Vitamin B12 deficiency means your body is short of this vitamin; it can cause tiredness, anaemia, pins and needles and numbness in the hands and feet, balance problems, forgetfulness or a sore tongue [1]. Treatment is simple and effective: when the cause is diet or a medicine, tablets are often enough; but when the body cannot absorb B12, as in pernicious anaemia or after the whole stomach has been removed, injections are needed, sometimes for life [1]. If you have numbness, poor balance or difficulty walking, do not put off treatment, so that nerve damage does not become permanent [1, 2].
Key points
- Vitamin B12 deficiency affects both the blood (anaemia) and the nerves and brain [3]. This vitamin is found mainly in animal foods such as meat, fish, eggs and milk [1, 3].
- It is more common in these people: vegetarians and especially vegans, older people, people with autoimmune inflammation of the stomach (pernicious anaemia), people who have had stomach or bowel surgery, and people taking metformin or stomach acid-reducing medicines for a long time [1, 3, 7].
- B12 deficiency does not always cause anaemia; sometimes it shows itself only as pins and needles, numbness, poor balance or memory problems [1, 2].
- A B12 blood test is usually enough; if the result is "borderline", your doctor may ask for another test called MMA or start treatment [1].
- Treatment works in most people. Symptoms may start to improve within 2 weeks, but sometimes it takes 3 months or longer [1].
- B12 deficiency is not cancer. But if a blood film (looking at the blood cells under a microscope) shows unusual changes, the doctor also checks for bone marrow diseases [7].
What is vitamin B12 deficiency?
Vitamin B12 (cobalamin) comes from food and is found mainly in animal foods such as meat, fish, eggs and milk [1, 3]. A lack of it can affect both the blood and the nerves and brain [3].
B12 deficiency has two main causes: either the diet does not contain enough B12, or the body cannot absorb or use it properly [1]. To absorb B12, the stomach needs to be healthy. In "autoimmune gastritis", also called pernicious anaemia, the immune system damages the stomach lining and B12 absorption is impaired [1]. Removal of the stomach or of the last part of the small intestine, some weight-loss operations, coeliac disease and some medicines also reduce absorption [1].
Mild deficiency that shows up only on a blood test is common, but severe deficiency with anaemia and nerve symptoms is less common [3]. It can happen at any age but is more common in older people [3]. Get to know other common types of anaemia too: iron-deficiency anaemia and thalassaemia minor.
Who is most at risk?
Vegetarian and vegan diets
Older age
Stomach and autoimmune conditions
Autoimmune gastritis (pernicious anaemia), coeliac disease and other autoimmune conditions such as thyroid disease or type 1 diabetes; also a family history of B12 deficiency or of an autoimmune condition [1].
Stomach or bowel surgery and radiotherapy
Removal of the stomach or of the last part of the small intestine, many weight-loss operations (such as a gastric bypass or sleeve gastrectomy) and previous radiotherapy to the abdomen or pelvis [1]. If your whole stomach has been removed (for example, as treatment for stomach cancer), deficiency is almost certain without B12 replacement [1].
Some medicines
Nitrous oxide
Recreational use of nitrous oxide ("laughing gas") interferes with how the body uses B12 and is one of the causes of deficiency [1].
Symptoms of B12 deficiency
Symptoms of B12 deficiency vary from person to person, and most of them can have other causes too [1]. Common symptoms are:
- Unexplained tiredness and signs of anaemia such as pale skin, shortness of breath, dizziness and a fast heartbeat [1, 9]
- Pins and needles, tingling or numbness in the hands and feet [1]
- Balance problems, falls and changes in the way you walk [1]
- Memory and concentration problems (sometimes called "brain fog"); sometimes depression, anxiety or more severe mental health changes [1]
- An inflamed, sore tongue [1]
- Blurred vision or loss of part of the field of vision [1]
B12 deficiency does not always cause anaemia or enlarged red blood cells, so a normal haemoglobin or MCV on a CBC (full blood count) does not rule it out [1]. Nerve symptoms can appear without any change in the blood count [2]. Read more: understanding your CBC results.
