Vitamin B12: who actually needs to worry, and why the damage can be permanent

Most nutrients forgive a stretch of low intake. B12 is the one where waiting has a cost you cannot take back, because the damage lands on nerves rather than on blood.

What it does in the body

• Vitamin B12 is needed to build and myelinate the central nervous system, to form healthy red blood cells and to synthesise DNA. Evidence E source

How much you need

• The RDA for vitamin B12 is 2.4 mcg a day for adults, 2.6 mcg in pregnancy and 2.8 mcg when breastfeeding. — adults, pregnancy, lactation Evidence E source
• Counted from the other end, how much B12 the body loses each day, the intake needed to replace it works out at 3.8 to 20.7 micrograms, far above the 1.4 to 3 micrograms most countries recommend. — apparently healthy adults and elderly people; bioavailability measured from real foods, from liver to mutton Evidence C source
• Doubling how much B12 you eat lifts blood B12 by only about 11 per cent: the relation between intake and status is remarkably flat. — healthy adults and elderly people in studies that supplied or measured dietary B12 intake and measured serum or plasma B12, methylmalonic acid or holotranscobalamin Evidence A source
• A daily intake recommendation assumes normal absorption: in older people with poor B12 status, even 500 micrograms a day for eight weeks left some of them still deficient. — elderly people with a combined plasma vitamin B12 below 250 pmol/L and a urinary methylmalonic acid ratio above 1.5, given 10, 100 or 500 µg a day Evidence B source
• Measured with the methods that tell real B12 from its look-alikes, a sheet of nori carries between 1 and 2.7 mcg and 20 g of dried shiitake about 1 mcg, while hijiki seaweed and white button mushrooms carry next to nothing. — foods, not people: the older studies used microbiological bioassay, ELISA and HPLC, the newer ones mass spectrometry able to separate true B12 from analogues Evidence D source
• Two packets of the same brand of nori, bought for the same trial, differed by a fifth in vitamin B12: 48.4 against 38.6 mcg per 100 g. — commercial roasted nori, one brand chosen from four tested plus one fresh sample from Penghu Evidence B source
• Five grams of nori a day, about four sheets, took vegetarians from 0.3 mcg of B12 a day to 2.0 mcg, which is roughly four fifths of the American recommendation. — vegetarians in Taiwan taking no B12 supplements and no nutritional yeast during the trial Evidence B source
• The trial that showed nori works says in the same breath that spirulina and wakame do not, because what they carry is a look-alike molecule rather than the vitamin. — sea vegetables as a food group Evidence B source
• Europe and the United States do not agree on how much B12 a day is enough, and the gap is not small: 4.0 mcg against 2.4 mcg. — adults aged 18 and over in the European Union Evidence E source

How well your body absorbs it

• B12 from supplements is absorbed about 50% better than B12 bound in food. Evidence E source
• Vitamin B12 is not naturally present in any plant food. Plant foods contain it only when fortified, such as many breakfast cereals and nutritional yeasts. Evidence E source
• The body can take up only about 1.2 micrograms of B12 from any one dose, however large that dose is. The rest of a big tablet is absorbed at roughly one per cent. — healthy Indian adults given 2.5, 5 and 10 µg doses in randomised order Evidence B source
• Swallowed vitamin B12 tablets normalise blood levels about as well as injections, and at 2000 micrograms a day one trial found them better. — people with vitamin B12 deficiency in three randomised trials, mean age 38.6 to 72 years, treated and followed for three to four months Evidence A source
• Pooling sixteen studies across oral, sublingual and injected B12, serum levels rose by about 400 pg/mL and the route made no significant difference. — people supplemented with vitamin B12 by oral, sublingual or intramuscular route, including elderly people, people after gastrectomy and people with unspecified deficiency; 16 studies in the quantitative synthesis Evidence A source
• Weighed on a mass spectrometer, three quarters of what spirulina offers as vitamin B12 is the inactive look-alike, in a ratio of one part real to three parts false. — two different spirulina samples, analysed in the laboratory Evidence D source
• One cultivated water plant breaks the rule that plants carry no usable B12: four real cobalamin forms were identified in it and no look-alike was found. — Wolffia globosa in the laboratory, and 294 participants in the DIRECT-PLUS trial with a baseline B12 of 420.5 pg/mL Evidence B source

What too little does

• Nerve symptoms of B12 deficiency can appear without anaemia, and delay in treatment risks damage that cannot be reversed. — people with B12 deficiency Evidence E source

