Vitamin B12 level
Serum vitamin B12 measures the cobalamin circulating in blood. Published low cut points run from about 200 to 300 pg/mL, and a meta-analysis found the test alone unreliable against methylmalonic acid. One cohort tied low B12 status to faster cognitive decline, while B vitamin trials found no cognitive effect. Single cohorts tie high levels to cancer diagnoses and deaths.
- Status
- A blood test ordered by a clinician and also sold direct to consumers by some US laboratories. FDA classifies vitamin B12 test systems, used in the diagnosis and treatment of anemias of gastrointestinal malabsorption, as class II devices [1].
- Measures
- The total concentration of vitamin B12 (cobalamin) circulating in serum or plasma.
- Also called
- serum vitamin B12, vitamin B12 serum, plasma vitamin B12, B12 level, total B12, cobalamin, serum cobalamin, vitamin B12 and folate panel
- Tested for
- vitamin B12 deficiency, fatigue, anemia workup, numbness and tingling, memory problems, vegan or vegetarian diet, checking a B12 supplement
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Linked in research4
- LimitedLimited evidence: one US survey linked low B12 status to 2.7 times the odds of anemia in older adults.
- LimitedLimited evidence: one Irish study linked the lowest quarter of pregnancy B12 to two to three times the odds of a neural tube defect.
- LimitedLimited evidence: one Dutch cohort linked higher plasma B12 to more deaths over 8 years, 25% more per standard deviation.
- LimitedLimited evidence: one Danish registry study linked B12 above the reference range to 3 to 6 times the expected cancer diagnoses in the following year.
Reported risks0
No risks sourced yet.
Reference ranges
Each range is the one its source published, in pg/mL. Also reported in pmol/L. Where sources differ, each is shown.
World Health Organization and Food and Agriculture Organization fortification guidelines, 2006
All population groups, as a cut-off for assessing vitamin B12 status at the population level · [2]
| Range | What the source calls it |
|---|---|
| below 203 pg/mL | "deficiency" |
| 203 or above pg/mL | No name given |
The table prints the cut-off as below 150 pmol/L and gives 203 as its mass equivalent, with the mass unit printed as mg/l. The figure is read here as pg/mL, which is what 150 pmol/L converts to [3]. The guidelines state that values above the cut-off do not necessarily indicate adequate status, and that analysis of methylmalonic acid is indicated if values are marginal. They report that abnormalities in the function of some enzymes may occur below 150 pmol/L [2].
Biomarkers of Nutrition for Development (BOND) expert panel, 2018
Adults · [3]
| Range | What the source calls it |
|---|---|
| below 102 pg/mL | "severe" A doctor, immediately |
| 102 to 202 pg/mL | "deficient" |
| 203 to 300 pg/mL | "depleted" |
| above 300 pg/mL | "adequate/normal" |
The panel's table is in pmol/L: severe below 75, deficient 75 to under 150, depleted 150 to 221, adequate or normal above 221. The figures here are converted with the review's own factor (1 pg/mL = 0.7378 pmol/L) and rounded to whole numbers. The text of the same review describes 150 to 250 pmol/L as depleted and adequacy as likely above 250 pmol/L, based on normal methylmalonic acid, so its table and text differ at the upper boundary. It notes that deficiency cut-offs typically range from 120 to 180 pmol/L depending on the assay used [3].
US National Library of Medicine, MedlinePlus Medical Encyclopedia, reviewed 2026
People having the test, as an example of a laboratory normal range · [4]
| Range | What the source calls it |
|---|---|
| below 299 pg/mL | "a possible sign of a vitamin B12 deficiency" |
| 299 to 1054 pg/mL | "normal values" |
| above 1054 pg/mL | No name given |
An encyclopedia entry licensed to the National Library of Medicine, not a guideline. It states that normal value ranges may vary slightly among laboratories and that deficiency is confirmed by checking methylmalonic acid. It calls an increased level uncommon and names no threshold for one beyond the top of its normal values [4]. Its lower limit sits above the WHO and BOND deficiency cut-offs [2][3].
Irish case-control studies of neural tube defects, 2009, women before pregnancy
Women before becoming pregnant · [5]
| Range | What the source calls it |
|---|---|
| 300 or below pg/mL | No name given |
| above 300 pg/mL | No name given |
The authors suggest that women have vitamin B12 levels above 300 ng/L (221 pmol/L) before becoming pregnant. One ng/L equals one pg/mL. The suggestion comes from blood taken at an average of 15 weeks of pregnancy in Irish women at a time when supplements and fortified food were rare, and concentrations below 250 ng/L carried the highest risks. The authors call a further reduction in risk above 300 ng/L uncertain. It is a proposal from one research group, not an adopted standard [5].
