Vitamin B12 deficiency can affect energy, blood formation, nerves, balance, memory and mood. For adults, teenagers and families in Newcastle West, Limerick, Midleton, Youghal, Cork, Dungarvan and Dublin, and ONLINE across Ireland, the crucial point is that low dietary intake is only one possible cause. Autoimmune gastritis, digestive disease, surgery, medicines and nitrous oxide can also interfere with B12. Correct testing, timely treatment and investigation of the cause matter.
Written and clinically reviewed by Claire Russell, MSc, BSc, DipNT, MNTOI, Registered Nutritionist, incorporating Functional Medicine, Clinical Medical Hypnotherapist, Clinical Hypnotherapist, Counsellor, Psychotherapist, RTT Practitioner and Advanced Rapid Transformational Therapist.
Last evidence search and clinical review: Reviewed 23 August 2026. Next planned review: 23 August 2027, or sooner if relevant guidance changes.
Summary
Vitamin B12 deficiency means that the body does not have enough biologically available cobalamin to maintain normal blood-cell production, neurological function and cellular metabolism. Possible features include unexplained fatigue, reduced stamina, breathlessness, a sore tongue, pins and needles, numbness, altered balance, memory difficulty, visual disturbance, low mood and confusion. Deficiency can be present even when haemoglobin and mean cell volume are normal.
B12 in 60 seconds !
- A normal full blood count does not rule it out. Neurological or cognitive symptoms can occur without anaemia or macrocytosis.
- Diet is only one part of the assessment. Autoimmune gastritis, coeliac disease, Crohn’s disease, stomach or ileal surgery, metformin and nitrous oxide can all be relevant.
- A borderline result needs context. Symptoms, risks, supplements, kidney function and tests such as methylmalonic acid may help clarify selected cases.
- Treatment should match the cause. High-dose oral B12 works for many people, while some causes require intramuscular replacement, sometimes for life.
- The goal is recovery, not the highest blood number. Follow-up should assess symptoms, function, adherence and the underlying cause.
- Timing matters. New or progressive neurological symptoms, severe anaemia, pregnancy, infancy and nitrous oxide-related symptoms require prompt medical attention.
NICE advises clinicians to use either total B12 or active B12 as an initial test in most people aged 16 and over. Active B12 is preferred during pregnancy where available. When nitrous oxide is suspected, methylmalonic acid or homocysteine is used as the initial biochemical test. Results must be interpreted with symptoms, risk factors, treatment already taken and the laboratory method.[1]
Important testing note: where it is safe to wait, diagnostic blood samples should be taken before high-dose replacement begins because tablets, sprays and injections can raise the measured B12 level. This must not delay urgent assessment or clinician-directed treatment when neurological deterioration or B12-related megaloblastic anaemia is suspected.[1]
Contents
- Summary
- What vitamin B12 does in the body
- Vitamin B12 deficiency in Ireland: what the evidence shows
- The B12 Absorption Breakpoint Map
- Vitamin B12 deficiency symptoms and urgent warning signs
- Who is more likely to develop low vitamin B12?
- Vitamin B12 foods and daily intake
- B12 blood tests: what to request and how to interpret the result
- The B12 TRACE Framework
- Finding the underlying cause
- Treatment and follow-up
- Pregnancy, breastfeeding, babies and children
- Mental health, cognition, fatigue and sleep
- An evidence-bounded functional medicine perspective
- What is established, emerging or unsupported?
- Two composite clinical illustrations
- What to do next: a practical B12 action plan
- Frequently asked questions about vitamin B12
- Book a Registered Nutritionist appointment
- About the author and clinical review
- Medical and nutrition disclaimer
- Scientific and clinical references
What vitamin B12 does in the body
Vitamin B12 is a water-soluble vitamin. Cobalamin is the name for the family of compounds with B12 activity. Natural food sources are almost entirely animal-derived, although selected breakfast cereals, plant drinks and nutritional yeasts are fortified with it. The body depends on B12 for two central enzyme reactions:[5,8]
- Methionine synthase helps convert homocysteine to methionine and returns folate to a form needed for DNA synthesis and cell division.
- Methylmalonyl-CoA mutase converts methylmalonyl-CoA to succinyl-CoA, linking fatty-acid and amino-acid metabolism with cellular energy pathways.
These reactions help explain why a shortage can affect fast-dividing blood cells and the nervous system at the same time. B12 is required for normal red blood cell production, myelin maintenance, neurological function and one-carbon metabolism. When B12-dependent metabolism is impaired, methylmalonic acid, known as MMA, usually rises. Homocysteine can also rise, although folate, vitamin B6, thyroid and kidney function, medicines and other factors influence it.[8,11]
The liver stores a substantial amount of B12. Deficiency may therefore emerge slowly, sometimes years after intake or absorption begins to fall. A gradual onset can make symptoms easier to normalise or misattribute. It does not make prolonged nerve injury harmless.
More B12 is not automatically better
Treating a genuine deficiency is important. Giving additional B12 to someone who is already sufficient has not been shown to act as a general stimulant, weight-loss treatment, antidepressant or cognitive enhancer. The clinical target is adequate replacement, recovery of function and management of the cause, not the highest achievable serum result.[5,12]
Vitamin B12 deficiency in Ireland: what the evidence shows
Irish research shows why B12 deserves attention in routine nutrition and medical assessment. Researchers from The Irish Longitudinal Study on Ageing, known as TILDA, analysed 5,158 total B12 results from community-dwelling adults aged 50 years and older after exclusions. Twelve per cent had a deficient or low result below 185 pmol/L. B12 supplement or injection use was the strongest positive predictor of status, while metformin use was the strongest negative predictor.[6]
The study also found that voluntary food fortification was not sufficient to maintain B12 and folate status across the older study population. This does not mean that every adult over 50 needs the same supplement. It does mean that actual intake, medicine use and age-related absorption risks deserve attention.
