More than 1 billion people worldwide are suffering from iron deficiency. And despite supplementing, so many people are finding their iron status doesn’t shift, or only moves very slowly over months and months.
The answer: hepcidin.
Hepcidin, is the master regulator of systemic iron. It is a protein made by your liver, that makes sure you don’t overdose on iron which would be very toxic. Humans and other mammals lack effective mechanisms to excrete excess iron, and therefore the sole means of maintaining iron balance is by regulating intestinal iron absorption to match systemic iron requirements.
How does hepcidin regulate iron levels?
High hepcidin levels block intestinal iron absorption. Dietary iron is absorbed predominantly in the duodenum (gut). Hepcidin reduces the iron entry to our blood from the absorptive duodenal cells. Absorption increases in response to increased iron requirements like iron deficiency or anaemia.
So if you are iron-deficient, or anaemic, hepcidin levels will naturally go lower so you get more iron from your diet/supplements, in comparison to someone's hepcidin levels if they had very high iron levels.
Hepcidin also increases when in an inflammatory state, or infection state.
Hepcidin synthesis is greatly increased during inflammation, autoimmune diseases, chronic infections, which means in these states a person will struggle to get the adequate amount of iron from their diet or supplements, and majority will be iron-deficient or anaemic. In these cases, we need to treat the inflammation levels to lower the hepcidin. Not just give them more and more iron, because this would worsen their hepcidin levels.
Interestingly, improvement in vitamin D status in patients with chronic kidney disease may reduce systemic hepcidin levels.
Research shows that higher dose iron supplements at doses of 60 mg Fe or higher increase hepcidin for up to 24-48 hours and are associated with lower iron absorption on the following day. A study completed showed an oral dose of 65 mg of iron in healthy volunteers caused a 5-fold increase in hepcidin within 1 day!!
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
