Knowledge · Natural Compounds

Vitamin B12

Q: Does Vitamin B12 help with status in vegan diets, older age and with medication? What the studies show

We evaluated 18 meta-analyses or systematic reviews, 24 controlled studies and 43 further studies; the controlled studies include 2,795 participants in total. Result of the controlled studies: mostly improved. Strength of evidence under our published rules: high. Sources: [3, 5, 6, 7]

Q: Does Vitamin B12 help with nerves and nerve damage? What the studies show

We evaluated 8 meta-analyses or systematic reviews, 24 controlled studies and 26 further studies; the controlled studies include 2,302 participants in total. Result of the controlled studies: mostly improved. Strength of evidence under our published rules: high. Sources: [4, 7, 9, 10]

Q: Does Vitamin B12 help with homocysteine, heart and blood vessels? What the studies show

We evaluated 8 meta-analyses or systematic reviews, 24 controlled studies and 27 further studies; the controlled studies include 2,467 participants in total. Result of the controlled studies: mostly improved. Strength of evidence under our published rules: high. Sources: [2, 5, 6, 17]

Q: Does Vitamin B12 help with memory and mood? What the studies show

We evaluated 7 meta-analyses or systematic reviews, 16 controlled studies and 18 further studies; the controlled studies include 1,756 participants in total. Result of the controlled studies: mixed. Strength of evidence under our published rules: high. Sources: [7, 20, 24, 31]

Q: Does Vitamin B12 help with blood formation and anaemia? What the studies show

We evaluated 6 meta-analyses or systematic reviews, 8 controlled studies and 14 further studies; the controlled studies include 2,163 participants in total. Result of the controlled studies: mixed. Strength of evidence under our published rules: high. Sources: [1, 6, 7, 14]

Q: Does Vitamin B12 help with pregnancy and children? What the studies show

We evaluated 3 meta-analyses or systematic reviews, 4 controlled studies and 20 further studies; the controlled studies include 1,599 participants in total. Result of the controlled studies: mixed. Strength of evidence under our published rules: high. Sources: [1, 14, 24, 38]

Q: Which forms of vitamin B12 were investigated in the studies?

Mainly cyanocobalamin, methylcobalamin, adenosylcobalamin and hydroxocobalamin were investigated. Methylcobalamin, also called mecobalamin, was mostly used as a tablet, sometimes also as a gel for application. Hydroxocobalamin was mostly given as an injection.

Q: Does vitamin B12 help with nerve damage?

In diabetic neuropathy, nerve conduction, vibration perception and pain improved with oral methylcobalamin over one year, while they worsened with placebo [91].

Vitamin B12: What 248 human studies show, including 93 randomized controlled trials – organized by area of application and strength of evidence.

Last updated: 2026-10-15

We evaluated 248 human studies on Vitamin B12, including 93 randomised controlled trials and 56 meta-analyses or systematic reviews; the controlled studies include 14,539 participants in total. As of 3 October 2026.

This page as PDF · Summary

1. What Is Vitamin B12? Occurrence, Origin and Forms

Vitamin B12 (cobalamin) is a water-soluble vitamin with a cobalt atom at its centre. The body needs it for blood formation, for the nerves and for breaking down homocysteine; it is absorbed in the small intestine only together with intrinsic factor from the stomach.

Only microorganisms make vitamin B12. It occurs in meaningful amounts in animal foods such as meat, liver, fish, eggs and dairy products; plant foods provide hardly any usable vitamin B12.

For supplements, vitamin B12 is produced by bacteria (fermentation). There are tablets, lozenges and sublingual tablets, drops, nasal sprays and intramuscular injections.

Forms and Preparations Studied

Cyanocobalamin
Methylcobalamin and adenosylcobalamin
Hydroxocobalamin, mostly as injection
Tablets, sublingual tablets, nasal spray and injection
Vitamin B12 combined with folic acid and vitamin B6

Not covered on this page:

Studies that measure vitamin B12 blood levels only as a side finding without studying intake or supplementation

2. What Does Vitamin B12 Do? Results by Area

Area	Result in controlled studies	Strength of evidence	Studies	Participants
Status in vegan diets, older age and with medication	mostly improved	high	18 meta-analyses · 24 controlled · 43 other	2,795
Nerves and nerve damage	mostly improved	high	8 meta-analyses · 24 controlled · 26 other	2,302
Homocysteine, heart and blood vessels	mostly improved	high	8 meta-analyses · 24 controlled · 27 other	2,467
Memory and mood	mixed	high	7 meta-analyses · 16 controlled · 18 other	1,756
Blood formation and anaemia	mixed	high	6 meta-analyses · 8 controlled · 14 other	2,163
Pregnancy and children	mixed	high	3 meta-analyses · 4 controlled · 20 other	1,599
Other outcomes	mostly improved	high	8 meta-analyses · 53 controlled · 45 other	9,028

How to read the table: counted are human studies whose results concern the area. “High” means at least one meta-analysis and two controlled studies showing improvement, or at least three controlled studies of which three quarters show improvement, with at least 300 participants in total. “Moderate” means at least two controlled studies showing improvement, as a majority, or one meta-analysis alongside controlled studies. “Low” means one controlled study showing improvement. Where an area has no controlled study, the strength of evidence is at most “low” (result “reviews only” or “observational data only”). Everything else is “unclear”. A study counts as showing improvement when at least half of its outcomes in this area improved. Reviews of combination products do not count as meta-analyses; results that only describe side effects or shares of users do not count as an effect. The same study is counted only once.

