Vitamin B12 injections
In deficient adults, B12 injections into a muscle corrected blood B12, methylmalonic acid, homocysteine and anemia, and high-dose tablets matched them over months in trials. No trial of B12 shots for weight loss was located, and energy evidence is one uncontrolled survey. Labels warn of low potassium early in treatment and of anaphylaxis.
Add to Bio HackChecked 2026-11-14
- Status
- Prescription drugs in the US. Cyanocobalamin injection, given into a muscle or deep under the skin, and hydroxocobalamin injection, given into a muscle, are FDA-approved for B12 deficiency from poor absorption, including pernicious anemia, and their labels say oral B12 is not dependable in pernicious anemia. High-dose hydroxocobalamin given into a vein (Cyanokit) is FDA-approved for known or suspected cyanide poisoning. Energy, fatigue and weight loss are not FDA-approved uses.
- Also called
- B12 shot, B12 shots, vitamin B12 injection, cyanocobalamin injection, hydroxocobalamin injection, hydroxocobalamin, cobalamin injection, Cyanokit, energy shot, B12 weight loss shot, lipotropic injection
- Taken for
- pernicious anemia, B12 deficiency, anemia, nerve damage from low B12, after gastric bypass, energy, fatigue, weight loss, metabolism, mood, cyanide poisoning, septic shock
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Shown to help2
- ModerateShown in trial injection arms to correct blood B12, methylmalonic acid, homocysteine and anemia in adults with B12 deficiency, with reticulocytes rising in every patient.
- LimitedLimited evidence: a 20-person pilot trial found a larger vasopressor drop than placebo in septic shock, and observational studies found higher blood pressure than methylene blue after heart surgery.
Reported risks7
- ModerateShown in healthy volunteers to turn urine red in all and skin red in 94% after 5 g into a vein, with blood pressure spikes in 18% against 0%.Very common
- LimitedThe labels warn that low potassium, and with cyanocobalamin sudden death, may occur when severe megaloblastic anemia is treated intensely, and that platelet counts can rise.How often is not known
- LimitedThe labels warn that anaphylactic shock and death have been reported after B12 injections, and that sensitivity to cobalt or B12 is a contraindication.How often is not known
- LimitedThe labels warn that people with early Leber's hereditary optic atrophy had severe, swift optic atrophy on cyanocobalamin, and that treatment may unmask polycythemia vera.How often is not known
- LimitedThe cyanocobalamin label warns its benzyl alcohol preservative has been linked to fatal gasping syndrome in premature infants, and its aluminum can build up with poor kidney function.How often is not known
- LimitedLinked to about 1.6 times the odds of acute kidney injury after smoke inhalation in one cohort. The label warns of kidney failure with oxalate crystals.How often is not known
- LimitedThe labels warn that chloramphenicol and other bone marrow suppressing drugs can blunt the response to B12, and that some antibiotics and methotrexate distort B12 blood tests.How often is not known
What people take it for, and what was found
Shown to help2
Correcting B12 deficiency and its anemia
Shown in trial injection arms to correct blood B12, methylmalonic acid, homocysteine and anemia in adults with B12 deficiency, with reticulocytes rising in every patient.
Compared with levels before treatment in the same people, within randomized trials [1][2]; the label's expected response [3]
The numbers and sources
- Effect
- After 4 months of cyanocobalamin 1 mg into a muscle on days 1, 3, 7, 10, 14, 21, 30, 60 and 90, mean serum B12 rose from 95 to 325 pg/mL, methylmalonic acid fell from 3,630 to 265 nmol/L and homocysteine from 40.0 to 12.2 µmol/L, with prompt correction of blood and nerve abnormalities [1]. With 1,000 µg into a muscle daily for 10 days, then weekly and monthly, reticulocytes rose in all patients, hemoglobin rose, mean corpuscular volume fell and B12 rose by day 90 [2]. The hydroxocobalamin label says reticulocytosis usually appears between the third and tenth day of therapy [3].
- Population
- 15 evaluable adults with newly diagnosed B12 deficiency in the injection arm [1]; 34 adults with megaloblastic anemia from B12 deficiency in the injection arm [2].
