Vitamin B12: what the studies show, status and safety
Summary
Vitamin B12 is not a peptide. It is an essential vitamin built around a cobalt atom, and it appears in this register because it is sold alongside weight-loss injections, often mixed into them. Its one proven use is treating and preventing a deficiency, including the one that long-term metformin can cause. In people without a deficiency, trials with more than 71,000 participants found no benefit for the heart, and pooled data on 22,000 people found none for memory and thinking. Injections need a prescription in the United States, Switzerland and the United Kingdom, but not in Germany.
Key findings at a glance
- It is here because of the weight-loss trade. The American medicines regulator names semaglutide combined with cyanocobalamin as its example of a compounded mix that may count as a copy of an approved drug [1].
- Mixed with tirzepatide, it formed a new impurity. The maker of approved tirzepatide found an unknown reaction product in compounded tirzepatide-B12 products in 2026 [2].
- In a deficiency, tablets and injections raised blood levels about equally. A Cochrane review covered three trials in 153 people; the evidence was of low quality [3].
- Metformin lowers B12. In a randomised trial of 390 people with type 2 diabetes, B12 fell 19 per cent against placebo over 4.3 years [4].
- No protection for the heart. A Cochrane review of 15 trials with 71,422 participants found no difference in heart attacks (relative risk 1.02) or deaths (1.01) [5].
- No protection for the ageing brain. Pooled data from 11 trials with about 22,000 people showed no effect on memory and thinking, although homocysteine fell by 26 to 28 per cent [6].
- A safety signal at high supplement use. In a cohort of 77,118 adults, men with the highest intake from single B12 supplements had almost twice the risk of lung cancer [7].
What it is
Vitamin B12 is the common name for a family of cobalt-containing compounds called cobalamins. Each has a large ring holding a cobalt atom at its centre. There is no chain of amino acids, so it is not a peptide [8], [9].
Cyanocobalamin, with a cyanide group on the cobalt, is the stable synthetic form in most medicines. Hydroxo-, methyl- and adenosylcobalamin carry other groups [10], [11].
The body cannot make it. Uptake from the gut needs a carrier protein from the stomach called intrinsic factor. Without it, only about 1 per cent (American label) or 1 to 3 per cent (German label) of an oral amount gets through [10], [9].
Why a vitamin appears in a peptide register. The reason is the market, not the molecule. In the weight-loss trade, cyanocobalamin is sold in three ways [1], [2], [12]:
- mixed into compounded semaglutide or tirzepatide;
- inside "lipotropic" injections with methionine and choline;
- as a stand-alone "energy" shot.
Quick facts
| Field | Value | Ref |
|---|---|---|
| Name | Vitamin B12; cyanocobalamin (international non-proprietary name) | [8] |
| Related forms | Hydroxocobalamin, methylcobalamin (mecobalamin), adenosylcobalamin (cobamamide) | [11], [13] |
| Class | Water-soluble vitamin; cobalt-containing corrinoid; not a peptide | [9] |
| Drug class | Anti-anaemic agent, ATC code B03BA01 | [9] |
| Formula and mass | C63H88CoN14O14P, 1355.4 g/mol; 4.34 per cent cobalt by weight | [8], [10] |
| Appearance | Dark red crystals or red powder; the active forms break down in light | [10] |
| Status | Prescription injection in the US, Switzerland and the UK; pharmacy-only in Germany; oral forms sold without prescription or as supplements | [14], [15], [16], [9] |
| First US approval | 1942, according to the nasal spray label | [17] |
| Example products | Cyanocobalamin Injection USP, many generics (US); NASCOBAL nasal spray (US); Vitaprompt injekt B12 (Germany); Vitarubin (Switzerland); Cobalin-H, hydroxocobalamin (UK); Neo-B12, hydroxocobalamin (Australia) | [10], [17], [9], [15], [18], [19] |
| Adequate intake, adults | 4 micrograms a day, as a European nutrition reference value | [20] |
| CAS registry number | 68-19-9 | [8] |
| UNII | P6YC3EG204 | [8] |
| PubChem CID | 166596686; an older record, 5311498, carries the DrugBank link | [8] |
| DrugBank, ChEMBL, ChEBI | DB00115, CHEMBL2110563, CHEBI:17439 | [8], [13] |
| InChIKey | RMRCNWBMXRMIRW-WZHZPDAFSA-L | [8] |
How it works
Vitamin B12 is a helper molecule (a cofactor) that two human enzymes cannot work without [9], [10].
- Recycling homocysteine. The methyl form serves methionine synthase, which turns homocysteine back into the amino acid methionine. This step is linked to folate and to the production of DNA [9].