3. What the Studies Show in Detail

Vitamin B12, Status in Vegan Diets, Older Age and with Medication: Human Studies

With a vegan diet without supplementation, reviews and one controlled trial found poorer vitamin B12 blood levels 48 51 115. Even a partial replacement of animal proteins with plant proteins lowered vitamin B12 status 141. With long-term use of omeprazole, vitamin B12 levels after twelve months were lower than with other acid inhibitors in a controlled trial 136. In metformin-treated type 2 diabetics with vitamin B12 deficiency, oral methylcobalamin or sucrosomial cyanocobalamin normalized the levels in one controlled trial each 91 133. Vitamin B12 together with folic acid, sometimes also with vitamin B6, increased vitamin B12 blood levels in meta-analyses 22 41. A salt enriched with iodine, iron, folic acid and other micronutrients provided inconsistent findings on vitamin B12 status 23. The strength of evidence is high; what remains open is how well the mostly short studies can be transferred to pregnant women, children or the very old.

Study	Design · participants	Preparation · dose · duration · comparison	Result
3 Lotti et al. 2026	meta-analysis · 48,626 participants	Lacto-ovo-vegetarian or vegan diet (vitamin B12 as nutrient); vs. Omnivorous diet	Vitamin B12 intake: worsened; Vitamin B12 deficiency in vegans: worsened
5 Mazur et al. 2025	meta-analysis · 6,098 participants	Vitamin B12 sublingual, oral or intramuscular; not reported; dose subgroup analysis showed no dose-response effect; vs. sublingual and oral versus intramuscular injection	Serum cobalamin: improved (pooled mean difference = +402.6 pg/mL; 95% CI: 293.6 to 511.5; p < 0.001); Cobalamin: oral/sublingual versus intramuscular: no difference (p = 0.270)
6 Abdelwahab et al. 2024	meta-analysis · 4,275 participants	Vitamin B12 (various administration routes); vs. Oral vs. intramuscular vs. sublingual	Vitamin B12 levels: no difference (MD = 94.09 and 43.31 pg/mL)
7 Larvie et al. 2026	systematic review · 4,083 participants	Oral vitamin B12 supplementation, alone or with other micronutrients; 0.9 µg/day to 150 µg/day; 28 days to 31 months; vs. Placebo	Vitamin B12 deficiency: improved (ARD 56 fewer per 1000, 95% CI 68 fewer to 24 fewer; 1.8% versus 7.6%; RR 0.27, 95% CI 0.11 to 0.69); Total vitamin B12 concentrations: improved (MD 68.53 pmol/L, 95% CI 41.83 to 95.23)
14 Finkelstein et al. 2024	systematic review · 984 participants	oral vitamin B12 supplementation; 5 µg/day to 250 µg/day; 8–16 to 32–38 weeks, from 8–28 weeks' gestation; vs. placebo or no vitamin B12 supplementation	Maternal vitamin B12 deficiency: improved (25.9% versus 67.9%; RR 0.38, 95% CI 0.28 to 0.51); Total vitamin B12 concentrations: improved (MD 60.89 pmol/L, 95% CI 40.86 to 80.92)
16 Shahid et al. 2025	systematic review · 693 participants	Proton pump inhibitors (PPIs), not vitamin B12; at least 6 months, up to 12 months; vs. no PPI or baseline	Serum vitamin B12: worsened (12-18% reduction in serum vitamin B12 over 12 months)
17 Ménétrier et al. 2023	systematic review · 574 participants	No B12 administration; measurement of total B12, holoTC, tHcy, MMA; vs. No comparison; prevalence of abnormal laboratory values	Proportion with low total vitamin B12: unclear (42.2% (95% confidence interval 37.8-46.6%, n = 486)); Proportion with low holotranscobalamin: unclear (28.6% (7.5-49.6%, n = 21))
18 Wirthensohn et al. 2023	systematic review · 292 participants	—	Maternal B12, exclusive breastfeeding and low-B12 maternal diet predicted infant B12, methylmalonic acid and total homocysteine: unclear

Further studies in this area: 22 23 25 26 28 33 34 39 40 41 47 48 50 51 54 61 62 64 81 85 86 91 92 94 102 112 115 116 119 121 125 127 129 132 133 136 139 141 152 154 155 158 159 160 161 162 163 168 169 170 171 185 186 189 195 201 203 204 205 210 213 214 215 217 218 220 223 224 225 226 227 228 230 231 233 235 237

Vitamin B12, Nerves and Nerve Damage: Human Studies

In type 2 diabetes with neuropathy, nerve conduction, vibration perception and pain improved with oral methylcobalamin over one year, while they worsened with placebo 91. In another study, methylcobalamin worked as well as acetyl-L-carnitine 72. A meta-analysis found better nerve conduction when vitamin B12 was injected into acupuncture points rather than given otherwise 9. After foot or ankle surgery, complex regional pain syndrome occurred less often with methylcobalamin than with placebo 65. During chemotherapy, nerve damage developed less often with vitamin B12 than with placebo 130. In neurological symptoms due to vitamin B12 deficiency, several studies found improvements 20 31 52. A review links a deficiency of vitamin B12 and other nutrients in vegan and vegetarian diets with a higher risk of mental decline 37. The findings are predominantly based on oral methylcobalamin preparations; combinations with alpha-lipoic acid and epalrestat, fasudil, prostaglandin E1, dapagliflozin, herbal medicines or Chinese patent medicine also showed improvements in meta-analyses 10 11 12 32 46, but cannot be attributed to vitamin B12 alone. What remains open are the optimal form, the best route of administration and the effect in non-diabetic neuropathy.

