Vitamin B12
Vitamin B12 is essential for nerves and blood formation. Supplementation helps most when intake or absorption is inadequate.
Overview
What is vitamin B12?
Vitamin B12 is a water-soluble vitamin and is one of 8 B vitamins.
Vitamin B12 is essential and is found in meat, dairy and fish in high concentrations. However, vitamin B12 from eggs is poorly absorbed relative to other sources (<9%).
Supplements are effective for treating a vitamin B12 deficiency and can help to maintain B12 levels in those who are deficient.
Dietary guidelines assume that 50% of dietary vitamin B12 is absorbed in adults with normal gastrointestinal function.
Dosage
The Recommended Daily Allowance (RDA) for healthy adults is 2.4 mcg per day. Dietary sources are preferred to supplements which often contain around 1000 mcg per serving.
Daily Recommended Dietary Allowances
Men: 2.4 mcg per day
Women: 2.4 mcg per day
Pregnant: 2.6 mcg per day
Lactating: 2.8 mcg per day
Children: 0.4 to 2.4 mcg per day depending on age
Effect graph
Effect heatmap
SupplementDEX Database
15 conditions for , , and rated at least stars. All purchase bands. No minimum star filter.
Database Snapshot
Most vitamin b12 research is concentrated in a handful of conditions.
- High homocysteine levels (hyperhomocysteinemia) accounts for 33 of 102 studies (32%).
- Vitamin B12 deficiency accounts for 17 of 102 studies (17%).
- Stroke accounts for 15 of 102 studies (15%).
- Sparse coverage remains for Canker sores, Cataracts (May exacerbate), Fall prevention (In combination with vitamin D supplementation).
Dietary Sources
Top dietary sources
Daily Value: 2.4 mcg per day
Ranked by amount per 100 g
- 98.9 mcg100 g4121% DV
- 85.7 mcg100 g3571% DV
- 36 mcg100 g1500% DV
- 28.8 mcg100 g1200% DV
- 24.3 mcg100 g1013% DV
- 24 mcg100 g1000% DV
- 20.1 mcg100 g838% DV
- 19 mcg100 g792% DV
Safety
Vitamin B12 is generally well tolerated and safe at the recommended dose. Doses of up to 1000 mcg per day have been used for up to 3 months. There is no tolerable upper intake level as B12 is water-soluble and readily excreted from the body.
Side effects
- Nausea
- Vomiting
- Dizziness
- Headaches
Special populations
Pregnancy & breastfeeding
Likely safeIn pregnant and breastfeeding women, vitamin B12 is safe at the daily recommended dietary intake.
Children
Likely safeIn children, vitamin B12 is safe at the daily recommended dietary intake.
Other notes
Whilst higher plasma B12 levels are associated with liver cancer (but not other cancers), high plasma B12 concentrations may be a consequence of cancer rather than a cause. Studies find that whilst vitamin B6 and B12 supplementation may increase the risk of certain cancers (lung, colorectal) in men and in male smokers, other studies find that B12 supplementation (>12.85 mcg per day) may decrease colorectal cancer risk. When combined with folic acid, vitamin B12 may increase the risk of colorectal cancer.
Frequently Asked Questions
Takeaway
Vitamin B12 is an essential vitamin that is abundant in a wide range of food sources including dairy, meats and seafood.
Vitamin B12 supplements can reliably treat B12 deficiency and reduce high levels of homocysteine in the blood.
Most supplements contain the cyanocobalamin form of vitamin B12, which needs to be converted into methylcobalamin, the active form.
Whilst vitamin B12 supplements contain doses above the recommended daily intake, they are generally safe.
References
Sources94 references
SupplementDEX uses only high-quality sources to determine supplement effectiveness.
SupplementDEX Database · Vitamin B12 deficiency
17 references1.SupplementDEX Database: Vitamin B12 deficiency — Vitamin B12 supplementation orally and intramuscularly in people with obesity undergoing gastric bypass2021
A study of 29 found that methylmalonic acid also remained within reference values in both groups, with no significant differences.
2.SupplementDEX Database: Vitamin B12 deficiency — Enteral Vitamin B12 Supplementation Is Effective for Improving Anemia in Patients Who Underwent Total Gastrectomy2021
A study of 133 found that vitamin B12 deficiency was found in 71.4% of postoperative patients who underwent total gastrectomy for gastric cancer, and enteral vitamin B12 supplements might be effective to improve anemia in these patients.
3.SupplementDEX Database: Vitamin B12 deficiency — Long-Term Iron and Vitamin B12 Deficiency Are Present after Bariatric Surgery, Despite the Widespread Use of Supplements2021
An observational study of 52 found that long-term nutritional deficiencies were greater than the general population among men for iron and among women for vitamin B12.
