1.
Gluten SensitivityA Systems Medicine Approach Keith Berndtson, MD

2.
What is gluten?A. A protein mainly found in wheat, rye, and barley.B. A chain of peptides including gliadins and glutenins.C. A substance that gives bread a pleasant texture, and lends dough more versatility.D. An additive used to stabilize processed foods.E. A potentially lethal substance.F. All of the above.

3.
Three Medical Conditions Related to Gluten Exposure Wheat Allergy Celiac Disease Gluten Sensitivity•Allergic •Autoimmune •“GS” cause unknown•Misc. wheat proteins •Gluten the cause •Innate immune system•IgE mediated •T-cell mediated •Cytokine mediated•Histamine release •Leaky gut the trigger •Spectrum of disorders•Allergy signs •Malabsorption •Malabsorption•GI, lungs, skin •Multiple tissues •No tissue damage•Anaphylaxis risk •Many symptoms •Many symptoms•Hours to minutes •Weeks to years •Hours to days•Accepted biomarkers •Accepted biomarkers •Proposed biomarkers

4.
The Two Types of Gluten SensitivityType 1: Celiac Permissive GS Type 2: Non-Celiac GS• 3 HLA-DQ genes permit celiac and pre- •No HLA genotype predictors thus far, celiac disease. research ongoing.• Celiac panels predict likelihood of celiac •Mechanisms and predictors poorly disease, not Type 2 non-celiac GS. understood.• Both malabsorption and leaky gut can •Malabsorption known to occur with this appear with this form. form but leaky gut may not be required.• G-free trial helpful to assess non-celiac •G-free trial warranted to help determine GS even when celiac panel is negative. if symptoms subside off gluten.•Affects ~1% of population. •Affects ~6% of population.•3 million Americans have it. •18 million Americans have a form of it.An estimated 21 million Americans have GS-related health problems.

5.
“If you’re suffering with Doctors are symptoms that make your life miserable and you’ve divided about “It is not a healthy diet for those who don’t need investigated all possible non-celiac it. These people are following a fad, causes, I don’t see anything wrong with going on a gluten sensitivity essentially, and that’s my biased opinion.” gluten-free diet.” - New York Times - Living Without Magazine Feb 4, 2013 Aug/Sep 2011 Alessio Fasano, MD Stefano Guandalini, MD University of Maryland University of ChicagoGoing gluten-free is no walk in the park. While unexplained symptomsoften resolve on a gluten-free diet, the diet can be unhealthy if it leads toincreased junk carb, salt, and fat intake. With leading experts divided... What is a concerned health consumer to do?

6.
When the scientific evidence is blurry... seek asystems medicine approach.

7.
vs.Systems Medicine Reformed MedicineSays it is patient-centered. Says it is patient-centered.Feels patient-centered. Feels like a conveyor belt.Splits cases into unique narratives. Lumps cases into disease groups. Explanatory power is king. Diagnostic labels suffice. Listens well. Hard of hearing. Shared decision-making. Top-down decision-making. Integrative medicine is valued. To be determined. Goal: restore functional integrity. Goal: hit productivity targets. Unhurried curiosity. HMO-like need for speed.Free to improvise. “Evidence-based” rules dictate. Accommodates complexity. Downplays complexity.

8.
The Wrong Approach to Diagnosing Gluten Sensitivity Your medically unexplained symptoms could be gluten-related. Your doctor orders a celiac panel: Your Celiac Panel Results 1. anti-transglutaminase IgA = 5 Antibody detected, but not high enough to be called (+). 2. total IgA = 243 The reference range is 81-463 mg/dL, so this is not a low amount of IgA. 3. anti-gliadin (deamidated) IgA = 11 Antibody detected, not high enough to be called (+). The results are “negative.” You’re told not to worry about gluten. The advice is incorrect. Here’s why:1. A celiac panel is not enough to decide if GS is related to your unexplained symptoms - you need to check your celiac genotype.2. If your genotype is positive, you could have pre-celiac GS. If it’s negative, you could nonetheless have non-celiac GS.

