Vitamin B12, active B12 and folate: which blood test does what

BPR Clinic20 October 20265 min readLer em português

Total B12, active B12, serum folate and red cell folate sound alike but answer slightly different questions. Here is how they compare and when people tend to check them.

Tests in this article:Vitamin B12,Vitamin B12 (Active),Folate (Vitamin B9),Folate (Red Cell),Methylmalonic acid (serum),Vitamin Profile

Someone switches to a plant-based diet, another person turns 60, a third has taken a stomach-acid medicine for years. Different stories, same question: is my vitamin B12 where it should be? Then comes the second question, the one people often ask us: should I test ordinary B12 or active B12, and what about folate?

This guide explains what each test in the BPR catalogue measures, how they relate to each other, and when looking at them tends to be useful.

Why vitamin B12 and folate are looked at together

Vitamin B12 and folate (vitamin B9) work closely together. Both are needed to make healthy red blood cells, and B12 also helps keep the nervous system healthy. The NHS explains that a lack of either can lead the body to produce abnormally large red blood cells that do not work properly, a type of anaemia. It also lists signs such as extreme tiredness, pins and needles, a sore red tongue, mouth ulcers and problems with memory, and notes that some of these can appear even before anaemia develops.

Because the two vitamins overlap so much, British haematology guidance discusses them side by side (Devalia et al., 2014), and laboratories often offer them together.

Total B12 or active B12?

Vitamin B12 (total)

The Vitamin B12 test measures all the B12 in the serum. Most of it is bound to a carrier protein that does not deliver it to cells. It is the long-established test and is widely available.

Vitamin B12 (Active)

The Vitamin B12 (Active) test measures holotranscobalamin, the fraction of B12 attached to the protein that actually delivers it to the body's cells. Reviews of B12 biomarkers describe it as a useful marker of the B12 that is available to tissues (Harrington et al., 2025).

What NICE says

The NICE guideline on vitamin B12 deficiency in people over 16 (NG239, 2024) recommends using either total B12 or active B12 as the first test, and active B12 in pregnancy. It also describes an "indeterminate" zone where the result is neither clearly low nor clearly fine. In that situation, NICE suggests considering a further test called methylmalonic acid (MMA), which is also in the BPR catalogue as Methylmalonic acid (serum).

NICE also flags that results can be affected by B12 supplements already being taken, and that the combined contraceptive pill can lower total B12 without there being a true shortage. That is a good reason to mention any supplements or medicines when you discuss your result.

Serum folate or red cell folate?

The catalogue lists two folate tests:

  • Folate (Vitamin B9) measures folate in the serum, a level that is influenced by recent intake (Devalia et al., 2014).
  • Folate (Red Cell) measures folate stored inside red blood cells. Because red cells live for months, this test is often described as reflecting a longer period (Devalia et al., 2014).

LML lists situations where folate is often looked at: malabsorption conditions such as coeliac disease or inflammatory bowel disease, regular heavy alcohol use, and pregnancy, where folate is particularly important for the developing baby.

Who tends to check B12 and folate?

Plant-based diets

The NHS lists meat, fish, eggs, dairy products and specially fortified foods as sources of B12, and notes that a lack in the diet is uncommon but can happen on a vegan diet without B12 supplements or fortified foods. LML highlights the test as particularly relevant for anyone on a plant-based diet. A recent systematic review found that functional B12 status in adult vegans varies a great deal, and is better in those who use supplements (Niklewicz et al., 2024).

People over 50

The NHS notes that B12 and folate deficiency become more common with age, affecting around 1 in 10 people aged 75 or over and 1 in 20 people aged 65 to 74.

Some medicines and health conditions

NICE lists several common risk factors, including long-term use of proton pump inhibitors or metformin, coeliac disease and other autoimmune conditions, and some types of stomach or bowel surgery.

Single tests or a profile?

If you want one picture rather than several separate tests, the Vitamin Profile combines vitamin B12, folate and vitamin D in a single sample. If the question is specifically about B12, the individual total or active B12 test may be enough. A professional can help you choose.

How often?

For people on vegan diets and for adults over 50, a yearly check is a common general guide. Others may only need a test when there is a specific reason. Talk to a professional about what fits your situation, especially if you take supplements, as they can change the result.

How the sample is collected

BPR does not collect samples. LML arranges every collection: a home kit, an LML collection point you can find by postcode, or a phlebotomist at your home. According to LML, results for total B12, active B12, serum folate and red cell folate are available 1 day after the sample reaches the laboratory. Under-18s visiting a collection point need to be accompanied by an adult.

These tests are all in the BPR catalogue. Questions are welcome at [email protected], through the form on our website or in the app.

Frequently asked questions

Is active B12 better than total B12? Neither is simply better. NICE accepts either as the first test, with active B12 preferred in pregnancy. Active B12 focuses on the fraction delivered to cells, while total B12 is the longer-established measure.

Should I stop my B12 supplement before testing? Do not change any supplement or medicine without advice. NICE notes that supplements can raise the result, so tell the professional interpreting it what you take.

Why would anyone test red cell folate instead of serum folate? Serum folate changes faster with recent intake, while red cell folate is often described as reflecting a longer period. Which one is more useful depends on the question being asked.

References

  1. Vitamin B12 deficiency in over 16s: diagnosis and management (NG239). nice.org.uk
  2. Vitamin B12 or folate deficiency anaemia - NHS. nhs.uk
  3. Devalia V, et al. Br J Haematol. 2014;166(4):496-513. PMID 24942828
  4. Harrington DJ, et al. Ann Clin Biochem. 2025;62(1):22-33. PMID 39367523
  5. Niklewicz A, et al. Nutr Bull. 2024;49(4):463-479. PMID 39373282

The tests in this article

Analysed by London Medical Laboratory. Choose a home kit, an LML collection point or a phlebotomist at home.

See the full catalogue

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This article is for general information and education only and is not a substitute for an individual assessment or treatment by a qualified healthcare professional. If you have significant, worsening or concerning symptoms, please seek advice from a suitably qualified clinician.