If you’re dealing with iron deficiency or struggling to raise your iron levels…Did you know your body has a secret iron bodyguard and all the old high dose iron supplements you’re taking actually cause that bodyguard to block iron absorption!?
What is this secret bodyguard? It’s called Hepcidin.
Hepdicin plays a super important role in regulating whether or not you can absorb the iron in your diet or from supplements…yet most doctors prescribe iron doses iron like they’ve never heard of it! (Click here to learn about the iron supplement I use & recommend.)
Today I’m gonna pull back the curtain and shed some light on this newly discovered piece of the iron absorption puzzle.
We’ll talk about why hepcidin is important, what triggers your body to release hepcidin, and how the old guidelines for iron supplementation actually work against you by activating your body’s hepcidin response!
But don’t worry, stick around to the end and we’ll talk about what you can do to reduce hepcidin production and allow for iron absorption.
So, What is Hepcidin?
Hepcidin is a polypeptide (or amino acid hormone) created in the liver that has been identified as one of the most important factors that regulates iron absorption. Hepcidin was discovered, actually by accident, by a group of researchers around 2000…which means that in the world of science and medicine this is still a very new discovery, and it has transformed our understanding of iron absorption.
Hepcidin is designed to protect you; it allows iron in when you need it, and blocks absorption when you don’t.
But why would your body WANT to block iron absorption? Well, while iron is an essential mineral and we HAVE to have it for our bodies to function effectively…iron is actually toxic if we have too much or it’s left free floating in the blood!
So our bodies have brilliantly designed safety systems in place to protect us from too much iron.
Then, because iron is dangerous if allowed to run free in our bodies, we use iron ‘chaperones’ like hemoglobin, ferritin, transferrin, and ferroportin to safely transport and store iron through the body.
So how does hepcidin work?
When hepcidin is released, it’s job is to seek out iron trying to enter your system and block it from being absorbed. It does this by binding itself to ferroportin, which is the iron ‘chaperone’ responsible for guiding iron absorption through the intestinal cells.
When hepcidin has wrapped itself around ferroportin it blocks iron absorption, because without ferroportin to ‘open the door’ iron has no way to make it past the intestines and into the bloodstream.
what causes your body to activate the hepcidin response?
There are three things primarily that will cause your body to release hepcidin; they are inflammation, adequate iron levels, and iron supplementation.
First we’ll talk about adequate iron levels.
Your body works hard to keep iron at healthy levels. In an ideal situation, when your body has enough iron in circulation and in storage, it will send the signal to release hepcidin.
It’s kinda like saying “Hey we’re good, the party is full…go ahead and shut the door. We don’t need anymore iron!” So hepcidin heads to the door and stops ferroportin from allowing in any more iron….because remember, too much iron is not a good thing!
On the other hand, when iron levels are low, as in anemia or iron deficiency, and the body is actively looking for and needing iron, it tries to keep hepcidin levels low to allow more iron to pass through the intestinal wall and enter the bloodstream.
The second reason your body will release hepcidin is when it detects inflammation.
Your body’s goal is to protect you and keep you healthy, and it knows that just like we need iron to survive…infections and pathogens that make us sick also require iron for their survival and growth.
Once hepcidin is standing guard at the door, your body then locks circulating iron safely away into storage, so it’s not available to be used by whatever threat or invading pathogen is causing the inflammatory response.
The challenge is, with chronic inflammatory conditions like irritable bowel syndrome, celiac, Crohn’s, and rheumatoid arthritis…the inflammation caused by these conditions keeps hepcidin levels elevated and blocks iron absorption. This ongoing pattern very often leads to low iron levels and iron deficiency over time. (Click here to see other common risk factors for low iron)
Which leads me to the next big thing we need to talk about…
The third factor that triggers hepcidin production is iron supplementation.
Once you’ve been diagnosed with low iron levels, the next logical step is to begin taking iron supplements to restore your iron to healthy levels.
In an attempt to quickly get more iron into their patients, many doctors prescribe high dose iron supplements, and often recommend taking those doses throughout the day.
The problem is, traditional non-heme iron supplements have a very low absorption rate and all of the unabsorbed iron is left bumping around in your gut, like an angry party guest, causing all the side effects you feel like cramps, nausea, and constipation…but more importantly they are causing oxidation and inflammation in the intestines.
The inflammation caused by every dose of those non-heme supplements makes your body go into protection mode and triggers hepcidin production, and hepcidin blocks iron absorption. This obviously just turns into a vicious cycle…the more iron you take, the more inflammation it causes, and the more you block your ability to absorb iron!
Studies have shown that supplemental doses of iron, over 60 mg per serving, trigger hepcidin production, and that each subsequent dose further increases hepcidin levels.
Once the iron supplement triggers hepcidin, it takes approximately 48 hours for hepcidin levels to return back to the baseline level.
