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Iron, B12 and vitamin D: the deficiencies behind most fatigue

Headshot of Dr. Nikola Topalovic, MD PhD
Medically reviewed by Dr. Nikola Topalovic, MD PhD · Last reviewed 4 September 2026

Before you investigate anything exotic about fatigue, rule out the three deficiencies that account for a large share of it — and measure them properly, because each has a well-known testing trap.

What people notice

  • Fatigue and breathlessness on stairs or in training
  • Restless legs at night
  • Pins and needles or numbness in hands and feet
  • Low mood and difficulty concentrating
  • Frequent illness through winter

Symptoms overlap between causes. This list is a prompt to measure, not a diagnosis.

Markers worth measuring

Ferritin
The best single measure of iron stores — but it rises with inflammation, so it must be read against CRP.
Transferrin saturation and iron studies
Distinguishes genuine deficiency from inflammatory sequestration when ferritin is equivocal.
Full blood count
Shows whether deficiency has progressed to anaemia, and the red cell indices point to the type.
Vitamin B12 and active B12
Total B12 includes an inactive fraction; active B12 (holotranscobalamin) is the more sensitive early marker.
Folate
Interpreted with B12 — treating one while the other is deficient can mask the problem.
Vitamin D (25-OH)
The storage form and the correct test. Deficiency is very common at higher latitudes and in indoor workers.
CRP
The context marker for ferritin, and an independent signal worth having.

The ferritin trap. Ferritin is an acute-phase reactant: infection, injury, obesity, heavy training and any inflammatory condition push it up. A man with genuine iron deficiency and ongoing inflammation can present with a 'normal' ferritin. Reading it alongside CRP and transferrin saturation is what separates a real store from an inflamed one. Endurance athletes and regular blood donors are the two groups most often caught out.

The B12 trap. Standard total B12 measures both active and inactive fractions, so a result can sit in range while the usable fraction is low. Active B12 is the more sensitive marker, and it matters because untreated B12 deficiency causes neurological damage that does not fully reverse. Vegans, vegetarians, long-term metformin users and people on acid-suppressing medication are the higher-risk groups.

The vitamin D trap. The right test is 25-hydroxyvitamin D. Levels are seasonal — a July result in southern Australia or New Zealand can be dramatically lower than the same person in January — so a single number should be read against when it was taken. Deficiency mimics hypothyroidism and depression closely enough that it is worth excluding first.

What these have in common. All three are cheap to measure, common to find, and correctable — which is why they belong on the first panel rather than the third. Any correction, and any investigation of why a deficiency exists, should involve your own doctor; unexplained iron deficiency in an adult man in particular always warrants a clinical look at the cause.

FAQs

What ferritin level counts as low?
Laboratory ranges vary, and the threshold for symptoms is higher than the threshold for anaemia. Ferritin must also be read against CRP, because inflammation raises it independently of iron stores.
Should I take iron before testing?
No. Supplementing before the test distorts the result. Test first, then decide with your doctor.
Is active B12 worth paying for?
It is the more sensitive early marker, particularly if total B12 sits in the lower half of the range while symptoms persist.
When should vitamin D be measured?
Any time, but note the season. Late winter gives the realistic low point; late summer gives the best case.

Measure it properly, in one morning draw.

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