NUTRITIONAL%20MEDICINE%20AND%20GASTROINTESTINAL%20PATHOLOGY - PowerPoint PPT Presentation

About This Presentation
Title:

NUTRITIONAL%20MEDICINE%20AND%20GASTROINTESTINAL%20PATHOLOGY

Description:

High soluble fiber and complex carbohydrate increases fermentation ... restrict sugar, starch, soluble fiber. Antimicrobials (in select cases) ... – PowerPoint PPT presentation

Number of Views:1028
Avg rating:3.0/5.0
Slides: 235
Provided by: leogal
Learn more at: http://www.mdheal.org
Category:

less

Transcript and Presenter's Notes

Title: NUTRITIONAL%20MEDICINE%20AND%20GASTROINTESTINAL%20PATHOLOGY


1
NUTRITIONAL MEDICINE AND GASTROINTESTINAL
PATHOLOGY
  • Leo Galland, M.D.
  • Foundation for Integrated Medicine
  • www.mdheal.org

2
WHY SPEND A HALF DAY TALKING ABOUT THE GUT?
  • The small bowel is where digestion and absorption
    of nutrients occurs
  • The food we eat creates the intestinal
    micro-environment
  • The intestinal microenvironment has an important
    influence on the pathophysiology of many
    different diseases
  • Diets dont treat diseases, they treat patients

3
BEYOND DIGESTION
  • The gut is a sensory organ. Protozoa know their
    environments by ingestion.
  • The gut is a neuroendocrine organ. Every
    neurotransmitter found in the brain is also found
    here.
  • The gut has a brain of its own, an intact and
    independent nervous system.
  • The gut is the largest organ of immune function
    in the body 70 of our lymphocytes live here.

4
BEYOND DIGESTION
  • The gut contents are an inner world that is
    outside the cellular body. Its surface is a
    frontier with an area 100 meters square and a
    thickness of one cell
  • Gut flora are an organ that contains as many
    microbial cells as the cellular body has
    mammalian cells (100 trillion)
  • -Over 500 species
  • -Over 90 are anaerobic

5
BEYOND DIGESTION
  • The normal intestinal microflora constitute a
    huge chemical factory that alters our food and
    our GI secretions
  • The normal intestinal microflora present our
    immune systems with a mass of antigens that are
    partially absorbed

6
(No Transcript)
7
(No Transcript)
8
(No Transcript)
9
Intestinal dysbiosis, altered permeability, food
intolerance and detoxification are
inter-connected parts of the same puzzle
10
MUCOSAL BACTERIA ARE USUALLY NOT ISOLATED FROM
STOOL
  • Colon Anaerobic spirochetes, fusiform bacteria
  • Ileum Coccobacilli
  • Stomach Lactobacilli, yeasts
  • Oral Anaerobes (Corynebacteria, Actinomyces,
    Bacteroides, Spirochaetes, Fusobacteria and
    Aerobes Streptococcus and Lactobacillus)

11
COMPOSITION OF NORMAL STOOL FLORA
  • Eubacterium, 26 spp 25.5
  • Bacteroides, 20 spp 22.6
  • Bifidobacterium, 8 spp 11.5
  • Peptostreptoccus 8.9
  • Fusobacterium, 5 spp 7.7
  • Ruminoccus, 11 spp 4.5
  • Lactobacillus, 7 spp 2.4
  • Streptococci 1.6
  • Clostridia 0.6
  • Enterobacteriacae 0.5

12
BENEFITS OF NORMAL GUT FLORA
  • Synthesize vitamins
  • Synthesize short chain fatty acids
  • Metabolize xenobiotics/toxins
  • Prevent colonization by pathogens
  • Stimulate normal immune system maturation
  • Convert dietary flavonoids to active aglycones

13
NUTRIENTS SYNTHESIZED BY NORMAL GUT FLORA
  • Biotin
  • Cobalamin
  • Folic acid
  • Pantothenic acid
  • Pyridoxine
  • Riboflavin
  • Vitamin K
  • Butyric acid
  • Amino acids

14
GUT MICROBIAL DETOXIFICATION
  • Demethylate methylmercury
  • Degrade N-nitrosamines
  • Degrade polycyclic aromatic hydrocarbons
  • Degrade aflatoxin B1 (limited)
  • Hydrolyze guanidinosuccinic acid

15
IMMUNOLOGICAL EFFECTS OF NORMAL GI MICROFLORA
  • Stimulate RES activity
  • Increase number of immunocompetent cells
  • Increase immunoglobulin synthesis
  • Increase complement levels
  • May stimulate dysfunctional immune responses

16
HOW NORMAL GI FLORA PROTECTS AGAINST GI PATHOGENS
  • Synthesis of short chain fatty acids
  • Synthesis of antibiotics
  • Competition for nutrients
  • Induction of a low re-dox potential
  • Deconjugation of bile acids
  • Blockage of adherance receptors
  • Degradation of bacterial toxins

17
POTENTIAL ADVERSE EFFECTS OF NORMAL GUT FLORA
  • Deactivate trypsin, chymotrypsin and intestinal
    disaccharidases, producing maldigestion
  • Produce ammonia
  • Consume Vitamin B12
  • Deconjugate bile salts

18
POTENTIAL ADVERSE EFFECTS OF NORMAL GUT FLORA
(continued)
  • Increase enterohepatic recirculation of estrogens
  • Activate pro-carcinogens
  • Stimulate dysfunctional immune responses

19
BACTERIAL ENZYMES OF TOXICOLOGICAL SIGNIFICANCE
TO THE HOST
ENZYME SAMPLE SUBSTRATE EFFECT
B-glucosidase Cycasin amydgalin Tumor promotion
B-glucuronidase Glucuronidides Recirculate estrogen, methemoglobin
Nitrate reductase Nitrate Nitrite production
Nitroreductase Nitrobenzene Tumor induction by nitrosamines
Azo reductase Brown FK Vacuolar myopathy
Urease Urea Ammonia toxicity
Methylmercury demethylase Methylmercury Reduction in neurotoxicity
20
TOXIC METABOLITES OF GI FLORA
  • Ammonia from hydrolysis of urea
  • Amines from amino acid decarboxylation
  • Phenols from dietary tryptophan
  • Secondary bile acids
  • Recycled estrogens
  • Nitrites from nitrates
  • N-nitrosamines from nitrates/nitrites

21
AMMONIA
  • Produced by urease from urea in gut
  • Klebsiella, Proteus, Bacteroides, Bifidobacteria
  • Inhibits oxidative metabolism in brain
  • Reduced by low protein diets, by substituting
    dairy for meat (flora changes)
  • Low colonic pH reverses absorption
  • Rapid transit inhibits absorption

22
AMINES PRODUCED BY GI FLORA
  • Inactivated by hepatic MAO
  • tyramine
  • octopamine
  • histamine
  • cadaverine
  • putrespecine
  • Piperidine

23
NITROSAMINES
  • From nitrates/nitrites secondary amines
  • lecithin, choline dimethylamine
  • lysine piperidine
  • arginine pyrrolidine
  • Water, vegetables, cured meats, cheese may
    contain nitrates, absorbed in jejunum
  • Hypochlorhydria increases formation