- Clearing products of propionic acid. The adenosyl form serves methylmalonyl-CoA mutase, which converts them into succinic acid [9].
- Every form is rebuilt inside the cell. A 2015 review describes how a cell protein called MMACHC strips all forms down to the same intermediate, from which the two active forms are made [21].
- Deficiency hits blood and nerves. Without enough B12, red blood cells come out large and immature (megaloblastic anaemia). Nerves and the spinal cord can be permanently damaged [9], [10].
Unlike the peptides in this register, B12 does not act on a receptor. It fills a gap when one exists.
What the studies found
The evidence splits in two. Treating a deficiency is well established. Every benefit claimed beyond that was either tested in large trials and not found, or never tested.
Treating a deficiency
Cochrane review Three randomised trials compared tablets with injections in 153 people with a deficiency over three to four months. Two found no clinically relevant difference in blood levels; in the third, the oral group ended 680 pg/ml higher (95 per cent confidence interval 392.7 to 967.3). The evidence was of low quality, and no trial reported symptoms [3].
Randomised trial In 33 analysable patients, blood and nerve findings corrected "promptly and indistinguishably" with tablets or injections. After four months blood B12 averaged 1005 against 325 pg/ml (p < 0.0005) [22].
Metformin and B12
Randomised trial The HOME trial followed 390 people with type 2 diabetes on insulin for 4.3 years. Against placebo, metformin lowered B12 by 19 per cent (95 per cent confidence interval 14 to 24; p < 0.001) [4].
Deficiency was 7.2 percentage points more common at the end (2.3 to 12.1; p = 0.004) [4].
Randomised trial, long-term follow-up In the Diabetes Prevention Program, 1073 people with prediabetes took metformin and 1082 placebo. Low or borderline B12 affected 19.1 against 9.5 per cent at 5 years (p < 0.01) and 20.3 against 15.6 per cent at 13 years (p = 0.02) [23].
Diabetes Prevention Program and its follow-up study, 1073 people with prediabetes on metformin and 1082 on placebo; values at or below 298 pg/ml. Differences p < 0.01 at 5 years and p = 0.02 at 13 years. Source [23].
Each year of metformin raised the odds of deficiency by 13 per cent (odds ratio 1.13; 1.06 to 1.20) [23].
Weight-loss drugs and B12
Reviews A 2026 review of six studies and 480,825 adults on GLP-1 drugs reports that thiamine and B12 deficits increased over time. It gives no B12 figure and calls causation unproven [24].
A second review names earlier weight-loss surgery, gut disease, poor diet, older age and lasting vomiting as the main risks. A 2026 case report describes severe nerve damage in a woman on semaglutide with persistent vomiting and low B12, thiamine and folate [25], [26].
Heart and blood vessels: no benefit
B12 and folic acid lower homocysteine, which goes with heart disease. Lowering it did not prevent heart attacks.
- NORVIT, 3749 patients after a heart attack, median 40 months. Homocysteine fell 27 per cent, but the combined outcome did not change (relative risk 1.08; 0.93 to 1.25) [27].
- HOPE-2, 5522 people with vascular disease or diabetes, about five years. The main outcome hit 18.8 against 19.8 per cent (relative risk 0.95; 0.84 to 1.07) [28].
- SEARCH, 12,064 heart attack survivors, 6.7 years. Major vascular events hit 25.5 against 24.8 per cent (relative risk 1.04; 0.97 to 1.12) [29].
Cochrane review Fifteen trials with 71,422 participants found no difference in heart attacks (relative risk 1.02; 0.95 to 1.10) or deaths (1.01; 0.96 to 1.06). There was a small benefit for stroke (0.90; 0.82 to 0.99). B6, folic acid and B12 were often given together, so a pure B12 effect cannot be separated out [5].
Main heart outcome of NORVIT (3749 patients, median 40 months), HOPE-2 (5522 people, about 5 years) and SEARCH (12,064 people, 6.7 years), and heart attacks in the Cochrane review of 15 trials with 71,422 participants. None of the four differed significantly from placebo. Sources [27], [28], [29], [5].
Memory and thinking: no benefit
Meta-analysis Eleven trials with data on about 22,000 older adults lowered homocysteine by 26 to 28 per cent. There was no effect on any area of thinking or on overall cognition (difference in standard scores 0.00; −0.05 to 0.06) [6].
Randomised trial In 195 people aged 70 or over with a mild deficiency, B12 tablets for 24 weeks improved no area of thinking. Memory improved more with placebo (p = 0.0036) [30].
Randomised trial, brain scans only In VITACOG, 168 people over 70 with mild memory problems took folic acid, B6 and B12 or placebo for 24 months. Brain shrinkage was 0.76 against 1.08 per cent a year (p = 0.001). This is an indirect measure from a three-vitamin pill [31].