Study	Design · participants	Preparation · dose · duration · comparison	Result
4 Lee et al. 2022	meta-analysis · 6,260 participants	oral methylcobalamin alone or with herbal medicines; vs. oral methylcobalamin alone	sensory nerve conduction velocity (SNCV): improved; motor nerve conduction velocity (MNCV): improved; total efficacy rate (TER): improved
7 Larvie et al. 2026	systematic review · 4,083 participants	Oral vitamin B12 supplementation, alone or with other micronutrients; 0.9 µg/day to 150 µg/day; 28 days to 31 months; vs. Placebo	Motor skill development (6 to 9 years, NEPSY-II): no difference
9 Yu et al. 2026	meta-analysis · 1,688 participants	vitamin B12 via acupoint injection; vs. other administration routes of vitamin B12	clinical effectiveness proportion: improved (RR 1.28, 95% CI 1.22-1.35); peroneal nerve motor nerve conduction velocity: improved (MD 4.43, 95% CI 2.83-6.03); peroneal nerve sensory nerve conduction velocity: improved (MD 3.82, 95% CI 3.23-4.41)
10 Ran et al. 2024	meta-analysis · 1,153 participants	Mecobalamin plus alpha-lipoic acid and epalrestat; vs. Monotherapy or dual therapy with the same drugs	Therapeutic outcome (total efficacy): improved (odds ratio: 3.74; 95 % confidence interval: 2.57-5.45; p < 0.00001); Median motor nerve conduction velocity (MNCV): improved; Sensory nerve conduction velocity (SNCV): improved
11 Jiang et al. 2018	meta-analysis · 1,148 participants	Methylcobalamin alone or with fasudil; vs. Methylcobalamin monotherapy	clinical efficacy: improved (RR 1.26, 95% CI 1.17-1.35, P < .00001); median motor nerve conduction velocity: improved (MD 6.69, 95% CI 4.74-8.64, P < .00001); median sensory nerve conduction velocity: improved (MD 6.71, 95% CI 1.77-11.65, P = .008)
12 Jiang et al. 2018	meta-analysis · 1,136 participants	Methylcobalamin plus prostaglandin E1; vs. Prostaglandin E1 monotherapy	Clinical efficacy: improved (RR 1.25, 95% CI 1.18-1.32, P < .00001); Median motor nerve conduction velocity: improved (MD 6.29, 95% CI 4.63-7.94, P < .00001); Median sensory nerve conduction velocity: improved (MD 5.68, 95% CI 3.53-7.83, P < .00001)
20 Blom et al. 2024	systematic review · 50 participants	cobalamin (monotherapy); mean 2 months; vs. no control (case series)	Disappearance of other neuropsychiatric manifestations: improved (60%)
31 Hamza et al. 2025	systematic review	Vitamin B12 supplements, oral or intramuscular; vs. oral versus intramuscular administration; supplementation versus control	Neurological symptoms in overt deficiency: improved; Symptom scores in diabetic neuropathy: improved; Objective neurological measures in diabetic neuropathy: no difference

Further studies in this area: 32 37 44 46 52 53 65 70 72 73 75 83 88 89 91 94 98 103 104 109 121 122 125 130 134 135 142 146 147 150 168 171 175 181 188 189 193 194 197 202 203 208 209 218 222 233 235 239 241 242

Vitamin B12, Homocysteine, Heart and Blood Vessels: Human Studies

In adults with vitamin B12 deficiency, the administration of vitamin B12 lowered the homocysteine blood level; oral and sublingual intake did not perform worse than intramuscular injection 5 31. Vitamin B12 together with folic acid, sometimes additionally with vitamin B6, also lowered homocysteine, among others in type 2 diabetes, mild cognitive impairment and Alzheimer's disease 22 27 30 35 41 43. The strength of evidence is high, but many studies tested only the homocysteine blood level, not heart attacks or strokes.