- Sources
- [1], [2], [3]
- Caveats
- No placebo arm, because untreated deficiency causes lasting nerve damage. Both trials were small. The label says deficiency left for more than 3 months may cause permanent spinal cord damage [4].
Shock after sepsis or heart surgery, hydroxocobalamin into a vein
Limited evidence: a 20-person pilot trial found a larger vasopressor drop than placebo in septic shock, and observational studies found higher blood pressure than methylene blue after heart surgery.
Compared with saline placebo [9]; methylene blue [10]
The numbers and sources
- Effect
- A single 5 g dose into a vein lowered vasopressor dose from randomization to after the infusion by 36%, against a 4% rise on placebo (P < .001), and by 28% against a 10% rise at 3 hours, with no serious adverse events [9]. Pooling 4 retrospective studies, mean arterial pressure at 1 hour was 5.30 mmHg higher than with methylene blue (95% CI 2.98 to 7.62), the primary vasopressor outcome did not differ, and mortality did not differ [10].
- Population
- 20 adults with septic shock [9]; 263 adults with vasoplegic shock after cardiopulmonary bypass [10].
- Sources
- [9], [10]
- Caveats
- Not an FDA-approved use. The trial was a feasibility pilot [9], and the pooled studies were observational with moderate to serious risk of bias [10].
Mixed results3
Injection compared with B12 by mouth
Mixed results: daily high-dose B12 tablets matched injections for blood levels and anemia over months, but fewer older adults kept normal levels at 1 year in one trial.
Compared with cyanocobalamin by mouth, 1 to 2 mg a day [1][2][5]
The numbers and sources
- Effect
- At 4 months, serum B12 was higher (1,005 against 325 pg/mL) and methylmalonic acid lower (169 against 265 nmol/L) on 2 mg a day by mouth than on injections, with blood and nerve corrections indistinguishable [1]. Blood counts and recovery patterns were similar with 1,000 µg by mouth or into a muscle, and nerve symptoms improved in 77.8% and 75.0% at day 30 [2]. In adults aged 65 and older, more than 90% in both arms had normal B12 at 8 weeks (difference -0.7%). At 52 weeks, 73.6% on tablets and 80.4% on injections had normal levels, and non-inferiority was unlikely. 83.4% preferred tablets [5].
- Population
- 33 evaluable adults with B12 deficiency [1]; 60 adults with megaloblastic anemia [2]; 283 adults aged 65 and older in 22 primary care centers in Madrid [5].
- Sources
- [1], [5], [2]
- Caveats
- None of these trials was limited to pernicious anemia, where the labels say oral therapy is not dependable [3][4]. Pooled reviews of route are on the vitamin B12 page. [2] was open-label.
Cyanide poisoning, high-dose hydroxocobalamin into a vein
Case series: of 72 smoke inhalation patients given hydroxocobalamin in Paris with known outcomes, 41.7% survived. FDA approval rests on a dog study, and one cohort found no survival link.
Compared with no comparison group [6]; ICU smoke inhalation patients not given hydroxocobalamin [7]; saline vehicle in poisoned dogs [8]
The numbers and sources
- Effect
- The Cyanokit label states effectiveness has not been determined in humans because inducing cyanide poisoning to test it is not ethical. In cyanide-poisoned dogs, 75 or 150 mg/kg into a vein raised survival at 4 hours and 14 days against vehicle and roughly halved blood cyanide by the end of infusion [8]. In 8 years of prehospital use, 30 of 72 patients with known outcomes survived, and 21 of 38 found in cardiac arrest regained circulation [6]. In 739 ICU patients after smoke inhalation, hydroxocobalamin was not linked to survival (adjusted OR 1.114, 95% CI 0.691 to 1.797) [7].
- Population
- Dogs [8]; 101 patients treated by the Paris Fire Brigade, 1995 to 2003 [6]; 739 ICU patients in 21 French units [7].