Energy, weight loss and performance: no trials
Small pilot trial, 1973 Twenty-eight people who complained of tiredness received hydroxocobalamin injections or placebo for two weeks each, in turn. Only the group given placebo first felt better in the second period (well-being p = 0.006). The result was never repeated [32].
No trials No randomised trial shows weight loss from B12 alone or from lipotropic B12 injections. A literature search for the latter returned one record, a 1984 study in bats. A non-exhaustive search found no trial on sports performance [33].
Methylcobalamin against cyanocobalamin
Reviews A 2015 review concludes that supplementing methyl- or adenosylcobalamin is "unlikely to be advantageous" compared with cyanocobalamin, because all forms follow the same route inside the cell [21].
A 2017 review still favours the natural forms, yet it too says that for most people all forms "may likely have similar bioavailabilities", meaning similar uptake. A search found no randomised trial comparing the two directly [34], [33].
Labels The Australian label says hydroxocobalamin gives higher, longer-lasting blood levels. The American label calls it "equally as effective as cyanocobalamin" [19], [10].
A different use: ALS in Japan
Phase 3 trial, manufacturer data In 130 people with early amyotrophic lateral sclerosis (ALS), a disease of the motor nerves, very high-dose mecobalamin injections differed from placebo by 2.0 points on a function scale after 16 weeks (p = 0.012). The result led to a Japanese approval and does not transfer to vitamin use [35].
What is still unknown
- Long-term safety of high-dose injections in people without a deficiency, as sold in wellness and weight-loss settings.
- How often GLP-1 drugs cause B12 deficiency [24], [25].
- What the impurity in tirzepatide-B12 mixes does in the body [2].
- Whether any form of B12 beats another in people [33].
Side effects and safety
Vitamin B12 has a wide safety margin. The German label reports no known overdose effects, and European experts set no upper intake limit because no harm had been observed. That means no threshold could be set, not that any amount is proven safe [9], [36].
- Potassium can fall sharply at the start of treatment. When severe megaloblastic anaemia is treated intensively, low potassium and sudden death may occur, the American label warns [10], [16].
- Early strain on the circulation. The American label lists fluid in the lungs, heart failure and clots early in treatment [10].
- Severe allergic reactions. The American label reports anaphylactic shock and death after injected B12; the German label calls this very rare [10], [9].
- In a British allergy study, 8 of 29 referred patients had anaphylaxis, 4 each to the hydroxo and the cyano form. Seven tolerated the other form [37].
- Cobalt allergy. Sensitivity to cobalt or B12 is a contraindication in the American labels, since the molecule is 4.34 per cent cobalt [10], [17].
- Acne. The German label lists acne-like and hive-like skin reactions as very rare, below 1 in 10,000. In a small study, B12 changed the activity of a skin bacterium linked to acne [9], [38].
- Leber's hereditary optic neuropathy. Early patients given cyanocobalamin suffered "severe and swift optic atrophy", the American label warns. British labels list hydroxocobalamin for this disease, so the warning concerns the cyanide form [10], [18].
- Masking. Folic acid can improve the anaemia of a B12 deficiency while nerve damage goes on. B12 can in turn mask a folate deficiency: "indiscriminate administration may mask the true diagnosis" [10].
- Milder reactions include passing diarrhoea, itching and a fleeting rash [10].
The cyanide question. The cyanide group makes up just under 2 per cent of the molecule's weight (our own calculation from the formula). No study was found showing that cyanocobalamin harms smokers; a 1972 study of 20 patients found no link between optic nerve inflammation and smoking [8], [39].
High intake without a deficiency
Some studies question whether high intake is harmless without a deficiency. The data are mixed, show no cause and effect, and are reported as a safety signal only [7], [40], [41], [29].
Observational The VITAL cohort followed 77,118 adults aged 50 to 76. Women showed no link. Men taking B12 from single supplements had a 30 to 40 per cent higher risk of lung cancer. In the top group, above 55 micrograms a day over ten years, the hazard ratio was 1.98 (1.32 to 2.97) [7].
Observational, genetic In 5183 matched pairs, each doubling of blood B12 went with slightly higher odds of lung cancer (odds ratio 1.15; 1.06 to 1.25) [42].
Randomised trials, pooled In NORVIT and WENBIT, 6837 Norwegian heart patients took folic acid plus B12 or not. New cancers occurred in 10.0 against 8.4 per cent (hazard ratio 1.21; 1.03 to 1.41), mostly lung cancer. Deaths were 16.1 against 13.8 per cent [40].
