Tag Archives: leaky gut

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 SECRET LIES IN THE INTESTINES

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

THE SCARCITY OF REAL FOODS

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 GOOD NEWS

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.

 

REFERENCES

[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.

Mind Your Microbes: Gut Health | The Paleo Diet

I have a gut feeling that things are about to become much more interesting in the science world.1, 2, 3 As researchers continue to discover more and more exciting news about just how our microbiomes can uniquely identify us, change our food cravings, and alter our health, we must continually realize the importance of keeping a ‘healthy gut’.4 While this phrase has become increasingly popular in the mainstream world of health, many still do not realize exactly is meant by having ‘good gut health’. Perhaps more troubling – they have no idea how to obtain it. A Paleo diet will be the single best thing you can do for your gut, by avoiding Western foods which have been proven to alter gut bacteria in a negative fashion.5, 6

Mind Your Microbes: Gut Health |  The Paleo Diet

Bischoff, Stephan C. “‘Gut Health’: A New Objective in Medicine?” BMC Medicine 9 (2011): 24. PMC. Web. 20 May 2015.

By adding in foods that help to promote gut health (fermented choices like sauerkraut) you will be moving things in the right direction.7, 8 Poor gut health is correlated with a multitude of negative symptoms and conditions, including a lifetime of antibiotic treatments (which have increasingly been shown to be detrimental to the microbiome), and is often the most common problem experienced by anyone with poor health. 9, 10, 11, 12

For over a decade, researchers have known that the gut microflora is a major part of metabolic activities that result in salvage of energy and absorbable nutrients.13 Researchers have also known that the microbiota plays a crucial role as a source of infection and environmental insult and also in protection against disease and maintenance of gut function.14 Since this is scientific information, the general public remained largely unaware of it – even as we became fatter, sicker and more likely to receive a host of antibiotic treatments.15, 16, 17

Mind Your Microbes: Gut Health | The Paleo Diet

Bischoff, Stephan C. “‘Gut Health’: A New Objective in Medicine?” BMC Medicine 9 (2011): 24. PMC. Web. 20 May 2015.

Sadly, it has taken illness, poor health and chronic pain for many to discover a Paleo diet. But this doesn’t have to be the case. Preventative – rather than reactive – measures are ideal when looking to maintain one’s health in the long term.18 Since your microbiome is a unique fingerprint, you want it to be in the best shape possible.19, 20, 21 Researchers at Harvard recently even warned that people may be able to be identified by their microbiome fingerprint (which has possible data privacy implications).22 Fast food has been shown to worsen the balance of good bacteria to bad bacteria in the gut, and also increases the likelihood of obesity.23, 24 These are all good reasons to adopt a Paleo diet and ‘mind your microbes’ – as the saying goes.

Mind Your Microbes: Gut Health | The Paleo Diet

Hoffmann, Christian et al. “Archaea and Fungi of the Human Gut Microbiome: Correlations with Diet and Bacterial Residents.” Ed. Chongle Pan. PLoS ONE 8.6 (2013): e66019. PMC. Web. 20 May 2015.

Lastly, many are unaware that they themselves carry more bacterial cells than human cells – meaning that bacteria literally run our lives.25, 26, 27 This is one of the biggest reasons to really focus on improving your own gut’s health – and in turn – adopt a better diet. Western diets have poor implications and results for the human microbiome – it is a bad idea to continue to eat that way.28, 29, 30 Instead, focus on a nutrient dense, anti-inflammatory Paleo Diet – and make your bacteria happy.

 

REFERENCES

[1] Cummings JH, Antoine JM, Azpiroz F, et al. PASSCLAIM–gut health and immunity. Eur J Nutr. 2004;43 Suppl 2:II118-II173.

[2] Choct M. Managing gut health through nutrition. Br Poult Sci. 2009;50(1):9-15.

[3] Bischoff SC. ‘Gut health’: a new objective in medicine?. BMC Med. 2011;9:24.

[4] Available at: http://www.sciencedaily.com/releases/2015/05/150511162914.htm. Accessed May 16, 2015.

[5] Brown K, Decoffe D, Molcan E, Gibson DL. Diet-induced dysbiosis of the intestinal microbiota and the effects on immunity and disease. Nutrients. 2012;4(8):1095-119.

[6] Martinez-medina M, Denizot J, Dreux N, et al. Western diet induces dysbiosis with increased E coli in CEABAC10 mice, alters host barrier function favouring AIEC colonisation. Gut. 2014;63(1):116-24.

[7] Selhub EM, Logan AC, Bested AC. Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry. J Physiol Anthropol. 2014;33:2.

[8] Van hylckama vlieg JE, Veiga P, Zhang C, Derrien M, Zhao L. Impact of microbial transformation of food on health – from fermented foods to fermentation in the gastro-intestinal tract. Curr Opin Biotechnol. 2011;22(2):211-9.

[9] Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therap Adv Gastroenterol. 2013;6(1):39-51.

[10] Kelder T, Stroeve JH, Bijlsma S, Radonjic M, Roeselers G. Correlation network analysis reveals relationships between diet-induced changes in human gut microbiota and metabolic health. Nutr Diabetes. 2014;4:e122.

[11] Hoffmann C, Dollive S, Grunberg S, et al. Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents. PLoS ONE. 2013;8(6):e66019.

[12] Catanzaro R, Anzalone M, Calabrese F, et al. The gut microbiota and its correlations with the central nervous system disorders. Panminerva Med. 2015;57(3):127-43.

[13] Guarner F, Malagelada JR. Gut flora in health and disease. Lancet. 2003;361(9356):512-9.

[14] Tuohy KM, Probert HM, Smejkal CW, Gibson GR. Using probiotics and prebiotics to improve gut health. Drug Discov Today. 2003;8(15):692-700.

[15] Rocca WA, Petersen RC, Knopman DS, et al. Trends in the incidence and prevalence of Alzheimer’s disease, dementia, and cognitive impairment in the United States. Alzheimers Dement. 2011;7(1):80-93.

