new diet therapy of ibs, migraine and fibromyalgia · limit pressor amines (chocolate, red wine,...

New Diet Therapy of Irritable Bowel Syndrome,

Migraine

Jan Patenaude, R.D.Jan Patenaude, R.D.Director of Medical NutritionDirector of Medical Nutrition

Signet Diagnostic Corp.Signet Diagnostic Corp.

OverviewCase PresentationCase PresentationGut ImmunologyGut ImmunologyFood Allergy vs. Food Intolerance vs. Food Food Allergy vs. Food Intolerance vs. Food Sensitivity Sensitivity –– and testingand testingOral ToleranceOral ToleranceIBS & Migraine IBS & Migraine -- Standard TreatmentStandard TreatmentMediator Release TestingMediator Release TestingLEAP Dietary ProtocolsLEAP Dietary ProtocolsReduction of Global and GI Symptoms StudyReduction of Global and GI Symptoms StudyCytokine Study Cytokine Study –– If time allowsIf time allowsSummarySummary

Symptoms Due to Food IntolerancesSymptoms suffered by 122 patients subsequently identifying food intolerances

Abdominal pain (73%)Abdominal pain (73%)Diarrhea (60%)Diarrhea (60%)Tiredness (42%)Tiredness (42%)Headaches (38%)Headaches (38%)Constipation (23%)Constipation (23%)Bloating (21%)Bloating (21%)Fluid retention (20%)Fluid retention (20%)

Gut Immunology

If you think about it, your intestinal tract is If you think about it, your intestinal tract is on the outside of your bodyon the outside of your bodyIt is bombarded with countless chemicals, It is bombarded with countless chemicals, proteins, bacteria and antigens on a daily proteins, bacteria and antigens on a daily basis that are trying to cross the gut basis that are trying to cross the gut mucosa and gain access to the bodymucosa and gain access to the bodyThe gut must decide what ‘contents’ are The gut must decide what ‘contents’ are healthy nutrients and allow them to be healthy nutrients and allow them to be absorbed and utilized by the bodyabsorbed and utilized by the body

Three Major Food Reactions

Food Allergy Food Allergy –– IgEIgEFood Intolerance Food Intolerance –– NonNon--immunologicimmunologicFood Sensitivity Food Sensitivity –– NonNon--IgE IgE ––But still a gut But still a gut immune response (GALT)immune response (GALT)Naming is Controversial Naming is Controversial –– NonNon--IgE IgE immune related responses called ‘nonimmune related responses called ‘non--IgE IgE allergy’ by someallergy’ by some

Food Allergy –Type 1IgEIgEUsually immediateUsually immediateCan result in anaphylaxisCan result in anaphylaxisOverall, a relatively small number of Overall, a relatively small number of patients with IgE mediated allergies patients with IgE mediated allergies -- 22--4%4%Peanut, milk, egg, fish, wheat, nuts, soyPeanut, milk, egg, fish, wheat, nuts, soy

Food Allergy ReactionAntigen is taken up by macrophages

Presented to T-lymphocytes

Rather than becoming tolerant, T-cells react to antigen

T-cells stimulate B-cells to produce IgE antibodies

IgE binds to mast cells Re-exposed to antigenAntigen binds to IgE on mast cells

Mast cells degranulate and release mediators including histamineHistamine causes flushing, shortness of breath, rapid heart rate and various GI symptoms

Allergy -Skin Prick Testing

Accurate for environmental IgE allergiesAccurate for environmental IgE allergiesNot accurate for food allergies Not accurate for food allergies –– Do we Do we really think our skin reacts the same as our really think our skin reacts the same as our gut immune system?gut immune system?Positive result is only 30Positive result is only 30--50% predictive50% predictiveIf If intradermalintradermal, , ‘‘maymay’’ increase sensitivity by increase sensitivity by ‘‘injectinginjecting’’ antigen into the bodyantigen into the body

IgE Allergy – Rast/Elisa Testing

RASTRAST-- RRadio adio AAllergollergo SSorbentorbent TTestestELISA ELISA -- EEnzyme nzyme LLinked inked IImmuno mmuno SSorbentorbentAAssayssayIf negative, does NOT mean “The food will If negative, does NOT mean “The food will be safe for you”be safe for you”If HIGH reactionIf HIGH reaction-- stay away from that foodstay away from that foodAbout 60% accuracy. May not show ‘safe’ About 60% accuracy. May not show ‘safe’ foodsfoods

Allergy testing-More

Jejunal perfusion Jejunal perfusion -- (research (research –– invasive)invasive)ColonoscopicColonoscopic allergen provocation test allergen provocation test --(research(research--invasive)invasive)Histamine Histamine -- only measures one mediator, only measures one mediator, not widely studied, accepted or used yet.not widely studied, accepted or used yet.