A separate four-year TILDA analysis reported that adults aged 50 and older with deficient or low B12 had a 51 per cent higher likelihood of developing depressive symptoms. This was an observational association, not proof that B12 caused the depression or that supplementation treats depression in people who are not deficient.[7,12]
The HSE notes that neurological and psychological features can occur even without anaemia.[2] The HSE National Cancer Control Programme haematology referral manual also cautions against assuming that vegetarian or vegan eating is the sole cause of a low result. Autoimmune gastritis and other absorption problems may still need investigation.[3]
The B12 Absorption Breakpoint Map
Eating B12 is only the first step. A person can consume an apparently adequate amount and still become deficient when one or more parts of the pathway fail. The Claire Russell Therapy B12 Absorption Breakpoint Map separates the process into five practical checkpoints.
| Breakpoint | What normally happens | What can interfere |
|---|---|---|
| 1. Supply | Food, fortified products or supplements provide B12. | Vegan eating without a reliable source, restrictive eating, low appetite, food insecurity, sensory food restriction, eating disorders or alcohol displacing meals. |
| 2. Release | Stomach acid and pepsin release food-bound B12 from protein. | Autoimmune or atrophic gastritis, gastric surgery and reduced stomach acid. Long-term acid suppression may contribute in a susceptible person. |
| 3. Binding | Pancreatic enzymes release B12 from haptocorrin, allowing it to bind intrinsic factor made by stomach parietal cells. | Autoimmune gastritis, gastrectomy, severe gastric disease or pancreatic insufficiency. |
| 4. Uptake | The B12 and intrinsic-factor complex is absorbed in the terminal ileum. | Crohn’s disease affecting the ileum, complete or substantial terminal ileal resection, coeliac disease, other malabsorption or altered anatomy. |
| 5. Transport and use | Transcobalamin carries B12 to tissues, where cells convert it into active coenzyme forms. | Nitrous oxide can inactivate B12. Rare inherited transport or metabolic disorders require specialist care. Kidney and liver disease can complicate biomarker interpretation. |
A small fraction of a large oral dose can cross the intestine by passive diffusion without intrinsic factor. This is why high-dose oral treatment can work in many situations. It does not make oral and intramuscular treatment interchangeable for every person. Severity, neurological features, adherence, anatomy and the cause of malabsorption all influence the safest route.[17,18]
Vitamin B12 deficiency symptoms and urgent warning signs
There is no single diagnostic symptom. B12 deficiency can resemble iron deficiency, folate deficiency, thyroid disease, diabetes-related neuropathy, perimenopause, poor sleep, anxiety, depression, infection and many other conditions. NICE specifically advises clinicians not to rule it out solely because anaemia or enlarged red cells are absent.[1]
| Body system | Possible symptoms or signs | Interpretation |
|---|---|---|
| General and blood-related | Unexplained fatigue, weakness, reduced exercise tolerance, pallor, headaches, breathlessness or palpitations. | These features are common and need a broader differential diagnosis. |
| Nervous system | Pins and needles, numbness, burning sensations, muscle weakness, poor balance, an unsteady gait or impaired awareness of joint position. | New, progressive or function-limiting change needs prompt medical assessment. |
| Cognition and mental health | Poor concentration, memory change, slowed thinking, irritability, low mood, confusion, anxiety-like symptoms or, rarely, psychosis. | B12 may be one contributor. Mental health and neurological assessment should continue in parallel. |
| Mouth and digestion | A smooth or sore red tongue, mouth ulcers, altered taste, low appetite, diarrhoea or unplanned weight loss. | Digestive symptoms may also point towards coeliac disease, inflammatory bowel disease, gastritis or another cause. |
| Vision | Blurred or altered vision associated with optic nerve involvement. | New visual change is time-sensitive and should not be self-diagnosed as B12 deficiency. |
| Babies and children | Feeding difficulty, faltering growth, lethargy, low muscle tone, irritability, abnormal movements, developmental delay or regression. | Urgent paediatric assessment is required. |
Macrocytic anaemia is a familiar presentation, but it is not compulsory. Coexisting iron deficiency can lower the average red-cell size and conceal macrocytosis. Folate use may improve the blood-cell picture while leaving B12-related neurological injury untreated. A normal full blood count therefore cannot safely overrule a persuasive neurological history.[1,8]
When symptoms need urgent medical help
Seek urgent same-day medical assessment for new or rapidly worsening weakness, difficulty walking, severe loss of balance, significant visual change, marked confusion, fainting, severe breathlessness, chest pain, loss of bladder or bowel control, or neurological symptoms after nitrous oxide use.
Call 112 or 999 for severe, sudden or life-threatening symptoms, including facial droop, one-sided weakness or speech disturbance. Do not assume that a sudden neurological event is caused by B12.
Babies and children with feeding difficulty, lethargy, low tone, abnormal movements, developmental regression or poor growth need urgent paediatric assessment. Prompt treatment matters because some neurological effects can become irreversible.[1,8]
Who is more likely to develop low vitamin B12?
Testing is most informative when compatible symptoms or signs occur alongside one or more plausible risks. Absence of a recognised risk does not prevent testing when clinical concern is strong.
| Risk area | Examples | Question to clarify |
|---|---|---|
| Low or unreliable intake | Vegan eating without reliable supplementation, vegetarian eating with low dairy or egg intake, restrictive eating, an eating disorder, sensory-based food limitation, low appetite, frailty or alcohol dependence. | Is B12 supplied consistently across a normal week, and has the label been checked? |
| Autoimmune conditions | Autoimmune gastritis, type 1 diabetes, autoimmune thyroid disease, vitiligo, Addison’s disease or a family history of B12 deficiency or autoimmune illness. | Could immune damage to stomach parietal cells be reducing intrinsic factor and acid production? |
| Digestive disease | Coeliac disease, Crohn’s disease involving the ileum, atrophic gastritis, pancreatic insufficiency or another malabsorption condition. | Are bowel symptoms, weight change, iron deficiency or an established diagnosis present? |
| Surgery | Total or partial gastrectomy, bariatric surgery, or terminal ileal resection. | Was lifelong monitoring or replacement agreed after surgery? |
| Medicines | Metformin, proton pump inhibitors, H2-receptor antagonists, colchicine and some anticonvulsants. | What dose and duration are involved, and are several risks present together? |
| Nitrous oxide | Repeated or heavy recreational use, or repeated occupational or clinical exposure. | Could B12 have been chemically inactivated even if the serum result is not low? |
| Higher-consequence life stages | Pregnancy, breastfeeding, infancy, childhood and adolescence. | Would delay increase neurological or developmental risk? |
| Older age and combined risks | Reduced intake, several medicines, atrophic gastritis, frailty or previous gastrointestinal surgery. | Is an apparently age-related symptom masking a correctable cause? |
Metformin requires particular attention
The UK Medicines and Healthcare products Regulatory Agency describes reduced B12 as a common adverse effect of metformin that may affect up to 1 in 10 people. Risk increases with a higher dose, longer duration and additional risk factors. It advises testing when deficiency is suspected and considering periodic monitoring in people at increased risk. The answer is not to stop metformin independently. Confirmed deficiency can usually be treated while necessary diabetes care continues.[13,14]
Acid-suppressing medicines need individual assessment
Proton pump inhibitors and H2-receptor antagonists can reduce the release of food-bound B12. NICE includes them as risk factors, but pooled research is inconsistent and does not establish that every user needs frequent testing. Duration, dose, age, diet, gastric health, metformin use and neurological symptoms alter the individual picture. Long-term need should be reviewed with the prescriber, not by abruptly stopping treatment.[1,15,16]
People managing digestive symptoms may also find the evidence-led guide to IBS, bloating, reflux and gut health useful. It does not replace investigation of suspected malabsorption.
