How Do Grains, Legumes and Dairy Cause a Leaky Gut? Part 2: Saponins and Protease Inhibitors

We make it clear that we are in no position to expertly and thoroughly explain the science behind the Paleo Diet. So many people, though, ask us about it. In response, we went out and found a scientist for you. Meet The Paleo Mom, a scientist-turned-at-home-mom. She has written a series of posts for us on the “why” of this way of eating. We hope this will be informative and fun for you. Check out her website, an adorable place full of interesting posts and cute drawings.

Part 3 of 4 in this guest series: How Do Grains, Legumes and Dairy Cause a Leaky Gut?  Saponins and Protease Inhibitors

One of the fundamental principles of paleolithic nutrition is to protect the lining of the gut by eliminating foods that damage it.  By prioritizing gut health, we are able to treat and prevent the many health issues associated with having a “leaky gut”.  But how exactly do grains, legumes and dairy wreak so much havoc on the digestive tract?  The damage caused by the lectins contained in grains and legumes (see Part 1) is made even worse by two other compounds found in these foods:  saponins and protease inhibitors.

Legumes and pseudo-grains (like quinoa and amaranth) are high in saponins. All plants contain saponins, often concentrated in the seed of the plant.  These compounds have detergent-like properties and are designed to protect the plants from consumption by microbes and insects by dissolving the cell membranes of these potential predators.  Saponins consist of a fat-soluble core (having either a steroid or triterpenoid structure) with one or more side chains of water-soluble carbohydrates (this combination of both a water-soluble and a fat-soluble component is what makes saponin act like a detergent, i.e., something that can make oil and water mix).  This detergent-like structure gives saponins the ability to interact with the cholesterol molecules imbedded in the surface membrane of every cell in the body and rearrange those cholesterol molecules to form a stable, pore-like complex.  Basically, dietary saponins create holes in the surface membrane of the cells which line the gut (enterocytes), allowing a variety of substances found in the gut to enter the cell.


There are many different types of saponins, and some bind more easily and more tightly to the cholesterol molecules in the cell membrane than others.  As such, different saponins can create larger or smaller pores, which may be more or less stable.  The larger, more stable and/or more numerous the pores, the more difficult it is for the enterocyte to recover.  Small doses of some dietary saponins (like those found in fruits and vegetables) might be important for aiding absorption of some minerals.  However, legumes, and pseudo-grains contain very high doses of saponins (and, in general, contain types of saponins that interact more strongly with cholesterol).  Dietary saponins from these foods are known to increase the permeability of the gut (i.e., cause a leaky gut), likely by killing enterocytes (cells, in general, do not survive large, irreversible changes in membrane permeability).  Interestingly, even when a sub-lethal amount of saponin pores form in the enterocyte surface membrane, the cell loses its ability to actively transport nutrients, especially carbohydrates.  While slowing down sugar transport from the gut to the bloodstream seems like a great thing on the surface (why beans are so often recommended as a carbohydrate source for diabetics!), the irreversible increase in gut permeability is just not worth it!

When large amounts of dietary saponins are consumed (especially in the presence of an already leaky gut), saponins can leak into the bloodstream.  When saponins enter the bloodstream in sufficient concentrations, they cause hemolysis (destruction of the cell membrane of red blood cells).  Saponins also have adjuvant-like activity, which means that they are able to affect the immune system leading to pro-inflammatory cytokine production (again those chemical messengers that tell white blood cells to attack) and can further contribute to inflammation in the body.

Grains, pseudo-grains (like buckwheat) and dairy contain protease inhibitors. Protease inhibitors are the seed’s attempt to escape digestion completely.  These are compounds designed to neutralize the digestive enzymes that would normally degrade the proteins (and toxins) found in those plants into their individual component amino acids.  However, when protease inhibitors are present in the digestive tract, it affects degradation of all proteins present at that time.  When the body senses the need to increase protein digestion, the pancreas secretes more digestive enzymes into the small intestine.  Because some digestive enzymes are being inhibited (the proteases which break down protein) while others are not, the balance between the different digestive enzymes is thrown off.  One enzyme that ends up in excessive quantities during this process is trypsin, an enzyme that is very good at destroying the connections between cells.  If there is a large concentration of trypsin in the small intestine, it can weaken the connections between the enterocytes, creating a pathway for the contents of the gut to leak into the blood stream.  To make matters worse, in the presence of an already leaky gut, incompletely digested proteins that cross the enterocyte layer stimulate the resident immune cells of the gut to release inflammatory cytokines and produce antibodies.  The result is generalized and/or specific inflammation.