- Sources
- [8], [6], [7]
- Caveats
- No controlled human trial exists. Treated patients in [7] were sicker. Not all smoke inhalation victims have cyanide poisoning [8].
Energy and fatigue
Limited evidence: one uncontrolled survey of 38 people with ME on weekly B12 injections found those on more frequent, higher doses rated themselves more improved.
Compared with higher and lower responders compared with each other, with no untreated group [11]
The numbers and sources
- Effect
- All patients had used B12 injections at least weekly for 6 months or more with oral folic acid. The 15 higher responders had used more frequent injections and higher doses for longer, and rated themselves very much or much improved. The 23 lower responders rated themselves much or minimally improved, and 70% of them used strong pain medicines daily [11].
- Population
- 38 people with myalgic encephalomyelitis, with or without fibromyalgia, in Sweden [11].
- Sources
- [11]
- Caveats
- A cross-sectional survey with no placebo or untreated group, so it cannot show the injections caused the improvement [11]. No controlled trial of B12 injections for energy in people without deficiency could be read: a 1973 pilot trial of B12 for tiredness was located, but neither an abstract nor an open text was available. The oral B12 page covers fatigue trials of B12 by mouth.
Claimed, not studied in people1
Weight loss
Not studied in people. No trial of B12 shots for weight loss was located, and the label describes B12's roles in blood cells and nerves, not fat loss.
No study in people. This rests on how it acts in the body.
The numbers and sources
- Effect
- The cyanocobalamin injection label describes vitamin B12 as essential to growth, cell reproduction, blood cell formation and nucleoprotein and myelin synthesis, and lists no weight effect among its actions or uses [4]. A review of 255 US IV hydration spa websites found 63.5% offered vitamin injections, all made claims of benefit, and only 0.8% cited a source for those claims [12].
- Population
- Label pharmacology [4]; 255 spa websites and 87 secret shopper calls [12].
- Sources
- [4], [12]
- Caveats
- The spa study shows the claims are widely marketed, not that they are true or false [12]. No weight data in people given B12 injections were found.
Doses studied
The cyanocobalamin label gives 100 µg daily for 6 or 7 days into a muscle or deep under the skin for pernicious anemia, then on alternate days and every 3 to 4 days until blood values normalize, then 100 µg monthly for life, and says to avoid the intravenous route because almost all of it is lost in the urine [4]. The hydroxocobalamin label gives 30 µg daily for 5 to 10 days, then 100 to 200 µg monthly into a muscle [3]. The trials used 1 mg into a muscle on a tapering schedule to monthly [1][5] or 1,000 µg daily for 10 days, then weekly and monthly [2]. For cyanide poisoning, the Cyanokit label gives 5 g into a vein over 15 minutes, with a second 5 g dose if needed [8]. The septic shock pilot trial used one 5 g dose into a vein [9].
Risks
Reported risks7
Red skin and urine, rash and blood pressure rise with high-dose hydroxocobalamin into a vein
Shown in healthy volunteers to turn urine red in all and skin red in 94% after 5 g into a vein, with blood pressure spikes in 18% against 0%.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- After 5 g of hydroxocobalamin into a vein, red urine occurred in all 66 subjects and skin redness in 62 (94%), against none of 22 on placebo. Oxalate crystals in urine appeared in 61% against 5%, mostly acne-like rash in 20% against 0%, blood pressure of 180 systolic or 110 diastolic or more in 18% against 0%, and infusion site reactions in 6%. At 10 g, rash rose to 44% and blood pressure spikes to 28% [8]. Of 101 prehospital patients, red or pink urine or skin was judged possibly related in 5 [6].
- Population
- 136 healthy adults in a double-blind, placebo-controlled dose study, 66 on 5 g and 22 on placebo [8]; 101 smoke inhalation patients [6].
- Sources
- [8], [6]
- Caveats
- The label says the dark red color also interferes with many colorimetric lab tests for up to days and can make hemodialysis machines shut down by falsely detecting a blood leak [8].