4.SupplementDEX Database: Vitamin B12 deficiency — Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care: a pragmatic, randomised, non-inferiority clinical trial (OB12)2020
A randomized trial of 143 found that 1 mg/day at week 52, the percentage of patients who achieved normal B 12 levels was 73.6% in the oral arm and 80.4% in the IM arm; these differences were -6.3% (103 out of 112 vs 115 out of 117; 95% CI: -11.9 to -0.1; p=0.025) and -6.8% (103 out of 140 vs 115 out of 143; 95% CI: -16.6.
5.SupplementDEX Database: Vitamin B12 deficiency — Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency2018
A systematic review of 153 studies found that 1000 μg/day for 6–72 years one trial used 2000 μg/day vitamin B 12 and demonstrated a mean difference of 680 pg/mL (95% confidence interval 392.7 to 967.3) in favour of oral vitamin B 12 .
6.SupplementDEX Database: Vitamin B12 deficiency — Guidelines for the diagnosis and treatment of cobalamin and folate disorders2014
A study found that the clinical picture is the most important factor in assessing the significance of test results assessing cobalamin status because there is no 'gold standard' test to define deficiency.
7.SupplementDEX Database: Vitamin B12 deficiency — Hematological response to short-term oral cyanocobalamin therapy for the treatment of cobalamin deficiencies in elderly patients2006
A study in older adults found that our findings support the view that one month of oral crystalline cyanocobalamin is effective to correct serum vitamin B12 levels and to obtain hematological responses in elderly patients with cobalamin deficiency related to FCM.
8.SupplementDEX Database: Vitamin B12 deficiency — Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial2005
A randomized trial of 120 older adults found that 2.5–1,000 µg cyanocobalamin/day for 16 weeks daily doses of 647 to 1032 mug of cyanocobalamin were associated with 80% to 90% of the estimated maximum reduction in the plasma methylmalonic acid concentration.
9.SupplementDEX Database: Vitamin B12 deficiency — [Early response to oral cobalamin therapy in older patients with vitamin B12 deficiency]2003
A study of 14 older adults found that 1,000 µg oral cyanocobalamin/day cyanocobalamin given orally during one week may be an effective treatment for cobalamin deficiency related to food-cobalamin malabsorption and nutritional deficiency and may avoid painful intra-muscular injections in older patients.
10.SupplementDEX Database: Vitamin B12 deficiency — A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations2002
A randomized trial of 10 older adults found that the change in the 10-microg cyanocobalamin group was not significantly different from that in the placebo group (P=.186).
11.SupplementDEX Database: Vitamin B12 deficiency — Is low-dose oral cobalamin enough to normalize cobalamin function in older people?2002
An observational study in older adults found that oral Cbl (2-37.5 microg/day) intake by community-dwelling healthy older adults is associated with higher serum levels of Cbl and improved or normalized Cbl function, as indicated by lower concentrations of the metabolites MMA, HCYS, and MCTR.
12.SupplementDEX Database: Vitamin B12 deficiency — Response of elevated methylmalonic acid to three dose levels of oral cobalamin in older adults2002
A study of 11 older adults found that 25–1,000 µg oral cobalamin/day for 6 weeks a dose of 1,000 microg/day proved to be the most effective in lowering MMA levels to within normal limits.
13.SupplementDEX Database: Vitamin B12 deficiency — Older men and women efficiently absorb vitamin B-12 from milk and fortified bread2001
A randomized trial in adults found that mean absorptions from water, milk and fortified bread were 55, 65 and 55%, respectively, and did not differ.
14.SupplementDEX Database: Vitamin B12 deficiency — Signs of impaired cognitive function in adolescents with marginal cobalamin status2000
An observational study of 24 children/adolescents found that a significant relation between test score and cobalamin deficiency (P: = 0.01) was observed for a test measuring fluid intelligence (correlation coefficient: -0.28; 95% CI: -0.48, -0.08).
15.SupplementDEX Database: Vitamin B12 deficiency — Oral or parenteral therapy for B12 deficiency1998
A study found that oral or parenteral therapy for B12 deficiency..
16.SupplementDEX Database: Vitamin B12 deficiency — Normalization of low vitamin B12 serum levels in older people by oral treatment1997
A study in older adults found that normalization of low vitamin B12 serum levels in older people by oral treatment..
17.SupplementDEX Database: Vitamin B12 deficiency — Vitamin B-12 deficiency in elderly individuals: diagnosis and requirements1994
A study in older adults found that vitamin B-12 deficiency in elderly individuals: diagnosis and requirements..
18.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Effect of Vitamin B6, B9, and B12 Supplementation on Homocysteine Level and Cardiovascular Outcomes in Stroke Patients: A Meta-Analysis of Randomized Controlled Trials2021
A meta-analysis of 8513 participants found that risk ratio (RR) was calculated for determining the risk of stroke, major cardiovascular disorder, and vascular death by using a fixed-effect model.