24
BILIARY STEROID METABOLISM BY GI MICROFLORA
  • chenodeoxycholate lithocholate
  • cholic acid deoxycholic(DCA)
  • -DCA in feces correlates with colon cancer
    incidence
  • -DCA may 20-CH3-cholanthrene
  • Deconjugation of bile salts

25
ESTROGEN METABOLISM AND GI MICROFLORA
  • conjugation biliary excretion
  • deconjugation increased

  • entero-hepatic

  • recirculation
  • increased blood and urine estrogen
  • Western diet higher plasma estrogen, lower
    stool estrogen

26
TRYPTOPHAN METABOLISM BY GI MICROFLORA
  • tryptophanase indole, absorbed by
    colon mucosa, potential carcinogen
  • GI flora quinaldic acid, 8-OH
    quinaldic bladder carcinogens
  • Aerobes E. Coli, Proteus spp
  • Anaerobes Bacteroides fragilis, ss.
    Thetaiotamicron (increased with stress)

27
PRODUCTS OF MICROBIAL CHO FERMENTATION IN GUT
  • SCFAs
  • Propanol
  • Acetaldehyde
  • Formic acid
  • CO2
  • Butylene glycol
  • Ethanol
  • Butanol
  • D-lactic acid
  • Hydrogen
  • Acetone

28
EFFECTS OF SHORT CHAIN FATTY ACIDS
  • Butyrate anti-neoplastic, reduces growth of
    human cancer cells
  • Propionate inhibits gluconeogenesis
  • Acetate stimulates salt and water absorption
  • All anti-bacterial, anti-fungal
  • lower pH reduced DCA and less NH4 absorption
  • stimulate growth of mucosal cells

29
FACTORS AFFECTING GI FLORA
  • GI secretions type, volume, content
  • Enzymes, cells, mucus, pH, re-dox
  • Diet
  • Fiber, fat, protein, CHO
  • Motility and transit time
  • Host immunity
  • Emotional distress

30
DIETARY EFFECTS ON GI FLORA
  • High Fat Bacteroides up, Lactobacilli and
    Enterococci down
  • Vegetarian anaerobes down
  • Cellulose lower yeasts, Staph, Proteus and
    Clostridia also total bacterial count and levels
    of bacterial enzymes

31
DIETARY EFFECTS ON GI FLORA(continued)
  • Galactomannans (guar gum locust bean gum),
    carboxymethylcellulose increase bacterial
    bio-mass and enzyme levels
  • Unrefined CHO vs refined increase bacterial
    content of ileostomy fluid
  • Wheat bran reduces methylmercury toxicity by
    increasing demethylation by GI flora

32
DIETARY EFFECTS ON GI FLORA(continued)
  • D-glucaric acid inhibits B-glucuronidase found
    in crucifers, citrus, cherry and human urine
  • Low fiber diets increase bacterial translocation
  • Pectins with high methoxy content increase
    nitroreductase activity may increase
    B-glucuronidase

33
SUMMARY OF DIET AND GI FLORA
  • High meat diets induce enzymes that may promote
    carcinogenesis and the formation of indoles and
    ammonia
  • High soluble fiber and complex carbohydrate
    increases fermentation
  • Insoluble fiber decreases carcinogenic enzyme
    concentrations
  • Phytochemicals may inhibit bacterial enzymes

34
STRESS AND GI MICROFLORA
  • ACTH injection increases jejunal E. coli
  • Cosmonauts lose Bifidobacteria and Lactobacillus
    before take-off
  • Fear and anger selectively increase Bacteroides
    fragilis spp, Thetaiotamicron this increases
    colonic tryptophanase, which increases skatole
    and indole production on high meat diets

35
DYSBIOSIS IS ECOLOGIC IMBALANCE
  • Disease or dysfunction produced by the
    interaction between the host and its normal
    flora, organisms of low intrinsic virulence.

36
DYSBIOSIS-ASSOCIATED DISEASES
  • Cancer colon/breast
  • Inflammatory bowel disease
  • Irritable bowel syndrome
  • Chronic fatigue syndromes
  • Rheumatoid arthritis
  • Spondyloarthropathies
  • Acne
  • Psoriasis
  • Eczema
  • Food allergy/intolerance
  • Malabsorption syndromes

37
DYSBIOSIS CAUSES DISEASE BY TWO MECHANISMS
  • Microbial enzymes act upon intestinal contents to
    produce noxious substances
  • Microbial components stimulate dysfunctional
    immune responses

38
GI MICROFLORA AND COLON CANCER
  • Large bowel cancer is associated with high fat,
    high protein, low fiber diets
  • This effect is in part mediated by bacterial
    enzymes induced by the nature of the diet, the
    substrates supplied for these enzymes and the
    carcinogenic products of enzyme activation

39
GI MICROFLORA AND COLON CANCER
  • Incidence proportional to DCA excretion
  • inversely proportional to Lactobacillus
    concentration
  • Vegetarians have less cancer and lower bacterial
    enzymes in stool Beta-glucuronidase,
    nitro-reductase, 7-alpha-dehydroxylase
  • Lactobacilli lower these when fed to omnivores
    and prevent colon cancer in rats given
    dimethylhydrazine

40
GI MICROFLORA AND COLON CANCER(continued)
  • High meat diets increase indole and skatole in
    stool inducing bacterial tryptophanase
  • Human fecal mutagen (FCM), a vinyl ether of
    propanediol, is associated with a Western diet.
    Requires bile and low oxygen. Produced by 5
    Bacteroides spp
  • High protein diets high GI ammonia and high
    fecal pH. This increases fecal LCFA and bile
    acid solubility

41
GI MICROFLORA AND COLON CANCER(continued)
  • High CHO/fiber diets high SCFA and low fecal
    pH. This decreases fecal LCFA and bile acid
    solubility
  • Dietary Ca also renders LCFA insoluble

42
DIETARY PREVENTION OF COLONIC DYSBIOSIS
  • Plant-based, high fiber diet
  • Fermented foods, Lactobacilli
  • Crucifers, flavonoid-rich vegetables fruits
  • Vegetable cellulose, an insoluble fiber
  • Colostrum, a source of lactoferrins
  • -Lactoferrins bind iron, inhibiting the growth
    of all bacterial species except lactic acid
    producers

43
SMALL BOWEL BACTERIAL OVERGROWTH
  • produces a different pattern of dysbiosis,
    associated with carbohydrate/fiber intolerance,
    bloating, altered bowel habit, fatigue and
    maldigestion

44
CAUSES OF UPPER GI BACTERIAL OVERGROWTH
  • Achlorhydria/hypo-chlorhydria
  • Surgical resection/blind loops
  • Stasis from abnormal motility
  • Strictures
  • Fistulas
  • Diverticulosis
  • Immune deficiency
  • Intestinal giardiasis
  • Tropical sprue
  • Malnutrition

45
EFFECTS OF UPPER GI BACTERIAL OVERGROWTH
  • Vitamin B12 deficiency
  • Bile salt dehydroxylation
  • Impairs formation of micelles
  • Formation of hydroxy fatty acids
  • Bile salt deconjugation
  • Increase colonic water secretion
  • Inhibit monosacchardide transport

