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The Exogenous Endotoxin Theory

The endotoxemia (bacterial toxins in the bloodstream) that follows a meal of animal products and results in inflammation and stiffened arteries may come from the food itself rather than from one’s own gut bacteria.

July 5, 2012 |
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Supplementary Info

The Exogenous Endotoxin Theory, 4.9 out of 5 based on 10 ratings

Sources Cited

Erridge C, Attina T, Spickett CM, Webb DJ. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. Am J Clin Nutr. 2007 Nov; 86(5):1286-92.

Erridge C. The capacity of foodstuffs to induce innate immune activation of human monocytes in vitro is dependent on food content of stimulants of Toll-like receptors 2 and 4. Br J Nutr. 2011 Jan; 105(1):15-23.

Ghanim H, Abuaysheh S, Sia CL, Korzeniewski K, Chaudhuri A, Fernandez-Real JM, Dandona P. Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care. 2009 Dec; 32(12):2281-7.

Selmi C, Cocchi CA, Lanfredini M, Keen CL, Gershwin ME. Chocolate at heart: the anti-inflammatory impact of cocoa flavanols. Mol Nutr Food Res. 2008 Nov; 52(11):1340-8.

di Giuseppe R, Di Castelnuovo A, Centritto F, Zito F, De Curtis A, Costanzo S, Vohnout B, Sieri S, Krogh V, Donati MB, de Gaetano G, Iacoviello L. Regular consumption of dark chocolate is associated with low serum concentrations of C-reactive protein in a healthy Italian population. J Nutr. 2008 Oct; 138(10):1939-45.

Acknowledgements

Image thanks to SuperManu via Wikimedia Commons and jeffreyw.

Transcript

To recap: until recently, the thinking was that the reason that a single meal of animal foods causes inflammation, is because animal foods have saturated fat, the saturated fat causes the breakdown of our intestinal barrier, which could cause a “fat-induced translocation of small quantities of bacterial endotoxin from the gut into our bloodstreams,” which triggers the acute inflammatory reaction… associated with egg and sausage mcmuffin consumption. So "To date, it has been widely considered that the source of this circulating endotoxin is the resident intestinal microflora.”
Wait a second, though. What’s wrong with this picture? Look at this time scale. The rise of inflammation starts within just a few hours of ingestion. But where are our bacteria? Not in our small intestine, but 20 feet farther down in our large intestine. That could take like 8 hours for a mcmuffin to get down there. So what’s going on? Where else could bacterial endotoxins be coming from if not the bacteria in our gut? Maybe the endotoxins are coming from the food itself.
 This is the new study that changed everything. For the first time ever, “they aimed to determine whether common foodstuffs may contain appreciable quantities of endotoxin.” “Forty extracts were therefore prepared from twenty-seven foodstuffs common to the Western diet, and the capacity of each to induce the secretion of inflammatory signals from human white blood cells was measured.”
They found whopping doses of endotoxin equivalents in some pork, poultry, dairy, and chocolate products. What’s with the chocolate? Well, the first step in chocolate making is bacterial fermentation of the beans, but thankfully the phytonutrients outweigh the effect of the bacteria and decrease inflammation overall.

To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring watch the above video. This is just an approximation of the audio contributed by Serena

To help out on the site please email volunteer@nutritionfacts.org

Dr. Michael Greger

Doctor's Note

This is the second video of a three-part series exploring the mechanism behind the spike of inflammation that follows within hours of a meal containing animal products. See yesterday's NutritionFacts.org video-of-the-day for part one: The Leaky Gut Theory of Why Animal Products Cause Inflammation. Food Mass Transit details intestinal transit time and for more on chocolate see Update on Chocolate, Healthiest Chocolate Fix, and A Treatment for Chronic Fatigue Syndrome. The chocolate thing reminds me of the nitrate story. When accompanied by phytonutrients, what could have an adverse effect ends up being beneficial—see Are Nitrates Pollutants or Nutrients?. Tomorrow I'll close up this fascinating topic by exploring the role fat may play in this endotoxic reaction to meat and other animal products in Dead Meat Bacteria Endotoxemia. In the meantime, there are hundreds of other videos on more than a thousand subjects for you to check out. 