[16] Roth J, Qiang X, Marbán SL, Redelt H, Lowell BC. The obesity pandemic: where have we been and where are we going?. Obes Res. 2004;12 Suppl 2:88S-101S.

[17] Available at: http://www.ncbi.nlm.nih.gov/pubmedhealth/behindtheheadlines/news/2014-10-10-antibiotic-resistance-continues-to-rise-/. Accessed May 16, 2015.

[18] Maciosek MV, Coffield AB, Flottemesch TJ, Edwards NM, Solberg LI. Greater use of preventive services in U.S. health care could save lives at little or no cost. Health Aff (Millwood). 2010;29(9):1656-60.

[19] Franzosa EA, Huang K, Meadow JF, et al. Identifying personal microbiomes using metagenomic codes. Proc Natl Acad Sci USA. 2015;

[20] Gillevet P, Sikaroodi M, Keshavarzian A, Mutlu EA. Quantitative assessment of the human gut microbiome using multitag pyrosequencing. Chem Biodivers. 2010;7(5):1065-75.

[21] Albenberg LG, Lewis JD, Wu GD. Food and the gut microbiota in inflammatory bowel diseases: a critical connection. Curr Opin Gastroenterol. 2012;28(4):314-20.

[22] Available at: http://www.sciencedaily.com/releases/2015/05/150511162914.htm. Accessed May 16, 2015.

[23] Available at: http://www.ibtimes.com/what-good-gut-bacteria-fast-food-kills-natural-allies-worsens-obesity-other-health-1916714. Accessed May 16, 2015.

[24] Slavin J. Fiber and prebiotics: mechanisms and health benefits. Nutrients. 2013;5(4):1417-35.

[25] Available at: http://www.scientificamerican.com/article/strange-but-true-humans-carry-more-bacterial-cells-than-human-ones/. Accessed May 16, 2015.

[26] O’hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO Rep. 2006;7(7):688-93.

[27] Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. 2009;1(6):6ra14.

[28] Myles IA. Fast food fever: reviewing the impacts of the Western diet on immunity. Nutr J. 2014;13:61.

[29] Poutahidis T, Kleinewietfeld M, Smillie C, et al. Microbial reprogramming inhibits Western diet-associated obesity. PLoS ONE. 2013;8(7):e68596.

[30] Wong JM, Esfahani A, Singh N, et al. Gut microbiota, diet, and heart disease. J AOAC Int. 2012;95(1):24-30.

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.

LOOSENING OUR BORDERS

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

PERMEABLE CONSEQUENCES

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

LOSING THE BARRIER TO DISEASE

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

REFERENCES

[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.

[26]Wucherpfennig, K.W. and J.L. Strominger, MOLECULAR MIMICRY IN T-CELL-MEDIATED AUTOIMMUNITY – VIRAL PEPTIDES ACTIVATE HUMAN T-CELL CLONES SPECIFIC FOR MYELIN BASIC-PROTEIN. Cell, 1995. 80(5): p. 695-705.

[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.

Food Allergy | The Paleo Diet

Within our intestines, we harbor some 100 trillion microbial cells, collectively known as the gut microbiome (GM). For better or worse, the GM profoundly influences our health, impacting physiology, metabolism, nutrition, and immune function. GM disruption can promote obesity, diabetes, and chronic inflammatory diseases, including irritable bowel syndrome and Crohn’s disease.1, 2, 3 In short, according to the human microbiome project (HMP), “we are supraorganisms composed of human and microbial components.”4

The HMP was an initiative launched in 2007 by the National Institutes of Health to study the role of microbes in human health and disease. The HMP sparked widespread interest in GM research, but we’re still just beginning to understand the complexities and intricacies of the GM. Nevertheless, preliminary research suggests the transition from being hunter-gathers to sedentary city dwellers resulted in significant GM changes.

For example, researchers recently compared the GMs of traditional Hadza hunter-gatherers of Tanzania with those of urban adults. The results, published in Nature Communications, showed the Hadza having significantly increased GM diversity.5 Notably, the Hadza have higher amounts of Clostridia, a class of gut bacteria, which according to recently published research, protects against food allergies (more on this below).6

The researchers studying the Hadza remarked, “Adaptation to the post-industrialized western lifestyle is coincident with a reduction in GM diversity, and as a result, a decline in GM stability.” Since the gastrointestinal tract is a gateway to pathogenic, metabolic, and immunological diseases, scientists are increasingly interpreting this decline in GM diversity as a major risk factor for degenerative diseases.

Why is Gut Microbiome Diversity Decreasing?

Many aspects of modern lifestyles promote decreased GM diversity, including birthing method (cesarean versus traditional vaginal births), decreased breastfeeding, decreased consumption of dietary fiber, increased early childhood exposure to antibiotics, and increased lifetime exposure to antibiotics. Cesarean births require the use of antibiotics, which is one reason why, according to research recently published by the Canadian Medical Association Journal, cesarean birthed infants exhibit “particularly low bacterial richness and diversity.”7

Antibiotics are notoriously overprescribed in the US, particularly for viral infections (which antibiotics don’t affect). A 2014 study found that doctors prescribe antibiotics for 60% of sore throat cases and 70% of cough cases.8 Dr. Jeffrey Linder, one of the study’s co-authors, says only 10% of sore throat cases are bacterial and multiple studies show antibiotics are ineffective against coughs.9 In short, modern lifestyles and diets are negatively impacting GM diversity.

The Connection Between Gut Microbiome and Food Allergies

According to Food Allergy Research & Education, 15 million Americans suffer from food allergies, including 1 in 13 children.10 Food allergies increased 18% among children from 1997 to 2007.11 Is the increasing food allergies trend related to the decreasing GM diversity trend? According to University of Chicago researchers, yes.

