1 treating food sensitivity related conditions using the leap protocol chris e. marquette, rd, ld,...
TRANSCRIPT
1
Treating Food Sensitivity Related Conditions Using the LEAP Protocol
Chris E. Marquette, RD, LD, CLTACSM Certified Health Fitness Specialist
Learning Objectives Identify and describe 3 types of adverse
food reactions Explain how foods can be one of the
causes of the development of conditions such as IBS, fibromyalgia, and migraines
Discuss how dietitians can use the LEAP protocol (lifestyle, eating, and performance) to develop an oligoantigenic plan
Overview Objectives Adverse food reactions Gut Immunology Food sensitivity related conditions Scientific Studies Mediator Release Testing & protocol Case Presentations Summary
Common Types of Adverse Food Reactions
The 3 Most Important Types of Adverse Food Reactions Immune Mediated (involves chemical mediator release):
Food Allergy (Type 1 Hypersensitivity – anaphylaxis)
Food Sensitivity (Defined as any other immune mediated but non-Type 1 Hypersensitivity reaction – IBS, Migraine, etc.)
Non-Immune Mediated (does not involve chemical mediator release):
Food Intolerance (Lactose Intolerance, bile salt deficiency, etc.)
Adverse Reactions
Immunologic
Non-Immunologic
Classes of Adverse Food Reactions
Non-Immunologic
Reactions
Pharmacologic
Enzyme Deficiencies
Toxic Reactions
MalabsorptionLectins
Histamine
Irritants
Non-Immunologic Reactions
Immune Reactions
Allergies
Type I
Antibody Mediated (IgE)
Sensitivities
Type III
Antibody Mediated IgG
IgM
Type IV
Cell Mediated
Immunologic Reactions
Type I(IgE)
Minutes to hours
VasodilationSmooth Muscle
Contraction
Mediator Release
Symptoms
Hives, Asthma, Swelling of Airways Anaphylaxis, Vomiting, Diarrhea
“True” Food Allergies
Should We Test for IgE IBS?
“In adult patients with staple food induced gastrointestinal symptoms, objectively verified by DBPCFC, there were no indications of IgE mediated allergy to the relevant foods, suggesting other mechanisms in adults than in children.”
Gut. 1996 Jul;39(1):130-5
Gut Immunology
GI tract has 2 major roles: Digestion and uptake of nutrients Immune homeostasis
Bombarded with chemicals, proteins, bacteria, antigens
Gut must decide what’s friend or foe
Type III(IgG IgM)
Antibody-Antigen Complex
2-8 hours
Deposit in vessel walls
Mediator Release
Tissue Damage
Rheumatoid ArthritisGlomerulonephritis
Lupus Tissue Damage
Food Sensitivities, Type 3 Mediated
What About IgG Testing? 150 outpatients with IBS Randomized X 3 months Test: diet excluding all foods which raised IgG Control: sham diet excluding the same number
of foods but not those to which they had antibodies.
Outcome measured: IBS and global symptoms
Food elimination based on IgG antibodies in irritable bowel sybndrome: a randomised controlled trial. Atkinson W, Sheldon TA, Shaath N, Whorwell PJ.
Gut. 2004 Oct;53(10):1459-64.
What About IgG Testing? Cont. In 12 weeks Elimination diet : > 10% reduction in symptom
score than the sham diet CONCLUSION: Food elimination based on IgG
antibodies may be effective in reducing IBS symptoms and is worthy of further biomedical research.
Food elimination based on IgG antibodies in irritable bowel syndrome: a randomized controlled trial.Atkinson W, Sheldon TA, Shaath N, Whorwell PJ.
Gut. 2004 Oct;53(10):1459-64.
World Allergy Organization 2003
“ food specific IgG antibodies in serum are not of clinical importance but merely indicate a previous exposure to the food.”