For more context, check out my associated blog posts: How Does Meat Cause Inflammation?, The True Shelf Life of Cooking Oils, Top 10 Most Popular Videos of the Year, and Lead Poisoning Risk From Venison

  • Michael Greger M.D.

    This is the second video of a three-part series exploring the mechanism behind the spike of inflammation that follows within hours of a meal containing animal products. See yesterday’s NutritionFacts.org video-of-the-day for part one: The Leaky Gut Theory of Why Animal Products Cause Inflammation. Food Mass Transit details intestinal transit time and for more on chocolate see Update on Chocolate, Healthiest Chocolate Fix, and A Treatment for Chronic Fatigue Syndrome. The chocolate thing reminds me of the nitrate story. When accompanied by phytonutrients, what could have an adverse effect ends up being beneficial—see Are Nitrates Pollutants or Nutrients?. Tomorrow I’ll close up this fascinating topic by exploring the role fat may play in this endotoxic reaction to meat and other animal products in Dead Meat Bacteria Endotoxemia. In the meantime, there are hundreds of other videos on more than a thousand subjects for you to check out. 

    • HemoDynamic, M.D.

      I remember reading an article back in about 1992 before I went to Med School that stated, ALL chronic diseases were the result of chronic low-grade inflammation.  Proof is in the print.   Fascinating to know the physiology!

      Knowledge — it’s what’s for Breakfast!

      Thank you from myself and all my patients for empowering us to become healthier and happier.

      • Stefan Juhl M.D.

        Hemo – do you rember when the (other) doctors learned that inflammation had something to do with CVD – they immediately invented bacterial infection in the endothelium as the main cause of CVD, and suggested that the solution could be antibiotics – a pill……!

        3 times a day with your McMuffin and coffee, your Pizza Hut and cola and your KFC with milk – pus – shake. So no problemo – NOT!

        • HemoDynamic, M.D.

          I don’t remember Stephan but I’m sure the Pharma people loved the idea of selling ABX’s to anybody and everybody!

          All back to the pill.

          Recently I had someone tell me that they work for a company called “Whole Food Supplements.”
          I thought that to be the ultimate oxymoron in the nutrition industry–convince people that all they have to do is take a Whole Food Supplement rather than chew it and then who cares what you eat; you’re protected from the supplements.

          How can it be a Whole Food when it’s been pulverized into dust and crammed into a gelatin capsule?

          • Stefan Juhl M.D.

            You are right – dust is dust – whole food is (surprise!) food, that you have to chew – brocholi, spinach, kale…yummi!

            oxymoron – nice!
             
             

      • Jenweix

        So nice to hear the docs jumping in here.  I guess it just took this amazing younger generation to come along!  Finally, all of us stand together, standing up to the “corporates!”  Then again things were never this bad, this very bad before.

    • Stefan Juhl M.D.

      Solution: Say no to McToxic

      Does white bread with sugar, a goblet of yellow fat, with some white stuff around and a thin slice of a carcinogenic pig sound like food…….?

      No. Eat food, not food-like things.

      • Jen

        LOL

    • BVG

      So what is the explanation for inflammation caused by certain plant foods? I follow a plant based diet and have lupus. I have noticed that certain foods – wheat, soy, tomatoes, red peppers give me joint pain and it is common for people with lupus to be sensitive to night shade vegetables (tomatoes, eggplant, potatoes, bell peppers). Is bacteria found in these foods as well?

      • Gale

        BVG can’t you just have food sensitivities to those foods?