By studying mice raised in perfectly sterile environments, these researchers discovered that Clostridia (the same bacterial strain observed at increased levels among the Hadza and decreased levels among urbanites) protects against food allergies.12 Lead researcher Dr. Cathryn Nagler explained, “The first step is for an allergen to gain access to the blood stream. The presence of Clostridia prevents the allergens from getting into the bloodstream.”13

So what does this mean with respect to the Paleo Lifestyle? For many people, particularly those with a history of antibiotic use, probiotic supplementation may be prudent. Dr. Cordain explains that both probiotic and prebiotic supplements promote healthy gut flora and reduced intestinal permeability for most people, although in some special cases they could agitate the gut.

Moreover, the Paleo Diet contains large amounts of fiber-rich vegetables. Think of fiber as food for the GM. Once inside the gastrointestinal tract, certain vegetable fibers ferment, creating short-chain fatty acids, which promote GM diversity and prevent the overgrowth of antagonistic bacterial strains.14

Remember the human microbiome project (HMP)? Thirty-seven HMP microbiologists were asked a series of questions regarding gut health, including one specific to the Paleo Diet: “Do you believe a high protein-fat diet, so long as it includes a significant amount and diversity of whole plants (fermentation sources) and minimal to no processed carbohydrates, is a strategy for a healthy microbiome?”15 With 1 representing “strongly disagree” and 10 “strongly agree,” the average response was 9.1. In other words, according to the world’s leading GM experts, the Paleo Diet, like the ancestral Hadza diet, promotes healthy, diverse gut microbiomes, thereby protecting against food allergies.

Christopher James Clark, B.B.A.
@nutrigrail
Nutritional Grail
www.ChristopherJamesClark.com

Christopher James Clark | The Paleo Diet TeamChristopher James Clark, B.B.A. is an award-winning writer, consultant, and chef with specialized knowledge in nutritional science and healing cuisine. He has a Business Administration degree from the University of Michigan and formerly worked as a revenue management analyst for a Fortune 100 company. For the past decade-plus, he has been designing menus, recipes, and food concepts for restaurants and spas, coaching private clients, teaching cooking workshops worldwide, and managing the kitchen for a renowned Greek yoga resort. Clark is the author of the critically acclaimed, award-winning book, Nutritional Grail.

REFERENCES

1 Ley, RE., et al. (December 2006). Microbial ecology: human gut microbes associated with obesity. Nature, 444 (7122). Retrieved October 2, 2014 from http://www.ncbi.nlm.nih.gov/pubmed/17183309/

2 Qin, J., et al. (October 2012). A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature, 490 (7418). Retrieved October 2, 2014 from http://www.ncbi.nlm.nih.gov/pubmed/23023125/

3 Frank, DN., et al. (August 2007). Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proceeding of the National Academy of Sciences, 104 (34). Retrieved 2, 2014 from http://www.ncbi.nlm.nih.gov/pubmed/17699621/

4 Turnbaugh, PJ., et al. (October 2007). The human microbiome project: exploring the microbial part of ourselves in a changing world. Nature, 449 (7164). Retrieved October 2, 2014 from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709439/

5 Schnorr, SL., et al. (April 2014). Gut microbiome of the Hadza hunter-gatherers. Nature Communications, 5 (3654). Retrieved October 2, 2014 from http://www.nature.com/ncomms/2014/140415/ncomms4654/full/ncomms4654.html

6 Stefka, AT., et al. (August 2014). Commensal bacteria protect against food allergen sensitization. Proceedings of the National Academy of Sciences, 111 (36). Retrieved October 2, 2014 from http://www.pnas.org/content/111/36/13145

7 Azad, MB., et al. (March 2013). Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. Canadian Medical Association Journal, 185 (5). Retrieved October 2, 2014 from http://www.cmaj.ca/content/185/5/385

8 Barnett, ML., (January 2014). Antibiotic Prescribing to Adults With Sore Throat in the United States, 1997-2010. JAMA Internal Medicine, 174 (1). Retrieved October 2, 2014 from http://archinte.jamanetwork.com/article.aspx?articleid=1745694

9 Singh, M. (October 4, 2013). Despite Many Warnings, Antibiotics Are Still Overprescribed. NPR. Retrieved October 2, 2014 from http://www.npr.org/blogs/health/2013/10/04/229167826/despite-many-warnings-antibiotics-are-still-overprescribed

10 Food Allergy Research & Education. About Food Allergies. Retrieved October 2, 2014 from http://www.foodallergy.org/about-food-allergies

11 Branum, AM., (October 2008). Food Allergy Among U.S. Children: Trends in Prevalence and Hospitalizations. NCHS Data Brief, 10. Retrieved October 2, 2014 from http://www.cdc.gov/nchs/data/databriefs/db10.pdf

12 Stefka, AT., et al. (August 2014). Commensal bacteria protect against food allergen sensitization. Proceedings of the National Academy of Sciences, 111 (36). Retrieved October 2, 2014 from http://www.pnas.org/content/111/36/13145

13 Gallagher, J. (August 26, 2014). Gut bugs ‘help prevent allergies.’ BBC News, Health. Retrieved October 2, 2014 from http://www.bbc.com/news/health-28887088

14 Kaczmarczyk, MM., et al. (August 2012). The health benefits of dietary fiber: Beyond the usual suspects of type 2 diabetes mellitus, cardiovascular disease and colon cancer. Metabolism, 61 (8). Retrieved October 2, 2014 from http://www.sciencedirect.com/science/article/pii/S0026049512000455

15 Leach, J. (September 26, 2012). Guts, Germs and Meals: what 37 microbiologist say about diet. Human Food Project. Retrieved October 2, 2014 from http://humanfoodproject.com/guts-germs-and-meals-what-37-microbiologist-say-about-diet/

Alfalfa Sprouts | The Paleo Diet

As the Paleo Diet concept increasingly gains traction worldwide, it has spawned an explosion of copy cat books over the past 3-4 years. Look no further than Amazon.com to literally see the hundreds of diet and cookbooks that manage to shoehorn the word “Paleo” into their titles. In a way, all of these books are a good thing because they tend to get more and more people involved in a lifetime way of eating that may improve health and well being, while reducing the risk for chronic diseases. The downside of this situation is that many authors are poorly informed and frequently provide misleading information about food, recipes and meals that are not “Paleo” by any stretch of the imagination.