Who is most likely to fall short

• People who eat no animal products have a higher risk of vitamin B12 deficiency. — vegans Evidence E source
• Between 3% and 43% of older adults living in the community have vitamin B12 deficiency. — community-dwelling older adults Evidence C source

What the evidence does and does not show

• Low vitamin B12 combined with high folic acid was associated with roughly two to three times higher risk of cognitive impairment. — adults in observational research Evidence C source
• In people who are not actually short of B12, supplements did nothing for any domain of thinking and nothing for depression across sixteen randomised trials. — patients without advanced neurological disorders and without overt vitamin B12 deficiency Evidence A source
• Pooling B-vitamin trials in people over sixty, the apparent cognitive benefit shrank to almost nothing once outlier and single-blind studies were removed, and what remains is a very small effect rated high certainty. — adults aged 60 and over, whether cognitively intact, mildly impaired or with dementia Evidence A source
• B vitamins including B12 reliably push homocysteine down in people with coronary heart disease, and just as reliably fail to change cardiovascular events or cardiovascular death. — patients with coronary heart disease Evidence A source
• A thousand micrograms of B12 a day for eight weeks did not reduce fatigue in people with normal B12 levels: the placebo group improved by the same amount. — outpatients with irritable bowel syndrome or inflammatory bowel disease, aged 18 to 65, with deactivating fatigue and normal blood B12 of 150 pmol/L or above Evidence B source
• When singers who swear by B12 shots got a real injection and a saline one in random order, they could not tell the difference: the placebo scored slightly better. — 20 active adult singers without dysphonia but with mild vocal symptoms, with known or suspected B12 deficiency excluded Evidence B source
• In children, B12 supplements cut biochemical deficiency from 7.6 to 1.8 per cent and raised blood levels by about 69 pmol/L. — children from two days to eleven years old in ten countries; 16 trials in the review, 3 trials for deficiency and 7 for concentrations; doses 0.9 to 150 µg a day for 28 days to 31 months Evidence A source
• The same review found the corrected blood levels did not translate into taller children, better attention scores or less anaemia. — children under twelve; 2 trials for height, 2 for cognitive function and 2 for anaemia Evidence A source
• In pregnancy the same split shows up: B12 supplements cut maternal deficiency from 67.9 to 25.9 per cent but left the anaemia rate unchanged. — pregnant women in low- and middle-income countries (India, Bangladesh, South Africa, Croatia); 5 trials in the review, 3 contributing to meta-analysis; doses 5 to 250 µg a day from 8 to 28 weeks' gestation Evidence A source
• Nori raised every vitamin B12 marker measured in vegetarians within four weeks, and eight grams a day worked no better than five. — 30 vegetarians using no B12 supplements, randomised to no nori, 5 g a day, or 8 g a day Evidence B source
• Vegetarians and vegans are not short of B12 by definition. In a church population where fortified foods and supplements are ordinary, their blood levels matched those of meat eaters. — 1 994 Seventh-day Adventists following plant-based diets, compared with omnivore controls who may or may not have been Adventists Evidence C source
• Nobody has systematically checked what storage and cooking do to the B12 in these foods. The review that gathered the numbers names that as the next job, which means today's figures describe the raw food. — seaweeds, mushrooms, plants and fermented foods Evidence D source

What too much does

• No Tolerable Upper Intake Level was set for vitamin B12 because of its low potential for toxicity. Evidence E source
• Across fifteen trials in 71,000 people taking B vitamins for up to seven years, serious adverse events and deaths were no more common than on placebo. — adults with and without pre-existing cardiovascular disease, given vitamin B6, B9 or B12; end-stage renal disease excluded Evidence A source
• In people with diabetic kidney disease, a daily tablet holding 1 mg of B12 with folic acid and B6 made kidney function fall faster and doubled vascular events, even though it lowered homocysteine as intended. — patients with type 1 or type 2 diabetes and a clinical diagnosis of diabetic nephropathy Evidence B source
• Two to three years of 500 micrograms of B12 with folic acid, followed up long term, went with 77 per cent more colorectal cancer than placebo. — older adults originally randomised in the B-PROOF fracture-prevention trial in the Netherlands Evidence B source
• A high B12 reading in the blood, above 600 pmol/L, went with half again the risk of dying, and the risk rose steadily with the level rather than only at the top. — adults in 22 cohort studies, with separate analyses for the general population and for older adults Evidence C source
• A second meta-analysis of the same question, with more studies and more deaths, concluded the opposite: a high B12 level does not predict dying, and the earlier signal may be an artefact. — adults aged 18 and over with hypervitaminosis B12, followed for all-cause mortality Evidence C source

