Iron in IBD (Danger Danger)

Last revision: 12-05-23

By Eugene L. Heyden, RN    

Iron is consumed in excess in our society, and not without negative consequences.  We are exposed to iron from dietary supplements, from meat, from iron-fortified foods, and from the water we drink.  When consumed in excess, iron promotes the growth and virulence of pathogenic bacteria, contributes to dysbiosis, and injures the cells that line the intestine.   If you have IBD, excessive iron consumption can only make matters worse.  This post includes an excerpt from my book, More to Consider in the Battle against Ulcerative Colitis, and is relevant to both ulcerative colitis and Crohn’s disease.

 

Iron in excess

“Accumulating evidence indicates that excess of unabsorbed iron that enters the colon lumen causes unwanted side effects at the intestinal host–microbiota interface.

“Notably, accumulating evidence suggests that unabsorbed iron can stimulate growth and virulence of bacterial pathogens in the intestinal environment.”  ~Kortman et al., 2014, emphasis added

“When iron meets the inflamed intestinal mucosa it may increase ROS [reactive oxygen species, leading to oxidative stress] and thereby tissue damage, as demonstrated in animal models of IBD.”  ~Erichsen et al.,   2005

“Oral iron supplementation anecdotally exacerbate inflammatory bowel disease and iron levels are elevated in the inflamed mucosa.”  ~Millar et al., 2000

 

In my book on Crohn’s, I spend a great deal of time warning of the dangers of iron, and how consuming it in excess, so commonplace in our society, leads to disease.  Excess iron exposure may have led to the very disease you have (Aamodt et al., 2008; Gisbert and Gomollón, 2008).  And it certainly has the power to amplify the disease process you are experiencing (Barollo et al., 2004; Uritski et al., 2004).  No one else seems to be telling you this, so I guess it’s up to me.  (If only people would listen.)  And why do I raise the alarm?  Because iron feeds and strengthens the pathogens in the gut.  It increases their numbers.  It makes them more aggressive and more likely to offend.  Furthermore, it can cause ongoing physical damage to intestinal mucosa.

“Besides the effects or iron on the gut microbiota, which may cause a shift towards a more pathogenic profile and an increase in virulence of enteric pathogens, iron may also directly exert unfavorable effects on the gut epithelium most likely by the promotion of redox stress.”  (Kortman et al., 2014)

 

Danger danger! (and I really mean this)

Don’t get me wrong, we need dietary iron.  But not in the amounts our society provides.  Bacteria need iron, too—many of which are young, aspiring pathogens.  Notably, “Acquiring iron is a fundamental step in the development of a pathogen.”  (Doherty, 2007)  They like all the excess iron we do not need.  Excess iron availability promotes their growth, virulence, and strengthens their numbers (Aamodt et al., 2008; Radek 2010; Kortman et al., 2014).  Iron excess is the gift of dysbiosis, favoring the growth of pathogenic bacteria.

“Ultimately, iron use allows for greater microbial growth and an increased capacity of the bacteria to adhere and possibly disseminate to distal sites to cause infection.”  (Radek, 2010)

“Iron is an important factor for the growth of bacteria and their expression of virulence.  When the level of iron increases, the balance between the quantities of different bacteria species in the gut is altered, depending on their ability to compete for iron.  The interaction between bacteria and host tissue will also be altered when iron levels are enhanced, including the ability for the bacteria to express virulence.”  (Aamodt et al., 2008, emphasis added)

Leave it to our society to “decide” that we need more iron than we could possibly use.  And so, we fortify.  Danger danger!

“Because > 90% of dietary iron is not absorbed, oral supplementation may elevate gastrointestinal iron concentration and amplify mucosal damage in patients with inflammatory bowel disease.” (Uritski et al., 2004, emphasis added)

 “In a laboratory study, the researchers found that human intestinal cells with excess iron were more susceptible to attack by bacteria that caused infection of the small intestine. The study suggests that enriching breakfast foods and other foods with high doses of iron—a nutritional strategy that has been widely adopted to eliminate iron deficiency—could be causing other health  problems.

 “The scientists found that cells containing high levels of iron were more easily invaded by the bacteria.

