Tag Archives: intestinal permeability

Autoimmune Disease: Drawing the Lines of Defense

The case for the Paleo Diet continues to grow as the modern diet leads to an epidemic of modern health problems. Over the last three decades, epidemiological data provide strong evidence of a steady rise in autoimmune disease, where the body fails to recognize the difference between its own cells and foreign invaders.1

We have to wonder why more people than ever are afflicted with the following conditions: multiple sclerosis, type 1 diabetes, inflammatory bowel diseases (mainly Crohn’s disease), systemic lupus erythematosus, primary biliary cirrhosis, myasthenia gravis, autoimmune thyroiditis, hepatitis and rheumatic diseases, bullous pemphigoid, and celiac disease.2 Indicators, based on the geoepidemiological distribution of autoimmune disease, point to an environmental factor.3 Although causality has not been proven, scientists hypothesize the answer lies in the relationship between the prevalence of industrialized foods and the environmental impact they have on our guts, specifically in the intercellular tight junctions of the epithelial lining.4


The idea of “leaky gut syndrome” has circulated for decades, but many health practitioners still don’t believe it actually exists, despite over thousands of published articles relating to intestinal permeability. Historically, the functions of the gastrointestinal tract have been believed to be limited to the digestion and absorption of nutrients and electrolytes, and to regulate water homeostasis.5 An additional function has been overlooked: to regulate macromolecules through the intestinal epithelial barrier mechanism, within tight intercellular junctions, to control the equilibrium between tolerance and immunity to non-self antigens.6

It shouldn’t seem that far fetched to believe molecules can pass from inside the intestines into the bloodstream, as only a single layer of epithelial cells separates the lumen from internal milieu.7 Our bodies even make modulating proteins, such as Zonulin, in response to certain bacteria and gluten8 that has been proven to open the intercellular tight junctions responsible for maintaining the integrity of the intestinal lining. When the intercellular junctions aren’t well sealed it allows for the passage of macromolecules into the bloodstream and triggers an immune response leading to intestinal and extraintestinal autoimmune disease as well as inflammatory disorders. 9


We are becoming more dependent on heavily processed food sources, 10 and evolving further away from what we are genetically designed to eat.11 There are seven food additives: sugar, salt, emulsifiers, organic solvents, gluten, microbial transglutaminase, and nanoparticles, increasingly added to processed food and are finding their way in record numbers onto grocery store shelves.  These industrial food additives are believed to dissolve the epithelial barrier function, leading to increased intestinal permeability and activating the autoimmune cascade. The rate usage of the food additives has also matched the increased incidence and prevalence of autoimmune diseases during the last few decades. 12


The Paleo Diet, clearly more than the meat lover’s way to keep weight off, might be the only solution to avoiding the onslaught of food additives and their effects on our health. Most of these additives can be completely avoided when following the Paleo Diet.13  Further, Paleo food provides important nutrients, often at the therapeutic levels, as well as high levels of Omega 3 fatty acids, all necessary to maintain and repair the intestinal tract.14,15

The current research has barely scratched the surface for fully understanding the effects of food additives exposure on intestinal permeability and autoimmune disease. There is enough evidence for those with autoimmune symptoms or a genetic predisposition to minimize the exposure to all processed foods. The best line of defense for those at risk for autoimmune disease may be following the Paleo diet.

Eat for gut health. Eat Paleo.



[1] Selmi, Carlo. “The worldwide gradient of autoimmune conditions.” Autoimmunity reviews 9.5 (2010): A247-A250.

[2] Okada, H., et al. “The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update.” Clinical & Experimental Immunology 160.1 (2010): 1-9.

[3] Parks, Christine G., et al. “Expert Panel Workshop Consensus Statement on the Role of the Environment in the Development of Autoimmune Disease.”International journal of molecular sciences 15.8 (2014): 14269-14297.

[4] Hollander, Daniel. “Intestinal permeability, leaky gut, and intestinal disorders.”Current gastroenterology reports 1.5 (1999): 410-416.

[5] Diamond, Jared. “Evolutionary design of intestinal nutrient absorption: enough but not too much.” Physiology 6.2 (1991): 92-96.

[6] Fasano, Alessio. “Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer.” Physiological reviews 91.1 (2011): 151-175.

[7] Shanahan, Fergus. “V. Mechanisms of immunologic sensation of intestinal contents.” American Journal of Physiology-Gastrointestinal and Liver Physiology 278.2 (2000): G191-G196.