Source: Krause’s Food Nutrition and Diet Therapy 2008
14
Type IVT-Cell
Mediated
MacrophagesActivated
4-72 hours
Mediator Release
Multiple Symptoms
Contact DermatitisTubercular lesions
IBS, Migraine, Fibromyalgia
Food Sensitivities, Type 4 Mediated
Type IV Hypersensitivity Reaction
Physiologic effects of released pro-inflammatory and pro-algesic mediators: IBS: Inflammation, smooth muscle contraction, diarrhea, cramping, visceral hypersensitivity Migraine: vasoconstriction, vasodilatation,
inflammation, WBC activation, pain receptor activation Others: muscle and joint aches and pain, fatigue anxiety, depression, acne, insomnia, mood swings, food
cravings. Possibly seizures, autism
Oral Tolerance
Immunologic process of determining that an intestinal antigen is not harmful and not reacting to it
Loss of oral tolerance triggers immunoreactivity
Oral tolerance measured by Mediator Release Testing
How Do Symptoms Develop?
How Do Foods Play a Role?
Ingestion Recognition Defense Chemical Warfare
Symptom Manifestation
Eat Something Your Immune System Reacts To.
Immune System Bumps Into Antigen and Perceives Substance as an Invader (Enemy).
White blood cells, Antibodies, and other Immune Components Work Together to Mount a Defense.
Chemical Mediators are Released Through Various Means To Destroy The Invader.
Mediators Cause Tissue Inflammation, Damage, and other Effects, that Lead to the Manifestation of Symptoms.
Histamine: Causes inflammation, smooth muscle contraction,
edema Cytokines:
Increase or dampen an immune reaction (many many actions and many different cytokines)
Prostaglandins Inflammation, pain receptor activation
Roughly 100 different mediators
Why Patients Get SickQ. What is the DIRECT CAUSE of
conditions/symptoms in food sensitivity?
A. MEDIATORS!
Conditions That May Be Associated with Food Sensitivity IBS Celiac disease Ulcerative colitis Crohn’s disease GERD Asthma Migraines Tinnitus Depression
Migraine Fibromyalgia Rhinitis/Sinusitis Secretory otitis media ADHD Urticaria Angio-edema Rheumatologic
disorders Atopy
IBS, Migraine, & Fibromyalgia Facts
Approx. 50,000 Americans suffer from these conditions
Chronic, costly problems IBS pts spend roughly $1000 more per year than non-IBS
pts year after year; Migraine similar; Fibro. Even higher costs
Often co-morbid Often refractory to conventional therapies Diet is often an important component, but is often
ignoredA dietary problem REQUIRES a dietary solution
What is Irritable Bowel Syndrome?
Symptom-based diagnosis of exclusion
Rome III Diagnostic Criteria Pain (cramping, distention, malaise) Co-morbid systemic symptoms 3 types: Diarrhea , Constipation,
Cyclic
Migraine Neurological disease
Headache is a symptom One-sided pain of the temple, forehead or eye Other symptoms
Nausea and vomiting Sensitivity to light Sensitivity to sound
Usually lasts for 4 – 72 hours Silent migraine Abdominal migraine
What is Fibromyalgia?
