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The WHYs behind the Autoimmune Protocol: Nightshades

August 22, 2012 in Featured Posts, Foods in Moderation, The WHYs of the AIP

Tomatoes, potatoes, eggplants, sweet and hot peppers (but not black pepper), and chili-based spices (including paprika) all come from plants which are members of the nightshade family.Nightshades can be problematic for many people due to their lectin, saponin and/or capsaicin content.They tend to be even more problematic for those with autoimmune disease and of all the foods restricted in the autoimmune protocol, are probably the least likely to be successfully reintroduced, especially tomatoes and chilies.

There are over 2000 plant species in the nightshade family, the vast majority of which are inedible and many are highly poisonous (like deadly nightshade and jimsomweed).Tobacco is also a nightshade, and is known to cause heart, lung, and circulatory problems as well as cancer and other health problems (clearly some of this has to do with the other toxins in tobacco products derived from the processing). Of the edible species in the nightshade family, poisoning can actually occur with excessive consumption and it is possible that the low-level toxic properties of the nightshade vegetables contribute to a variety of health issues as they progress over time 1.So, let’s talk about two (okay, three) key compounds in nightshades that make them such a common food sensitivity and a problematic food for those with autoimmune disease.

Nightshades contain lectins.Actually, all plants (and even animals) contain some lectins, a class of sugar-binding proteins with many biological roles, including protecting plants (especially the seeds of the plant) against predation.Not all lectins are problematic (I have an entire post in the works explaining why the lectins in wheat can be such an issue but the lectins in blueberries aren’t).The lectins which we avoid in the paleo diet are the ones with the ability to increase intestinal permeability (see this post on how lectins do this).These are lectins which resist digestion (typically due to high proline content), are relatively heat-stable (so there are still sufficient quantities to cause an issue after cooking), and have the ability to strongly interact with proteins in the membrane of the cells that line the intestine (and some can even bind to receptors in those membranes and be transported intact across the intestinal barrier).There is huge variability the effect of different dietary lectins, from proinflammatory and promoting a leaky gut on one end of the spectrum to completely harmless and even potentially therapeutic on the other.Until a systematic analysis is performed of all plant lectins and their physiological effects, the foods advocated and restricted on a paleo diet really only represents our best guess based on what is known so far.So, what do we know about nightshade lectins?Tomato lectin is known to enter the blood stream relatively quickly in humans, which suggests that tomato lectin can contribute to the development of a leaky gut 2.This information has led me to recommend that tomatoes should be eaten in moderation for most people.People with autoimmune disease are more likely have a leaky gut and have more challenges to healing a leaky gut once it has developed.For these sensitive individuals, tomato lectin should be avoided.

Nightshades contain saponins.The flowers, fruit, and foliage of the nightshade family contain a type of saponin called glycoalkaloids (e.g.the α-solanine and α-chaconine in potato, α-solanine in eggplant, and the α-tomatine in tomato) and contain steroidal drugs (e.g. the stimulating capsaicin in peppers, the tranquilizing nicotine in tobacco)3.I explained in detail how saponins can contribute to a leaky gut in this post (also see reference 4).Very importantly for those with autoimmune conditions, saponins, such as α-tomatine, have adjuvant activity.An adjuvant is a chemical that stimulates and exaggerates an immune response.The glycoalkaloid α-tomatine is such a potent adjuvant that it is used in vaccines to ensure that the recipient develops immunity against the virus they are being inoculated against.This is critical in the discussion of autoimmune disease because dietary saponins are believed to rev up the immune response to proteins leaking out of the gut 5.When antibodies are formed against proteins (like gluten) that have amino acid sequences that look very similar to sequences of other normal proteins (like transglutaminase) in the human body, the chances of developing an antibody against one’s self increases.When this happens, the immune system attacks normal healthy proteins/cells in your own body and this is the development of autoimmunity.Beyond these actions of saponins, glycoalkaloids inhibit a key enzyme, acetyl cholinesterase, which is required for nerve impulse conduction.There is also evidence that diets high in potatoes, in particular, result in increased markers of inflammation (this could also be due to the carbohydrate load that potatoes provide and not an effect of the glycoalkaloids themselves).Glycoalkaloid poisoning can occur with excessive consumption of nightshade vegetables, and many researchers have hypothesized that the low level toxic exposure from more moderate consumption of nightshades can contribute to a variety of health conditions 1.Another problematic substance is capsaicin, a steroidal stimulant found in chili peppers (it is one of the substances in peppers that give them heat).While a variety of health benefits have been attributed to capsaicin, it is also a potent irritant to a variety of tissues, including skin, eyes and mucous membranes.Very importantly, there is evidence that capsaicin can increase intestinal permeability 6.

