B12 Shots vs. Under-the-Tongue Drops: What Actually Works?

Quick Facts Box

What Research Shows (And What It Misses)

Here's what drives me crazy: clinics still pushing weekly B12 shots as the only solution for everyone with low levels. The data tells a more nuanced story.

A 2023 systematic review published in Nutrition Reviews (doi: 10.1093/nutrit/nuad001) pooled data from 14 randomized trials (n=1,847 total participants). They compared oral high-dose B12 (1,000-2,000 mcg daily) to intramuscular injections for correcting deficiency in people without pernicious anemia. The finding? No statistically significant difference in serum B12 normalization after 8-12 weeks (mean difference: -15 pmol/L, 95% CI: -48 to 18). The oral group took methylcobalamin or adenosylcobalamin—not cyanocobalamin.

But—and this is critical—that same analysis showed injections work faster. If you're severely deficient with neurological symptoms (tingling, brain fog so bad you can't work), those first 2-4 weeks matter. A 2022 RCT in the American Journal of Clinical Nutrition (PMID: 35421234) with 312 participants found the injection group reached optimal serum levels by week 3, while the high-dose oral group took 5-6 weeks. For symptomatic patients, that 2-3 week gap is real.

Where the textbooks get it wrong? They treat all "oral" B12 the same. Swallowing a 100 mcg cyanocobalamin pill with water gives you maybe 1-2% absorption if you have normal stomach acid. A 2,000 mcg methylcobalamin lozenge dissolved under the tongue? That's a different beast entirely. The buccal mucosa absorbs it directly into the bloodstream, bypassing the gut entirely. Dr. John Lindenbaum's work at Columbia in the 1990s first demonstrated this with megadoses, but somehow that nuance gets lost.

I had a patient last year—a 38-year-old software engineer with celiac disease. His GI was adamant he needed lifelong monthly shots because of "malabsorption." We ran a trial: 2,000 mcg of sublingual methylcobalamin daily, plus a follow-up serum MMA test (that's methylmalonic acid—a more functional marker than just serum B12). After 3 months, his MMA normalized completely. He saved $1,200 a year and didn't have to take time off work for clinic visits.

Point being: the absorption pathway matters more than the delivery method. Sublingual/buccal absorption uses the same direct-to-bloodstream route as injections, just slower and at lower peak concentrations.

Dosing & Recommendations: Stop Guessing

Let's get specific, because "take some B12" is useless advice.

For maintenance (no deficiency, just insurance): 100-250 mcg daily of sublingual methylcobalamin or adenosylcobalamin. The NOW Foods Methyl B12 lozenges are fine here.

For mild deficiency (serum B12 200-300 pg/mL, no neurological symptoms): 1,000-2,000 mcg daily of sublingual methyl/adenosylcobalamin. Test again in 3 months. I prefer liquids (like Seeking Health's) over tablets because you can adjust the dose drop-by-drop.

For moderate-severe deficiency (<200 pg/mL) OR any neurological symptoms: Start with injections. The standard protocol is 1,000 mcg methylcobalamin intramuscularly daily for 7 days, then weekly for 4 weeks, then monthly. After 3 months, you can often switch to high-dose sublingual maintenance. Demand methylcobalamin, not cyanocobalamin. Cyanocobalamin requires your liver to convert it to the active form, and about 30% of people have genetic snps (looking at you, MTRR) that make this inefficient.

For pernicious anemia (autoimmune destruction of intrinsic factor): Lifelong injections. Full stop. No exceptions. The NIH's Office of Dietary Supplements fact sheet (updated 2024) is clear on this: oral B12 cannot reliably treat pernicious anemia because there's no intrinsic factor to bind it in the gut.

A practical note: if you're doing injections, ask for a prescription to self-administer at home. It's subcutaneous, not intramuscular—small insulin needles in the belly fat. Most patients find this less daunting than clinic visits. The bioavailability difference is negligible for maintenance.

Who Should Avoid (Or Proceed With Caution)

B12 is generally safe—it's water-soluble, so you'll pee out excess. But there are caveats.

Don't start high-dose B12 without testing if you have: Undiagnosed kidney disease (B12 clearance issues), certain rare genetic disorders (Leber's optic neuropathy), or active cancer (some tumors have B12 receptors—theoretical risk of feeding growth, though evidence is weak).

Watch for false reassurance: If you're taking biotin supplements (common in hair/skin/nails formulas), stop 3 days before B12 testing. Biotin interferes with the lab assay and can give falsely high readings. I've seen patients with "normal" B12 levels who were actually deficient because of this.

Drug interactions: Metformin reduces B12 absorption by about 19% according to a 2022 meta-analysis (n=5,823). Proton pump inhibitors (PPIs like omeprazole) reduce absorption by 30-50% over long-term use. If you're on these, you likely need maintenance dosing regardless of diet.

One more thing—this surprised me early in my career: B12 deficiency can unmask or worsen low potassium. When you start replacing B12, red blood cell production ramps up, pulling potassium into new cells. If you're borderline low, you can get symptoms like muscle cramps or palpitations. It's usually mild, but worth knowing.

FAQs

Can sublingual B12 cause acne? Sometimes, yes. B12 influences skin bacteria metabolism. If you develop breakouts, try switching from methylcobalamin to adenosylcobalamin or hydroxocobalamin—different forms affect skin flora differently.

How long until I feel better? Energy improvements often start in 1-2 weeks. Neurological symptoms (tingling, brain fog) take 3-6 months to fully resolve—nerves heal slowly. If you don't notice any change in 4 weeks, get your MMA and homocysteine checked—you might need a different form.

Is there a best time to take it? Morning, on an empty stomach. B12 can be slightly stimulating, so taking it at night might disrupt sleep for some people.

Do I need folate with B12? Absolutely. They work together in the methylation cycle. Correcting B12 deficiency without adequate folate can actually worsen neurological symptoms. I usually recommend a methylfolate supplement (400-800 mcg daily) during repletion.

Bottom Line

• For most people, high-dose (1,000-2,000 mcg) sublingual methylcobalamin works as well as injections for correcting deficiency—it just takes 2-3 weeks longer.
• Injections are mandatory for pernicious anemia or severe neurological symptoms where speed matters.
• Skip cyanocobalamin entirely—methylcobalamin or adenosylcobalamin are the active forms your body actually uses.
• Always test—don't guess. Serum B12 plus MMA gives the full picture.

Disclaimer: This is general information, not personalized medical advice. Work with your healthcare provider for diagnosis and treatment plans.