Vitamin B12 foods and daily intake
EFSA sets an adequate intake of 4 micrograms per day for adults, 4.5 micrograms during pregnancy and 5 micrograms during breastfeeding. These values describe population intake for generally healthy people. They are not treatment doses for established deficiency. Children and teenagers have age-specific requirements.[4]
| Food | Approximate B12 in a usual serving | Practical point |
|---|---|---|
| Beef liver, 75 g cooked | More than 40 micrograms | Exceptionally rich, but liver is not needed for B12 adequacy and is not advised during pregnancy because of its preformed vitamin A content. |
| Clams or mussels, 85 to 100 g cooked | Often 10 to 20 micrograms or more | Content varies by species and source. |
| Sardines, trout or salmon, about 100 g | Roughly 3 to 9 micrograms | Fish also supplies protein and other nutrients. |
| Beef, about 100 g cooked | Roughly 2 to 3 micrograms | Values vary by cut and preparation. |
| Cow’s milk, 250 ml | About 1 microgram | Several dairy servings may contribute across the day. |
| Yoghurt, 150 to 170 g | About 0.7 to 1 microgram | Check the serving and product. |
| Egg, one large | About 0.5 micrograms | Eggs alone may not meet adult needs if the wider diet supplies little B12. |
| Fortified breakfast cereal | Varies widely | Read the B12 value per serving and compare it with the portion actually eaten. |
| Fortified plant drink, 250 ml | Often around 1 microgram, but variable | Not every product is fortified. Shake the carton and recheck labels because recipes change. |
| Fortified nutritional yeast | Varies widely | Only a product that lists B12 on the label is dependable. |
Food values are approximate. Species, brand, serving size, production and the food-composition source all affect the number.[5] Unfortified plant foods do not provide a reliable amount of biologically useful B12. Spirulina, chlorella, seaweed, mushrooms, fermented vegetables and unfortified nutritional yeast should not be relied upon to prevent deficiency.
Food can improve long-term intake and prevent dietary inadequacy. It cannot reliably correct serious deficiency caused by autoimmune gastritis, major gastrointestinal surgery, terminal ileal disease or significant neurological involvement. Once deficiency exists, ordinary food portions or a low-dose multivitamin may not provide therapeutic replacement.
A Registered Nutritionist assessment can help establish what is actually consumed, including fortified brands, accepted foods and supplements. Claire’s Registered Nutritionist services are available ONLINE across Ireland and internationally, with selected in-person appointments.
B12 blood tests: what to request and how to interpret the result
Blood should ideally be taken before replacement starts. Tell the GP or laboratory about multivitamins, fortified drinks, tablets, drops, sprays and injections, including the dose and most recent use. These can increase the measured serum concentration and complicate interpretation.[1]
NICE initial test thresholds for people aged 16 and over
| Initial test | Confirmed deficiency | Indeterminate or possible deficiency | Deficiency unlikely |
|---|---|---|---|
| Total serum B12 | Below 180 ng/L, or below 133 pmol/L | 180 to 350 ng/L, or 133 to 258 pmol/L | Above 350 ng/L, or above 258 pmol/L |
| Active B12, holotranscobalamin | Below 25 pmol/L | 25 to 70 pmol/L | Above 70 pmol/L |
These are NICE guide thresholds, not universal laboratory reference intervals. Laboratories use different analysers, so the range printed with the individual result still matters. The same numerical value cannot be compared across ng/L, pg/mL and pmol/L without correct unit conversion. Pregnancy, oral contraception, kidney or liver disease, inflammation and binding-protein abnormalities can also affect interpretation.[1,11]
What each test contributes
| Test | Main role | Important limitation |
|---|---|---|
| Full blood count and blood film | Identifies anaemia, macrocytosis and other cell abnormalities. | A normal result does not exclude neurological B12 deficiency. Iron deficiency can mask macrocytosis. |
| Total serum B12 | Widely available initial measure of circulating B12. | Includes B12 bound to several carrier proteins. Recent supplements and altered binding proteins can make the number misleading. |
| Active B12 | Measures holotranscobalamin, the fraction available for cellular uptake. | Availability and reference ranges vary. It still requires clinical interpretation. |
| Methylmalonic acid, MMA | Often the most specific functional marker when an initial result is indeterminate. | Kidney impairment and age can raise MMA independently of B12 deficiency. |
| Homocysteine | May rise when B12-dependent metabolism is impaired; useful in selected cases and nitrous oxide assessment. | Folate, vitamin B6, kidney and thyroid function, medicines and genetics reduce specificity. |
| Anti-intrinsic factor antibody | Supports autoimmune gastritis when positive. | A negative result does not exclude autoimmune gastritis. |
| Additional cause tests | May include coeliac serology, iron and folate studies, thyroid, kidney or liver tests, depending on the history. | There is no single universal panel. Testing should follow a clinical question. |
What an indeterminate result means
An indeterminate result is not proof of deficiency and not permission to dismiss compatible symptoms. NICE recommends considering MMA when symptoms or signs are present and the initial total or active B12 result is indeterminate. Treatment may begin while additional testing is arranged if neurological or haematological deterioration, pregnancy, major surgery or another high-consequence situation makes delay unsafe.[1]
The opposite problem also matters. Repeating an isolated B12 panel indefinitely can delay recognition of iron deficiency, thyroid disease, diabetes, sleep disorders, medication effects, neurological disease or another cause. The result must sit inside a structured assessment.
The B12 TRACE Framework
The Claire Russell Therapy B12 TRACE Framework is an educational structure for organising information before and alongside medical assessment. It is not a diagnostic test.
| TRACE step | Questions to organise |
|---|---|
| T: Timeline and treatment | What began first? Is the problem progressive? What function has changed? Which supplements or injections were taken, at what dose and when? |
| R: Risks and replacement needs | What is the usual diet? Are metformin, acid suppression, nitrous oxide, pregnancy, older age, surgery or restrictive eating relevant? Could reliable daily treatment be difficult? |
| A: Absorption and autoimmune clues | Is there coeliac disease, Crohn’s disease, gastric or ileal surgery, gastritis, type 1 diabetes, autoimmune thyroid disease or a family history? |
| C: Confirm, contextualise and check alternatives | Are units and reference ranges correct? Would active B12, MMA, homocysteine or cause testing add value? Could iron, folate, thyroid, kidney, liver, glucose, sleep or neurological factors better explain the symptoms? |
| E: Evaluate response and the enduring plan | Are symptoms and daily function improving? Is the route adequate? Has the cause been documented? Is replacement temporary, reviewed or lifelong? |
TRACE prevents two common errors: treating a number without investigating the person, and treating a symptom label without checking the biochemical and medical context. It also creates a concise record to bring to a GP, pharmacist, dietitian, Registered Nutritionist or specialist.