19.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Effects of 2-year vitamin B12 and folic acid supplementation in hyperhomocysteinemic elderly on arterial stiffness and cardiovascular outcomes within the B-PROOF trial2015
A randomized trial of 569 older adults found that 500 µg vitamin B12 + 400 µg folic acid/day for 2 years analysis of covariance showed no effect of supplementation on PWV levels, and this was not different for patients without increased arterial stiffness at baseline.
20.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Combined analyses and extended follow-up of two randomized controlled homocysteine-lowering B-vitamin trials2010
A meta-analysis of 6837 participants found that 40 mg for 1–2 months folic acid plus vitamin B12 treatment lowered homocysteine levels by 25% but did not influence MACE incidence (hazard ratio, 1.07; 95% CI, 0.95-1.21) during 39 months of follow-up, or cardiovascular mortality (hazard ratio, 1.12; 95% CI, 0.95-1.31) during 78 months of.
21.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Homocysteine lowering and cardiovascular events after acute myocardial infarction2006
A randomized trial of 3749 adults found that 0.8 mg folic acid + 0.4 mg vitamin B12 + 40 mg vitamin B6/day the mean total homocysteine level was lowered by 27 percent among patients given folic acid plus vitamin B12, but such treatment had no significant effect on the primary end point (risk ratio, 1.08; 95 percent confidence interval, 0.93 to 1.25; P=0.31).
22.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials2005
A meta-analysis of 2596 participants found that after standardization for sex and to pretreatment plasma concentrations of 12 micromol homocysteine/L and 12 nmol folate/L, daily doses of 0.2, 0.4, 0.8, 2.0, and 5.0 mg folic acid were associated with reductions in homocysteine of 13% (95% CI: 10%, 16%), 20% (17%, 22%), 23%.
23.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Decrease of carotid intima-media thickness in patients at risk to cerebral ischemia after supplementation with folic acid, Vitamins B6 and B122005
A randomized trial of 50 found that 2.5 mg/day for 1 year the mean individual changes of IMT between both groups differed significantly (-0.08 +/- 0.17 versus 0.07 +/- 0.25 mm, P = 0.019).
24.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial2004
A randomized trial of 1853 adults found that 2.5 mg folic acid + 25 mg vitamin B6 + 0.5 mg vitamin B12/day for 2 years a 3- micromol/L lower total homocysteine level was associated with a 10% lower risk of stroke (P =.05), a 26% lower risk of CHD events (P<.001), and a 16% lower risk of death (P =.001) in the low-dose group and a nonsignificantly lower risk in the high-dose gro
25.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — The challenge of stroke prevention2004
A study found that the challenge of stroke prevention..
26.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Vitamin supplementation reduces the progression of atherosclerosis in hyperhomocysteinemic renal-transplant recipients2003
A randomized trial of 28 found that 5 mg/day for 6 months fasting Hcy levels markedly decreased in group A after treatment (21.8 [15.5-76.6] micromol/L vs. 9.3 [5.8-13] micromol/L; P<0.0001), whereas no significant changes were observed in group B (20.5 [17-37.6] micromol/L vs. 20.7 [15-34] micromol/L; P=not significant).
27.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Optimization of folic acid, vitamin B(12), and vitamin B(6) supplements in pediatric patients with sickle cell disease2002
A study in children/adolescents found that 400–1,000 µg folic acid + 1–5 RDA vitamin B12 + 1–3 RDA vitamin B6/day for 7–16 years rBC folate is less valuable for folate status assessment in SCD patients.
28.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Oral vitamin B(12) and high-dose folic acid in hemodialysis patients with hyper-homocyst(e)inemia2001
A randomized trial in hemodialysis patients found that homocyst(e)ine levels were reduced further from 22.3 to 18.6 micromol/L (mean reduction 16.7%, 95% CI 11.8 to 21.6%, P < 0.001) after four weeks of therapy with vitamin B(12) (1 mg/day).
29.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Treatment of hyperhomocysteinemia in hemodialysis patients and renal transplant recipients2001
A randomized trial of 50 hemodialysis patients found that 15 mg/day for 12 weeks the mean percentage (%) reductions (+/- 95% confidence intervals) in predialysis tHcy were not significantly different [MTHF 17.0% (12.0 to 22.0%), FA 14.8% (9.6 to 20.1%), P = 0.444 by matched analysis of covariance adjusted for pretreatment tHcy].
30.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Homocysteine lowering effect of different multivitamin preparations in patients with end-stage renal disease2001
A randomized trial in healthy adults found that 800 µg folic acid + 6 µg vitamin B12 + 10 mg vitamin B6, 3×/week preparation A reduced the tHcy concentration significantly by nearly 50%, whereas preparation B did not change the tHcy concentration in comparison with placebo.
31.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Diagnosis and treatment of hyperhomocysteinemia2001
A study found that vitamin therapy, particularly with folic acid, reduces plasma homocysteine significantly and improves other surrogate markers of cardiovascular risk such as endothelial function.
