Recommendations | Vitamin B12 deficiency in over 16s: diagnosis and management | Guidance

1.1 Information and support

1.1.1

When providing information and support to people with suspected or confirmed vitamin B12 deficiency (and their families and carers, if appropriate), follow the recommendations on:

knowing the patient as an individual, essential requirements of care and enabling patients to actively participate in their care in NICE's guideline on patient experience in adult NHS services
putting shared decision making into practice in NICE's guideline on shared decision making
supporting decision making in NICE's guideline on decision making and mental capacity.

1.1.2

Explain to people with suspected vitamin B12 deficiency (and their families and carers, if appropriate) that:

the symptoms and signs of vitamin B12 deficiency may also be associated with many other conditions
a single blood test can be enough to support a diagnosis of vitamin B12 deficiency, but some people may need further tests to diagnose the condition.

1.1.3

Explain to people with confirmed vitamin B12 deficiency (and their families and carers, if appropriate) that:

vitamin B12 deficiency affects each person differently
it can be caused by either, or both, a lack of vitamin B12 in the diet or problems with the way the body processes the vitamin that are linked to certain medications, operations, conditions or the recreational use of nitrous oxide
symptoms can affect daily activities, family and social life, work and education
treatment with vitamin B12 replacement is effective in most people
for some, the dose, frequency and way vitamin B12 replacement is given may need to be adjusted or changed for it to work properly
it is important to continue with treatment as advised so that symptoms do not return or get worse
people with some causes of vitamin B12 deficiency will need (and should receive) lifelong vitamin B12 replacement, such as deficiency caused by autoimmune gastritis.

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on information and support.

Full details of the evidence and the committee's discussion are in evidence review A: information and support.

1.2 Recognising vitamin B12 deficiency

1.2.1

Be aware that symptoms and signs of vitamin B12 deficiency:

can vary from person to person and
are often not exclusive to vitamin B12 deficiency.

1.2.2

Take into account that vitamin B12 deficiency is highly likely in people after total gastrectomy or complete terminal ileal resection, if they are not receiving either oral or intramuscular vitamin B12 replacement.

1.2.3

Do not rule out a diagnosis of vitamin B12 deficiency based solely on the absence of either anaemia or macrocytosis.

1.2.4

Be aware that vitamin B12 deficiency can be associated with mental health problems, including symptoms of depression, anxiety or psychosis.

When to test

1.2.5

Offer an initial diagnostic test for vitamin B12 deficiency to people who have:

at least 1 common symptom or sign (see box 1) and
at least 1 common risk factor for the condition (see box 2).

1.2.6

Use clinical judgement when deciding whether to test people who have at least 1 common symptom or sign (see box 1) but no common risk factors (see box 2).

See the recommendations on initial tests.

Box 1

Common symptoms and signs of vitamin B12 deficiency

abnormal findings on a blood count such as anaemia or macrocytosis
cognitive difficulties such as difficulty concentrating or short-term memory loss (sometimes described as 'brain fog'), which can also be symptoms of delirium or dementia
eyesight problems related to optic nerve dysfunction:
- blurred vision
- optic atrophy
- visual field loss (scotoma)
glossitis
neurological or mobility problems related to peripheral neuropathy, or to central nervous system disease including myelopathy (spinal cord disease):
- balance issues and falls caused by impaired proprioception (the ability to sense movement, action and location) and linked to sensory ataxia (which may have been caused by spinal cord damage)
- impaired gait
- pins and needles or numbness (paraesthesia)
symptoms or signs of anaemia that suggest iron treatment is not working properly during pregnancy or breastfeeding
unexplained fatigue.