Why do nerve symptoms need prompt treatment? Early treatment is essential to prevent permanent nerve damage [2]. If your doctor suspects B12 deficiency with anaemia and nerve symptoms, they will not delay treatment while waiting for test results; they only take a blood sample before starting treatment [1].
Which tests?
B12 blood test. The first test measures B12 in the blood: either "total" B12, which is more common, or "active" B12 [1]. Doctors ask for this test especially when you have at least one symptom and one risk factor [1].
A total B12 result is usually read like this [1]:
- Below 180: B12 deficiency is confirmed.
- 180 to 350: "borderline"; you may have a deficiency.
- Above 350: deficiency is unlikely.
These numbers are in nanograms per litre; some laboratories report the same number in picograms per millilitre, which is the same thing. If your laboratory uses different cut-offs, your doctor will use those [1].
If the result is borderline. If you have symptoms, your doctor may ask for another test called MMA (methylmalonic acid); this substance rises when B12 is lacking [1, 3]. In pregnancy and breastfeeding, when autoimmune gastritis is suspected, after stomach surgery, or if you have symptoms that could get worse quickly, your doctor may start treatment without waiting for the second test result [1]. If you have no symptoms, it is usually enough to come back if symptoms appear [1].
Finding the cause. If your doctor suspects autoimmune gastritis, they will ask for an "intrinsic factor antibody" test. A positive result points to the cause, but a negative result does not rule it out [1, 2]. If no cause is found, a coeliac disease test is also done [1].
Before the test, tell your doctor if you are using B12 tablets, injections or patches, or taking the combined contraceptive pill. Supplements raise the B12 number without necessarily treating the deficiency fully, and the pill lowers the B12 number without necessarily meaning there is a deficiency [1].
If a blood film (looking at the blood cells under a microscope) shows unusual changes, the doctor also considers bone marrow diseases and refers you to a blood specialist (haematologist) [7]. This referral does not mean cancer; it only means a fuller assessment is needed. Read more: blood cancers.
For physicians
| Result | Total B12 (serum cobalamin) | Active B12 (serum holotranscobalamin) |
|---|---|---|
| Confirmed deficiency | Below 180 ng/L (133 pmol/L) [1] | Below 25 pmol/L [1] |
| Indeterminate (possible deficiency) | 180 to 350 ng/L (133 to 258 pmol/L) [1] | 25 to 70 pmol/L [1] |
| Deficiency unlikely | Above 350 ng/L (258 pmol/L) [1] | Above 70 pmol/L [1] |
In pregnancy, active B12 is the initial test; with recreational nitrous oxide use, plasma homocysteine or serum MMA. Where validated local laboratory thresholds differ substantially, use the laboratory's thresholds [1].
Interpretation and next steps. Take samples before starting replacement [1]. With an indeterminate result and symptoms, interpret serum MMA against the laboratory's reference range; for homocysteine, take other causes of a rise, such as folate deficiency, into account [1]; interpret both in relation to renal function [2]. With an indeterminate result, consider replacement (if MMA has been requested, without waiting for the result) when there is a condition that may deteriorate rapidly (such as ataxia or anaemia), a likely irreversible cause (autoimmune gastritis), relevant surgery (gastrectomy, terminal ileal resection, some bariatric operations), or pregnancy or breastfeeding [1]. A result suggesting deficiency is unlikely, with persisting symptoms: look for other causes and consider repeating the test after 3 to 6 months [1]. Over-the-counter supplements raise levels without fully treating the deficiency, and the combined oral contraceptive pill lowers total B12 without deficiency [1]. The absence of anaemia or macrocytosis does not rule out deficiency [1], and a neurological presentation without haematological change is possible [2].