Chronic pain in muscle & connective tissues Associated symptoms:
Fatigue Sleep disturbances Chronic headaches IBS Anxiety Cognitive impairment
Food Allergy Specific type of immune reaction to food
IgE Antibody – Type 1 hypersensitivity Release of chemicals like histamine cause symptoms
Quick onset of symptoms – from minutes to hours 1 molecule of allergic food can trigger a rxn (peanut dust,
kissing) Can be life threatening (anaphylaxis) 1-2 allergic foods When diet is involved in IBS, migraine, or fibromyalgia, food allergy causes symptoms approximately 4-7% of the time
Identifying Allergic Foods Careful history from
your doctor RAST testing to measure
specific IgE to foods Skin Testing
Dangerous due to risk of anaphylaxis
Food Allergy Treatment
Careful avoidance of allergic foods Be Careful when eating out Read ingredients list on packaged foods
Keep an Epi-pen or Benedryl with you just in case
Food Intolerance
Lactose Intolerance is best known example Lactase deficiency
Can’t digest lactose Bacteria in the gut eat the undigested lactose
Bacteria produce hydrogen gas and lactic acid Bloating, gas distention Abdominal discomfort/pain Diarrhea loose stools
Can produce IBS type symptoms Not involved in migraine or fibromyalgia, but can be co-
morbid
Diagnosing Food Intolerance
Breath hydrogen testing Measures amount of hydrogen in breath
Blood test Measures amount of hydrogen in the blood
Food Intolerance Treatment
Avoidance OR in the case of lactose intolerance:
Lactase treated foods Lactaid
Lactase enzymes as supplement with dairy foods
Food Sensitivity Often involved in IBS, migraine, and fibromyalgia Immune reaction to foods – different from food
allergy Type 3 & type 4 (mostly type 4)
Difficult to diagnose Delayed – hours to days after ingestion Dose-related (small amount of reactive food may not
produce symptoms) Many reactive items (foods & chemicals) Highly patient specific (no single IBS, migraine, or
fibromyalgia diet)
Food Sensitivity: Identifying trigger foods
Beware of these tests if you have food sensitivities (because they don’t work) RAST & skin testing – good for type 1
hypersensitivity but not for types 3 & 4 Diet diaries – often show no clear pattern
Delayed, dose related, many reactive items makes it difficult to determine
Food Sensitivity: Identifying trigger foods
If you do it on your own, use an elimination diet: Caveman/Stone age diet Developed in England in the 1950s 2 wk base diet with non-reactive protein, non-reactive starch,
something tasty but non-reactive to break monotony (lamb, rice, pear spring water)
During 2 wks of following diet, gauge symptom remission Better? Diet is involved No Change? Diet not likely involved
If symptoms remit, follow w/oral challenge to ID trigger foods Challenge 1 new food every 3 days until all triggers are identified
Food Sensitivity: Identifying trigger foods
Elimination Diet Pros:
Very accurately identified reactive foods whether allergic, intolerant, or sensitive
Cons: Not very practical
Takes a long tie American diet is mostly packaged foods (lots of
ingredients) Not that good for food-chemical reactions Nutritionally compromised if prolonged
Food Sensitivity: Identifying trigger foods
ELISA IgG testing Limited usefulness (useful for type 3 hypersensitivity only) Cannot test food-chemical reactions
LEAP MRT Most accurate blood test available for food sensitivities Good for type 3 & 4 pathways Can test food-chemical reactions Shortcuts the process of elimination dieting Focuses on building a healthy diet
Food Sensitivity Treatment
Avoidance of reactive items The more closely you follow it, the better you’ll
feel Totally up to the individual
Rotation of non-reactive items Prevents new sensitivities from developing
Oral tolerance may be restored after a period of avoidance (3 – 6 months) Not always, but many times
Scientific Studies:
The Role of Mediator Release&
Symptom Provocation
Intestinal Perfusion Studies
BalloonBalloon
JejunumStomach
Catheter
Knutson et al, J. of Allergy and Clin. Immunology 93; 91(2): 553-9
Intestinal Perfusion Studies Segment of jejunum isolated by two
balloons Segment perfused with potential food
allergen Jejunal contents collected Patients with sensitivity to allergen had
increased production of mediators No response seen in controls
Knutson et al, J. of Allergy and Clin. Immunology 93; 91(2): 553-9
Jejunal Inflammation in IBS
MAJOR FINDINGS: 9 in 10 IBS patients, low-grade infiltration of lymphocytes in the myenteric plexus was found.
No intraganglionic lymphocytes in control group
CONCLUSION: “Our findings indicate that inflammation and neuronal degeneration in the myenteric plexus are involved in the pathogenesis of IBS.”