Box 2

Common risk factors for vitamin B12 deficiency

diet low in vitamin B12 (without the regular use of over-the-counter preparations), for example, in people who:
- follow a diet that excludes, or is low in, animal-source foods (such as a vegan diet, or diets excluding meat for religious beliefs)
- do not consume food or drinks fortified with vitamin B12
- have an allergy to some foods such as eggs, milk or fish
- find it difficult to buy or prepare food (for example, people who have dementia or frailty, or those with mental health conditions)
- find it difficult to obtain or afford foods rich in vitamin B12 (for example, people on low income)
- have a restricted diet (for example, because of an eating disorder)
family history of vitamin B12 deficiency or an autoimmune condition
health conditions:
- atrophic gastritis affecting the gastric body
- coeliac disease or another autoimmune condition (such as thyroid disease, Sjögren's syndrome or type 1 diabetes)
medicines:
- colchicine
- H₂-receptor antagonists
- metformin (see the MHRA safety advice on metformin and reduced vitamin B12)
- phenobarbital
- pregabalin
- primidone
- proton pump inhibitors
- topiramate
previous abdominal or pelvic radiotherapy
previous gastrointestinal surgery:
- many bariatric operations (for example, Roux-en-Y gastric bypass or sleeve gastrectomy)
- gastrectomy or terminal ileal resection
recreational nitrous oxide use.

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on recognising vitamin B12 deficiency.

Full details of the evidence and the committee's discussion are in evidence review B: risk factors and symptoms and signs.

1.3 Diagnosing vitamin B12 deficiency

Initial tests

1.3.1

Use either total B12 (serum cobalamin) or active B12 (serum holotranscobalamin) as the initial test for suspected vitamin B12 deficiency unless:

the test needs to be done during pregnancy, or
recreational nitrous oxide use is the suspected cause of deficiency.

1.3.2

Use active B12 as the initial test for suspected vitamin B12 deficiency during pregnancy.

1.3.3

If the person has suspected vitamin B12 deficiency caused by recreational use of nitrous oxide:

use plasma homocysteine or serum methylmalonic acid (MMA) as the initial test and
if using plasma homocysteine, refer the person to phlebotomy services in secondary care for this test.

1.3.4

Take blood samples for diagnostic tests before starting vitamin B12 replacement.

1.3.5

When offering an initial diagnostic test, ask the person if they are already using an over-the-counter preparation that contains vitamin B12 (including vitamin B12 tablets, injections or transdermal patches), and what type and dosage they are using. See the section on factors that can affect total or active B12 test results.

1.3.6

Do not delay vitamin B12 replacement while waiting for the test results of people with suspected megaloblastic anaemia and neurological symptoms, especially symptoms related to sub-acute combined degeneration of the spinal cord (see the section on managing vitamin B12 deficiency).

1.3.7

Consider starting vitamin B12 replacement while waiting for the test results of people with suspected vitamin B12 deficiency that is a side effect of taking medicine (see recommendation 1.5.7 in the section on managing medicine-induced deficiency).

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on initial tests.

Full details of the evidence and the committee's discussion are in evidence review C: diagnosis.

Factors that can affect total or active B12 test results

1.3.8

Use caution when interpreting the total or active B12 test results of people who are:

already using an over-the-counter preparation containing vitamin B12 (including vitamin B12 tablets, injections, or transdermal patches), because this may increase total or active B12 concentrations without fully treating a deficiency
taking the combined oral contraceptive pill because this can lower total B12 concentrations without causing a deficiency (however, low total B12 concentrations may still mean the person has a deficiency).

For a short explanation of why the committee made this recommendation and how it might affect practice, see the rationale and impact section on factors that can affect total or active B12 test results.

Full details of the evidence and the committee's discussion are in evidence review C: diagnosis.

Thresholds for initial test results

1.3.9

For total or active B12 tests:

use the thresholds in table 1 to guide diagnosis or
where there is substantial local variation in total B12 validated thresholds, use those set by the laboratory doing the testing.

Table 1

**Interpreting total or active B12 test results**
Results if testing total B12 concentrations	Results if testing active B12 concentrations	Likelihood of vitamin B12 deficiency
Less than 180 nanograms (133 pmol) per litre	Less than 25 pmol per litre	Confirmed vitamin B12 deficiency
Between 180 and 350 nanograms (133 and 258 pmol) per litre	Between 25 and 70 pmol per litre	Indeterminate test result – possible vitamin B12 deficiency
More than 350 nanograms (258 pmol) per litre	More than 70 pmol per litre	Test result suggests vitamin B12 deficiency is unlikely

1.3.10

Use the laboratory's reference ranges to interpret serum MMA test results when deciding if vitamin B12 deficiency is likely.

1.3.11

Use laboratory reference ranges to interpret plasma homocysteine test results when deciding if vitamin B12 deficiency is likely, but take into account additional factors that may increase plasma homocysteine levels (such as folate deficiency).