Medicines it interacts with

• Metformin may reduce B12 absorption and significantly lower blood B12 levels. — people taking metformin Evidence E source
• Acid-reducing drugs (proton pump inhibitors and H2 blockers) can interfere with absorbing B12 from food and lead to deficiency. — people on long-term acid suppression Evidence E source
• Metformin lowers blood vitamin B12 by about 57 pmol/L within six weeks to three months, enough to push some people with type 2 diabetes into deficiency. — people with type 2 diabetes of any age taking any dose or duration of metformin; 10 of 17 observational studies found significantly lower B12 on metformin Evidence C source

What to do with this

Most people can stop reading here. If you eat meat, fish, eggs or dairy with any regularity, B12 from food is not your problem.

Three groups should keep going. People who eat no animal products, where a supplement or fortified food is the only reliable route. People over about 50, who absorb B12 from food less well. And anyone on long-term metformin or acid-suppressing medication, both of which interfere with getting B12 out of food.

What makes B12 different from everything else on this site is the shape of the risk. Too little, left long enough, damages nerves in a way that does not fully reverse. Too much sits on the milder side of that asymmetry, and it is no longer a blank. When in doubt, test rather than wait.

If a test does show you are low, a tablet is usually as good as an injection. Three randomised trials found no clinically relevant difference at 1,000 micrograms a day, and the tablets came out ahead at 2,000. None of those trials recorded whether anyone felt better, only what the blood showed.

Myth. B12 does not give you energy or sharpen your memory if you are not short of it. Sixteen randomised trials in 6,276 people found no effect on any domain of thinking and none on depression. A thousand micrograms a day for eight weeks did nothing for fatigue that the placebo did not also do. Twenty singers who swore by B12 injections were given a real one and a saline one in random order, and the saline scored slightly better.

Unsettled. The recommended 2.4 micrograms may be too low. Working from how much B12 the body loses in a day, the intake needed to replace it comes out at 3.8 to 20.7 micrograms. That rests on pooled kinetic studies in 135 people rather than on a trial, the range is enormous, and the researchers behind it asked for better evidence rather than for a higher number. It is a reason to test if you are in one of the three groups above. It is not a reason to start counting micrograms.

Unsettled. The flat line that no plant food carries B12 no longer holds as written. Nori does, at 1.03 to 2.68 micrograms a sheet, and 5 g a day moved every blood marker in a randomised trial of thirty vegetarians. Spirulina and wakame do not, because what they carry is a look-alike molecule. What nobody has measured is what storage and cooking do to the nori, and one brand's own packets varied by a fifth.

Not for everyone. If you eat no animal products, read that as interesting rather than as permission. The trial ran in adults who could eat four sheets a day and did. It says nothing about a pregnancy, an infant, someone whose gut cannot get B12 out of food, or anyone already being treated for a low level. In all of those the supplement or the fortified food stays, and the blood test is what settles it.