We have recently written a number of comprehensive articles about some of these items including sea salt, dairy foods, honey and nut flours. I even understand that a popular Paleo influencer now added beans and legumes to his list of foods which are acceptable in contemporary Paleo diets.  Apparently he has not read my lengthy article on the topic, nor is he aware of the notion that almost all beans and legumes are either inedible, poorly digestible or toxic in their raw state. Hence until humanity acquired the technology to create fire at will, legumes were not on the original menu that helped to shape our present day genome.

As I have previously explained, legumes both in their raw and cooked state contain a number of antinutrients (lectins, saponins, protease inhibitors, phytate, thaumatin like proteins among others) which can impair nutrition/health, adversely affect gut function, increase intestinal permeability and promote autoimmune disease.  Increasingly, scientists studying autoimmune disease now recognize that a leaky gut represents a key environmental factor in triggering autoimmune disease in genetically susceptible individuals.1-3 Although the link between autoimmunity and legumes is poorly documented in humans, at least one legume is known to cause an autoimmune disease. Except for gluten containing grains (wheat, rye and barley), only alfalfa sprouts, seeds and supplements are known to elicit an autoimmune disease.

A long line of intriguing research in humans, primates and rodents4-33 demonstrates that alfalfa sprouts, seeds and supplements may cause an autoimmune disease known as systemic lupus erythematosus (SLE), particularly when consumed in excessive quantity. The classical explanation is that alfalfa contains an amino acid called L-canavanine which is thought to cause SLE via dysregulation of T and B lymphocytes in the immune system.6, 13, 14, 16, 18, 19, 30, 31, 33

However, this explanation may not fully explain why alfalfa sprouts, seeds and supplements cause autoimmunity.20 With the increasing realization that a leaky gut represents a fundamental environmental factor that underlies autoimmunity,1-3 then any food which has the potential to increase intestinal permeability may be suspect in autoimmune diseases.

Below is a table showing the saponin content of various foods. Note alfalfa sprouts tops the list.

Total Saponins | The Paleo Diet

One of the few raw legumes that we eat in the typical western diet are alfalfa sprouts. In vegetarian diets, they are standards in meatless sandwiches and vegetable salads. Alfalfa sprouts, seeds and supplements are potent sources of saponins23-28 which increase intestinal permeability. Most people eat alfalfa sprouts irregularly, so the potential adverse health effects of sporadic alfalfa consumption are probably of minor consequence, except for people suffering from autoimmune disease.

As a contemporary Paleo dieter, we should learn from the wisdom of our ancestral diet: a diet that rarely or never consisted of legumes.

Cordially,

Loren Cordain, Ph.D., Professor Emeritus

References

1. Fasano A. Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol. 2012 Feb;42(1):71-8.

2. 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

3. Fasano A, Shea-Donohue T.Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol. 2005 Sep;2(9):416-22

4. Livingston AL, Whitehand LC, Kohler GO. Microbiological assay for saponin in alfalfa products. J Assoc Off Anal Chem. 1977 Jul;60(4):957-60.

5. Malinow MR, McNulty WP, McLaughlin P, Stafford C, Burns AK, Livingston AL, Kohler GO. The toxicity of alfalfa saponins in rats. Food Cosmet Toxicol. 1981 Aug;19(4):443-5.

6. Malinow MR, Bardana EJ Jr, Pirofsky B, Craig S, McLaughlin P. Systemic lupus erythematosus-like syndrome in monkeys fed alfalfa sprouts: role of a nonprotein amino acid. Science. 1982 Apr 23;216(4544):415-7.

7. Bardana EJ Jr, Malinow MR, Houghton DC, McNulty WP, Wuepper KD, Parker F, Pirofsky B. Diet-induced systemic lupus erythematosus (SLE) in primates. Am J Kidney Dis. 1982 May;1(6):345-52.

8. Malinow MR, McNulty WP, Houghton DC, Kessler S, Stenzel P, Goodnight SH Jr, Bardana EJ Jr, Palotay JL, McLaughlin P, Livingston AL. Lack of toxicity of alfalfa saponins in cynomolgus macaques. J Med Primatol. 1982;11(2):106-18.

9. Roberts JL, Hayashi JA. Exacerbation of SLE associated with alfalfa ingestion.N Engl J Med. 1983 Jun 2;308(22):1361

10. Podell RN. Systemic lupus erythematosus. Does diet play a causative role? Postgrad Med. 1984 Jan;75(1):251-4.

11. Livingston AL, Knuckles BE, Teuber LR, Hesterman OB, Tsai LS. Minimizing the saponin content of alfalfa sprouts and leaf protein concentrates. Adv Exp Med Biol. 1984;177:253-68.

12. Malinow MR, McLaughlin P, Bardana EJ Jr, Craig S. Elimination of toxicity from diets containing alfalfa seeds. Food Chem Toxicol. 1984 Jul;22(7):583-7.

13. Weissberger LE, Armstrong MK. Canavanine analysis of alfalfa extracts by high performance liquid chromatography using pre-column derivatization. J Chromatogr Sci. 1984 Oct;22(10):438-40.

14. Alcocer-Varela J, Iglesias A, Llorente L, Alarcón-Segovia D. Effects of L-canavanine on T cells may explain the induction of systemic lupus erythematosus by alfalfa. Arthritis Rheum. 1985 Jan;28(1):52-7.

15. Corman LC. The role of diet in animal models of systemic lupus erythematosus: possible implications for human lupus. Semin Arthritis Rheum. 1985 Aug;15(1):61-9.

16. Prete PE. The mechanism of action of L-canavanine in inducing autoimmune phenomena. Arthritis Rheum. 1985 Oct;28(10):1198-200.