When results are indeterminate or suggest deficiency is unlikely

1.3.12

Consider a further test to measure serum MMA concentrations in people who have symptoms or signs of vitamin B12 deficiency and an indeterminate total or active B12 test result (see table 1). For when to consider starting treatment without waiting for a serum MMA test result, see recommendation 1.3.14.

1.3.13

Be aware that people of Black ethnicity may have a higher reference range for serum vitamin B12 concentrations than people of White or Asian ethnicity.

1.3.14

Consider vitamin B12 replacement for people who have an initial test result that is indeterminate (see table 1) and meet any of the following criteria:

they have a condition or symptom that may deteriorate rapidly and have a major effect on quality of life (for example, neurological or haematological conditions such as ataxia or anaemia)
they have a condition or suspected condition that is an irreversible cause of vitamin B12 deficiency (for example, autoimmune gastritis)
they have had surgery that can cause vitamin B12 deficiency (such as a gastrectomy, terminal ileal resection or some types of bariatric surgery)
they are pregnant or breastfeeding.

If also carrying out a further test to measure serum MMA concentrations, start vitamin B12 replacement while waiting for this test result.

1.3.15

Advise people with no symptoms or signs of vitamin B12 deficiency and an indeterminate total or active B12 test result (see table 1) to seek medical help if they develop symptoms or signs of deficiency.

1.3.16

If the person's initial test result suggests vitamin B12 deficiency is unlikely (see the sections on thresholds for initial test results and factors that can affect total or active B12 test results):

investigate other causes of their symptoms and
if they are still experiencing symptoms 3 to 6 months later, consider a repeat of the initial test.

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on thresholds for initial test results.

Full details of the evidence and the committee's discussion are in evidence review C: diagnosis.

1.4 Identifying the cause of vitamin B12 deficiency

1.4.1

Consider an anti-intrinsic factor antibody test for people with vitamin B12 deficiency if autoimmune gastritis is suspected and they have not previously had:

a positive anti-intrinsic factor antibody test at any time or
an operation that could affect vitamin B12 absorption (such as total gastrectomy or complete terminal ileal resection).

1.4.2

If vitamin B12 deficiency is diagnosed in pregnancy or during breastfeeding and autoimmune gastritis is the suspected cause:

offer an anti-intrinsic factor antibody test if the criteria in recommendation 1.4.1 is met and
start treatment with intramuscular vitamin B12 replacement in line with recommendation 1.5.3 in the section on managing vitamin B12 deficiency where malabsorption is the confirmed or suspected cause, without waiting for the test result.

1.4.3

When interpreting anti-intrinsic factor antibody test results:

follow the guidance provided by the laboratory doing the test and
be aware that a negative test result does not rule out the presence of autoimmune gastritis.

1.4.4

Laboratories should provide information on what their anti-intrinsic factor antibody assay detects and how to interpret results.

1.4.5

If autoimmune gastritis is still suspected despite a negative anti-intrinsic factor antibody test, consider further investigations such as:

an anti-gastric parietal cell antibody test
a test to measure gastrin levels
a CobaSorb test to measure whether vitamin B12 can be absorbed
gastroscopy with gastric body biopsy (to be carried out by a specialist).

1.4.6

Offer serological testing for coeliac disease where the cause of vitamin B12 deficiency is still unknown after further investigations (see the recommendations on recognising coeliac disease in NICE's guideline on coeliac disease).

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on identifying the cause of vitamin B12 deficiency.

Full details of the evidence and the committee's discussion are in evidence review D: identifying cause.

1.5 Managing vitamin B12 deficiency

1.5.1

Explain to people starting treatment with vitamin B12 replacement:

that response to treatment can vary and depends on the cause of the vitamin B12 deficiency
that their symptoms could start to improve within 2 weeks, but this may take up to 3 months
that it can take much longer for symptoms to disappear altogether, and that although their symptoms could get worse initially during treatment, this should improve
when to seek medical help (without waiting for any scheduled appointments) if their symptoms have not improved, get worse or return, or they get new symptoms, after starting treatment.

1.5.2

Continue with vitamin B12 replacement if treatment was started before pregnancy or breastfeeding and review this treatment at a later date.

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on managing vitamin B12 deficiency.

Full details of the evidence and the committee's discussion are in evidence review E: vitamin B12 replacement and self-administration.

