How to Spot Iron, B12 & Folate Deficiency Before Anaemia Starts (Using Routine Blood Tests)
Have you experienced B12/Folate or Iron Deficiency in IBD?
Vitamin deficiencies can be extremely common in IBD patients. We see a lot. It’s more common in Crohn's than UC, due the location of the disease being in the ileum, jejunum, or large segments of small intestine (where digestion occurs) rather than the large intestine/colon.
It can also be caused by an avoidance styled diet, or probably the bigger cause, inflammation reduced absorption.
The main reason for me trying to write this post: they aren’t to be avoided or taken lightly. Yet, very easy to diagnose. Is your doctor requesting them regularly? Is he picking up trends before symptoms occur?
As a biomedical scientist for over a decade, my job is to test and validate your results. My whole goal is to empower patients to understand the results from the lab and the meaning/reason behind them.
What is B12/Folate and Iron?
They are essential vitamins needed to make new cells. Especially red blood cells (the part of your blood that carries oxygen to your cells). Tired walking up the stairs? Memory loss, heart palpitations? They impact your quality of life massively, and are easily treatable.
Essential means the body can’t naturally produce them - so you must acquire them from your diet.
- B12 (aka Cobalamin): Needed for DNA synthesis, red blood cell production, and nerve function; Found mainly from animal products (meat, eggs, dairy); Absorbed in the terminal ileum (in Crohn’s this is a common inflammatory hot spot).
- Folate (aka Vitamin B9): Also essential for DNA synthesis; Found in green vegetables, legumes, fortified foods; Folate stores are small (weeks–months) and therefore more common in the general population; Absorbed in the small intestine.
- Iron: Required to make haemoglobin, the molecule that carries oxygen; Found in red meat, legumes, leafy greens; Absorbed in the duodenum and jejunum.
Iron gets a double hit in IBD. As bleeding depletes iron stores significantly. Commonly found routinely in menstruating females - but females also tolerate it much better than males.
Interesting fact: In Cambodia iron deficiency is very common. Their solution: ‘The lucky Iron Fish’. By cooking soups and adding a fish shaped solid chunk of iron into it - it has helped boost bioavailable iron levels. The same is true by cooking in an iron skillet.
Why is B12 and Folate always linked together?
The short answer is: having plenty of Folate is pointless without plenty of B12, and vice versa. They are biochemically intertwined by something called the methyl-folate trap. One is trapped (and therefore functionally deficient) if the other is missing. So we check them both together.
How do we identify deficiencies in the lab?
The Full Blood Count (FBC) (also known as CBC)
FBC is one of the most routine tests a doctor will request. Why? Because it's composed of 13 parameters, from white cells to red cells to platelets. Each can teach us a lot about your overall health that will directly affect your quality of life. This one test can teach us a lot about how your bone marrow (the blood cell factory) is operating, and for the purpose of this article: does your body have what's needed to create oxygen carrying red cells.
Megaloblastic Anaemia (caused by a B12 or Folate deficiency)
Increased Mean Corpuscular Volume (MCV): MCV looks at the size of the red cell. When DNA synthesis is impaired, due to a deficiency in B12/Fol, red cells do not divide efficiently. Meaning they grow into large red cells known as Macrocytes and Megaloblasts. These are hallmark features of B12/Fol deficiency. The result is fewer number of red cells which means overall less oxygen to your cells, which makes you feel tired all the time, or shortness of breath.
Typically this would show as an MCV >108 fL. And should trigger B12/Fol levels to be tested.
Low Haemoglobin: Haemoglobin is the molecule within a red cell that carries oxygen. This parameter measures the overall amount of haemoglobin circulating. Ineffective production of red cells and cell division within the bone marrow (due to impaired DNA synthesis) result in reduced red cells being released. Less red cells = less haemoglobin.
Normal haemoglobin ranges:
Men: ~130–180 g/L
Women: ~115–165 g/L
Mild anaemia: Men: ~110–129 g/L. Women: ~100–114 g/L.
Severe anaemia: <80 g/L
Increased Mean Corpuscular Haemoglobin (MCH): This parameter looks at the average amount of haemoglobin within each individual red cell (rather than the total amount of circulating haemoglobin above). MCH is increased because each large red cell has an abnormally high amount of haemoglobin within.
Hypersegmented Neutrophils on the blood film: Any abnormal results in the above, will prompt us to look down the microscope. Here a common feature of B12/Fol deficiency is hypersegmented (mature) neutrophils. Just another clue to trigger your doctor for further testing.
Microcytic Anaemia (caused by low Iron)
Low Haemoglobin: Haemoglobin is an iron based molecule. With low iron stores the body cannot create a sufficient amount of haemoglobin.
While the body will adjust and compensate for lack of oxygen, trends will show over months that iron deficiency may be starting before symptoms occur. Symptoms can go from mild and tired all the time, to severe and physically looking pale. Women can handle low Haemoglobin better than men. This can be fatal in men (and women) if ignored, but it is unlikely to be ignored for long enough!
