Vitamin B12, also known as cobalamin, is the oddball of the B vitamin family. It’s the only B vitamin that contains a metal ion (cobalt, hence “cobalamin”), and its molecular structure is surprisingly complex for a water-soluble vitamin.

If you’re deficient, the consequences go beyond just feeling tired. Pernicious anaemia is the classic presentation, but B12 deficiency can also cause elevated homocysteine levels (linked to cardiovascular problems), peripheral neuropathy, cognitive decline, loss of appetite, and general exhaustion that doesn’t improve with rest.

What does vitamin B12 actually do?

B12 has several distinct roles in the body: it’s involved in red blood cell formation, nervous system maintenance, energy production, DNA synthesis, maintaining the gut lining, and metabolising proteins, fats, and carbohydrates.

Humans can’t make B12. It has to come from diet, and it’s found almost exclusively in animal-derived foods. A typical Western diet provides roughly 3-30 mcg daily, though only about 1-5 mcg of that gets absorbed. The recommended daily allowance sits between 1-3 mcg.

One peculiarity of B12: your body stores quite a lot of it (somewhere between 2000-5000 mcg), which explains why deficiency symptoms often take years to appear. You can stop eating B12 entirely and still have enough in your liver to last several years.

Who’s at risk of B12 deficiency?

B12 comes primarily from animal foods: fish, meat, shellfish, milk, and eggs. Plant sources are scarce, with seaweed containing some, though its bioavailability is questionable.

Absorption depends heavily on gut function and diet, so people at higher risk include:

Vegetarians and vegans (particularly those avoiding eggs and dairy)
Older adults (stomach acid production decreases with age, and B12 needs acid for absorption)
People with gastrointestinal conditions (Crohn’s disease, coeliac disease, Helicobacter pylori infection, or those who’ve had stomach or intestinal surgery)
People with eating disorders
Those taking long-term acid-suppressing medications
People with diabetes, AIDS, or certain genetic conditions affecting B12 transport

The tricky part: “normal” blood levels don’t always mean you’re fine

Here’s something worth knowing. One case report noted that up to 50% of patients with clear B12 deficiency symptoms had blood levels above 200 pg/mL, which most labs consider “normal” [1].

This matters because if your doctor sees a normal result, they might dismiss B12 as the problem. If symptoms persist despite “normal” B12 levels, measuring methylmalonic acid and homocysteine can help clarify things. Both markers rise when B12 is functionally insufficient, even when serum levels look acceptable.

What does the research say about B12 benefits?

I should be upfront here: a lot of the research on B12 has limitations. Small sample sizes, short follow-up periods, and difficulty separating B12’s effects from other factors are common problems. That said, here’s what we know.

1. Diabetic neuropathy

Diabetic neuropathy is one of the most common complications of diabetes, affecting up to 50% of patients. It causes sensory symptoms, foot infections, ulcers, and in severe cases can lead to amputation. About a third of affected patients develop painful neuropathy with burning sensations, numbness, and shock-like pain.

A meta-analysis of 6 trials with 669 participants found that B12 supplementation (alone or combined with other treatments) reduced neuropathic symptoms and improved pain compared to placebo [2]. The proposed mechanism involves B12 affecting noradrenaline and serotonin pathways.

My honest take: the results look promising, but 669 participants across 6 studies isn’t a lot. More research is needed before drawing strong conclusions.

2. Autism spectrum disorder

Children with autism spectrum disorder often have various metabolic abnormalities, including issues with oxidative stress, mitochondrial function, and nutrient levels. A systematic review and meta-analysis covering 17 studies found that B12 supplementation, particularly methylcobalamin given subcutaneously, improved certain clinical symptoms and metabolic markers [3].

The caveat: measurement bias in the included studies makes interpretation difficult. This is promising early research, not established treatment.

3. Vitamin B12 selective absorption disorder syndrome

Imerslund-Grasbeck syndrome (IGS) is a rare genetic disorder affecting B12 absorption. Children with IGS develop megaloblastic anaemia, intermittent proteinuria, and growth problems between ages 1-5 [4].

The treatment is straightforward: lifelong B12 injections or high-dose oral supplementation, similar to pernicious anaemia treatment. This is one area where B12’s benefit is unambiguous.