Finding the underlying cause
The cause determines whether food changes are enough for prevention, whether high-dose tablets are appropriate, whether injections are preferable and whether treatment must continue for life.
Autoimmune gastritis and the term pernicious anaemia
Autoimmune gastritis damages parietal cells in the stomach. This can reduce acid and intrinsic-factor production, impairing the release and absorption of B12. Iron deficiency may appear before B12 deficiency because gastric acid also matters for iron handling. The historical term pernicious anaemia describes a later haematological consequence, but NICE now recommends the more specific term autoimmune gastritis when that is the cause.[1,19]
A positive anti-intrinsic factor antibody supports the diagnosis. A negative test does not rule it out. Further assessment may include specialist antibody testing, gastrin or endoscopy according to the clinical picture. Because autoimmune gastritis is associated with a higher incidence of gastric adenocarcinoma and type 1 gastric neuroendocrine tumours, new or worsening upper gastrointestinal symptoms need medical review.[1]
Digestive disease and altered anatomy
Coeliac disease, Crohn’s disease involving the terminal ileum, pancreatic insufficiency, bacterial overgrowth in selected contexts and gastrointestinal surgery can affect different stages of absorption. If the cause remains unexplained, NICE advises considering testing for coeliac disease.[1] Symptoms such as persistent diarrhoea, unplanned weight loss, abdominal pain, vomiting, swallowing difficulty or gastrointestinal bleeding require medical assessment rather than nutrition treatment alone.
Claire’s resource on H. pylori, IBS, diverticulitis, SIBO and digestive symptoms explains why similar digestive complaints can arise from different causes. H. pylori has been associated with altered micronutrient status in research, but association does not establish that it is the cause of every low B12 result.[24]
Dietary insufficiency should be demonstrated, not assumed
A credible dietary assessment records portions, frequency, product labels, fortified foods and supplements across an ordinary week. It also examines why intake is limited. Low appetite, financial constraints, eating disorders, sensory preferences, autism, ADHD, gastrointestinal fear and alcohol use can each create different practical barriers. The response should be individual and respectful, not based on the diet label alone.
Alcohol can reduce food quality and may coexist with other nutritional risks. Anyone concerned about their use can read Claire’s evidence-led overview of addiction therapy and related care in Ireland. Medical assessment is still required when withdrawal, dependence or physical complications are possible.
Treatment and follow-up
Treatment has three jobs: correct the deficiency, protect neurological and blood function, and manage the reason it developed. Dose, route, loading schedule and duration are clinical decisions.[1,10]
When intramuscular replacement is usually needed
NICE recommends lifelong intramuscular B12 when autoimmune gastritis is the cause or is suspected, and after total gastrectomy or complete terminal ileal resection. Intramuscular treatment may also be preferable when neurological impairment is severe, deterioration is rapid, absorption is uncertain or dependable daily tablets are unlikely.[1]
When oral replacement may be appropriate
High-dose oral B12 can be effective for many people, including some with malabsorption, because a small amount is absorbed passively. NICE states that when oral replacement is used for confirmed or suspected malabsorption, the dose should be at least 1 mg daily. A Cochrane review found similar short-term serum responses with oral and intramuscular treatment in the three small trials available, involving 153 participants. Evidence quality was low and symptom outcomes were insufficient to declare the routes interchangeable in every situation.[17]
Follow-up should measure function
NICE advises explaining that symptoms may start to improve within two weeks, but improvement can take up to three months to begin and much longer to complete. Blood-cell production often responds before numbness, balance or cognition. Long-standing neurological injury may be incomplete or irreversible.[1]
Initial follow-up is generally around three months, or earlier if symptoms are severe. During pregnancy or breastfeeding, NICE advises follow-up at about one month. Review should cover treatment use, missed doses, adverse effects, symptoms and functional outcomes. Useful measures include walking distance, falls, hand sensation, concentration, tongue pain and ability to complete normal activities.
After intramuscular treatment, repeating the original serum B12 test usually adds little because the result is expected to be high. If symptoms have not improved, the clinician should reconsider adherence, route, dose, diagnosis, cause and competing conditions rather than pursuing a target serum number.[1]
Pregnancy, breastfeeding, babies and children
Pregnancy, breastfeeding, infancy and childhood are periods of rapid growth and neurological development. A parent with deficiency may have anaemia, fatigue or neurological symptoms. Low maternal stores can also leave an exclusively breastfed infant with insufficient B12, particularly when the parent’s diet has no reliable source or absorption is impaired.
NICE recommends active B12 as the initial test during pregnancy where it is available. Treatment follow-up should occur earlier than usual, generally after one month. Routine folic acid or a pregnancy multivitamin should not be assumed to correct established B12 deficiency.[1]
The HSE advises people following a vegan diet during pregnancy to take 10 micrograms of B12 daily. It also identifies vegetarians and people who do not consume dairy products as being at increased risk of low B12.[25] This preventative advice is not a treatment dose for diagnosed deficiency. European paediatric guidance likewise emphasises a reliable B12 supply and appropriate monitoring for infants, children and adolescents following vegan diets.[22]
Infant or child warning signs include poor feeding, lethargy, low muscle tone, faltering growth, abnormal movements, developmental delay or regression. These require urgent paediatric assessment. Adult supplement doses should never be extrapolated to a child without the appropriate clinician.
Mental health, cognition, fatigue and sleep
B12 deficiency can contribute to low mood, irritability, anxiety-like symptoms, slowed thinking, poor concentration, memory change and, less commonly, severe cognitive or psychiatric disturbance. Correcting genuine deficiency is clinically important. It is not evidence that B12 is a universal treatment for depression, anxiety, fatigue or dementia.[8,12]
Randomised trial evidence has not shown a clear cognitive, depressive or fatigue benefit from B12 supplementation in people without overt deficiency or advanced neurological disease.[12] Persistent symptoms therefore need a broader assessment that may include iron and folate status, thyroid function, glucose regulation, sleep disorders, medicines, alcohol, infection, cardiopulmonary causes, life circumstances and mental health.
Readers whose main difficulty is persistent worry may use the detailed guide to anxiety disorders and evidence-based care in Ireland. Those with disrupted sleep can review insomnia and poor sleep. These resources complement, but do not replace, assessment for a nutritional or medical contributor.