Causes of Food Intolerance

Food aversion Food aversion –– “I hate liver”“I hate liver”Food poisoning (infectiousFood poisoning (infectious--bacterial, viral bacterial, viral or parasitic)or parasitic)Food intoleranceFood intolerance

IrritantIrritantMalabsorption issues Malabsorption issues –– Hydrogen Breath TestHydrogen Breath TestEnzymaticEnzymatic

Non-Immunologic Food Intolerance

Lactose intoleranceLactose intoleranceFructose intolerance Fructose intolerance –– 60 lbs/year average60 lbs/year averageSIBOSIBO

http://www.uihc.uiowa.edu/FRUCTOSE/index.htmhttp://www.uihc.uiowa.edu/FRUCTOSE/index.htm

Artificial sweeteners (sugar alcohols)Artificial sweeteners (sugar alcohols)Sorbitol, Sorbitol, XylitolXylitol

Caffeine and other dietary chemicalsCaffeine and other dietary chemicalsCeliac Disease Celiac Disease –– www.celiachealth.orgwww.celiachealth.org

http://www.uihc.uiowa.edu/FRUCTOSE/index.htm

Non-Immunologic Food IntoleranceHistamine ReactionsHistamine Reactions

Aged beef, smoked meatsAged beef, smoked meatsOlder leftovers, esp. fishOlder leftovers, esp. fishImmediate reactionImmediate reaction

LectinLectin ReactionsReactionsCarbohydrate binding proteinsCarbohydrate binding proteinsSeeds, tubers, grains, beans, potatoSeeds, tubers, grains, beans, potatoMay get past the gut wall, attach to mast cellsMay get past the gut wall, attach to mast cellsImmediate or delayed reactionImmediate or delayed reaction

Food Sensitivity - Type IV

NonNon--IgE/IgG immune responseIgE/IgG immune responseInvolves different mechanisms, different Involves different mechanisms, different cells, different mediatorscells, different mediatorsMuch more common than allergy Much more common than allergy -- 1515--20%20%

Oral Tolerance

The immunologic process of determining that an The immunologic process of determining that an intestinal antigen is not harmful and subsequently intestinal antigen is not harmful and subsequently not reacting to it is termed not reacting to it is termed oral toleranceoral toleranceIt is the loss of oral tolerance with subsequent It is the loss of oral tolerance with subsequent food reactivity that causes a large component of food reactivity that causes a large component of the symptoms of Dthe symptoms of D--IBS, migraine and other IBS, migraine and other symptomssymptomsThrough the Mediator Release Testing it is Through the Mediator Release Testing it is possible to determine to which foods oral possible to determine to which foods oral tolerance has been lost and tolerance has been lost and immunoreactivityimmunoreactivity is is occurring. occurring.

Type IV Hypersensitivity Reaction

Antigen is taken up by macrophages

Presented to T-lymphocytes

Rather than becoming tolerant, T-cells react to antigen

Cytokines released

Cytokines cause various GI and systemic symptoms

Type IV Hypersensitivity ReactionFoods and food additives trigger non-allergic (non-IgE mediated) immune reaction causing mediator release by immunologic cells

HistamineSerotoninProstaglandinsLeukotrienesCytokinesDopamine Others

Type IV Hypersensitivity Reaction

This in turn leads to physiologic effects of released pro-inflammatory and pro-algesic mediators

IBS: Inflammation, smooth muscle contraction, diarrhea, cramping, and visceral hypersensitivityMigraine: Changes in blood flow (vasoconstriction or vasodilatation), inflammation, WBC activation, pain receptor activationOther symptoms: fibromyalgia, muscle and joint aches and pain, fatigue, anxiety, depression, acne, insomnia, mood swings, food cravings. Possibly seizures, autism

Is there any scientific evidenceto support the theory of immunologically mediated food sensitivities?