Low potassium early in treatment of severe anemia
The labels warn that low potassium, and with cyanocobalamin sudden death, may occur when severe megaloblastic anemia is treated intensely, and that platelet counts can rise.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- The cyanocobalamin label warns that hypokalemia and sudden death may occur in severe megaloblastic anemia treated intensely, and says serum potassium must be watched closely for the first 48 hours [4]. The hydroxocobalamin label warns of hypokalemia and thrombocytosis as blood production recovers [3]. The cyanocobalamin label also lists pulmonary edema and congestive heart failure early in treatment, and peripheral vascular thrombosis [4].
- Population
- Label statements [4][3].
- Sources
- [4], [3]
- Caveats
- The labels give no rate [4][3].
Anaphylaxis and allergic reactions
The labels warn that anaphylactic shock and death have been reported after B12 injections, and that sensitivity to cobalt or B12 is a contraindication.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- The cyanocobalamin label reports anaphylactic shock and death after injected B12, recommends an intradermal test dose in people suspected of sensitivity, and lists itching, a passing rash, mild diarrhea and a feeling of whole-body swelling [4]. The hydroxocobalamin label lists anaphylaxis, itching, rash and pain after injection [3].
- Population
- Label statements [4][3].
- Sources
- [4], [3]
- Caveats
- No rate is given [4][3].
Optic nerve damage in Leber's disease and unmasking polycythemia vera
The labels warn that people with early Leber's hereditary optic atrophy had severe, swift optic atrophy on cyanocobalamin, and that treatment may unmask polycythemia vera.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- The cyanocobalamin label reports severe and swift optic atrophy in patients with early Leber's disease treated with cyanocobalamin, and lists polycythemia vera among adverse reactions [4]. The hydroxocobalamin label says B12 deficiency may suppress the signs of polycythemia vera and treatment may unmask it [3].
- Population
- Label statements [4][3].
- Sources
- [4], [3]
- Caveats
- No rate is given [4][3].
Benzyl alcohol and aluminum in multi-dose vials
The cyanocobalamin label warns its benzyl alcohol preservative has been linked to fatal gasping syndrome in premature infants, and its aluminum can build up with poor kidney function.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- The label states benzyl alcohol has been reported to be associated with a fatal gasping syndrome in premature infants, and that aluminum may reach toxic levels with prolonged injected use when kidney function is impaired, with premature neonates most at risk [4].
- Population
- Label statement [4].
- Sources
- [4]
- Caveats
- Applies to the products that contain these ingredients [4].
Kidney injury with high-dose hydroxocobalamin into a vein
Linked to about 1.6 times the odds of acute kidney injury after smoke inhalation in one cohort. The label warns of kidney failure with oxalate crystals.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- In ICU patients after smoke inhalation, intravenous hydroxocobalamin was linked to acute kidney injury (adjusted OR 1.597, 95% CI 1.055 to 2.419) and severe acute kidney injury (adjusted OR 1.772, 95% CI 1.137 to 2.762) [7]. The Cyanokit label reports acute renal failure with acute tubular necrosis and calcium oxalate crystals in urine, sometimes needing dialysis, and advises monitoring kidney function for 7 days [8].
- Population
- 739 ICU patients after smoke inhalation, 386 given hydroxocobalamin [7]; label reports [8].
- Sources
- [7], [8]
- Caveats
- Observational, and treated patients were sicker [7].
With chloramphenicol and drugs that affect B12 tests or absorption
The labels warn that chloramphenicol and other bone marrow suppressing drugs can blunt the response to B12, and that some antibiotics and methotrexate distort B12 blood tests.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- The hydroxocobalamin label says a blunted response may be due to infection, uremia, iron or folic acid deficiency, or bone marrow suppressing drugs such as chloramphenicol [3]. The cyanocobalamin label says most antibiotics, methotrexate and pyrimethamine invalidate folic acid and B12 blood assays, and colchicine, para-aminosalicylic acid and heavy alcohol use for over 2 weeks may cause B12 malabsorption [4].
- Population
- Label statements [3][4].
- Sources
- [3], [4]
- Caveats
- No rates are given [3][4].