[8] Fasano, Alessio, et al. “Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease.” The Lancet 355.9214 (2000): 1518-1519.

[9] Fasano, Alessio. “Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer.” Physiological reviews 91.1 (2011): 151-175.

[10] Monteiro, Carlos Augusto, et al. “Increasing consumption of ultra-processed foods and likely impact on human health: evidence from Brazil.” Public health nutrition 14.01 (2011): 5-13.

[11] O’Keefe, James H., and Loren Cordain. “Cardiovascular disease resulting from a diet and lifestyle at odds with our Paleolithic genome: how to become a 21st-century hunter-gatherer.” Mayo Clinic Proceedings. Vol. 79. No. 1. Elsevier, 2004.

[12] A. Vojdani. “A potential link between environmental triggers and autoimmunity.”Autoimmune Diseases 2014.

[13] Lerner, Aaron, and Torsten Matthias. “Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease.” Autoimmunity reviews 14.6 (2015): 479-489.

[14] Li, Yousheng, et al. “Oral glutamine ameliorates chemotherapy-induced changes of intestinal permeability and does not interfere with the antitumor effect of chemotherapy in patients with breast cancer: a prospective randomized trial.” Tumori 92.5 (2006): 396.

[15] Simopoulos, Artemis P. “Omega-3 fatty acids in inflammation and autoimmune diseases.” Journal of the American College of Nutrition 21.6 (2002): 495-505.

Wheat: Opening the Barrier to Poor Gut Health | The Paleo Diet

Did you miss The Wheat Series Part 1: Wheat and the Immune System? Read it HERE.

It was a comment I’ve heard too many times. I was watching tennis with a friend who knew me as a cyclist, not as someone who researches nutrition. The commentators were discussing world No. 1 ranked tennis player Novak Djokovic’s newfound success since going on a gluten-free diet. My friend got noticeably irritated and finally blurted “I’m tired of this gluten-free fad! There’s not a scrap of evidence it makes a difference unless you have celiac disease.” As much as I wanted to, I chose not to respond, but thought to myself, “The bottom drawer of my research cabinet is awfully heavy for not having a scrap of anything in it.

This viewpoint that the health benefits of a gluten-free diet are more fad than science is a pervasive one. But what has led so many, including doctors and scientists, to say the research doesn’t exist?

Certainly the science is extensive for celiac disease where the role of gluten is indisputable. Gliadin, a protein in gluten, binds to a molecule in our bodies called tissue transglutaminase. In celiac patients it’s this new, combined molecule that sets off the inappropriate immune response.1, 2, 3

Without gluten, celiac disease couldn’t exist.

Recently other gluten-related disorders like gluten allergies and gluten ataxia have been identified.4, 5  But admittedly, these conditions affect only about 2% – 10% of the population. Outside of these diseases my friend has a point; research showing gluten having a direct pathogenic role, as it does in celiac disease, isn’t there.

But perhaps this is where the disconnect exists.

While a great deal of published research is showing that wheat and gluten can promote a large range of chronic conditions4, 6, 7, 8, gluten’s role is not so direct. Instead, gluten may breakdown the body’s natural defenses, setting up an inflammatory environment. This environment is highly conducive to a variety of chronic diseases in those of us who are unfortunate enough to have the wrong genetics.9, 10 Gluten sets the stage.

Looking at gluten this way, the bottom drawer of my cabinet suddenly gets a lot heavier. I hope to share a few posts on the ways in which wheat can set the stage for unwanted inflammation and disease. Let’s start with a surprising function that came out of celiac research.


One of the most important roles of our gut, beside processing nutrients and hosting a rich microflora, is to provide a barrier blocking the entry of unwanted particles. Fortunately tight junctions (TJ) between the epithelial cells of our intestine carefully regulate entry of all but a few small molecules and essential nutrients.

Over the last 20 years, Dr. Alessio Fasano at the University of Maryland has researched breakdowns in this barrier, ultimately identifying a molecule produced in our guts called zonulin.14 Zonulin has the unique ability to dissolve the occludins, claudins, zonular occluden, and ZO-1 proteins that make up the structural cytoskeletons of our tight junctions.6, 15, 16, 17, 18

Put simply, zonulin can breakdown our barrier and increase intestinal permeability. An effect that’s often referred to around the web as “leaky gut.” It is rapid, reproducible, and fortunately, reversible.16

To date, two powerful triggers for zonulin have been identified.