Randomised trial In B-PROOF, 2524 older adults took folic acid plus B12 for two to three years. Cancer overall occurred in 13.6 against 11.3 per cent (hazard ratio 1.25; 1.00 to 1.53; p = 0.05), bowel cancer in 3.4 against 2.0 per cent. This was a secondary outcome [41].
Randomised trial, no signal SEARCH, with 12,064 participants over 6.7 years, found cancer in 11.2 against 10.6 per cent, not a significant difference [29].
In both positive trials folic acid was given too, so a B12 effect cannot be separated out. The American label finds no evidence that long-term cyanocobalamin causes cancer in pernicious anaemia, though animal studies were never done [40], [41], [10].
Why this page lists no doses
This page gives no treatment amounts for vitamin B12, for injections, sprays or tablets. Injectable cyanocobalamin is a prescription medicine in the United States, Switzerland and the United Kingdom, and injections are sold to lay people in wellness settings, where a figure would read as an instruction [10], [15], [16], [12].
Three figures do appear, and none is a target. The European intake reference is nutrition information, the German proposal is a limit for supplement makers, and the cohort figure marks a risk [20], [36], [7].
Development and approval status
Vitamin B12 has been an approved medicine since 1942 in the United States. Its legal status depends on the country and on the form [17], [9].
From an old vitamin medicine to an extra in weight-loss mixes
- 1942First US approvalThe nasal spray label gives 1942 as the initial approval of cyanocobalamin in the United States, ref [17]
- 2005A nasal sprayA cyanocobalamin nasal spray is approved on 31 January as a prescription medicine, ref [14]
- 2006Heart trials failNORVIT and HOPE-2 find no protection against heart attacks, refs [27], [28]
- 2007An antidote in the EUHigh-strength hydroxocobalamin is approved centrally for cyanide poisoning, ref [43]
- 2010Metformin link confirmedThe HOME trial shows metformin lowers B12 against placebo; SEARCH finds no heart benefit, refs [4], [29]
- 2024Japan approves mecobalamin for ALSApproval on 24 September, based on a 130-patient trial, ref [35]
- 2026The weight-loss connectionThe FDA names semaglutide plus cyanocobalamin as a compounding example; a tirzepatide-B12 impurity is published, refs [1], [2]
- January 2005 a prescription nasal spray is approved; it is now listed as discontinued, not for safety reasons [14].
- November 2007 the EU approves high-strength hydroxocobalamin for cyanide poisoning, its only central approval of a B12 form [43].
- September 2024 Japan approves mecobalamin injections for ALS [35].
- April 2026 the American regulator names semaglutide plus cyanocobalamin as a possible copy of an approved drug [1].
| Market | Status | Since or note |
|---|---|---|
| United States | Prescription | Injection and spray; oral as supplements |
| European Union | National | Only the antidote approved centrally |
| Germany | Pharmacy-only | No prescription needed |
| United Kingdom | Prescription | Injections |
| Australia | Registered | Not scheduled |
| Canada | Approved | "Ethical" schedule |
| Switzerland | Prescription | Category B injections |
These entries were checked on 23 September 2026 [14], [44], [16], [19], [45], [15].
Germany. The official list of prescription-only substances does not name cyanocobalamin or vitamin B12; it covers hydroxocobalamin only for cyanide poisoning. A German injection label reads "Apothekenpflichtig", meaning pharmacy-only [44], [9].
United Kingdom and Switzerland. British hydroxocobalamin injections are prescription-only medicines. Swiss injections sit in category B, which needs a prescription, and oral products in category D, which does not [16], [18], [15].
Australia and Canada. The Australian injection is "Not Scheduled", checked against the June 2024 poisons schedule. Canadian injections carry the schedule "Ethical", which is not a prescription status [19], [46], [45].
Food supplements. The EU has no binding maximum for B12 in supplements. In 2021 Germany's risk assessment institute proposed a limit of 25 micrograms per daily portion for supplement makers, which is not law [36].
The wider legal picture is under are peptides legal and FDA-approved peptides.
Anti-doping
Vitamin B12 is not prohibited in sport. The 2026 prohibited list does not mention cobalamin, B12 or vitamins at all [47].
The confusion comes from cobalt. Class S2.1.2 bans substances that activate the body's oxygen-sensing switch (HIF activators), "e.g. cobalt". The American anti-doping agency stated: "It is reiterated that vitamin B12, which contains cobalt, is not prohibited" [47], [48].
Laboratories can tell the two apart. In 20 volunteers, only inorganic cobalt, not cyanocobalamin, raised cobalt levels significantly [49].
Rule M2.2 separately bans drips of more than 100 ml per 12 hours outside hospital care. B12 is also absent from the annex to the German anti-doping act [47], [50]. The full picture is at peptides banned in sport.