Where to get it from food

The bottom line

Three groups should take this seriously: people who eat no animal products, people over roughly 50, and anyone on long-term metformin or acid-suppressing medication. Metformin lowers blood B12 by around 57 pmol/L within six weeks to three months, which is enough to tip some people with type 2 diabetes under. For everyone else, B12 from food is rarely a problem. Part of the reason is that your gut takes in roughly a fixed 1.2 micrograms from any one dose, whatever its size, and doubling your intake lifts blood B12 by about 11 per cent. Two things have shifted since this page was written. The first is that the recommended intake is genuinely in question. Counted from how much B12 the body loses each day, the intake needed to replace it works out at 3.8 to 20.7 micrograms, against the 1.4 to 3 that recommendations use. That comes from pooled kinetic studies in 135 people rather than from trials, and the researchers who ran the sum asked for better evidence rather than for a bigger number. The second is that the flat line about too much B12 having no established harm no longer survives as written. Fifteen trials in 71,422 people found no excess of serious adverse events or deaths, and that is the strongest safety result B12 has. Every one of those trials gave B12 together with folic acid and B6. No randomised trial of high-dose B12 on its own has ever been run. Inside that same mixed-tablet evidence, 238 people with diabetic kidney disease lost kidney function faster on B vitamins and had twice the rate of heart attack, stroke and death. Older adults taking 500 micrograms with folic acid had 43 colorectal cancers against 25 on placebo. Two meta-analyses of whether a high blood level predicts dying disagree outright, and both are observational. What B12 does not do is now well mapped. In 6,276 people who were not short of it, supplements did nothing for any domain of thinking and nothing for depression. A thousand micrograms a day for eight weeks left fatigue where the placebo left it. Singers who swore by B12 injections could not tell one from saline. In coronary heart disease, B vitamins lower homocysteine every time and leave cardiovascular events and deaths exactly where they were. The asymmetry still holds at the bottom of the scale. Too little, caught late, can leave nerve damage that does not heal. One sentence on this page has to change, and we took it from an expert fact sheet: that B12 is not naturally present in any plant food. Nori carries the real vitamin. A sheet holds 1.03 to 2.68 micrograms. In a randomised trial 5 g a day, about four sheets, took vegetarians from 0.3 to 2.0 micrograms of intake and moved every marker measured. Serum B12 rose 59 pmol/L against control and homocysteine fell 3.7 micromol/L. Eight grams did no better than five. This belongs to nori rather than to sea vegetables as a category. Spirulina came out at one part real B12 to three parts of the inactive look-alike, wakame carries analogues too, and hijiki holds 0.003 micrograms in a 7 g portion. Two packets of one brand of nori differed by a fifth, 48.4 against 38.6 micrograms per 100 g, and nobody has measured what storage and cooking take out. For someone who eats no animal products, that makes nori a finding rather than a plan, and the supplement stays. The one cultivated plant that passed the same laboratory test with no look-alike at all is Wolffia globosa. Two more results sit alongside. Europe and the United States disagree about the requirement itself, 4.0 micrograms a day against 2.4. And plant-based eating does not mean low B12 by definition: in 1,994 Seventh-day Adventists, where fortified food and supplements are ordinary, serum B12 and daily intake matched those of omnivore controls.

