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Lexicon
Lexicon

B12

High-dose vitamin B12 to support energy metabolism and cognitive function in research contexts.

2 min read 9 sources

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B12 vial with red solution, blue cap and the black TPD label on a white podium, next to a large blue 3D molecule model in a bright lab
Compound approved · as a medicine for B12 deficiency

Summary

At a glance

Sources checked on 26 Oct 2026

Need B12 as a helper
2 enzymes

Methylmalonyl-CoA mutase in the mitochondria and methionine synthase in the methionine cycle2

Deficiency without symptoms
≤26 %

2.5 to 26 percent of the population depending on the definition, mostly older adults1

Tablet versus injection
3 trials

153 participants with B12 deficiency, similar blood levels, low certainty4

B12 on metformin
−19 %

versus placebo after about 4 years, 390 people with type 2 diabetes5

  • Vitamin B12 (cobalamin) is a water-soluble vitamin. The body needs it as a helper for two enzymes: one in the energy metabolism of the mitochondria, one in the methionine cycle, which breaks down homocysteine and supplies methyl groups.2
  • A clear deficiency with anaemia and nerve damage is uncommon. A deficiency without symptoms affects 2.5 to 26 percent of the population depending on the definition, mostly older adults.1
  • Injected or swallowed: in a randomised trial a high daily amount as a tablet raised B12 levels after 4 months even more than injections into the muscle. A Cochrane review sees both routes as similar, but the evidence is small.34
  • Metformin lowered B12 levels by 19 percent versus placebo in a long-term trial. Extra B12 lowered homocysteine by a further 7 percent in a meta-analysis.56
  • Cyanocobalamin is approved as a medicine for B12 deficiency. For people without a deficiency these sources give no evidence of more energy. Everything here is the state of research, not a recommendation.91
Profile

Updated June 2026

How long does it stay in the body?

Share left after one dose, calculated with a half-life of ~6 days

Half-life ~6 days
After 12 days: 25 %
Day 6 · 50 %Day 12 · 25 %Day 18 · 12.5 %Day 30 · 3.1 %

Simplified model without an absorption phase, half-life from the TPD lexicon.

Class
Water-soluble vitamin

Cobalamin

Use
Energy metabolism

neurological function

Half-life
~6 days

B12 binds to transcobalamin

Status
Essential vitamin

non-prescription

Sizes
2 sizes

10ml/1mg/ml, 10ml/10mg/ml

Contents 12 sections
  1. At a glance
  2. What is B12?
  3. How it works
  4. Application and dosing
  5. What the research shows
  6. Research status
  7. Side effects
  8. Storage
  9. Related compounds
  10. FAQ
  11. Glossary
  12. Sources

What is B12?

Vitamin B12 (Cyanocobalamin) is an essential water-soluble vitamin that plays a central role in DNA synthesis, myelin formation and energy metabolism. In research contexts, high-dose B12 is provided in two concentrations: 1mg/ml and 10mg/ml for various research designs.

B12 occurs naturally only from bacteria and archaea. It must be obtained through diet or supplementation.

This information is for research and educational purposes only. No medical advice.

Comparison

B12 and related entries

B12 alone and in blends, as stated in the TPD lexicon. Tap a card to open its entry.

Vitamin as an injection B12 Methionine synthase
Blend with B12 Lipo-B 216mg Methionine synthase Blend with B12 Lipo-C 120mg Methionine synthase Different coenzyme NAD+ Inject

Simplified: the blends contain B12 next to other substances. The studies here concern B12 alone. 2

How it works

B12 functions as a cofactor for two main enzymes:

  • Methylmalonyl-CoA mutase: catalyzes conversion of methylmalonyl-CoA to succinyl-CoA in energy metabolism
  • Methionine synthase: catalyzes methylation of homocysteine to methionine, essential for DNA synthesis and nerve function

These functions make B12 essential for cell division, neural myelination and homocysteine metabolism.

Where it acts

Where the body needs B12

Tap a point or a card. Colour = enzyme, grey = finding from studies and reviews.

  1. Blood and blood formation

    Without B12 the DNA synthesis of new blood cells stalls, typically an anaemia with large cells1

    Methionine synthase
  2. Nerves and brain

    Deficiency can damage nerves, neurological findings improved with injection and tablet alike3

    Observed in trials
  3. Gut

    Poor absorption is a main cause of deficiency, metformin lowered the level by 19 percent5

    Observed in trials
  4. Cells and mitochondria

    Methylmalonyl-CoA mutase breaks down certain amino acids for energy in the mitochondria2

    Observed in trials

Known targets2

Compound CHEMBL2110563: one described target, Helper (cofactor) as methylcobalamin, converts homocysteine into methionine.

Methionine synthase
Gene
MTR
UniProt
Q99707
ChEMBL
CHEMBL2150844
Action
Helper (cofactor) as methylcobalamin, converts homocysteine into methionine
Blue 3D molecules on a translucent blue nerve fibre with its sheath and inside a glass mitochondrion
B12 is needed in nerves and in the mitochondria. Symbolic image.