Compared with related peptides
| Substance | What it is | Link to vitamin B12 | Status |
|---|---|---|---|
| Vitamin B12 (cyanocobalamin) | Cobalt vitamin, synthetic stable form | — | Prescription injection in US, CH, UK [14], [15], [16] |
| Hydroxocobalamin | Natural B12 form | Usual injection form in UK and Australia | Prescription in UK; not scheduled in Australia [16], [19] |
| Methylcobalamin | Active B12 form | Marketed as superior; no trial shows it | Prescription in Japan; under evaluation for US compounding [11], [51] |
| Semaglutide | GLP-1 peptide for diabetes and weight | Mixed with B12 in compounding | See its own page [1] |
| Tirzepatide | GIP and GLP-1 peptide | Reacts with some B12 forms in mixes | See its own page [2] |
The first three rows are one vitamin in different forms, which differ in storage and marketing more than in effect [21], [19].
The last two rows are peptides, and their only link to B12 here is compounding. The regulator may still treat such a mix as essentially a copy of the approved drug, and no trial shows that the added B12 does anything [1], [2], [33].
A real medical link runs the other way. Metformin lowers B12, and weight-loss drugs may do so when vomiting persists. That is a reason for a doctor to test, not for an extra injection [4], [25].
Common misconceptions
- "B12 is a peptide because peptide shops sell it." It is a vitamin with no amino-acid chain [8], [1].
- "B12 shots burn fat." No randomised trial shows weight loss from B12. The real link runs the other way: metformin lowers B12, and weight-loss drugs may do so [33], [4], [24].
- "Methylcobalamin is the active form; cyanocobalamin is useless or toxic." Every form is processed into the same intermediate in the cell. A 2015 review finds an advantage unlikely, and no head-to-head trial was found [21], [33].
- "B12 injections need a prescription throughout the EU." Wrong for Germany, where they are pharmacy-only [9], [44].
- "It contains cobalt, so it is doping." Inorganic cobalt is banned; vitamin B12 expressly is not [47], [48].
- "There is no upper limit, so more is harmless." No limit means none could be set. Some studies found more cancers at high intake without deficiency, while SEARCH found no signal [36], [7], [40], [41], [29].
Frequently asked questions
Is vitamin B12 a peptide?
No. Vitamin B12 is a cobalt-containing vitamin with no chain of amino acids. It appears in a peptide register only because it is sold alongside peptide weight-loss injections.
Why is vitamin B12 mixed into compounded semaglutide or tirzepatide?
No published trial shows that the added B12 improves weight loss. The American regulator names semaglutide plus cyanocobalamin as an example of a mix it may still treat as a copy of the approved drug. In 2026 the maker of approved tirzepatide reported a new impurity formed when tirzepatide reacts with certain B12 forms.
Do vitamin B12 injections help with weight loss or energy?
No randomised trial shows weight loss from vitamin B12 alone or from lipotropic B12 injections. For energy without a deficiency, the only controlled study found is a 1973 pilot with 28 people, and its result depended on the order of treatment. Tiredness can be a sign of deficiency, which a doctor can check.
Does metformin lower vitamin B12?
Yes. In a randomised trial of 390 people with type 2 diabetes, B12 fell 19 per cent against placebo over 4.3 years, and deficiency was 7.2 percentage points more common.
Do vitamin B12 supplements protect the heart or the memory?
Not in people without a deficiency. A Cochrane review of 15 trials with 71,422 participants found no difference in heart attacks or deaths. Pooled data from 11 trials with about 22,000 older adults found no effect on memory and thinking, even though homocysteine fell.
Is methylcobalamin better than cyanocobalamin?
That has not been shown. Inside the cell, every form of vitamin B12 is processed into the same intermediate and rebuilt into the two active forms. A 2015 review calls an advantage of the methyl form unlikely, and no head-to-head randomised trial of their uptake was found.
Do vitamin B12 injections need a prescription?
It depends on the country. Injections need a prescription in the United States, Switzerland and the United Kingdom. In Germany they are pharmacy-only without a prescription, the Australian injection is not scheduled, and Canadian injections are not prescription-only. Tablets are sold without a prescription.
What are the side effects of vitamin B12 injections?
Most are mild, such as itching, a passing rash or diarrhoea, and acne is listed as very rare. Serious risks include severe allergic reactions, cobalt allergy and a sharp fall in potassium at the start of treating a severe deficiency. Cyanocobalamin carries a warning for Leber's hereditary optic neuropathy.
Can high intake of vitamin B12 be harmful?