Sources

1. b12-01 · Position of an expert body · expert body statement
   Vitamin B12 is required for the development, myelination, and function of the central nervous system; healthy red blood cell formation; and DNA synthesis.
   NIH Office of Dietary Supplements, Health Professional Fact Sheet: Vitamin B12 · checked 2026-09-15 · extracted
2. b12-02 · Position of an expert body · expert body recommendation
   19+ years [require] 2.4 mcg; Pregnancy [requires] 2.6 mcg; Lactation [requires] 2.8 mcg. (value from the source's table, not a sentence)
   NIH Office of Dietary Supplements, Health Professional Fact Sheet: Vitamin B12 · checked 2026-09-15 · extracted
3. b12-r2-1 · Observational data · systematic review with pooled analysis of physiological studies
   Daily vitamin B12 losses in apparently healthy adults and elderly probably range from 1.4 to 5.1 µg. Vitamin B12 intakes needed to compensate for these losses seem to range from 3.8 to 20.7 µg.
   Doets et al., Annals of Nutrition and Metabolism, 2013 · checked 2026-09-17 · independently re-checked
4. b12-r2-2 · Meta-analysis or systematic review · systematic review with dose-response meta-analysis
   The pooled dose-response relation of all studies between vitamin B-12 intake and status indicated that a doubling of the vitamin B-12 intake increased vitamin B-12 concentrations by 11% (95% CI: 9.4%, 12.5%). This increase was larger for studies in elderly persons (13%) than in studies in adults (8%).
   Dullemeijer et al., American Journal of Clinical Nutrition, 2013 · checked 2026-09-17 · independently re-checked
5. b12-r2-4 · Randomised controlled trial(s) · randomised double-blind placebo-controlled trial
   Improvements in plasma vitamin B-12 and serum holoTC were achieved at cobalamin supplements of 10 μg/d, but even 500 μg/d for 8 wk did not normalize plasma vitamin B-12 in 8% and serum holoTC in 12% of people.
   Hill et al., The Journal of Nutrition, 2013 · checked 2026-09-17 · independently re-checked
6. b12-e2-01 · Mechanistic or laboratory data · systematic review of food composition studies
   Real B12 content varied from mean (SD) mcg/portion size of seaweed hijiki 3 × 10-3/7 g to nori 1.03 - 2.68/sheet; mushroom white button cap 2 × 10-3(7 × 10-4)/20 g dry weight (dw) to shiitake 0.79(0.67)-1.12 (0.78)/20 g dw; and fermented foods from soy yogurt 20/cup.
   Niklewicz et al., Critical Reviews in Food Science and Nutrition, 2023 · checked 2026-09-18 · independently re-checked
7. b12-e2-02 · Randomised controlled trial(s) · food analysis within a randomised controlled trial
   However, when we sampled the nori from the batch used for the actual trial, it contained a lower amount of vitamin B12 (38.6 µg/100 g).
   European Journal of Nutrition, 2024 · checked 2026-09-18 · independently re-checked
8. b12-e2-03 · Randomised controlled trial(s) · randomised controlled trial
   Our study found that 5 g of nori per day improved vitamin B12 intakes (from a meagre 0.3 µg to 2.0 µg [83% RDA]) in vegetarians, accompanied by improvement in vitamin B12 biomarkers.
   European Journal of Nutrition, 2024 · checked 2026-09-18 · independently re-checked
9. b12-e2-05 · Randomised controlled trial(s) · randomised controlled trial, discussion
   Other algae, such as spirulina and wakame, have been found to contain analogues
   European Journal of Nutrition, 2024 · checked 2026-09-18 · independently re-checked
10. b12-e2-10 · Position of an expert body · expert body statement
    For cobalamin, the Panel set AIs of 4 µg/day for adults (18 years and above)
    Dietary reference values: vitamin E and cobalamin, European Food Safety Authority, 2015 · checked 2026-09-18 · independently re-checked
11. b12-07 · Position of an expert body · expert body statement
    Bioavailability of vitamin B12 from dietary supplements is about 50% higher than that from food sources.
    NIH Office of Dietary Supplements, Health Professional Fact Sheet: Vitamin B12 · checked 2026-09-15 · extracted
12. b12-11 · Position of an expert body · expert body statement
    Vitamin B12 is found in foods of animal origin. It is not naturally present in plant foods, but some plant foods are fortified with vitamin B12, including many breakfast cereals and nutritional yeasts.
    NIH Office of Dietary Supplements, Vitamin B12 - Health Professional Fact Sheet · checked 2026-09-16 · extracted
13. b12-r2-3 · Randomised controlled trial(s) · randomised crossover study with meta-analysis
    Up to a dose of 2.6 µg, there was a significant steep positive correlation, with a slope (bioavailability) of 43%/µg suggesting an active process with a maximum of 1.2 µg. At higher doses, the slope was 1%/µg, not significantly different from zero, possibly a passive process.
    Kashyap et al., Nutrients, 2024 · checked 2026-09-17 · independently re-checked
