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Vitamin B12

Vitamin B12 is a vitamin, not a peptide — a cobalt-containing molecule your body needs to make red blood cells and keep nerves working. It is one of the few injectables in this catalog with an actual FDA label: Cyanocobalamin Injection, USP, 1,000 mcg/mL, approved for B12 deficiency caused by poor absorption (pernicious anemia, stomach or bowel surgery, and similar).

Methylcobalamin, the form one certified vendor line contains (the other line does not state its form), has no FDA-approved injectable in the US; any methylcobalamin shot is compounded or unapproved and carries no reviewed dose, warnings, or safety data.

The label regimen is small — 100 mcg daily for 6–7 days, stepping down to 100 mcg once a month for life — and it is written for people with a diagnosed deficiency, not for healthy people. For people whose B12 is already normal, there is no trial evidence that injections improve energy, fatigue, mood, or weight.

Best for

Adults with a documented low B12 and a reason they cannot absorb it from food or tablets — that is what the label covers.

The evidence points to three groups worth testing before anything else: long-term metformin users (a randomized trial found metformin lowered B12 by about 19% over 4.3 years and raised the risk of deficiency by 7 percentage points; a 13-year US study found low or borderline B12 in about one in five long-term metformin users, against roughly one in six on placebo, with the odds of deficiency rising about 13% for each year of use), long-term users of acid-suppressing drugs (two or more years of proton-pump inhibitors carried 65% higher odds of deficiency in a 210,000-person study), and vegans who do not take a B12 supplement (adult vegetarian surveys range from 0 to 86.5% deficient, with the highest rates in unsupplemented vegans; unsupplemented Czech vegans had 4.4 times the odds of low B12 versus supplementing vegans, who matched non-vegans).

Where trials exist (metformin users, vegans), oral supplementation is what was studied and it raised levels; for acid-suppressant users the documented step is a blood test. Injections are for people who cannot absorb oral B12.

If your B12 is normal, the strongest review available — 16 randomized trials, 6,276 people without overt deficiency — found no effect on cognition or mood and could not even analyze fatigue because only one trial measured it. That is the honest answer to the 'energy shot' idea: not supported.

What to expect

After an intramuscular injection the plasma level peaks within one hour (label), but most of a 100–1,000 mcg dose — 50 to 98% — leaves in the urine within 48 hours, the bulk of it in the first eight hours; what stays is what counts.

In people with true deficiency, the blood-count and nerve-symptom correction in the 1998 oral-versus-injection trial was described as prompt and indistinguishable between routes. In people with only a mildly raised deficiency marker and no diagnosis, a 140-person placebo-controlled trial found B12 fixed the lab numbers but symptom scores for anemia, nerve and gut complaints were no different from placebo at three months.

No trial was found that measures an 'energy' onset in people with normal B12, so none is stated.

Pairs with

Nothing on an evidence basis. Two things to know: folic acid is not a substitute — the label warns that folic acid above 0.1 mg a day can make the blood count look better while nerve damage from untreated B12 deficiency keeps going, and that B12 given blindly can mask a folate problem, so test both before starting.

Lipotropic 'Lipo-B' shots are labeled by their vendors with roughly 1 mg of cyanocobalamin per mL (vendor labeling); running both is double-counting the same vitamin. Chloramphenicol may blunt the anemia response (per the cyanocobalamin nasal-spray label).

If you take metformin or a long-term acid suppressant, the relevant pairing is a blood test, not another injection.

Research protocol

Every number here comes from the FDA label for cyanocobalamin injection, and the label is written for diagnosed deficiency due to malabsorption — not for healthy users.

Avoid the intravenous route: the label says nearly all of an IV dose is lost in the urine. Vendor labeling, not evidence: vendor vials sold under the 'B12' name differ ten-fold. One product line is labeled 10 mg total per vial with no stated concentration or fill volume; another is labeled methylcobalamin 10 mg/mL in a 10 mL vial (100 mg total) — ten times the strength of the FDA product. A '1 mL' habit carried over from a lipotropic shot or the USP product would deliver 10 mg from the stronger vial, ten times the label ceiling. Read your vial's concentration before you draw, and dose in micrograms.