4. Cyanide poisoning from fire smoke inhalation

This one might surprise you. Hydroxocobalamin, a B12 precursor, was approved by the US FDA in 2006 specifically for treating cyanide poisoning.

When cyanide enters the body, it binds to cytochrome oxidase and blocks aerobic metabolism, causing symptoms ranging from dizziness and headache to seizures and coma. A retrospective study found that routine hydroxocobalamin administration in suspected smoke inhalation cases reduced pneumonia rates, shortened time on ventilators, and decreased ICU stays [5].

5. Gestational diabetes

About 14% of pregnant women worldwide develop gestational diabetes, affecting roughly 18 million newborns annually. A meta-analysis of 6 observational studies (1810 pregnant women, 309 with gestational diabetes) found that B12 deficiency (below 200 pg/mL) was associated with higher gestational diabetes risk [6].

This doesn’t prove B12 deficiency causes gestational diabetes, just that the two are associated. But it’s another reason pregnant women should ensure adequate B12 intake.

6. Cardiovascular and cerebrovascular disease

This is where things get complicated. B vitamins lower homocysteine levels, and elevated homocysteine is associated with cardiovascular disease. So B vitamins should help prevent heart attacks and strokes, right?

Not quite. A meta-analysis of 11 randomised controlled trials involving 26,395 patients found no overall effect of B vitamin supplementation on cardiovascular events, including heart attacks [7].

However, subgroup analysis showed B vitamins did reduce stroke risk with longer follow-up, particularly in people with low folate intake, higher B12/B6 doses, and existing cardiovascular history.

The bottom line: combined B vitamin supplementation probably doesn’t prevent heart attacks generally, but may reduce stroke risk in specific populations.

7. Post-herpetic neuralgia

Post-herpetic neuralgia is a chronic pain syndrome affecting 5-20% of people who develop shingles. Risk increases with age, and the pain can be severe and long-lasting.

A meta-analysis of 4 randomised controlled trials (383 patients with shingles) found that subcutaneous B12 improved pain scores and quality of life compared to placebo, and reduced painkiller use [8]. The mechanism likely involves B12 improving nerve conduction and promoting nerve regeneration.

With only 383 participants, this remains preliminary evidence, but the results are encouraging.

8. Colorectal cancer

Diet and lifestyle factors account for a substantial portion of colorectal cancer risk. A meta-analysis of 17 studies with 10,601 participants found that B12 intake above approximately 4.5 mcg daily was inversely associated with colorectal cancer risk [9].

Interestingly, blood B12 levels weren’t significantly associated with colorectal cancer, just dietary intake. This suggests the association might be about overall diet quality rather than B12 specifically.

9. Osteoporosis

A systematic review of 17 studies examined whether B12 affects bone density and fracture risk [10]. The results were inconsistent, especially for postmenopausal women (the group most at risk for osteoporosis).

As of now, the relationship between B12 and bone health remains unclear. This might be a case where B12 deficiency is a marker of poor overall nutrition rather than a direct cause of bone problems.

10. Neural tube defects

Neural tube defects (spina bifida, anencephaly) are serious birth defects affecting roughly 0.5-2 per 1000 pregnancies worldwide. Folate supplementation before and during early pregnancy reduces risk substantially.

A meta-analysis of 9 studies found that maternal B12 deficiency during pregnancy also increased neural tube defect risk, with odds ratios up to 2.41 [11].

This makes sense biochemically: B12 and folate work together in several metabolic pathways. Pregnant women should ensure adequate intake of both.

11. Depression

Depressive disorder affects about 17% of people at some point in their lives. A meta-analysis of 11 randomised controlled trials found that short-term folate and B12 supplementation (days to weeks) didn’t improve depressive symptoms in people already taking antidepressants [12].

However, longer-term use (weeks to years) may reduce recurrence risk in people predisposed to depression. So B12 probably isn’t useful for treating acute depression, but might have a role in prevention for vulnerable individuals.

12. Preterm birth

Preterm birth causes nearly one million infant deaths annually and can lead to lasting developmental problems. A meta-analysis of 18 studies (11,216 participants) found that lower maternal B12 levels increased preterm birth risk, with deficient mothers having a 21% higher chance of preterm delivery [13].