Intestinal Perfusion Studies

Segment of jejunum is endoscopically isolated by Segment of jejunum is endoscopically isolated by placement of two balloonsplacement of two balloonsSegment of jejunum between balloons is perfused Segment of jejunum between balloons is perfused with potential food allergen and then jejunal with potential food allergen and then jejunal contents are collectedcontents are collectedPatients with known sensitivity to the allergen had Patients with known sensitivity to the allergen had increased production histamine and increased production histamine and prostaglandin E2. prostaglandin E2. No response seen in controlsNo response seen in controls

Knutson et al, J. of Allergy and Clin. Immunology 93; 91(2): 553-9

Increased Mast Cells in IBS

In 1962 Hiatt and Katz reported increased In 1962 Hiatt and Katz reported increased numbers of mast cells in muscular layer of numbers of mast cells in muscular layer of large bowel in four surgically resected large bowel in four surgically resected specimens from patients with IBSspecimens from patients with IBSCecal and terminal ileal mast cell density Cecal and terminal ileal mast cell density was significantly higher in IBS patients as was significantly higher in IBS patients as compared to controls compared to controls

Above data from various studies

Increased Mast Cells in IBS

Mast cells noted in close proximity to Mast cells noted in close proximity to unmyelinated nerve cells in the lamina unmyelinated nerve cells in the lamina propria at the ileopropria at the ileo--cecal regioncecal regionIn one study of DIn one study of D--IBS patients, rectal mucosal IBS patients, rectal mucosal mast cell concentration was positively correlated mast cell concentration was positively correlated with increasing anxiety levelswith increasing anxiety levels

Above data from various studies

IBS Standard Treatment(Diarrhea Predominant IBS)

Interest, compassion, and reassuranceInterest, compassion, and reassuranceMedications:Medications:

AntiAnti--cholinergics/anticholinergics/anti--spasmoticsspasmoticsBentyl (dicyclomine)Bentyl (dicyclomine)Levbid (hyoscyamine)Levbid (hyoscyamine)

AntiAnti--diarrhealsdiarrhealsLomotil (diphenoxylate/atropine)Lomotil (diphenoxylate/atropine)Imodium (loperamide)Imodium (loperamide)


Medications (con’t)Medications (con’t)AntiAnti--depressantsdepressants

Elavil (amitriptyline) Elavil (amitriptyline) (nortriptyline)(nortriptyline)SSRIsSSRIs

“Avoid trigger foods”“Avoid trigger foods”Modify Fiber (Add/avoid)Modify Fiber (Add/avoid)Appropriate monitoring and follow upAppropriate monitoring and follow up

Consider more extensive work up if symptoms don’t Consider more extensive work up if symptoms don’t improveimprove


However, there is no solid scientific However, there is no solid scientific evidence supporting any of these treatments evidence supporting any of these treatments Typically, they merely mask the symptoms Typically, they merely mask the symptoms and do not treat the underlying problemand do not treat the underlying problemMany have unwanted side effectsMany have unwanted side effectsNone improve global IBS symptomsNone improve global IBS symptoms

Frequently, patients state that they think something/sin their diet is causing their symptoms

Patients Believe That Their IBS Symptoms Are Food Related

330 IBS patients and 80 controls completed 330 IBS patients and 80 controls completed a food questionnairea food questionnaireAsked to subjectively grade their response Asked to subjectively grade their response to 35 different foodsto 35 different foodsFood related GI symptoms were Food related GI symptoms were significantly higher in the IBS group as significantly higher in the IBS group as compared to controls (p<0.0001)compared to controls (p<0.0001)

Simren et al, Digestion 2001;63(2):108-115

Patients Believe That Their IBS Symptoms Are Food Related

Most frequent offending foods were:Most frequent offending foods were:CarbohydratesCarbohydratesFatsFatsCoffeeCoffeeAlcoholAlcoholHot spicesHot spices

Females and patients with anxiety had higher Females and patients with anxiety had higher frequency of foodfrequency of food--related symptomsrelated symptoms

