1. How lectins interact with your gut
2. Lectins effect your gut microbiome
3. Lectins, hormones, and muscle loss
4. Lectins shrink tumors, but should we still avoid them?
5. Lectins activate your immune system and stress your cells
6. Conclusion
In Part 1, we covered the basics of lectins: what they are, what foods they're in, as well as some overarching concepts of how lectins impact the immune and endocrine systems. In Part 2, we will dive into some specifics of how lectins play a role in human health and disease.
How lectins interact with your gut
In Part 1, we discussed the mechanism by which lectins bind to the intestines and initiate a system wide response. In addition to what was described in the previous blog, lectins are able to interact with the intestinal lining and act like a growth factor, causing a hyperplastic (growth enhancing) effect on the intestines. Lectins do this by recruiting polyamines, a nutrient necessary for the grow of the intestinal lining (1). In normal circumstances, the intestinal mucosa (the layer that touches the food) is thin and continuous. Constant exposure to lectins in the diet, like the kidney bean lectin, makes this layer thicker an more uneven. In some situations, lectin consumption can causes a weakening in the intestinal mucous barrier (1).
The effects of lectins do not stop at the weakening of the intestinal lining. The damage to the intestines can lead to interference with absorption and digestion. Lectins are also able to influence the gut microbiome (the various different critters that live in our bodies) and modulate (influence) the localized immune system within the gut (2).
Because the gastrointestinal tract is under a large amount of mechanical stress from the digestive process (food sliding through it constantly), repair mechanisms are necessary to keep your gut in tip-top shape. Lectins that bind strongly to the cell surfaces of the intestines inhibit the repair mechanisms (4). It just so happens that diseases like muscular dystrophy are associated with inappropriate cellular repair mechanisms, and because lectins have been shown to potently block repair mechanisms as well, there has been speculation about a link between the two (4).
Lectins are able to harm the repair mechanisms of your gut in two ways. First, your gut is unable to reseal itself after being exposed to mechanical stress (like digesting food), leading to cell death. Second, the cells that normally secrete mucus (which is protective) are unable to do so. If you've ever greased two pieces of metal, you know that having the fluid in there is very beneficial to help them slide easier and prevent wear. In a similar way, by not having the mucus on the lining of your gut, this can increase the amount of mechanical stress from digestion (4). Now you see why lectins may not be beneficial for optimal gut health and gut repair.
Lectins effect your gut microbiome
The effect of lectins extends beyond just making the intestines grow and disrupting the repair mechanisms of the gut. Consuming different lectins can modify the microbiome. The microbiome consists of all of the bacteria living in our digestive tract that help with digestion and many other things. Lectins cause agglutination (the clumping together) of particular bacterial species in the intestines, which can then lead to their elimination (1).
In a study, rats that were fed high doses of PHA (the kidney bean lectin), developed an overgrowth of coliform bacteria in their guts whereas those not fed the kidney bean lectin had lower bacterial counts and furthermore, the intestinal lining wasn't effected. It is thought that lectins cause an increased expression of carbohydrates molecules on the lining of the intestines that bacteria were then able to interact with. This led to an overgrowth of the bacteria. After removing lectins from the diet for 3 days, these changes were reversible (1).
Lectins, hormones, and muscle loss
Lectins are capable of eliciting an effect on the endocrine system, the system that releases hormones to control processes all throughout the body. Once we ingest lectins and they are in the gut, they are able to bind to receptors here and initiate hormone changes that can have implications on the entire endocrine system (1).
Insulin receptors are found on muscles all throughout your body. PHA, the kidney bean lectin, is capable of binding to insulin receptors on muscle cells. However, it binds to these receptors but does not initiate protein synthesis in the muscles (1). What does this mean? After receiving high amounts of kidney bean lectin over several days, a major reduction in muscle mass has been reported, likely caused by the lectins preventing from insulin from binding to the insulin receptors on the muscles(1).
Lectins shrink tumors, but should we still avoid them?