32.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Preventive health care, 2000 update: screening and management of hyperhomocysteinemia for the prevention of coronary artery disease events. The Canadian Task Force on Preventive Health Care2000
A meta-analysis found that if population-based studies are correct, tHcy may be responsible for up to 10% of CAD events and thus may represent an important and potentially modifiable risk factor for cardiovascular disease.
33.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Vitamin supplements and cardiovascular risk: review of the randomized trials of homocysteine-lowering vitamin supplements2000
An observational study found that after standardization for a pretreatment homocysteine concentration of 12 micromol/L and folate concentration of 12 nmol/L (approximate average concentrations for western populations), dietary folic acid reduced homocysteine levels by 25% (95% confidence interval [CI]: 23 to.
34.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Treatment of mild hyperhomocysteinemia in renal transplant recipients versus hemodialysis patients2000
A study of 39 hemodialysis patients found that 2.4 mg/day the mean percent (%) reductions (+/-95% confidence interval) in tHcy were: RTR=28.1% (16.2-40.0%); HD=12.1% (6.6-17.7%), P=0.027 for comparison of between-groups differences by analysis of covariance adjusted for baseline tHcy levels.
35.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Therapeutic potential of total homocysteine-lowering drugs on cardiovascular disease2000
A study in patients with impaired renal function found that total homocysteine plasma levels can be lowered or normalised by folic acid and/or vitamin B(6) and vitamin B(12) supplementation.
36.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Cardiovascular risk factors in vegetarians. Normalization of hyperhomocysteinemia with vitamin B(12) and reduction of platelet aggregation with n-3 fatty acids2000
A study of 18 adults found that 700 mg/day for 8 weeks whether this supplementation improves the already reduced cardiovascular morbidity and mortality associated with vegetarian diet has yet to be demonstrated.
37.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Hyperhomocysteinemia in hemodialysis patients: effects of 12-month supplementation with hydrosoluble vitamins2000
A randomized trial of 168 found that after six months, the mean reduction in tHcy was slightly but significantly greater for patients receiving intravenous folic acid (12.2 +/- 18.5 micromol/L) compared with patients not receiving it (8.3 +/- 9.8 micromol/L, P < 0.05).
38.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Relationship between plasma homocysteine and vitamin status in the Framingham study population. Impact of folic acid fortification2000
An observational study found that prevalence of stenosis > or = 25% was 43% in men and 34% in women, with an odds ratio of 2.0 for individuals in the highest homocysteine quartile (> or = 14.4 mumol/L) compared with those in the lowest quartile ( 13 mumol/L) decreased from 18.7 to 9.8% (P < 0.001) between.
39.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Low serum folate concentrations are associated with an excess incidence of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study2000
An observational study of 734 men found that in a Cox model adjusting for age, examination years, and plasma lycopene concentration, in men with higher serum folate concentrations the relative risk for an acute coronary event was 0.31 (95% CI 0.11-0.90, P=0.031) when compared with men with lower serum folates.
40.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — The controversy over homocysteine and cardiovascular risk2000
A randomized trial in children/adolescents found that thus, only placebo-controlled intervention studies with tHcy-lowering B vitamins and clinical endpoints can provide additional valid arguments for the debate over whether tHcy is a causal CVD risk factor.
41.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — What level of plasma homocyst(e)ine should be treated? Effects of vitamin therapy on progression of carotid atherosclerosis in patients with homocyst(e)ine levels above and below 14 micromol/L2000
A study of 101 patients with vascular disease found that 2.5 mg folic acid + 25 mg pyridoxine + 250 µg cyanocobalamin/day high levels of plasma homocyst(e)ine (H[e]) are associated with increased vascular risk.
42.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Enhanced reduction of fasting total homocysteine levels with supraphysiological versus standard multivitamin dose folic acid supplementation in renal transplant recipients1999
A randomized trial of 29 found that 50 mg/day for 12 weeks moreover, a chi(2) analysis of participants with pretreatment tHcy levels >/=15 micromol/L (n=29) indicated that a significantly greater proportion of those in group 1 achieved posttreatment levels <12 micromol/L: group 1, 5 of 10 (50%); group 2, 1 of 11 (9%); and group 3, 0.
43.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Whole blood folate, homocysteine in serum, and risk of first acute myocardial infarction1999
An observational study of 107 found that an increase of 50 nmol/l whole blood folate was associated with an OR for MI of 0.75, and an increase of 5 micromol/l tHcy with an OR for MI of 1.57.
44.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists' Collaboration1998
A meta-analysis of 1114 participants found that 16.5 mg/day typically in Western populations, daily supplementation with both 0.5-5 mg folic acid and about 0.5 mg vitamin B-12 would be expected to reduce blood homocysteine concentrations by about a quarter to a third (for example, from about 12 mumol/l to 8-9 mumol/l).
45.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers1998
A randomized trial of 227 healthy adults found that 5 mg folic acid + 0.4 mg hydroxycobalamin + 50 mg pyridoxine/day our study shows that combined vitamin supplementation reduces homocysteine levels effectively in patients with venous thrombosis and in healthy volunteers, either with or without hyperhomocysteinemia.