The first trigger is exposure to bacteria in the intestine. Interestingly, infection by both pathogenic and “healthy” bacteria can have a triggering effect. However, it’s amplified with the “bad guys” as we can see from the chart below on the left.19

Wheat: Opening the Barrier to Poor Gut Health | The Paleo Diet
Wheat: Opening the Barrier to Poor Gut Health | The Paleo Diet
It is believed that zonulin evolved to protect us against bacterial colonization in the gut.6, 17, 19 When there’s an overload of bacteria in an otherwise healthy digestive tract, zonulin opens up the tight junctions allowing fluid to rush into the gut and flush out microorganisms.

The second powerful activator of the zonulin system is gliadin.

Gliadin fragments bind to the CXCR3 receptor on the epithelial cells of the gut. Then through a MyD88 signaling process, these epithelial cells release zonulin and cause an opening of tight junctions.6, 15, 17, 20, 21

It’s a complex process, but all you need to know is that gliadin can do this from inside the gut. It doesn’t have to get into our systems. More importantly, gluten is inappropriately high jacking a powerful defense mechanism designed to handle bacterial contamination.17

In the above right figure, we can see from Dr. Fasano’s research how gliadin’s ability to stimulate zonulin can be as powerful as bacterial triggers.6

Finally, while gliadin’s effect is much stronger in individuals with celiac disease, gliadin does not discriminate, and it happens in all peoples guts.6, 17


With a healthy gut barrier, large molecules are degraded before entering the body and are well tolerated by the immune system.12 Intestinal permeability caused by gluten and bacteria allows these large molecules to get into circulation and act as antigens (activators) for the immune system.15, 17, 22

This becomes a real concern considering gluten is normally consumed with a meal. Its rapid effect on gut permeability happens at the same time that the gut is being hit by a large number of foreign antigens.


Wheat: Opening the Barrier to Poor Gut Health | The Paleo Diet

Dr. Fasano and his group proposed that once these antigens gain entry, they can be misinterpreted by the immune system in genetically susceptible individuals. The result is an inappropriate immune response that ultimately leads to chronic illness.6, 12, 15, 23, 24, 25In a healthy gut, these antigens would never gain access to the immune system.

The image above provides a nice representation of how gluten can open tight junctions and lead to diseases such as celiac disease and type 1 diabetes.6


So, what does this all amount to? Intestinal permeability caused by either bacterial overgrowth or gluten (both of which are heavily influenced by diet) may be a key early step to set the body up for many chronic illness.

But is there any research? Fortunately, this is where I have to start using more drawers in my research cabinet.

Higher zonulin levels and intestinal permeability have been associated with and often precede many autoimmune conditions including type 1 diabetes,16, 30, 3132, 33celiac disease,17, 28, 34 multiple sclerosis,35, 36 rheumatoid arthritis,37, 38ankylosing spondylitis,37, 39 and Crohn’s disease.40, 41Eating wheat has been directly linked to diabetes.31, 42, 43, 44

A popular theory of autoimmune disease – called the molecular mimicry theory – proposed that autoimmune disease is initiated by viruses that mimic our bodies.26, 27 Dr. Fasano and his group suggested instead that dietary antigens passing through a leaky gut may be the environmental trigger. To test their theory, they were able to use a zonulin inhibitor to reduce the severity of celiac disease symptoms in humans 28 and the incidence of type 1 diabetes in mice.29

Intestinal permeability isn’t just associated with autoimmune conditions. Permeability may affect asthmatics by increasing their exposure to allergens.45, 46 Elevated zonulin levels have been found in irritable bowel disease 47, 48 and cancer.4950Even schizophrenia has recently been linked to gluten consumption and zonulin levels.51, 52

But a final question remains.

In a world where most people reach for a bagel and toast as soon as they get out of bed, intestinal permeability may just be a part of western life that gets an unfair rap by association. In other words, is it too easy to just link permeability with chronic disease? Does it really play a role?

In his 2011 review of zonulin and disease, Dr. Fasano addressed this question pointing out a number of studies where symptoms and incidence rates were reduced when gluten was removed from the diet or when zonulin’s effects were blocked.6

Wheat, a no-no for any good Paleo dieter, was clearly opening doors.