Application and dosing

Dosing

Dosing, titration and syringe

Loading the dosing information …

  • Getting started and stepping up, drawn as a staircase
  • Units on the U-100 syringe for every step
  • How long one vial lasts

What the research shows

Extensive literature supports B12's role in energy metabolism and neurological function. Injected B12 is used in studies examining:

  • Metabolism and mitochondrial energy production
  • Neural myelination and cognitive function
  • Homocysteine level regulation
  • Blood formation support and erythrocyte proliferation

Research shows B12 deficiency is associated with cognitive problems, polyneuropathy and megaloblastic anemia.

Study results

What the trials measured

Interactive: switch tabs, tap points, show or hide arms. Arms are named relative to each other, no dosing advice.

B12 in the blood before and after 4 months3

Mean values in pg/ml, 33 evaluable people with B12 deficiency, normal range 200 to 900

Before3
Injection into the muscle 95 pg/ml
Tablet, high daily amount 93 pg/ml
After 4 months3
Injection into the muscle 325 pg/ml
Tablet, high daily amount 1,005 pg/ml

Blood count and nerve findings improved equally fast in both groups. Injections were given several times a week at first and monthly later, the tablet daily in a high amount. A small study.

Homocysteine in the blood before and after 4 months3

Mean values in µmol/l, same study, normal range 5.1 to 13.9

Before3
Injection into the muscle 40.0 µmol/l
Tablet, high daily amount 37.2 µmol/l
After 4 months3
Injection into the muscle 12.2 µmol/l
Tablet, high daily amount 10.6 µmol/l

Homocysteine rises in B12 deficiency because methionine synthase stalls without B12. In both groups it fell into the normal range.

What metformin changed over more than 4 years5

Change versus placebo in percent, 390 people with type 2 diabetes on insulin

Vitamin B125
Placebo 0%
Metformin -19%
Folate5
Placebo 0%
Metformin -5%
Homocysteine5
Placebo 0%
Metformin +5%

The risk of a true B12 deficiency was 7.2 percentage points higher than on placebo at the end. The rise in homocysteine was not statistically certain.

Loss of daily function in early ALS7

Change in the ALSFRS-R function score after 16 weeks, 130 participants, injections into the muscle

ALSFRS-R after 16 weeks7
Placebo -4.63%
Methylcobalamin, very high amount -2.66%

Methylcobalamin is a different form of B12 from the cyanocobalamin in the vial, given in a very high amount. The decline was 1.97 points smaller than on placebo, side effects occurred about as often.

Stacked red blood cells in a bright lab, surrounded by glowing red arcs of light
Without B12 blood formation stalls. Symbolic image.

Research status

Where the research stands

A selection of registered trials with vitamin B12 as an injection or tablet. Besides cyanocobalamin some trials test other forms (methylcobalamin, hydroxocobalamin), as noted for each. As of 26 Oct 2026. 8

  1. Preclinical Biochemistry: helper of two enzymes
  2. Phase 1 no registered trial
  3. Phase 2 no registered trial
  4. Phase 3 4 trials, 2 completed
  5. Approval as a medicine for B12 deficiency
1,530 participants in phase 3 Planned figures for running trials Cyanocobalamin is approved as a medicine, ChEMBL lists it at the highest stage 4, for example in anaemia. The trials test B12 in further situations.9
Show all 7 phase 3 and 4 trials on a timelineHide timeline 5 completed 2 running 1 with results
Phase 3
Phase 4

Bar: start to primary endpoint (planned for running trials). Green = completed, blue = progress until 26 Oct 2026.

Side effects

  • Very rare: Local irritation or pain at injection site
  • Hypersensitivity reactions: Extremely rare; anaphylactic reactions to cyanocobalamin are documented but exceptionally rare
  • Systemic: Headache, nervousness, rapid pulse (rare, possibly placebo effect or expected stimulation response)
  • Long-term data: B12 is generally considered very safe in high-dose forms as excess is excreted

Storage

Store cool and dry, protected from light (ideally 2-8°C). Keep vial in original carton. Use within 4 weeks of opening. Do not freeze. Visually inspect for cloudiness or discoloration after opening; B12 should be clear and colorless.

Related

Related compounds

Blends with B12 or a different path: all in the TPD lexicon.

B12
Lipo-B 216mg Contains B12 next to other B vitamins Lipo-C 120mg Contains B12 plus methionine, inositol and choline Lipo-C FAT BLASTER Contains B12 and L-carnitine Metformin (Glucophage) Can lower B12 levels over time NAD+ Inject Different coenzyme in energy metabolism L-Carnitine Another substance from energy metabolism Vitamin D3 Another vitamin in the lexicon

FAQ

Common questions about B12

Short answers, each backed by the sources below.

What does the body need B12 for?