Simren, et al, Digestion 2001;63(2):108-115

PostPost--Infectious Infectious Diarrhea Predominant IBS (DDiarrhea Predominant IBS (D--IBS)IBS)

25% of patients hospitalized for severe 25% of patients hospitalized for severe infectious gastroenteritis developed Dinfectious gastroenteritis developed D--IBSIBSColonic biopsies showed increased numbers Colonic biopsies showed increased numbers of gut mucosal lymphocytes as compared of gut mucosal lymphocytes as compared to controlsto controlsAbnormal presence of lymphocytes lasted Abnormal presence of lymphocytes lasted at least a year after the initial infection at least a year after the initial infection

Spiller et al, Gut 2000 Dec;47(6):804-811

Stress and IBS

Stress has been repeatedly shown to Stress has been repeatedly shown to trigger IBS symptomstrigger IBS symptomsBoth acute and chronic life stresses have Both acute and chronic life stresses have been shown to affect intestinal motility and been shown to affect intestinal motility and pain sensitivitypain sensitivityIt is probably a complex neural, hormonal, It is probably a complex neural, hormonal, and immunologic interactionand immunologic interaction

Inflammatory Mediators Can Affect the CNS

Some mediators can open and/or cross the Some mediators can open and/or cross the blood brain barrier blood brain barrier Systemic cytokines can alter such Systemic cytokines can alter such neurologic functions as food intake and neurologic functions as food intake and temperaturetemperatureImportantly, cytokines are potent regulators Importantly, cytokines are potent regulators of the neuroendocrine system that regulates of the neuroendocrine system that regulates the body’s response to stress the body’s response to stress

Conditions That May Be Associated with Food Sensitivity

Celiac diseaseCeliac diseaseUlcerative colitisUlcerative colitisCrohn’s diseaseCrohn’s diseaseGERDGERDAsthmaAsthmaMigrainesMigrainesInterstitial cystitisInterstitial cystitisTinnitus

Rhinitis/SinusitisRhinitis/SinusitisSecretory otitis mediaSecretory otitis mediaADHDADHDUrticariaUrticariaAngioAngio--edemaedemaRheumatologic Rheumatologic disordersdisordersAtopyAtopyTinnitus

Typical Dietary Recommendations for D-IBS

““Increase Dietary Fiber Intake”Increase Dietary Fiber Intake”-- often brings gas often brings gas and discomfort requiring much experimentationand discomfort requiring much experimentation“Eat Small Frequent Meals”“Eat Small Frequent Meals”“Eat Low Fat Content Meals”“Eat Low Fat Content Meals”“Drink Lots of Water”“Drink Lots of Water”“Avoid Gas Forming Foods”“Avoid Gas Forming Foods”“Avoid Spicy Foods”“Avoid Spicy Foods”““Avoid FOOD TRIGGERS Avoid FOOD TRIGGERS ””

Typical Dietary Recommendations for Migraine

Limit Pressor Amines Limit Pressor Amines (chocolate, red wine, aged (chocolate, red wine, aged cheeses, beer, liver, smoked meats, ripe fruits, etc.)cheeses, beer, liver, smoked meats, ripe fruits, etc.)Limit dietary histamine (aged/cured meats, liver, Limit dietary histamine (aged/cured meats, liver, leftovers/older fish, sauerkraut, etc.)leftovers/older fish, sauerkraut, etc.)Avoid dehydrationAvoid dehydration--drink plenty of waterdrink plenty of waterAvoid hypoglycemiaAvoid hypoglycemiaEat lower fat mealsEat lower fat mealsEliminate caffeineEliminate caffeineAvoid MSGAvoid MSGAvoid FOOD TRIGGERS Avoid FOOD TRIGGERS

A Typical Elimination Diet

Lamb, turkeyLamb, turkeyCarrots, spinach, sweet potatoCarrots, spinach, sweet potatoRice, cream of rice, rice flour, rice cakesRice, cream of rice, rice flour, rice cakesPears, apricots, plumsPears, apricots, plumsGhee or clarified butter Ghee or clarified butter Olive OilOlive OilWaterWater

What Are The Usual Results Of These Wide Ranging Restrictions?

