The Role of Iron Overload in Metabolic Disease | Chris Kresser
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Iron Behaving Badly: The Role of Iron Overload in Metabolic Disease

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Screen Shot 2013-07-14 at 9.46.00 PMAt the Ancestral Health Symposium last year, I presented a talk entitled “Iron Behaving Badly: The Role of Iron Overload in Metabolic Disease” about the pathophysiology of iron-related metabolic disease, and propose a clinical framework for diagnosing and treating it.

We’ve known for almost a hundred years that aggressive iron storage disorders like hereditary hemochromatosis (HH) are associated with increased morbidity and mortality. Yet recent research suggests that even mild iron accumulation (at ferritin levels still well within the laboratory reference range) can cause significant metabolic problems, including insulin deficiency, insulin resistance and hepatic dysfunction. Studies have shown that the frequency of diabetes is increased in HH, that elevated ferritin levels are associated with increased incidence of diabetes, and that reducing iron stores reverses or improves the metabolic abnormalities associated with excess iron.

The talk is now available on Vimeo, so I’ve posted it here so that my readers can access the talk easily. I hope you enjoy it, and I’d love to hear your thoughts and opinions on the topic in the comments below.

  1. I have the opposite problem from an overload. I am iron deficient (29 ug/dl instead of normal range of 50-170) and my ferritin is within normal range (54.4) and my saturation is only 11% instead of 20%-50%. My doctor prescribed iron supplements for me, but I have 2 problems with that: I have Crohn’s disease and when I take the supplement my colon swelled up and was cramping. It exasperated an already inflammatory condition. The other problem is that I wonder if I have “Anemia of Inflammation” because my C Reactive Protein and my SED rate are both high right now (I am in a flare up). I have Ankylosing Spondylitis also, by the way (another inflammatory condition). If it is true that my iron levels are off because of inflammation and my auto immune conditions, then I don’t know how to read these results and what treatment to accept. I read somewhere that it is dangerous to take iron supplements if you have Anemia of Inflammation with normal ferritin levels, because then you can get iron overload. In your video, however, you mentioned that ferritin can give a false “normal” on blood tests because inflammation can make it appear higher than it really is. So maybe I really do have low ferritin along with the obvious low serum iron. If that’s the case, then I suppose iron supplementation would be the course of action, except that my colon cannot tolerate it. My doctor suggested intravenous iron supplementation. I just am afraid to make an already horrible situation worse. I am sooooo dizzy, and also weak, with muscle cramps, restless legs, and insomnia. I have pain behind my eyes and feel like they are swollen. What should I do?

    • Magnesium should help your muscle crampa and restless legs. You should also check for low thyroid hormone (free T3, and Free T4. TSH is not a good indicator of thyroid status. High reverse T3 has the opposite effects of thyroxine and is probably inversely related to it.

      • Thank you. I already take Magnesium every day. It does help somewhat for the muscle cramps and restless legs. But it does not help with the dizziness and fatigue. And yes, I am Hypothyroid (diagnosed 20 years ago). I take Armor thyroid every day and have the levels tested every 3 months (free T3 and free T4). Everything is within normal range with the supplements.

        But this does not answer my question regarding what I should do for the low iron?

        • Hi Amy,

          I tried to post a longer answer with a few links but it wasn’t allowed. So I’m trying a shorter answer with no links and hope that will be allowed.

          Suggesting intravenous iron must mean that your doctor does think that you are low on iron. The American Society of Hematology has more information on IV iron. You might want to ask your doctor about possible causes for your iron being low, such as low-level bleeding from an inflamed intestine and/or not absorbing minerals in general very well? If mineral absorption is a problem, you might not be absorbing fat and fat-soluble vitamins very well either. A few things like vitamin D3 and magnesium can be absorbed through the skin, so you could ask your doctor about absorption vitamin D3 drops in oil for vitamin D, and magnesium chloride oil or lotion for magnesium.