46
EFFECTS OF UPPER GI BACTERIAL OVERGROWTH(continue
d)
  • Inhibition of folate conjugases
  • Increased fecal nitrogen, hypoalbumenia
  • Bacterial degradation of CHO
  • Villi blunted and broadened
  • Lamina propria increased mononunuclear cells

47
EFFECTS OF UPPER GI BACTERIAL OVERGROWTH(continue
d)
  • Mucosal damage by bacterial enzymes
  • Loss of brush border
  • Endotoxemia/antigenemia
  • Liver damage
  • Joint disease

48
BREATH TESTING FOR BACTERIAL OVERGROWTH
  • FALSE POSITIVES
  • Smoking, sleeping, eating
  • Soluble fiber/FOS
  • Rapid intestinal transit
  • FALSE NEGATIVES
  • Colonic hyperacidity (low stool pH)
  • Absence of appropriate flora
  • Delayed gastric emptying
  • Antibiotics

49
BACTERIAL OVERGROWTH IS MORE COMMON THAN SUSPECTED
  • 202 patients with IBS underwent hydrogen breath
    testing
  • 157 (78) had SBBO and were treated with
    antibiotics
  • 25/47 patients had normal breath tests at
    follow-up
  • Diarrhea and abdominal pain were significantly
    improved by treatment

50
SBBO AND IBS CONCLUSIONS
  • Elimination of SBBO eliminated IBS in 12/25 of
    patients
  • 48 of patients with IBS and abnormal breath
    tests who responded to antibiotics with normal
    breath tests no longer met Rome criteria for IBS
  • Pimentel M et al, AM J Gastroenterol 2000

51
MANAGEMENT OF UGI BACTERIAL OVERGROWTH INVOLVES
DIET, ANTIBIOTICS
  • Low fermentation diet
  • -restrict sugar, starch, soluble fiber
  • Antimicrobials (in select cases)
  • Metronidazole (anaerobes)
  • Tetracyclines (anaerobes)
  • Ciprofloxacin (aerobes)
  • Bismuth
  • Bentonite

52
Low Fermentation Diet
  • Basic diet no wheat, sucrose, lactose
  • Additional restrictions
  • -no glutinous grains
  • -no cereal grains, potatoes
  • -restrict fruits, juices, honey
  • -avoid legumes
  • -cook all vegetables

53
IRRITABLE BOWEL SYNDROME IS ASSOCIATED WITH
SPECIFIC FOOD INTOLERANCE
  • Specific food intolerance, present in 48 of
    patients with diarrhea and pain, is associated
    with unstable fecal flora, high aerobeanaerobe
    ratios and high stool PGE2 levels
  • Alun Jones et al, Lancet, 1982

54
The Addenbrookes Hospital Exclusion Diet for IBS
  • 1-2 meats
  • lamb, turkey, fish, chicken, beef
  • 1 fruit
  • pears, pineapple, banana, apple
  • Rice, water
  • Commonest diet was lamb, pears, rice

55
Outcome of Exclusion Diet in 182 IBS Patients
  • No improvement after 7 days 38 (21)
  • Improved after 7 days 144 (79)
  • -Provoking foods identified, established
  • dietary control of IBS 122 (67)
  • -Intolerant of one food 5
  • -Intolerant of 2-5 foods 28
  • -Intolerant of 6-10 foods 35
  • -Intolerant of gt 10 foods 32

56
Foods Provoking IBS
  • Wheat 60
  • Milk 44
  • Corn 44
  • Cheese 39
  • Oats 34
  • Coffee 33
  • Rye 30
  • Eggs 26
  • Tea 25
  • Butter 25
  • Yogurt 24
  • Citrus 24
  • Barley 24
  • Chocolate 22
  • Nuts 22
  • Preservatives 20

57
Foods Provoking IBS
  • Potatoes 20
  • Cabbage 19
  • Sprouts 18
  • Peas 17
  • Beef 16
  • Carrots 15
  • Lettuce 15
  • Rice 15
  • Pork 14
  • Broccoli 14
  • Soy 13
  • Chicken 13
  • Spinach 13
  • Yeast 12
  • Lamb 11
  • Sugar 12

58
Food Intolerance in IBS Is not Associated with
Atopy
  • Only 10 of patients were atopic
  • 40 could relate onset of symptoms to
  • -A course of antibiotics (11)
  • -A bout of gastroenteritis (12)
  • -Abdominal or pelvic surgery (15)
  • Unstable fecal flora was common
  • Hunter et al,Topics in Gastroenterology, 1985

59
IBS with Food Intolerance Is Associated with
Excess Fermentation, Corrected by Diet
  • 6 patients, 6 controls, whole body chamber
  • Total body hydrogen production greater with IBS,
    fell with exclusion diet. (No grains except rice,
    no dairy or beef, restrict yeast, citrus,
    caffeine, tap water)
  • King et al, Lancet 352 1187-1189 (1998)

60
(No Transcript)
61
IMMUNE SENSITIZATION AND DYSBIOSIS
  • Immune responses to intestinal microorganisms may
    provoke inflammatory and auto-immune disorders
  • Specific bacterial antigens mimic auto-antigens
  • Non-specific polyclonal activation, RES
    hyperstimulation, APC activation

62
MOLECULAR MIMICRY (Cross Reactivity)
  • MECHANISM
  • Microbes colonize positive individuals
  • Cross-reactivity with bacterial antigens leads to
    secondary immune damage
  • Antibodies against microbes bind to cells
    carrying HLA antigens
  • Increased cytotoxic damage
  • Inflammation from complement or cytokine cascades

63
INTESTINAL INFLAMMATION AND SPONDYLOARTHOPATHIES
  • sIgA is increased in AS (suggest enteritis)
  • Sub-clinical ileitis occurs in many pts with
    primary spondyloarthropathies
  • 10-20 of IBD patients get AS
  • Bowel infections often precede reactive arthritis
  • Silent carriage of Salmonella can precipitate
    reactive arthritis

64
KLEBSIELLA AND ANKYLOSING SPONDYLITIS (AS)
  • MOLECULAR MIMICRY
  • Klebsiella antigens cross-react with HLA-B27
  • Initiates inflammatory cascade
  • Leads to reactive arthritis

65
KLEBSIELLA AND ANKYLOSING SPONDYLITIS (AS)
(continued)
  • THE EBRINGER RESEARCH
  • 96 of AS patients have HLA-B27 gene
  • Many AS patients grow Klebsiella on stool culture
  • AS pts have higher serum IgA against Klebsiella
    than controls

66
Nutritional Therapy for Ankylosing Spondylitis
  • A diet free of grains and disaccharides reduced
    levels of Klebsiella in stool, lowered the level
    of anti-Klebsiella IgA and improved the symptoms
    of patients with AS
  • Ebringer, Ballieres Clin Rheumatol, 1989

67
VS, 41 year old male event planner with hip, knee
and back pain and fatigue
  • Prior history chronic rhinitis,
    hypercholesterolemia, Lyme disease 1993 and 1994,
    hypothyroidism 1994
  • Past several years persistent tightness in back,
    persistent pain in calves,hips, knees, poor
    response to physical therapy, fluctuating
    fatigue, poor sleep, dizziness, alternating
    constipation and diarrhea.
  • Food single, lives alone,eats out all the time,
    sweets.
  • Family history Crohns disease, hyperlipidemia,
    hypertension. Mother had been ill with ASVD and
    breast cancer most of his life.