Study	Design · participants	Preparation · dose · duration · comparison	Result
2 Ulloque-Badaracco et al. 2023	meta-analysis · 87,988 participants	Vitamin B12 (level measurement, no supplementation); vs. higher vs. lower vitamin B12 levels	Metabolic syndrome with higher vitamin B12 levels: improved (OR = 0.87; 95% CI: 0.81-0.93; p < 0.01); Metabolic syndrome with higher homocysteine levels: worsened (OR = 1.19; 95% CI: 1.14-1.24; p < 0.01); Metabolic syndrome with higher folate levels: no difference (OR = 0.83; 95% CI: 0.66-1.03; p = 0.09)
5 Mazur et al. 2025	meta-analysis · 6,098 participants	Vitamin B12 sublingual, oral or intramuscular; not reported; dose subgroup analysis showed no dose-response effect; vs. sublingual and oral versus intramuscular injection	Homocysteine: improved (pooled mean difference = -4.83 μmol/L; 95% CI: -6.55 to -3.11; p < 0.001); Homocysteine: oral/sublingual versus intramuscular: no difference (p = 0.485)
6 Abdelwahab et al. 2024	meta-analysis · 4,275 participants	Vitamin B12 (various administration routes); vs. Oral vs. intramuscular vs. sublingual	Homocysteine levels: no difference
17 Ménétrier et al. 2023	systematic review · 574 participants	No B12 administration; measurement of total B12, holoTC, tHcy, MMA; vs. No comparison; prevalence of abnormal laboratory values	Proportion with elevated homocysteine: unclear (79.7% (75.9-83.5%, n = 429))
22 Liu et al. 2026	meta-analysis	Vitamin B12, alone or with folic acid and vitamin B6; vs. Randomized controlled trials of nutritional supplements	Blood homocysteine level: improved (varying improvements in blood biomarkers, including homocysteine, vitamin B12, and serum folate levels)
27 Li et al. 2025	systematic review	B vitamins (vitamin B6, vitamin B12, partly folate); vs. Control groups of included trials	Plasma homocysteine: improved (effectively reduce plasma homocysteine levels); Thrombotic risk: unclear (remains uncertain)
30 Yin et al. 2025	meta-analysis	Folic acid plus vitamin B12 (some with vitamin B6); vs. Control (placebo/no supplementation)	Serum homocysteine: improved (SMD = -2.77, 95% CI [-3.23, -2.30], P < 0.0001)
31 Hamza et al. 2025	systematic review	Vitamin B12 supplements, oral or intramuscular; vs. oral versus intramuscular administration; supplementation versus control	Homocysteine levels: improved

Further studies in this area: 33 35 41 43 48 53 59 68 73 81 85 87 95 97 102 107 110 111 114 115 118 119 123 132 137 145 148 149 150 151 157 159 167 168 170 174 176 177 187 188 190 202 206 211 212 217 229 230 237 243 244

Vitamin B12, Memory and Mood: Human Studies

A systematic review reports that hallucinations in vitamin B12 deficiency improved with vitamin B12 alone 20. Another review links a good vitamin B12 status in pregnant women with better language, better memory and better thinking performance in the children 24. In possible mild cognitive impairment, vitamin B12 brought no advantage for memory and depressive symptoms in a meta-analysis 45. Also in children under twelve years, a systematic review found no difference in thinking performance 7. In adults with mild deficiency without symptoms, another review showed no advantages for thinking and nerves 31. Together with folic acid, the results were inconsistent. In Alzheimer's disease, a meta-analysis found a better MMSE value, but no difference in the ADAS-Cog value 43. In mild cognitive impairment, a randomized study found no difference overall, only with greater brain shrinkage in the left frontal area 68. In older adults, an advantage appeared only with higher blood levels of the omega-3 fatty acid DHA 74. The evidence strength is high, but the result is mixed: forms, groups and measures differ greatly, and it remains open which form and dose benefits whom.

Study	Design · participants	Preparation · dose · duration · comparison	Result
7 Larvie et al. 2026	systematic review · 4,083 participants	Oral vitamin B12 supplementation, alone or with other micronutrients; 0.9 µg/day to 150 µg/day; 28 days to 31 months; vs. Placebo	Cognitive function (e.g. attention): no difference (SMD 0.09, 95% CI -0.10 to 0.28)
20 Blom et al. 2024	systematic review · 50 participants	cobalamin (monotherapy); mean 2 months; vs. no control (case series)	Full amelioration of hallucinations: improved (75%); Partial amelioration of hallucinations: improved (25%); Therapy-resistant hallucinations fully resolved under cobalamin monotherapy: improved (a quarter of the cases)
24 Franco et al. 2026	systematic review	Maternal vitamin B12 status or supplementation, with vitamin D and folic acid; vs. Children with adequate vs. inadequate maternal vitamin B12 status	Language, memory and cognitive performance: improved
31 Hamza et al. 2025	systematic review	Vitamin B12 supplements, oral or intramuscular; vs. oral versus intramuscular administration; supplementation versus control	Cognitive and neurological outcomes in subclinical deficiency: no difference
41 Zhao et al. 2025	meta-analysis	Vitamin B12 alone or with folate; vs. Network meta-analysis of several interventions	Cognitive decline: improved
43 Lee et al. 2024	meta-analysis	Vitamin B12 and folic acid; 6 months; vs. Placebo	MMSE score: improved (SMD = 0.21, 95% CI = 0.01 to 0.32, p = 0.04); ADAS-Cog score: no difference (SMD = 0.06, 95% CI = -0.22 to 0.33, p = 0.68)
45 Alzahrani et al. 2024	meta-analysis	Vitamin B12 supplementation (vitamin B12 complex); vs. Control groups of included RCTs	Cognitive memory function: no difference (average standardized mean difference of -0.03 (95% confidence interval (CI): -0.07 to 0.01)); Depressive symptoms: no difference (average standardized mean difference of -0.01 (95% CI: -0.0773 to 0.0525))
49 Jembere et al. 2024	systematic review	Vitamin B12 (status, dietary intake, supplementation)	Children's brain and neurodevelopment: unclear; Cognitive, language and motor development: unclear

Further studies in this area: 52 54 62 68 74 78 90 96 97 99 106 112 113 119 124 127 132 144 163 166 176 177 183 193 194 200 202 218 219 230 231 244 245

Vitamin B12, Blood Formation and Anaemia: Human Studies

In blood formation and anemia, the studies show a mixed picture. For hemoglobin, tablet, sublingual tablet and injection did not differ in a meta-analysis 6. Also in children, administration under the tongue and injection into the muscle yielded the same hemoglobin values 101. Before heart operations, a combination of iron as infusion, erythropoietin, vitamin B12 and folic acid reduced the number of blood transfusions compared with placebo in a randomized study 63. It remains open which form and which route are actually superior in which patient group.

