Editorial NexoScience
That monthly trip to the clinic for a vitamin B12 shot might be buying you nothing that a bottle of pills from the pharmacy could not already give you.
Vitamin B12 deficiency is common, especially among older adults, people on long-term metformin, those who have had gastric bypass surgery, and anyone eating a mostly plant-based diet. Left uncorrected, it can cause anemia, nerve damage and cognitive problems. For decades, intramuscular injections have been treated as the gold-standard fix, particularly when doctors suspect the gut cannot absorb the vitamin properly. A new analysis pooling every comparative trial on the subject puts that assumption to the test. Researchers combined data from 13 studies and 4,275 patients with vitamin B12 deficiency to directly compare the three ways the vitamin is usually delivered: oral pills, sublingual tablets or sprays dissolved under the tongue, and intramuscular injections.
All three routes worked. Regardless of how patients received their vitamin B12, their blood levels went up. When the team ranked the routes against each other, the injection route came out on top for raising B12 levels, followed by the sublingual route, both ahead of oral pills. But the gap was not statistically meaningful given how few trials exist. Put simply, the numbers hinted that shots might edge out pills, without actually proving it.
The picture got even less favorable for injections once the researchers looked past raw B12 levels. On hemoglobin, the marker doctors actually care about because it reflects whether the anemia is resolving, oral pills ranked first, ahead of injections. Across every other blood marker checked, including red blood cell size, platelet count, white blood cell count and homocysteine, there was no meaningful difference between routes at all.
One statistical model did flag a significant difference between oral and intramuscular dosing for raising B12 levels specifically. The authors are upfront that this did not translate into any measurable clinical benefit, since it never showed up in hemoglobin or the other markers that determine whether a patient is actually recovering.
Sublingual delivery came out looking like the quiet winner. It performed on par with both oral and intramuscular routes across the board, while avoiding the pain and clinic visits that come with injections and sidestepping any concern about gut absorption that can complicate oral dosing. The authors point to it as a reasonable middle option for patients who struggle with either extreme, such as people on long-term metformin or those with a history of gastric surgery.
Cost adds another layer to the decision. Intramuscular vitamin B12 is consistently more expensive than oral or sublingual formulations, on top of requiring a clinic visit or a caregiver comfortable giving injections. If the pills and the sprays work just as well for most people, that recurring expense and inconvenience may not be buying much.
None of this means injections should disappear from clinical practice. Current guidelines still favor the intramuscular route for people with confirmed malabsorption or severe, symptomatic deficiency, and this analysis is not positioned to overturn that for the sickest patients. What it does challenge is the reflex to default to needles for everyone else. The researchers frame the choice as one that should hinge on the individual, factoring in how severe the deficiency is, whether the gut can absorb nutrients normally, how the patient tolerates each option and, increasingly, what it costs.
The study, “Efficacy of different routes of vitamin B12 supplementation for the treatment of patients with vitamin B12 deficiency: A systematic review and network meta-analysis,” was led by Omar Ahmed Abdelwahab and colleagues and published in the Irish Journal of Medical Science (2024). DOI: 10.1007/s11845-023-03602-4.