17. Morimoto I. A study on immunological effects of L-canavanine. Kobe J Med Sci. 1989 Dec;35(5-6):287-98.

18. Morimoto I, Shiozawa S, Tanaka Y, Fujita T.L-canavanine acts on suppressor-inducer T cells to regulate antibody synthesis: lymphocytes of systemic lupus erythematosus patients are specifically unresponsive to L-canavanine. Clin Immunol Immunopathol. 1990 Apr;55(1):97-108.

19. Montanaro A1, Bardana EJ Jr. Dietary amino acid-induced systemic lupus erythematosus. Rheum Dis Clin North Am. 1991 May;17(2):323-32.

20. Herbert V, Kasdan TS. Alfalfa, vitamin E, and autoimmune disorders. Am J Clin Nutr. 1994 Oct;60(4):639-40.

21. Whittam J, Jensen C, Hudson T. Alfalfa, vitamin E, and autoimmune disorders. Am J Clin Nutr. 1995 Nov;62(5):1025-6.

22. Farnsworth NR. Alfalfa pills and autoimmune diseases. Am J Clin Nutr. 1995 Nov;62(5):1026-8.

23. Timbekova AE, Isaev MI, Abubakirov NK. Chemistry and biological activity of triterpenoid glycosides from Medicago sativa. Adv Exp Med Biol. 1996;405:171-82.

24. Tava A, Odoardi M. Saponins from Medicago Spp.: chemical characterization and biological activity against insects. Adv Exp Med Biol. 1996;405:97-109.

25. Oleszek W. Alfalfa saponins: structure, biological activity, and chemotaxonomy. Adv Exp Med Biol. 1996;405:155-70.

26. West PR, Waller GR, Geno PW, Oleszek W, Jurzysta M. Liquid secondary ion mass spectrometry and linked scanning at constant B/ELSIMS/MS for structure confirmation of saponins in Medicago sativa (alfalfa). Adv Exp Med Biol. 1996;405:339-52

27. Lee MK, Ling YC, Jurzysta M, Waller GR. Saponins from alfalfa, clover, and mungbeans analyzed by electrospray ionization-mass spectrometry as compared with positive and negative FAB-mass spectrometry. Adv Exp Med Biol. 1996;405:353-64.

28. Bialy Z1, Jurzysta M, Oleszek W, Piacente S, Pizza C. Saponins in alfalfa (Medicago sativa L.) root and their structural elucidation. J Agric Food Chem. 1999 Aug;47(8):3185-92.

29. Brown AC. Lupus erythematosus and nutrition: a review of the literature. J Ren Nutr. 2000 Oct;10(4):170-83.

30. Bell EA. Nonprotein amino acids of plants: significance in medicine, nutrition, and agriculture. J Agric Food Chem. 2003 May 7;51(10):2854-65.

31. Akaogi J1, Barker T, Kuroda Y, Nacionales DC, Yamasaki Y, Stevens BR, Reeves WH, Satoh M. Role of non-protein amino acid L-canavanine in autoimmunity. Autoimmun Rev. 2006 Jul;5(6):429-35.

32. Nunn PB, Bell EA, Watson AA, Nash RJ. Toxicity of non-protein amino acids to humans and domestic animals. Nat Prod Commun. 2010 Mar;5(3):485-504.

33. Huang T, Jander G, de Vos M. Non-protein amino acids in plant defense against insect herbivores: representative cases and opportunities for further functional analysis.
Phytochemistry. 2011 Sep;72(13):1531-7.

Gut Healing | The Paleo Diet

Many of those that have made the switch to The Paleo Diet, previously subsisted on a Standard American Diet (SAD) that relies heavily on grains, dairy, simple carbohydrates, sugars, and unhealthy oils. A diet rich in SAD foods can contribute to gut dysbiosis or “leaky gut” which can lead to autoimmune disorders and other ailments such as chronic fatigue, inflammatory bowel disease, rashes, diabetes, mental disorders, and other health related problems. To add insult to injury, the modernized human being has typically had their fair share of gut damaging antibiotics and prescription drugs which only serve to further throw off the intricate balance in one’s digestive tract.

If you have yet to achieve success after adopting your Paleo lifestyle, there is a good chance that your gut functioning is not up to par and your digestive system could be allowing toxins into your bloodstream and preventing adequate nutrient uptake regardless of how healthy you may be eating.

To support immune function and overall well being one must account for the importance of gut health. Fortunately, there are many foods and lifestyle practices you can adopt to restore your gut’s equilibrium.

Gut Healing Foods

As obvious as it may seem, the gut should be thought of as the primary interface between the human body and the environment. Every food that is put into your system will create a reaction in your gut. Certain foods will increase gut permeability with long term exposure, thus allowing normally digested food particles into the bloodstream invoking an immune system response. Over time, this response can lead to the formation of autoimmune illnesses and other health issues. Avoid these foods on a gut healing protocol:

  • Grains
  • Legumes
  • Dairy
  • Sugars
  • Unhealthy oils (corn, vegetable, soybean, cottonseed)
  • Alcohol and caffeine
  • Excessive carbohydrate consumption

Individuals with autoimmune disease may want to limit or omit:

By removing the foods outlined above, you should be able to reduce overall body inflammation and assist in restoring gut health.

Certain foods, however, should be incorporated into your Paleo Diet to accelerate the healing process.

Gut Healing Foods

Probiotic rich foods are essential. The gut is home to roughly 100 trillion organisms, and many gut related problems stem from loss of gut flora diversity. These foods are tremendously rich in probiotics and should be consumed regularly:

  • Fermented vegetables (sauerkraut, kimchi)
  • Kombucha
  • A multi-species dairy-free probiotic supplement can also be equally beneficial

Heal the Intestinal Wall

  • Bone Broth, rich in glycine, gelatin, and glutamine which is essential for intestinal repair
  • Fermentable fibers, like sweet potatoes
  • Healthy fats sources including pasture raised animals, avocado, coconut oil, pure olive oil
  • Omega-3 rich foods like seafood and salmon

Finally, a vital part of gut health is to be able to adequately manage stress. Excessive stress results in heightened cortisol levels which can over time wreak havoc on hormone functionality and other bodily processes including gut functioning.