Of all the foods restricted on the paleo diet autoimmune protocol, nightshades are the least likely to be reintroduced successfully.In fact, many people are sensitive to nightshades independent of illness or autoimmune issues.In my own experiences, two meals (on two consecutive days) containing a small amount of tomatoes nearly two months ago resulted in a massive lichen planus flare (it was also timed with some stressful life events, which I’m sure didn’t help).Two meals of tomatoes set me back months in my recovery.I am only in the last week or two starting to see some improvement to the new lesions that formed nearly overnight.While frustrating, I try and focus on the positive:I now know that tomatoes are not good for me.And avoiding them is worth it.

1 Childers N.F., and Margoles M.S. “An Apparent Relation of Nightshades (Solanaceae) to Arthritis” Journal of Neurological and Orthopedic Medical Surgery (1993) 12:227-231

2 Carreno-Gómez B et al. “Studies on the uptake of tomato lectin nanoparticles in everted gut sacs.” Int J Pharm. 1999 Jun 10;183(1):7-11.

3 Gee JM, et al “Effects of saponins and glycoalkaloids on the permeability and viability of mammalian intestinal cells and on the integrity of tissue preparations in vitro.” Toxicol In Vitro. 1996 Apr;10(2):117-28.

4 Francis G et al.“The biological action of saponins in animal systems: a review.” Br J Nutr. 2002 Dec;88(6):587-605.

5http://video.google.com/videoplay?docid=-8901290975296745403

6 Jensen-Jarolim E et al. “Hot spices influence permeability of human intestinal epithelial monolayers.” J Nutr. 1998 Mar;128(3):577-81.

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How Do Grains, Legumes and Dairy Cause a Leaky Gut? Part 1: Lectins

March 22, 2012 in Gut Health, The WHYs Behind Paleo

(Created as a guest post for The Paleo Parents)

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?  There are several ways in which these foods create holes in the gut lining.  The best understood is the damage caused by lectins.

Grains and legumes contain lectins.  Lectins are a class of proteins found in many types of seeds (like wheat, oats, barley, rice, peanuts, soy, etc.) that are part of the plant’s natural defense mechanism.  A digested seed is not one that can grow a new plant.  To defend itself, the seed from these plants either deter predators (like us) from eating them by making us sick or resist digestion completely or both.  The grains and legumes that have become a part of the human diet since the Agricultural Revolution 10,000 years ago aren’t toxic enough to make most of us severely ill immediately after eating them (otherwise humans never would have domesticated them!).  Instead, their effects are more subtle and can take years to manifest as a life-threatening disease.  You may be wondering why other seeds (like the ones in berries or kiwi or bananas) are okay to eat.  These come from plants with a friendlier defense strategy:  we get to eat the delicious fruit encasing the seeds and then the seeds, which pass through our digestive tracts intact, get to be planted in rich manure.  How do you know the difference between a harmless seed and one that contains damaging lectins?  Here’s the rule:  if you can eat it raw, then it’s okay to eat.  If you have to cook it, it has damaging lectins. 

Lectins are not broken down in the normal digestive process, both because the structure of these proteins are not compatible with our bodies’ digestive enzymes but also because the foods that contain these lectins also contain protease inhibitors (compounds that stop the enzymes from breaking down proteins; more on these in Part 2).  Lectins, which remain largely intact throughout the digestive tract, can damage the gut lining in several ways.  First, lectins trick the enterocytes (the cells that line the gut) into thinking they are simple sugars.  The enterocytes “willingly” transport the lectins from the “inside-the-gut” side of the cell to the “outside-the-gut” side of the cell.  While in transit, the lectins may cause changes inside the enterocyte that either kill the cell or render it ineffective at its job, which leads to more pathogens leaking out of the gut.  Once outside the gut, these lectins activate the resident immune cells of the gut which respond by producing inflammatory cytokines (the chemical messengers that circulate in the blood and tell white blood cells to attack) and antibodies against these foreign proteins.  Because at least part of this response is not specific to the lectin itself, the enterocytes (being the closest innocent bystanders) can be targeted and killed by the body’s immune cells, leading to the microscopic holes that create a leaky gut.