Dairy is designed to create a leaky gut. Scientists still don’t understand all the mechanisms through which dairy products can create a leaky gut.  However, it seems to be an important aspect for what dairy is designed to do:  feed babies (of the same species) optimal nutrition for rapid growth.  In newborn infants, a leaky gut is essential so that some components of mother’s milk can get into the blood stream, like hormones and all the antibodies that a mother makes that helps boost her child’s immune system.  While this is essential for optimal health in babies, it becomes a problem in the adult digestive tract where there are more things present that we don’t want to leak into the blood stream.  Drinking milk from a different species seems to make matters worse since the foreign proteins can cause a larger immune response.

The damage to the gut lining caused by saponins has been heavily studied in the context of animal feed for poultry, cattle and fish farms.  But, while there is a better understanding of the damaging effects of dietary gluten (at least in humans), the gut irritation and inflammation that can be caused by saponins and protease inhibitors should not be underrated.


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  • So I assume sunflower and pumpkin seeds are high in saponins? What about almonds? Should these not be eaten in the paleo diet or at least limited. (Please say no!)

    • I’m trying to figure out why nuts are considered paleo too. Didn’t evolutionary pressure cause them to protect themselves from microbes and insects also?

      • ThePaleoMom

        The main difference between the nuts and seeds that are included in a paleo diet and grains and legumes, which are also seeds but not included, is that things like almonds and sunflower seeds developed a different type of protective mechanism to protect it from being eaten, which is its hard shell. They do contain phytic acid, which can be a gut-irritant for very sensitive individuals and they do contain some lectins, but these again are generally very well tolerated. These can be reduced by sprouting the it’s first (soaking in water overnight and then drying on your ovens lowest temperature). They also tend to contain more of their fats as the pro inflammatory omega-6 fats. Most people tolerate fairly generous servings of nuts, but they can be a problem for people with severly leaky guts and autoimmune diseases. They generally get a proceed with caution label.

  • Monique

    What’s your opinion on goat milk? I’ve been making kefir everyday with goat milk and have no problem with it, whereas cow’s milk kefir is completely out of the question for me (so I’m not going to bother trying any other cow milk products). I was wondering if I could also try incorporating other goat milk products into my diet.  

  • I’ve read what you’ve written with interest but it leaves me perplexed as to how my son became “cured” of Crohn’s Disease on the Specific Carbohydrate Diet whilst eating beans every day! Maybe some beans are worse than others? Only certain beans are permitted on the SCD perhaps these beans have fewer saponins?

    The one thing that is certain is he recovered extremely quickly and while he continues to eat beans (navy) most days (6 years) he has remained healed with no inflammation!

    There must be an additional factor in the equation.

  • Tanya

    God I do love science – and the drawings are fun too. You know, I never thought to much about this before but – I wonder how long the “leakiness” lasts in human infants. I know in cattle that for optimal colostrum uptake they (the calves) need it within 6 and not more than 12 hours. I bet humans are close to the same, and we also have to remember that this is colostrum that is being “leaked” out of the gut, which is quite different than milk. Very interesting post – Thanks!

  • Ogushi_fj

    But i have read in many places that amaranth does not contain saponins, and even cientific test have determine that after germination and all they detected almost no saponins

    AbstractThe concentrations of four triterpene saponins present in amaranth seeds were determined with high-performance liquid chromatography. It was shown that the total concentration of saponins in seeds was 0.09−0.1% of dry matter. In germinating seeds an increase in concentration to 0.18% was observed after 4 days of germination, which remained stable for the next 3 days and later dropped to 0.09%. Highly purified extracts from the seeds were tested for their toxicity against hamsters. The hydrophobic fraction obtained by the extraction of seeds with methylene chloride showed no toxicity; the behavior of tested animals was similar to that of the group given an equivalent dose of rapeseed oil. A crude saponin fraction, containing 70% of pure saponins in the matrix, showed some toxicity; the approximate lethal dose was calculated as 1100 mg/kg of body weight. It is concluded that low contents of saponins in amaranth seeds and their relatively low toxicity guarantee that amaranth-derived products create no significant hazard for the consumer.Keywords: Amaranth; Amaranthus cruentus; saponins; concentration; toxicity

  • The Paleo Mom

    This is a great question!  The paper you have cited is actually th exact paper that Prof. Lorain Cordain’s cites in his most recent book The Paleo Answer to support his case against amaranth consumption.  I think the confusion arises from how different communities evaluate high versus low saponin content.  Prof. Cordain would argue that the accepted threshold for “safe human consumption” is actually far above what the threshold for optimal human health.  I would also point out that this paper showed that the level of saponins increased upon germination.  

