Ulcerative Colitis and This

Last update: 08-27-22

 

By Eugene l. Heyden, RN

There is danger in red meat.  The levels of its consumption in the Western diet not only increases the risk of acquiring ulcerative colitis but can help perpetuate it, complicate it, and keep remission at bay.  This post is an edited excerpt from my book, More to Consider in the Battle against Ulcerative Colitis.  Although written with the ulcerative colitis patient in mind, what follows may apply to the patient with Crohn’s disease, as well.  Here we will discuss danger.

But before we get too far along in our discussion, please consider the following:

“Red meat is also a hallmark of the Western diet pattern.  Its consumption is associated with an increased IBD risk . . ..”  (Marion-Letellier et al., 2016)

 “High protein intake was associated with a 3.3-fold increased risk of IBD, suggesting a diet high in animal protein is a major risk factor for the development of IBD.”  (Haskey and Gibson, 2017, emphasis added)

And with that, here you go!

 

Red meat

 

“Heme, the iron porphyrin pigment, primarily found in red meat, poultry and fish is poorly absorbed in the small intestine. Approximately 90% of dietary heme transits to the colon, and is exploited by colonic bacteria as a growth factor.  

“Dietary heme directly injures colonic surface epithelium by generating cytotoxic and oxidative stress.”  ~Khalili et al., 2017, emphasis added

“. . . the irritating influence of heme is continuously present in the colon and not just a single “hit,” meaning the dietary heme can constantly modulate the severity of colitis.

“A diet high in red meat might be a risk factor for inflammatory bowel  disease development.”  ~Schepens et al., 2011, emphasis added 

 

Anything that directly damages the epithelial lining of the colon and affects the severity of colitis should probably command our attention.

I have mentioned the dangers of red meat before, particularly with respect to iron.  Now, we will drill down a little deeper and see why red meat poses such a threat to you, the patient suffering from ulcerative colitis, and to me, an individual who has no interest at all in developing colon cancer, much less increasing my risk of ulcerative colitis.

Red meat is rich in what is called “heme.”  Heme is the molecule the red blood cell hides all its iron within.  Iron, as we have previously discussed, should not be present in abundance in the colon.  However, given the right circumstances, it arrives in the colon in large amounts, contained in the heme of red meat or contained in the heme of red blood cells that enter the colon from GI bleeding (Constante et al., 2017).

The meats high in heme are “beef, veal, lamp, mutton, pork, and offal” (Bastide et al., 2011).  When I first read this, I didn’t know exactly what an offal was.  Is it cute?  Is it furry?  Is it cuddly?  Is it similar to a gopher—a particularly rich source of dietary heme which I strenuously avoid?  No.  An offal is none of these.  It is the organ meats and the butcher block scraps (of who knows what) that wind up on the dinner plate.  And while we’re at it, let’s not overlook the processed meats that are also high in heme: “sausages, meat burgers, ham, bacon, and salami” (Santarelli et al., 2010)  They pose danger, too—perhaps even more danger due to additives that, shall we say, have been added.

On the other hand, chicken also contains heme, but “the heme content of red meat is 10-fold higher than that of white meat (such as chicken)” (Bastide et al., 2011).  Fish is also low in heme (Sesink et al., 1999).  The low heme content of both chicken and fish is credited for a lack of association between these two food items and the risk of colon cancer (de Vogel et al., 2008; Ijssennagger et al., 2012).

Willingly and delightfully, on the Western diet we eat our fill of dietary heme.  What happens next?  The heme winds up within the colon where pathogenic bacteria catch a break.  For the pathogen, it’s another awesome day!

“Dietary heme is poorly absorbed in the small intestine, and approximately 90% of dietary heme proceeds to the colon where it can be used by colonic bacteria as a growth factor.”  (Ijssennagger et al., 2012)

“Bacteria pathogens are particularly efficient at capturing heme and thriving in heme-rich environments.”  (Constante et al., 2017, emphasis added)

As we have previously discussed, heme is loaded with iron.  I’m sure you could use at least some of that iron, but so can pathogenic bacteria.  And they can “extract” all they need from heme (Constante et al., 2017).  In as much as heme is a growth factor for pathogens, heme also becomes a driver of dysbiosis (Ijssennagger et al., 2012; Constante et al., 2017).   Heme also contains amino acids that are useful for bacterial growth (Constante et al., 2017)  Now if you were a pathogen, you would be all in favor of the dietary heme we consume on the Western diet—the more, the better!  For pathogens, it’s a win-win.  And they don’t seem to care what happens to you.