          To increase iron absorption from food, it helps to eat iron-containing plant foods together with with vitamin C. Iron from iron-containing animal food tends to get absorbed well with or without vitamin C. Also avoid taking high-calcium food or tea or antacids with iron-containing foods because calcium, tea, and antacids can reduce iron absorption.

          Other possible thoughts on iron – people who have stomach infections with Helicobacter pylori don’t absorb iron (or B12) very well, so you might want to check with your doctor that you don’t have H. pylori infection.

          Another possible cause for not absorbing iron very well is celiac disease. I mention this because people who have celiac disease are both more likely to have Crohn’s and more likely to have thyroid disease. Also, a 2013 study on genes found a connection between gene mutations involved in ankylosing spondylitis, Crohn’s, ulcerative colitis, and celiac disease. So it might be worth talking with your doctor about getting tested for celiac disease, if you haven’t done that already? (You have to be eating gluten when you have testing done for celiac disease or the tests can turn out negative even when you do have celiac disease.)

          Even if the tests for celiac disease turn out to be negative, you might still want to ask your doctor about trying a gluten-free diet, because research has found that people whose tests for celiac disease are negative may react to foods like wheat, rye, or barley with gut symptoms and also with non-gut symptoms like fatigue and trouble thinking.

          I hope some of this might be helpful for you in talking with your doctor –

  2. For those with eye-health issues there is literature documenting the role of iron overload in causing Age-related Macular Degeneration (AMD), and other retinal degeneration illnesses.

    See at the following link:
    https://www.ncbi.nlm.nih.gov/pubmed/24160731

    During a recent eye exam, my ophthalmologist informed me I had a retinal hole in my right eye. That eye exam prompted me to revisit a my most recent annual blood lab results, now two years old.

    That two year old lab showed low ceruloplasmin and high free copper levels. My MD did not alert me of the fact and I was ignorant of its significance to overall health, much less to ocular health.
    I have now requested my MD to order a full iron lab panel to discover the status of my iron metabolism, as there are several studies linking iron overload to ocular illnesses.

    • Thanks, Edgar, for mentioning MD. I’ve been on the warpath of iron dysregulation/overload/toxicity…whatever you want to call it, but your comment reminds me of a friend who has this. I need to make sure he knows about iron overload. Most people are….I know I am. ?

  3. Can high iron serum levels increase your B12 levels? I have both high iron and B12 levels. I don’t take any iron supplements and I do take B12 but not in excess.

  4. I am a 55 year old female with high ferritin 530 – nil to haemachromatosis.
    In 3 months the ferritin went up 100.
    Doctor doesn’t seem to be as concerned as I think should???
    No to venesection – i am trying to get to bottom of it all – I have been having stevi tablets rather than sugar ? Is this the the las test source of problem?
    Naro

    • Did you have dna testing? Or been refered to a hemotologist those results are high, would recommend a test on transferrtin saturation may be something else going on. Or a carrier. If you have fatigue or joint pain….. get second opinion if you can. I have hemochromatosis and I go up about that much in 3 months and have venisections.

    • N Ross,

      How are you. Ferritin that high needs to come down, for sure.

      Not sure where you are located to know how possible blood donation is for you, but anything over 50 for ferritin is not healthy. ..Please check out the Iron Toxicity articles by Morley Robbins on http://www.magman.org.

  5. It is very depressing when people do not give credit, where credit is clearly due. Chris, you should have acknowledged Dr. Douglas Kell as the source for your presentation as used his work and attempt to pass it off as your own. Its a shame.

  6. I don’t know how I missed this two years ago. Fantastic resource! Thank you so much Chris. I am a C282Y carrier with high iron levels (a pre-menopausal woman with ferritin of 230, low UIBC, iron saturation of 58%, etc.) and have been trying to find more information on iron overload issues. One thing that got me back on track with this recently is that I eat extremely healthy paleo about 95% of the time, and yet my glucose metabolism is getting worse over time. I’ve become fairly certain that I’m experiencing some level of insulin resistance, but WHY? I eat well, exercise, etc. But recently I read that iron overload is strongly correlated with insulin resistance. I’m going to start taking all the steps suggested in this video. I purchased ip6 recently, but you say it doesn’t help reduce stored iron. Many ip6 users (based on online reports) claim it has helped enormously with ferritin levels. Shouldn’t lowering iron levels in the blood prompt stored iron to be released (which could then be removed as well)? I would love to see more articles on iron, and especially its relationship to insulin resistance, as it is such a ubiquitous and challenging health issue.