It is important to avoid chronic stress and to incorporate activities you enjoy in your day-to-day. Activities such as hiking, meditation, playing with your kids, or socializing with friends and family are all great ways to reduce stress.

Stick to these tips and you will be well on on your way to achieving a healthy gut!

Kyle Cordain, The Paleo Diet Team

Hidraenitis Suppurativa | The Paleo Diet

Hi Dr. Cordain,

I’m not sure if you remember me- I was one of the women who interviewed you last August at the Ancestral Health Symposium in LA.

The reason I’m writing you today is 1) to thank you and 2) to ask you some questions. When we spoke, I asked you about Hidradenitis Suppurativa (HS). You told me that you suspected it had an autoimmune connection, but didn’t have any more information to add. I suffered from HS for over 20 years, Stage II, so I was very motivated to get rid of it for good. Once you mentioned “autoimmunity,” I went on an autoimmune Paleo protocol and my HS disappeared. With experimentation, I found my trigger- potatoes. I never would have known, or even tried the AlP, had you not mentioned autoimmunity. For that, I thank you from the bottom of my heart. 3) I had a guest post on robbwolf.com about the issue (I’ve now been in clinical remission off medication for almost a YEAR) and am currently writing a book about it. My background is in Journalism, though, not science or any medical field, so I am quoting the hell out of your book, Robb Wolf’s book, and others.

1. I can’t find any documentation of HS being autoimmune in nature, except for what you told me in the hallway of the AHS building. Doctors currently treat it with antibiotics or don’t treat it at all. You did say when we spoke that you were going to look into it. Do you know of any medical literature that suggests that HS is autoimmune in nature?

2. When I experimented on myself by removing nightshades and went into remission, and then flared up when I reintroduced potatoes, did I not prove the autoimmune nature of HS in myself? I have been talking to other people who have been also putting their HS into remission by removing nightshades and it seems to be working across the board. Some have diagnosed wheat as their trigger, but the overwhelming majority of us have found nightshades to be the offender. I did do my elimination and reintroduction quite scientifically, but I’m not a scientist, so do my results “count” or are they just anecdotal?

3. You say that the white blood cells in our guts have become sensitized to proteins from bacteria or food or both. For people who have become sensitized to the bacteria, what options are available to them? Obviously antibiotics don’t work in this case, so would taking probiotics and something like Allimed (a garlic extract which has been shown to have antibacterial effects in the body) help? Since I didn’t have this particular problem, I would like to present options in my new book and help those who do. Obviously I am putting the dietary changes at the forefront of the treatment, but if those fail, then I would like to have another line of treatment, unless the dietary changes plus probiotics are enough if kept up in the long run (long enough to allow the gut to fully heal)?

That’s it! Thank you so much for your time and consideration. And thank you again for giving me the tools to change my life. I’ve had a few emails from people who say they want to kill themselves and I am driven to help them end their symptoms.

Cheers,

Tara Grant

Tara Grant has transformed from 235 pounds to 159 pounds since going Primal in 2009. Tara suffered a litany of serious health problems related to the Standard American Diet and repeated failures of western medicine to cure her. Empowered by the reclaiming of her health, Tara has made it her mission to inform and inspire others about Primal living. Her motto, “Empower. Enlighten. Evolve”, has been put into play in numerous ways! Her book, The Hidden Plague – A Comprehensive Guide to Surviving Hidradenitis Supprativa – details her struggle with this debilitating skin condition, and how sufferers can take matters into the own hands and heal naturally.

Tara is a veteran presenter of numerous PrimalCons, where she holds court detailing her Primal transformation from health to wellness. Tara is also a contributing writer for the Primal Blueprint Expert Certification program and is working with Carrie Sisson on her upcoming Primal Woman book. A dynamic speaker, Tara presents the Primal Transformation Seminar in numerous cities, and counsels individuals as a certified CHEK Holistic Life Coach. Tara holds a degree in Journalism from Carleton University in Ottawa, Canada and blogs regularly at www.primalgirl.com. She currently lives in Phoenix, Arizona with her husband Derek and their twin boys, Taylor and Gibson.

Dr. Cordain’s Response:

Hi Tara,

Let me dive into your questions. Specific white blood cells called dendritic cells process protein fragments (antigens) of gut bacteria and/or food antigens in a manner that may promote inflammation and autoimmunity in genetically susceptible people. When the gut becomes leaky, it allows these antigens to interact with dendritic cells and other immune system cells to set the stage for autoimmune diseases. Hence, dietary and environmental factors which promote a leaky gut need to be removed.

1. Nightshade plants contain a variety of compounds which promote a leaky gut, but also can be sources of immunological adjuvants (compounds used in vaccines to rev up the immune response).

2. Alpha tomatine in tomatoes has been demonstrated to be a powerful adjuvant.

3. Probiotics and Prebiotics represent good supplements for most people to promote and healthy gut flora and to reduce intestinal permeability. I know of one physician who healed his alopecia completely only after adopting Paleo and then adding probiotics. However, I also know of a few cases where probiotics may agitate the gut and make things worse.

4. Garlic has been used in traditional medicine for thousands of years to cure a variety of health problems. I haven’t examined the literature on the topic of autoimmunity and garlic, but garlic is a concentrated source of saponins which in most cases disrupt membrane function and can lead to a leaky gut.

In my most recent book, The Paleo Answer, I list all of the known dietary factors which promote a leaky gut.

Below are the references which led me to believe HS is a gut mediated autoimmune disease that has the potential to be improved or put into remission by contemporary Paleo diets – gluten free, dairy free, grain free, legume free, and nightshade free. In your case nightshades were the major triggering factor, and we believe it is because certain glycoalkaloids in tomatoes and potatoes may act to increase intestinal permeability and also contain certain immunological adjuvants (alpha tomatine in tomatoes) that up-regulate the immune response in genetically susceptible HLA haplotypes.

Good luck with your book!