Cause. Intrinsic factor antibody (IFAB) if autoimmune gastritis is suspected, unless previously positive or after total gastrectomy or complete terminal ileal resection; sensitivity is low (positive in 40 to 60%) and a negative result does not rule out autoimmune gastritis [1, 2]. A high IFAB titre can interfere with cobalamin assays and give a falsely normal level; with marked clinical features (megaloblastic anaemia or subacute combined degeneration of the cord) and a normal level, send IFAB [2]. Negative IFAB with persisting suspicion: gastric parietal cell antibody, gastrin, a CobaSorb test or gastroscopy with gastric body biopsy; unknown cause: coeliac serology [1]. Medicines: a 2-year or longer supply of a PPI (OR 1.65; 95% CI 1.58 to 1.73) or of an H2 receptor antagonist (OR 1.25; 1.17 to 1.34) was associated with B12 deficiency, and more than 1.5 PPI pills a day more strongly (OR 1.95; 1.77 to 2.15) [5]. Metformin label: a fall to subnormal B12 in about 7% of patients in 29-week trials; check haematological parameters yearly and B12 every 2 to 3 years [6]. In macrocytosis, a peripheral blood film and reticulocyte count come first, and abnormalities on the film should prompt consideration of MDS or malignancy, with haematology consultation [7].
Treatment: tablets or injections?
B12 deficiency is treated by replacing the vitamin, with tablets or with injections into a muscle [1]. The choice between them depends mostly on the cause of the deficiency:
| Cause of deficiency | Usual treatment |
|---|---|
| Autoimmune gastritis (pernicious anaemia), removal of the whole stomach or of the whole last part of the small intestine | Injections, for life; even when you feel well [1] |
| Other absorption problems (coeliac disease, removal of part of the stomach, some weight-loss operations) | Injections are often preferred; if tablets, a high dose [1] |
| Some medicines (such as metformin or an acid-reducing medicine) or nitrous oxide | Tablets or injections, by your choice and your doctor's judgement; while the cause continues [1] |
| Diet low in B12 (such as a vegetarian diet) | Usually tablets; injections if you have nerve symptoms or anaemia that could get worse quickly, or if taking tablets regularly is hard for you [1] |
| Unknown cause (no absorption problem) | Usually tablets first, with the response checked at the follow-up visit [1] |
If you have nerve symptoms, treatment usually starts with injections given closer together [1, 2].
Do tablets work as well as injections? For people without an absorption problem, tablets are usually suggested [1]. In a few small studies, high-dose tablets (1000 to 2000 micrograms a day) raised blood B12 as much as injections and cost less, but there were few such studies [4]. If you buy a supplement over the counter, be aware that some do not contain enough B12 or the right type; choose one that contains cyanocobalamin, methylcobalamin or adenosylcobalamin [1].
How often are injections given? Usually several injections are given in the first 2 weeks, then one injection every 2 to 3 months; if you have nerve symptoms, the injections are closer together at the start [2]. Your doctor decides the exact schedule.
Do not stop treatment on your own. If the cause of the deficiency cannot be reversed, such as autoimmune gastritis or removal of the whole stomach, injections are needed for life [1]. If the cause goes away, for example your diet comes to contain enough B12, your doctor may reduce or stop treatment [1].
If a medicine such as metformin or an acid-reducing medicine caused the deficiency, do not stop it yourself; your doctor will check whether it is still needed or can be changed, and will replace B12 in the meantime [1]. If you have taken metformin for a long time, ask your doctor whether your blood B12 should be checked from time to time [6].