9.
The Right Approach to Diagnosing Gluten Sensitivity Moderate to severe medically unexplained symptoms? Check the celiac panel and the HLA celiac genotype. (+) celiac panel (-) celiac panel (-) celiac panel(+) celiac genotype (+) celiac genotype (-) celiac genotype >90% have possible possible celiac disease pre-celiac GS non-celiac GSPermanently G-free 3-month G-free trial 3-month G-free trial Better Not better Better Not better Continue Re-evaluate Continue Re-evaluate Monitor

10.
What is celiac disease?An autoimmune disease that damages the small intestinal lining. Marsh 0 Marsh 1 Marsh 2 Marsh 3a Marsh 3b Marsh 3c The Marsh system for classifying degree of abnormality on biopsy. From Shag to Berber Progression from a normal gut lining (0) to total villous atrophy (3b) can take months to decades for reasons we cannot yet predict. figure from: Kneepkens, CMF, vonBlomberg BME, Coeliac Disease. European J Pediatrics. 2012 Jul;171(7):1011-1021

11.
Gliadin: the Pros and Cons Gliadin’s Benefits Cross-linked amino acids make gliadin a sticky molecule that holds together as baked dough rises. The higher the gliadin content in the dough, the more chewy the bread or crust. Lower gliadin content results in a flakier bread and crust. No gluten Sticky free grains contain a perfect disulfide bridges substitute for gliadin.Normal digestion breaks protein down into short peptides and single amino acids.Due to its disulfide bridges, gliadins can resist complete digestion. In people whoare genetically predisposed, undigested gliadin fragments trigger furious immuneresponses that can cascade into a surprisingly broad range of health problems.

12.
Some of the health problemsassociated with celiac disease Obesity Cerebellar ataxia Microscopic colitis Neuroimmune disease Food sensitivities Neuropathy Iron deficiency Autoimmune arthritis Magnesium deficiency Autoimmune thyroiditis Vitamin D deficiency Diabetes Vitamin B12 deficiency Failure to thrive Insomnia Infertility Migraine headaches Osteoporosis Anxiety Dermatitis herpetiformis Depression Endometriosis ADHD Hepatitis Cognitive dysfunction Recurrent canker sores Dementia Growth delay

13.
Celiac DiseaseLeaky Gut Needed to Flip the GS Switch Diagram source: Fasano A. Surprises from Celiac Disease. Scientific American. 2009 Aug:32-9.

14.
Celiac DiseaseSuspected Triggers for Leaky GutAntibiotics.Steroids, NSAIDs.Antacids. Allergies, toxicities.GI infections/dysbiosis.Food sensitivities.Excess sugar/junk food.Excess alcohol.Immunosuppressants. Are you at increased risk for intestinal hyper-permeability?Inflammatory disease.

15.
Celiac Disease Ways of Testing for Leaky Gut Labs that evaluate intestinal permeability: Intestinal Lactulose Permeability: to mannitol Direct ratio GI Effects: Comprehensive Indirect stool analysis Intestinal GI-specific Antigenic antibody Permeability: Indirect panelIf a leaky gut flipped your GS switch, ongoing gluten exposure could beruining your life! Let’s get a celiac genotype check for leaky gut.

16.
Celiac DiseaseA Commonly Missed Diagnosis For every 1 person with known celiac disease, 19 others are undiagnosed. Ascher H, Kristiansson B. Childhood celiac disease in Sweden. Lancet, 1994;44:340 Most cases are missed because they lack typical gastrointestinal symptoms. Fasano A, Catassi C. Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. Gastroenterology. 2001;120:636.

17.
Celiac Disease Global Prevalence Kamin DS, Furuta GT. The iceberg cometh: establishing the prevalence of celiac disease in the United States and Finland. Gastroenterology. 2003;126(1):359.In 1980, celiac disease was thought to exist in 1 of 10,000 people. Today the globalprevalence of celiac disease is 1 in 130 - as high as 1 in 30 to 40 in people of Irish or Italiandescent. The prevalence has increased 100-fold because we’re diagnosing more cases, butalso because more cases are occurring as a result of increasing exposure to gluten,unhealthy lifestyles, and more triggers for leaky gut.