    http://www.ncbi.nlm.nih.gov/pubmed/10535879
    http://care.diabetesjournals.org/content/28/8/2061.full
    http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003547
    http://www.sciencedirect.com/science/article/pii/S0016508599704014

    • There is certainly debate about how exactly IP6 works. Some claim that IP6 works as a chelator, removing stored iron from the body. Others dispute this, saying that it only acts as an iron inhibitor, in other words, only by preventing your body from absorbing more iron. Whatever the exact mechanism, it does seem to lower body iron stores over time. I personally used it a supplement on an empty stomach while also undergoing phlebotmies, and ferritin dropped a lot quicker than I expected. The only other thing to be concerned about with IP6 is that it can have a similar effect on other minerals (like magnesium and calcium).

      • Thanks for commenting! I have HH and struggling with low blood sugar and mineral deficiencies (magnesium, zinc so far …but having my levels checked soon for chromium, calcium and any others that iron competes with). I was on a high protein low carb (basically paleo diet) prior to this discovery and considering taking some Registered Dieticians’ advice to limit my meat/heme iron and go semi vegetarian.

        I’ve been taking mag supplements and my iron is much lower despite my current meat consumption. But the hypoglycemia is concerning as it can be a precursor to full on diabetes.

  7. I wrote to Dr. Keith Roach and his reply to me was, “Well, based on the genetic test, you have two abnormal copies of the gene, but because you don’t have iron overload (the ferritin is the best test), you are unlikely to develop any problems. The abnormal gene mutation you have 2 copies of confers a lower risk that the C282Y mutation. Only about 1% of women with your genes will have iron overload (versus 50% of women (and 85% of men) with 2 copies of C282Y). Donating blood periodically is a good idea, since your iron levels are slightly high, so you will help yourself and others by donating.”

    • New information all the time as more is discovered and made known:

      http://haemochromatosis.org.uk/conference-2017/

      “Professor Brissot clarified that both tests are very important indeed, and that the measure of transferrin saturation is, in his view, probably even more important that the measure of serum ferritin. He explained that ferritin is the iron STORAGE protein in the body, and transferrin is the iron TRANSPORT protein – which he illustrated by using the analogy of a loaded ship moving materials from place to place. His premise was that once the transport system for iron was overloaded, excess “unbound” iron was the result, leading to toxicity and overload.

      It became clear therefore that transferrin saturation is a crucial test in the diagnosis of GH – even more so than serum ferritin which can be elevated by other factors such as metabolic syndrome, alcohol consumption, and infections/inflammations.”

      “…anyone loading iron should be regarded as haemochromatotic, irrespective of the exact genetic mutation or combination of mutations involved.”

  8. I am 43/f have an abnormal iron panel (low TIBC/UIBC; high iron serum/saturation; normal but high end of reference range for ferritin). Also have C282Y and H63D mutations for HH. Have extreme fatigue/foggy thinking at times but otherwise very healthy & active. All reading suggests donating blood helps and that avoiding vitamin c is essential. However, one DO recommended vitamin C flushes and taking 3/4 of flush dose daily and flushes weekly instead of phlebotomy. Something about converting fe3+ to fe2+ which can be used and/or eliminated. Any thoughts. Is it safe or not to use vitamin C with HH? Any more articles about HH and treatment? I don’t want to wait until my labs are even worse to take action. Thanks!