Fatigue that persists despite rest is not automatically low B12. Claire’s guide to feeling tired, sluggish or low in energy explains how several causes can overlap. Sudden or severe breathlessness, chest pain, fainting or neurological change requires urgent medical care.
An evidence-bounded functional medicine perspective
An integrative functional medicine approach can be useful when it means building a clear timeline, mapping diet and medicines, identifying absorption risks, checking related deficiencies, examining why the problem recurred and coordinating nutrition with medical care. It should not mean ordering large untargeted panels, diagnosing from one non-standard marker or assigning every symptom to a single pathway.
Reasonable questions include:
- Was the sample taken before supplementation?
- Does the result match the symptoms and risk profile?
- Could autoimmune gastritis, coeliac disease, ileal disease or surgery explain impaired absorption?
- Are iron, folate, thyroid, kidney, liver or glucose findings relevant?
- Is the prescribed route realistic and adequate?
- Are symptoms and daily function changing as expected?
The intestinal microbiome participates in B12 competition and metabolism, but human evidence is not yet strong enough to justify microbiome tests or probiotics as a treatment for B12 deficiency. A systematic review found a small and varied evidence base, including in-vitro, animal and observational human studies.[20] A 2026 critical review also describes plausible links between B vitamins, immune function, ageing and the microbiome, but plausible mechanisms are not a treatment protocol.[21]
What is established, emerging or unsupported?
| Evidence level | What can reasonably be said | What should not be concluded |
|---|---|---|
| Established | B12 deficiency can cause haematological and neurological illness without macrocytosis. Total or active B12 are usual initial tests, with MMA useful in selected indeterminate cases. Autoimmune gastritis, major gastric or ileal surgery, metformin and nitrous oxide are recognised risks. | A normal full blood count does not exclude deficiency. |
| Supported but context-dependent | High-dose oral treatment can work for many people. PPIs may contribute in susceptible users. Active B12, MMA and homocysteine can clarify selected cases. | No single treatment route or additional biomarker is best for every person. |
| Emerging | The microbiome may influence B12 availability and metabolism. H. pylori and several chronic conditions have reported associations with B12 status. | Association and mechanism do not establish an individual cause or effective treatment. |
| Unsupported or overstated | There is no good evidence that B12 injections cause fat loss, that methylcobalamin is universally superior, or that common MTHFR variants diagnose B12 deficiency. | Marketing claims cannot replace diagnosis, cause assessment or an adequate treatment plan. |
Two composite clinical illustrations
The following illustrations combine and alter common features from practice and published guidance. They do not describe identifiable clients and are not treatment instructions.
Composite 1: tingling attributed to perimenopause
A 49-year-old adult in County Limerick reported fatigue, disturbed sleep, poor concentration and tingling in both feet. The symptoms had been attributed to stress and perimenopause. A TRACE review identified metformin use, autoimmune thyroid disease, a history of low ferritin and recent multivitamin use. These factors made it unsafe to assume that hormones explained everything.
The GP assessed the progressive sensory symptoms, interpreted B12-related testing in light of recent supplementation and investigated a plausible cause. Nutrition work documented usual intake, meal regularity, iron-containing foods, fortified products and supplement timing. Medical treatment addressed the deficiency; follow-up measured sensation, balance and daily function rather than chasing the serum number.
This example shows why symptom overlap matters. Perimenopause can coexist with nutritional, endocrine, metabolic or neurological problems, so a new progressive symptom still needs its own assessment.
Composite 2: a restricted accepted-food range in adolescence
A 15-year-old in County Cork had autism, ADHD, sensory sensitivity and a narrow range of accepted foods. Fatigue and reduced concentration had increased gradually. The family had tried several multivitamins, but product choice and frequency varied and one product contained little B12.
The response was not to blame the young person or force unfamiliar foods. A GP-led assessment considered B12 alongside iron, folate, thyroid, coeliac and other relevant factors. Nutrition work mapped foods the teenager could reliably eat, fortified products with known label amounts, supplement acceptability and barriers such as texture and smell. Any treatment dose was set by the medical team, not inferred from the food record.
Claire’s overview of overstimulation and sensory overload provides additional context for recognising sensory needs without mislabelling them as defiance.
What to do next: a practical B12 action plan
If you have symptoms but have not been tested
- Record each symptom, when it began, whether it is progressing and what normal activity it now limits.
- List medicines, digestive diagnoses, operations, pregnancy or breastfeeding, diet pattern, alcohol and nitrous oxide exposure.
- Photograph every supplement label and note the dose, form, frequency and last use.
- Arrange a GP review and mention neurological symptoms directly rather than describing everything as tiredness.
- Where it is safe, have diagnostic blood samples taken before high-dose replacement. Do not delay urgent assessment or prescribed treatment.
If the B12 result is borderline
- Check the unit and the laboratory reference range.
- Review symptoms, risk factors and supplements with the clinician.
- Ask whether MMA would clarify possible cellular deficiency and whether kidney function affects interpretation.
- Disclose nitrous oxide use because it changes the initial biochemical approach.
- Investigate a plausible cause instead of repeating the same isolated panel indefinitely.
If treatment has started
- Follow the prescribed dose, route and schedule.
- Track two to four meaningful outcomes, such as walking steadiness, hand sensation, tongue soreness, concentration or ability to complete ordinary activities.
- Record injection dates or tablet use and any missed doses.
- Attend follow-up even when the serum result has risen. Cause, symptoms and duration still need review.
- Seek reassessment if symptoms worsen, new neurological symptoms appear or the expected response does not occur.
What to bring to a nutrition appointment
- Recent laboratory reports with units and reference ranges.
- The GP or consultant diagnosis and treatment plan, if available.
- A current medicine and supplement list.
- Three to seven days of food and drink information, including brands of fortified products.
- Relevant digestive disease, surgery, pregnancy, food restriction, sensory needs and alcohol history.
- The main question you want answered and the practical change that would make the appointment useful.
Frequently asked questions about vitamin B12
1. What are usually the first signs of B12 deficiency?
Early symptoms are often non-specific. Unexplained fatigue, reduced stamina, breathlessness during ordinary exertion, headaches, a sore red tongue, mouth ulcers and difficulty concentrating can occur. Some people notice pins and needles, numbness, clumsiness, reduced balance, altered vision, memory change or low mood before anaemia appears. Because onset may be gradual, a person can adapt to reduced function without recognising how much has changed.