        • BVG

          I guess I didn’t explain my question well. I clearly have food sensitivities, so I’m wondering what the mechanism is behind them to see if I can do anything about it. For example, if it’s a leaky gut, then I can work on healing my gut.

    • BVG

      Does the leaky gut theory still apply to the development of plant food sensitivities?  What is the mechanism behind the development of inflammatory responses to wheat, soy, and certain plant foods? If these are cut out of the diet long enough, and the leaky gut healed, would it be possible to one day reintroduce these foods back in one’s diet?
      Thanks!

      • http://www.DonForresterMD.com/ Don Forrester MD

         It might explain some but it is still possible to have reactions to plant foods or substances. This can occur on your skin such as the common photo-sensitivity reaction many folks get if they rub lime juice on their skin and expose the skin to sun light or true allergies which can be mediated in the gut without the substances getting into the body itself. There are differences between sensitivities and true allergies. If you have true allergic reactions to plant substances it is best to avoid these altogether and only reintroduce the food under the care of and with the recommendation of a physician who is an allergy specialist. It is difficult to be more specific without knowing the symptoms and foods involved. Best to work with your physician on this one. Good luck.

  • http://poxacuatl.wordpress.com/ Strix

    There’s no end to the evil of Mc Foods. 

  • April Lillie

    Phew! Dark chocolate remains safe! You scared me there for a little whole :)

    • Valnaples

      HELL yes April! LOVE my 90% dark Lindt and am now incorporating cocoa powder into many snacks…like dipping some walnut halves into cocoa powder, etc…!

    • http://www.facebook.com/darryl.roy.752 Darryl Roy

      Not all endotoxins are dietary. Our digestive tracts also harbor gram-negative bacteria, the lipopolysaccharide (LPS) cell walls of which are almost synonymous with endotoxin in the literature. I’ve read somewhere (and sadly, can’t find my source) that the human digestive tract contains on the order of a full gram of LPS.

      Saturated fats, like those in palm, coconut, and cocoa oil, seem to increase endotoxin transit through the intestinal wall:
      http://www.nutritionandmetabolism.com/content/10/1/6/

      That said, vegans may harbor less endogenous endotoxins, as their colonic microbiota have significantly less gram-negative E. coli or Enterobacteriaceae:
      http://www.hablemosclaro.org/pdf/noticias/A_vegan_diet_alters_the_human_colonic_faecal_microbiota.pdf

      Also, low-fat and high fiber diets are both associated with reducing gram-negative Fermicutes and increasing gram-positive Bacteroidetes. Here’s a good recent review:
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493718/

  • http://www.facebook.com/profile.php?id=583799778 Sandy Kelly

    It sounds to me like we’re redefining “leaky gut” syndrome then to not include any gut leakage? It’s simply toxins in the animal proteins consumed that are wreaking havoc?

    • Stefan Juhl M.D.

      I think both.

      • http://www.facebook.com/profile.php?id=583799778 Sandy Kelly

        Sure doesn’t sound like that’s what he’s saying. I don’t get it then. Need clarification…

  • MJ

    This is worth sharing with anyone you know who is affected, directly or indirectly, with heart disease. Or anyone who you would like to see not suffer from cardiovascular diseases.

  • HemoDynamic, M.D.

    What the heck is Twitter anyway?  Is it what happens to the body when we eat animal products?  Because all those uppercase number symbols leaves me confused, just like I feel when I have eaten meat?

  • DLS

    Doc, how would eggs contain endotoxins? Are eggs themselves not sterile?

  • HemoDynamic, M.D.

    Dr. G,

    Not that you aren’t busy but I was just perusing the citations, and I linked into another related article at PubMed:
     
    Stimulants of Toll-like receptor (TLR)-2 and TLR-4 are abundant in certain minimally-processed vegetables.
    http://www.ncbi.nlm.nih.gov/pubmed/21376773
     
    Excerpts from above link:
     
    Interestingly it states, “Of 5 classes of MPV’s (Minimally Processed Vegetables)  3 classes of related vegetable products considered to be likely to contain a high microbial load, diced onion and bean sprouts (endobacterial spoilage or fecal contamination?) contained the highest levels of stimulants of TLR2 and TLR4.
     