For physicians
| Situation | Treatment | Schedule |
|---|---|---|
| No neurological symptoms | Hydroxocobalamin 1000 micrograms IM | Three times a week for 2 weeks; maintenance 1000 micrograms every 3 months [2] |
| Neurological symptoms | Hydroxocobalamin 1000 micrograms IM | On alternate days until there is no further improvement (BNF); BSH suggestion: review the need to continue alternate-day dosing after 3 weeks; maintenance 1000 micrograms every 2 months [2] |
| Autoimmune gastritis, total gastrectomy or complete terminal ileal resection | Intramuscular replacement | Lifelong, even after symptoms resolve [1] |
| Other malabsorption (coeliac disease, partial gastrectomy, some bariatric operations) | Consider IM rather than oral; oral at least 1 mg daily | According to clinical response [1] |
| Medicine-induced or recreational nitrous oxide use | IM or oral, based on clinical judgement and the patient's preference | While the cause continues; review the causative medicine and advise stopping nitrous oxide [1] |
| Dietary | Oral (cyanocobalamin, methylcobalamin or adenosylcobalamin); IM if a neurological or haematological condition may deteriorate rapidly or adherence is a concern | Consider stopping once the cause is addressed and symptoms improve [1] |
| Pregnancy and breastfeeding | Oral at least 1 mg daily; if autoimmune gastritis is suspected, IM without waiting for the IFAB result | First follow-up 1 month after starting [1] |
The BSH doses are for hydroxocobalamin and are based on the BNF [2]; NICE refers to the summary of product characteristics for adjusting injection frequency [1].
Monitoring. In anaemia, a reticulocyte response should be seen within 7 to 10 days, provided iron and folate are adequate; no haematological response means reviewing the diagnosis, and a suboptimal response may reveal previously masked iron deficiency or another coexisting cause [2]. In severe anaemia, transient hypokalaemia occurs after starting treatment (clinical significance unknown) and potassium replacement can be considered [2]. During IM treatment, do not repeat the initial test [1, 2]. First follow-up 3 months after starting (earlier depending on symptom severity) [1]. Oral treatment with an insufficient response: increase to the maximum licensed oral dose or switch to IM; with new or worsening symptoms, consider an alternative diagnosis and, if not done before, MMA or homocysteine [1]. IM treatment with an insufficient response: increase the injection frequency and consider other diagnoses [1].
Oral forms and side effects. High-dose oral cyanocobalamin (1000 to 2000 micrograms) is licensed in several countries outside the UK [2]. Cochrane review (2018): three trials, 153 patients; 1000 micrograms oral daily showed no clinically relevant difference in B12 levels from IM, and 2000 micrograms daily a mean difference of 680 pg/mL in favour of oral (95% CI 392.7 to 967.3); low-quality evidence [4]. Hydroxocobalamin is generally well tolerated; itching, rash, chills, fever, hot flushes, nausea, dizziness and, rarely, anaphylaxis; there is cross-sensitivity with cyanocobalamin [2]. Autoimmune gastritis: higher risk of gastric neuroendocrine tumours and possibly adenocarcinoma; with new or worsening upper gastrointestinal symptoms, consider endoscopy [1].
Folic acid and B12
A lack of folic acid (folate), another B vitamin, also enlarges red blood cells and can cause the same symptoms as B12 deficiency, which is why doctors usually check both together [2, 7].
Do not start folic acid for anaemia on your own. If both B12 and folic acid are low, your doctor will start treatment with B12 and then add folic acid [2].
If you are planning a pregnancy: the World Health Organization recommends that all women take 400 micrograms of folic acid a day from the time they start trying to conceive until week 12 of pregnancy [8].
For physicians
Folate (BSH 2014, based on the BNF). Megaloblastic anaemia due to folate deficiency (dietary insufficiency, pregnancy or antiepileptic drugs): folic acid 5 mg daily for 4 months, in pregnancy until term; in malabsorption up to 15 mg daily for 4 months; chronic haemolytic states and dialysis: prophylaxis 5 mg daily to weekly depending on diet and rate of haemolysis; prophylaxis in pregnancy 200 to 500 micrograms daily [2]. If folate and cobalamin are both low, start cobalamin before adding folate; serum folate is the first-line test of folate status [2]. WHO: 400 micrograms of folic acid daily from the time of trying to conceive until week 12; after a previous pregnancy affected by a neural tube defect, 5 mg daily [8].
Pregnancy and breastfeeding
If you were already on B12 treatment before pregnancy or breastfeeding, continue it [1]. In pregnancy, total B12 naturally falls and is less reliable, so the "active" B12 test is better for diagnosis [1, 2].
