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How Long Does it Take the Gut to Repair after Gluten Exposure?

September 27, 2012 in FAQ, FAQ, Featured Posts, Gut Health

This is a very relevant question for those who are just embarking on their gluten-free journey.  But, it’s also extremely important for anyone who has been following a paleo/primal/gluten-free diet for a while, but has been inadvertently exposed to gluten.  It sometimes feels as though the longer we avoid gluten, the more sick we feel after accidentally eating some.  This is in large part because the body stops protecting itself from gluten (for example, there may be less mucus in the gut) so when we do consume some, we are defenseless.  It may also be because we forget how we used to feel and are so used to feeling so much healthier.  Whether you are new to paleo or have been eating this way for a while, a common question is:  how long does it take the gut to heal after gluten exposure? 

I have talked about the irritation, inflammation and damage to the lining of the small intestine that can be caused gluten (I promise I will go back and add references to this post soon) and I have mentioned that it can take up to 6 months for the body to fully heal after a single gluten exposure.  After delving into the research more thoroughly, I have discovered that this statement is simultaneously a gross understatement and an overstatement.  Just like the extent of damage that gluten causes varies from individual to individual (see this post for a little bit more on variability in tolerance), so does the length of time it takes to recover.  And it’s not as simple as the more damage you have, the longer it takes to recover.  There are factors that control how sensitive you are (genetics, overall health, diet, stress, nutritional-deficiencies, gut microflora) and there are factors that affect how quickly you heal (okay, it’s the same list of factors, but it’s more complicated than A+B=C).

The cells that line the gut, called enterocytes or gut epithelial cells are organized into hills and valleys (to help maximize the surface area of the gut), forming finger-like columns of cells called villi separated by valleys called crypts.  The enterocytes are constantly regenerating themselves (a pool or resident stem cells supplies the new enterocytes).  As the cells age, they migrate higher up the villi and are eventually shed into the gut to be redigested (yes, we are constantly cannibalizing ourselves).  This is called the “turnover” of the gut epithelium.  In the normal healthy gut, the enterocytes migrate to the top of the villi in in 1-4 days, meaning that all of the villi cells are replaced with new cells every 3-5 days (this gets slower as we age) 1,2,3.  The cells that migrate toward the bottom of the crypts have a longer lifespan of 2-3 weeks.  What does this mean?  A healthy person has an entirely new intestinal lining every 2-3 weeks.

Repairing the intestine following injury (whether that is caused by ingested toxins, infection, or some other injury) is a more involved and complex process that is tightly regulated and controlled by the body (for a detailed understanding of this process, see reference 4).  The healing time varies depending on the extent of injury and studies trying to understand the role of the resident stem cells of the gut show that repair of the crypt and villi structure of the intestinal wall after injury can take anywhere from 2 to 12 weeks (depending on whether the stem cells themselves are injured) in the absence of confounding factors 4,5.

What does this mean?  For healthy individuals without celiac disease or gluten sensitivity (where their bodies are producing antibodies against gluten), the damage to individual cells and the junctions between them that can be caused by gluten is relatively fast to heal, anywhere from a few days to 3 weeks.  For these healthy individuals, most of this time is likely asymptomatic.  Many people report symptoms that only last from a couple of hours to a couple of days after gluten exposure.  This also means that healthy individuals should be able to heal their guts completely after following a 30-day paleo challenge such as a Whole30.

For those with confounding factors, healing is slower. Confounding factors are numerous and include gluten sensitivity (where the body is producing antibodies against gluten which increases inflammation and slows healing), celiac disease (an autoimmune condition), uncontrolled inflammation in the gut (which could be caused by food allergies, food sensitivities or diseases such as Inflammatory Bowel Disease), nutritional deficiencies (which can be caused by having a very inflamed and damaged gut, but slows healing because not all of the raw materials needed to repair are available), gut dysbiosis (the wrong type, amount and/or location of microorganisms in the gut), infections, stress, body-wide inflammation, and chronically elevated insulin.