    “The accumulation of TLR-stimulants in MPVs correlated well with growth of enterobacterial spoilage organisms.
     
    “In conclusion, the modern trend towards eating
     
    >>>> minimally processed vegetables (MPV’s) rather than whole foods <<<<
     
    is likely to be associated with increased oral exposure to stimulants of TLR2 and TLR4."
     
    OK, my questions are (if you are too busy to respond I understand completely and this may be a good topic for your Ask the Doc Blog):

    1) what is the difference between MPVs compared to  Whole Foods? 
     
    A whole food is a minimally processed vegetable, or isn't it.  Maybe it means something different in Britain where the study was performed.

    2) Clearly I will not knowingly eat Spoiled foods but are the TLR stimulants (LPS's and such) able to be washed or cleaned off in some way?

    2a) If not are there some MPV's we should avoid?

  • Dbloch

     If I eat organic non-fat yogurt, do I avoid the endotoxins since the yogurt has no fat?

    • Toxins

       You have alot more to worry about with dairy then just endotoxins. Your exposing your body to xenoestrogens and insulin like growth factor which are great at promoting tumor growth, throwing hormone balance off and accelerating the aging process.
      http://nutritionfacts.org/videos/dairy-sexual-precocity/

      • Dbloch

        What about just  half a cup of yogurt a day and no other dairy?

        • Toxins

           I cannot comfortably recommend half a cup of yogurt a day knowing the harmful side affects it entails. If you really like yogurt, then you can find soy yogurt or almond yogurt that tastes close to exactly the same but is much healthier for you.

  • http://nikolay.com/ Nikolay Kolev

    So, you either get endotoxins from meat products or mycotoxins from plant-based foods.

  • BLong

    Very interesting! In looking at the original article by Erridge in 2011 you referenced, if I read the charts correctly it appears the TLR2 and/or TLR4 are high is some animal products but not all. For example, none or low amounts found in 2 beef samples, 2 lamb samples, 2 sausage samples (where I’d expect high levels) 1 turkey sample, 2 milk samples. But yogurt, ice cream, a second turkey sample, pork and cheese were relatively high. Next question is the source of the endotoxins. Are they a result of CAFO (confined animal feeding operations)? Why one turkey and not the other? Why ice cream and not milk? Why NOT sausage? Is it possibly like the fecal contamination where a high percentage of meat samples are contaminated but it is not a property of meat from healthy animals?

  • http://www.naturallifeenergy.com/ Aqiyl Henry

    You sacred me a bit which the news about dark chocolate. I was like “Noooooooooo!” Thanks for the good news.

  • Drew

    I wonder how you would account for the numerous health benefits of live, fermented food products such as kimchi, saeurkraut, fermented dairy products, etc. These foods must contain FAR more lipopolysaccharide than cooked meats and such, and thus should theoretically increase the endotoxin load substantially over even meats.

    The research however even shows probiotics may DECREASE endotoxemia and intestinal permeability.
    http://www.ncbi.nlm.nih.gov/pubmed/20094783

  • Toxins
  • Tian Collen

    Question for the doc: Does organic meat (or other animal products) also transmit endotoxins? I’ve followed your videos for some time and you ever say. Grass feed, grass finished organic beef?

    • Toxins

      It should make no difference as they are all exposed to bacteria. Would you ever consider eating raw, untreated beef? Whether it be grass fed or not the difference should be none.

    • http://nutritionfacts.org/ Michael Greger M.D.

      I did a video in which the inflammation caused by store-bought compared to wild (kangaroo) meat is compared: http://nutritionfacts.org/video/modern-meat-not-ahead-of-the-game/

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