What has been shown to move it
Shown to lower it1
Low vitamin B12
One trial found low or borderline B12 more often on metformin than placebo, 19.1% against 9.5% at 5 years, with odds rising each year of use.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Low B12 (203 pg/mL or less) was more common on metformin than placebo at 5 years (4.3% vs 2.3%) but not significantly at 13 years (7.4% vs 5.4%). Low or borderline B12 (298 pg/mL or less) was more common at 5 years (19.1% vs 9.5%) and 13 years (20.3% vs 15.6%). Each year of use raised the odds of deficiency (OR 1.13, 95% CI 1.06 to 1.20). Anemia was more common on metformin, and neuropathy was more common among metformin users with low B12 [12].
- Population
- Participants with stored samples from the Diabetes Prevention Program and its outcomes study, 1,715 at 5 years and 1,520 at 13 years [12].
- Sources
- [12]
- Caveats
- A secondary analysis. The randomized phase lasted 3.2 years, and metformin was open-label after that [12]. In children and adolescents, pooled B12 deficiency after 12 months or more was 1.4% in RCTs and 18.7% in observational studies, and the fall in B12 levels at 6 and 12 months was not significant [22].
Shown to raise it2
Correcting B12 deficiency by mouth instead of injection
Shown to raise blood B12 by mouth about as well as injection in people with B12 deficiency. One small trial in children favored injection.
One trial using 2,000 µg a day by mouth found blood B12 680 pg/mL higher than injection (95% CI 392.7 to 967.3).
The numbers and sources
- Effect
- In two trials using 1,000 µg a day by mouth, blood B12 levels showed no clinically relevant difference from intramuscular injection. One trial using 2,000 µg a day by mouth found blood B12 680 pg/mL higher than injection (95% CI 392.7 to 967.3) [1]. Across 16 studies, serum B12 rose by a pooled 402.6 pg/mL (95% CI 293.6 to 511.5) and homocysteine fell by 4.83 µmol/L, with no significant difference between oral, sublingual and intramuscular routes (p = 0.270) and no dose relationship [2]. A 2026 review of 13 studies in adults found that all three routes raised serum B12, several with comparable or larger rises by mouth [3]. In a 2026 trial, hemoglobin recovery at 28 days did not differ by route after adjustment, comparing B12 given in the nose, into a vein or into muscle [4].
- Population
- 3 RCTs, 153 people with B12 deficiency, mean ages 38.6 to 72, treated for 3 to 4 months [1]; 16 RCTs and observational studies with 6,098 participants [2]; 13 studies of adults with an indication for replacement in 10 countries [3]; 153 adults with B12 deficiency anemia [4].
- Sources
- [1], [2], [3], [4]
- Caveats
- The Cochrane review rated its evidence low quality, and no trial reported symptoms of deficiency, quality of life or acceptability [1]. The 2025 meta-analysis pooled RCTs with observational studies, heterogeneity was above 80% in most comparisons, and it found signs of publication bias [2]. The 2026 review did not pool, judged every trial at some risk of bias, and was funded by Myralis Indústria Farmacêutica [3]. In children with deficiency anemia, the only trial, at high risk of bias, found larger rises in B12 and hemoglobin with injection [5]. Graded B rather than A because the 2025 meta-analysis mixed in observational studies and the 2026 review did not pool.
Infant development with B12 in pregnancy
One trial found slightly higher infant mental development scores at 250 µg than at 50 µg a day in vegetarian pregnant women in India and Nepal.
The numbers and sources
- Effect
- Infants of mothers given 250 µg of methylcobalamin a day had higher mental development scores at 9 to 12 months than infants of mothers given 50 µg (103.7 against 101.7, p = 0.008). Motor scores did not differ. Maternal B12 rose more on the higher dose (104.9 against 47.5 pg/mL) [9].
- Population
- 531 vegetarian women in India and Nepal, from the first trimester to 6 months after birth [9].
- Sources
- [9]
- Caveats
- One trial comparing two doses, with no placebo group. Newborn size, APGAR scores and illness did not differ [9].
How it compares with the reference method
Matched the reference method1
Methylmalonic acid and holotranscobalamin when B12 is borderline
One study in older adults found holotranscobalamin separated deficiency better than serum B12, leaving 14% of results indeterminate against 45%.