It cannot be ruled out. In one large cohort, men with the highest intake from single B12 supplements had almost twice the risk of lung cancer. Two randomised trials of folic acid plus B12 found more cancers, while a third found no difference. None of these studies proves cause and effect.
Is vitamin B12 banned in sport?
No. The 2026 prohibited list bans cobalt as an activator of the body's oxygen-sensing switch, but vitamin B12 is not listed, and the American anti-doping agency confirms that it is not prohibited. Separately, drips of more than 100 ml per 12 hours are banned outside hospital care, whatever they contain.
Sources
- US Food and Drug Administration (page as of 1 April 2026). FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize. Names a compounded product combining semaglutide and "vitamin B12 (cyanocobalamin)" as a possible essential copy. https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize
- Jordan B, et al. (2026). A novel, widespread impurity in mass-compounded tirzepatide/B12 products: potential patient safety implications. Expert Opinion on Drug Safety 25(5):837-845. PMID 42010938. The authors are employees of Eli Lilly, the maker of approved tirzepatide, which is a conflict of interest.
- Wang H, Li L, Qin LL, Song Y, Vidal-Alaball J, Liu TH (2018). Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database of Systematic Reviews 3:CD004655. PMID 29543316.
- de Jager J, Kooy A, Lehert P, Wulffelé MG, van der Kolk J, Bets D, et al. (2010). Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ 340:c2181. PMID 20488910. Trial NCT00375388.
- Martí-Carvajal AJ, Solà I, Lathyris D, Dayer M (2017). Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database of Systematic Reviews 8:CD006612. PMID 28816346.
- Clarke R, Bennett D, Parish S, Lewington S, Skeaff M, Eussen SJPM, et al. (2014). Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals. American Journal of Clinical Nutrition 100(2):657-666. PMID 24965307.
- Brasky TM, White E, Chen CL (2017). Long-term, supplemental, one-carbon metabolism-related vitamin B use in relation to lung cancer risk in the Vitamins and Lifestyle (VITAL) cohort. Journal of Clinical Oncology 35(30):3440-3448. PMID 28829668.
- National Center for Biotechnology Information. PubChem compounds 166596686 and 5311498 (cyanocobalamin), queried 23 September 2026 for formula, mass, InChIKey, CAS number, UNII and cross-references. https://pubchem.ncbi.nlm.nih.gov/compound/166596686
- mibe GmbH Arzneimittel (2026). Summary of product characteristics, Vitaprompt injekt B12 solution for injection, authorisation no. 3000296.00.00, as of January 2026. Sections 4.8, 5.1 and 11 ("Apothekenpflichtig"). Retrieved from fachinfo.de, document 010834.
- Hikma Pharmaceuticals USA (revised December 2023, DailyMed version May 2026). Cyanocobalamin Injection USP, prescribing information, Rx only. DailyMed setid a66eb3c4-3e1d-4d49-b963-4fa2334cc9b6. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a66eb3c4-3e1d-4d49-b963-4fa2334cc9b6
- KEGG DRUG, entries D03246 (mecobalamin) and D00166 (cyanocobalamin), queried 23 September 2026, including Japanese prescription and switch listings. https://rest.kegg.jp/get/D03246
- Product page of a US compounding pharmacy for a "Lipo-B" injection (methionine, choline and cyanocobalamin), retrieved 23 September 2026. Used only as evidence of how such products are described and marketed, including the statement that they are not FDA-approved; never as a scientific reference.
- Wikidata, items Q252251 (cyanocobalamin), Q73972 (hydroxocobalamin), Q250442 (methylcobalamin) and Q239593 (cobamamide), queried by SPARQL on 23 September 2026. https://www.wikidata.org/wiki/Q252251
- US Food and Drug Administration. Drugs@FDA via openFDA, queried 23 September 2026 for cyanocobalamin: numerous generic injection approvals with marketing status prescription; NDA 021642 (NASCOBAL, approved 31 January 2005) listed as discontinued, not for reasons of safety or effectiveness. https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:cyanocobalamin
- Swissmedic. List of authorised packs of human medicines, as of 31 August 2026: cyanocobalamin and hydroxocobalamin injections in dispensing category B, oral single-ingredient products in category D. https://www.swissmedic.ch/dam/swissmedic/de/dokumente/internetlisten/zugelassene_packungen_human.xlsx.download.xlsx/zugelassene_packungen_ham.xlsx
- Mercury Pharmaceuticals (2024). Hydroxocobalamin Solution for Injection, summary of product characteristics, PL 12762/0008, legal category prescription only medicine. https://www.medicines.org.uk/emc/product/100455/smpc
- Par Health (revised March 2024, DailyMed version 28 May 2026). NASCOBAL (cyanocobalamin) nasal spray, prescribing information, including Table 1 of adverse events and the statement "Initial U.S. Approval: 1942". DailyMed setid 697e0e52-c01b-4b53-9994-f79c46eb6b4f. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=697e0e52-c01b-4b53-9994-f79c46eb6b4f
- Amdipharm UK (2024). Cobalin-H Injection, summary of product characteristics, PL 20072/0217, prescription only medicine; indications include tobacco amblyopia and Leber's optic atrophy. https://www.medicines.org.uk/emc/product/4662/smpc
- Pfizer Australia (revised 4 November 2022). Australian product information, Neo-B12 Injection (hydroxocobalamin), section 7: "Not Scheduled". https://medsinfo.com.au/api/documents/Neo-B12_Injection_PI?format=pdf
- EFSA Panel on Dietetic Products, Nutrition and Allergies (2015). Scientific opinion on dietary reference values for cobalamin (vitamin B12). EFSA Journal 13(7):4150. DOI 10.2903/j.efsa.2015.4150.