 Gluten is both the best known example of a lectin, and also the most damaging.  In many individuals (like those with diagnosed gluten sensitivity and celiac disease), gluten can weaken the connections between enterocytes, essentially creating a space in between the cells through which gut contents can leak through, adding yet another way that this particular lectin can cause a leaky gut.  Once gluten has passed through the gut lining, it stimulates the resident immune cells of the gut to start producing antibodies.  Gluten is especially insidious because parts of this protein closely resemble many proteins in the human body, so there’s a high likelihood that some of the antibodies produced to target it will also target human cells.  One extremely commonly formed antibody is one against our enzyme transglutaminase.  Transglutaminase is an essential enzyme in every cell of the body, which makes important modifications to proteins as they are produced inside the cell.  It also stimulates wound healing, but if antibodies have formed against it, then when it is secreted by damaged cells in inflamed areas of the small intestine (or any other damaged tissue in the body), rather than helping to heal the surrounding tissue, it instead turns it into a target of the immune system.  This is yet another way in which gluten can cause a leaky gut.  Importantly, when antibodies against transglutaminase form, every cell and organ in the body becomes a potential target.  Because an exaggerated sensitivity to gluten is the cause of Celiac Disease, which affects at least 1 in 133 people, its effects on the gut have been the most studied.  Scientists still don’t know which of the many ways that gluten can harm the body apply to all lectins and which are specific to gluten.

Gluten sensitivity has already been linked to dozens of autoimmune diseases.  Even in individuals who do not have celiac disease or gluten sensitivity, it can take up to six months for the gut to fully heal after a single gluten exposure.  While other lectins may not be quite as damaging as gluten, scientists continue to discover new ways in which foods that contain lectins can contribute to a leaky gut, inflammation and autoimmune diseases.

 

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What Is A Leaky Gut? (And How Can It Cause So Many Health Issues?)

March 15, 2012 in Featured Posts, Gut Health, Paleo Philosophy, The WHYs Behind Paleo

(Created as a guest post for The Paleo Parents)

One of the fundamental principles of paleolithic nutrition is avoiding foods that damage the lining of the gut.  Essentially, the gut is just a long, wrinkly tube.  Inside this tube, food is digested by enzymes and friendly resident bacteria, breaking down the components of our food to their simplest forms: proteins are broken down into amino acids; carbohydrates are broken down into monosaccharaides; and, fats are broken down into fatty acids.  What can’t be digested by our bodies is excreted as waste.  Amazingly, a single layer of highly specialized cells (called enterocytes) is all that separates the inside of the tube from the outside.  These enterocytes have two very specific jobs:  1) transport the digested nutrients from the “inside-the-gut” side of the cell to the “outside-the-gut” side of the cell; and 2) keep everything else on the inside of the tube.  Immediately outside this tube are two important parts of the digestive system: 1) the resident immune cells of the gut whose job it is to protect against pathogens which might accidentally find their way through the enterocytes; and 2) a network of blood vessels and lymphatic vessels that carry the digested nutrients from our food to the tissues in our body that need them (amino acids and monosaccharaides are transported through the blood while fatty acids are transported through the lymphatic system). 

A “leaky gut” occurs when either the enterocytes are damaged or the proteins that form the tight bond between these cells and hold them together as a solid layer are damaged (or altered).  When this happens, it creates microscopic holes through which some of the contents of the gut can leak out into the blood stream or lymphatic system.  What leaks out isn’t big chunks of food.  Instead, it’s a combination of many different pathogens: incompletely digested proteins, bacteria or bacterial fragments from those friendly bacteria that are supposed to stay inside your gut, or a variety of toxic substances or waste products that would normally be excreted.  When these pathogens leak out, the resident immune cells of the gut recognize them as foreign invaders and mount a response against them (when large quantities of pathogens leak out, other parts of the body, especially the liver, also contribute to the response).  Exactly what leaks out, and how much, determines the precise nature of this immune response. 

 Some pathogenic substances (like bacterial fragments and toxins) cause generalized inflammation by triggering the release of chemicals called inflammatory cytokines (the chemical messengers that circulate in the blood and tell white blood cells to attack).  This type of inflammation has no target so any cell in the body can be an innocent victim.  It is the liver’s job to both control this type of inflammation and to filter out the toxins that may be triggering it.  When the liver is overworked, the toxins build in the body and the inflammation spreads.  This type of inflammation can be a major contributor to health issues ranging from psoriasis and asthma to ADHD and depression.