“A variable proportion of heme and amino acids, contained in animal proteins, are not absorbed by the small bowel and reach the colonic lumen, where they are metabolized by the microflora.  This results in a number of end products, which include hydrogen sulfide, phenolic compounds, and amines and ammonia, some of which are potentially toxic to the colon.”  (Jantchou et al., 2010)

Oh, we’ve discussed hydrogen sulfide before, just recently in fact.  Recall, hydrogen sulfide is an unfortunate byproduct of sulphate-reducing bacteria, and is toxic to the intestinal epithelial cell (Magee et al., 2000; Jowett et al., 2004; Kushkevych, 2014)  And, if that wasn’t bad enough, hydrogen sulfide actually damages, “breaks,” the mucus layer of protection (Ijssennagger et al., 2016).

“Hydrogen sulfide, produced by sulfate-reducing bacteria (SRB) and some other bacteria, reduces disulfide bonds present in the mucus network, thereby breaking the mucus barrier.

“Inflammatory bowel disease (IBD) is characterized by decreased mucus barrier function, which may be due to increased sulfide production by altered microbial species present in IBD patients with active disease.

“Lowering hydrogen sulfide concentrations in the gut lumen could represent an exciting potential therapeutic strategy for treating IBD.”  (Ijssennagger et al., 2016)

And if that wasn’t enough evil in one meal, another poison created in a “considerable amount” during the cellular metabolism of heme, is hydrogen peroxide (Gemelli et al., 2014).  “There is substantial evidence that hydrogen peroxide can have deleterious effects on the colon.”  (Jacobs et al., 2009)

Hydrogen peroxide generated within the cell can damage the cells DNA and, among other negative things, can contribute to the production of proinflammatory cytokines (Gemelli et al., 2014).  So, all I can say is “danger danger!”

But it’s not as if we are defenseless.  We do have an enzyme that degrades heme, called heme oxygenase-1 (HO-1) (Vijayan et al., 2010).  “HO-1 not only protects against oxidative stress and apoptosis [programed cell death], but has received a great deal of attention in recent years because of its potent anti-inflammatory functions.”  (Vijayan et al., 2010)  Indeed, the upregulation of this enzyme “amplifies the effects of IL-10”—a cytokine that restrains inflammation (if it can) (Chang et al., 2015).  Interestingly, in a laboratory model of ulcerative colitis, 5-ASA drugs (Asacol; Pentasa; sulfasalazine) upregulate HO-1 (Chang et al., 2015)—yet another potential beneficial action offered by this class of drugs.  However, while HO-1 is trying to save you from heme, this enzyme turns heme into the poisonous hydrogen peroxide molecule, and in a “considerable amount,” right inside the cell where it can do the most damage (Gemelli et al., 2014).  The cell is not too happy.  The cell is under threat.  A cry for help can be heard.

Regardless of HO-1’s role as a defense mechanism against heme, and regardless of its attractiveness as a therapeutic target in IBD, “it seems questionable whether HO-1 induction is useful for treatment of established IBD, but rather might be useful as a preventive measure.”  (Vijayan et al., 2010)  Besides, it is probably already working overtime, as “there has been no other enzyme described to date that is affected by so many stimuli of diverse nature as HO-1” and it is already upregulated in the inflamed tissues of the colon (Zhu et al., 2011).  So, it looks like we’re left with reducing our consumption of red meat, and all the heme therein, to avoid the ongoing damage it can inflict.  But there are other defensive measures we can take.

Heme does have an antidote, and it is found in green vegetables (de Vogel et al., 2005; Ijssennagger et al., 2012).   It is known as chlorophyll.  Chlorophyll is high in spinach, and the supplement chlorophyll extract appears to be just as protective as spinach against the damage heme can cause (de Vogel et al., 2005).  Chlorophyll seems to work because it structurally looks a lot like heme, and may, in this manner be able to compete with heme during metabolic degradation (de Vogel et al., 2005).   Experimentally, when rats were fed chlorophyll along with heme, the fecal output of heme increased, as opposed to rats only consuming heme (de Vogel et al., 2005).  The rats taking chlorophyll were pleased to learn that they were among those of us with a lower colon cancer risk.  You should join us.  “Supplementation of the heme diet with chlorophyll and spinach completely inhibited this heme-induced increase in cytotoxicity.”  (de Vogel et al., 2005)

Besides spinach and chlorophyll extract, this “antidote” can be found on other leafy green vegetables such as Swiss chard, beet greens, bok choy, green cabbage and collard greens.  You can also find chlorophyll in celery, green beans, peas, and green bell peppers.  And the list could go on.

Other heme “antidotes” include calcium, polyphenols (a class of beneficial, bioactive components found in fruits and vegetables), and vitamin C (Bastide et al., 2011).  But please be careful with vitamin C, particularly in the doses found in supplements, as it can act with available iron to exacerbate oxidative stress in the cells that line the colon, which can lead to ulceration and increased severity of GI inflammation as well as an increased risk of colon cancer.  (see Fisher and Naughton, 2004)  It should be noted that diets high in chlorophyll are also higher in calcium and polyphenols.  The Western diet is low in all three of these defenders of colon health.