How much do these confounding factors slow healing?  The extreme end of the spectrum is those with Celiac Disease, an autoimmune condition triggered by gluten exposure.  One hallmark of Celiac Disease is a shortening or blunting of the intestinal villi which is observed by performing a biopsy of the small intestine (they are typically 3-5 times longer in healthy individuals than those with Celiac Disease).  For those with celiac disease, one study showed that only 66% of patients had a normal intestinal biopsy after 5 years on a gluten-free diet 6.  This means that even after 5 years, 34% of Celiac Disease sufferers had not recovered.  There are no good similar studies evaluating intestinal repair in people with non-celiac gluten-sensitivity, but medical professionals who specialize in treating gluten-sensitivity report time frames of approximately 1½-2 years 7.

It’s probably worth mentioning here that current reports suggest that both Celiac Disease and gluten-sensitivity are ridiculously underdiagnosed.  It is estimated that 1 in every 100 Americans suffer from Celiac Disease but only 5% are ever diagnosed 8.  This means that there is something like 2.5-3 million Americans with celiac disease that have no idea that they have it (when you extrapolate this statistic globally, it’s even scarier!).  Gluten intolerance is estimated to affect 15-20% of the population 9.  The take home message here?  Even if you have never been diagnosed with celiac disease or gluten intolerance, you may have one of these conditions which could be contributing to slowed intestinal repair after switching to a paleo diet or after accidental gluten exposure.

How much gluten can cause a problem?  This is highly individual.  For those with Celiac disease (whether confirmed or undiagnosed), even a minute amount of gluten can cause significant damage to the small intestine in the majority of sufferers 10.  Interestingly, a not unsubstantial percentage of these people (22%) will have significant damage to their small intestine but not suffer any gastrointestinal symptoms.  For healthy individuals, the threshold amount to suffer symptoms is highly variable.  Unfortunately, you don’t know until you test it on yourself.

So, how long does it take the gut to repair after gluten exposure?  Once again, like so many topics I cover on this blog, the answer is “it depends”.  For healthy individuals, healing likely takes only a couple of weeks.  For those with celiac disease (and perhaps autoimmune diseases in general), fully healing the lining of the small intestine may take years.  The rest of us can be anywhere in between.

1 Creamer B et al. “The turnover and shedding of epithelial cells–Part I The turnover in the gastro-intestinal tract”. Gut 1961 2: 110-116

2 Lipkin M et al. “Cell Proliferation Kinetics In The Gastrointestinal Tract Of Man. I. Cell Renewal In Colon And Rectum” J Clin Invest. 1963 June; 42(6): 767–776.

3 Godlewski MM et al “Into the Unknown–The Death Pathways in the Neonatal Gut Epithelium”  Current Pediatric Reviews. 2011. 7(4):337-345

4 Blikslager AT et al. “Restoration of Barrier Function in Injured Intestinal Mucosa” Physiol Rev 87:545-564, 2007.

5 Booth C and Potten CS “Gut instincts: thoughts on intestinal epithelial stem cells” J Clin Invest. 2000;105(11):1493–1499.

6 Rubio-Tapia A “Mucosal recovery and mortality in adults with celiac disease after treatment with a gluten-free diet.” Am J Gastroenterol. 2010 Jun;105(6):1412-20.

7 http://glutendoctors.blogspot.com/2010/04/healing-time-after-removing-gluten.html

8 Lohi S et al. “Increasing prevalence of coeliac disease over time.” Aliment Pharmacol Ther. 2007 Nov 1;26(9):1217-25.

9 http://www.gastroendonews.com/ViewArticle.aspx?d=In%2Bthe%2BNews&d_id=187&i=October%2B2010&i_id=672&a_id=16015

10 Lähdeaho ML et al. “Small- bowel mucosal changes and antibody responses after low- and moderate-dose gluten challenge in celiac disease.” BMC Gastroenterol. 2011 Nov 24;11:129.

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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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