Read The Wheat Series Part 3: Setting Off the Bacterial Alarm Bells – With or Without the Bacteria HERE


[1]Dieterich, W., et al., Identification of tissue transglutaminase as the autoantigen of celiac disease. Nature Medicine, 1997. 3(7): p. 797-801.

[2]Molberg, O., et al., Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nature Medicine, 1998. 4(6): p. 713-717.

[3]Plenge, R.M., Unlocking the pathogenesis of celiac disease. Nat Genet, 2010. 42(4): p. 281-2.

[4]Sapone, A., et al., Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med, 2012. 10: p. 13.

[5]Hadjivassiliou, M., et al., Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics. Brain, 2003. 126(Pt 3): p. 685-91.

[6]Fasano, A., Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev, 2011. 91(1): p. 151-75.

[7]Biesiekierski, J.R., et al., Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol, 2011. 106(3): p. 508-14; quiz 515.

[8]Bernardo, D., et al., Is gliadin really safe for non-coeliac individuals? Production of interleukin 15 in biopsy culture from non-coeliac individuals challenged with gliadin peptides. Gut, 2007. 56(6): p. 889-890.

[9]Palova-Jelinkova, L., et al., Gliadin fragments induce phenotypic and functional maturation of human dendritic cells. J Immunol, 2005. 175(10): p. 7038-45.

[10]De Palma, G., et al., Effects of a gluten-free diet on gut microbiota and immune function in healthy adult human subjects. Br J Nutr, 2009. 102(8): p. 1154-60.

[11]Yu, Q.H. and Q. Yang, Diversity of tight junctions (TJs) between gastrointestinal epithelial cells and their function in maintaining the mucosal barrier. Cell Biol Int, 2009. 33(1): p. 78-82.

[12]Fasano, A., Physiological, Pathological, and Therapeutic Implications of Zonulin-Mediated Intestinal Barrier Modulation Living Life on the Edge of the Wall. American Journal of Pathology, 2008. 173(5): p. 1243-1252.

[13]Shen, L. and J.R. Turner, Role of epithelial cells in initiation and propagation of intestinal inflammation. Eliminating the static: tight junction dynamics exposed. Am J Physiol Gastrointest Liver Physiol, 2006. 290(4): p. G577-82.

[14]Di Pierro, M., et al., Zonula occludens toxin structure-function analysis. Identification of the fragment biologically active on tight junctions and of the zonulin receptor binding domain. J Biol Chem, 2001. 276(22): p. 19160-5.

[15]Sander, G.R., et al., Rapid disruption of intestinal barrier function by gliadin involves altered expression of apical junctional proteins. FEBS Lett, 2005. 579(21): p. 4851-5.

[16]Visser, J., et al., Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci, 2009. 1165: p. 195-205.

[17]Drago, S., et al., Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol, 2006. 41(4): p. 408-19.

[18]Fasano, A., et al., Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro. J Clin Invest, 1995. 96(2): p. 710-20.

[19]El Asmar, R., et al., Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure. Gastroenterology, 2002. 123(5): p. 1607-15.

[20]Lammers, K.M., et al., Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology, 2008. 135(1): p. 194-204 e3.

[21]Clemente, M.G., et al., Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut, 2003. 52(2): p. 218-23.

[22]Fasano, A., Intestinal zonulin: open sesame! Gut, 2001. 49(2): p. 159-62.

[23]Cereijido, M., et al., New diseases derived or associated with the tight junction. Arch Med Res, 2007. 38(5): p. 465-78.

[23]Fasano, A., Surprises from celiac disease. Sci Am, 2009. 301(2): p. 54-61.

[24]Mowat, A.M., Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol, 2003. 3(4): p. 331-41.

[25]Oldstone, M.B.A., MOLECULAR MIMICRY AND AUTOIMMUNE-DISEASE. Cell, 1987. 50(6): p. 819-820.


[27]Paterson, B.M., et al., The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study. Aliment Pharmacol Ther, 2007. 26(5): p. 757-66.

[28]Watts, T., et al., Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Natl Acad Sci U S A, 2005. 102(8): p. 2916-21.

[29]Bosi, E., et al., Increased intestinal permeability precedes clinical onset of type 1 diabetes. Diabetologia, 2006. 49(12): p. 2824-7.

[30]Mojibian, M., et al., Diabetes-specific HLA-DR-restricted proinflammatory T-cell response to wheat polypeptides in tissue transglutaminase antibody-negative patients with type 1 diabetes. Diabetes, 2009. 58(8): p. 1789-96.