    That being said, dietary saponins are mostly problematic when consumed in conjunction with lectins (especially gluten) or in the presence of an already leaky gut. This is because saponins have adjuvant activity and can magnify immune responses.  There is also a genetic factor here, which is why some people can tolerate large amounts of dietary legumes (and see great success reducing inflammation on SCD or GAPS for example) and others do not see resolution of their inflammation until legumes and pseudo-grains are removed from their diet.  Many people within the paleo community can tolerate occasional consumption of non-gluten containing grains, pseudo-grains and legumes, such as amaranth, corn, rice, and beans.  I typically recommend an elimination diet approach, i.e., after symptoms of any health issues have resolved, try small amounts of these foods and see if you have a reaction.   

    It might also be interesting to point out that saponins are not the only substance in amaranth worthy of concern.  It also contains a lectin which has been linked to colon cancer:  http://www.ncbi.nlm.nih.gov/pubmed/11169464

  • erin

    Raw milk and pasteurized milk are different animals. A woman I knew with leaky gut drank raw milk every day to help her. She moved from a state where it was legal to purchase raw milk to one where it wasn’t and she said it just killed her until she found a new source. So…something is off there..

  • This is an excellent article with regards to comsuming grains and leaves us understanding that quinoa needs to be washed. These grains have high levels of saponin and we can wash some of the saponin off these grains to reduce the effects of the sponin on the gut if we are die hard grain consumers.
    If you taste an astringency in your food or have a slightly upset tummy after eating something there is a good chance you have one or both of these factors at risk. Its amazing how we can think we are eating healthy and still ruining the inside of our bodies. Sometimes it feels as if there is nothing good we can do. Balance, variety and moderation and there shouldn’t be too many problems.
    Chef Daniel Janetos

  • Interesting theory on the anti nutrients causing leaky gut. I have eliminated all wheat and dairy from my diet but I still consume a decent amount of quinoa, brown rice, oatmeal and beans. They do not appear to cause me any problems. Do you by any chance have any scientifically peer reviewed research studies to back up Dr. Cordain’s theoretical research? I need to see evidence of actual clinical disease caused by eating grains (specifically brown rice, oatmeal, & quinoa) and legumes, and such disease is cured by their omission. Thanks!!

  • MBC

    How about some references? Where are the rat or mice studies on grains and intestinal permeability? There are plenty of scientific studies out there to show the breach of the intestinal lining from excessive prolonged exercise, heat stress, NSAIDs, and psychological stress. Animal studies are mandatory for confirmation about this run-away claim regarding grains, legumes and dairy products. Let us all not be like sheep following the recommendations of authors with Celiac disease for whom it is imperative that they totally avoid glutens.

  • thwap

    TL;DR: sprouting (and/or good gut health) negates ALL this anti-grains hoopla that has been spreading around the Internet!

    I think ALL these anti-nutrient scares, (phytic acid, lectins, saponin, gliadin) are short-sighted in that they don’t take the factor of gut health variability into account. If the individual has GOOD gut bacteria, (and that’s not a common thing – it takes real good health to have this – I certainly do, though many aderents of both well-done paleo AND veganism also do), this BALANCES OUT the issues that these ‘gut killers’ and ‘anti-nutrients’ apparently cause in the first place. (Doesn’t this teach us once again, to not look at things in test tubes but the WHOLE of human health [which includes the bacteria outnumbering us by ten-fold in our own bodies?]!)

    As we know, phytic acid is NEUTRALISED by the enzyme PHYTASE. Many good bacteria in the gut (such as lactobacilli, but that’s not all) PRODUCE phytase, and what’s more, sprouting activates phytase too, and if you are digesting your food well, this should only be proliferated in the gut in addition to that.

    As for lectins, the awesome paleo leader Mark Sisson has himself gone on record (e.g. on a video interview that I only watched yesterday) saying that with good gut health, perhaps the whole lectins issue isn’t one, after all.

    With saponin, if it’s a gut issue, well then sprouting and/or good gut bacteria, once more, silences this scare and may I add also that good gut health affects UMPTEEN issues in health like epigenetics, immune system, hormone regulation, so many powerful things it’s incredible.

    So really, sprouting and gut health really needs to be looked at by the entire Paleo movement and for those who let the science dictate one’s views, and not let what one believes ‘what we were evolved to eat’ dictate what you choose to believe from science, will see the light like Mark Sisson humbly and awesomely has!

    Personally, I believe both Paleo and Veganism can both work. We have an OMNIVORE body (now), and I think it’s clear you can adapt to EITHER end of the spectrum. Perhaps gut health, in the end, is that thing in the middle that can help us adapt and work with us for whatever route we go!

    I love those little guys down there, in fact I think I’ll go check how my sauerkraut’s going right now! 😛

    • barry

      glyphosate which is sprayed on grains/cereals are the cause for leaky gut… not the grains