) supplements can interfere with B12 assays. Stop biotin for at least 72 hours before testing.
• Pregnancy can lower total B12 readings slightly without true deficiency - MMA may be more useful if testing in pregnancy.

Most people with a low B12 can be treated with high-dose oral or sublingual B12 supplements (typically 1000 to 2000 mcg per day) for several months, then a maintenance dose. Canadian and UK guidelines (BC Guidelines and NICE) accept high-dose oral B12 as effective for most patients - even those with absorption problems like pernicious anemia, because at very high doses a small amount is absorbed passively without the usual transport mechanism.

Injectable B12 is reserved for:

• Severe symptoms (clear nerve damage, severe anemia)
• People who cannot tolerate oral supplementation
• Severe absorption problems where oral high-dose has failed

Discuss your situation with your clinician to choose oral versus injectable B12.

If you have symptoms or risk factors for B12 deficiency, your clinician may add methylmalonic acid (MMA) and homocysteine. If MMA is elevated, treat as B12 deficient. If MMA is normal, true deficiency is unlikely, although a trial of supplementation is sometimes reasonable when symptoms strongly suggest deficiency.

Pernicious anemia is an autoimmune disease in which the body attacks the stomach cells that produce intrinsic factor, a protein needed to absorb B12 from food. People with pernicious anemia need lifelong B12 replacement, either as a high oral dose or as injections. Diagnosis is supported by:

• Anti-intrinsic-factor antibodies (most specific)
• Anti-parietal-cell antibodies
• An elevated MMA
• Sometimes endoscopy if other gastric symptoms are present

Most pernicious anemia is managed by a family doctor or a hematologist, not in a telehealth setting.

A high B12 is usually because of supplementation or a high intake of animal foods. B12 is water-soluble, so any excess from supplements is cleared by the kidneys. There is no established toxicity threshold for B12 from supplements.

A few medical conditions can cause a high B12 without supplementation - such as liver disease, certain blood disorders, and some cancers - but in someone without symptoms this is rarely the cause.

Practical advice:

• If you feel well and take a B12 or multivitamin supplement: consider reducing the dose and rechecking in 6 to 12 months
• If you feel unwell (unexplained weight loss, new symptoms, abnormal liver tests, abnormal CBC): see a clinician in person to look for an underlying cause

Most people do not. Canadian guidelines (including BC Guidelines) and other international guidelines accept that high-dose oral B12 (1000 to 2000 mcg per day) is effective for most cases of B12 deficiency, including pernicious anemia. Injections are usually reserved for:

• Severe symptoms, especially nerve damage
• People who cannot tolerate or absorb oral supplements
• People who have tried high-dose oral therapy and not responded

If you are currently on B12 injections without a clear reason, ask your clinician whether oral supplementation is appropriate. Many people switch successfully.

Vegans should take a B12 supplement regularly. Common approaches:

• 250 mcg or more daily
• 1000 mcg twice weekly
• 2000 mcg weekly

Fortified plant milks, fortified breakfast cereals, and nutritional yeast (B12-fortified) help, but a supplement is the most reliable option.

Yes. Long-term use of either can reduce B12 absorption from food over time. If you take either of these medications for more than a few years, a periodic B12 check (every 1 to 2 years) is reasonable. If your B12 is low, a daily oral B12 supplement is usually all that is needed - you generally do not need to stop the underlying medication.

• Energy and fatigue often improve within a few weeks
• Mouth and tongue symptoms improve within weeks
• Anemia takes 2 to 3 months to fully correct
• Nerve symptoms (numbness, tingling, balance) can take 6 to 12 months to improve, and very long-standing nerve damage may not fully reverse

In most provinces, B12 testing is covered when there is a clinical reason (symptoms, anemia, risk factors, monitoring known deficiency). TeleTest will only order B12 as an insured test when there is a documented reason. Otherwise, you can pay an uninsured fee at the lab.

MMA is generally an uninsured test in most provinces. Homocysteine is sometimes covered when added to investigate a borderline B12, but coverage varies. Holotranscobalamin ("active B12") is uninsured.

Oral B12 is inexpensive - typically $10 to $25 for several months' supply. High-dose B12 (1000 mcg) is available over the counter without a prescription. Sublingual (under-the-tongue) tablets cost slightly more but offer no major advantage over swallowed tablets at high doses.