No single symptom proves B12 deficiency. Suspicion rises when several compatible features occur with a recognised risk, such as a vegan diet without reliable supplementation, autoimmune disease, metformin, acid-suppressing medication, stomach or bowel surgery, coeliac disease, Crohn’s disease or nitrous oxide use. A full blood count alone cannot rule it out. The most useful first step is a structured medical history and appropriate testing before high-dose supplements where it is safe to wait. New weakness, difficulty walking, significant loss of coordination, visual change, confusion or rapidly progressing neurological symptoms require prompt assessment because delayed treatment can increase the risk of lasting nerve injury.[1,8]
2. Can I have B12 deficiency without anaemia?
Yes. B12 deficiency can affect nerves, cognition, mood, the mouth and energy before haemoglobin falls or red blood cells become enlarged. NICE explicitly advises clinicians not to exclude deficiency because anaemia or macrocytosis is absent.[1] Pins and needles, numbness, balance difficulty, memory change, a sore tongue or unexplained fatigue may therefore deserve investigation even when the full blood count appears reassuring.
The blood-cell picture can also be obscured. Coexisting iron deficiency may pull the mean cell volume down, while folic acid can improve blood formation without correcting B12-related neurological injury. Recent B12 supplements may raise the serum result before tissue function and symptoms have recovered. A sound assessment combines symptoms and neurological findings with diet, medicines, gastrointestinal surgery and autoimmune or digestive risks. When the initial result is indeterminate or conflicts with the clinical picture, active B12, MMA or homocysteine may sometimes clarify the situation. Severe or progressive neurological features should not wait for anaemia to develop before they are assessed and treated.
3. What B12 level is low or borderline?
For people aged 16 and over, NICE interprets an initial total B12 below 133 pmol/L, or below 180 ng/L, as confirmed deficiency. A result from 133 to 258 pmol/L, or 180 to 350 ng/L, is indeterminate. Above 258 pmol/L, or above 350 ng/L, makes deficiency less likely. For active B12, below 25 pmol/L is confirmed, 25 to 70 pmol/L is indeterminate and above 70 pmol/L makes deficiency less likely.[1]
These thresholds guide rather than replace clinical judgement. Laboratories use different methods and reference intervals. Symptoms, neurological examination, diet, medicines, pregnancy, kidney function and recent supplements or injections all affect interpretation. When deficiency remains plausible after an indeterminate result, MMA may help because it rises when a B12-dependent reaction is impaired. Kidney impairment can also raise MMA. Homocysteine is less specific because folate, vitamin B6, thyroid and kidney function affect it. Severe neurological symptoms may justify treatment while confirmation is arranged. Conversely, repeatedly treating a number without reconsidering other diagnoses can delay appropriate care.
4. Can my B12 be normal while I still have functional deficiency?
It is possible, but the mismatch should be investigated rather than assumed. Total serum B12 measures B12 attached to several carrier proteins, much of which is not immediately available to cells. Recent supplements or injections can raise the concentration. Altered binding proteins can produce an apparently reassuring or high result. Nitrous oxide can inactivate B12-dependent enzymes without necessarily lowering total B12.[1,9,11]
Active B12 measures the fraction available for cellular uptake. MMA rises when a B12-dependent reaction is impaired and is often the most useful functional marker in an indeterminate case. Homocysteine may also rise, but folate, vitamin B6, thyroid and kidney function reduce its specificity. MMA itself can be elevated in kidney impairment, so no marker should be interpreted alone.
A normal total result with persuasive neurological symptoms and recognised risks deserves clinical review. Equally, “functional deficiency” should not become a catch-all diagnosis for every persistent symptom. If appropriate treatment produces little improvement, the original diagnosis, adherence, cause, route and competing medical explanations should be reconsidered.
5. Can B12 deficiency cause anxiety, depression or brain fog?
Deficiency can contribute to low mood, irritability, anxiety-like symptoms, slowed thinking, poor concentration, memory difficulty and, less commonly, severe psychiatric or cognitive change. B12 is required for normal neurological function, so a genuine shortage matters even when the most noticeable complaint is “brain fog”. Irish TILDA researchers found that low B12 status in adults aged 50 and older was associated with a 51 per cent higher likelihood of developing depressive symptoms over four years. The observational design cannot prove that B12 caused those symptoms.[7]
Confirmed or strongly suspected deficiency should be corrected and its cause investigated. B12 is not, however, a universal antidepressant or cognitive enhancer. A meta-analysis of randomised trials found no clear cognitive, depressive or fatigue benefit in people without overt deficiency or advanced neurological disease.[12] Thyroid disease, iron deficiency, diabetes, sleep disorders, medicines, alcohol, infection, neurodegenerative disease and life circumstances can produce similar symptoms. B12 assessment should complement, not replace, appropriate mental health and neurological care, particularly when symptoms are severe, changing rapidly or affecting safety.
6. Will B12 injections give me energy or help me lose weight?
B12 treatment can improve energy when deficiency is an important cause of fatigue. An injection is not a stimulant. B12 supports red blood cell formation, neurological function and cellular metabolism. Correcting a shortage allows these processes to work normally; giving extra B12 to a sufficient person has not been shown to create additional energy. B12 injections also do not directly burn fat, suppress appetite or cause meaningful weight loss in someone with adequate status.[5]
When a deficient person feels better, improved stamina may make ordinary movement, cooking and self-care easier. That is different from a direct weight-loss effect. Persistent fatigue deserves a wider assessment that may include sleep, iron and folate, thyroid function, glucose regulation, infection, mood, medicines, diet and heart or lung causes. Unplanned weight loss needs medical review rather than an injection course. Treatment route should be chosen for cause, severity, absorption and adherence, not because injections are assumed to be stronger. If fatigue does not improve as expected, revisiting the diagnosis is more useful than repeatedly increasing B12 without a clear clinical indication.
7. Are tablets as effective as B12 injections?
High-dose oral B12 can be effective for many people because a small fraction crosses the intestine by passive diffusion even when intrinsic-factor absorption is impaired. A Cochrane review reported similar short-term serum responses with oral and intramuscular treatment in the three small trials available. Only 153 participants were included, evidence quality was low and symptom outcomes were too limited to prove that both routes are interchangeable in every clinical situation.[17]
Cause, severity, neurological findings, adherence and preference all matter. NICE recommends lifelong intramuscular replacement when autoimmune gastritis is confirmed or suspected, and after total gastrectomy or complete terminal ileal resection. Injections may also be preferred for severe neurological impairment, rapid deterioration, uncertain absorption or unreliable daily treatment.[1] Oral therapy avoids needles and can be convenient, but the prescribed dose must be adequate and taken consistently. A rise in the blood number is encouraging; recovery in sensation, balance, cognition and daily function is more meaningful. Any route change should be agreed with the prescriber, especially when treatment is lifelong.