Label regimen for pernicious anemia: 100 mcg once daily by intramuscular or deep subcutaneous injection for 6–7 days. If blood counts respond, the same 100 mcg every other day for seven doses, then every 3–4 days for another 2–3 weeks, then 100 mcg once a month for life.

The label says to check serum potassium closely during the first 48 hours, and to get a blood count, B12, folate and iron levels before starting. For people who absorb normally but need a stronger start, the label allows a similar initiation and then says long-term treatment should be oral tablets.

Hydroxocobalamin has its own FDA label: 30 mcg intramuscular daily for 5–10 days, then 100–200 mcg once a month; its label allows the intramuscular route only, not subcutaneous.

The largest single dose the label names anywhere is 1,000 mcg (1 mg) — one full mL of the USP product — and that is the flushing dose for a diagnostic test, not a treatment dose. Weekly or monthly 1,000 mcg schedules, and any milligram-scale dose, are not on the label.

In the randomized trials that compared routes, 2 mg oral daily matched a 1 mg intramuscular schedule tapering to monthly for correcting blood counts and nerve findings (a 1998 trial of 38 patients; Cochrane 2018, three trials, low-quality evidence). In a 2020 trial of 283 adults aged 65 and over, 1 mg oral daily matched injections at 8 weeks, but after switching to 1 mg oral weekly, fewer stayed normal at one year (74% versus 80% on monthly injections); 83% still preferred tablets.

Cycling has no rationale here: the label's maintenance phase is monthly for life, and the vitamin is stored in the liver. These are starting points from the label; the end goal is your own measured B12 and how you respond, checked with bloodwork rather than by feel.

Typical research dosing
Typical start100 mcgstart · FDA label dose (diagnosed deficiency)1,000 mcgceiling · largest single dose on the label
How often
As needed
When
Morning
Route
Intramuscular
Premixed
10 mg premixed in 10 mL = 1 mg/mL · 100 mcg = 10 units on a U-100 syringe
Cycle
The FDA label regimen for diagnosed deficiency steps DOWN in frequency, not up in dose: 100 mcg daily for 6–7 days, then every other day for 7 doses, then every 3–4 days for 2–3 weeks, then 100 mcg once a month for life. No cycling rationale exists — B12 is stored in the liver and the label's maintenance phase is lifelong monthly. The catalog has no 'monthly' cadence, so after the initiation phase set your own schedule from the label and from your measured B12, not by feel.
⚠ Research-compound safetyNOT A PEPTIDE — a cobalt-containing vitamin. The only labeled contraindication is sensitivity to cobalt or B12; do NOT use in early Leber's disease (hereditary optic nerve atrophy — swift optic atrophy reported). Anaphylactic shock and death have been reported after injected B12; a test dose is advised if sensitivity is suspected. When severe anemia is treated intensely, potassium can fall dangerously — the label requires potassium checks in the first 48 hours. Folic acid can hide B12 deficiency while nerve damage progresses, and B12 can hide folate deficiency: get B12, folate and a blood count BEFORE starting. Multi-dose vials contain benzyl alcohol (not for premature infants) and aluminum (caution with impaired kidneys). The energy-in-healthy-people and weight-loss uses are NOT supported by any trial. Long-term metformin and acid-suppressant use are documented reasons to test your level. Not prohibited in sport. Not medical advice — a measured B12 belongs before any injection.

The same numbers the goodtides app and the Dose Calc use — a research reference, not a prescription. Responses are individual; research protocols start at the low end.

How it works

Cyanocobalamin is a corrinoid: a ring built around a single cobalt atom (4.34% of the molecule by weight), formula C63H88CoN14O14P, molecular weight 1,355.39. It is a vitamin, not a chain of amino acids, so nothing about peptide storage, reconstitution, or degradation applies to it.