68
VS, 41 year old male event planner with hip, knee
and back pain and fatigue
  • Physical exam
  • -Nodular thyroid
  • -Decreased range of motion of hips and LS
    spine, diminished straight leg raising
    bilaterally, no joint tenderness, scattered
    tender points of lower extremities
  • Lab
  • - HLA B27
  • -ANA 140 speckled
  • -Normal X-rays of SI joints, spine
  • -E. histolytica in stool

69
VS, 41 year old male event planner with hip, knee
and back pain and fatigue
  • Treatment
  • -Ebringer diet (eliminate grains, sucrose,
    lactose)
  • -Doxycycline, paromomycin
  • Initial response
  • - I cant prepare my own food.
  • - Hip and knee pain markedly improved.
  • - Lost 20 lbs.
  • Further response
  • My friends cant believe that Im cooking for
    myself.
  • My friends cant believe how good I look.
  • My physical therapist cant believe how flexible
    I am.
  • 90 pain-free, modifies diet to his life style.

70
PROTEUS AND RHEUMATOID ARTHRITIS (RA)
  • Frequency of HLA-DR4 in RA patients 50 to 75.
    Those without HLA-DR4 usually have DR-4
    mothers.
  • Controls 20 HLA-DR4 positive
  • RA patients often have elevated serum IgG titers
    to Proteus spp that cross-react with HLA-DR4

71
Proteus, RA and Diet
  • RA patients in England, Spain and Norway have
    higher anti-Proteus IgG than controls
  • Anti-Proteus IgG correlates with disease activity
    and C-reactive protein levels
  • Fasting, followed by a one year gluten-free vegan
    diet improves symptoms and indices of disease
    activity, only in patients whose Proteus
    antibodies decrease and who show a change in
    fecal bacterial fatty acid profiles. E coli
    antibodies are not affected

72
SKIN DISEASES AND THE GI FLORA
  • Cystic acne endotoxemia
  • Atopic eczema dramatic reduction of
    Lactobacilli, Bifidobacteria, Enterococci
    increased Candida, Clostridia, Staph aureus,
    Proteus, Klebsiella, atypical coliforms
  • Psoriasis, scalp seborrhea intestinal yeasts

73
DYSBIOSIS MAY INVOLVE YEASTS AND PROTOZOA
  • Yeasts are normal inhabitants of the alimentary
    canal and are glucose fermenters
  • Yeasts are powerful chemical factories
  • Yeasts are highly antigenic
  • -90 of people have type 4 immunity
  • -10 of people have type 1 immunity
  • -type 3 immunity was found in asthmatics
  • Yeast polysaccharides exert immune activating
    (zymosan) and immune suppressing (mannan)
    activity

74
GUT FERMENTATION AND YEAST
  • (Hunnisett et al, J Nutr Med 1990)
  • 61 of chronically ill polysymptomatic patients
    developed measurable ethanol in blood after
    ingesting 6 gm glucose
  • Mean rise of 2.5 mg/dl, range from 1 to 7

75
TREATMENT RESULTS SUGGEST YEAST AS A CAUSE OF
FERMENTATION AND SYMPTOMS
  • Low sugar diet cleared 42
  • Diet nystatin cleared 86
  • 116/149 clinically better
  • Diet tetracycline cleared 21, worsened 35
  • 2/22 clinically better

76
AS, 31 year old woman with angioedema
  • Prior Recurrent yeast vaginitis, SAR
  • 1999 OCP for one year, tetracycline for acne for
    one month edema of face, feet, fingers,
    hives. Oral steroids.
  • 2000-2001 edema, urticaria, fatigue, brain
    fog50 of time. Antihistamines ineffective.
    Diuretics prn. Allergy evaluation neg.
  • Self-started a yeast elimination diet less
    moody, a bit less swollen.

77
AS, 31 year old woman with angioedema
  • Physical exam mild acne with scarring,
    peri-orbital swelling, angioedema of left palm,
    distended abdomen with LLQ tenderness, normal
    genitalia
  • Intradermal C. albicans antigen marked delayed
    reaction, starting after 6 hours, lasting for
    several days with diffuse erythema, edema and
    tenderness of forearm, healing with scaling of
    skin
  • Lab impaired lymphocyte proliferative response
    to C. albicans (1.2, refgt3), low plasma zinc (597
    mcg.dL, ref 600-1300), borderline retinol 39
    mcg/dL (ref 38-106)

78
AS, 31 year old woman with angioedema
  • Treatment
  • Continue diet
  • Zinc 25 mg/day
  • Vitamin A 10,000 IU/day
  • Lactobacillus plantarum 10 billion units/day
  • Nystatin 3 million units p.o. tid.
  • Initial response was more swelling, lip edema
  • Raised dose to 13 million units/day
    diuresis, followed by clearing of edema and
    increased energy

79
NOMENCLATURE
  • CHRONIC CANDIDIASIS
  • CANDIDA SENSITIZATION SYNDROME
  • POLYSYSTEMIC CHRONIC CANDIDIASIS
  • YEAST SYNDROME
  • YEAST PROBLEM
  • YEAST DISEASE
  • CANDIDA
  • THIS PROBLEM
  • CANDIDA-RELATED COMPLEX (CRC)

80
CRC SYMPTOMS
  • MUCOSAL INFECTION
  • FATIGUE
  • DEPRESSION
  • PMS
  • G.I. DISTURBANCES
  • POOR CONCENTRATION/MEMORY
  • ALLERGIC REACTIONS
  • ORGAN SPECIFIC
  • SKIN RASH, ECZEMA, URTICARIA
  • HEADACHE
  • OTHER

81
INTESTINAL YEASTS MAY CAUSE SYMPTOMS BY 3
MECHANISMS
  • Tissue invasion (oral, esophageal, intestinal
    thrush)
  • Fermentation of sugars (production of ethanol,
    arabinitol and other toxins)
  • Sensitization (asthma, urticaria, allergic
    vaginitis, IBS, Crohns disease, psoriasis).
    Cross-sensitization with food yeast may occur

82
CRC IS RELATED TO THE HOST-YEAST INTERACTION
  • Rectal cultures of patients who respond to
    anti-fungal drugs are less likely to grow yeasts
    than those of a normal population
  • These patients produce mucosal factors that are
    abnormally active at inhibiting yeast growth

83
(No Transcript)
84
(No Transcript)
85
(No Transcript)
86
COMPARISON STUDY 87 PATIENTS 42 CRC/45 CRC-
  • POSITIVE RECTAL YEAST CULTURE (41)
  • 10 CRC/31CRC-
  • NEGATIVE RECTAL YEAST CULTURE (46)
  • 32 CRC/14 CRC-
  • POSITIVE SMEAR (37)
  • 32 CRC/5 CRC-
  • NEGATIVE SMEAR (9)
  • 0 CRC/9CRC-

87
CRC RETROSPECTIVE STUDY
  • YEAST SEEN IN RECTAL SWABS
  • PRE-TREATMENT SMEAR (CALFLOR STAIN)
  • 0-trace 0
  • 4
  • / 36
  • POST-TREATMENT SMEAR (CALFLOR STAIN)
  • 0-trace 28
  • 0
  • / 3