Full Thickness Biopsy of the Jejunum Reveals Inflammation and Enteric Neuropathy in Irritable Bowel Syndrome Gastroenterology 2002 Dec;123(6):1972-9
Myenteric plexus
Ganglion
Enteric Nervous System
Mucosa
Sub-Mucosa
Circular Muscle
Longitudinal Muscle
Submucousplexus
Interganglionicfiber tract
“IBS is characterized by an augmented cellular immune response with enhanced production of proinflammatory cytokines”
Gastroenterology. 2007 Mar;132(3):913- 20. Epub 2007 Jan 26
Cytokine Profile in D-IBS Patients Versus Normal Controls
Normal Controls No reactivity Consistent with intact
oral tolerance
mechanism
D-IBS Patients Many reactive foods Consistent with loss of
oral tolerance
Use of The LEAP Mediator Release Test To Identify Non-IgE Mediated Immunologic Food Reactions That Trigger Diarrhea Predominant IBS Symptoms
Results in Marked Improvement of Symptoms; Fred H. Williams, M.D., 69th Annual Scientific Meeting and Postgraduate Course, American College of Gastroenterology, November, 2004.
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
Human Plasma Cytokine Levels
An overview on immune system and migraine
Authors state that although pathogenesis of migraine is still unclear……
Cytokines considered pain mediators in neurovascular inflammation.
Cytokines may be a cause of migraine pain
High levels of chemokines could stimulate the activation of trigeminal nerves, the release of mediators, and then cause inflammation.
Eur Rev Med Pharmacol Sci. 2007 Jul-Aug;11(4):245-8
Cytokines play an aetiopathogenetic role in fibromyalgia: a hypothesis and pilot study
Objective: To measure soluble factors
56 FM patients compared with controls
Cytokines and cytokine-related molecules were measured
Conclusion: Patients with FM had increased levels of IL-8 which promotes sympathetic pain and IL-6 which induces hyperalgesia, fatigue and depression, it is hypothesized that they may play a role in modulating FM symptoms.
Rheumatology 2001; 40: 743-749
What is the quickest way to lower cytokine levels in each patient?
Remove those foods or chemicals that are triggering the immune response!
Cytokine Profile in D-IBS
40 year old male with lifelong IBS On LEAP diet for > 1 yr and symptom free Baseline plasma cytokine profile obtained Patient then violated LEAP diet and consumed
known reactive foods Typical GI and systemic symptoms quickly
recurred Second plasma cytokine profile obtained
Fred H. Williams, M.D., 69th Annual Scientific Meeting and Postgraduate Course, American College of Gastroenterology, November, 2004.
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
/ml Series1
Series2
Series3
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-12
13 IL-13
14 IL-17
15 G-CSF
16 MCP-1(MCAF)Patient on LEAP diet
Patient off LEAP diet
Cytokine Profile of IBS-D Patient
The Biggest Problem Concerning Non-IgE Mediated Food Reactions?
IDENTIFYING Reactive Foods!
Challenges Historically Faced When Identifying Reactive Foods
51
Unlike allergies, food sensitivity reactions are:
1. Dose dependent
2. Delayed onset (up to 72 hours)
3. Multiple foods can cause symptoms
4. Single elimination trials are useless
5. NO universal bad food - very patient specific
Until now, it was hard to find those “triggers”
Mediator Release Testing: Eliminating
The Guesswork
Mediator Release Test (MRT) 150 foods and non-food chemicals are tested
Each sample analyzed and compared to the patients own control samples
Checked for any mediator release from the cells
Cells should 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
Mediator Release Test (MRT) Common end-point of ANY Cellular Reaction
can be measured Degree of reactivity determined
by mediator release from cells Degree of reactivity can be
quantified
LEAP Oligoantigenic Diet
Patient specific Week 1: 20-25 least
reactive of the Non-reactive foods
Weeks 2-4: Slowly introduce new Non-reactive foods
Test for oral tolerance
LEAP Oligoantigenic Diet
Patients avoid all Moderately Reactive and Reactive foods
In time, they are advised to rotate all foods
Add ‘untested’ foods and
test for oral tolerance
Symptom Survey
Filled out by patient Prior to LEAP program 7-10 days 4 weeks 2 months 3 months
Evaluation and documentation of symptoms
Easy visual of patient progress
Case Presentation - IBS
Charles, 53 yo male dx with D-IBS, colitis and depression.