“’Instead of fortifying everyone’s diet with excess iron, we should diagnose iron deficiency and then provide supplemental iron only to those who need it.’”  —Quoting Dr. Mark Failla (Ohio State Research News, 2001)

As I said, we need iron.  Particularly, we need sufficient quantities of iron for transfer to the 200 billion new red blood cells we make each day—each with a pressing need for iron (Hentze et al., 2004).  To replace losses when red blood cells meet their maker (killed by design at a rate of 2–3 million each second), we have sophisticated recycling mechanisms in play that capture the iron from the dead and dying and deliver it to the next generation of red blood cells, cells which we create at the rate of 2–3 million each second (Gasche et al., 2004).  Unless bleeding is an issue, or an inflammatory disease process like IBD is present, we need only small amounts of iron in our diet—only about 1 to 2 mg/day (Hentze et al., 2004).  Iron consumed in excess of our need, and above what we can absorb in the upper portions of the small intestine, accumulates in the colon and can be problematic, as the quotations I am sharing with you indicate.  Read them again and again.  (You are free to tremble.)

Iron, of course, is at the heart of the hemoglobin molecule, the molecule hidden within the red blood cell that allows it to carry oxygen to the various parts of the body.  Astonishingly, each red blood cell—a cell we cannot see with the naked eye—contains 270 million molecules of hemoglobin (Wikipedia, 2018), allowing one single red blood cell to contain over 1 billion atoms of iron!  (Cassat and Skaar, 2013)   Now that’s a lot of iron, all packed into a single little cell.  (You are free to be amazed.)

Fortunately, we have systems in place that allow us to extract all the iron we need from our food—and the cells that perform this noble service are found primarily in the duodenum and upper jejunum, far, far away from the colon (Gasche, 2000; Kortman et al., 2014).  These specialized iron-uptake cells are under tight regulatory control; and after extracting their fill of dietary or supplemental iron, they take a break for a few days, then things reset, and they resume iron uptake all over again (and the cycle repeats over and over again) (Papanikolaou and Pantopoulos, 2005).

The iron that does make it past the absorptive cells in the duodenum and jejunum have the protentional to accumulate in the colon where it can stir up trouble.  Trouble!  The colon can absorb iron to “a small extent,” (Kortman et al., 2014), or perhaps in “significant” quantities (Chua et al., 2010), but it is hoping you are eating a lot of vegetables, legumes, whole grains, and taking supplements like tumeric and quercetin—all of which will bind iron, withhold it from bacteria, and keep it from physical contact with inflamed mucosa (Gasche et al., 2004; Guo et al., 2007; Weinberg and Miklossy, 2008; Jiao et al., 2009; Kortman et al., 2014).  The colon is also hoping you will lay off all the red meat you are eating, at least in the excessive amounts you are probably accustomed to.

“The Western diet is characteristically rich in sources of iron, especially red meat, and UC has historically been more prevalent in Western countries.

“The potentially deleterious effects of a high-iron diet on UC are attributed to the accumulation of iron in the colonic lumen in high concentrations, a direct result of the tight regulation of body iron levels and the restriction of dietary iron absorption.”  (Seril et al., 2006, emphasis added)

At this point in the conversation, I should mention this:  Your colon has one final wish on its wish list.  It is hoping you will come to your senses and reduce your exposure to iron to decrease its risk of cancer.  The iron that arrives in the colon accumulates in the cells of the colon and damages their DNA (Seril et al., 2006; Chua et al., 2010).  And, as I have mentioned previously, ulcerative colitis carries a substantial risk of colon cancer—with the longer you have the disease, the more elevated the risk becomes (Chen et al., 2013).  Combined with rectal cancer, colon cancer rates for ulcerative colitis patients are “10-fold higher than in the normal population.”  (Chua et al., 2010)  Experimentally, “Iron has been found to be a complete carcinogen and to induce tumors without other co-carcinogen treatment.”  (Liehr and Jones, 2001)

In the midst of all this iron, typically more than we need, anemia can rear its ugly head.  Leave it to you to come down with a disease commonly complicated by anemia.  Indeed, approximately one out of three IBD patients have anemia (Gasche et al., 2004)  Typically, “The only way to lose iron is by menstrual and intestinal bleeding.”  (Gasche et al., 2004)  Actually, there are a few other ways to lose iron: Bleeding from trauma and blood loss due to blood donation serve as examples.  But with respect to the ulcerative colitis patient, anemia is often due to blood loss from the diseased colon (Seril et al., 2006; Bayraktar and Bayraktar, 2010; Weiss, 2011).  But the anemia in ulcerative colitis is not always due to blood loss or at least from blood loss alone (Oldenburg et al., 2001).