18.
Celiac Permissive HLA-DQ Genotypes DQ2.5 DQ8 DQ2.2DQA1:05 / DQB1:0201 or 0202 DQA1:03 / DQB1:0302 DQA1:02 / DQB1:0202 1 copy enough, 2 copies high risk. 1 copy enough, 2 copies high risk. 2 copies permissive, one possibly. A celiac permissive genotype is a necessary but not sufficient condition for progression to celiac disease. These HLA-DQ variants are present in more than 25% of the global population, but only 1% of the population has celiac disease. The big question is what percentage of people with celiac permissive genes suffer from pre-celiac disease? If you have medically unexplained symptoms, you have a higher pre-test likelihood for celiac, pre-celiac, or non-celiac GS. If you have unexplained symptoms, the presence of one or more of these genes always warrants a 3-month G-free trial to rule out pre-celiac disease.

19.
HLA Test Reporting Format Matters! The truth: all labs could do aLocal Hospital Labs better job of HLA DQ reporting.HLA DQ reports should clearly list detected alpha and beta pairs sointerpreters can tell if a DQ2.2 genotype is present.Going forward, HLA DQ reports should be viewed as relevant not justfor celiac risk, but also for pre-celiac disease risk.

20.
Reasons for Gluten-Free Trial Failures In one study, a G-free diet for one year proved curative in 70% of adults diagnosed with CD by biopsy.What could have gone wrong for the other 30%? Inadequate nutritional repletion. Might involve protein, iron, B12, vitamin D, vitamin A, or minerals in various combinations. Tag-along problems that followed in the wake of CD. These include weak digestion, other food sensitivities, and gut floral imbalances that could persist to perpetuate leaky gut and frustrate recovery. Co-morbid conditions. Separate problems that need to be treated in their own way for someone to feel better (“the two-thumbtack theory”). Genetics and lifestyle. Genes load the gun, environment pulls the trigger.

21.
CD Natural Histories: Four Cases Normal Leaky gut pre-celiac celiac onset age 7 celiac dx age 22 dx delay: 15 yrs LG: frequent antibiotics for URIs? PC: nausea, fatigue, growth delay.Case 1 onset age 24 celiac dx age 45 dx delay: 21 yrs LG: frat lifestyle? PC: anxiety, insomnia, joint pains.Case 2 onset age 20 celiac dx age 59 dx delay: 39 yrs LG: steroids? PC: IBD, cerebellar ataxia,Case 3 migraines. Died age 70. onset age 27 Celiac dx by autopsy. dx delay: 43 yrs LG: parasite? PC: multipleCase 4 diagnoses, many admissions, dermatitis herpetiformis. 0 20 40 60 80 100

22.
The goal of diagnosis:Stop missing cases!Crowd = 100,000 Celiacs = 1,000 Known Celiacs = 50 Pre-Celiacs = ? Leaky guts = ? Non-Celiac gluten sensitivity = ?

23.
Clearing the HurdlesSo, you’ve been advised to go gluten free and you’re thinking... OMIGOD! Where do I start?What have I done?

24.
Clearing the Hurdles With Gluten Gluten-free light, airy, and springy dense and crumblyAn initial hurdle for many people who’ve been advised to begin agluten free lifestyle is finding a satisfying gluten free bread. Suchpeople routinely clear the hurdle through trial and error and with helpfrom friends, support groups, and online resources.

25.
Some fan favorites

26.
Clearing the Hurdles Certain people with GS also suffer from tag-along food sensitivities. These sensitivities commonly include dairy and sugar, but can include any GF-grains Meats, nuts number of foods. fruits, healthy legumes, carbs dairy To get well, such people may need to identify and restrict exposure to tag- along reactive foods. Vegetables Tag-along reactive food restriction is almost always temporary (less than 6 months). Still, some will find that for certain foods, long-term avoidance works best.The G-free Plate Method

27.
Congratulations!You’ve learned a systems medicine approach to gluten sensitivity. Treat yourself to a gluten-free feast! An app et with no izer G-free bre t: and G-f ad desser ree breadin g: refills! Free An entree with G-free bread: to ward off A cup of Joe a? ing food com your impend Yes, a G-free diet can be unhealthy - but that’s up to you.

28.
You can take control of your health! Now that you know how to solve the gluten puzzle...and where to find any help you may need along the way.

29.
Patient-centered systems medicine. 15 N. Prospect Park Ridge, IL 60068 847-232-9800(for nutrition consults by phone)www.parkridgemultimed.com