Cordially,

Loren Cordain, Ph.D., Professor Emeritus

References

1. Rambhatla PV, Lim HW, Hamzavi I. A systematic review of treatments for hidradenitis suppurativa. Arch
Dermatol. 2012 Apr;148(4):439-46 Epub 2011 Dec 19.

2. Nazary M, van der Zee HH, Prens EP, Folkerts G, Boer J. Pathogenesis and pharmacotherapy of
Hidradenitis suppurativa. Eur J Pharmacal. 2011 Dec 15;672(1-3):1-8. Epub 2011 Sep 14.

3.Dreno B, Khammari A, Brocard A, Moyse D, Blouin E, Guillet G, Leonard F, Knol AC. Hidradenitis
suppurativa: the role of deficient cutaneous innate immunity. Arch Dermatol. 2012 Feb;148(2):182-6.
Epub 2011 Oct 17.

4.Brocard A, Dreno B. Innate immunity: a crucial target for zinc in the treatment of inflammatory dermatosis. J Eur Acad Dermatol Venereal. 2011 Oct;25(10):1146-52. doi: 10.1111/j.1468-
3083.2010.03934.x. Epub 2011 Jan 24.

5. van der Zee HH, de Ruiter L, van den Broecke DG, Dik WA, Laman JD, Prens EP. Elevated levels of tumour necrosis factor (TN F)-a, interleukin (IL)-1[3 and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TN F-a and IL-1[3. Br J Dermatol. 2011 Jun;164(6):1292-8. doi: 10.1111/j.1365-
2133.2011.10254.x. Epub 2011 May 17.

6. van der Zee HH, van der Woude CJ, Florencia EF, Prens EP. Hidradenitis suppurativa and inflammatory bowel disease: are they associated? Results of a pilot study. Br J Dermatol. 2010 Jan;162{1):195-7. Epub
2009 Aug 14.

7. van der Zee HH, Laman JD, de Ruiter L, Dik WA, Prens EP. Adalimumab (antitumour necrosis factor-a) treatment of hidradenitis suppurativa ameliorates skin inflammation: an in situ and ex vivo study. Br J
Dermatol. 2012 Feb;166(2):298-305.

8. Giamarellos-Bourboulis EJ, Antonopoulou A, Petropoulou C, Mouktaroudi M, Spyridaki E, Baziaka F,
Pelekanou A, Giamarellou H, Stavrianeas NG. Altered innate and adaptive immune responses in patients with hidradenitis suppurativa. Br J Dermatol. 2007 Jan;156(1):51-6.

9. Hunger RE, Surovy AM, Hassan AS, Braathen LR, Yawalkar N. Toll-like receptor 2 is highly expressed in lesions of acne inversa and colocalizes with C-type lectin receptor. Br J Dermatol. 2008 Apr;158(4) :691-7. Epub 2008 Jan 30.

10. Schlapbach C, Hanni T, Yawalkar N, Hunger RE. Expression ofthe IL-23/Th17 pathway in lesions of
hidradenitis suppurativa. JAm Acad Dermatol. 2011 Oct;65(4):790-8.

Hidradenitis Suppurativa | The Paleo Diet

Dear Professor Cordain,

I read very useful information on your website regarding the importance of nutrition for health, therefore I have a few questions and hope you will find time to provide the answers.

My fiance have been struggling with Hidradenitis Suppurativa (HS) for about 12 years. Doctors and antibiotics did not provide much help. The only thing that helped him about 10 years ago was his trip to Malaysia that resulted in total change of food (no bread, no meat – except fish, no diary, but a lot of turmeric).

Unfortunately, the illness returned about two years ago and has been getting worse. As a psychologist, and Ph.D. candidate in psychology, I know how stress can be related to this disease.

But, I also read on Internet (Primagirl Blog, more precisely), that The Paleo Diet can heal this disease, because it is always certain types of food that triggers it. I also found your name and information on your book there, therefore I decided to contact you.

I would really appreciate if you could help me with your advice. If you know what kind of food can trigger this disease, or if you can recommend something, I would strongly appreciate.

Thank you in advance.

Sincerely,

Alma

Dr. Cordain’s Response:

Hi Alma,

Abundant scientific evidence exists in Hidradenitis Suppurativa (HS) patients showing that pro-inflammatory cytokines (local hormones) are elevated in the blood are almost certainly involved in the skin lesions presenting in HS patients. Two major categories of circulating white blood cells (macrophages and dendritic cells) likely have become activated (sensitized) in the gut to specific gut proteins (either bacteria or food or both) and these gut borne cells then initiate an immune response which affects cells lining either the hair follicle or apocrine sweat glands in other parts of the body, particularly the groin and armpit areas. Hence, it seems likely that HS, although it presents clinically as a single disease, is actually at least two diseases, one in the hair follicle and one in the apocrine sweat glands, both likely to be autoimmune in nature. Women are more likely to have the form of HS involving the cells lining the hair follicle. To date, it has not been conclusively demonstrated that HS is autoimmune in nature. Nevertheless, work from our group as far back as 2002 and from Alessio Fasano’s group at the University of Maryland suggest that a key triggering event in most autoimmune diseases is a leaky gut.

My suggestion for all autoimmune patients is to restrict foods which are known to increase intestinal permeability. These food restrictions form the basis for the contemporary Paleo Diet, however for autoimmune patients a few more restrictions should be included.

General food restrictions for all Paleo Dieters include:

1. All cereal grains (wheat, rye, barley, oats, rice, corn, sorghum and millet). Wheat is probably the grain which should be avoided strictly because of its combination of antinutrients (wheat germ agglutinin, gliadin, thaumatin like proteins, and phytic acid) which have varying degrees of toxicity in humans.

2. All dairy products. The rationale for this food group restriction can be found in my new book, The Paleo Answer, in a single chapter I have written with hundreds of scientific references to support these conclusions.

3. All beans, legumes (including, green beans, soy, peas and peanuts). Again, I have extensively documented the rationale for these restrictions in The Paleo Answer.