Malabsorption as the confirmed or suspected cause of vitamin B12 deficiency

1.5.3

Offer lifelong intramuscular vitamin B12 replacement to people if:

autoimmune gastritis is the cause, or suspected cause, of vitamin B12 deficiency or
they have had a total gastrectomy, or a complete terminal ileal resection.

1.5.4

If the person has a vitamin B12 deficiency because of malabsorption that is not caused by autoimmune gastritis, or a total gastrectomy or complete terminal ileal resection (for example, malabsorption caused by coeliac disease, partial gastrectomy or some forms of bariatric surgery):

offer vitamin B12 replacement and
consider intramuscular instead of oral vitamin B12 replacement.

1.5.5

When offering oral vitamin B12 replacement to people with vitamin B12 deficiency caused, or suspected to be caused, by malabsorption, prescribe a dosage of at least 1 mg a day.

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on managing vitamin B12 deficiency when malabsorption is the confirmed or suspected cause.

Full details of the evidence and the committee's discussion are in evidence review E: vitamin B12 replacement and self-administration.

Medicine-induced vitamin B12 deficiency

1.5.6

For people with vitamin B12 deficiency that is a side effect of taking a medicine:

offer either intramuscular or oral vitamin B12 replacement, based on clinical judgement and the person's preference, while they are taking the medicine causing the side effect, and
if appropriate, review use of the medicine that is causing the side effect to see if it is still needed or can be changed.

1.5.7

Review the need for vitamin B12 replacement if the medicine causing the side effect is stopped or changed and the person no longer has symptoms of vitamin B12 deficiency.

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on managing medicine-induced vitamin B12 deficiency.

Full details of the evidence and the committee's discussion are in evidence review E: vitamin B12 replacement and self-administration.

Recreational nitrous oxide use as the cause of vitamin B12 deficiency

1.5.8

Offer either intramuscular or oral vitamin B12 replacement to people with a vitamin B12 deficiency caused by recreational nitrous oxide use, based on clinical judgement and the person's preference.

1.5.9

Advise the person to stop using nitrous oxide recreationally.

1.5.10

Review the need for vitamin B12 replacement if the person stops using nitrous oxide recreationally and they no longer have symptoms of vitamin B12 deficiency.

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on managing vitamin B12 deficiency caused by recreational nitrous oxide use.

Full details of the evidence and the committee's discussion are in evidence review E: vitamin B12 replacement and self-administration.

Dietary vitamin B12 deficiency

1.5.11

If the person has vitamin B12 deficiency where diet is the suspected cause:

ask what they eat or drink, including any foods or drinks that contain vitamin B12
ask if they are taking, or planning to take, any over-the-counter preparations containing vitamin B12 (when giving advice on over-the-counter oral supplements, see recommendation 1.5.13)
check whether they have any symptoms, signs or risk factors that could suggest another cause of vitamin B12 deficiency
be aware that diet (for example, a vegetarian or vegan diet) may not be the cause, or the only cause, of a person's vitamin B12 deficiency.

1.5.12

Consider further investigations to explore other causes of vitamin B12 deficiency if, during discussions, the person suggests or gives information that raises suspicion that the deficiency is not linked to their diet (see the sections on recognising vitamin B12 deficiency and identifying the cause of vitamin B12 deficiency).

1.5.13

If the person is taking, or plans to take, over-the-counter oral supplements that contain vitamin B12:

explain that some supplements do not contain enough, or the right type, of vitamin B12 to be effective and
advise them to pick an oral supplement that contains at least 1 of the following types of vitamin B12:
- cyanocobalamin
- methylcobalamin
- adenosylcobalamin.

1.5.14

If the person has suspected or confirmed vitamin B12 deficiency because their diet is lacking in vitamin B12:

tell them where to find information on how to improve their intake of vitamin B12, including information about sources in food (see the NHS webpage on B vitamins) and
consider oral vitamin B12 replacement.

1.5.15

When offering oral vitamin B12 replacement in pregnancy or during breastfeeding, consider a dosage of at least 1 mg a day.

1.5.16

Consider intramuscular vitamin B12 injections instead of oral replacement for suspected or confirmed vitamin B12 deficiency caused by diet if:

the person has another condition that may deteriorate rapidly and have a major effect on their quality of life (for example, a neurological or haematological condition such as ataxia or anaemia)
there are concerns about adherence to oral treatment, for example, if the person:
- is older, is or has recently been in hospital and has either multimorbidity or frailty
- has delirium or cognitive impairment
- is affected by social issues that may prevent them accessing care, such as homelessness.