Study	Design · participants	Preparation · dose · duration · comparison	Result
1 Keats et al. 2021	systematic review · 451,723 participants	Single and multiple micronutrient supplements, including vitamin B12; vs. Supplementation vs. folic acid, iron-folic acid or other controls	Maternal anaemia (IFA vs. folic acid): improved (48% reduction (average RR 0.52, 95% CI 0.41 to 0.66))
6 Abdelwahab et al. 2024	meta-analysis · 4,275 participants	Vitamin B12 (various administration routes); vs. Oral vs. intramuscular vs. sublingual	Hemoglobin level: no difference
7 Larvie et al. 2026	systematic review · 4,083 participants	Oral vitamin B12 supplementation, alone or with other micronutrients; 0.9 µg/day to 150 µg/day; 28 days to 31 months; vs. Placebo	Anaemia: no difference (ARD 21 more per 1000)
14 Finkelstein et al. 2024	systematic review · 984 participants	oral vitamin B12 supplementation; 5 µg/day to 250 µg/day; 8–16 to 32–38 weeks, from 8–28 weeks' gestation; vs. placebo or no vitamin B12 supplementation	Maternal anaemia: no difference (70.9% versus 65.0%; RR 1.08, 95% CI 0.93 to 1.26)
18 Wirthensohn et al. 2023	systematic review · 292 participants	—	Mean age at first symptoms (anemia, neurological symptoms): unclear (four months)
19 Abe et al. 2016	systematic review · 52 participants	Multiple-micronutrient supplement (three or more micronutrients); vs. Placebo or no supplementation	Maternal anaemia: improved
20 Blom et al. 2024	systematic review · 50 participants	cobalamin (monotherapy); mean 2 months; vs. no control (case series)	Comorbid pernicious anaemia: unclear (32%)
21 Chen et al. 2026	meta-analysis	Combined treatment with vitamin B12, iron, EPO, folic acid; vs. Placebo and other interventions	Intraoperative blood loss: improved (MD: 126.33 mL, 95% CrI [23.27, 229.49], P < 0.05)

Further studies in this area: 34 40 61 63 64 80 95 101 102 152 164 169 173 188 195 196 198 203 210 235

Vitamin B12, Pregnancy and Children: Human Studies

In pregnancy, the studies show a mixed picture. Observational studies from India link low vitamin B12 values in pregnant women with more neural tube defects, pregnancy complications and lower birth weight 54. In randomized studies, vitamin B12 promoted the mental development of the children; the effect on birth weight remained open 54. In women undergoing artificial fertilization, a fertility-promoting diet with omega-3, vitamin D, folate and vitamin B12 increased the fertilization rate compared with usual counseling 76. The share of vitamin B12 in this cannot be separated. A meta-analysis found lower vitamin B12 levels in mothers with neural tube defects 38. The evidence strength is high, but the forms and routes examined are inconsistent, and several studies tested vitamin B12 only in combination with other nutrients.

Study	Design · participants	Preparation · dose · duration · comparison	Result
1 Keats et al. 2021	systematic review · 451,723 participants	Single and multiple micronutrient supplements, including vitamin B12; vs. Supplementation vs. folic acid, iron-folic acid or other controls	Low birthweight (IFA vs. folic acid): improved (12% reduction (average RR 0.88, 95% CI 0.78 to 0.99)); Low birthweight (MMN vs. iron with or without FA): improved (15% (average RR 0.85, 95% CI 0.77 to 0.93)); Stillbirths (MMN): improved (average RR 0.91; 95% CI 0.86)
14 Finkelstein et al. 2024	systematic review · 984 participants	oral vitamin B12 supplementation; 5 µg/day to 250 µg/day; 8–16 to 32–38 weeks, from 8–28 weeks' gestation; vs. placebo or no vitamin B12 supplementation	Preterm birth: unclear (RR 0.97, 95% CI 0.55 to 1.74); Low birthweight: unclear (RR 1.50, 95% CI 0.93 to 2.43)
24 Franco et al. 2026	systematic review	Maternal vitamin B12 status or supplementation, with vitamin D and folic acid; vs. Children with adequate vs. inadequate maternal vitamin B12 status	Child neurodevelopment: improved
38 Nie et al. 2025	meta-analysis	Maternal blood vitamin B12 (no supplement given); vs. Neural tube defect group vs. non-NTD controls	Maternal blood vitamin B12 level in neural tube defects: worsened (SMD = -0.23, 95% CI (-0.32, -0.14), p < 0.001); Vitamin B12 level in NTD with no folate difference: worsened (SMD: -0.19, 95% CI (-0.28, -0.10))
54 Behere et al. 2021	systematic review	Vitamin B12 (form not specified); vs. low vs. higher maternal B12 status; supplementation vs. control	neural tube defects: improved; pregnancy complications: improved; birth weight: improved
58 Kvestad et al. 2026	randomised controlled · 800 participants	vitamin B-12 or placebo; from early pregnancy to 6 months postpartum; vs. placebo	Infant motor development (TIMP score): worsened; Interaction with plasma folate: unclear (P-interaction = 0.015)
62 Nagpal et al. 2026	randomised controlled · 531 participants	Daily oral methylcobalamin; 250 µg (group A) vs. 50 µg (group B); From enrolment to 6 months post partum; vs. Higher dose 250 µg versus lower dose 50 µg	Newborn anthropometry, APGAR scores and morbidity: no difference (p>0.05)
76 Ghadimi et al. 2026	randomised controlled · 180 participants	Pro-fertility diet plus supplement combination with vitamin B12; vitamin B12 500 µg/day; 60 days; vs. general dietary advice plus 500 µg/day folic acid	fertilization rate: improved (0.81 ± 0.16 versus 0.66 ± 0.24; P < 0.001); embryo formation rate: improved (0.79 ± 0.26 versus 0.62 ± 0.30; P < 0.001); number of embryos formed: improved (3.78 ± 2.34 versus 2.22 ± 1.46; P < 0.001)