Should you take the plunge and substantially reduce your intake of red meat, you will be substantially reducing your intake of another dietary item that inflicts harm upon the IBD patient and upon others.  You can read all about it in my post Iron in IBD (Danger danger).

 

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References

Bastide NM, Pierre FH, Corpet D. Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved. Cancer prevention research. 2011 Jan 5:canprevres-0113.

Chang M, Xue J, Sharma V, Habtezion A. Protective role of hemeoxygenase-1 in gastrointestinal diseases. Cellular and molecular life sciences. 2015 Mar 1;72(6):1161-73.

Constante M, Fragoso G, Calvé A, Samba-Mondonga M, Santos MM. Dietary heme induces gut dysbiosis, aggravates colitis, and potentiates the development of adenomas in mice. Frontiers in microbiology. 2017 Sep 21;8:1809.

de Vogel J, Jonker-Termont DS, Van Lieshout EM, Katan MB, van der Meer R. Green vegetables, red meat and colon cancer: chlorophyll prevents the cytotoxic and hyperproliferative effects of haem in rat colon. Carcinogenesis. 2005 Feb 1;26(2):387-93.

de Vogel J, van-Eck WB, Sesink AL, Jonker-Termont DS, Kleibeuker J, van der Meer R. Dietary heme injures surface epithelium resulting in hyperproliferation, inhibition of apoptosis and crypt hyperplasia in rat colon. Carcinogenesis. 2008 Jan 3;29(2):398-403.

Fisher EO, Naughton DP Iron Supplements: The Quick Fix with Long-Term Consequences.  Nutrition Journal 2004 3:2

Gemelli C, Dongmo BM, Ferrarini F, Grande A, Corsi L. Cytotoxic effect of hemin in colonic epithelial cell line: Involvement of 18 kDa translocator protein (TSPO). Life sciences. 2014 Jun 27;107(1-2):14-20.

Ijssennagger N, Derrien M, van Doorn GM, Rijnierse A, van den Bogert B, Müller M, Dekker J, Kleerebezem M, van der Meer R. Dietary heme alters microbiota and mucosa of mouse colon without functional changes in host-microbe cross-talk. PloS one. 2012 Dec 11;7(12):e49868.

Ijssennagger N, van der Meer R, van Mil SW. Sulfide as a mucus barrier-breaker in inflammatory bowel disease?. Trends in molecular medicine. 2016 Mar 1;22(3):190-9.

Jacobs DM, Gaudier E, Duynhoven JV, Vaughan EE. Non-digestible food ingredients, colonic microbiota and the impact on gut health and immunity: a role for metabolomics. Current drug metabolism. 2009 Jan 1;10(1):41-54.

Jantchou P, Morois S, Clavel-Chapelon F, Boutron-Ruault MC, Carbonnel F. Animal protein intake and risk of inflammatory bowel disease: The E3N prospective study. The American journal of gastroenterology. 2010 Oct;105(10):2195.

Khalili H, de Silva PS, Ananthakrishnan AN, Lochhead P, Joshi A, Garber JJ, Richter JR, Sauk J, Chan AT. Dietary iron and heme iron consumption, genetic susceptibility, and risk of Crohn’s disease and ulcerative colitis. Inflammatory bowel diseases. 2017 Jun 9;23(7):1088-95.

Schepens MA, Vink C, Schonewille AJ, Dijkstra G, van der Meer R, Bovee-Oudenhoven IM. Dietary heme adversely affects experimental colitis in rats, despite heat-shock protein induction. Nutrition. 2011 May 1;27(5):590-7.

Vijayan V, Mueller S, Baumgart-Vogt E, Immenschuh S. Heme oxygenase-1 as a therapeutic target in inflammatory disorders of the gastrointestinal tract. World journal of gastroenterology: WJG. 2010 Jul 7;16(25):3112.

Zhu X, Fan WG, Li DP, Kung H, Lin MC. Heme oxygenase-1 system and gastrointestinal inflammation: a short review. World Journal of Gastroenterology: WJG. 2011 Oct 14;17(38):4283.

 

Disclaimer: This article is presented solely for informational purposes. The information contained herein should be evaluated for accuracy and validity in the context of opposing data, new information, and the views and recommendations of a qualified healthcare professional, and is not to be substituted for professional judgment and guidance or to provide reason to neglect or delay appropriate medical care.  It is the reader and reader only who bears the responsibility for any actions that could be construed as being a response to the information contained herein.  The statements and opinions expressed by the author have not been reviewed or approved by the FDA or by any other authoritative body, nor is the author endorsing any product or specific therapy.  This article is offered to the reader to broaden his or her understanding of the issues discussed and to help identify options that may be suitable for the individual to pursue, on behalf of self or others, under approval and direction of a qualified physician.  The author and publisher offer no guarantees of the accuracy or validity of the quotations incorporated into this article or the accuracy or validity of the information presented by the references used in this article.

 

 

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