14. b12-r3-01 · Meta-analysis or systematic review · Cochrane systematic review of randomised trials
    In two trials employing 1000 μg/day oral vitamin B12, there was no clinically relevant difference in vitamin B12 levels when compared with IM vitamin B12. One trial used 2000 μg/day vitamin B12 and demonstrated a mean difference of 680 pg/mL (95% confidence interval 392.7 to 967.3) in favour of oral vitamin B12.
    Cochrane Database of Systematic Reviews, 2018 · checked 2026-09-17 · independently re-checked
15. b12-r3-02 · Meta-analysis or systematic review · systematic review and meta-analysis
    Vitamin B12 supplementation was associated with a significant increase in serum cobalamin levels across all routes of administration (pooled mean difference = +402.6 pg/mL; 95% CI: 293.6 to 511.5; p < 0.001)...No statistically significant differences were observed between oral, sublingual, and intramuscular (IM) routes of administration (p = 0.270 for cobalamin levels and p = 0.485 for homocysteine levels), nor between randomised controlled trials and observational studies (p = 0.268 for cobalamin levels).
    Frontiers in Pharmacology, 2025 · checked 2026-09-17 · independently re-checked
16. b12-e2-06 · Mechanistic or laboratory data · laboratory food analysis
    the data revealed the presence of CN-B12 and pseudo CN-B12 in a ratio 1:3 in two different spirulina samples, whereas no pseudo CN-B12 was detected in the Mankai samples
    Sela et al., Nutrients, 2020 · checked 2026-09-18 · independently re-checked
17. b12-e2-07 · Randomised controlled trial(s) · randomised controlled trial with laboratory analysis
    Several cobalamin congeners (Hydroxocobalamin(OH-B12); 5-deoxyadenosylcobalamin(Ado-B12); methylcobalamin(Me-B12); cyanocobalamin(CN-B12)) were identified in Mankai extracts, whereas no pseudo B12 was detected.
    Sela et al., Nutrients, 2020 · checked 2026-09-18 · independently re-checked
18. b12-06 · Position of an expert body · expert body statement
    These neurological symptoms can occur without anemia, so early diagnosis and intervention is important to avoid irreversible damage.
    NIH Office of Dietary Supplements, Health Professional Fact Sheet: Vitamin B12 · checked 2026-09-15 · extracted
19. b12-04 · Position of an expert body · expert body statement
    Vegans who consume no animal products...have a higher risk of developing vitamin B12 deficiency
    NIH Office of Dietary Supplements, Health Professional Fact Sheet: Vitamin B12 · checked 2026-09-15 · extracted
20. b12-05 · Observational data · observational data cited by expert body
    between 3% and 43% of community-dwelling older adults...have vitamin B12 deficiency
    NIH Office of Dietary Supplements, Health Professional Fact Sheet: Vitamin B12 · checked 2026-09-15 · extracted
21. b12-10 · Observational data · observational studies cited by expert body
    low vitamin B12...combined with high folic acid...was associated with an almost two to three times higher risk of cognitive impairment.
    NIH Office of Dietary Supplements, Health Professional Fact Sheet: Vitamin B12 · checked 2026-09-15 · extracted
22. b12-r5-1 · Meta-analysis or systematic review · meta-analysis of randomised controlled trials
    A total of 16 RCTs with 6276 participants were included. Regarding cognitive function outcomes, we found no evidence for an effect of B12 alone or B complex supplementation on any subdomain of cognitive function outcomes. Further, meta-regression showed no significant associations of treatment effects with any of the potential predictors. We also found no overall effect of vitamin supplementation on measures of depression.
    Markun et al., Nutrients, 2021 · checked 2026-09-17 · independently re-checked
23. b12-r5-2 · Meta-analysis or systematic review · meta-analysis of randomised controlled trials
    A small to moderate improvement (Hedges' g = 0.423; 95% CI: 0.188 to 0.657) in global cognitive function after supplementation was observed with considerable heterogeneity (I2 = 92.71; Grading of Recommendations, Assessment, Development, and Evaluations [GRADE] = very low certainty). A meta-regression identified that statistical outliers and single-blinded studies contributed to the pooled g and heterogeneity. Omitting these studies resulted in a small effect (g = 0.110; 95% CI: 0.034 to 0.186), with negligible heterogeneity (I2 = 15.39; GRADE = high certainty).
    Berg et al., Nutrition Reviews, 2025 · checked 2026-09-17 · independently re-checked
24. b12-r5-3 · Meta-analysis or systematic review · meta-analysis of randomised controlled trials