Further studies in this area: 93 158 161 162 164 175 181 182 184 187 190 191 192 200 216 221 228 232 236

Vitamin B12: Further Outcomes in Studies

Oral methylcobalamin improved quality of life in a controlled study in type 2 diabetics with long-term metformin intake and diabetic neuropathy 91. For linear growth in children, a systematic review found no difference from placebo 7. For quality of life under oral cyanocobalamin, a controlled study found no difference 130. The evidence strength is high; most of these studies tested methylcobalamin, and it is open whether other forms act the same.

Study	Design · participants	Preparation · dose · duration · comparison	Result
7 Larvie et al. 2026	systematic review · 4,083 participants	Oral vitamin B12 supplementation, alone or with other micronutrients; 0.9 µg/day to 150 µg/day; 28 days to 31 months; vs. Placebo	Height/length: no difference (MD -0.19 cm, 95% CI -2.44 to 2.06)
8 Kuo et al. 2025	meta-analysis · 1,723 participants	Topical vitamin B12 (cobalamin), partly with vitamins D3, E, B3; vs. Placebo	Pruritus severity (all vitamins combined): improved (SMD: -0.578, 95% CI: -0.736 to -0.419, p = 0.000); Pruritus severity (topical vitamin B12 subgroup): improved
9 Yu et al. 2026	meta-analysis · 1,688 participants	vitamin B12 via acupoint injection; vs. other administration routes of vitamin B12	fasting blood glucose: no difference (MD -0.18, 95% CI -0.44 to 0.08); 2-h postprandial blood glucose: no difference (MD -0.02, 95% CI -0.36 to 0.33); adverse event incidence (RR 1.44, 95% CI 0.44-4.70)
10 Ran et al. 2024	meta-analysis · 1,153 participants	Mecobalamin plus alpha-lipoic acid and epalrestat; vs. Monotherapy or dual therapy with the same drugs	Adverse effects (No statistic difference)
13 Li et al. 2025	meta-analysis · 1,130 participants	Folate and vitamin B12 (dietary intake or serum levels); vs. lower versus higher intake/levels	HPV persistence and CIN progression: improved (SMD = 0.80 [0.65, 0.95]; p < 0.00001; I2 = 0%; GRADE: High)
15 Gupta et al. 2021	systematic review · 701 participants	Vitamin B12 among other agents; vs. Placebo or other agents	Hearing outcome in noise-induced hearing loss: unclear
16 Shahid et al. 2025	systematic review · 693 participants	Proton pump inhibitors (PPIs), not vitamin B12; at least 6 months, up to 12 months; vs. no PPI or baseline	Calcium and parathyroid hormone: worsened (declined significantly in a 12-month cohort); Bone turnover markers: worsened (increased despite stable bone mineral density); Magnesium status: unclear (ranging from no change after 12 months to pharmacokinetic alterations without systemic depletion)
17 Ménétrier et al. 2023	systematic review · 574 participants	No B12 administration; measurement of total B12, holoTC, tHcy, MMA; vs. No comparison; prevalence of abnormal laboratory values	Proportion with increased methylmalonic acid: unclear (79.6% (71.5-87.7%, n = 98))

Further studies in this area: 18 29 30 32 35 36 40 42 43 54 55 56 57 60 61 62 64 65 66 67 69 71 77 79 82 83 84 86 87 90 91 92 94 95 97 99 100 103 104 105 108 109 111 115 116 117 119 120 121 122 123 124 126 127 128 130 131 134 137 138 140 142 143 144 148 151 153 156 165 167 169 172 173 174 175 176 178 179 180 181 182 183 189 193 199 204 207 212 217 218 219 230 233 234 238 240 242 243

4. How Is Vitamin B12 Dosed? Preparation, Dose and Duration in Studies

The studies predominantly used oral, sublingual, intranasal, intramuscular, intravenous and subcutaneous preparations of cyanocobalamin, methylcobalamin, adenosylcobalamin and hydroxocobalamin. Methylcobalamin, also called mecobalamin, was mostly used as a tablet, sometimes also as a gel for application. Several studies tested vitamin B12 only as a component of mixtures, for example with folic acid and vitamin B6, with iron and folic acid or with other micronutrients.