Anemia in ulcerative colitis can be intentional, a result from a purposeful block on iron absorption, a block imposed on iron uptake cells—an “immune-mediated” strategy aimed “at restricting the supply of the essential nutrient iron to pathogens.”  (Nairz et al., 2010; Oldenburg et al., 2001).  Inflammation is a big clue that bacteria are present and on the move (Nairz et al., 2010; Oldenburg et al., 2001).  The body is taking extraordinary measures to keep you safe, by drastically limiting iron availability for pathogen acquisition.  And often, anemia follows—due to the protective efforts the immune system employs to block iron absorption and keep iron away from bacteria bent on evil.  And in our hour of need, iron supplementation is generally considered, and often employed, to correct the anemia that results from the iron-withholding efforts or from chronic blood loss.  But regardless or the cause, with iron supplementation I see trouble ahead.

“Oral iron supplementation renders high fecal iron concentrations.  Since only a fraction of supplemented iron will be absorbed, virtually the entire dose winds up in the distal parts of the bowel.  In an already inflamed bowel, this may reinforce the inflammation by catalyzing production of ROS [reactive oxygen species] . . ..”  (Erichsen et al., 2003, emphasis added)

“Moreover, iron and reactive oxygen species can amplify inflammation, increasing mucosal permeability, recruiting neutrophils, and activating NF-ĸB.”  (Barollo et al., 2004, emphasis added

“Another mechanism by which iron may exert a proinfammatory effect is the activation of nuclear factor-kappa B (NF-κB), a transcription factor which regulates the expression of many genes involved in inflammatory responses.”  (Oldenburg et al., 2001)

 

I’m sure by now you have a few questions

“Taken into account the harm that iron may inflict on the already inflamed intestinal mucosa, the question remains whether inflammatory bowel disease patients with anemia should be treated with iron supplements.”  ~Oldenburg et al., 2001

Now that you are aware of the dangers of iron excess and how it can feed the pathogens in your life and amply the disease process you are experiencing, you probably have a few questions.  Let’s see if I can round up a few physicians and scientists to help you out.  (I know where to look and I have a feeling they can.)

Question 1: “Should I limit the consumption of red meat as a measure to reduce my exposure to iron?”  Answer: “Yes,” according to these guys:

“The Western diet is characteristically rich in sources of iron, especially red meat, and UC has historically been more prevalent in Western countries.

“The potentially deleterious effects of a high-iron diet on UC are attributed to the accumulation of iron in the colonic lumen in high concentrations, a direct result of the tight regulation of body iron levels and the restriction of dietary iron absorption.”  (Seril et al., 2006, emphasis added)

“Specifically, we observed a 14% increase in risk of UC for every one serving increase in weekly red meat intake.”  (Khalili et al., 2017, emphasis added)

Question 2: “If my anemia is symptomatic, should it be treated?”  Answer: “I would certainly think so.”

“. . . there is enough evidence to support the following statements: (a) anemia is very common in IBD, (b) anemia should be investigated with care because many factors can be responsible, (c) treatment of anemia results in clear improvement in the objective parameters of well-being especially in the quality of life . . ..”  (Gisbert and Gomollón, 2008)

Question 3: “Should I use oral iron supplements to correct my anemia?”  Answer: “Maybe not.”

“Unless the host response is impaired by severe iron deficiency, there is rarely an urgency to supplement iron and it is likely to contribute little to host iron status due to the block on absorption associated with inflammation.”  (Doherty, 2007, emphasis added)

“. . . oral iron replacement therapy is poorly tolerated and may even contribute to the inflammatory process and tissue pathology in patients with IBD.”  (Werner et al., 2011)

Question 4: “Should I take high-dose iron supplementation to correct my anemia?”  (Don’t be silly!)  Answer: “For heaven’s sake, No!”