88
CRC RETROSPECTIVE STUDY
  • MICROBIOLOGY OF RECTAL SWABS
  • PRE-TREATMENT CULTURES (BIGGY AGAR)
  • POSITIVE 11
  • NEGATIVE 32
  • 31 PATIENTS WITH CRC HAD A RECTAL SMEAR THAT WAS
    / AND A SIMULTANEOUS RECTAL CULTURE THAT WAS
    NEGATIVE (78 OF TOTAL WITH PRE-TREATMENT SMEARS
    CULTURES)

89
  • Patients with CRC who had strongly positive
    rectal mucus smears and negative rectal cultures
    had something in their mucus that inhibited the
    growth of Candida albicans in culture

90
(No Transcript)
91
(No Transcript)
92
TREATMENT OF YEAST DYSBIOSIS INVOLVES DIET AND
MEDICATION
  • Sugar restriction
  • Avoidance of dietary yeasts (fermented foods,
    dried fruits, fruit juices, bread)
  • Anti-fungal medication (may provoke a
    Herxheimer-type response before symptoms improve)
  • Restoration of normal bacterial flora with
    pro-biotic supplements

93
THE SPECTRUM OF DISEASE INDUCED BY INTESTINAL
PARASITES
  • Diarrhea, dysentery, enteritis, colitis
  • Non-specific chronic GI complaints
  • UGI bacterial overgrowth
  • Extra-intestinal tissue invasion
  • Malabsorption syndrome
  • Immune supression
  • Allergy (urticaria, atopic reactivity)
  • Food intolerance
  • Fatigue
  • Rheumatologic syndromes

94
MECHANISM OF SYSTEMIC EFFECTS OF INTESTINAL
PARASITES
  • Increased intestinal permeability
  • Immune sensitization/suppression
  • Malabsorption

95
PARASITIC RHEUMATISM
  • Inflammatory arthropathy
  • Elevated ESR
  • Inconsistent eosinophilia
  • Inefficacy of anti-inflammatory drugs
  • Demonstration of parasitic infection
  • Prompt response to anti-parasitic treatment
  • Immune complex formation

96
INTESTINAL PARASITES CAUSING PARASITIC RHEUMATISM
  • Giardia lamblia
  • Entamoeba histolytica
  • Endolimax nana
  • Taenia Saginata
  • Schiostosoma mansoni
  • Ascaris lumbricoides
  • Strongyloides stercoralis

97
A UNIQUE ROLE FOR INTESTINAL HELMINTHS
  • Stimulate development of TH-2 cells and
    down-regulate TH-1 cells
  • Stimulate production of the anti-inflammatory
    cytokine IL-10
  • Lack of helminths may account for the increasing
    prevalence of inflammatory disorders in the
    developed world, both atopic and mediated by TH-1
    autoimmunity

98
LACTOBACILLI BENEFICIAL EFFECTS
  • Produce organic acids lower bowel pH
  • Produce H202
  • Antagonize enteropathogenic E. Coli, Salmonella,
    Staphylococci, Candida albicans, and Clostridia
    spp
  • Degrade N-nitrosamines
  • Anti-tumor glycopeptides (L. bulgaricus)
  • Stimulate balanced immune responses

99
Lactobacilli for Prevention of Food Allergy in
Infants
  • DBPCT Lactobaciilus GG given to high risk
    mothers during last 2 weeks of pregnancy and for
    6 months after birth to their offspring
  • Atopic eczema at 2 years
  • Controls 31/68 (46)
  • Lactobacillus 15/64 (23), RR0,51
  • Kalliomaki et al, Lancet 357 1076-79 (2001)

100
Lactobacilli for Managing Food Allergy
  • Infants with atopic eczema and cows milk allergy
    fed hydrolyzed whey formula with or without
    Lactobacillus GG
  • -Clinical improvement associated with 95
    decline in fecal TNF-alpha in the Lactobacillus
    group, signifying reduced GI inflammation
  • Majamaa, Isolauri, J All Clin Immunol 1997

101
BENEFITS OF BACILLUS LATERSPORUS
  • Laterosporamine antibiotic
  • Suppress auto-antibody formation
  • Suppress murine lupus nephritis
  • Spergualin anti-tumor, antibiotic

102
BENEFITS OF SACCHAROMYCES BOULARDII
  • Stimulates production of sIgA
  • Protects against antibiotic diarrhea
  • Helps reverse C difficile colitis

103
E. COLI BENEFICIAL EFFECTS
  • Prevents infection of animals with Cholera,
    Shigella, Pseudomonas and staph aureus (no effect
    on Candida or Salmonella)
  • Degrades N-nitrosamines and polycyclic aromatic
    amines and N-hydroxyl aryl amines

104
E.COLI AND ULCERATIVE COLITIS
  • E. coli in colonic crypts of UC patients shows
    abnormal adherence
  • Burke, Axon J Clin Path 40 782-786 (1987)
  • After inducing remission with gentamycin and
    prednisone,Nissle 917 strain E. coli were as
    effective as mesalamine in maintaining remission
    at 12 months
  • Rembacken et al, Lancet 354 635-640 (1999)

105
EPITHELIAL PERMEABILITY REGULATES TRANSPORT OF
WATER, SOLUTES AND PARTICULATE MATTER
  • The intestinal epithelium is the site of
    vectorial transportbetween the intestinal lumen
    and the circulation. The net effect of transport
    is regulated by the tightness (or leakiness) of
    the barrier and vice versa. Both transport and
    barrier functions are physiologically regulated,
    and both can be dramatically altered under
    disease conditions.

106
MECHANISMS WHICH SUPPORTNORMAL INTESTINAL
PERMEABILITY
  • Intestinal mucus
  • Secretory IgA
  • Mucosal epithelium
  • Intramural macrophages
  • Intramural lymphocytes
  • intra-epithelial
  • in Peyers patches

107
TWO TYPES OF EPITHELIAL PERMEABILITY
  • Trans-Cellular
  • Para-Cellular

108
(No Transcript)
109
TRANS-CELLULAR PERMEABILITY
  • The principal route for the absorption of
    solutes, fluid and macromolecules

110
ACTIVE TRANSPORT
  • Monosaccharides
  • Amino acids, peptides
  • Sodium, zinc, copper, iron, calcium
  • Vitamins

111
NUTRIENT ABSORPTION BY DIFFUSION
  • Magnesium
  • Free fatty acids
  • Monoglycerides, lysolecithin

112
ENDOCYTOSIS
  • Micelles
  • Macromolecules
  • Antigens
  • Microbes

113
INTESTINAL ANTIGEN TRANSPORT IS A PHYSIOLOGICAL
PROCESS
  • M-Cells
  • Particulate/insoluble antigens
  • Overlie Peyers Patches
  • Response is mostly CD4
  • Enterocytes
  • Soluble antigen
  • Response is mostly CD-8

114
(No Transcript)
115
(No Transcript)
116
INCREASED TRANS-CELLULAR PERMEABILITY
  • Results from impairment of mucosal metabolism
  • Represents a breakdown in the normal activity
    known as Gut Antigen Sampling

117
PARA-CELLULAR PERMEABILITY IS LIMITED BY CELL
ADHERANCE MOLECULES (CAMs)
  • Tight junctions contain claudins
  • Adherens junctions and desmosomes contain
    cadherins
  • Contraction of the cytoskeleton opens junctions
    (glucose absorption is a stimulus)