    Combined B-vitamin supplementation significantly reduced serum Hcy levels [mean difference: -2.36; 95% confidence interval (CI): (-3.09 to -1.62); p < 0.01] compared with any single-nutrient regimen. The incidence of vascular restenosis was lower in the intervention group than in the control group (risk ratio: 0.65; 95% CI: 0.44-0.95; p < 0.05). However, no significant differences were observed in the incidence of major cardiovascular events (p = 0.78) or cardiovascular-related mortality (risk ratio: 0.96; 95% CI: 0.85-1.07; p = 0.44).
    Guo et al., Annals of Medicine, 2026 · checked 2026-09-17 · independently re-checked
25. b12-r5-4 · Randomised controlled trial(s) · randomised controlled trial
    No significant difference in scores of the CIS subscale 'subjective fatigue' was observed between the intervention group and the control group with changes in scores of -8.1 ± 9.5 and -8.3 ± 10.6 (95% CI -11.65 to 6.71), respectively.
    Scholten et al., Clinical Nutrition ESPEN, 2018 · checked 2026-09-17 · independently re-checked
26. b12-r5-5 · Randomised controlled trial(s) · randomised controlled crossover trial
    At 72 hours after the vitamin B12 injection, the median difference in the SVHI-10 score was 1 (95% CI, -1 to 2) compared with 3 (95% CI, 0-4) after placebo. The median difference between differences at 72 hours between placebo and vitamin B12 injections were 1.5 (95% CI, -2 to 5) for the SVHI-10, 1 (95% CI, -9 to 9) for the VFI, and -1 (95% CI, -3 to 2) for the EASE.
    Shoffel-Havakuk et al., JAMA Otolaryngology-Head & Neck Surgery, 2021 · checked 2026-09-17 · independently re-checked
27. b12-r3-03 · Meta-analysis or systematic review · Cochrane systematic review and meta-analysis
    Vitamin B12 supplementation in children reduces vitamin B12 deficiency (absolute risk difference (ARD) 56 fewer per 1000, 95% CI 68 fewer to 24 fewer; 1.8% versus 7.6%; risk ratio (RR) 0.27, 95% CI 0.11 to 0.69; 3 trials, 642 children; high-certainty evidence), and probably increases total vitamin B12 concentrations (MD 68.53 pmol/L, 95% CI 41.83 to 95.23; 7 trials, 705 children; moderate-certainty evidence), compared to placebo, with an average increase of 68.5 pmol/L.
    Cochrane Database of Systematic Reviews, 2026 · checked 2026-09-17 · independently re-checked
28. b12-r3-04 · Meta-analysis or systematic review · Cochrane systematic review and meta-analysis
    There may be little to no difference between groups in height/length (mean difference (MD) -0.19 cm, 95% confidence interval (CI) -2.44 to 2.06; 2 trials, 143 children; low-certainty evidence)...There may be little to no difference between groups in cognitive function (e.g. attention) (standardised mean difference (SMD) 0.09, 95% CI -0.10 to 0.28; 2 trials, 438 children, low-certainty evidence)...There may be little to no difference between groups in anaemia (ARD 21 more per 1000, 95% CI 26 fewer to 191 more; 9.1% versus 4.5%; RR 1.48, 95% CI 0.41 to 5.27; 2 trials, 144 children; low-certainty evidence).
    Cochrane Database of Systematic Reviews, 2026 · checked 2026-09-17 · independently re-checked
29. b12-r3-05 · Meta-analysis or systematic review · Cochrane systematic review and meta-analysis
    Maternal anaemia: there may be little to no difference for maternal anaemia by intervention group, but the evidence is very uncertain (70.9% versus 65.0%; risk ratio (RR) 1.08, 95% confidence interval (CI) 0.93 to 1.26; 2 trials, 284 women; very low-certainty evidence). Maternal vitamin B12 status: vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain (25.9% versus 67.9%; RR 0.38, 95% CI 0.28 to 0.51; 2 trials, 272 women; very low-certainty evidence).
    Cochrane Database of Systematic Reviews, 2024 · checked 2026-09-17 · independently re-checked
30. b12-e2-04 · Randomised controlled trial(s) · randomised controlled trial
    Vitamin B12 status appeared to plateau at low dose (5 g of nori), which compared with control group, improved serum vitamin B12 (lease square mean [95% CI] = + 59 [25, 93] pmol/L, P = 0.0014); holoTC (+ 28.2 [10.1, 46.3] pmol/L, P = 0.0035); Hcy (-3.7 [-6.8, -0.6] µmol/L, p = 0.0226); and 4cB12 score (+ 0.67 [0.24, 1.09], p = 0.0036).
    European Journal of Nutrition, 2024 · checked 2026-09-18 · independently re-checked
31. b12-e2-08 · Observational data · meta-analysis of observational studies
    Meta-analysis showed no significant differences in serum vitamin B12 levels (MD: -9.85 pmol/L; 95% CI: -45.64 to 25.94 pmol/L; P = 0.54, I2 = 50%) or daily intake (MD: 3.31 mcg/d; 95% CI: -4.70 to 11.32 mcg/d; P = 0.42, I2 = 90%) between plant-based Adventists and omnivore controls, although there was high heterogeneity between the studies.
    American Journal of Health Promotion, 2025 · checked 2026-09-18 · independently re-checked
32. b12-e2-09 · Mechanistic or laboratory data · systematic review of food composition studies
    Future research should consider different methods of storage, preparation, fermented foods and standardization of the production of certain foods.