- Obeid R, Fedosov SN, Nexo E (2015). Cobalamin coenzyme forms are not likely to be superior to cyano- and hydroxyl-cobalamin in prevention or treatment of cobalamin deficiency. Molecular Nutrition and Food Research 59(7):1364-1372. PMID 25820384.
- Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J (1998). Effective treatment of cobalamin deficiency with oral cobalamin. Blood 92(4):1191-1198. PMID 9694707.
- Aroda VR, Edelstein SL, Goldberg RB, Knowler WC, Marcovina SM, Orchard TJ, et al. (2016). Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. Journal of Clinical Endocrinology and Metabolism 101(4):1754-1761. PMID 26900641.
- Urbina J, et al. (2026). Micronutrient and nutritional deficiencies associated with GLP-1 receptor agonist therapy: a narrative review. Clinical Obesity 16(1):e70070. PMID 41549912.
- Simancas-Racines D, et al. (2026). Micronutrient risk with GLP-1 receptor and dual incretin agonists in obesity. Obesity Pillars 19:100290. PMID 42382663.
- Cohan CJ, et al. (2026). Acute nutritional axonal neuropathy in the setting of semaglutide-associated gastrointestinal intolerance: a case report. Case Reports in Neurology 18(1):402-412. PMID 42549476.
- Bønaa KH, Njølstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, et al. (2006). Homocysteine lowering and cardiovascular events after acute myocardial infarction (NORVIT). New England Journal of Medicine 354(15):1578-1588. PMID 16531614. Trial NCT00266487.
- Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, et al. (2006). Homocysteine lowering with folic acid and B vitamins in vascular disease (HOPE-2). New England Journal of Medicine 354(15):1567-1577. PMID 16531613. Trial NCT00106886.
- SEARCH Collaborative Group (2010). Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors. JAMA 303(24):2486-2494. PMID 20571015. ISRCTN74348595.
- Eussen SJ, de Groot LC, Joosten LW, Bloo RJ, Clarke R, Ueland PM, et al. (2006). Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency. American Journal of Clinical Nutrition 84(2):361-370. PMID 16895884.
- Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G, et al. (2010). Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment (VITACOG). PLoS ONE 5(9):e12244. PMID 20838622.
- Ellis FR, Nasser S (1973). A pilot study of vitamin B12 in the treatment of tiredness. British Journal of Nutrition 30(2):277-283. PMID 4583554. DOI 10.1079/bjn19730033. Abstract read.
- PubMed searches run on 23 September 2026 for lipotropic B12 injections and weight loss (1 record, a 1984 study in bats), B12 supplementation and body weight in randomised trials (18 records, none testing B12 alone on weight), B12 and athletic performance (35 records, not screened exhaustively), and a direct randomised comparison of methyl- and cyanocobalamin uptake (no record). https://pubmed.ncbi.nlm.nih.gov/
- Paul C, Brady DM (2017). Comparative bioavailability and utilization of particular forms of B12 supplements with potential to mitigate B12-related genetic polymorphisms. Integrative Medicine 16(1):42-49. PMID 28223907.
- Eisai Co., Ltd. (24 September 2024). News release: Rozebalamin (mecobalamin) for injection approved in Japan for amyotrophic lateral sclerosis; results of the phase 3 JETALS trial. https://www.eisai.com/news/2024/news202469.html
- German Federal Institute for Risk Assessment (BfR) (2021). Maximum levels for vitamin B12 in foods including food supplements. Cites the Scientific Committee on Food (2000), which set no tolerable upper intake level. https://www.bfr.bund.de/cm/343/hoechstmengenvorschlaege-fuer-vitamin-b12-in-lebensmitteln-inklusive-nahrungsergaenzungsmitteln.pdf
- El Rhermoul FZ, et al. (2024). Vitamin B12 hypersensitivity: a retrospective multicenter study. Journal of Allergy and Clinical Immunology: In Practice 12(3):699-704. PMID 37898177.