In the body B12 is a cofactor for two enzymes — one that recycles homocysteine to methionine (the methylation cycle) and one that handles methylmalonyl-CoA in energy metabolism — which is why the two lab markers of functional deficiency are homocysteine and methylmalonic acid, and why a British haematology guideline names methylmalonic acid as the second-line test when serum B12 is borderline. Absorbed B12 travels on carrier proteins (transcobalamin I and II) and the liver is the main storage organ.

All of the commercial forms — cyano-, hydroxo-, methyl- and adenosylcobalamin — ride the same carriers into cells, where a chaperone protein strips the attached group off (decyanation of cyanocobalamin, dealkylation of methylcobalamin) and the cell builds its own active coenzymes. A 2015 review concluded that supplementing the 'active' methyl or adenosyl forms is unlikely to be advantageous compared with cyanocobalamin; the 'bioidentical is better' claim traces to a 2017 review whose own results section says all supplemental forms are stripped to core cobalamin and likely have similar bioavailability for most people, yet whose conclusion favors the 'bioidentical' forms; its second author is listed as chief medical officer of a supplement company.

Hydroxocobalamin is a separate FDA-approved injectable (intramuscular only) whose label reports a smaller share lost in urine (16–66% over 72 hours) than cyanocobalamin's (50–98% over 48 hours), but those are two labels with different doses and windows, not a head-to-head trial; a 2024 cell-culture study found hydroxocobalamin is taken up and processed by cells about twice as fast, with similar total uptake. The claim that cyanocobalamin releases harmful cyanide appears on no label and in no verified source — decyanation is normal processing.