The numbers and sources
- Compared with
- Red blood cell cobalamin below 33 pmol/L as the definition of deficiency
- Effect
- Methylmalonic acid and holotranscobalamin are separate tests with their own units, so a serum B12 result cannot be placed against their cut points. Methylmalonic acid rises when the supply of B12 is low. WHO and FAO list above 271 nmol/L as the cut-off and call it highly specific to B12 deficiency [2], and the BOND panel lists above 376 nmol/L as deficient in adults [3]. Holotranscobalamin is the fraction of B12 bound to transcobalamin. The BOND panel lists below 35 to 40 pmol/L as deficient and reports an analysis in which deficiency was likely below 25 pmol/L and unlikely above 50 pmol/L [3]. In 700 older adults, the area under the curve for detecting deficiency was 0.90 (95% CI 0.86 to 0.93) for holotranscobalamin, 0.80 (0.75 to 0.85) for serum B12 and 0.78 (0.72 to 0.83) for methylmalonic acid. The share of results in an indeterminate zone was 14%, 45% and 50%. Renal dysfunction compromised the accuracy of methylmalonic acid and not of the other two [13].
- Population
- 700 adults aged 63 to 97 [13].
- Sources
- [2], [3], [13]
- Caveats
- One study, with deficiency defined by red cell cobalamin, which is not an accepted reference method [13]. The published cut points for both tests vary by source [2][3].
Mixed results2
Agreement between automated assays
One study of four automated B12 assays found results correlated closely, while one analyzer read a mean 122 pg/mL lower than the others.
The numbers and sources
- Compared with
- Three other automated serum B12 immunoassays run on the same samples
- Effect
- Correlation coefficients between the four analyzers ranged from 0.898 to 0.987. One analyzer showed a mean bias of -122 pg/mL (range -616 to 125 pg/mL). All four methods showed similar relationships with methylmalonic acid and homocysteine. The authors state that standardization of serum B12 assays is not complete [14]. The BOND panel lists between-run imprecision above 12% for chemiluminescence B12 assays [3].
- Population
- 69 serum samples from routine B12 requests, measured on four immunoassay analyzers [14].
- Sources
- [14], [3]
- Caveats
- One laboratory study of 69 samples. A result near a cut point may be classed differently on another analyzer [14].
Week to week variation in one person
One small study found serum B12 varied about 9% from week to week within the same person over five weeks.
The numbers and sources
- Compared with
- The same person's results on 5 weekly draws
- Effect
- Within-person variation was 8.6% (95% CI 6.8 to 10.5), variation between people was 39.6% and analytical variation was 7.5%. The authors calculated that two results in one person need to differ by 31.6% to exceed expected variation [15].
- Population
- 22 apparently healthy volunteers aged 18 to 55 in Turkey, sampled once a week for five weeks [15].
- Sources
- [15]
- Caveats
- Twenty-two people and one laboratory. The study states no threshold for agreement, so the result is given as numbers only [15].
Did not match the reference method1
Detecting deficiency with serum B12 alone
Not shown to detect deficiency reliably on its own: against methylmalonic acid, pooled studies gave a positive likelihood ratio of 2.72 and a negative one of 0.59.
The numbers and sources
- Compared with
- Methylmalonic acid, or a clinical reference standard
- Effect
- In a meta-analysis of 54 studies, serum B12 had a positive likelihood ratio of 2.72 (95% CI 1.95 to 3.81) and a negative likelihood ratio of 0.59 (95% CI 0.49 to 0.72) in studies using methylmalonic acid as the referent. Against a clinical reference standard the figures were 3.33 (95% CI 0.92 to 12.10) and 0.34 (95% CI 0.13 to 0.89). Performance did not vary by clinical indication, test method or age, and the authors concluded that diagnosis on the serum level alone is not a reliable approach [11]. In US survey data, the choice among commonly used cut-offs moved the share of adults classed as low from 3% to 26% for serum B12, against 2% to 6% for methylmalonic acid. About 1% of adults had both low B12 and raised methylmalonic acid, and 2% had low B12 with normal methylmalonic acid [12].
- Population
- 54 diagnostic accuracy studies published from 1990 to 2009 [11]. 12,612 US adults older than 19 in the 1999 to 2004 National Health and Nutrition Examination Survey [12].
- Sources
- [11], [12]
- Caveats
- The included studies rated poorly on quality criteria, and no gold standard test for deficiency exists [11].