- Kang D, Shi B, Erfe MC, Craft N, Li H (2015). Vitamin B12 modulates the transcriptome of the skin microbiota in acne pathogenesis. Science Translational Medicine 7(293):293ra103. PMID 26109103.
- Wadia NH, et al. (1972). Role of vegetarianism, smoking, and hydroxocobalamin in optic neuritis. British Medical Journal 3(5821):264. PMID 4339973.
- Ebbing M, Bønaa KH, Nygård O, Arnesen E, Ueland PM, Nordrehaug JE, et al. (2009). Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 302(19):2119-2126. PMID 19920236.
- Oliai Araghi S, Kiefte-de Jong JC, van Dijk SC, Swart KMA, van Laarhoven HW, van Schoor NM, et al. (2019). Folic acid and vitamin B12 supplementation and the risk of cancer: long-term follow-up of the B-PROOF trial. Cancer Epidemiology, Biomarkers and Prevention 28(2):275-282. PMID 30341095.
- Fanidi A, Carreras-Torres R, Larose TL, Yuan JM, Stevens VL, Weinstein SJ, et al. (2019). Is high vitamin B12 status a cause of lung cancer? International Journal of Cancer 145(6):1499-1503. PMID 30499135.
- European Medicines Agency. Cyanokit (hydroxocobalamin), European public assessment report, EMEA/H/C/000806, authorised 23 November 2007 for known or suspected cyanide poisoning. https://www.ema.europa.eu/en/medicines/human/EPAR/cyanokit
- Germany, Ordinance on Prescription-Only Medicines (AMVV), Annex 1, full text checked 23 September 2026. The search pattern "obalamin" returns one entry, hydroxocobalamin for known or suspected cyanide poisoning; cyanocobalamin, cobalamin, mecobalamin and vitamin B12 are not listed, while control substances such as semaglutide are. https://www.gesetze-im-internet.de/amvv/anlage_1.html
- Health Canada, Drug Product Database, queried 23 September 2026: cyanocobalamin injections with schedule "Ethical", for example DIN 02463393, marketed since 16 January 2018. https://health-products.canada.ca/api/drug/drugproduct/?lang=en&type=json&brandname=CYANOCOBALAMIN
- Australia, Therapeutic Goods (Poisons Standard, June 2024) Instrument 2024, F2024L00589, full text searched 23 September 2026: no entry for cobalamin; Schedule 4 covers cobalt for human therapeutic use. The current edition was not checked. https://faolex.fao.org/docs/pdf/aus227554.pdf
- World Anti-Doping Agency. The 2026 Prohibited List, class S2.1.2 and method M2.2. Full text searched 23 September 2026: no match for cobalamin, B12 or vitamin. https://www.wada-ama.org/en/prohibited-list
- US Anti-Doping Agency. "Updated 2017 WADA Prohibited List Now Available", athlete advisory: "It is reiterated that vitamin B12, which contains cobalt, is not prohibited." https://www.usada.org/athlete-advisory/updated-2017-wada-prohibited-list-now-available/
- Knoop A, et al. (2020). Analysis of cobalt for human sports drug testing purposes using ICP- and LC-ICP-MS. Drug Testing and Analysis 12(11-12):1666-1672. PMID 33142033.
- Germany, Anti-Doping Act, annex (BGBl. 2023 I no. 67), full text searched 23 September 2026: no entry for cobalamin, vitamins or cobalt, with control substances such as somatropin found.
- US Food and Drug Administration (updated 14 May 2026). Bulk drug substances nominated for use in compounding under section 503A, category 1 (under evaluation), listing methylcobalamin. https://www.fda.gov/media/94155/download
Cite this page
The facts on this page were checked on 23 and 24 September 2026. Three points could still move: the British status of cyanocobalamin injections, the current Australian schedule, and any study measuring B12 under weight-loss drugs.
myPeptides Research & Editing. (2026). Vitamin B12: what the studies show, status and safety. Version 1.0, 24 September 2026. myPeptides Peptide Register. Retrieved from https://mypep.app/peptides/vitamin-b12
How pages in this register are compiled and graded is described under methodology; the full register is at peptides.
| Version | Date | Change |
|---|---|---|
| 1.0 | 2026-09-24 | Initial publication |
Last verified: 24 September 2026. Next review: on any change in prescription status, on a trial of B12 levels under weight-loss drugs, or on new data on compounded mixes.