On extended sick leave from work r/t severe and frequent diarrhea
Patient on 13 medications for: Diarrhea HTN Anxiety
Insomnia IBS Depression No known food sensitivities Original symptom survey: 107 points
Case Presentation - IBSLEAP MRT results
Reactive foods: Olive Green Pea Shrimp
Moderately reactive foods/chemicals Broccoli Blueberry Nutmeg Green Pepper Egg Lentil Cauliflower Cola Nut Cow’s Milk Oat Salicylic Acid Blue Cheese Millet Ginger Swiss Cheese Cantaloupe Basil
Mint
Dill
Garlic
Mushroom
Grape
Grapefruit
Case Presentation - IBSElimination Diet foods allowed (Week 1)
Beef Tuna Clam Soybean Barley Corn Amaranth Tomato Yellow Squash Asparagus Beet
Raspberry Cranberry Honeydew Melon Watermelon Yogurt Corn oil Sunflower Seeds Pistachio Paprika Oregano Turmeric
Pre-LEAP 10 days 4 weeks0
20
40
60
80
100
120
107
52
2022
2 3
Total Digestive
Symptom Survey – IBS Patient
Case Presentation – Migraine & Fibromyalgia
Christine 40 yo female with migraines, fibromyalgia,
ulcerative colitis, allergies, rhinitis, blepharitis
Original symptom survey: 69 points 8 very reactive foods and 1 chemical 20 moderately reactive foods and 6
chemicals 116 allowed foods and chemicals!
Case Presentation – Migraine, Fibromyalgia and Ulcerative Colitis Reactive foods/chemicals Zucchini Turkey Rye
Moderately reactive foods/chemicals Lettuce Pork Lentil Green Pepper Egg Coffee Spinach Trout Cow’s Milk Pumpkin Dill Blue Cheese Cherry Turmeric Swiss Cheese Banana Peanut Saccharine Aspartame Benzoic Acid Sodium Metabisulfite FD&C Blue #1 FD&C Yellow #5
Sole
Tuna
Phenylethylamine
Ginger
Cola Nut
Pre-LEAP 8 days 4 weeks 2 months 3 months
69
1812
5 2
11
2 1 1 16 4 1 0 0
12
0 0 0 0
Total Score Head/EarsMusculoskeletal Digestive
Symptom Survey – Migraine, Fibromyalgia & Ulcerative Colitis
Average % improvement from 86 patients following 30 days adherence to the LEAP Program.
1 2 3 4 5 6 7 8 9 10
22
28
9
29
27
18
16
19
25
12
2
9
3
9
13
9
5
7
12
0
Initial SS 1 week SS
10 IBS Pts – Digestive Improvement 1 wk – 67%
1 2 3 4 5 6 7 8 9 10
22
28
9
29
27
18
16
19
25
12
3
9
32
4
12
3
5
0
Initial SS
10 IBS Pts – Digestive Improvement 1 month – 85%
LEAP Is Easily Integrated Into The Practice
1. Select appropriate patients
2. Verify insurance
3. Schedule blood draw
4. FedEx blood to Signet’s lab
5. Schedule patient to get results
6. Implement customized, clinically proven protocol
7. Initial consult – instruct patient on Patient-Specific Oligoantigenic Diet
8. Follow-ups after 7, 30, 60, 90 days or as needed
Certified LEAP Therapist Training 10-20 CPE hours for CLT 30-40 additional hours for SIL Mentoring by experienced CLT LEAP list-serve membership Training Materials Include:
8-Narrated Power Point Modules on CD Plus : Forms, templates, handouts and more
FAQ’s
Does insurance cover the test? Many PPO’s do
How much does the test cost the patient?
How can I become a Certified LEAP Therapist?
Summary Adverse food reactions can be immune or non-
immune Immune reactions can be antibody or cell mediated IBS, Migraine & Fibro are mainly cell-mediated Mediators responsible for GI and systemic
symptoms Consuming non-reactive foods, no cytokines are
released Symptoms dramatically improve LEAP is unique approach
Lab Test Dietitian