B12 deficiency also increased low birth weight risk by about 15%.

When should you take vitamin B12?

B12 is water-soluble and generally absorbs best on an empty stomach. The standard recommendation is to take it before breakfast, or at least 30 minutes before eating or 2 hours after a meal.

Are there side effects?

For most healthy people at normal doses, B12 is considered safe with minimal side effects. No “upper tolerable intake level” has been established because toxicity is rare.

That said, very high doses may cause:

Dizziness and headache
Anxiety
Nausea and vomiting
Itching
Acne or rosacea flare-ups

Severe allergic reactions are extremely rare but can include facial swelling, difficulty breathing, and throat tightness. If these occur, seek medical attention immediately.

Safety precautions

There are some situations where B12 supplementation requires caution:

A placebo-controlled study in older adults found that daily folate (400 mcg) plus B12 (500 mcg) for 2-3 years may increase colon cancer risk [14]. This needs more investigation.
In patients with diabetic nephropathy, high-dose B vitamins (including 1000 mcg B12) may worsen kidney function and increase cardiovascular events [15].
Sublingual and dissolvable B12 supplements often contain sugar alcohols, which may cause bloating and diarrhoea in sensitive individuals.
One observational study found that pregnant women with blood B12 levels above 600 pmol/L had higher rates of autism in their children [16]. The recommended daily intake for pregnant women is 2.6 mcg, not megadoses.
Taking folate, vitamin B6, and B12 after coronary artery stenting may increase in-stent restenosis risk [17].
Megaloblastic anaemia treatment with B12 should be supervised by a medical professional.
Chloramphenicol (an antibiotic) may interfere with B12’s role in red blood cell production.
Many medications can inhibit B12 absorption: anti-epileptic drugs (phenytoin, primidone), chemotherapy drugs (methotrexate), gout medication (colchicine), bile acid binders (cholestyramine, colestipol), proton pump inhibitors, and metformin.
Long-term high-dose folate (over 800 mcg) can mask B12 deficiency by correcting the anaemia while neurological damage progresses. This is why multivitamins typically contain both.

What forms of B12 are available, and does it matter?

The two most common supplement forms are cyanocobalamin and methylcobalamin.

Cyanocobalamin is synthetic, doesn’t exist in nature, and is the most common and cheapest form. Once absorbed, the body converts it to methylcobalamin or adenosylcobalamin, the active forms.

Methylcobalamin is a naturally occurring form (the “active methyl” B12) also found in foods like fish, meat, eggs, and milk. Some studies suggest it has higher absorption and retention rates.

Adenosylcobalamin is another active form. Taking methylcobalamin alone doesn’t raise adenosylcobalamin levels, so some people prefer supplements containing both.

In practice, the bioavailability difference between forms may be small, and factors like age and genetics probably matter more than which form you choose.

If you suspect B12 deficiency, talk to a healthcare provider about testing and the most appropriate treatment approach. For people with absorption problems (such as those with pernicious anaemia or after gastric surgery), injections may work better than oral supplements.

References

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Jayabalan B, Low LL. Vitamin B supplementation for diabetic peripheral neuropathy. Singapore Med J. 2016;57(2):55-59. doi:10.11622/smedj.2016027
Rossignol DA, Frye RE. The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. J Pers Med. 2021;11(8):784. doi:10.3390/jpm11080784
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Wang ZP, Shang XX, Zhao ZT. Low maternal vitamin B(12) is a risk factor for neural tube defects: a meta-analysis. J Matern Fetal Neonatal Med. 2012;25(4):389-394. doi:10.3109/14767058.2011.580800
Almeida OP, Ford AH, Flicker L. Systematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin B12 for depression. Int Psychogeriatr. 2015;27(5):727-737. doi:10.1017/S1041610215000046
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House AA, Eliasziw M, Bhattacharyya O, et al. High-Dose B Vitamin Supplementation and Progression of Diabetic Nephropathy: The DIVINe Randomized Controlled Trial. JAMA. 2010;303(16):1603-1609. doi:10.1001/jama.2010.490
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National Institutes of Health Office of Dietary Supplements. Vitamin B12 Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/