Normal haemoglobin ranges:
Men: ~130–180 g/L
Women: ~115–165 g/L
Mild anaemia: Men: ~110–129 g/L. Women: ~100–114 g/L.
Severe anaemia: <80 g/L
Reduced Mean Corpuscular Volume (MCV): Classic sign of iron deficiency. As the body struggles to supply oxygen around the body, the bone marrow pumps out whatever red cells it can muster into the blood to compensate (quantity over quality isn’t great, but it will keep you alive i guess!). These red cells are small (microcytic). Therefore we see a low MCV.
Reduced Mean Corpuscular Haemoglobin Concentration (MCHC): Measures the average concentration of haemoglobin within your red cells. Without iron, the body can't create enough haemoglobin. So each red cell doesn't have much haemoglobin (called hypochromic) = cells in the body don’t get enough oxygen.
Blood Film: As before, any abnormal results from the FBC trigger a blood film to be looked at down the microscope. In iron deficiency, generally just confirm the above results. That the red cells look small (low MCV) and pale (not much haemoglobin in them - low MCHC). Other features may be variation in size (Anisocytosis) and variation in shape (Poikilocytosis).
I've spent a good chunk of time on the FBC (full blood count) there. Mainly because, while doctors may not always routinely request Iron/B12/Fol levels directly. They almost always request a FBC. Looking at the Haemoglobin, MCV, MCH, MCHC, and in particular trends in the wrong direction - should prompt further investigation before symptoms occur.
Further investigation
The doctor's next step is to request B12/Folate levels. As well as Iron Studies, which includes the tests: Ferritin (iron stores), Serum Iron, Transferrin / TIBC, Transferrin Saturation (TSAT). I'm going to write a separate article on the further investigation. As this is a large topic. And to be honest - I need to learn a bit more too!
The Broader Impact
B12, folate, and iron are essential far beyond blood counts. Vitamin B12 maintains the myelin sheath that insulates nerves. Without it, symptoms such as numbness, balance problems and cognitive changes can occur even before anaemia sometimes. These changes can even be permanent if ignored for a long time. Folate supports DNA synthesis and tissue repair, including the gut lining. Iron is required not only for oxygen delivery but also for brain energy metabolism and neurotransmitter function, meaning deficiency can impair concentration and mental stamina even without severe anemia. These sound scary, but the likelihood of it being missed is very rare!
So what can you do?
Well this bit really, is for your doctor to fix. We identify it, they fix it. Adjusting diet can be one aspect you can take charge of. Simple changes such as orange juice with a steak (vitamin C increases absorption of Iron, or cooking in an iron skillet). There is a wealth of information out there for this!
But now you know the importance of B12/Folate and which parameters are used to monitor it. My hope is you can take ownership and the power to ask your doctor the right questions.
These results are not just numbers to me or you. They are directly proportional to your quality of life. That’s why I do what I do. You must provide the body with the right nutrients in IBD, and maintain it. With IBD, inflammation makes it difficult but not impossible.
So don't give up, if you ever find yourself in this situation. Once we give you the answer in the form of blood results. Work with your doctor, and take ownership and power of understanding what your blood cells need, and give them and yourself the best chance.
I hope this has been somewhat helpful. As always, you aren’t alone in this. Reach out to me if you need anything.
The original article can be found on:
I’ve created some check lists for you to ask your doctor on your next visit to make sure these aren’t being missed: Questions to ask your doctor about B12, folate & iron in IBD
Chris
My Health Care and Professions Council (HCPC) registration: BS67486 (HCPC Register)

Our microscopes. Often two people will be sitting here 8 hours a day looking at films!

Blood is spread on a glass slide and stained using special stains to highlight the key areas of the blood we are looking at.

In B12/Folate deficiency we see neutrophils (A type of white cell) has lots of purple lobes (known as Hypersegmented). A normal neutrophil has 2 to 5 lobes. Hypersegmented means it has >6 lobes.

Comparison of large B12/Folate deficient red cells on the left known as macrocytes, and normal red cells right.

Iron deficient cells are small in size, and have a very large pale, pallor colour due to the lack of haemoglobin present. Each cell cannot carry very much oxygen around the body.


The reagents used to test for B12 or Folate in the blood.


Iron and Ferritin reagents.

The biochemistry analyser line to process B12/Fol/Iron/Fer (as well as lots of other tests). Our lab has 3 of these lines for up to 10,000 tests a day.

Our Sysmex XN Line is used to process full blood count results.

The entire process is automatic, capable of running 600 samples an hour.

RBC’s (red blood cells) are plotted on this bell curve based on size, and number. The process for counting RBC’s involves sending the cell through a tiny aperture just one cell at a time, every time a cell passes though it generates electricity which counts the red cells.