Vitamin B12

What It Does

Absorption takes several steps. Gastric acid and pepsin free B12 from food protein; it binds haptocorrin, then intrinsic factor secreted by gastric parietal cells, and the complex is absorbed in the terminal ileum. The intrinsic factor route saturates at about 1.5-2 mcg per meal. Independently, about 1% of any dose crosses the gut by passive diffusion, which is why large oral doses work even without intrinsic factor (Berlin 1968). A Cochrane review found 1,000-2,000 mcg daily by mouth about as effective as intramuscular injection at normalizing B12 levels, on low-quality evidence from three small trials (Wang 2018).

Diagnosis is where most errors happen. Serum B12 measures total cobalamin, much of it bound to haptocorrin and unavailable to cells. Values in the low-normal range, roughly 200-350 pg/mL, do not exclude deficiency. Methylmalonic acid and homocysteine rise when cells are short of B12; methylmalonic acid is the more specific of the two, though kidney disease raises it independently (Stabler 2013).

The populations at risk are defined by the absorption pathway. Older adults with atrophic gastritis lose acid and pepsin. Pernicious anemia destroys parietal cells and intrinsic factor. Gastrectomy, gastric bypass, ileal resection, and Crohn's disease of the ileum interrupt it mechanically. Metformin users had more low B12 after five years in the Diabetes Prevention Program, with risk rising each year of use (Aroda 2016), and two or more years of proton pump inhibitor use was associated with a 65% higher odds of deficiency (Lam 2013). Vegans have no reliable food source. Nitrous oxide, including recreational use, oxidizes cobalamin and can precipitate myelopathy in someone with marginal stores.

Forms and Bioavailability

Absorption ratings are broad tiers. Head-to-head human trials rarely support a finer ranking among well-absorbed forms.

Labels column: number of labels named as vitamin B12 products that list this form. A product can list more than one form, and some labels do not state a form at all.

Cyanocobalamin is synthetic, stable, cheap, and the form used in most trials, including the oral-versus-injection studies. The cyanide it releases is about 20 mcg per 1,000 mcg dose, trivial next to dietary sources. Methylcobalamin is sold as the "active" form, but cells strip the upper ligand from every cobalamin on uptake and rebuild both methylcobalamin and adenosylcobalamin from the same intermediate. The form you swallow matters less than the dose. Methylcobalamin is also less stable to light.

Hydroxocobalamin is the injectable standard in much of the world because it binds plasma proteins more tightly and is retained longer than cyanocobalamin. Adenosylcobalamin has little oral data. Sublingual tablets produce serum levels similar to swallowed tablets; they work, but not because of any special mucosal route.

Typical Dosing

Adults over 50 are advised to meet the RDA mainly from fortified foods or supplements. Oral doses of 1,000-2,000 mcg daily can correct deficiency even without intrinsic factor.

Food sources: clams, beef liver, fortified nutritional yeast, fortified breakfast cereals, trout, salmon, tuna, milk, eggs.

What to Look For

The panel lists B12 in micrograms. The RDA is 2.4 mcg, but the right supplemental dose depends on why you are taking it. For someone with intact absorption on a vegan diet, a daily 25-100 mcg or a weekly 1,000-2,000 mcg is enough. For older adults, metformin or PPI users, and anyone with known malabsorption, 500-1,000 mcg daily relies on passive diffusion and makes intrinsic factor irrelevant. Diagnosed deficiency with neurologic signs should be treated under a clinician, often starting with injections.

High serum B12 in someone who is not supplementing is itself a finding worth explaining; liver disease and myeloproliferative disorders can raise it.

Red flags: B12 "energy" shots sold to people with normal levels, and expensive multi-form blends sold as superior to cyanocobalamin. Green flags: a single named form, mcg per dose stated plainly, and third-party testing.

Products on Titrate

27,513 of the 214,745 labels in the NIH Dietary Supplement Label Database list vitamin B12 as an active ingredient (14,100 on market). 1,903 are sold as vitamin B12 products by name.

Top on-market labels, ranked by label completeness and simplicity:

1. B-12 / Methyl Folate 1000 mcg/800 mcg Vital Nutrients · 1 mg as methylcobalamin
2. B12 Folate Pure Encapsulations · 800 mcg as methylcobalamin
3. Intrinsi B12-Folate Metagenics · 500 mcg as methylcobalamin
4. Intrinsi B12-Folate Metagenics · 500 mcg as methylcobalamin
5. 5-MTHF Plus B12 Natural Cherry Flavor XYMOGEN · 2.5 mg as methylcobalamin

Search B-complex supplements

Supplement Search loads one category at a time. Choose the B-Complex tab, then type a form such as "cyanocobalamin" under Must contain, or a form to avoid under Must not contain.

Related Tools

• B-Vitamin Form Guide
• Methylation Load Estimator
• Drug-Nutrient Depletion Checker
• Cyanocobalamin vs Hydroxocobalamin
• Cyanocobalamin vs Methylcobalamin
• Hydroxocobalamin vs Methylcobalamin
• Adenosylcobalamin vs Cyanocobalamin
• Adenosylcobalamin vs Hydroxocobalamin
• Adenosylcobalamin vs Methylcobalamin
• All vitamin B12 form comparisons
• Best B-Complex Without Cyanocobalamin
• All supplement guides

References

NIH Office of Dietary Supplements. Vitamin B12: Fact Sheet for Health Professionals.

Berlin H, Berlin R, Brante G. Oral treatment of pernicious anemia with high doses of vitamin B12 without intrinsic factor. Acta Med Scand. 1968;184(4):247-258.

Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160.

Lam JR, et al. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442.

Aroda VR, et al. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101(4):1754-1761.

Wang H, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev. 2018;3(3):CD004655.