The sources used here name several risk groups and several tests. A British Committee for Standards in Haematology guideline abstract states that definitive cut-off points to define clinical and subclinical deficiency states are not possible, given the variety of methodologies used and technical issues, and that local reference ranges should be established. MedlinePlus states that an MMA test is most often used to diagnose a vitamin B12 deficiency.
How deficiency is found
MedlinePlus, a patient information page, lists symptoms of a vitamin B12 deficiency that may lead to the test: fatigue, diarrhea, dizziness, shortness of breath, loss of appetite, tingling in hands and/or feet, mood changes, confusion, irritability and pale skin. These are symptoms the page links to a deficiency. They are not a diagnosis.
The NHLBI patient page on vitamin B12-deficiency anemia states that a blood test measures vitamin B12 levels in the blood and that you may still have the condition even if your vitamin B12 levels are normal. A selective literature review states that total serum vitamin B12 is a late, relatively insensitive and unspecific biomarker of deficiency.
A review in American Family Physician states that measurement of serum methylmalonic acid should be used to confirm deficiency in asymptomatic high-risk patients with low-normal levels of vitamin B12. The same review states that screening average-risk adults for vitamin B12 deficiency is not recommended.
Who the sources say is at risk
The American Family Physician review lists, as examples of risk factors, gastric or small intestine resections, inflammatory bowel disease, use of metformin for more than four months, use of proton pump inhibitors or histamine H2 blockers for more than 12 months, vegans or strict vegetarians, and adults older than 75 years. The NHLBI page states that older adults are more likely to have digestive problems that make it harder to absorb vitamin B12.
A 2009 review states that approximately 6% of those aged 60 years or older are vitamin B-12 deficient (plasma vitamin B-12 below 148 pmol/L), with the prevalence of deficiency increasing with age, and that closer to 20% have marginal status (plasma vitamin B-12: 148-221 pmol/L) in later life. Another review states that, although it has long been known that strict vegetarians (vegans) are at risk, evidence now indicates that low intakes of animal-source foods, such as occur in some lacto-ovo vegetarians and many less-industrialized countries, cause vitamin B12 depletion.
Drugs and lower B12
An observational case-control study concluded that previous and current gastric acid inhibitor use was significantly associated with the presence of vitamin B12 deficiency. An observational study cannot show cause and effect. A 2018 review in Advances in Nutrition states there is clear evidence that proton-pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), and metformin can reduce serum vitamin B-12 concentrations by inhibiting the absorption of the vitamin. The same review states that it is unclear if the effects of these drugs on serum vitamin B-12 are associated with increased risk of biochemical, functional or clinical deficiency.
Each source, its group and its limits
| Source and type | Group it describes | Limit |
|---|---|---|
| MedlinePlus MMA page, patient information | People with symptoms; deficiency not confirmed | Not a guideline |
| NHLBI page, patient information | Vitamin B12-deficiency anemia (the page topic); older adults | Not a trial |
| Guideline, abstract only | Clinical and subclinical deficiency states | No definitive cut-offs |
| American Family Physician review, abstract only | Average-risk adults; asymptomatic high-risk patients with low-normal levels, deficiency not confirmed | Risk factors are examples |
| 2009 review | Adults aged 60 years or older, with and without deficiency | Prevalence figures, not individual diagnosis |
| 2008 selective literature review | Deficiency biomarkers; group not stated here | Selective, abstract only |
| 2008 review of causes | Strict vegetarians; some lacto-ovo vegetarians; many less-industrialized countries | Review, abstract only |
| Observational study | People with and without deficiency, by acid inhibitor use | Shows association only; size not stated here |
| 2018 review | Effects of PPIs, H2RAs and metformin on serum B-12; group not stated here | Link to clinical deficiency unclear |
What this does not tell you
No source here settles a person's status with one test or one cut-off. The 2009 figures use that review's own plasma cut-offs and are not a diagnosis for an individual. The symptom list is not a diagnosis, and the risk lists are examples, not a score. The drug findings do not show that any drug causes deficiency in any person. None of these sources reports what an injection does, and none describes a compounded vial. A licensed provider interprets test results.