“Oral iron supplementation renders high fecal iron concentrations.  Since only a fraction of supplemented iron will be absorbed, virtually the entire dose winds up in the distal parts of the bowel.  In an already inflamed bowel, this may reinforce the inflammation by catalyzing production of ROS [reactive oxygen species] . . ..”  (Erichsen et al., 2003, emphasis added)

“Although conventional wisdom dictates administration of 200 mg elemental iron daily for correction of IDA [iron deficiency anemia], there is no rationale for using such a high dose of oral iron.  Iron absorption from the GI tract is highly efficient but saturable.  Accordingly, Rimon et al demonstrated that oral iron preparations at doses as low as 15 mg/d could be used to correct iron deficiency.”  (Bayraktar UD, Bayraktar S, 2010, emphasis added)

“Common misconception: When oral iron is administrated, high doses—higher than usual—should be prescribed as iron absorption is generally impaired in IBD patients.”  (Gisbert and Gomollón, 2008)

Question 5: “My doctor is pleased that I am following a diet high in iron to correct my anemia.  Should he or she be pleased?”  Answer: “No!  He or she should be trembling.”

“The potentially deleterious effects of a high-iron diet on UC are attributed to the accumulation of iron in the colonic lumen in high concentrations, a direct result of the tight regulation of body iron levels and the restriction of iron absorption.”  (Seril et al., 2006)

Question 6: “Should I take vitamin C with my iron supplement to increase its absorption?”  Answer: “Probably not a good idea.  Probably a bad idea.  Perhaps a very bad idea.”

“Co-supplementation of ferrous salts (iron) with vitamin C exacerbates oxidative stress in the gastrointestinal tract leading to ulceration in healthy individuals, exacerbation of chronic gastrointestinal inflammatory diseases and can lead to cancer.”    (Fisher and Naughton, 2004)

Question 7: “Should I take enteric-coated iron to reduce GI upset?”  Answer: “Not recommended.”

“In general, enteric-coated formulations should be avoided, because they may release their iron content beyond the intestinal site of maximal iron absorption.”  (Gasche, 2000)

Question 8: “Should I ask my physician for intravenous iron to correct my anemia?”  Answer: “Perhaps you should.”

“Intravenous iron sucrose has a good safety profile and a 65–75% response within 4–8 weeks, which is paralleled by improvement in the quality of life.”  (Gasche et al., 2004)

Question 9: “Should I ask my physician for EPO, whatever the heck that is?”  Answer: “Sure you can!”

“The best way to treat anaemia of chronic disease is by curing the underlying disease and the administration of iron in such patients should be avoided.  Recombinant erythropoietin [EPO] has been shown to raise haemoglobin levels in inflammatory bowel disease patients with anaemia refractory to treatment with iron . . ..”  (Oldenburg et al., 2001)

“Intravenous iron sucrose has a good safety profile and a 65–75% response within 4–8 weeks, which is paralleled by improvement in the quality of life.  Combination therapy with erythropoietin (Epo) leads to a faster and larger haemoglobin increase.”  (Gasche et al., 2004)

(Note: Erythropoietin is a hormone that stimulates red blood cell production.)

Question 10: “What else besides blood loss and the anemia due to inflammation should be considered as a cause of my anemia?”  Answer: “There are few things.”

“In some cases, anemia may be drug induced (Mesalazine, ulfasalazine, azathioprine, mercaptopurine) of due to folate/vitamin B12 deficiency.”  (Bayraktar and Bayraktar, 2010)

Thank you, physicians and scientists!

 

In conclusion

This post has a simple take-home message: Be ever-so-careful when it comes to iron.  Make no mistake about it.  Work closely with a physician (one who clearly understands the issues) in all things iron.  Perhaps measures to control inflammation in IBD will be more effective when factors that contribute to both inflammation and its perpetuation are effectively addressed.

 

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References

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Wikipedia 2018 Red Blood Cell. https://en.wikipedia.org/wiki/Red_blood_cell

 

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