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on managing dietary vitamin B12 deficiency.

Full details of the evidence and the committee's discussion are in evidence review E: vitamin B12 replacement and self-administration.

Unknown causes of vitamin B12 deficiency

1.5.17

In people with a vitamin B12 deficiency where the cause is uncertain, and malabsorption is not suspected based on the results of further testing or investigations:

offer vitamin B12 replacement and
consider oral instead of intramuscular vitamin B12 replacement and review response to treatment at the person's first follow-up appointment (see the section on ongoing care and follow up).

For a short explanation of why the committee made this recommendation and how it might affect practice, see the rationale and impact section on managing vitamin B12 deficiency when the cause is unknown.

Full details of the evidence and the committee's discussion are in evidence review E: vitamin B12 replacement and self-administration.

Self-administration

NICE has made a recommendation for research about self-administration of intramuscular or subcutaneous vitamin B12 replacement.

For a short explanation of why the committee made this recommendation for research, see the rationale section on self-administration of vitamin B12 replacement.

Full details of the evidence and the committee's discussion are in evidence review E: vitamin B12 replacement and self-administration.

1.6 Ongoing care and follow up

1.6.1

Offer an initial follow-up appointment to people who are having vitamin B12 replacement:

at 3 months after they started treatment, or earlier depending on severity of symptoms, or
at 1 month after they started treatment if they are pregnant or breastfeeding.

1.6.2

At each follow-up appointment, ask the person if their symptoms have improved or worsened, or if they are experiencing new symptoms that could be linked to vitamin B12 deficiency.

Follow-up appointments for people taking oral replacement

1.6.3

If the person is taking oral vitamin B12 replacement, check they are taking the correct dosage (if there are any concerns, follow the recommendations on supporting adherence in NICE's guideline on medicines adherence).

Symptoms have not sufficiently improved, got worse or are new

1.6.4

If the person's symptoms have not sufficiently improved so they are still interfering with their normal daily activities, take into account their treatment preferences and either:

increase the oral dosage to the maximum licensed dosage or
if they are already taking the maximum licensed dosage for oral treatment, switch to intramuscular vitamin B12 injections.

1.6.5

If the person has new or worsening symptoms, think about an alternative diagnosis and do 1 of the following:

if the person did not have serum MMA or plasma homocysteine as an initial diagnostic test, consider further testing with:
- serum MMA, or plasma homocysteine if this test is not available and
- continue with existing treatment while waiting for the test result.
if the person had serum MMA or plasma homocysteine as an initial diagnostic test, take into account their treatment preferences and either:
- increase the oral dosage to the maximum licensed dosage or
- if they are already taking the maximum licensed dosage for oral treatment, switch to intramuscular vitamin B12 injections.

1.6.6

If a further test to measure either serum MMA or plasma homocysteine suggests a vitamin B12 deficiency, or the result is uncertain, take into account the person's treatment preferences and either:

increase the oral dosage to the maximum licensed dosage or
if they are already taking the maximum licensed dosage for oral treatment, switch to intramuscular vitamin B12 injections.

1.6.7

Explore alternative diagnoses if the person still has symptoms but a further test to measure serum MMA or plasma homocysteine suggests they no longer have a vitamin B12 deficiency.

Improved or resolved symptoms

1.6.8

Continue with oral vitamin B12 replacement and agree a date for reassessment with the person if:

their symptoms have resolved or improved so that they are no longer affecting their normal daily activities and
the cause, or suspected cause, of the vitamin B12 deficiency has not been addressed (for example, the person is still taking a medicine that could affect vitamin B12 absorption), or
the cause of deficiency is unknown.

1.6.9

Consider stopping treatment if:

the person's symptoms have resolved or improved so they are no longer affecting their normal daily activities and
the cause, or suspected cause, of the vitamin B12 deficiency has been addressed (for example, the person has increased their dietary intake of the vitamin).

If stopping treatment, advise the person to come back if symptoms get worse, reappear or they get new symptoms.

Follow-up appointments for people receiving intramuscular replacement

1.6.10

Do not repeat the initial diagnostic test in people who are having intramuscular vitamin B12 replacement.