8. How long does recovery from B12 deficiency take?
Recovery varies with severity, duration, cause and the tissues affected. NICE advises explaining that symptoms may begin to improve within about two weeks, but it can take up to three months for improvement to start and considerably longer for symptoms to disappear.[1] Mouth soreness, blood counts and some aspects of fatigue may change relatively quickly. Numbness, balance, memory and other neurological features often recover more slowly because damaged nerves need time. Long-standing neurological injury may be incomplete or irreversible.
Useful follow-up looks beyond a laboratory number. Track a few meaningful outcomes, such as walking distance, falls, hand sensation, ability to work, concentration or tongue pain. Serum B12 is expected to become high after injections, so repeating it may not show whether symptoms or tissue function have recovered. When improvement does not occur, clinicians should review the dose and route, treatment adherence, underlying cause and competing diagnoses. New weakness, worsening balance, significant visual change, bladder symptoms or rapidly advancing numbness needs prompt reassessment rather than waiting for the next routine appointment.
9. Do vegetarians and vegans need B12 supplements?
People following a vegan diet need a dependable B12 source because unfortified plant foods do not reliably provide biologically useful B12. This usually means a suitable supplement, foods with a clearly stated B12 content consumed consistently, or both. Vegetarian diets can supply B12 through eggs and dairy, but intake varies. What matters is the actual weekly pattern, not the diet label.[5]
Check the amount per serving, frequency, expiry date and whether the dose suits age, pregnancy or an established deficiency. Seaweed, spirulina and fermented foods are not dependable substitutes because content and biological activity are inconsistent. Children, teenagers, pregnant people and breastfeeding families need particular care because neurological development raises the consequences of inadequate supply.
Supplements do not rule out malabsorption. A vegan or vegetarian with persistent low status despite a credible intake still needs assessment for autoimmune gastritis, coeliac disease, bowel inflammation, surgery or medicines. Once deficiency is present, an ordinary multivitamin may contain too little B12 for treatment. The therapeutic dose and route should follow clinical guidance.
10. Should people taking metformin or a proton pump inhibitor be tested?
Metformin is a well-established risk factor for reduced B12, particularly with higher doses, longer use and additional risks. The medicines regulator describes low B12 as a common adverse effect that may affect up to one in ten people taking metformin. It advises testing when deficiency is suspected and considering periodic monitoring in people with risk factors.[13] New neuropathy, unusual fatigue, a sore tongue or cognitive change should not automatically be attributed to diabetes or ageing.
Proton pump inhibitors and other acid-suppressing medicines can reduce the release of food-bound B12. NICE lists them as risk factors, although pooled research is mixed and does not justify the same frequent testing schedule for every user.[1,15,16] Duration, dose, age, diet, gastrointestinal disease, surgery and concurrent metformin all affect likelihood. A medicine review should ask whether treatment remains indicated, whether the lowest effective dose is used and whether symptoms or combined risks justify testing. Do not stop metformin or acid suppression independently. Treating confirmed B12 deficiency usually allows necessary medicine to continue while the prescriber plans monitoring and replacement.
11. Is B12 especially important in pregnancy and childhood?
Yes. Pregnancy, breastfeeding, infancy and childhood involve rapid growth and neurological development. Deficiency in a pregnant person may cause anaemia, fatigue or neurological symptoms, while low maternal stores can leave a breastfed infant with insufficient B12. Infant warning signs include poor feeding, lethargy, low muscle tone, faltering growth, abnormal movements, developmental delay or regression. These require urgent paediatric assessment because early treatment can affect the outcome.
NICE recommends active B12 as the initial test during pregnancy where available and advises earlier treatment follow-up, usually at one month rather than three.[1] Diet needs careful attention when animal foods are excluded, but dietary insufficiency should not be assumed until absorption risks are considered. European paediatric guidance recommends a dependable source and appropriate monitoring for children following vegan diets.[22]
A routine pregnancy multivitamin or folic acid tablet should not be assumed to correct established B12 deficiency. Families should agree the product, dose, route and follow-up with their GP, midwife, dietitian, paediatrician or obstetric team. An adult supplement plan should never be transferred to a child without clinical advice.
12. What does a high B12 result mean?
Supplements and recent injections are the most common explanations for a high B12 result. After prescribed replacement, a raised serum concentration is expected. It does not show toxicity, prove that every symptom has resolved or justify stopping lifelong treatment. Interpretation should account for the dose, route and timing. Repeating serum B12 after injections is often less informative than checking clinical recovery and the cause.[1]
Persistently high B12 without supplementation deserves proportionate medical assessment, not panic. Increased carrier proteins or reduced clearance can occur with liver disease, kidney impairment, inflammation and some blood disorders. Macro-B12, in which B12 is bound within an immunoglobulin complex, can produce a high measured value that may not reflect biologically available B12.[23]
Population research has found associations between unexplained high B12 and serious illness, but association is not diagnosis and B12 is not a stand-alone cancer test. A GP may review the full blood count, liver and kidney results, inflammation, medicines and clinical history, then investigate further where indicated. One laboratory number should be explained without being ignored or turned into a frightening conclusion.
13. Is methylcobalamin better than cyanocobalamin, and does MTHFR matter?
No B12 form has been shown to be universally superior. Cyanocobalamin is stable, well studied and widely used in oral supplements. Methylcobalamin is a coenzyme form and is also a suitable source. Hydroxocobalamin is commonly used for injections in Ireland and the UK because it is retained well. The body converts suitable cobalamin forms into the coenzymes it needs, and available evidence does not show a consistent absorption advantage for one supplemental form over another.[5]
MTHFR is an enzyme in folate metabolism. Common MTHFR variants do not diagnose B12 deficiency, demonstrate impaired absorption or automatically require methylcobalamin. Testing should be driven by symptoms, recognised risks and clinical guidance, not a genetic variant in isolation.
In practice, adequate dose, route, adherence, product reliability and treatment of the underlying cause matter more than marketing about “active” forms. Sublingual sprays or lozenges may be convenient, but they have not been shown to be universally better than an adequate swallowed dose. People with neurological symptoms, significant malabsorption or a lifelong indication should not change a prescribed regimen because another chemical form is promoted online.
14. Why is nitrous oxide linked to B12 deficiency?
Nitrous oxide oxidises the cobalt centre of B12 and inactivates B12-dependent enzymes. A person can therefore develop functional deficiency even when total serum B12 sits within the laboratory range, particularly after supplementation. This can disrupt myelin and cause numbness, pins and needles, weakness, poor balance, an unsteady gait, bladder disturbance or cognitive change. Repeated or heavy exposure can cause serious spinal cord and peripheral nerve injury, and pre-existing low B12 increases vulnerability.[1,8]
When exposure is suspected, NICE advises using MMA or homocysteine as the initial biochemical test rather than relying on total or active B12.[1] Exposure should stop and neurological symptoms need prompt medical assessment. Severe weakness, inability to walk, rapidly spreading numbness, new bladder or bowel difficulty, confusion or visual change is urgent.