In studies, mice were injected with non-Hodgkin lymphoma cells into their abdomens. Some of the mice were fed the kidney bean lectin, and others were fed a lectin-free diet. It turns out that those who were fed the lectins had a decreased level of 70kDa Heat Shock Protein (HSP70). Don't get overwhelmed, HSP70 is just a protein that prevents a normal cell from dying, thus making the cell cancerous (1). The result of decreasing the levels of HSP70 Is reduced tumor growth. Therefore, the consumption of the kidney bean lectins appears to slow the progression of cancer growth in this scenario. Another lectin called the mistletoe lectin (ML-1) has been able to completely eradicate non-Hodgkin lymphoma tumors when consumed, potentially by activating the immune system (macrophages and natural killer cell activation) (1).
In one report discussing the effects of plant lectins on cancerous cells, they state that eating lectins can decrease cancer cell growth. Remember how earlier we mentioned how the intestines use up a bunch of molecules called "polyamines" to grow? Well it just so happens that tumors use polyamines to grow too. When lectins are present in the diet, polyamines are used for intestinal growth, leaving fewer polyamines available for the growth of tumors. Feeding mice kidney bean lectin resulted in a reduction of tumor size whereas those who were fed a high concentration of polyamines increased tumor size (1). This speaks to the competition between the intestines and the tumor for polyamines in the diet, that are significantly decreased when lectins are consumed (1). Lectins are also thought to be able to elicit a variety of immune system effects that slow down cancer cell growth as well (1).
Before getting carried away that lectins are a very beneficial food, it is important to note that some of these studies mentioned use mice that already had cancer or tumors. With this being said, the positive effects that consuming high concentrations of lectins had on decreasing cancer growth doesn’t necessarily imply that eating high concentrations of lectins would be beneficial in preventing the development of these cancers in the first place. Let me us a metaphor to help explain this concept.
You may know that Type II diabetics need to take insulin (or another blood sugar regulating drug) in order to keep their blood sugar within a normal range. If their blood sugar gets too high (from not taking their medication), or if it gets too low (by taking to much medication), the effects could be harmful. To Type II Diabetics, insulin is beneficial, helpful, and necessary. Why? Because they already have Type II Diabetes. Now let's say that you are a non-diabetic, and heard that all the Type II Diabetics were taking insulin and that it really helped them out. You, being the health savy, person that you are decide this is the next addition to your health regimen because it made a positive impact on the Type II Diabetics. After overdosing on insulin, you find yourself on the floor floating in and out of consciousness searching for some gummy worms because you gave yourself too much insulin and tanked your blood sugar. As you can see, context is relative here! Just because the insulin helped a Type II Diabetic doesn't mean that it will help you. And just because lectins decreased tumor growth in mice that already had tumors doesn't mean lectins will help those who don't have tumors.
Lectins activate your immune system and stress your cells
Our immune system is responsible for initiating inflammation to protect us from dangers like viruses and bacteria. One way that it does this is through using "pattern recognition receptors" that respond to "danger signals" in the environment like toxins or harmful molecules from infections. The pattern recognition receptors then help signal the formation of proteins called "inflammasomes." The end result is that the immune system is activated and the troops are ready for combat (3).
Don't let that sciency stuff overwhelm you, let's break it down. Envision a lifeguard at the pool. When the lifeguard sees a child splashing and struggling to swim, the lifeguard blows the whistle to notify everyone that an event is happening. The lifeguard then dives in to save the child. In this example the lifeguard is the "pattern recognition receptor" just sitting there minding their own business. All of a sudden, the lifeguard sees splashing and the struggling child. The struggling child is the "danger signal." In the cell, this could be a toxin or harmful molecule. Now, the lifeguard better do something about it so they blow the whistle. This is like the cell making "inflammasomes," or proteins that will initiate the immune response. Finally, the lifeguard dives into the water to save the child. In the same way, the inflammasomes cause a the immune response, essentially rallying the troops to war against whatever infection, toxin, or harmful substance that caused the problem in the first place.
One inflammasome of particular significance is the NLRC4 inflammasome which is activated by pathogen-associated molecular patterns (PAMPs) like the RNA of viruses, surface proteins of bacteria, or toxins from microbes. The NLRC4 inflammasome is also activated by danger-associated molecular patterns (DAMPs) like too much ATP outside of the cell, monosodium urate, silica, aluminum adjuvant, hyaluronan, and amyloid-beta (3). All that this means is that when something has gone wrong, like you got food poisoning or a virus or came in contact with some environmental toxins, your body can recognize this and fight against it by activating the immune system.
