GP Dr Ed Pooley summarises NICE’s new guidance on vitamin B12 deficiency in over 16s
Vitamin B12 is an essential water-soluble vitamin required for metabolism, DNA synthesis, nerve cell functioning and maturation of erythrocytes. It is widely found in meat, shellfish, liver, eggs, poultry, dairy products, and as a fortification agent in breakfast cereals.
Symptoms of B12 deficiency are variable, specific to individuals and wide-ranging, often producing symptoms that are not exclusive to B12 deficiency. In the UK, there are several risk factors for B12 deficiency. NICE advises that we should offer a test for B12 deficiency if patients fall within the risk categories in Box 1 and present with a common symptom or sign (Box 2). However, clinical judgement often leads to testing of those with symptoms who may not fall into a typical at-risk group.
Box 1: Risk factors for B12 Deficiency
- Low dietary B12 intake (vegan or low animal-sourced diet), avoidance of unfortified foods, low/no egg, shellfish or fish consumption.
- Genetic risk factors such as a family history of vitamin B12 deficiency or autoimmune conditions
- Medical conditions including atrophic gastritis, coeliac disease, Sjogren’s syndrome, or type 1 diabetes[KH1]
- Medication use: metformin, pregabalin, PPIs, topiramate, colchicine, phenobarbital, primidone, H2-receptor blockers
- Surgical procedures affecting absorption: Bariatric surgery, gastrectomy, terminal ileal resection, radiotherapy to the abdomen or pelvis
- Recreational use of nitrous oxide[AS2]
Testing for B12
The preferred test is either total B12 (cobalamin) or active B12 (holotranscobalamin). Active B12 is the recommended test in pregnancy. If you suspect nitrous oxide misuse, the preferred test is plasma homocysteine or serum methylmalonic acid (MMA) with plasma homocysteine testing done in secondary care settings.
Ask if the patient is taking over-the-counter B12 supplements. These may increase B12 concentrations without fully treating a deficiency. Conversely, combined oral contraceptive use may lower B12 levels when there is no deficiency state.
Be guided by lab reference ranges and interpret these in the context of serum MMA levels, plasma homocysteine levels and plasma folate levels. Ethnicity influences the reference ranges for B12 . Patients from Asian and White ethnic groups have a lower range than those of Black ethnic groups.
Box 2: Symptoms and Signs of B12 Deficiency
- Blood test findings – low Hb or macrocytosis and lack of response to iron in anaemia in pregnancy
- Ophthalmological symptoms – blurred vision, visual field loss
- Cognitive dysfunction, memory impairment or brain ‘fog’
- Altered neurology due to peripheral neuropathy or myelopathy – this may present as gait disturbance, altered proprioception, sensory ataxia, or paraesthesia
- Glossitis
- Unexplained fatigue
Identifying the Cause of B12 Deficiency
- Consider an anti-intrinsic factor antibody test for those with B12 deficiency where autoimmune gastritis is suspected but who have not previously had a positive antibody test or surgery that could influence B12 absorption.
- In pregnant women with B12 deficiency, only offer an anti-intrinsic factor antibody test if they meet the criteria in the point above. Start treatment with IM B12.
- Refer to laboratory guidance when interpreting anti-intrinsic factor antibodies but be aware that a negative test does not rule out the condition. Consider referral for further testing, such as an anti-gastric parietal cell antibody test, gastrin level quantification, CobaSorb testing, or gastric body biopsy.
- Consider coeliac disease testing if the cause remains unknown after further tests.
- For those diagnosed with autoimmune gastritis, have a lower threshold for referral for upper GI endoscopy given their greater risk for developing gastric malignancy.
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
When to replace B12
Offer B12 replacement when the initial result is indeterminate with specific conditions or low. Specific conditions that merit a lower threshold for treatment are anaemia, ataxia, autoimmune gastritis, gastrectomy, GI surgery or pregnant/breastfeeding.
Do not delay treatment whilst waiting for test results – this is especially true for those patients with neurological symptoms and anaemias, and where vitamin B12 deficiency may relate to medication use.
Managing B12 Deficiency
The preferred route of vitamin B12 replacement depends on the factors that contributed to deficiency and the severity of symptoms and signs on presentation.
Lifelong IM B12 is most appropriate if there is an ongoing malabsorption state such as autoimmune gastritis or after total gastrectomy or terminal ileal resection. In other malabsorption situations, e.g. coeliac disease or bariatric surgery, the patient can be offered IM B12 or oral B12 at a dose of at least 1mg per day.
For medication-induced B12 deficiency, offer IM or oral B12 replacement while the patient is at risk of medication-induced deficiency, dependent on clinical judgement and patient preference. It may be appropriate to consider medication review and switching as an alternative. Once the risk is reduced or absent, re-evaluate the need for continued replacement of B12.
In the case of recreational nitrous oxide use, use B12 IM or oral and advise the patient to stop nitrous oxide use.
Where there is a dietary deficiency, try to correct low B12 by exploring the patient’s current diet and where B12 may be added in foods or when supplements may be suitable. Over-the-counter supplements should be one of the following types of B12: cyanocobalamin, methylcobalamin, or adenosylcobalamin. Oral B12 replacement should be considered if the diet is inadequate and oral B12 should be offered in those who are pregnant or breastfeeding at a dosage of at least 1mg/day.
B12 IM replacement is preferred over oral replacement where:
- The patient has a condition that may deteriorate rapidly or have a major effect on quality of life related to vitamin B12 deficiency, or
- There are concerns about adherence, e.g. frailty, multimorbidity, delirium, cognitive impairment or social issues that affect access to care.
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.
After commencing B12 replacement, patients should be followed up and monitored (see diagram). Undertake follow-up for those on replacement B12 at 3 months after starting treatment (or earlier if severe symptoms) or 1 month if pregnant or breastfeeding.
Dr Edward Pooley is a GP in Nottingham, and is the author of Managing Time in Medicine: Developing Efficient Consulting in Primary Care
We get alot of asymtomatic low B12. Like Marginal Hb, WBC and folate this seems overmedicalised. Alot of AHP routinely add these test for no obvious indication and it makes many very anxious. Neither the health of the nation nor GP workload is helped!