What studies tie it to
Linked in research4
Anemia and enlarged red cells
Limited evidence: one US survey linked low B12 status to 2.7 times the odds of anemia in older adults.
The numbers and sources
- Effect
- Low compared with normal B12 status was associated with anemia (OR 2.7, 95% CI 1.7 to 4.2) and macrocytosis (OR 1.8, 95% CI 1.01 to 3.3), after control for demographic characteristics, cancer, smoking, alcohol intake, serum ferritin and serum creatinine. Low status was defined as serum B12 below 148 pmol/L (about 200 pg/mL) or methylmalonic acid above 210 nmol/L [7].
- Population
- 1,459 seniors with normal serum creatinine and no history of stroke, alcoholism, recent anemia therapy, or liver, thyroid or coronary disease [7].
- Sources
- [7]
- Caveats
- One cross-sectional survey, so it cannot show which came first. The definition of low status combined two tests [7].
Neural tube defects in pregnancy
Limited evidence: one Irish study linked the lowest quarter of pregnancy B12 to two to three times the odds of a neural tube defect.
The numbers and sources
- Effect
- In 3 independent nested case-control groups, mothers of affected children had significantly lower B12 status. Women in the lowest quartile, compared with the highest, had between two and threefold higher adjusted odds of being the mother of an affected child. Pregnancy blood concentrations below 250 ng/L (250 pg/mL) were associated with the highest risks [5].
- Population
- Irish women sampled at an average of 15 weeks of pregnancy: 95 affected pregnancies and 265 controls, 107 women with a previous affected birth and 414 controls, and 76 affected pregnancies and 222 controls [5].
- Sources
- [5]
- Caveats
- Observational, from one population with a high prevalence of neural tube defects and no folic acid fortification. No trial of B12 for this outcome is cited here [5].
Death from any cause at high levels
Limited evidence: one Dutch cohort linked higher plasma B12 to more deaths over 8 years, 25% more per standard deviation.
The numbers and sources
- Effect
- Mortality was 33.8 deaths per 10,000 person-years in the quartile with the lowest plasma B12 and 65.7 per 10,000 person-years in the highest. After adjustment for age, sex, kidney function and other clinical and laboratory variables, the hazard ratio per 1 standard deviation higher B12 was 1.25 (95% CI 1.06 to 1.47). The median concentration was 394 pg/mL (interquartile range 310 to 497) [9].
- Population
- 5,571 adults in Groningen, the Netherlands, mean age 53.5, not using B12 supplements, 226 deaths over a median 8.2 years [9].
- Sources
- [9]
- Caveats
- Observational and a post hoc analysis. The authors state that the mechanisms are not established, so a high level may mark an illness and need not be its cause [9].
Cancer diagnosis after a high result
Limited evidence: one Danish registry study linked B12 above the reference range to 3 to 6 times the expected cancer diagnoses in the following year.
The numbers and sources
- Effect
- Among people referred for a B12 measurement, 6% had levels above the upper reference limit of the Danish laboratories (601 pmol/L or more, about 815 pg/mL). In the first year of follow-up the standardized incidence ratio for cancer was 3.44 (95% CI 3.14 to 3.76) at 601 to 800 pmol/L and 6.27 (95% CI 5.70 to 6.88) above 800 pmol/L (about 1,084 pg/mL). Risks were particularly raised for blood cancers and cancers related to smoking and alcohol [10].
- Population
- 333,667 people in Northern Denmark without known cancer and not receiving B12 treatment, tested from 1998 to 2009 [10].
- Sources
- [10]
- Caveats
- Observational, in people whose clinician had ordered the test. The excess was mostly within the first year, which fits a cancer already present raising the level. The pg/mL figures are converted here from the study's pmol/L [10][3].
Mixed results1
Cognitive decline in older adults
Mixed results: cohort and survey data linked low B12 status to faster cognitive decline, while pooled trials of B vitamins found no effect on cognitive function.
The numbers and sources
- Effect
- In an Oxford cohort followed for 10 years, holotranscobalamin, methylmalonic acid and homocysteine predicted cognitive decline and folate did not. A doubling of holotranscobalamin from 50 to 100 pmol/L went with a 30% slower rate of decline, and a doubling of methylmalonic acid from 0.25 to 0.50 µmol/L with a decline more than 50% faster [6]. In a US survey of older adults, low B12 status (serum B12 below 148 pmol/L or methylmalonic acid above 210 nmol/L) was associated with cognitive impairment (OR 2.5, 95% CI 1.6 to 3.8) [7]. In a meta-analysis of 11 trials, B vitamins lowered homocysteine by 26% to 28% and had no significant effect on global cognitive function (z score difference -0.01, 95% CI -0.03 to 0.02) or on individual cognitive domains [8].