What happens when the NLRP3 inflammasome is activated? It causes the maturation and released of IL-1beta and IL-18 which are pro-inflammatory cytokines that have been proposed to be involved in various inflammatory disease development like gout, diabetes, Alzheimerr's disease, atherosclerosis, and arthritis (3).
We know that things like infection and toxins activate the NLRP3 inflammasome pathway inducing inflammation, but what about plant lectins? What does this have to do with your whole grain bread in the drawer? A study was performed using bone-marrow derived macrophages (BMDMs) (fancy for bone cells) and were investigated whether plant lectins from jack beans, lentils, wheat, soybeans, peanut, gorse, and jackfruit would cause an NLRP3 inflammatory response (through IL-1B and caspase-1 activation) (3). All this means is "did the darn foods that have lectins in them make the immune system angry?"
Jack beans, lentils, wheat, and soybeans all caused an inflammatory reponse. All of these plants are members of the mannose or N-acetylglucosamine-binding lectin family. This is one of the lectin families that we talked about earlier in the blog series. After some more investigation, it was determined that the plant lectins were responsible for activating the NLRP3 inflammasome after comparing cells that contained NLRP3 versus those that did not (3).
Side note: You may be thinking, only a few of the lectins caused a response, so the others must be non-inflammatory. However, it is very plausible that the cells used in the study lack receptors for these lectins (3). We know that there are different receptors throughout the body that allow lectins or molecules to bind to a varying degree depending on the location, like the small intestines (3). Location, location, location.
After they determined that lectins were responsible for activating the NLRP3 inflammasome, their task was then to isolate the origin of where this inflammation cascade begins. After looking at several different potential pathways, they found that lectins were stimulating endoplasmic reticulum (a component inside the of the cell) stress, mitochondrial damage, mitochondrial reactive oxygen species (ROS) production, and NLRP3 inflammasome activation (3). Hang with me. Additionally, the lectins caused a pro-inflammatory cytokine release that led to tissue damage, suggesting the relationship between plant dietary lectins and inflammatory diseases (3).
They decided to look specifically at the lectin found in wheat, because it is so commonly consumed. It has been shown previously that healthy individuals even have antibodies to wheat germ agglutinin (WGA), the wheat lectin. Low and behold, the wheat lectin induced the NLRP3 inflammasome and promoted inflammation (3).
This study concluded that plant lectins can activate the NLRP3 inflammasome, leading to the release of inflammatory cytokines, which may contribute to chronic inflammation and inflammatory diseases brought upon by dietary consumption of plant lectins (3).
It should be noted that the concentrations of lectins used in these studies are higher than what would normally be present because the intestines would naturally help lower the entry of lectins into the circulation (3). When the intestinal barrier is disrupted, it may allow for the entry of more lectins into the circulation. This is actually the case with wheat germ agglutinin (WGA), the wheat lectin, in patients with inflammatory bowel disease (3).
Conclusion
In this blog, we discussed how lectins are able interact and effect our guts, contributing to weakening of the intestinal lining, how lectins can negatively alter the microbiome, and how they can exert effects all throughout the body, even in the muscles and joints. Lectins are also able to shrink tumors in certain scenarios. Amongst the multitude of effects lectins can elicit, primarily lectins are able to activate the immune system and inflammatory pathways through the NLRC4 inflammasome which may point to an association between inflammation caused by dietary consumption of lectins and inflammatory diseases. In Part 3, we will discuss specific diseases and their links to lectins.
1. Aricigil, Selma and Pryme, Ian F. 2015. Potential Beneficial Effects of Dietary Plant Lectins on Health. Natural Products: Research Reviews. 2: 1-27.
2. Vasconcelos, IM and Oliverra, JT. 2004. Antinutritional properties of plant lectins. Toxicon. 44(4): 385-403.
3. Gong, Tao et al. 2017. Plant Lectins Activate the NLRP3 Inflammasome To Promote Inflammatory Disorders. The Journal of Immunology. 198: 2082-2092.
4. Hamid, Rabia and Masood, Akbar. 2009. Dietary Lectins as Disease Causing Toxicants. Pakistan Journal of Nutrition. 8(3): 293-303.
5. Dr. Steven Gundry. 2017. Dr. Gundry Approved Foods (a print-friendly list). Retrieved: May 20, 2019. From: https://gundrymd.com/plant-paradox-shopping-list/
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