This question comes up all the time. Patients or practitioners are baffled when their serum iron levels come back elevated and their ferritin levels come back low even though they have all of the symptoms of iron depletion.

What’s going on?

Often doctors or even patients who see this think ‘oh no we better stop taking iron support’ or ‘iron isn’t the issue’ because they see the high serum iron. The medical community is so afraid of high iron and its potential for creating oxidative damage that any marker related to iron coming back high immediately shuts down iron replenishment.

However, usually, this is a misunderstanding of what serum iron is testing and what elevated levels mean versus what low ferritin levels mean.

What is serum iron actually measuring?

Serum iron measures the total amount of iron in the liquid portion of the blood, the vast majority of which is bound to transferrin.

That brings us to ‘what is transferrin’?

Transferrin is a protein responsible for transporting iron to the spleen, liver, and bone marrow. Transferrin levels rise with iron deficiency. As iron is depleted or the need for iron increases, the liver responds by creating more transport vehicles (transferrin). Hence, serum iron is elevated in the case of anemia or low iron stores (aka low ferritin).

Out of the gate, it is paramount that we test the same way consistently in order to get consistent results.

How to test for iron

Optimally you want to complete the blood draw in the morning in a fasted state. Patients should also not take any iron supplement within 24 hours of a blood draw.

This is especially crucial for iron deficiency anemia patients as they will likely be on iron supplements or prenatal supplements and will show up with normal or high serum iron.

If using iron dextran injection, high serum iron levels can be elevated for several weeks.

In a non-fasting state, you can get significant swings in transferrin levels, especially in iron-deficient patients depending on what kind of food has been consumed.

Serum iron concentration is a poor measure of iron status in the body as levels fluctuate significantly due to diurnal variation, iron supplements, and fasting status.

Diurnal variation is often over looked but can make life very confusing if not explained to patients or if blood is drawn at different times during the day. Consistent values are found in the mid-morning, low values are found in mid-afternoon, and even lower values are found near midnight. Diurnal variation disappears at values below 45 µg/dL.

Even when both morning and fasting blood draws are completed, accuracy is still hampered by the fact that iron is an acute phase reactant and could be falsely low in the case of acute inflammation.

Specific tests to order: CBC, Ferritin, TIBC, Iron (Transferrin) Saturation and Serum Iron levels checked at the same time.

Understanding your iron test

If you have consistently high serum iron levels and low ferritin without iron supplementation, you may want to check for underlying infections, oral contraceptive use, B6 deficiency, thyroid disorders and consider testing based on history for heavy metals (especially lead).

The use of cast iron skillets can be another reason for elevated levels of serum iron, especially if used in the hours before a blood draw.  Serum iron will often be at the top end of normal or even over while ferritin is slower to reach normal levels with initial supplementation.

As iron deficiency is improved ferritin will rise and serum iron will normalize.

When ferritin levels drop below 25, the liver will often compensate by synthesizing more transferrin which leads to a pooling of iron in the blood and increased serum iron levels in the face of iron deficiency. This occurs when there’s an iron deficiency or in patients with high estrogen levels such as in pregnancy or with oral contraceptive use.

The bottom line of serum iron levels

Remember, serum iron testing cannot reliably determine iron deficiency or identify hemochromatosis or other iron overload states. That’s why it’s imperative to check Ferritin, TIBC, and transferrin saturation percentage levels.

We often forget that oral contraceptives increase the serum iron level. Iron dextran elevates serum iron levels for several weeks. Ingestion of even small amounts (i.e. multivitamin, cast iron skillet) of iron may transiently increase serum iron levels.

Ferritin levels of less than 75 mcg/L can result in fatigue and an increased risk of miscarriage. This is why it is paramount we test patients and ensure they have optimal iron levels and not just a ferritin within the ‘normal’ range’.

Have you had low ferritin levels and tried supplementing with iron? I’d love to hear about your experience in the comments below.