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Functional Iron Deficiency in Obesity



Iron is essential for numerous bodily functions not least the production of the red blood cell oxygen transporter hemoglobin and myoglobin, a related molecule essential for muscle function. Iron deficiency is one of the most common nutritional deficiencies, especially in, but not limited to, premenopausal women.

Clinical signs of iron deficiency include anemia, difficulty in concentration, poor memory, depression, dizziness, weakness, labored breathing, anginal pain, brittle lusterless, flattened or spoon-shaped nails, swollen ankles, hair loss, pale skin, and exhaustion.

Paradoxically, obesity, a state more commonly considered in the context of over- than under-nutrition, is associated with a higher risk of iron deficiency compared to normal-weight individuals.

Several hypotheses have been suggested for this paradox including dilutional (pseudo) hypoferremia, poor dietary iron intake, increased iron requirements (in part due to the earlier onset and often more severe periods associated with excess weight), and/or impaired iron absorption in obese individuals.

However, there is now accumulating data that iron deficiency in obesity may also be mediated by the low-grade chronic inflammation commonly seen in individuals with excess weight.

This topic is elegantly reviewed by Ana Cepeda-Lopez and colleagues from the Netherlands, Mexico and Switzerland, in a paper just published in the International Journal of Vitamin and Nutrition Research.

The article summarizes the abundant data from epidemiological studies, dating as far back as 1962, documenting the inverse associations between adult and childhood adiposity and poor iron status (defined in most studies as low serum iron concentration).

With regard to possible mechanisms, the authors describe their own work in obese volunteers demonstrating decreased intestinal iron absorption using stable iron isotopes.

Iron absorption from the gut is dependent on both a divalent metal transporter and the iron exporter ferroportin, which delivers enteral iron to the blood stream and appears to be the rate-limiting step in this process.

Ferroportin in turn is largely regulated by hepcidin, a 25-amino acid peptide hormone, which is both an inhibitor of intestinal iron absorption as well as macrophage iron release.

Hepcidin is produced both in the liver and in fat tissue and is modulated by body iron stores and hypoxia, but also, as recently recognised, by proinflammatory cytokines, which are commonly elevated in individuals with excess weight and can promote hepcidin formation.

In addition, lipocalin 2, an iron binding protein is also produced by fat cells and could lead to sequestration of iron stores making them unavailable for hemoglobin or myoglobin formation.

Thus, irrespective of actual iron intake, a ‘low’ iron status in obese individuals may result both from reduced absorption and functional iron deficiency – the latter perhaps being more important than the former.

The authors conclude their article by summarizing the findings from three recent intervention studies: one in 15 obese children, where weight loss resulted both in a decrease in hepcidin levels and improved enteral iron absorption as well as two studies in bariatric surgical patients showing reduction in inflammation markers, decrease in hepcidin levels and improved iron status.

These findings are important as both low ‘absolute’ and ‘functional’ iron deficiency have been associated not only with anemia but also a wide range of other health problems including myocardial dysfunction and heart failure.

Clinicians should monitor obese patients for both absolute and functional iron deficiency and be aware that iron deficiencies may well be independent of and unresponsive to enteral iron intake.

AMS
Edmonton, Alberta

Cepeda-Lopez AC, Aeberli I, & Zimmermann MB (2010). Does obesity increase risk for iron deficiency? A review of the literature and the potential mechanisms. International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition, 80 (4-5), 263-70 PMID: 21462109

7 Comments

  1. Is there any suggestion as to what we should do to get more iron? What if we can’t lose weight? It sounds like iron supplements won’t work…

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  2. “Is there any suggestion as to what we should do to get more iron? What if we can’t lose weight? It sounds like iron supplements won’t work…”

    Treatment should not come before diagnosis: the first step is to diagnose iron deficiency – then do the tests to see if they are nutritional or functional. Treatment and supplementation will of course depend on what the problem is – if lack of nutritional iron is the problem – sure, iron supplements can work.

    The point of this post is that simply putting people on more iron supplements when lack of iron is not due to poor iron intake is not going to be effective.

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  3. This is relevant to me, because I’ve had bizarre blood test results for about 10 months now — my hemoglobin and hematocrit are really low, though my ferritin is normal…and my sed rate is way high. Despite having gone gluten-free, and having lost just under 40 pounds, every time I get bloodwork, the same info comes up. I’ve been tested for everything under the sun, since it was suspected that I had IBS, or Crohn’s, or Ulcerative Colitis, or any number of other malabsorption diseases and cancers and everything is negative…now my primary care doc is talking about a bone marrow biopsy, which I am extremely not excited to consider. We’ve made the deal that I’ll take an iron supplement for a month and see if that helps and if not, I need to sign up for the bone marrow invasion. But this article, and your comment, make it sound like a supplement might not help.

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  4. “But this article, and your comment, make it sound like a supplement might not help.”

    Thank you for sharing your story – best always to discuss this with your doc.

    As I say in the disclaimer:

    Any medical discussion on this page is intended to be of a general nature only. This page is not designed to give specific medical advice. If you have a medical problem you should consult your own physician for advice specific to your own situation.

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  5. My iron was tested a couple of years ago before I was to have surgery. Even though I use a cast iron pan to cook almost everything, it was too low. I was mildly anemic. Nobody suggested trying to figure out why (I assumed it was because I don’t eat a lot of red meat), but I did start taking liquid iron supplements. I’ve been taking the iron with a dairy-free meal – either breakfast or lunch – because calcium blocks the absorption of iron. I’ve also been taking calcium and vitamin D supplements before bed. I have had a higher energy level ever since I started doing this.

    If this is related to weight, then doctors should definitely be testing for it and suggesting iron supplements when appropriate. I’ve often thought that there’s way too much emphasis on how to make people lose wight (which never really seems to work long term) and not nearly enough on how to help fat people be healthier. This is one of those cases where the problem can easily be addressed without falling back on “lose 50 pounds and call me in the morning,” and it can make a BIG difference in how you feel.

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  6. i too have been having classic iron deficiency symptoms and talked with a dr who suggested i try iron supplements yesterday…so I have just now begun them. Immediately I did notice more energy less fatigue easier breathing.

    I can see that being overly tired and lethargic from the lack of iron could actually LEAD to the obesity..as if you can’t move how do you keep active enough to keep the weight off ?

    This is a new eye opener for me as I’ve been trying to get 100 extra pounds off for most of my adult life..but have so little energy..maybe this will help?

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  7. iron deficiency can cause low grade infections and lethargy which could cause weight gain. I believe that my inability to lose weight is due to iron deficiency more than the other way round. I lose weight when following an exercise program and diet until I start to feel exhausted. It’s at this point that I start to gain weight for no reason even with exercising. Then when I get too tired to exercise I get a blood test which is positive for anemia but the damage is already done, I’ve put back on all the weight and have to start again.

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