Possible, not studied in people1
Use in pregnancy
Not studied in people. Animal studies of high-dose hydroxocobalamin into a vein found skeletal and soft tissue abnormalities, while ordinary B12 needs rise in pregnancy.
No study in people. This rests on animal studies.
The numbers and sources
- Effect
- In pregnant rats and rabbits, hydroxocobalamin during organogenesis caused skeletal and soft tissue abnormalities, including in the central nervous system, at exposures similar to the cyanide-poisoning dose. The Cyanokit label says human case data are insufficient to identify a risk and that treatment for cyanide poisoning is not to be withheld because of pregnancy [8]. The cyanocobalamin label says no adequate studies in pregnant women have been done and that B12 requirements rise in pregnancy [4].
- Population
- Pregnant rats and rabbits [8]; label statements [4].
- Sources
- [8], [4]
- Caveats
- The animal findings are for doses thousands of times those used for deficiency [8][4].
Claims tested and not found
- That B12 by mouth cannot correct deficiency that injections correct. In randomized trials of deficient adults, 1 to 2 mg a day by mouth corrected blood levels and anemia as well as injections over 3 to 4 months [1][2].
- That hydroxocobalamin improves survival in smoke inhalation in the ICU. In 739 patients, it was not linked to survival after adjustment (OR 1.114) [7].
Related
Sources
- Kuzminski AM, Del Giacco EJ, Allen RH, et al. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998. https://doi.org/10.1182/blood.v92.4.1191
- Bolaman Z, Kadikoylu G, Yukselen V, et al. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study. Clinical Therapeutics. 2003. https://doi.org/10.1016/s0149-2918(03)90096-8
- Hydroxocobalamin injection USP, for intramuscular use, prescribing information (Actavis Pharma). 2024. DailyMed, US National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a3087a39-f218-4f16-a1e7-17c39bb2eb69
- Cyanocobalamin injection USP, prescribing information (Plano Pharmaceuticals). 2025. DailyMed, US National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4cbc05f6-4b31-4a5f-e063-6394a90a676c
- Sanz-Cuesta T, Escortell-Mayor E, Cura-Gonzalez I, 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. 2020. https://doi.org/10.1136/bmjopen-2019-033687
- Fortin JL, Giocanti JP, Ruttimann M, Kowalski JJ. Prehospital administration of hydroxocobalamin for smoke inhalation-associated cyanide poisoning: 8 years of experience in the Paris Fire Brigade. Clinical Toxicology. 2006. https://doi.org/10.1080/15563650600811870
- Dépret F, Hoffmann C, Daoud L, et al. Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study. Critical Care. 2019. https://doi.org/10.1186/s13054-019-2706-0
- Cyanokit (hydroxocobalamin) for injection, for intravenous infusion, prescribing information (BTG International). 2023. DailyMed, US National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d56fcc8d-bd64-46ab-b0c0-2124bd745a6b
- Patel JJ, Willoughby R, Peterson J, et al. High-Dose IV Hydroxocobalamin (Vitamin B12) in Septic Shock: A Double-Blind, Allocation-Concealed, Placebo-Controlled Single-Center Pilot Randomized Controlled Trial (The Intravenous Hydroxocobalamin in Septic Shock Trial). Chest. 2023. https://doi.org/10.1016/j.chest.2022.09.021
- Cadd M, Watson U, Kilpatrick T, et al. Hydroxocobalamin Versus Methylene Blue for Treatment of Vasoplegic Shock Following Cardiopulmonary Bypass: A Systematic Review and Meta-analysis. Journal of Cardiothoracic and Vascular Anesthesia. 2024. https://doi.org/10.1053/j.jvca.2024.09.135
- Regland B, Forsmark S, Halaouate L, et al. Response to vitamin B12 and folic acid in myalgic encephalomyelitis and fibromyalgia. PLOS ONE. 2015. https://doi.org/10.1371/journal.pone.0124648
- Sivakumar A, Forman HP, Wang I, et al. State Policies and Facility Practices of IV Hydration Spas in the US. JAMA Internal Medicine. 2025. https://doi.org/10.1001/jamainternmed.2025.5028