118
(No Transcript)
119
CAUSES OF INCREASED PARA-CELLULAR PERMEABILITY
  • Infectious agents
  • Parasites
  • Bacteria
  • Viruses
  • Yeasts
  • Continued

120
CAUSES OF INCREASED PARA-CELLULAR PERMEABILITY
  • Enterotoxins
  • Ethanol
  • NSAIDs
  • Cytotoxic drugs
  • Dysoxia
  • Ischemia
  • Reactive oxygen species

121
PSYCHOLOGICAL STRESS CAN INCREASE GUT
PERMEABILITY THROUGH A CHOLINERGIC MECHANISM
  • Rats cold stress increases both para-cellular
    permeability and endocytosis.
  • -This effect is greater when cholin-
    esterase activity is weak
  • -The effect is blocked by atropine
  • -It may depend upon vagal activation of
    mast cells
  • Similar effects occur in humans

122
DIET ALTERS INTESTINAL PERMEABILITY
  • Fasting
  • Controls Increased I.P.
  • R.A. Decreases I.P.
  • Continued

123
  • Increased I.P. induced by
  • Low-fiber diets
  • Carrageenan
  • Pectin/guar gum
  • Castor oil
  • Alcohol
  • Allergens

  • Continued

124
  • Mucosal Inflammation
  • Food allergy
  • Idiopathic

125
EFFECTS OF INCREASED PERMEABILITY
  • Antigen Overload
  • Sensitization
  • Immune suppression
  • Toxic Overload
  • Hepatic stress
  • Sepsis

126
INTESTINAL PERMEABILITY IS MEASURED BY PROBES
ABSORBED AND EXCRETED UNCHANGED BY THE KIDNEYS
  • Probes used for small bowel permeability include
    Cr51-EDTA, PEGs and the ratio of lactulose to
    mannitol.
  • Colonic permeability can only be measured if the
    probe is administered by enema.

127
INCREASED INTESTINAL PERMEABILITY (LEAKY GUT) IS
NOT A DISEASE OR SYNDROME
  • It contributes to the pathophysiology of many
    different diseases.
  • Improvement of the related disease usually
    improves the leaky gut.
  • Decreased intestinal permeability often improves
    the associated disease.

128
LEAKY GUT SYNDROMES
  • Enteritis, colitis Infectious/inflam-matory
  • Arthritis, chronic inflammatory
  • Food allergic disorders
  • AIDS
  • CFIDS
  • MCS
  • Chronic pancreatic disease
  • Chronic non-infectious hepatitis
  • Acne
  • psoriasis

129
THE FOUR VICIOUS CYCLES OF THE LEAKY GUT
  • Food Allergy
  • Malnutrition
  • Dysbiosis
  • Hepatic Distress

130
CYCLE ONE FOOD ALLERGY
  • Increased baseline permeability
  • Marked increase after challenge
  • Increase blocked by sodium cromoglycate

131
ABNORMAL INTESTINAL PERMEABILITY IN FOOD ALLERGY
  • 42 of children with eczema had reduced
    jejunal villuscrypt ratios (malabsorption)
  • Increased PEG-4K absorption (leakiness)
  • Increased PEG absorption blocked by cromolyn
    pre-treatment
  • Increased fasting lactulose absorption in adults
    with food allergy (eczema, hives) further
    increase with offending food blocked by cromolyn
    300mg

132
  • Evaluation of I.P provides an effective means
    of diagnosing food allergy
  • Barau E and Dupont C, Modifications
  • of Intestinal Permeability during Food
  • Provocation Procedures in Pediatric
  • Irritable Bowel Syndrome,
  • J Pediatr Gastroenterol Nutr, 1172-77,
  • 1990

  • Continued

133
  • 17 children with IBS
  • 9 with with food-induced alterations of
    intestinal permeability
  • All 9 were completely cured with diet (7 diet
    alone, 2 diet plus oral cromolyn before meals)

134
  • After ingesting food allergens,
    lactulose/mannitol (L/M) ratios rose
    significantly
  • Taking sodium cromoglycate prevented the rise in
    L/M ratios

  • Continued

135
(No Transcript)
136
(No Transcript)
137
CYCLE TWO MALNUTRITION
  • Most nutrients require active transport
  • Factors which increase I.P. may hinder active
    transport
  • Resulting malnutrition disrupts intracellular
    adhesion

138
CYCLE THREE DYSBIOSIS
  • Bacterial proteases disrupt cellular adhesion
    molecules
  • Increased I.P. leads to bacterial sensitization
  • Bacterial sensitization causes leukocyte
    migration which increases permeability

139


140
CYCLE FOUR HEPATIC DISTRESS
  • Increased permeability causes
  • Toxic stimulation of mono-oxygenases
  • Increased free radical generation
  • Damage to hepatocytes and bile ducts

141
  • Biliary excretion of reactive oxygen species
  • Reflux of toxic bile into pancreatic ducts
  • Loss of factors
  • Pancreatic insufficiency
  • Toxic bile enteropathy

142
HEPATIC COST OF INCREASED PERMEABILITY
  • Kupffers Cell Paralysis
  • Stimulation of Mono-Oxygenases
  • Depletion of substrates for conjugation
  • GSH, Glycine

  • Continued

143
HYPER-PERMEABILITY IN RHEUMATOID ARTHRITIS
  • NSAIDs increase intestinal permeability
  • Increased I.P. allows sensitization to gut flora
  • Bacterial sensitization causes enteritis and
    formation of circulating immune complexes


144
HYPER-PERMEABILITY IN RHEUMATOID
ARTHRITIS(continued)
  • I.P. is further increased
  • Systemic inflammation exacerbates
  • Metronidazole and minocycline break the cycle

145
TREATMENT OF HYPER-PERMEABILITY
  • Avoid enterotoxins
  • Treat intestinal infection/bacterial overgrowth
    with antimicrobials
  • Diet high nutrient density
  • non-irritating
  • allergen-free

146
HELPING TO REPAIR THE DAMAGED INTESTINE
  • Glutamine
  • Essential fatty acids
  • Antioxidants
  • Glutathione
  • Bioflavonoids
  • Vitamin E
  • Gamma-oryzanol
  • Epidermal growth factor

147
A.F., a 6 year old girl with fever of unknown
origin
  • Prior history vesicoureteric reflux and
    recurrent UTI used co-trimoxazole from 12 to 36
    months of age and it cleared.
  • Age 5 developed cycling fever with daily
    temperature spikes to 105 F, lasting 5 days and
    recurring every 10 to 21 days.
  • Appendectomy (normal appendix) followed by 2
    months of metronidazole in September 1998.
    Microscopic colitis was found in transverse
    colon, not though to be Crohns or ulcerative
    colitis.
  • Fevers continued but with decreased severity and
    frequency

148
A.F., a 6 year old girl with fever of unknown
origin
  • Parents started a diet eliminating sugar, junk
    food, wheat and milk products, with improvement
  • -Fevers occurring every 5 to 7 weeks, lasting
    only 3 days, spiking only to 102 F. In between
    fevers, patient appears very healthy. ESR 38 with
    fever
  • Seen in July 1999.
  • ESR 16 (afebrile)
  • intestinal permeability low mannitol
    excretion (3), high lactulose/mannitol ratio
    (0.313)
  • IgG to casein in blood, not to gluten