Preparation or form	Dose	Duration	Study
Cyanocobalamin plus folate and vitamin B6, optionally with omega-3 fatty acids	Cyanocobalamin 0.02 mg, folate 0.56 mg, vitamin B6 3 mg daily	5 years	57
vitamin B-12 or placebo	—	from early pregnancy to 6 months postpartum	58
Vitamin B12 (1.8 µg) and/or folic acid (150 µg)	1.8 µg vitamin B12, 150 µg folic acid daily	6 months supplementation, follow-up after 6-7 years	59
Vitamin B12 (about 2 RDA) and/or folic acid (about 2 RDA) or placebo	about 2 RDA daily	6 months supplementation, follow-up 6 years later	60
Lipid-based nutrient supplement (LNS) with milk/soy protein and whey permeate/maltodextrin	100 g per day	12 weeks	61
Daily oral methylcobalamin	250 µg (group A) vs. 50 µg (group B)	From enrolment to 6 months post partum	62
1 mg vitamin B12 subcutaneously plus iron, erythropoietin, folic acid	1 mg vitamin B12 subcutaneously once on the day before surgery	Single dose on the day before surgery	63
Quintuply-fortified salt (QFS) with vitamin B12	—	12 months	64
Mecobalamin (methylcobalamin) versus placebo	—	12 months follow-up	65
Intramuscular ultra-high-dose methylcobalamin	25 mg or 50 mg	up to week 182	66
Topical methylcobalamin gel 6% w/w	—	12 sessions over four weeks	67
500 µg methylcobalamin plus 400 µg folic acid or placebo	500 µg methylcobalamin and 400 µg folic acid daily	24 months, follow-up at 12 and 24 months	68
Folic acid 400 µg + vitamin B12 5 µg or placebo	400 µg folic acid + 5 µg B12 daily	12 weeks	69
vitamin B1-6-12 combination or vitamin B12 alone	—	4 and 12 weeks	70
oral methylcobalamin versus placebo	0.5 mg orally, three times daily	maximum 24 weeks	71

5. Is Vitamin B12 Safe? Side Effects in Studies

The studies predominantly report good tolerability of vitamin B12 in the forms and routes investigated. A review on strongly elevated vitamin B12 levels describes antibodies against the transport protein transcobalamin II after supplementation 25.

Study	Reported side effects
4 Lee et al. 2022	relatively safe
7 Larvie et al. 2026	Adverse effects assessed as critical outcome
9 Yu et al. 2026	no significant difference in adverse events (RR 1.44, 95% CI 0.44-4.70)
10 Ran et al. 2024	No statistical difference in adverse effects
11 Jiang et al. 2018	no serious adverse events
12 Jiang et al. 2018	No serious adverse events with combination therapy
14 Finkelstein et al. 2024	spontaneous abortion reported, no quantitative data; no clear definition
16 Shahid et al. 2025	vitamin B12 and calcium depletion, inconsistent magnesium findings
19 Abe et al. 2016	not reported
25 Fernández-Téllez et al. 2026	Formation of anti-transcobalamin II autoantibodies after supplementation
30 Yin et al. 2025	Overall incidence and types of diabetes-related complications
31 Hamza et al. 2025	oral therapy better tolerated than intramuscular injections

6. What Remains Open: Limits of the Evidence

Many studies are short and investigate different forms and routes of administration, which makes direct comparison difficult.
The transferability to special groups such as pregnant women, children or the very old remains open.
For the heart and blood vessels, many studies tested only the homocysteine blood level as an intermediate marker, not hard cardiovascular endpoints.
For memory and mood, the populations and outcome measures are very heterogeneous, so no uniform statement is possible.

7. Bottom Line: What Is Established About Vitamin B12

In controlled trials, vitamin B12 reliably improves vitamin B12 biomarkers in the blood, regardless of whether it is given orally, sublingually or intramuscularly. For nerve damage due to diabetes and for the homocysteine blood level, improvements are also predominantly seen with methylcobalamin or vitamin B12. With a vegan diet without supplementation and with long-term use of proton pump inhibitors, however, the supply is poorer.

The situation is less uniform for memory, mood, blood formation and in pregnancy: here improvements and results without difference stand side by side. Many studies also tested vitamin B12 only in combination with other nutrients, and several were short or investigated different forms and routes. Tolerability is predominantly described as good.

Frequently Asked Questions

How well has Vitamin B12 been studied in humans?