    Niklewicz et al., Critical Reviews in Food Science and Nutrition, 2023 · checked 2026-09-18 · independently re-checked
33. b12-03 · Position of an expert body · expert body statement
    The FNB did not establish a UL for vitamin B12 because of its low potential for toxicity.
    NIH Office of Dietary Supplements, Health Professional Fact Sheet: Vitamin B12 · checked 2026-09-15 · extracted
34. b12-sf-1 · Meta-analysis or systematic review · Cochrane systematic review and meta-analysis
    Compared with placebo, there were no differences in effects of homocysteine-lowering interventions on myocardial infarction (homocysteine-lowering = 7.1% versus placebo = 6.0%; RR 1.02, 95% confidence interval (CI) 0.95 to 1.10, I2 = 0%, 12 trials; N = 46,699; Bayes factor 1.04, high-quality evidence), death from any cause (homocysteine-lowering = 11.7% versus placebo = 12.3%, RR 1.01, 95% CI 0.96 to 1.06, I2 = 0%, 11 trials, N = 44,817; Bayes factor = 1.05, high-quality evidence), or serious adverse events (homocysteine-lowering = 8.3% versus comparator = 8.5%, RR 1.07, 95% CI 1.00 to 1.14, I2 = 0%, eight trials, N = 35,788; high-quality evidence).
    Martí-Carvajal et al., Cochrane Database of Systematic Reviews, 2017 · checked 2026-09-17 · independently re-checked
35. b12-sf-2 · Randomised controlled trial(s) · randomised controlled trial
    At 36 months, radionuclide GFR decreased by a mean (SE) of 16.5 (1.7) mL/min/1.73 m(2) in the B-vitamin group compared with 10.7 (1.7) mL/min/1.73 m(2) in the placebo group (mean difference, -5.8; 95% confidence interval [CI], -10.6 to -1.1; P = .02). There was no difference in requirement of dialysis (hazard ratio [HR], 1.1; 95% CI, 0.4-2.6; P = .88). The composite outcome occurred more often in the B-vitamin group (HR, 2.0; 95% CI, 1.0-4.0; P = .04).
    House et al., JAMA, 2010 · checked 2026-09-17 · independently re-checked
36. b12-sf-3 · Randomised controlled trial(s) · randomised controlled trial, long-term follow-up
    Allocation to B vitamins was associated with a higher risk of overall cancer [171 (13.6%) vs. 143 (11.3%); HR 1.25; 95% confidence interval (CI), 1.00-1.53, P = 0.05]. B vitamins were significantly associated with a higher risk of colorectal cancer [43(3.4%) vs. 25(2.0%); HR 1.77; 95% CI, 1.08-2.90, P = 0.02].
    Oliai Araghi et al., Cancer Epidemiology, Biomarkers & Prevention, 2019 · checked 2026-09-17 · independently re-checked
37. b12-sf-4 · Observational data · dose-response meta-analysis of cohort studies
    A linear trend dose-response analysis showed that each 100 pmol/L increase in serum vitamin B12 concentration was associated with a 4 % higher risk of all-cause mortality in the general population (adjusted HR 1.04, 95 % confidence interval CI 1.01 to 1.08; n = 8; P non-linearity = 0.11) and a 6 % higher risk for all-cause mortality in older adults (adjusted HR 1.06, 95 % CI 1.01 to 1.13; n = 4; P non-linearity = 0.78)...The meta-analysis of cohort studies showed a positive association between a high serum vitamin B12 concentration (>600 pmol/L) and all-cause mortality (adjusted HR 1.50, 95 % CI 1.29 to 1.74; n = 10; p < 0.01)
    Liu et al., Archives of Gerontology and Geriatrics, 2024 · checked 2026-09-17 · independently re-checked
38. b12-sf-5 · Observational data · meta-analysis of observational longitudinal studies
    A total of 28 studies were included in the meta-analysis (among the 69,610 participants, 15,815 all-cause deaths were reported). High serum levels of B12 increased marginally the risk of all-cause mortality specifically among chronic diseases (RR = 1.40; 95% IC = 1.05 to 1.85) and hospitalized (RR = 1.57; 95% IC = 1.19 to 2.07). In the meta-regression, these results were not statistically significant.
    Valdez-Martínez et al., Nutrients, 2025 · checked 2026-09-17 · independently re-checked
39. b12-08 · Position of an expert body · expert body statement
    might reduce the absorption of vitamin B12 and significantly reduce serum vitamin B12 concentrations.
    NIH Office of Dietary Supplements, Health Professional Fact Sheet: Vitamin B12 · checked 2026-09-15 · extracted
40. b12-09 · Position of an expert body · expert body statement
    can interfere with vitamin B12 absorption from food by slowing the release of gastric acid into the stomach and thereby lead to vitamin B12 deficiency.
    NIH Office of Dietary Supplements, Health Professional Fact Sheet: Vitamin B12 · checked 2026-09-15 · extracted
41. b12-r3-06 · Observational data · systematic review and meta-analysis, mostly observational studies
    Meta-analysis performed on four trials demonstrated a statistically significant overall mean B12 reducing effect of metformin of 57pmol/L [WMD (fixed)=-0.57 (95% CI: -35 to -79pmol/L)] after 6weeks to 3months of use.
    Diabetes & Metabolism, 2016 · checked 2026-09-17 · independently re-checked