B12 is a helper for two enzymes. Methylmalonyl-CoA mutase breaks down certain amino acids in the mitochondria. Methionine synthase converts homocysteine into methionine, from which the cell's most important methyl donor is made. This affects DNA synthesis, blood formation and nerves.21

Is an injection better than a tablet?

Not necessarily. In a trial with 33 evaluable people with deficiency the B12 level after 4 months was 1,005 pg/ml with a high daily tablet amount and 325 pg/ml with injections into the muscle. Blood count and nerves improved equally fast. A Cochrane review of 3 trials with 153 participants sees both routes as similar but rates the evidence as weak.34

Who is more often low in B12?

According to a review mainly older adults, plus people who eat few animal foods and anyone with impaired absorption. In a trial over more than 4 years metformin lowered B12 by 19 percent versus placebo, the risk of deficiency rose by 7.2 percentage points.15

What does B12 have to do with homocysteine?

Without B12 the breakdown of homocysteine stalls and the blood level rises. In a meta-analysis of 1,114 people folic acid lowered homocysteine by 25 percent, extra B12 by a further 7 percent. Whether lower homocysteine also protects the heart and vessels is not answered by this work.62

Does B12 give more energy without a deficiency?

The sources here give no evidence for that. The studies concern people with deficiency or specific diseases. In early ALS methylcobalamin, a different B12 form in a very high amount, slowed the loss of function over 16 weeks by 1.97 points versus placebo. That cannot be transferred to healthy people.17

Which side effects are known?

Hardly any in the comparison trials: one trial saw no treatment-related side effects, in another 2 of 30 people on tablets stopped because of side effects. The quality of these data is very low. In the ALS trial side effects occurred about as often on methylcobalamin as on placebo.47

Glossary

Terms explained briefly

Dotted words in the text open these explanations directly.

Cobalamin
Collective name for vitamin B12 and its forms such as cyanocobalamin, methylcobalamin or hydroxocobalamin. A cobalt atom sits at its centre.
Cochrane review
A systematic analysis of all suitable studies on one question under the strict rules of the Cochrane organisation.
Cofactor
A small molecule an enzyme needs in order to work. B12 is the cofactor for two enzymes.
Homocysteine
An intermediate in metabolism. It rises in the blood with a lack of B12 or folate and therefore serves as a marker.
Intramuscular
Injected into the muscle, as opposed to subcutaneous, under the skin.
Megaloblastic anaemia
Anaemia with oversized, immature red blood cells, typical of B12 or folate deficiency.
Methionine synthase
An enzyme that converts homocysteine into the amino acid methionine with the help of B12 and folate.
Methylmalonic acid
A build-up product when methylmalonyl-CoA mutase cannot work without B12. Regarded as a sensitive marker of B12 deficiency.
Mitochondria
The power plants of the cell, where much of its energy is produced.
Myelin
A fatty sheath around nerve fibres that makes signals travel faster. It can be damaged in B12 deficiency.

Evidence

Sources

Show all 9 sourcesHide sources 7 Studies1 Trial registry1 Database checked 26 Oct 2026

Studies

  1. Review of B12 deficiency: causes, markers, supplementation

    Green et al., Nature Reviews Disease Primers, 2017

    DOI 10.1038/nrdp.2017.40 PMID 28660890
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  2. B12, folate and the methionine cycle (review)

    Froese et al., Journal of Inherited Metabolic Disease, 2019

    DOI 10.1002/jimd.12009 PMID 30693532
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  3. B12 tablet versus injection in deficiency, randomised

    Kuzminski et al., Blood, 1998

    DOI 10.1182/blood.V92.4.1191 PMID 9694707
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  4. Cochrane review: B12 swallowed or injected into the muscle

    Wang et al., Cochrane Database of Systematic Reviews, 2018

    DOI 10.1002/14651858.CD004655.pub3 PMID 29543316
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  5. Metformin over more than 4 years and B12 levels

    de Jager et al., BMJ, 2010

    DOI 10.1136/bmj.c2181 PMID 20488910 NCT00375388
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  6. Lowering homocysteine with folic acid and B vitamins, meta-analysis

    Homocysteine Lowering Trialists' Collaboration, BMJ, 1998

    DOI 10.1136/bmj.316.7135.894 PMID 9569395
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  7. JETALS: very high dose methylcobalamin in early ALS

    Oki et al., JAMA Neurology, 2022

    DOI 10.1001/jamaneurol.2022.0901 PMID 35532908 NCT03548311
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed

Trial registry

  1. Trials with B12 on ClinicalTrials.gov

    ClinicalTrials.gov, U.S. National Library of Medicine

    Checked 26 Oct 2026 via ClinicalTrials.gov API v2

Database

  1. Cyanocobalamin in ChEMBL (approved)

    ChEMBL, EMBL-EBI (CHEMBL2110563)

    Checked 26 Oct 2026 via ChEMBL

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B12 in the catalog

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