The Global Iron Deficiency Crisis
More than 1 billion people worldwide suffer from iron deficiency. Despite supplementing, many struggle to improve their iron status, with levels shifting very slowly over months and months.
The answer? Hepcidin.
What is Hepcidin?
Hepcidin is the master regulator of systemic iron. It is a protein produced by the liver that ensures the body doesn’t absorb excessive iron, which can be toxic. Unlike other nutrients, humans and mammals lack effective mechanisms to excrete excess iron, making intestinal iron absorption regulation the primary way of maintaining iron balance.
How Does Hepcidin Regulate Iron Levels?
High hepcidin levels block intestinal iron absorption. Dietary iron is absorbed mainly in the duodenum (gut), and hepcidin reduces iron entry into the bloodstream from absorptive duodenal cells. Iron absorption increases when there is a higher systemic iron requirement, such as in iron deficiency or anemia.
So if you are iron-deficient or anemic, your hepcidin levels naturally decrease to allow more iron absorption from diet and supplements, compared to someone with high iron levels, where hepcidin remains elevated.
The Impact of Inflammation on Hepcidin
Hepcidin also increases during inflammation or infection.
When Hepcidin is Elevated:
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Chronic inflammation
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Autoimmune diseases
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Chronic infections
In these states, a person will struggle to absorb adequate iron from their diet or supplements, making them more likely to become iron-deficient or anemic. Simply increasing iron intake won’t help—we need to treat inflammation to lower hepcidin levels. Excess iron intake can actually worsen hepcidin levels.
Interestingly, improving vitamin D status in patients with chronic kidney disease may reduce systemic hepcidin levels.
The Effect of Iron Supplements on Hepcidin
Research shows that high-dose iron supplements (60 mg Fe or higher) increase hepcidin for up to 24-48 hours, leading to lower iron absorption the following day.
A study found that an oral dose of 65 mg iron in healthy volunteers caused a 5-fold increase in hepcidin within 1 day!
This means that excessive iron supplementation may hinder absorption, and adjusting dosage based on hepcidin regulation could be crucial for effective iron therapy.
This shows, that with increasing dose of iron, fractional absorption decreased.
The duration of the hepcidin response supports alternate day supplementation, because if you took an iron supplement Monday morning at 9am. Your hepcidin levels will remain high anywhere to Tuesday 9am to Wednesday 9am. So if we skip every second day, we are allowing our hepcidin to naturally go back down, so we maximise absorption from our supplement.
References:
https://www.frontiersin.org/articles/10.3389/fphys.2019.01294/full