4. All processed foods containing refined sugars, grains, vegetable oils and salt. The rationale for these restrictions can be found in all of my popular books and in my scientific writings which are available across the website.

An Elimination Diet

For Autoimmune patients including those with HS, I suggest restricting the following foods for a 30 day period to determine if symptoms improve. This strategy is called an “elimination diet” in which foods are removed from the diet and then added back in to determine if they are problematic.

1. All nightshades (potatotes, tomatoes, eggplants, tomatillos, tobacco and all capsaicin containing peppers [cayenne, serrano, jalapeno, paprika, habanera and all foods made with these- salsa, hot sauce, tomato pastes & sauces etc.]. The nightshade family of plants contain a variety of compounds which increase intestinal permeability. In potatoes, it is the glycoalkaloids (alpha solanine and alpha chaconine); in tomatoes it is alpha tomatine; in spicy peppers it is capsaicin. The scientific references showing how nightshade compounds increase intestinal permeability can be found in my new book, The Paleo Answer. In HS patients, smoking tobacco (a nightshade plant) has been shown to aggravate the disease symptoms in HS patients.

2. Alcohol (ethanol) found in beer wine and all alcoholic beverages increases intestinal permeability.

3. Aluminum hydroxide (alum) in antacids increases intestinal permeability.

4. Alfalfa sprouts contain high concentrations of compounds called saponins which increase intestinal permeability.

5. Psuedo grains (quinoa, amaranth) contain saponins which increase intestinal permeability in a dose dependent manner – meaning the more you consume the leakier the gut becomes. Chia seeds also likely increase intestinal permeability.

6. Oral contraceptives

7. NSAIDS (Nonsteroidal anti-inflammatory drugs) like aspirin and ibuprofen.

8. Egg whites contain a substance called lysozyme which increases intestinal permeability.

9. A foaming agent called Quillaja found in many brands of root beer increases intestinal permeability and potently stimulates the immune system.

10. In addition to peanuts, which are not a not at all, but a legume, tree nuts (almonds, walnuts, pecans, brazil nuts, etc.) are one of the most common allergenic foods. To date, tree nuts have been poorly studied for antinutrient content, and it is unclear if they increase intestinal permeability or adversely affect the immune system. This would be one of the last foods I suggest restricting.

Supplementation

Zinc supplementation (90 mg/day for 3 months) has been shown to reduce inflammation in HS patients. Supplements which improve intestinal integrity and which may reduce intestinal permeability include:

1. Probiotics

2. Prebiotics

3. Viamin D3

4. Fish oil (EPA and DHA)

5. Zinc

6. Medium chain triglycerides (Coconut Oil)

There are no guarantees that these food restrictions will improve symptoms or cure autoimmune diseases.

Nevertheless, I know of hundreds of anecdotal cases worldwide which demonstrate contemporary Paleo diets to be therapeutic in autoimmune patients. Together with my graduate students we are currently writing up a large case study involving nearly 100 autoimmune patients who have reported varying degrees of success in managing their conditions following The Paleo Diet.

Cordially,

Loren Cordain, Ph.D., Professor Emeritus

References

1. Rambhatla PV, Lim HW, Hamzavi I. A systematic review of treatments for hidradenitis suppurativa. Arch
Dermatol. 2012 Apr;148(4):439-46 Epub 2011 Dec 19.

2. Nazary M, van der Zee HH, Prens EP, Folkerts G, Boer J. Pathogenesis and pharmacotherapy of
Hidradenitis suppurativa. Eur J Pharmacal. 2011 Dec 15;672(1-3):1-8. Epub 2011 Sep 14.

3.Dreno B, Khammari A, Brocard A, Moyse D, Blouin E, Guillet G, Leonard F, Knol AC. Hidradenitis
suppurativa: the role of deficient cutaneous innate immunity. Arch Dermatol. 2012 Feb;148(2):182-6.
Epub 2011 Oct 17.

4.Brocard A, Dreno B. Innate immunity: a crucial target for zinc in the treatment of inflammatory dermatosis. J Eur Acad Dermatol Venereal. 2011 Oct;25(10):1146-52. doi: 10.1111/j.1468-
3083.2010.03934.x. Epub 2011 Jan 24.

5. van der Zee HH, de Ruiter L, van den Broecke DG, Dik WA, Laman JD, Prens EP. Elevated levels of tumour necrosis factor (TN F)-a, interleukin (IL)-1[3 and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TN F-a and IL-1[3. Br J Dermatol. 2011 Jun;164(6):1292-8. doi: 10.1111/j.1365-
2133.2011.10254.x. Epub 2011 May 17.

6. van der Zee HH, van der Woude CJ, Florencia EF, Prens EP. Hidradenitis suppurativa and inflammatory bowel disease: are they associated? Results of a pilot study. Br J Dermatol. 2010 Jan;162{1):195-7. Epub
2009 Aug 14.

7. van der Zee HH, Laman JD, de Ruiter L, Dik WA, Prens EP. Adalimumab (antitumour necrosis factor-a) treatment of hidradenitis suppurativa ameliorates skin inflammation: an in situ and ex vivo study. Br J
Dermatol. 2012 Feb;166(2):298-305.

8. Giamarellos-Bourboulis EJ, Antonopoulou A, Petropoulou C, Mouktaroudi M, Spyridaki E, Baziaka F,
Pelekanou A, Giamarellou H, Stavrianeas NG. Altered innate and adaptive immune responses in patients with hidradenitis suppurativa. Br J Dermatol. 2007 Jan;156(1):51-6.

9. Hunger RE, Surovy AM, Hassan AS, Braathen LR, Yawalkar N. Toll-like receptor 2 is highly expressed in lesions of acne inversa and colocalizes with C-type lectin receptor. Br J Dermatol. 2008 Apr;158(4) :691-7. Epub 2008 Jan 30.

10. Schlapbach C, Hanni T, Yawalkar N, Hunger RE. Expression ofthe IL-23/Th17 pathway in lesions of hidradenitis suppurativa. JAm Acad Dermatol. 2011 Oct;65(4):790-8.

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