Ferritin vs iron: what is the difference?

Each ferritin molecule is a hollow protein shell that can store up to about 4,500 iron atoms [4]. Most of it sits inside cells in the liver, marrow and immune cells; the small amount in blood tracks the size of those stores when there is no inflammation [5].

Iron in the blood travels on a different protein, transferrin, on its way to the bone marrow and other tissues. Its level reflects what was absorbed or released recently, and hepcidin can lower it quickly during inflammation [3].

Across 55 studies, ferritin outperformed every other blood test for diagnosing iron deficiency anemia [1]. A ferritin cutoff of 30 µg/L found 92% of iron-deficient anemic patients with 98% specificity [6].

Serum iron alone is a poor test because it changes through the day and with food. Its main use is to calculate transferrin saturation, which matters most in two situations:

• Inflammation. ASH treats transferrin saturation below 20% as supporting iron deficiency when ferritin is below 100 ng/mL in inflamed patients [7].
• High ferritin. Saturation above 45% in women or 50% in men points to overload rather than inflammation [2] [8].

• Low ferritin, normal serum iron. Stores are low even if the moment-to-moment level looks fine. Low ferritin is highly specific for iron deficiency [2].
• Normal ferritin, low iron or low saturation. Common when inflammation inflates ferritin; iron deficiency may still be present [7]. Check CRP.
• High ferritin, low iron. Inflammation raises hepcidin, which holds iron in storage and lowers serum iron [3].
• High ferritin, normal saturation. Points to reactive causes such as metabolic syndrome, fatty liver or alcohol [2].
• High ferritin, high saturation. Raises the question of hemochromatosis or another overload [8].

Liver disease can make transferrin saturation look high without overload, because the liver makes less transferrin [2]. These patterns guide a clinician; they are not a self-diagnosis.

Most of the body's iron sits in hemoglobin [9]. When iron runs short, the body uses its ferritin stores first, so ferritin drops while hemoglobin stays normal. Only when stores are exhausted does hemoglobin production suffer, which is why iron deficiency without anemia is common [3].

Physiology studies mark this turning point: hemoglobin begins to fall when ferritin drops to about 25 µg/L in women [10] [11]. A normal hemoglobin therefore does not rule out low iron stores.

The reverse also happens: hemoglobin can be low with normal ferritin when anemia has another cause, such as low vitamin B12 or folate, kidney disease or inflammation. Related markers such as homocysteine can help a clinician look at the B vitamin side.

Transferrin saturation is a calculated value reflecting the proportion of iron-binding sites on transferrin that are occupied [2]. TIBC estimates how much transferrin is available.

In iron deficiency, the body makes more transferrin, so TIBC rises while saturation falls. In inflammation, saturation falls but TIBC does not rise. In overload, saturation climbs above 45% to 50% [2]. Reading ferritin and transferrin saturation together resolves most ambiguous results.

One caution: transferrin saturation depends on serum iron, so it shares the same swings with meals and time of day. A single high saturation is usually repeated, ideally on a morning sample, before anyone talks about overload. In hemochromatosis, EASL bases the diagnosis on both a raised saturation and a raised ferritin, plus genetic testing [8].