Poor patient acceptance and compliancePoor patient acceptance and compliancePoor outcomes and Poor outcomes and FRUSTRATIONFRUSTRATIONFrequent revisits and guess workFrequent revisits and guess workPoorer quality of life Poorer quality of life –– for everyonefor everyoneIncreased meds and cost to patient/insurerIncreased meds and cost to patient/insurerResponsibility placed on RD or physician Responsibility placed on RD or physician in the mind of the patient.in the mind of the patient.

Lifestyle Eating And Performance Mediator Release Test (LEAP MRT)

A patient blood sample is A patient blood sample is tested for 150 common tested for 150 common foods and foodfoods and food--chemicalschemicals

The Signet STS 100 MRT Device Circa 2000

Lifestyle Eating And Performance Mediator Release Test (LEAP MRT)Each sample is then analyzed in sequence Each sample is then analyzed in sequence and compared to the patients own control and compared to the patients own control samples (patients immunocytes samples (patients immunocytes unchallenged) to check for unchallenged) to check for anyany mediator mediator release from the cells regardless of cell class release from the cells regardless of cell class or mechanism. or mechanism.

The cells should The cells should not react.not react.

Pasula et al, Amer. Clin. Lab., May 99; 18(4): 16-18Pasula et al, Amer. Clin. Lab., Oct 99; 18(4): 14-15

The degree of reactivity to the The degree of reactivity to the food substance is determined by food substance is determined by the degree of actual mediator the degree of actual mediator release from the cells as release from the cells as detected by the instrumentdetected by the instrumentThe degree of reactivity The degree of reactivity can be semican be semi--quantifiedquantified

LLifestyle ifestyle EEating ating AAnd nd PPerformance erformance MMediator ediator RRelease elease TTest (est (LEAP MRTLEAP MRT))


A patient specific A patient specific elimination diet is elimination diet is then developedthen developed

Patients initially eat Patients initially eat only the least only the least reactive of the reactive of the NonNon--reactivereactive foodsfoods


Slowly, they are Slowly, they are allowed to allowed to reintroduce new reintroduce new NonNon--reactivereactive foodsfoodsThey are advised to They are advised to avoid all avoid all Moderately Moderately ReactiveReactive and and Reactive foodsReactive foods


In time, they are In time, they are advised to rotate all advised to rotate all foodsfoodsThey continue to They continue to add ‘untested’ add ‘untested’ foods and monitor foods and monitor tolerancetoleranceIn time, reactive In time, reactive foods are addedfoods are added

RD’s Role

Possibly ordering or requesting testingPossibly ordering or requesting testingProviding general instructionProviding general instructionProviding recipe/menu ideasProviding recipe/menu ideas--creativitycreativitySupport client in lifestyle changeSupport client in lifestyle changeMonitor for complianceMonitor for compliance--hidden ingredientshidden ingredientsDocument outcomes!Document outcomes!

Cytokine Profile in D-IBS

40 year old male with lifelong IBS40 year old male with lifelong IBSHad been on LEAP MRT elimination diet for Had been on LEAP MRT elimination diet for greater than one year and symptom freegreater than one year and symptom freeA baseline plasma cytokine profile was obtainedA baseline plasma cytokine profile was obtainedPatient then purposefully violated his diet and Patient then purposefully violated his diet and consume foods to which he was known consume foods to which he was known to be intolerantto be intolerantHis typical GI and systemic symptoms His typical GI and systemic symptoms quickly recurredquickly recurred

IBS-D PATIENT PLASMA CYTOKINES DURING D-EPISODE v BETWEEN EPISODES

0

50

100

150

200

250

300

350

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

See Specific Cytokine Key

pg/m

l Series1Series2Series3

1 IL-2 2 IL-4 3 IL-6 4 IL-8 5 IL-10 6 GM-CSF 7 IFN-g 8 TNF-a 9 IL-1b 10 IL-5 11 IL-7 12 IL-1213 IL-1314 IL-1715 G-CSF16 MCP-1(MCAF)Patient on LEAP diet