[31]Sapone, A., et al., Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes, 2006. 55(5): p. 1443-1449.

[32]De Magistris, L., et al., Altered mannitol absorption in diabetic children. Ital J Gastroenterol, 1996. 28(6): p. 367.

[33]De Palma, G., et al., Intestinal dysbiosis and reduced immunoglobulin-coated bacteria associated with coeliac disease in children. BMC Microbiol, 2010. 10: p. 63.

[34]Westall, F.C., Abnormal hormonal control of gut hydrolytic enzymes causes autoimmune attack on the CNS by production of immune-mimic and adjuvant molecules: A comprehensive explanation for the induction of multiple sclerosis. Med Hypotheses, 2007. 68(2): p. 364-9.

[35]Yacyshyn, B., et al., Multiple sclerosis patients have peripheral blood CD45RO+ B cells and increased intestinal permeability. Dig Dis Sci, 1996. 41(12): p. 2493-8.

[36]Smith, M.D., R.A. Gibson, and P.M. Brooks, Abnormal bowel permeability in ankylosing spondylitis and rheumatoid arthritis. J Rheumatol, 1985. 12(2): p. 299-305.

[37]Edwards, C.J., Commensal gut bacteria and the etiopathogenesis of rheumatoid arthritis. J Rheumatol, 2008. 35(8): p. 1477-14797.

[38]Liu, J., et al., Identification of disease-associated proteins by proteomic approach in ankylosing spondylitis. Biochem Biophys Res Commun, 2007. 357(2): p. 531-6.

[39]D’Inca, R., et al., Increased intestinal permeability and NOD2 variants in familial and sporadic Crohn’s disease. Aliment Pharmacol Ther, 2006. 23(10): p. 1455-61.

[40]Irvine, E.J. and J.K. Marshall, Increased intestinal permeability precedes the onset of Crohn’s disease in a subject with familial risk. Gastroenterology, 2000. 119(6): p. 1740-4.

[41]Maurano, F., et al., Small intestinal enteropathy in non-obese diabetic mice fed a diet containing wheat. Diabetologia, 2005. 48(5): p. 931-7.

[42]Ziegler, A.G., et al., Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies. JAMA, 2003. 290(13): p. 1721-8.

[43]Funda, D.P., et al., Gluten-free but also gluten-enriched (gluten+) diet prevent diabetes in NOD mice; the gluten enigma in type 1 diabetes. Diabetes-Metabolism Research and Reviews, 2008. 24(1): p. 59-63.

[44]Knutson, T.W., et al., Effects of luminal antigen on intestinal albumin and hyaluronan permeability and ion transport in atopic patients. J Allergy Clin Immunol, 1996. 97(6): p. 1225-32.

[45]Hijazi, Z., et al., Intestinal permeability is increased in bronchial asthma. Arch Dis Child, 2004. 89(3): p. 227-9.

[46]Arrieta, M.C., et al., Reducing small intestinal permeability attenuates colitis in the IL10 gene-deficient mouse. Gut, 2009. 58(1): p. 41-8.

[47]Weber, C.R. and J.R. Turner, Inflammatory bowel disease: is it really just another break in the wall? Gut, 2007. 56(1): p. 6-8.

[48]Lai, C.H., et al., Proteomics-based identification of haptoglobin as a novel plasma biomarker in oral squamous cell carcinoma. Clin Chim Acta, 2010. 411(13-14): p. 984-91.

[50]Dowling, P., et al., 2-D difference gel electrophoresis of the lung squamous cell carcinoma versus normal sera demonstrates consistent alterations in the levels of ten specific proteins. Electrophoresis, 2007. 28(23): p. 4302-10.

[51]Wan, C., et al., Abnormal changes of plasma acute phase proteins in schizophrenia and the relation between schizophrenia and haptoglobin (Hp) gene. Amino Acids, 2007. 32(1): p. 101-8.

[52]Kalaydjian, A.E., et al., The gluten connection: the association between schizophrenia and celiac disease. Acta Psychiatr Scand, 2006. 113(2): p. 82-90.