  9. great presentation!
    I’m 52 – when I was 17 they told me my iron was high.
    Consistently the blood test showed over the years iron above the reference range. Through the years had unexplained liver enzyme tests above the normal range. In my forties I learned my mom’s brother and sister had HH. That prompted the genetic test and confirmed I had 1 copy of C282Y. I started donating blood and the liver enzymes fell back within range. Unfortunately 5 years ago a false positive in the donation screening prevented me from donating at this blood bank so if I was to remove the iron I would need an order from my doctor. Unfortunately the doctor will not order the therapeutic blood draw since is is not much higher than the reference range. As I get older I am noticing other issues and I suspect the prolong iron accumulation. I’m surprised my dr will advise a baby aspirin or Vitim D tablet in the interest of general good health but wont takes measures to keep iron optimum.
    Can you direct me to where you uploaded the research references? Its great info.

    • I am in a similar situation, Jack. I have the rarest blood type, AB negative, and the blood bank won’t take my blood because they never need it. The woman at the Red Cross told me that my blood would just take up space in the refrigerator and then have to be thrown out.

      Some of us have all the luck!

  10. Chris,

    Did you know that the obesity epidemic can be traced directly to iron fortification?

    Here are the countries that fortify foods. Note the countries that fortify with iron.

    Now cross reference that list with countries that consume the most meat per capita.

    The countries that consume the most iron, through food fortification and meat consumption, are the ones that have the most obesity and morbidity. It lines up perfectly.

    Due to significant fortification increases, and increased meat consumption as the country became wealthier, iron per capita content in the US food supply has nearly than doubled since WWII (see dramatic chart in that link). The FDA started at 8-12.5mg per pound of flour in 1943. 10 years later the first images of a new obesity epidemic was published in LIFE magazine.

    The FDA raised iron fortification to 12.5-16mg per pound of flour after the War. In the 1970s they tried to raise it to 40mg per pound of flour but rescinded after outcry from scientists. Finally, in 1983, they raised it to 20mg of iron per pound of flour. 10 years later, we had the latest obesity epidemic, which is finally leveling off.

    I don’t think people realize that 50% of iron in the SAD diet comes from grains now.

    In France, the French eat twice as much wheat as we do (largely as baguettes and pastries) but they have 1/3 the obesity we do. The French do not fortify their flour with iron. Furthermore, the French consume lots of non-heme iron inhibitors (tannins, coffee, tea, dairy, legumes).

    Iron fortification also explains the Pima Indians. They were lean and thin eating lots of beans, maize and squash (three sisters carbs), but got fat and diabetic on iron-fortified carbs from the government. Their obesity appeared 10 years after the government started giving them iron-fortified flour.

    The island of Nauru is considered the fattest place on the face of the Earth. They also have among the highest meat consumption per capita. They also import much of their food from Western main trading partners Australia, USA and the UK. The USA and UK fortify their foods with iron. This is a double-whammy.

    Nearly every obesity epidemic can be explained by iron fortification and increased meat consumption!

    A few months ago, a study came out linking niacin fortification in foods to obesity. However, B-vitamins are generally non-toxic and very easily excreted. Niacin is almost always fortified alongside iron. The researchers likely blamed the wrong culprit. Note in the niacin study the charts showing a 10-year lag from food fortification increases to obesity epidemics and a 26-year lag to diabetes. The data is all there linking iron overload from fortification (or lack thereof) to all these dietary paradoxes and obesity epidemics of the world.

    For instance, it explains the Northern Ireland Paradox—a population with a great deal of coronary heart disease, but which doesn’t have high rates of the expected ‘risk factors’. Belfast has a coronary artery disease death rate that is more than 4 times higher than in Toulouse, France, despite almost identical coronary ‘risk factors’ [1][2]. Nobody knows why. It’s a mystery… But guess what? Unlike the rest of Ireland, Northern Ireland fortifies flour with Iron and France does not.

    Incidentally, iron fortification is also considered to be obsolete and ineffective for modern countries in modern societies.

    And finally, iron fortification has been found to disrupt the gut flora…

    Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants (2014)

    The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Côte d’Ivoire (2010)

    This would explain why gluten free diets seem to be popular in fortified countries, but not in unfortified countries. (Gluten free is almost impossible to find in France). Gut flora are responsible for metabolizing and detoxifying gluten.

    Ladies and gentlemen, we appear to have a major culprit in the obesity epidemic—iron overload from fortification combined with increased meat consumption.