149
A.F., a 6 year old girl with fever of unknown
origin
  • Treatment
  • -casein-free diet
  • -L-glutamine 3.7 gm bid
  • -microcrystalline cellulose 3.7 gm bid
  • -N-acetyl-glucosamine 185 mg bid
  • - Ulmus rubra bark (slippery elm) 110 mg bid
  • -Methylsulfonylmethane (MSM) 160 mg bid
  • -Aloe vera extract (30 MPS) 1 tsp qd
  • Mixed together in apple sauce

150
A.F., a 6 year old girl with fever of unknown
origin
  • Initial response
  • -Radiant and happy, energy better than in her
    whole life
  • - No fever until April, 2000, following Easter
    festivities
  • -Temp 102 F, lasting 2 days, recurred 3 weeks
    later.
  • -Intestinal permeability low mannitol
    excretion (3), lactulose/mannitol ratio
    improved at 0.107
  • Advised to follow casein-free diet 100 for at
    least a month
  • Further response
  • -No fever during subsequent year
  • -Normal intestinal permeability by 10/00.
    Mannitol excretion 12, lactulose mannitol ratio
    0.04.
  • -Glutamine, NAG, MSM, slippery elm, aloe
    discontinued.
  • -Able to tolerate casein when away from home.

151
INTESTINAL PERMEABILITY AND CROHNS DISEASE
  • Patients have increased I.P.
  • First degree relatives have high I.P.
  • Patients have abnormal reactivity of mucosal
    lymphocytes to normal gut flora and Candida
    antigens

152
  • For patients in remission, the rate of relapse
    correlates with I.P. measured prospectively
  • Wyatt J et al, Intestinal Permeability and the
    Prediction of Relapse in Crohns Disease, Lancet
    3411437-1439, 1993

153
(No Transcript)
154
(No Transcript)
155
NUTRITIONAL THERAPY FOR CROHNS DISEASE
  • 20 patients, age 21 to 59, ill 6 mo to 12 yrs
    followed for 6 months to 8 years
  • symptoms scored diarrhea, abdominal pain, fever,
    fatigue, blood/mucus in stool, weight
  • lab tests scored hemoglobin, ESR, albumen,
    intestinal permeability (lactulose/mannitol
    fractional excretion)

156
THE SPECIFIC CARBOHYDRATE DIET
  • EAT fruits, vegetables, meat, fish, poultry,
    eggs, nut flours and butters, most legumes, eggs,
    some hard cheeses and yogurts
  • AVOID all grains, disaccharides (lactose and
    sucrose), soy, potatoes

157
DIETARY SUPPLEMENTSSTAGE I
  • Fish oil, delayed release, supplying 875 mg of
    eicosapentaenoic acid (EPA)/ day
  • vitamin E 400 mg/day
  • zinc 20 mg/ day
  • selenium 200 mcg/day
  • folic acid 800 mcg/day

158
STAGE II DIET OPTIONS
  • complete milk avoidance
  • yeast/mold elimination diet
  • avoidance of nuts and nut flours
  • addition of non-glutinous starch (e.g., rice and
    potatoes)
  • As modifications to the Specific Carbohydrate
    Diet

159
STAGE II SUPPLEMENTS
  • glutamine 3000 mg/day
  • Aloe vera mucopolysaccharide concentrate (ace
    mannan) 4 grams/day

160
CLINICAL RESPONSES
  • complete clinical remission 6
  • reduction in symptom scores 14
    range 90 to 40, mean 65
  • response to Stage I diet
    11
  • response to yeast/mold diet
    5
  • response to milk elimination diet 5
  • required elimination of nuts
    4

161
SYMPTOM SCORES
162
SEDIMENTATION RATE
163
INTESTINAL PERMEABILITY
  • Lactulose/mannitol ratio, ref range is 0.01 to
    0.06
  • measured in 13 patients
  • decreased in 84
  • initial mean 0.275 (range 0.024 to 0.645)
  • final mean 0.074 (range 0.018 to 0.186)

164
SERUM ALBUMEN
  • Mean serum albumen increased
  • initial 32 G/L (range 24 to 38)
  • final 41 (range 28 to 46)

165
MEDICATION USE
  • ASA derivatives (16 patients), mean dose
    decreased 33
  • prednisone (6 patients), mean dose decreased from
    17 mg/day (range 10 to 40) to 5 mg/day (range 0
    to 7.5)
  • azathioprine (3 patients), mean dose decreased
    from 100 mg/day to 33 mg/day (range 0 to 50)

166
CASE REPORT
  • 28 year old male, sick for 3 years, disabled
  • prednisone 40 mg, azathioprine 100 mg/day
  • fever 40 degrees C, bloody diarrhea 6 times/day,
    30 pound weight loss, ESR 90, albumen 26 g/L,
    oxalic acid excretion 164 mg/day

167
CASE REPORT
  • Stage I diet for 3 weeks led to complete clearing
    of symptoms
  • Addition of stage I supplements and maintenance
    of diet led to ESR of 5, albumen of 4.2, weight
    gain of 15 pounds over 60 days
  • all medications discontinued

168
CASE REPORT
  • 1-year follow-up maintenance of clinical
    remission, lactulose/mannitol ratio 0.026,
    oxalic acid excretion of 32 mg/day
  • complete remission of all parameters for 3 years

169
Food Allergy
  • Leo Galland M.D.
  • Foundation for Integrated Medicine

170
HOW PREVALENT IS FOOD ALLERGY/INTOLERANCE?
  • 33 of 1000 teachers (56 response rate) reported
    avoidance specific foods because of unpleasant
    physiological reactions.
  • A poll of 5000 US physicians on prevalence of
    food allergy (14 response rate) 0-80 (mean 10)

171
Immunologic Mechanisms of Food Intolerance
  • Type I (IgE mediated, TH2 promoted)
  • Type II (IgG and complement mediated, cytotoxic,
    TH1 promoted)
  • Type III (IgG immune complex mediated, TH1
    promoted)
  • Type IV (cell-mediated, TH1 promoted)

172
Non-immunologic Mechanisms of Food Intolerance
  • Digestive (e.g., lactase deficiency)
  • Pharmacologic (e.g., caffeine, ethanol)
  • Biochemical (histamine, tyramine, salicylates,
    sulphites, MSG)
  • Non-specific mast cell degranulation
  • Lectin-mediated glycoprotein agglutination

173
Poor Sulphoxidation and Food Allergy (Scadding
1988)
  • 74 adults with non-IgE food allergy diagnosed by
    elimination and challenge
  • 78 slow carbocisteine sulfoxidizers vs 33 of
    controls (plt0.005)
  • Carbon oxidation (debrisoquine) normal
  • Theory altered metabolism of food chemicals
    toxic/immunogenic metabolites by novel pathways

