If you are looking for info on Hepcidin, you’ve come to the right place. Here at Anemia Central, we seek to educate people about anemia and all of the problems and challenges of the diagnosis and treatment of this hidden damaging health condition. If you are interested in Iron Deficiency Anemia or Hemachromatosis, then you absolutely must become educated about the major substance in the body that is responsible for limiting or allowing the absorption of iron in the body.

In fact, after reading this page, you’ll know more than most doctors about iron absorption, and you’ll see why most doctors dose iron so that it will be difficult, if not impossible for you to absorb.

This molecule, responsible for the body’s major feedback loop of Iron Absorption, and that, incidentally is an antimicrobial good at fighting bacteria and fungi, is known as hepcidin. Understanding how this substance works is vital in understanding more about taking Iron Pills, getting the right Dosage of Iron, taking iron at the proper times- and why taking iron often does not work to bring up Blood Iron Levels.

Hepcidin, a small circulating cysteine-rich peptide,
exhibits a broad range of antimicrobial and antifungal activities”
C/EBP Regulates Hepatic Transcription of Hepcidin

It’s a complex feedback system that most doctors have not been educated about, and their patients are suffering, not absorbing the iron they are being prescribed, and ending up frightened and given a referral to a hematologist unnecessarily because of lack of knowledge about the body’s intricate feedback mechanism that protects us from getting too much iron.

Unfortunately, blood tests are not widely used, as of yet, and are mainly used for research only. So, you’ll not be able to get a hepcidin blood test in order to prove to your doctor that his method of dosing is incorrect, you’ll just have to go on the currently available research.

The Feedback Loop of Hepcidin

Hepcidin is the CEO of one of the most important iron feedback loop in the body. It is a molecule produced by the liver, where most of the body’s excess iron is stored, and directs iron traffic for storage or for elimination, depending upon what the body needs. When hepcidin is low, more iron can be absorbed; when levels are high, it signals that the body already has enough iron and that absorption should be slowed or stopped.

When this feedback loop works well, it’s fantastic, and put iron in the ‘Goldilocks’ situation in your body- not too much and not too little. When it isn’t working well, it can lead to serious Iron Deficiency Anemia or to iron excess, a condition known as Hemachromatosis, both of which are seriousproblems.

How the Feedback Loop Works

When the hepcidin feedback loop is working properly, levels are low when you need iron, and levels are high when you don’t. So, for instance, a menstruating woman should have lower levels than the average adult male. That’s so that they can absorb more iron and offset the losses they incur from menstruation.

In a certain genetic condition, known as Hemachromatosis, and in certain disease states, hepcidin remains low and allows the continued high absorption of iron even when iron levels are high. This leads to high iron levels and the subsequent health problems that result.

On the other hand, there are certain circumstances where hepcidin might be high even when iron levels are low, causing less iron to be absorbed even when more is needed. In some of these cases, hepcidin is even the target of drug therapies that might be able to reduce these abnormally high hepcidin levels. Some of these circumstances where hepcidin remains high despite high iron levels are:

Notice that the last circumstance on the list that causes hepcidin levels to rise and to allow the body to absorb less iron is taking iron pills! Unfortunately for those who are iron deficient, taking iron pills actually leads to a rise in hepcidin and a decrease in the amount of iron absorbed. Even with one iron pill, hepcidin begins to increase. But keep reading, because it gets even worse.

Hepcidin and its Daily Variations

Not only does hepcidin rise with each dose of iron taken, but it also has its own daily cycle where it is at its lowest first thing in the morning and rises throughout the day, hitting its peak around 8 pm and gradually decreasing throughout the night where the cycle repeats. So your dinner of red meat and spinach your doctor suggested in order to raise your iron levels is virtually wasted because hepcidin levels are at their peak, not to mention the fact that Spinach is a Poor Source of Iron.