Does Vitamin B12 help with status in vegan diets, older age and with medication? What the studies show

We evaluated 18 meta-analyses or systematic reviews, 24 controlled studies and 43 further studies; the controlled studies include 2,795 participants in total. Result of the controlled studies: mostly improved. Strength of evidence under our published rules: high. Sources: 3 5 6 7

Does Vitamin B12 help with nerves and nerve damage? What the studies show

We evaluated 8 meta-analyses or systematic reviews, 24 controlled studies and 26 further studies; the controlled studies include 2,302 participants in total. Result of the controlled studies: mostly improved. Strength of evidence under our published rules: high. Sources: 4 7 9 10

Does Vitamin B12 help with homocysteine, heart and blood vessels? What the studies show

We evaluated 8 meta-analyses or systematic reviews, 24 controlled studies and 27 further studies; the controlled studies include 2,467 participants in total. Result of the controlled studies: mostly improved. Strength of evidence under our published rules: high. Sources: 2 5 6 17

Does Vitamin B12 help with memory and mood? What the studies show

We evaluated 7 meta-analyses or systematic reviews, 16 controlled studies and 18 further studies; the controlled studies include 1,756 participants in total. Result of the controlled studies: mixed. Strength of evidence under our published rules: high. Sources: 7 20 24 31

Does Vitamin B12 help with blood formation and anaemia? What the studies show

We evaluated 6 meta-analyses or systematic reviews, 8 controlled studies and 14 further studies; the controlled studies include 2,163 participants in total. Result of the controlled studies: mixed. Strength of evidence under our published rules: high. Sources: 1 6 7 14

Does Vitamin B12 help with pregnancy and children? What the studies show

We evaluated 3 meta-analyses or systematic reviews, 4 controlled studies and 20 further studies; the controlled studies include 1,599 participants in total. Result of the controlled studies: mixed. Strength of evidence under our published rules: high. Sources: 1 14 24 38

Which forms of vitamin B12 were investigated in the studies?

Mainly cyanocobalamin, methylcobalamin, adenosylcobalamin and hydroxocobalamin were investigated. Methylcobalamin, also called mecobalamin, was mostly used as a tablet, sometimes also as a gel for application. Hydroxocobalamin was mostly given as an injection.

Does vitamin B12 work with a vegan diet?

Does vitamin B12 help with nerve damage?

In diabetic neuropathy, nerve conduction, vibration perception and pain improved with oral methylcobalamin over one year, while they worsened with placebo 91.

Does vitamin B12 lower the homocysteine blood level?

In adults with vitamin B12 deficiency, the administration of vitamin B12 lowered the homocysteine blood level; oral and sublingual intake did not perform worse than intramuscular injection 5 31. Vitamin B12 together with folic acid, sometimes additionally with vitamin B6, also lowered homocysteine 22 27 30 35 41 43. However, many studies tested only the homocysteine blood level as an intermediate marker, not hard cardiovascular endpoints.

How tolerable is vitamin B12?

The studies predominantly report good tolerability. A review on strongly elevated vitamin B12 levels describes antibodies against the transport protein transcobalamin II after supplementation 25.

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Healing from the Inside Out: Vitamins and Nutritional Strategies for Complex Regional Pain Syndrome and Chronic Postsurgical Pain
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The Role of Micronutrient Deficiencies in Nutritional Anemia Beyond Iron: An Expert Perspective on the Scope and Strength of the Current Evidence
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Neglected micronutrients-considering a broader set of vitamins and minerals in public health nutrition programs worldwide: a narrative review
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Analytical Review on Nutritional Deficiencies in Vegan Diets: Risks, Prevention, and Optimal Strategies
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Desensitization for Vitamin B12 Hypersensitivity and How to Do It
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Cardiac Manifestations of Nutritional Deficiencies
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Medicinal Mushrooms, Probiotics and Combination of Natural Compounds in the Management of HPV: A Comparative Look at Viral Clearance and Lesion Resolution
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Advanced Applications of Vitamin B Complex in Plastic and Cosmetic Surgery: Mechanisms and Therapeutic Benefits
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Aeronutrient Therapy: A New Frontier in Systemic Drug Delivery
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Exploring Vitamin B12 Supplementation in the Vegan Population: A Scoping Review of the Evidence
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The Role of One-Carbon Metabolism and Methyl Donors in Medically Assisted Reproduction: A Narrative Review of the Literature
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Emerging Roles of Vitamin B12 in Aging and Inflammation
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Parkinson's disease and vitamins: a focus on vitamin B12
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Green strength: The role of micronutrients in plant-based diets for athletic performance enhancement
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Vegan Diets for Children: A Narrative Review of Position Papers Published by Relevant Associations
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Vitamin B12 - a scoping review for Nordic Nutrition Recommendations 2023
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Early Detection of Subclinical Atherosclerosis: Hyperhomocysteinemia as a Promising Marker in Adolescents With Vitamin B Deficiency
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The role of vitamin B12 in viral infections: a comprehensive review of its relationship with the muscle-gut-brain axis and implications for SARS-CoV-2 infection
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Mechanistic Link between Vitamin B12 and Alzheimer's Disease
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The role of nutrients in human neurodevelopment and their potential to prevent neurodevelopmental adversity
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Nutrients to Improve Mitochondrial Function to Reduce Brain Energy Deficit and Oxidative Stress in Migraine
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242
Vitamin B12 as a Treatment for Pain
Buesing S, Costa M, Schilling JM, Moeller-Bertram T · 2019
243
B vitamins for stroke prevention
Hankey GJ · 2018
244
Potential Links between Impaired One-Carbon Metabolism Due to Polymorphisms, Inadequate B-Vitamin Status, and the Development of Alzheimer's Disease
Troesch B, Weber P, Mohajeri MH · 2016
245
The role of nutrition in children's neurocognitive development, from pregnancy through childhood
Nyaradi A, Li J, Hickling S, Foster J, Oddy WH · 2013

Every statement on this page carries its evidence tier — proven, plausible or hypothesis — and leads to the original work. The decision in the individual case rests with the practitioner; we provide the connections.