Other substances (like incompletely digested proteins) cause specific inflammation, which can take the form of an allergy or an auto-immune disease.  An allergy is caused by immune cells creating IgE-type antibodies targeting a part of a protein that is specific to the food it originated from (like an antibody targeting the casein in milk resulting in a milk allergy).  A very similar type of immune response is caused by immune cells creating IgA-, IgM- or IgG-type antibodies targeting a part of a protein that is specific to the food it originated from.  This type of immune response is technically considered a food sensitivity (and not an allergy), and can cause both allergy-type symptoms and symptoms that you might not normally attribute to an allergy, such as: pain, fatigue, and eczema.  It is also the formation of these types of antibodies that can cause auto-immune diseases.  Antibodies target only a short sequence of amino acids, and not all of the amino acids that form an individual protein.  In the case of food allergies and sensitivities, this short sequence of amino acids is still specific to the food it originated from.  But, sometimes the antibodies that form in response to “leaked-out” proteins target a sequence of amino acids that isn’t unique to that protein, but instead is a sequence of amino acids also found in many other normal proteins in the human body.  When this happens, the body attacks itself thinking its own cells are foreign invaders.  For example, an antibody could form against a sequence of amino acids that is found in the insulin-secreting beta cells of the pancreas.  When the body attacks those cells, it causes Type I Diabetes.  An enormous range of autoimmune diseases can be caused in this way, from lupus to celiac disease to Graves’ disease (many of which include genetic susceptibility as confounding factor). 

It is important to know that, for some individuals, a leaky gut can develop slowly over years or decades.  Stress, sleep-deprivation and/or some infections can make matters worse very quickly (and unpredictably).  Once you have a leaky gut, it is only a matter of time before related health conditions begin to crop up.  Depending on the extent of the damage to the gut lining, the exact substances that leak out, and your specific genetics, the inflammation and immune reactions caused by having a leaky gut can add up to any of a huge variety of different health conditions, many of which can be life-threatening.  This is why the gut-friendly, anti-inflammatory paleo diet is known to address so many different health issues:  if your gut is healthy, then so are you.

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Why Grains Are Bad–Part 1

November 28, 2011 in The WHYs Behind Paleo

Before committing to paleolithic nutrition, I read a whole lot about it.  I read scientific journal articles, books, and some great blogs.  As I delved deeper and deeper into the reasons why paleolithic nutrition is so remarkably healthful, I found myself learning the detailed physiology and biochemistry behind many aspects of this diet.  Although you don’t need to go into as much detail as I have, much of this information is relevant to you and will help inform your choices as you continue to experiment with a paleolithic lifestyle.  I will try to distill the most salient points for you.  First, up:  Why are grains bad for you?

Grains have a particularly high concentration of lectins, a class of proteins (of which gluten is one) that are present in all plant life to some degree.  Lectins are part of a plant’s natural protective mechanism (from predators and pests) and are usually concentrated in the seeds of the plant (which is why grains and legumes have so much).  So what happens when we eat these proteins?  Similar to what occurs in individuals with celiac disease (basically, a super exaggerated form of the sensitivity we all have to gluten and other lectins), lectins damage and kill the cells that line your intestines.  This causes little holes in your intestines; so, things that are not supposed to get into your blood stream leak out.  This “leak” is made worse by the fact that lectins bind to sugars and other molecules in the gut and then “help” these random other molecule leak into the blood stream.  There are many things in your gut (like E. coli) that are supposed to stay there; and, when they leak into the blood stream, they cause a low level of systemic inflammation.  This can set the stage for many health conditions, including cardiovascular and auto-immune diseases.

There are many lectins and some are more harmful than others.  Gluten is by far the most damaging lectin, but non-gluten containing grains still contain lectins.  And while some of the other “blacklisted” foods are okay for occasional consumption (like dairy, beans and rice), I suggest a lifelong dedication to gluten avoidance.  It can take up to six months for your gut to fully heal after a single gluten exposure.  Dose is another important factor here.  The vegetables and fruits that our prehistoric ancestors ate in large quantities are generally very low in lectins.  Grains (especially wheat) and legumes (especially soy) are very high in lectins.  And, if damaging your gut lining and causing systemic inflammation isn’t enough, lectins are also anti-nutrients, which means that they stop you from absorbing many of the vitamins and minerals in your food (like calcium!).  

On top of all this, grains are highly acidic foods (at the level of your kidneys, not your stomach).  Another aspect of paleolithic nutrition is to balance your intake of acidic and alkaline foods (I will expound on acid-base balance in a future post).  Generally, meat, eggs and fish are acidic and we balance this with lots of vegetables and some fruit, which are alkaline.  When grains are in our diet, it is nearly impossible to eat enough alkaline foods to balance this out and the result is strain on the kidneys, liver and pancreas. 

If all this just whets your appetite for more detailed information, I suggest starting with Dr. Loren Cordain’s website http://thepaleodiet.com/ 

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