- Population
- 1,648 older adults in Oxford, United Kingdom, tested on 3 or more occasions over 10 years [6]. 1,459 senior participants in the 1999 to 2002 US National Health and Nutrition Examination Survey [7]. 22,000 participants in 11 trials, with treatment lasting a mean of 2.3 to 5 years [8].
- Sources
- [6], [7], [8]
- Caveats
- The cohort and survey findings are observational, and the survey measured status and cognition at one point in time. The trials tested B vitamins given to lower homocysteine and were not trials of treating B12 deficiency [8].
Sources
- US Food and Drug Administration. 21 CFR 862.1810, Vitamin B12 test system. Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/section-862.1810
- Allen L, de Benoist B, Dary O, Hurrell R, eds. Guidelines on food fortification with micronutrients. Geneva: World Health Organization and Food and Agriculture Organization of the United Nations, 2006. ISBN 92-4-159401-2. https://iris.who.int/handle/10665/43412
- Allen LH, Miller JW, de Groot L, et al. Biomarkers of Nutrition for Development (BOND): Vitamin B-12 Review. The Journal of Nutrition. 2018. https://doi.org/10.1093/jn/nxy201
- US National Library of Medicine. Vitamin B12 level. MedlinePlus Medical Encyclopedia, review date January 10, 2026. https://medlineplus.gov/ency/article/003705.htm
- Molloy AM, Kirke PN, Troendle JF, et al. Maternal Vitamin B12 Status and Risk of Neural Tube Defects in a Population With High Neural Tube Defect Prevalence and No Folic Acid Fortification. Pediatrics. 2009. https://doi.org/10.1542/peds.2008-1173
- Clarke R, Birks J, Nexo E, et al. Low vitamin B-12 status and risk of cognitive decline in older adults. The American Journal of Clinical Nutrition. 2007. https://doi.org/10.1093/ajcn/86.5.1384
- Morris MS, Jacques PF, Rosenberg IH, Selhub J. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. The American Journal of Clinical Nutrition. 2007. https://doi.org/10.1093/ajcn/85.1.193
- Clarke R, Bennett D, Parish S, et al. Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals. The American Journal of Clinical Nutrition. 2014. https://doi.org/10.3945/ajcn.113.076349
- Flores-Guerrero JL, Minovic I, Groothof D, et al. Association of Plasma Concentration of Vitamin B12 With All-Cause Mortality in the General Population in the Netherlands. JAMA Network Open. 2020. https://doi.org/10.1001/jamanetworkopen.2019.19274
- Arendt JFB, Pedersen L, Nexo E, Sørensen HT. Elevated Plasma Vitamin B12 Levels as a Marker for Cancer: A Population-Based Cohort Study. JNCI: Journal of the National Cancer Institute. 2013. https://doi.org/10.1093/jnci/djt315
- Willis CD, Elshaug AG, Milverton JL, et al. Diagnostic performance of serum cobalamin tests: a systematic review and meta-analysis. Pathology. 2011. https://doi.org/10.1097/PAT.0b013e3283486435
- Bailey RL, Carmel R, Green R, et al. Monitoring of vitamin B-12 nutritional status in the United States by using plasma methylmalonic acid and serum vitamin B-12. The American Journal of Clinical Nutrition. 2011. https://doi.org/10.3945/ajcn.111.015222
- Valente E, Scott JM, Ueland PM, et al. Diagnostic Accuracy of Holotranscobalamin, Methylmalonic Acid, Serum Cobalamin, and Other Indicators of Tissue Vitamin B12 Status in the Elderly. Clinical Chemistry. 2011. https://doi.org/10.1373/clinchem.2010.158154
- İspir E, Serdar MA, Ozgurtas T, et al. Comparison of four automated serum vitamin B12 assays. Clinical Chemistry and Laboratory Medicine. 2015. https://doi.org/10.1515/cclm-2014-0843
- Ozkanay H, Arslan FD, Narin F, Koseoglu MH. Biological variation of plasma 25-Hydroxyvitamin D3, serum vitamin B12, folate and ferritin in Turkish healthy subject. Scandinavian Journal of Clinical and Laboratory Investigation. 2023. https://doi.org/10.1080/00365513.2023.2278537