Intestinal Permeability | The Paleo Diet

In the U.S., Mexican cuisine has become enormously popular in the past 30 years. A recent USA Today poll1 listed the 15 “Best” Tex-Mex chain restaurants in the U.S. as follows:

  1. Chipotle
  2. Baja Fresh
  3. Qdoba
  4. Moe’s Southwest
  5. On the Border
  1. Taco Bell
  2. El Pollo Loco
  3. Wahoo’s Fish Taco
  4. Chevys Fresh Mex
  5. Chuy’s
  1. Del Taco
  2. Chili’s
  3. El Torito
  4. Taco Cabana
  5. Pappasito’s Cantina

It has certainly been argued that fast American “Mexican” food is a far cry from the authentic cuisine actually found in the 31 Mexican federal states. Genuine Mexican cooking clearly is not uniform from one area or State of the country to the next. The foods of northern Mexican States differ from those in the south which in turn vary from coastal regions. Distinctive cuisines have arisen in Oaxaca, Mexico City, Yucatan, Veracruz, Chiapas, Querétaro and other regions and reflect historical, cultural and environmental differences among these discrete geographical areas.

As with most eating traditions found worldwide, current day Mexican cuisine is derived from an amalgamation of people, cultures, historical events and available foods. Prior to the European “discovery” of the Americas by Columbus in 1492, the indigenous peoples of the area we now call Mexico were necessarily reliant upon native plant and animal foods that could either be collected wild or domesticated. Notable domesticated plant foods native to Mexico and the Americas were corn (maize), chile peppers (all varieties), tomatoes, squash, certain bean species (Phaseolus vulgaris [kidney, pinto, black and navy beans], Phaseolus lunatus [lima beans]), tomatillos, maguey (mescal), cassava, avocadoes, chocolate and potatoes, among others.

With the arrival of Europeans came the introduction of cows (beef, dairy products: milk, butter, sour cream and cheese), pigs (pork), goat, and sheep (lamb, mutton) which were rapidly incorporated into the native Mexican cuisine. Other European/Asian food introductions that are frequently found in the present day Mexican cuisine are wheat, rice, barley, hops, lettuce, onions, green onions (scallions), garlic, cilantro, limes, olives, olive oils, cumin, black pepper, vinegar, and sugar.

Regardless of the region or individual federal States, Mexican cuisine is characterized by the plant foods native to Mexico and the Americas and primarily include chili peppers (multiple varieties), tomatoes and corn (maize). Beans (pinto, black and kidney) follow a close second. Corn is most frequently made into tortillas and consumed almost daily, but also is used to make a wide variety of foods including tamales, sopes, drinks (atole, pozol) and soups. Chile peppers (all varieties) almost uniformly define Mexican cuisine as they are in one form or another (salsas, sauces, diced, chopped, pureed, dried, stuffed or pickled) included into foods and meals daily. These spicy foods add the characteristic flavor to virtually all Mexican dishes, but also the “heat” which characterizes this distinctive dining tradition.

What follows is a laundry list (obviously non-comprehensive) of Mexican dishes and beverages, some of which are found worldwide, others almost always in specific regions or federal States of Mexico:

  • Tacos
  • Enchiladas
  • Chile rellenos
  • Burritos
  • Fajitas
  • Quesadillas
  • Chimichangas
  • Tamales
  • Tostadas
  • Taquitos
  • Flautas
  • Carnitas
  • Empanadas
  • Sopes
  • Huaraches
  • Tlacoyo
  • Gorditas
  • Garnachas
  • Memelas
  • Chalupas
  • Salbutes
  • Panuchos
  • Entomatadas
  • Gringas
  • Molletes
  • Salbutes
  • Nachos
  • Chili con carne
  • Chili con queso
  • Ceviche
  • Huevos rancheros
  • Huevos divorciados
  • Huevos motuleños
  • Taco salad
  • Menudo
  • Tripas
  • Chorizo
  • Mixiote
  • Queso flameado
  • Carne asada
  • Chilorio
  • Birria
  • Salsa verde
  • Salsa roja
  • Salsa
  • Camarones
  • Jalapeño poppers
  • Black beans
  • Refried beans
  • Rice
  • Corn tortillas
  • Wheat tortillas
  • Corn chips
  • Tortilla chips
  • Totopo
  • Guacamole
  • Hot sauce
  • Fresh peppers (all varieties)
  • Dried peppers (all varieties)
  • Pickeled peppers (all varieties)
  • Pico de gallo
  • Mole sauce
  • Nopales
  • Mexican beers
  • Bohemia
  • Dos Equis
  • Corona
  • Carte Blanca
  • Estrella
  • Modelo
  • Pacifico
  • Sol
  • Superior
  • Tecate
  • Victoria
  • Tequila
  • Mescal
  • Pulque
  • Margaritas