46.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Effects of folic acid and combinations of folic acid and vitamin B-12 on plasma homocysteine concentrations in healthy, young women1998
A randomized trial of 150 women found that the effect observed with the combination of folic acid + 400 microg vitamin B-12 (total homocysteine, -18%) was significantly larger than that with a supplement containing folic acid alone (total homocysteine, -11%) (P < 0.05).
47.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Elevated homocysteine levels indicate suboptimal folate status in pediatric sickle cell patients1998
A study of 20 children/adolescents found that vitamin B6 and B12 supplementation did not change their homocysteine levels, but folate supplementation caused a 53% reduction (to 5.7 +/- 1.6).
48.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Treatment of hyperhomocysteinemia in renal transplant recipients. A randomized, placebo-controlled trial1997
A randomized trial of 8 found that 50 mg/day these results occurred after adjustment for age; sex; and pretreatment levels of total homocysteine, B vitamins, and creatinine.
49.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid1995
A randomized trial of 20 patients with myocardial infarction found that 2.5–10 mg folic acid appears to be an effective treatment for the reduction of both normal and increased plasma homocysteine concentrations in patients with myocardial infarction.
50.SupplementDEX Database: High homocysteine levels (hyperhomocysteinemia) — A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes1995
A meta-analysis of 27 studies found that the odds ratio (OR) for CAD of a 5-mumol/L tHcy increment is 1.6 (95% confidence interval [CI], 1.4 to 1.7) for men and 1.8 (95% CI, 1.3 to 1.9) for women.
51.SupplementDEX Database: Imerslund-Gräsbeck syndrome — Imerslund-Gräsbeck syndrome (selective vitamin B(12) malabsorption with proteinuria)2006
A study in children found that management includes life-long vitamin B(12) injections, and with this regimen, the patients stay healthy for decades.
SupplementDEX Database · Canker sores
2 references52.SupplementDEX Database: Canker sores — The Effectiveness of Vitamin B12 for Relieving Pain in Aphthous Ulcers: A Randomized, Double-blind, Placebo-controlled Trial2015
A randomized trial of 42 patients with mouth ulcers found that the results of this research study provide evidence that vitamin B12 is an effective analgesic treatment for aphthous ulcers.
53.SupplementDEX Database: Canker sores — Effectiveness of vitamin B12 in treating recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled trial2009
A randomized trial of 58 found that 1000 mcg/day for 6 months the duration of outbreaks, the number of ulcers, and the level of pain were reduced significantly (P < .05) at 5 and 6 months of treatment with vitamin B(12), regardless of initial vitamin B(12) levels in the blood.
54.SupplementDEX Database: Cyanide poisoning (Hydroxocobalamin) — Review article: management of cyanide poisoning2012
A systematic review of 74 studies found that no case series using dicobalt edetate or 4-dimethylaminophenol were identified, but successful use in single cases has been reported.
55.SupplementDEX Database: Cyanide poisoning (Hydroxocobalamin) — Smoke inhalation injury in a pregnant patient: a literature review of the evidence and current best practices in the setting of a classic case2012
A study in women found that although burned and presenting with concomitant smoke inhalation injury, both the woman and her child fared well with no significant complications due to the smoke inhalation at 6 months of follow-up.
56.SupplementDEX Database: Cyanide poisoning (Hydroxocobalamin) — Empiric management of cyanide toxicity associated with smoke inhalation2011
A study in adults found that prehospital studies have demonstrated the feasibility and safety of empiric treatment with hydroxocobalamin for patients with suspected smoke inhalation cyanide toxicity.
57.SupplementDEX Database: Cyanide poisoning (Hydroxocobalamin) — Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation2007
A study of 42 adults found that 5 g hydroxocobalamin (max 15 g) empiric administration of hydroxocobalamin was associated with survival among 67% of patients confirmed a posteriori to have had cyanide poisoning.
SupplementDEX Database · Postherpetic neuralgia
3 references58.SupplementDEX Database: Postherpetic neuralgia — Local Administration of Methylcobalamin and Lidocaine for Acute Ophthalmic Herpetic Neuralgia: A Single-Center Randomized Controlled Trial2016
A randomized trial of 98 found that the mean pain scores in A1 (2.6 ± 0.7) and B1 (1.2 ± 0.8) decreased significantly compared with those in A0 (7.0 ± 1.7) and B0 (5.6 ± 1.9), and the difference between the two therapeutic strategies significantly increased over time.
59.SupplementDEX Database: Postherpetic neuralgia — Thiamine, cobalamin, locally injected alone or combination for herpetic itching: a single-center randomized controlled trial2014
A randomized trial of 16 patients with herpetic itching found that however, lidocaine did not provide significant itch or pain relief than the other groups.
