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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