This means that, if you take a large dose of iron three times per day, you have likely increased your hepcidin levels each time, and thereby significantly decreased your ability to absorb the iron.
So basically, you’ll wind up enduring all the miserable side effects, not be able to absorb the iron, and continually struggle with low iron levels.
if increased hepcidin blocks iron absorption, is there anything we can do to decrease hepcidin production?
Fortunately, there are a few factors that help keep hepcidin levels lower, to encourage iron absorption.
The first step in minimizing hepcidin is reducing inflammation.
I realize this is certainly easier said than done for those struggling with chronic inflammatory conditions, but there are a couple things you can proactively do to minimize inflammation. (These are for both those with chronic inflammation or anyone looking to improve their ability to absorb iron.)
Take a collagen supplement. There is a ton of science behind the benefits of taking collagen, but as it relates to iron absorption, Collagen Peptides have a powerful amino acid profile that work to heal the lining of the intestinal wall, which is what we often hear referred to as ‘leaky gut’, and Collagen helps to improve nutrient absorption, and reduce inflammation.
Then choose an iron supplement that has better bioavailability and is easier on the gut, so that it doesn’t cause the intestinal inflammation that will trigger the release of hepcidin. Heme iron supplements are easier on the stomach, because they are naturally more bioavailable than non-heme supplements.
The second factor in decreasing hepcidin production is timing.
Without the supplement induced inflammation, studies show us that Hepcidin is naturally lowest earlier in the day and peaks in the evening to fall and repeat the cycle again the next day.
So taking your bioavailble iron supplement earlier in the day can harness hepcidin’s natural rhythm.
However, If you have to take high dose non-heme supplements, there is a study that suggests that taking a single large dose every other day will allow time for the rise and fall of inflammation and hepcidin they cause before taking the next dose.
The feedback about the effectiveness of that strategy is mixed…but it may be worth talking to your doctor about if you must take those high doses.
The final factor that has been shown to reduce hepcidin levels is optimal Vitamin D.
We’ve known for a while that optimal vitamin D levels reduce inflammation, but now scientists are finding that there is a strong link between vitamin D and hepcidin.
Vitamin D is an extremely common nutrient deficiency and it often accompanies low iron. Studies have revealed that daily vitamin D supplementation reduces circulating hepcidin levels by 34% for 24 hours!
As you can see, understanding hepcidin’s role in iron absorption is key to effectively using supplementation to improve iron levels.
Products I created to Support Healthy iron Levels:
Suppression of Iron-Regulatory Hepcidin by Vitamin D Justine Bacchetta, Joshua J. Zaritsky, Jessica L. Sea, Rene F. Chun, Thomas S. Lisse, Kathryn Zavala, Anjali Nayak, Katherine Wesseling-Perry, Mark Westerman, Bruce W. Hollis, Isidro B. Salusky, Martin Hewison JASN Mar 2014, 25 (3) 564-572
Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Diego Moretti, Jeroen S. Goede, Christophe Zeder, Markus Jiskra, Vaiya Chatzinakou, Harold Tjalsma, Alida Melse-Boonstra, Gary Brittenham, Dorine W. Swinkels, Michael B. Zimmermann;Blood 2015; 126 (17): 1981–1989. doi
Protein Hydrolysates as Promoters of Non-Haem Iron Absorption. Li Y, Jiang H, Huang G. Nutrients. 2017;9(6):609. Published 2017 Jun 15. doi:10.3390/nu9060609
Utilization of iron from an animal-based iron source is greater than that of ferrous sulfate in pregnant and nonpregnant women. Young MF, Griffin I, Pressman E, et al.J Nutr. 2010;140(12):2162‐2166. doi:10.3945/jn.110.127209
The role of vitamin D in regulating the iron-hepcidin-ferroportin axis in monocytes Susu M.ZughaieradJessica A.AlvarezbJohn H.SloancRobert J.KonradcVinTangprichabd13 December 2013
IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin Elizabeta Nemeth,1 Seth Rivera,1 Victoria Gabayan,1 Charlotte Keller,2 Sarah Taudorf,2 Bente K. Pedersen,2 and Tomas Ganz1 First published May 1, 200
Disclaimer: This content is strictly the opinion of Krystal Moore or Three Arrows Nutra, LLC and is for informational and educational purposes only. It is not intended to provide medical advice or to take the place of medical advice or treatment from a personal physician. All viewers of this content are advised to consult their doctors or qualified health professionals regarding specific health questions. Neither Krystal Moore, Three Arrows Nutra, LLC nor the publisher of this content takes responsibility for possible health consequences of any person or persons reading or following the information in this educational content. All viewers of this content, especially those taking prescription or over-the-counter medications, should consult their physicians before beginning any nutrition, supplement or lifestyle program.