Patient off LEAP diet

Cytokine Profile of Individual D-IBS Patient

Cytokine Profile in D-IBS Patients Versus Normal Controls

Normal people without DNormal people without D--IBS symptoms IBS symptoms were tested by the LEAP MRT and found to were tested by the LEAP MRT and found to have no reactivity to the 150 food antigens have no reactivity to the 150 food antigens consistent with a generally intact oral consistent with a generally intact oral tolerance systemtolerance systemTheir plasma cytokine levels were Their plasma cytokine levels were also measuredalso measured

Cytokine Profile in D-IBS Patients Versus Normal Controls

A group of DA group of D--IBS patients whose blood was IBS patients whose blood was submitted by referring physicians for the submitted by referring physicians for the LEAP MRT also had plasma cytokine LEAP MRT also had plasma cytokine profile performedprofile performedThe LEAP MRT showed that these patients The LEAP MRT showed that these patients had a number of reactive foods consistent had a number of reactive foods consistent with a loss of oral tolerancewith a loss of oral tolerance

Plasma Cytokines: IBS-D vs Normals

0 50 100 150 200 250 300 350 400

1

2

IBS-

D v

s N

orm

als

Plasma Cytokine Levels

Mean Human Plasma Cytokine Levels Healthy Controls (upper bars) vs. IBS-D Subjects (lower bars

Evidence Based MedicinePer JADA March 2005EvidenceEvidence--based practice uses:based practice uses:

The best available evidenceThe best available evidenceThe results of peerThe results of peer--reviewed scientific reviewed scientific studiesstudiesAnd, when science is lacking, expert And, when science is lacking, expert opinion and experienceopinion and experience

Per ADA President, Susan H Per ADA President, Susan H LarameeLaramee

Functional Medicine - A science-based field of healthcare that is grounded in the following principles:

Biochemical individualityBiochemical individualityPatientPatient--centered carecentered careDynamic balance of internal and external Dynamic balance of internal and external factorsfactorsWebWeb--like interconnections of physiological like interconnections of physiological factorsfactorsHealth as a positive vitalityHealth as a positive vitality

SummaryFood Allergy, Food Intolerance and Food Food Allergy, Food Intolerance and Food Sensitivity (as discussed) are three different Sensitivity (as discussed) are three different processesprocessesFood Sensitivity causes significant Food Sensitivity causes significant problems for millions of people and can problems for millions of people and can dramatically reduce quality of life, reduce dramatically reduce quality of life, reduce productivity and costs billions of dollars in productivity and costs billions of dollars in health care, diagnosis and medicationhealth care, diagnosis and medication

SummaryStandard therapy with various medications Standard therapy with various medications is frequently ineffective and often causes is frequently ineffective and often causes significant side effectssignificant side effectsThese medications do not treat the These medications do not treat the underlying cause of the problem, underlying cause of the problem, but merely mask the symptoms.but merely mask the symptoms.MRT/LEAP MRT/LEAP -- Part of the puzzle Part of the puzzle –– but not but not the entire puzzlethe entire puzzle

SummaryLEAP is a revolutionary approach to the LEAP is a revolutionary approach to the treatment of Dtreatment of D--IBS, migraine and IBS, migraine and FibromyalgiaFibromyalgiaThe diet gets right to the “guts” of the The diet gets right to the “guts” of the matter which is namely a loss of oral matter which is namely a loss of oral tolerance to common foods with subsequent tolerance to common foods with subsequent nonnon--IgE cell mediated reactivity to foodsIgE cell mediated reactivity to foodsThe mediators released by these activated The mediators released by these activated immunologic cells are responsible for immunologic cells are responsible for evoking the GI and systemic symptomsevoking the GI and systemic symptoms

SummaryBy selectively removing the reactive foods, By selectively removing the reactive foods, immunoreactivity does not occur and hence, immunoreactivity does not occur and hence, no cytokines are releasedno cytokines are releasedPatients often have a dramatic improvement Patients often have a dramatic improvement in their systemic symptomsin their systemic symptomsUnlike medications, it is safe and Unlike medications, it is safe and has no side effectshas no side effectsBy having LEAP MRT available, it is By having LEAP MRT available, it is changing how food sensitivities are treatedchanging how food sensitivities are treatedQuality of Life is significantly improvedQuality of Life is significantly improved

new diet therapy of ibs, migraine and fibromyalgia · limit pressor amines (chocolate, red wine,...

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