Nutritional Shortcomings of Mexican Cuisine

Almost all of us have enjoyed some of these dishes and beverages, simply because the Tex-Mex food culture pervades American fast food restaurants and supermarkets. Unfortunately many Mexican dishes which have been produced commercially or in restaurants are not Paleo for the following reasons:

  1. Inclusion of cereal grains (corn, wheat, rice) or beverages made from grains (beer) in daily staple foods and recipes.
  2. Inclusion of beans (black, pinto, kidney, lima etc.) in many recipes and meals
  3. Inclusion of salt (either refined or sea salt) in almost all dishes, recipes and sauces

Intestinal Permeability

Besides being nutritional lightweights, cereal grains2 and legumes promote increased intestinal permeability. Wheat in particular contains at least three compounds known to promote a “leaky gut” including gluten, wheat germ agglutinin (WGA), and thaumatin like proteins. Corn, like all cereal grains, is rich in antinutrients including lectins which are known to decrease intestinal absorption of many key nutrients and may cause villous flattening.2 As I have previously pointed out beans and all legumes are concentrated sources of saponins which have been demonstrated in human studies to increase intestinal permeability.

When the cells lining the gastrointestinal tract become compromised leading to increased intestinal permeability (e.g. a leaky gut), it allows the gut contents (food and microorganisms) to chronically interact with the immune system. Accordingly, many immunologists now believe that increased intestinal permeability represents an initial environmental trigger for autoimmune diseases in genetically susceptible individuals.3-7

A leaky gut also allows entry of a compound called lipopolysaccharide (LPS), found in gut gram negative bacteria, into the bloodstream. Systemically, LPS may produce a chronic low level inflammatory condition called endotoxemia, which is increasingly being recognized as an underlying factor in insulin resistance, the metabolic syndrome, cardiovascular disease and obesity.8-11

In addition to gluten containing grains, WGA and bean saponins, a number of other foods and beverages commonly included in Tex-Mex cuisine also may impair intestinal barrier function and promote a leaky gut. These foods include chili peppers, tomatillos and unripe, green tomatoes.12 Because they contain ethanol, note too that all alcoholic beverages including Mexican beers, tequila, mescal and pulque may cause a leaky gut.

Chili peppers

Chili peppers are members of the nightshade family of plants and are among the most heavily consumed spices throughout the world. The table below shows the five most common species of chili peppers and lists a few of the more familiar varieties within each species.

Common Scientific Names | The Paleo Diet
Chili peppers are favorite spices throughout the world because of their pungent or “hot” taste and aroma. The “heat” from chili peppers comes from a group of compounds called capsaicinoids or capsaicins. The greater the concentration of capsaicins in the chili pepper, the “hotter” it tastes. More than 20 capsaicins are found in chili peppers, and their total concentrations range from 0% to more than 2% by weight. Daily per capita consumption of capsaicins in the U.S. and Europe is ~1.5mg whereas in India, Mexico and Thailand it is ~ 25-200mg. The table below shows the concentrations of total capsaicins in a variety of chili peppers and foods.

Concentrations of Capsaicins | The Paleo DietChili peppers seem to have both beneficial and harmful health effects. They have long been used in Mayan and Ayurvedic healing remedies and more recently have found therapeutic application in modern medicine with pain relief. One of the potential shortcomings of chili peppers is their ability to increase intestinal permeability, and herein lies perhaps their greatest threat to human health. As far back as 1998 it was suggested by Dr. Jensen-Jarolim and colleagues13 that chili peppers, because of their capsaicins “may modulate the absorption of low molecular weight food constituents that are involved in the pathogenesis of food allergy and intolerance.” This statement simply means that chili pepper capsaicins increase intestinal permeability13-18 and, therefore, allow gut microorganisms and food proteins access to our immune systems which in turn may promote allergy, autoimmune diseases and chronic low level inflammation.