1.6.11

If the person's symptoms have got worse or have not sufficiently improved so they are still interfering with their normal daily activities, or they have new symptoms of vitamin B12 deficiency:

increase the frequency of injections if needed, in line with the summary of product characteristics and
think about alternative diagnoses and
agree a date for reassessment of the person's symptoms.

1.6.12

If a person has, or is suspected of having, an irreversible cause of vitamin B12 deficiency:

continue with lifelong intramuscular injections, even if their symptoms have improved or are no longer present, and
advise them to come back if symptoms get worse, reappear, or they get new symptoms.

1.6.13

If the person's symptoms have improved, or are no longer present, and they have either a reversible cause of vitamin B12 deficiency that has not been addressed, or the cause is unknown:

continue with intramuscular injections and
agree a date for their next follow up.

1.6.14

If the cause, or suspected cause, of vitamin B12 deficiency has been resolved and the person's symptoms have improved, or are no longer present:

think about stopping or reducing the frequency of the intramuscular injections and
advise them to come back if their symptoms get worse, reappear, or they get new symptoms.

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on ongoing care and follow up.

Full details of the evidence and the committee's discussion are in evidence review F: follow up.

1.7 Monitoring for gastric cancer in people with suspected or confirmed autoimmune gastritis

1.7.1

At follow up, take into account that people who have autoimmune gastritis:

are at higher risk of developing gastric neuroendocrine tumours and
may also be at higher risk of developing gastric adenocarcinoma.

1.7.2

If the person has suspected or confirmed autoimmune gastritis and new, or worsening, upper gastrointestinal symptoms (for example, dyspepsia, nausea or vomiting):

consider referral for a gastrointestinal endoscopy and
follow the recommendations on upper gastrointestinal tract cancers in NICE's guideline on suspected cancer.

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on monitoring for gastric cancer in people with suspected or confirmed autoimmune gastritis.

Full details of the evidence and the committee's discussion are in evidence review G: monitoring for gastric cancer.

Terms used in this guideline

This section defines terms that have been used in a particular way for this guideline.

Autoimmune gastritis

A chronic inflammatory condition that can lead to vitamin B12 deficiency. Autoimmune gastritis is associated with the presence of auto-antibodies that work against gastric parietal cells and intrinsic factor. These can be detected in the blood but are not always present. Even if they are present, this is not always indicative of autoimmune gastritis.

Autoimmune gastritis is characterised by an inflammation of the body of the stomach, which by itself does not usually cause symptoms but can destroy the parietal cells. In turn, this can reduce the secretion of gastric acid, preventing the release of vitamin B12 from food and impairing iron absorption. Autoimmune gastritis can affect the ability of parietal cells to produce intrinsic factor, which further impairs the absorption of vitamin B12.

Autoimmune gastritis is sometimes referred to as pernicious anaemia. Pernicious anaemia can be a consequence of chronic, severe vitamin B12 deficiency, including deficiency caused by autoimmune gastritis. However, pernicious anaemia in its true sense (that is, life-threatening anaemia) is now extremely rare because of developments in testing and treatment for, and greater awareness of, vitamin B12 deficiency. For this reason, and to prevent any confusion with autoimmune gastritis, we have not used the term 'pernicious anaemia' in the recommendations.

Irreversible cause

A cause of vitamin B12 deficiency that is permanent, even if the deficiency itself can be treated with lifelong vitamin B12 replacement. Examples of irreversible causes include autoimmune gastritis and some types of gastrointestinal surgery, such as major gastric resection, terminal ileal resection and many bariatric operations.

Over-the-counter preparations

Vitamin B12 supplements (including sublingual vitamin B12 tablets and multivitamin supplements containing the vitamin), injections or transdermal patches that can be obtained without a prescription (for example, in a pharmacy or supermarket, or online).

Reversible cause

A cause of vitamin B12 deficiency that can be reversed, so that the deficiency is resolved, with or without the need for vitamin B12 replacement. Examples of reversible causes include insufficient dietary intake of vitamin B12, and factors that affect absorption such as coeliac disease, some medicines and recreational nitrous oxide use.

Vitamin B12 replacement

Vitamin B12 replacement is where a deficiency is treated with prescribed doses of the vitamin, either as tablets or intramuscular injections, to increase the concentrations in the body.