60.SupplementDEX Database: Postherpetic neuralgia — A single-center randomized controlled trial of local methylcobalamin injection for subacute herpetic neuralgia2013
A randomized trial of 33 patients with subacute herpetic neuralgia found that subjects were randomized to receive local methylcobalamin injection (N = 33), oral methylcobalamin (N = 33), or subcutaneous 1.0% lidocaine injection (N = 32) for 4 weeks.
61.SupplementDEX Database: Age-related cognitive decline — Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression2021
A meta-analysis of 6276 participants found that in most cases, such complaints are not associated with overt vitamin B12 deficiency or advanced neurological disorders and the effectiveness of vitamin B12 supplementation in such cases is uncertain.
62.SupplementDEX Database: Age-related cognitive decline — Results of 2-year vitamin B treatment on cognitive performance: secondary data from an RCT2014
A randomized trial of 759 older adults found that 400 µg folic acid + 500 µg vitamin B12/day for 2 years hcy concentrations decreased 5.0 (95% confidence interval -5.3 to -4.7) µmol/L in the B-vitamin group and 1.3 (-1.6 to -0.9) µmol/L in the placebo group.
63.SupplementDEX Database: Age-related cognitive decline — Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials2012
A meta-analysis found that b-vitamin supplementation did not show an improvement in cognitive function for individuals with (SMD = 0.10, 95%CI -0.08 to 0.28) or without (SMD = -0.03, 95%CI -0.1 to 0.04) significant cognitive impairment.
64.SupplementDEX Database: Age-related cognitive decline — Vitamin B6, B12, and folic acid supplementation and cognitive function: a systematic review of randomized trials2007
A systematic review of 3 studies found that six trials of combinations of the B vitamins all concluded that the interventions had no effect on cognitive function.
65.SupplementDEX Database: Age-related cognitive decline — Randomized trial of the effect of supplementation on the cognitive function of older people with subnormal cobalamin levels1998
A randomized trial in older adults found that supplemented subjects improved in performance IQ, but the amount of improvement was not significantly more than that of control subjects.
SupplementDEX Database · Alzheimer's disease
3 references66.SupplementDEX Database: Alzheimer's disease — Effects of Folic Acid and Vitamin B12 Supplementation on Cognitive Impairment and Inflammation in Patients with Alzheimer's Disease: A Randomized, Single-Blinded, Placebo-Controlled Trial2021
A randomized trial of 120 dementia patients found that 1.2 mg/day moreover, supplementation significantly increased plasma SAM (P<0.001) and SAM/SAH (P<0.001), and significantly decreased the levels of serum Hcy (P<0.001), plasma SAH (P<0.001), and serum TNFα (P<0.001) compared to in the control subjects.
67.SupplementDEX Database: Alzheimer's disease — High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial2008
A randomized trial of 340 dementia patients found that 5 mg/day for 18 months prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline.
68.SupplementDEX Database: Alzheimer's disease — Relation of higher folate intake to lower risk of Alzheimer disease in the elderly2007
An observational study of 192 older adults found that the highest quartile of total folate intake was related to a lower risk of AD (hazard ratio, 0.5; 95% confidence interval, 0.3-0.9; P=.02 for trend) after adjustment for age, sex, education, ethnic group, the epsilon4 allele of apolipoprotein E, diabetes mellitus,.
69.SupplementDEX Database: Cataracts (May exacerbate) — Folic Acid, Vitamin B6, and Vitamin B12 in Combination and Age-Related Cataract in a Randomized Trial of Women2016
A randomized trial of 3925 women found that 2.5 mg/day for the secondary endpoint of cataract extraction, there were 155 in the combination treatment group and 120 in the placebo group (HR 1.28, 95% CI 1.01-1.63; p = 0.04).
SupplementDEX Database · Depression
6 references70.SupplementDEX Database: Depression — Associations of dietary vitamin B1, vitamin B2, vitamin B6, and vitamin B12 with the risk of depression: a systematic review and meta-analysis2021
A meta-analysis of 18 studies found that the pooled RR (95% CI) of depression for the highest vs the lowest category of dietary vitamin B2 was 0.80 (0.64-0.99) in females and 0.83 (0.67-1.02) in males, for dietary vitamin B6 was 0.71 (0.59-0.86) in females and 0.92 (0.76-1.12) in males, and for dietary vitamin B12.
71.SupplementDEX Database: Depression — Vitamin B12 Supplementation: Preventing Onset and Improving Prognosis of Depression2020
A study in women found that numerous studies were reviewed, and based on these studies, it was concluded that supplementation of Vitamin B12 early enough can delay the onset of depression and improve the effect of anti-depressants when used in conjunction with Vitamin B12.
72.SupplementDEX Database: Depression — Risk of depression in pregnant women with low-normal serum Vitamin B122019
An observational study of 174 women found that in multivariate logistic regression models, pregnant women with low-normal serum Vitamin B12 levels (OR = 3.82, 95% CI [1.10-13.31], p < 0.04) were 3.82 times more likely to experience depression, controlling for sociodemographic characteristics, pre-pregnancy BMI, and the.