Hepcidin, a peptide hormone produced by the liver, constitutes
the master regulator of iron homeostasis in mammals
allowing iron adaptation according to the body iron needs.”
Hepcidin, the iron watcher

There are many problems with this that doctors and their patients simply do not realize. Iron is not like other nutrients, such as magnesium, where if someone is low in that nutrient, they can simply take more. With iron, many people find that simply taking more iron just does not work, and they keep taking iron without getting higher levels. The hepcidin cycle, and the ignorance of their doctors about the cycle is why this occurs.

Doctors’ Ignorance Revealed in Iron Dosing

Many doctors, in an effort to get more iron into their patients, and to avoid the Iron Side Effects that are inherent with this nutrient, will do one of a few things: they often have their patients take Iron Pills in the evening with dinner, or they have them take iron 3 times a day with meals. These strategies ignore The Many Foods that Prevent Iron Absorption, and that hepcidin levels both rise throughout the day and rise upon taking each iron pill.

So, if you are taking your iron with dinner, not only are the nutrients in the foods you are eating, particularly healthy foods with antioxidants, preventing the absorption of iron, but you are taking iron at the time of day you are least likely to absorb it.

Taking iron 3 times a day is far worse strategy than taking it at dinner. Each time iron is taken, it raises hepcidin levels in addition to its daily normal variations. And with each iron pill, hepcidin levels don’t come down for 24 hours, causing an ever increasing rise in hepcidin each time iron is taken.

Hepcidin Levels

From the study Circulating Human Hepcidin-25 Concentrations Display a Diurnal Rhythm

Therefore in a normal situation, hepcidin would be low in the morning and at its peak in the evening. When you take iron 3 times a day, you are raising hepcidin even higher WITH EACH DOSE 6. By dinnertime, hepcidin is higher than it would be normally.

By breakfast the NEXT day, hepcidin from breakfast, lunch and dinner the day before will have accumulated to make levels higher than at the previous day’s breakfast. When you’ve taken iron for three days in a row, 3 times a day, the third day’s morning and evening hepcidin levels will be higher than the 2 day’s levels. The 4th day’s levels will be higher than the 3rd day’s, and on and on.

You simply cannot absorb iron by taking it three times a day. If your doctor recommends taking iron 3 times a day, run! That doctor is probably not someone who is well-versed in how to help you overcome iron deficiency. Better strategies that have been employed effectively in studies are to dose iron once every other day or even once a week! These strategies allow for hepcidin to reduce to baseline before another dose is given, tricking the body into absorbing more iron than it would with three times a day, or even once a day dosing.

Factors that Decrease Hepcidin

Now that we know about things that increase hepcidin and decrease iron absorption, we can discuss factors that decrease hepcidin and increase iron absorption. Unfortunately, this list is pretty short, and there is not much you can actively do to decrease hepcidin to absorb iron better. However, a few of these factors and substances are:

  • Epogen- a hormone made famous by Lance Armstrong. It’s used frequently in cancer patients and those with serious kidney problems to help them produce more red blood cells.
  • High Altitude Living
  • Lack of Oxygen (which is why altitude works)
  • Carbon Monoxide Poisoning 7
  • Vitamin D. Even one supplementary dose can decrease hepcidin by up to 35%. See our page on Vitamin D and Iron. 8
  • Reducing inflammation in the body
  • Low iron levels

So, aside from putting leeches on your body, finding a doctor who will provide you with Epogen (not an easy task) or moving to the Andes, one of the few things you can actually do to reduce hepcidin levels is to have Optimal Vitamin D Levels and to reduce inflammation in the body, both to help reduce hepcidin and to prevent Increased Intestinal Permeability from impairing absorption of iron. Reading the pages on Vitamin D and Iron  and how Vitamin C Improves Iron Absorption  are imperative if you are interested in iron absorption or anemia.

OK, so now you know more about hepcidin than 99% of people on the planet, including your doctor. I hope that this benefits you and helps you to better resolve your anemia. Please use the share buttons on the page to share this on social media so that everyone with Iron Deficiency Anemia can benefit from this knowledge.