If a test result is borderline during pregnancy or breastfeeding, your doctor will consider treatment [1]. If tablets are prescribed, the dose during this time is at least 1 milligram (1000 micrograms) a day; if autoimmune gastritis is suspected, injections are started without waiting for the test result [1]. The first follow-up visit is one month after starting treatment [1].
True B12 deficiency in babies is rare and is mostly due to B12 deficiency in the mother, especially when the mother follows a strict vegetarian diet [2]. Tell your baby's doctor about poor weight gain, falling behind in growth and development, or unusual movements; B12 deficiency in a baby needs prompt treatment so that nerve damage does not become permanent [2].
Follow-up
The first follow-up visit is usually 3 months after starting treatment, or sooner if symptoms are severe; in pregnancy and breastfeeding, after one month [1]. Your doctor will ask whether your symptoms have improved or got worse, or whether you have new symptoms [1].
Improvement may start within 2 weeks but sometimes takes up to 3 months, and symptoms may take much longer to go completely; sometimes symptoms get slightly worse at the start of treatment and then improve [1]. If you are treated with injections, the B12 test does not need to be repeated [1, 2]. If you take tablets and your symptoms have not improved enough, your doctor will increase the dose or switch you to injections [1].
People with autoimmune gastritis are more likely to develop some stomach tumours [1]. If you have new or worsening indigestion, nausea or vomiting, tell your doctor; you may need an endoscopy [1]. Read more: What are the symptoms of stomach cancer?
When should I see a doctor urgently?
Call your local emergency number or go to an emergency department if you have anaemia with severe shortness of breath or fainting [9].
See a doctor the same day if [1, 2]:
- numbness or tingling in your hands or feet is getting worse quickly
- your balance is affected, you are falling or walking has become difficult
- your vision has become blurred or you have lost part of your vision
- you have severe memory or concentration problems, or a sudden change in mood or behaviour
See your doctor before your next scheduled appointment if, after starting treatment, your symptoms have not improved, have got worse or have come back, or you have new symptoms [1].
Frequently asked questions
Are B12 injections better than tablets?
It depends on the cause. If the body cannot absorb B12, as in autoimmune gastritis or after removal of the whole stomach, injections are needed [1]. If the cause is diet or a medicine, tablets are often enough, and in a few small studies high-dose tablets raised B12 as much as injections [1, 4]. If you have nerve symptoms, treatment usually starts with injections [1, 2].
My B12 is 250; am I deficient?
A level between 180 and 350 is "borderline" [1]. If you have symptoms, your doctor may ask for an MMA test or start treatment, especially in pregnancy and breastfeeding, after stomach surgery, or with nerve symptoms or anaemia [1]. If you have no symptoms, it is usually enough to come back if symptoms appear [1].
Can metformin cause B12 deficiency?
It can. Taking metformin is one of the risk factors for B12 deficiency [1]. In studies of this medicine, B12 fell below normal in about 7 in 100 people, which is why its prescribing information recommends checking B12 every 2 to 3 years [6]. Do not stop metformin yourself; if a deficiency is found, B12 is replaced [1].
Can stomach medicines such as omeprazole cause B12 deficiency?
Long-term use of stomach acid-reducing medicines is one of the risk factors for B12 deficiency [1]. In a large study, using these medicines for 2 years or more was linked to B12 deficiency [5]. If you take these medicines long term and have tiredness, numbness or memory problems, talk to your doctor about a B12 test [1].
I am vegetarian; how can I get enough B12?
Can B12 deficiency be cured? Does nerve damage recover?
Do B12 injections have side effects?
B12 injections are usually well tolerated. Reported side effects include itching, skin rash, chills, fever, hot flushes, nausea and dizziness, and a severe allergic reaction is very rare [2].
Related links
References
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Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1Vitamin B12 deficiency in over 16s: diagnosis and management (NICE guideline NG239) — RecommendationsSource Back to text: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104
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