73.SupplementDEX Database: Depression — A Systematic Review and Meta-Analysis of B Vitamin Supplementation on Depressive Symptoms, Anxiety, and Stress: Effects on Healthy and 'At-Risk' Individuals2019
A meta-analysis of 958 participants found that a benefit to depressive symptoms did not reach significance ( n = 568, SMD = 0.15, 95% CI = -0.01, 0.32, p = 0.07), and there was no effect on anxiety ( n = 562, SMD = 0.03, 95% CI = -0.13, 0.20, p = 0.71).
74.SupplementDEX Database: Depression — Intakes of folate, vitamin B6 and B12 and risk of depression in community-dwelling older adults: the Quebec Longitudinal Study on Nutrition and Aging2016
An observational study of 1368 adults found that women in the highest tertile of B6 intake from food were 43% less likely to become depressed when adjusting for demographic and health factors (multivariate odds ratio (OR) 0.57, 95% confidence interval (CI) 0.39-0.96), but adjustment for energy intake attenuated the effect.
75.SupplementDEX Database: Depression — Systematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin B12 for depression2015
A meta-analysis of 5 studies found that this systematic review aimed to clarify if, compared with placebo, treatment with folate and/or vitamin B12 reduces depression scale scores, increases remission, and prevents the onset of clinically significant symptoms of depression in people at risk.
76.SupplementDEX Database: Physical performance (Elderly) — A Randomized Controlled Trial to Examine the Effect of 2-Year Vitamin B12 and Folic Acid Supplementation on Physical Performance, Strength, and Falling: Additional Findings from the B-PROOF Study2016
A randomized trial of 2919 older adults found that 600 IU/day for 2 years moreover, time to first fall was not significantly different (HR: 1.0, 95% CI 0.9-1.2).
SupplementDEX Database · Osteoporosis
3 references77.SupplementDEX Database: Osteoporosis — Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease: Extended follow-up of the B-PROOF trial2021
A randomized trial of 662 older adults found that 400 μg for 5–7 years no effect was observed of the intervention on osteoporotic fracture or any fracture risk after a follow-up (HR: 0.99, 95% CI: 0.62-1.59 and HR: 0.77; 95% CI: 0.50-1.19, respectively), nor on cardiovascular or cerebrovascular disease risk (OR: 1.05; 95%CI: 0.80-1.44 and OR:.
78.SupplementDEX Database: Osteoporosis — Effect of daily vitamin B-12 and folic acid supplementation on fracture incidence in elderly individuals with an elevated plasma homocysteine concentration: B-PROOF, a randomized controlled trial2014
A randomized trial of 2919 adults found that 600 IU/day osteoporotic fracture risk was not significantly different between groups in the intention-to-treat analyses (HR: 0.84; 95% CI: 0.58, 1.21) or per-protocol analyses (HR: 0.81; 95% CI: 0.54, 1.21).
79.SupplementDEX Database: Osteoporosis — The effect of homocysteine-lowering with B-vitamins on osteoporotic fractures in patients with cerebrovascular disease: substudy of VITATOPS, a randomised placebo-controlled trial2013
A randomized trial of 8164 patients with cerebrovascular disease found that 2 mg folic acid + 25 mg vitamin B6 + 500 µg vitamin B12/day for 2.8 years participants had a mean age of 62.6 years (SD 12.5 years) and 64% were male, 42% of Western European descent and 75% were functionally independent (Oxford Handicap Scale of two or less).
80.SupplementDEX Database: Circadian rhythm sleep disorders — Clinical features of circadian rhythm sleep disorders in outpatients1998
An observational study of 86 found that the 56 (65.1%) cases with primary CRSD showed good response to vitamin B12 and bright light therapy; however, 28 (70.0%) cases with secondary CRSD did not respond to such therapies.
81.SupplementDEX Database: Circadian rhythm sleep disorders — Circadian rhythm sleep disorders in adolescents: clinical trials of combined treatments based on chronobiology1998
A study of 20 children/adolescents found that after consideration of these results, a step-by-step procedure of combined treatments for the circadian rhythm sleep disorders is proposed.
82.SupplementDEX Database: Circadian rhythm sleep disorders — Vitamin B12 treatment for delayed sleep phase syndrome: a multi-center double-blind study1997
A randomized trial of 50 (ages 13–55) found that 3 mg/day for 4 weeks no significant differences were observed between the 2 groups in subjective evaluations of mood or drowsiness during the daytime or in night sleep by sleep-log evaluation.
83.SupplementDEX Database: Circadian rhythm sleep disorders — A multicenter study of sleep-wake rhythm disorders: therapeutic effects of vitamin B12, bright light therapy, chronotherapy and hypnotics1996
A study found that these therapies caused moderate or remarkable improvement in 32% of the non-24, 42% of DSPS, 45% of irregular and 67% of long sleepers.