    • Hello- you’re the 1st person who has also made this connection about the timing of iron fortification to flour and the multiple of autoimmune disorders and obesity rising at the same time. I’ve been avoiding flour products and eating very little meat, especially red meat for about 7 years. I also donate blood. My mother passed away from complications due to Myelodysplasia Syndrome (MDS) which is a blood/ bone marrow cancer. I feel that all my lifestyle changes will help prevent/ delay a possible onset of this sad decline in quality of life. My mother originally had the autoimmune disorder diabetes 2 and I have been fighting hypothyroidism. I consider these 2 disorders “canaries in the coal mine”. A forewarning to change my lifestyle before larger disorders develop. I’m glad to hear France doesn’t fortify it’s flour. Somebody is aware! Also, another gene that predisposes one to iron disorders that is not well known is DMT1 (divalent metal transporter 1). It is more prevalent in Polish people and other Eastern European populations. The “divalent metal” that is transported includes “ferrous divalent iron compound (+2 oxidation state)” which is the “ferrous sulfate” that is fortified or “enriched” in flour, flour products and “enriched rice” also. Many, many Northern Europeans are predisposed as mentioned on this web page to hemachromatosis and fortification of flour and rice have been exacerbating the problem and autoimmune disorders for our generation for the last 60 years. Coincidentally iron is being attributed to the recent curiously multiplying cases of the neurodegeneration of Alzheimers also. In relation, I also believe iron overload could be the attribute for the increasing rates of Autism disorders due to neurodegenerative issues and “poor ‘pruning’ of brain neurons leading to excess synapses”. The diagnosis of Autism suspiciously has also been increasing during this fortification time.

    • Excellent info, Duck.
      Thank you!

      I’ve been learning this and I like all the details you provide.

    • Also know that B6 stores in muscle! Not necessarily water soluble and ‘safe.’ It can be toxic and leave permanent nerve damage. Unfortunately, I know, and hopi g time reveals complete healing. (I became B6 toxic when I used the P5P form.)

  11. I’m a 59 year old female. My iron level was tested, at my request, during my recent annual physical. The results were FE @ 167, TRFN @ 230, TIBC @ 322, & FESAT @ 52. So, both FE & FESAT were High. My Primary Care Physician (PCP) ordered a Ferritin level and a Hereditary Hemochromatosis DNA test. The Ferritin came back normal at 30 but the Hereditary Hemochromatosis DNA test came back indicating “two copies of H63D mutation identified”.
    My PCP was uncertain about these results so he consulted with my Gastroenterologist who said, “If her Ferritin is normal she does not have Hemochromatosis”. This still left me with no action plan as to what to do about having too much iron. On my own I decided to give blood and felt really good the next day. Do I need to be concerned? What should my next steps be?

    • Margaret – I am a 40 year old female, and your numbers and lab values are nearly identical to mine. My bloodwork was done initially to investigate a relatively rapid onset of fatigue and lightheadedness (constant). As I have Celiac Disease, we tested iron, expecting it to be low, due to malabsorption. My iron was at 167, and saturation was 55%. My ferritin was within a normal range (29). but the genetic test showed homozygous H63D mutation. I noticed your post was from April, wondering how things have gone since then? I still have to talk to my doc, but my fear is with the normal ferritin level, that phlebotomies (or any sort of treatment) won’t be recommended. I’m desperate to get back to my “normal” self. Any input or follow up to your own situation would be most helpful!! Thanks!

      • Moni, I am doing great. I am voluntarily giving blood every couple of months. I feel good. I haven’t had my Ferritin or Iron test since April except when I give blood. I think I mentioned that I wrote to Dr. Keith Roach (the newspaper doc) who said that the H63D confers a lower risk than the C282Y mutation and that only about 1% of women with my genes will have iron overload. Interestingly when this all started, I had my sister and my son get tested and my son (age 31) also tested really high for iron AND Ferritin. He also has the two copies of H63D. I feel very blessed that this was discovered so my son can be monitored and treated as necessary. Hope this helps!