The Bottom Line with Mexican Cuisine

If you are a Paleo Dieter and like an occasional night out with friends and family at your local Tex-Mex restaurant – go for it. Enjoy your enchiladas, tacos, chili rellenos, refried beans, chips, salsa and even sip a margarita. However, try to avoid wheat flour tortillas and beer.If you decide to have a margarita, order it without salt. For Paleo Dieters even better choices on a night out might be a Mexican salad with pork, chicken or beef; or a meat/fish tostada; or how about a beef, pork, chicken or fish main dish and replace the beans, rice and tortillas with a big salad or steamed veggies.

Even the most dedicated Paleo Dieter probably would find it difficult to be 100% compliant with all foods known to increase intestinal permeability. However you don’t have to. Most people find that by being about 85% compliant with the Paleo Diet, they experience significant improvement in their health and well being. Food elements typically found in Mexican cuisine which may increase intestinal permeability (flour tortillas, chili peppers, salsa, beans, tequila, beer, green tomatoes, tomatillos) operate in a dose dependent manner meaning that all of these foods must be regularly consumed to chronically increase the risk of a leaky gut. However here’s an important exception: If you have an autoimmune disease, you should be cautious in consuming Mexican cuisine or any food known to increase intestinal permeability.


Loren Cordain, Ph.D., Professor Emeritus



1. //www.usatoday.com/story/travel/destinations/2014/01/04/best-tex-mex-mexican-restaurants-food/4308625/

2. Cordain, L. Cereal grains: humanity’s double edged sword. World Rev Nutr Diet 1999; 84:19-73.

3. Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011 Jan;91(1):151-75
4. Fasano A. Surprises from celiac disease. Sci Am. 2009 Aug;301(2):54-61

5. Visser J, Rozing J, Sapone A, Lammers K, Fasano A. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci. 2009 May;1165:195-205.

6. Joscelyn J, Kasper LH. Digesting the emerging role for the gut microbiome in central nervous system demyelination. Mult Scler. 2014 Jul 28. pii: 1352458514541579. [Epub ahead of print]

7. Vaarala O. Is the origin of type 1 diabetes in the gut? Immunol Cell Biol. 2012 Mar;90(3):271-6.

8. Cani PD, Osto M, Geurts L, Everard A. Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes. 2012 Jul-Aug;3(4):279-88.

9. Geurts L, Neyrinck AM, Delzenne NM, Knauf C, Cani PD.Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: novel insights into molecular targets and interventions using prebiotics. Benef Microbes. 2014 Mar;5(1):3-17.

10. Everard A, Cani PD. Diabetes, obesity and gut microbiota. Best Pract Res Clin Gastroenterol. 2013 Feb;27(1):73-83.

11. Jayashree B, Bibin YS, Prabhu D, Shanthirani CS, Gokulakrishnan K, Lakshmi BS, Mohan V, Balasubramanyam M. Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes.Mol Cell Biochem. 2014 Mar;388(1-2):203-10.

12. Cordain, L. The Food – Autoimmune Disease Connection. In: Cordain, L., The Paleo Answer, John Wiley & Sons, New York, NY, 2012, pp. 161-179.

13. Jensen-Jarolim E, Gajdzik L, Haberl I, Kraft D, Scheiner O, Graf J. Hot spices influence permeability of human intestinal epithelial monolayers. J Nutr. 1998 Mar;128(3):577-81.

14. Han J, Isoda H, Maekawa T. Analysis of the mechanism of the tight-junctional permeability increase by capsaicin treatment on the intestinal Caco-2 cells. Cytotechnology. 2002 Nov;40(1-3):93-8.

15. Han JK, Akutsu M, Talorete TP, Maekawa T, Tanaka T, Isoda H. Capsaicin-enhanced Ribosomal Protein P2 Expression in Human Intestinal Caco-2 Cells. Cytotechnology. 2005 Jan;47(1-3):89-96.

16. Isoda H, Han J, Tominaga M, Maekawa T. Effects of capsaicin on human intestinal cell line Caco-2. Cytotechnology. 2001 Jul;36(1-3):155-61.

17. Komori Y, Aiba T, Nakai C, Sugiyama R, Kawasaki H, Kurosaki Y. Capsaicin-induced increase of intestinal cefazolin absorption in rats. Drug Metab Pharmacokinet. 2007 Dec;22(6):445-9.

18. Tsukura Y, Mori M, Hirotani Y, Ikeda K, Amano F, Kato R, Ijiri Y, Tanaka K. Effects of capsaicin on cellular damage and monolayer permeability in human intestinal Caco-2 cells. Biol Pharm Bull. 2007 Oct;30(10):1982-6.

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