84.SupplementDEX Database: Circadian rhythm sleep disorders — Treatment of persistent sleep-wake schedule disorders in adolescents with methylcobalamin (vitamin B12)1991
A study in children/adolescents found that serum concentrations of vitamin B12 during treatment were in the high range of normal or above normal.
SupplementDEX Database · Stroke
10 references85.SupplementDEX Database: Stroke — B vitamins in stroke prevention: time to reconsider2017
A meta-analysis found that the potential benefits of B vitamin therapy with folic acid and methylcobalamin or hydroxycobalamin, instead of cyanocobalamin, to lower homocysteine concentrations in people at high risk of stroke warrant further investigation.
86.SupplementDEX Database: Stroke — Homocysteine-lowering interventions for preventing cardiovascular events2017
A meta-analysis of 3929 participants found that compared with placebo, homocysteine-lowering interventions were associated with reduced stroke outcome (homocysteine-lowering = 4.3% versus comparator = 5.1%, RR 0.90, 95% CI 0.82 to 0.99, I 2 = 8%, 10 trials, N = 44,224; high-quality evidence).
87.SupplementDEX Database: Stroke — Efficacy of Supplementation with B Vitamins for Stroke Prevention: A Network Meta-Analysis of Randomized Controlled Trials2015
A meta-analysis of 393 studies found that the risk of stroke was lower with folic acid plus vitamin B6 as compared with folic acid plus vitamin B12 and was lower with folic acid plus vitamin B6 plus vitamin B12 as compared with placebo or folic acid plus vitamin B12.
88.SupplementDEX Database: Stroke — Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials2013
A meta-analysis of 294478 participants found that in a fixed effect meta-analysis of the 50 trials, supplementation with vitamins and antioxidants was not associated with reductions in the risk of major cardiovascular events (relative risk 1.00, 95% confidence interval 0.98 to 1.02; I(2)=42%).
89.SupplementDEX Database: Stroke — Vitamin B supplementation, homocysteine levels, and the risk of cerebrovascular disease: a meta-analysis2013
A meta-analysis of 54913 participants found that we observed a reduction in overall stroke events resulting from reduction in homocysteine levels following B vitamin supplementation (RR 0.93; 95% CI 0.86-1.00; p = 0.04) but not in subgroups divided according to primary or secondary prevention measures, ischemic vs.
90.SupplementDEX Database: Stroke — Effects of vitamin B12 supplementation on cognition, depression, and fatigue in patients with lacunar stroke2013
A randomized study in lacunar stroke patients finding that B12 supplementation improved biochemical status but produced limited changes in cognition, fatigue, or depressive symptoms. A study of 14 stroke patients found that vitamin B12 (1 mg/day hydroxocobalamine for at least 3 months administered by general practitioner) led to a significant improvement in verbal learning in 43% of patients. Vitamin B12 did not improve depression or fatigue.
91.SupplementDEX Database: Stroke — B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial2010
A randomized trial of 4089 found that 2 mg folic acid + 25 mg vitamin B6 + 500 µg vitamin B12/day patients were followed up for a median duration of 3.4 years (IQR 2.0-5.5). 616 (15%) patients assigned to B vitamins and 678 (17%) assigned to placebo reached the primary endpoint (risk ratio [RR] 0.91, 95% CI 0.82 to 1.00, p=0.05; absolute risk reduction 1.56%, -0.01 to 3.16).
92.SupplementDEX Database: Stroke — Homocysteine lowering interventions for preventing cardiovascular events2009
A meta-analysis of 24210 participants found that hLI did not reduce the risk of non-fatal or fatal myocardial infarction, stroke, or death by any cause (pooled RR 1.03, 95% CI 0.94 to 1.13, I(2) = 0%; pooled RR 0.89, 95% CI 0.73 to 1.08, I(2) = 15%); and pooled RR 1.00 (95% CI 0.92 to 1.09, I(2): 0%), respectively.
93.SupplementDEX Database: Stroke — The effect of long-term homocysteine-lowering on carotid intima-media thickness and flow-mediated vasodilation in stroke patients: a randomized controlled trial and meta-analysis2008
A meta-analysis found that 2 mg folic acid + 25 mg vitamin B6 + 0.5 mg vitamin B12/day although short-term treatment with B-vitamins is associated with increased FMD, long-term homocysteine-lowering did not significantly improve FMD or CIMT in people with a history of stroke.
94.SupplementDEX Database: Stroke — Folate, vitamin B12, and risk of ischemic and hemorrhagic stroke: a prospective, nested case-referent study of plasma concentrations and dietary intake2005
A study found that plasma folate was statistically significantly associated with risk of hemorrhagic stroke in an inverse linear manner, both in univariate analysis and after adjustment for conventional risk factors including hypertension (odds ratio [OR] for highest versus lowest quartile 0.21.