Pharmacokinetics
Half-life
NOT STATED on the FDA label, and published figures could not be verified. The cyanocobalamin label gives only the peak (within one hour after intramuscular injection) and the urinary loss (50–98% of a 100–1,000 mcg dose within 48 hours, most of it in the first eight). The classic 1950s–60s radiolabel studies of plasma and whole-body B12 turnover exist in PubMed as titles only, with no abstracts, so the plasma-days and body-stores-of-a-year figures circulating online could not be verified and are deliberately not printed. The only verifiable elimination figure at replacement-scale dosing is from a 20-man healthy-volunteer study of oral cyanocobalamin: an elimination rate constant of 0.025–0.028 per hour, which works out to an apparent serum half-life of roughly 25–28 hours (the paper reports the rate constant, not a half-life, and its first author worked for the formulation's sponsor). For intravenous hydroxocobalamin at cyanide-antidote doses of 5–10 grams, the Cyanokit label reports a half-life of about 26–31 hours for total cobalamins — gram-scale IV numbers that do not describe a microgram shot. Practical reading: the vitamin is stored in the liver, which is why the label's maintenance dose is monthly.
Peak
Plasma level peaks within one hour after intramuscular injection (label). No subcutaneous peak time is published. Oral: about 6.8 hours to peak for a 5 mg tablet in healthy men (single small study).
Absorption
Intramuscular or deep subcutaneous injection: 'quantitatively and rapidly absorbed' (label) — the label gives no percentage. Intravenous: avoided, because almost all of the dose is excreted in urine with little chance of liver storage (label). Oral: gut absorption depends on intrinsic factor from the stomach and on calcium; without intrinsic factor about 1% of a swallowed dose crosses by simple diffusion, which the label calls adequate only at very large doses — the basis for high-dose oral treatment. Absorbed B12 is carried by transcobalamin I and II; the liver is the main storage organ (label). Hydroxocobalamin (intramuscular only): half the dose has left the injection site within 2.5 hours; it is bound to plasma proteins, stored in the liver and excreted in bile with some recycling (hydroxocobalamin label).
Bioavailability
Injection: complete uptake from the site, but 50–98% of a 100 or 1,000 mcg dose appears in the urine within 48 hours, the major portion within the first eight hours (label) — retention, not absorption, is the limiting number. Hydroxocobalamin label: 16–66% of a 500–1,000 mcg dose in urine within 72 hours, mostly in the first 24 hours (a different product and window, not a controlled comparison). Oral: about 1% by passive diffusion (label); a 5 mg cyanocobalamin tablet measured 2.16% absolute bioavailability against 1 mg IV in a 20-man study (six men on the tablet, four on IV; first author employed by the formulation's sponsor). In a 4,281-person retrospective study, sublingual B12 raised serum levels at least as much as intramuscular (mean rise 252 vs 218 ng/L), though doses were not stated and it was not randomized.
References35
  1. Cyanocobalamin Injection, USP 1,000 mcg/mL — FDA prescribing information (DailyMed, ANDA080515)FDA label · 2023
  2. Cyanocobalamin Injection, USP 1,000 mcg/mL — FDA prescribing information (DailyMed, current revision)FDA label · 2026
  3. Hydroxocobalamin Injection, USP 1,000 mcg/mL — FDA prescribing information (DailyMed, ANDA085998)FDA label · 2017
  4. Nascobal (cyanocobalamin) nasal spray — FDA prescribing information (DailyMed; chloramphenicol interaction, Leber's, polycythemia vera)FDA label · 2024
  5. Cyanokit (hydroxocobalamin) for injection — FDA prescribing information (DailyMed; gram-dose IV half-life only)FDA label · 2023
  6. Cyanocobalamin — PubChem compound record CID 5311498PubChem · 2026
  7. Methylcobalamin — PubChem compound record CID 10898559PubChem · 2026
  8. Markun S et al. Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression (Nutrients; 16 RCTs, 6,276 people without overt deficiency)PubMed · 2021
  9. Hvas AM et al. Vitamin B12 treatment normalizes metabolic markers but has limited clinical effect: a randomized placebo-controlled study (Clin Chem; n=140)PubMed · 2001
  10. Wang H et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency (Cochrane Database Syst Rev; 3 RCTs, 153 participants)PubMed · 2018
  11. Kuzminski AM et al. Effective treatment of cobalamin deficiency with oral cobalamin (Blood; n=38 randomized)PubMed · 1998
  12. Sanz-Cuesta T et al. Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care: a pragmatic, randomised, non-inferiority clinical trial (OB12) (BMJ Open; n=283, age 65+)PubMed · 2020
  13. Bensky MJ et al. Comparison of sublingual vs. intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency (Drug Deliv Transl Res; retrospective, n=4,281)PubMed · 2019
  14. Castelli MC et al. Pharmacokinetics of oral cyanocobalamin formulated with sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC): an open-label, randomized, single-dose, parallel-group study in healthy male subjects (Clin Ther; n=20 across four arms, sponsor-affiliated author)PubMed · 2011
  15. Obeid R et al. Cobalamin coenzyme forms are not likely to be superior to cyano- and hydroxyl-cobalamin in prevention or treatment of cobalamin deficiency (Mol Nutr Food Res; review)PubMed · 2015
  16. Paul C, Brady DM. Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms (Integr Med (Encinitas); narrative review — conclusion favoring coenzyme forms not supported by its own results; author employed by a supplement company)PubMed · 2017
  17. Fedosov SN et al. Kinetics of Cellular Cobalamin Uptake and Conversion: Comparison of Aquo/Hydroxocobalamin to Cyanocobalamin (Nutrients; HeLa cell culture, not human)PubMed · 2024
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  20. Lam JR et al. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency (JAMA; case-control, n=210,155)PubMed · 2013
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This page is educational reference material about compounds studied in research settings. It is not medical advice, and nothing here is a recommendation to buy, possess, or use any compound. Research findings described are from published literature; individual compounds may not be approved for human use. Talk to a licensed clinician about anything that affects your health.