Management may include intramuscular or high-dose oral B12 according to clinical judgement, alongside investigation of other deficiencies and causes. Honest disclosure about amount and frequency helps the clinician select the right tests and treatment. Taking B12 does not make continued nitrous oxide use safe.
Book a Registered Nutritionist appointment
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About the author and clinical review
Claire Russell, MSc, BSc, DipNT, MNTOI, is a Registered Nutritionist, Clinical Medical Hypnotherapist, Clinical Hypnotherapist, Counsellor, Psychotherapist, RTT Practitioner and Advanced Rapid Transformational Therapist. She has more than 20 years of clinical experience with adults, teenagers, children and couples across Ireland, the UK, Europe and internationally.
Claire’s nutrition work integrates nutritional science, functional medicine assessment and practical behaviour change while recognising the boundaries between nutrition, primary care, specialist medicine and mental health care. Learn more about Claire Russell’s qualifications and professional approach.
How this resource was produced
- Written and clinically reviewed by Claire Russell.
- Primary clinical framework: NICE NG239 for vitamin B12 deficiency in people aged 16 and over.
- Irish context: current HSE public guidance, the HSE NCCP Haematology Referral Information Manual and TILDA research.
- Nutrition reference values: EFSA, with food, form and absorption context from the US National Institutes of Health.
- Evidence hierarchy: guidelines and systematic reviews prioritised; observational and mechanistic findings labelled; composite examples separated from research claims.
- No supplement brand, laboratory or pharmaceutical company paid for inclusion.
- Last evidence search and clinical review: 23 August 2026.
Medical and nutrition disclaimer
This resource provides general education. It is not a personal diagnosis, prescription or substitute for assessment by a GP, pharmacist, registered dietitian, Registered Nutritionist or relevant specialist. Laboratory interpretation and treatment depend on age, pregnancy, symptoms, cause, medicines, kidney and liver function, laboratory method and clinical examination. Do not stop prescribed medicine, alter an injection schedule, or begin high-dose B12 or folic acid solely from online information. Seek urgent care for severe or progressive neurological symptoms, visual change, marked confusion, chest pain, severe breathlessness or concerns about a baby or child.
Scientific and clinical references
- National Institute for Health and Care Excellence. Vitamin B12 deficiency in over 16s: diagnosis and management. NICE guideline NG239. Published 6 March 2024.
- Health Service Executive. Vitamin B12 or folate deficiency anaemia. HSE Health A to Z. Reviewed 10 November 2024.
- Health Service Executive National Cancer Control Programme. NCCP Haematology Referral Information Manual (Adult). Version 2. 2026.
- EFSA Panel on Dietetic Products, Nutrition and Allergies. Scientific Opinion on Dietary Reference Values for cobalamin (vitamin B12). EFSA Journal. 2015;13(7):4150. doi:10.2903/j.efsa.2015.4150.
- National Institutes of Health Office of Dietary Supplements. Vitamin B12: Fact Sheet for Health Professionals. Accessed 23 August 2026.
- Laird EJ, O’Halloran AM, Carey D, O’Connor D, Kenny RA, Molloy AM. Voluntary fortification is ineffective to maintain the vitamin B12 and folate status of older Irish adults: evidence from the Irish Longitudinal Study on Ageing (TILDA). British Journal of Nutrition. 2018;120(1):111–120.
- Laird EJ, O’Halloran AM, Molloy AM, et al. Low vitamin B12 but not folate is associated with incident depressive symptoms in community-dwelling older adults: a 4-year longitudinal study. British Journal of Nutrition. 2023;130(2):268–275.
- Green R, Allen LH, Bjorke-Monsen AL, et al. Vitamin B12 deficiency. Nature Reviews Disease Primers. 2017;3:17040.
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- Markun S, Gravestock I, Jager L, Rosemann T, Pichierri G, Burgstaller JM. Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression. Nutrients. 2021;13(3):923.
- Medicines and Healthcare products Regulatory Agency. Metformin and reduced vitamin B12 levels: new advice for monitoring patients at risk. Drug Safety Update. 20 June 2022.
- de Jager J, Kooy A, Lehert P, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ. 2010;340:c2181.
- Choudhury A, Jena A, Jearth V, et al. Vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis. Expert Review of Gastroenterology and Hepatology. 2023;17(5):479–487.
- Parnham O, Patient W. Association Between Long-Term Proton Pump Inhibitor Therapy and Vitamin B12 Status: A Systematic Review and Meta-Analysis. Cureus. 2025;17(8):e90038.
- Wang H, Li L, Qin LL, Song Y, Vidal-Alaball J, Liu TH. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database of Systematic Reviews. 2018;3:CD004655.
- Guéant JL, Guéant-Rodriguez RM, Alpers DH. Vitamin B12 absorption and malabsorption. Vitamins and Hormones. 2022;119:241–274.
- Shah SC, Piazuelo MB, Kuipers EJ, Li D. AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis: Expert Review. Gastroenterology. 2021;161(4):1325–1332.e7.
- Guetterman HM, Huey SL, Knight R, Fox AM, Mehta S, Finkelstein JL. Vitamin B-12 and the Gastrointestinal Microbiome: A Systematic Review. Advances in Nutrition. 2022;13(2):530–558.
- Shabbir U, McNulty H, Hughes C, Ward M, Dooley J, Hoey L. B vitamins, immune function and the ageing brain: a critical review of the evidence, mechanisms and potential role of the gut microbiome. Proceedings of the Nutrition Society. 2026. First View:1–12.
- Verduci E, Köglmeier J, Haiden N, et al. Vegan diet and nutritional status in infants, children and adolescents: A position paper based on a systematic search by the ESPGHAN Nutrition Committee. Journal of Pediatric Gastroenterology and Nutrition. 2025;81(5):1318–1345.
- Fedosov SN, Nexø E. Macro-B12 and Unexpectedly High Levels of Plasma B12: A Critical Review. Nutrients. 2024;16(5):648.
- Cai X, Li X, Jin Y, et al. Vitamins and Helicobacter pylori: An Updated Comprehensive Meta-Analysis and Systematic Review. Frontiers in Nutrition. 2022;8:781333.
- Health Service Executive. Vegetarian and vegan diets in pregnancy. Reviewed 26 June 2025.