174
(No Transcript)
175
FOOD ALLERGY/INTOLERANCE WELL-DOCUMENTED
MANIFESTATIONS
  • Atopic Eczema
  • Allergic Rhinitis, Asthma
  • Anaphylaxis, Angioedema, Urticaria
  • Oral Allergy Syndrome (Ortolani)
  • Aphthous Ulceration
  • Alveolitis, Hemosiderosis
  • Infantile Colic
  • Vomiting, Diarrhea, Abdominal Pain
  • Irritable Bowel Syndrome
  • Hematochyzia, Colitis
  • Pediatric Enteropathies
  • Celiac Disease
  • Protein-losing Enteropathy
  • Failure to thrive
  • Crohns Disease (exacerbation)
  • Migraine headches
  • Migraine-associated Epilepsy
  • ADHD
  • Nephrotic Syndrome
  • Allergic Arthritis
  • Rheumatoid Arthritis (exacerbation)

176
FOOD ALLERGY IN PEDIATRIC ATOPIC ECZEMA
  • 25-60 are food reactive
  • Increased gut permeability
  • at baseline
  • after food challenges
  • blocked by cromolyn
  • Histamine release
  • Circulating immune complexes
  • Multi-system reactivity in 2/3
  • 49 gastrointestinal
  • 23 rhinitic
  • 17 asthmatic
  • Poor correlation between food responses and prick
    tests, RAST milk, egg, citrus, additives, nuts,
    fish, wheat, tomatoes, lamb, chicken, soy

177
FOOD ALLERGY IN PERENNIAL RHINITIS(Ortolani et
al)
  • 210 patients over 1 year
  • 3-week oligoantigenic diet
  • 52 improved (24.8)
  • 28 IgE mediated (13.3), based upon
    correlation with RAST, skin testing
  • 24 no correlation

178
FOOD ALLERGY IN RECURRENT APHTHOUS STOMATITIS
  • Cytotoxic lymphocytes/antibodies
  • Histamine release to foods (23/60)
  • 30 correlation of HR and ulcers
  • Gluten, milk, food additives

179
FOOD ALLERGY IN HYPERKINETIC SYNDROME(Egger et
al, Lancet 1985)
  • 76 children seen on referral
  • (60 boys, 16 girls)
  • age 2-15 (mean 7.3)
  • 37 from dysfunctional families
  • 4 weeks oligoantigenic diet
  • 2 meats, 2 starch sources, 2 fruits,
  • 1 vegetable, calcium, multivitamin

180
RESPONSE TO OLIGOANTIGENIC DIET IN HYPERKINETIC
SYNDROME
  • Pre-diet Diet
  • Total number 76
    76 Hyperactivity
  • Normal 0 21
  • Mild 6 28
  • Moderate 31 19
  • Severe 39
    8
  • Conners score 24 12
  • Antisocial acts 32 13
  • Headache 48 9
  • Seizures 14 1
  • Abdominal pain 54
    8
  • Limb pain 33 6
  • Eczema, rash 29
    9
  • Aphthous ulcers 15
    5
  • Atopic (prick test) 30
    (39)

181
Summary of Eggers Results
  • Open trial 82 of children responded favorably
    to the oligoantigenic diet
  • DBPCT 28 participated, with rating of response
    by parents, a neurologist and a psychologist
  • DBPCT 51-74 of the food intolerances confirmed

182
FOODS PROVOKING HYPERACTIVITY IN DOUBLE-BLIND,
PLACEBO-CONTROL TRIAL
  • REACTIVE
  • Additives 79
  • Soy 73
  • Milk 64
  • Chocolate 59
  • Grapes 50
  • Wheat 49
  • Oranges 45
  • Cheese 40
  • Eggs 39
  • Peanuts 32
  • Corn 29
  • Fish 23
  • Oats 23
  • Melon 21
  • Tomato 20

183
Cognitive-Emotional Symptoms and Food Allergy
(King, 1981)
  • DBPCT 30 adults, 28 food extracts, sub-lingual,
    multiple measures, 2 judges
  • Symptoms associated with allergen exposure
    anxiety, depression, brain fog, irritability,
    detachment, euphoria pruritus, cold hands,
    myalgia, nasal congestion, tinnitus, fatigue,
    headache
  • Occurrence p0.001, Severity p0.002

184
FOOD ALLERGY IN PEDIATRIC MIGRAINE (Egger, 1983)
  • 88 children, oligoantigenic diet
  • 93 cleared by 2 weeks
  • 90 relapsed on open challenge
  • 40 of these, DBPC TRIAL
  • 26 confirmed (4 reacted to placebo, 8 reacted to
    neither)
  • Atopy 55, 46 hyper, 16 seizures
  • Milk, egg, chocolate, orange, wheat
  • benzoate, cheese, tomato, tartrazine, rye, fish,
  • pork, beef, corn, soy, tea

185
MIGRAINE-ASSOCIATED SYMPTOMS AND FOOD INTOLERANCE
  • 88 PATIENTS
  • Pre-diet Diet
  • Abdominal pain,
  • diarrhea 61 8
  • Hyperactivity 41 5
  • Limb pain 41 7
  • Rhinitis 34
    15
  • RAS 15 2
  • Vaginal discharge 11 1
  • Asthma 7 3
  • Eczema 6 3
  • 27/40 provoked by DBPC food trial
  • 10/40 provoked by placebo also
  • 3/40 provoked by neither

186
EVIDENCE FOR ALTERED IMMUNE ACTIVATION IN
RESPONSE TO FOODS IN MIGRAINE(Marteletti 1991,
Acta Neurologica)
  • Increased circulating immune complexes
  • Increased activated T cells and total T cells
  • Increased plasma IL-2 levels
  • Effective prophylaxis with oral sodium
    cromoglycate

187
Food Allergy in Idiopathic Nephrotic Syndrome
  • Basophile histamine release test
  • - 65 of 34 patients
  • - 5 of 19 controls
  • wheat, beef, milk, egg, pork
  • 26 patients with refractory nephrosis
  • - 6 remitted on oligoantigenic diet

188
TM, a 26 old woman with massive proteinuria,
anasarca
  • Prior aesthetician, applying artificial nails,
    developed asthma, multiple inhalant allergies,
    provoked by allergy immunotherapy
  • Severe anasarca emergency
    hospitalization, furosemide, steroids
  • Proteinuria 4 gm/day, serum albumen 1.3 gm/L,
    marked hyperlipidemia, normal biopsy
  • Required prednisone 20 mg/day maintenance

189
TM, a 26 old woman with massive proteinuria,
anasarca
  • Initial evaluation Cushingoid, 3 proteinuria
  • Method modified fast, supported by a rice-based,
    oligoantigenic food supplement, tapering down
    prednisone and daily examination of urine protein
    by dipstick
  • Result clearing of proteinuria in 7 days, return
    of proteinuria within 24 hours of ingesting hens
    eggs
  • Total remission for 7 years, avoids eggs

190
Food Intolerance and Rheumatoid Arthritis
  • 5-46 of patients in various studies have
    exacerbation of symptoms provoked by specific
    foods, mostly wheat, milk, tomatoes, various
    additives, some confirmed with DBPC trials
  • An 18-year open study of foods provoking pain in
    100 patients found that certain spices and food
    additives were commonest agents

191
GLUTEN INTOLERANCE IS PREVALENT AND PROTEAN
  • Gliadin antibodies were found in 30/53 patients
    with neurological disease of unknown cause (73
    had abnormal small bowel biopsies)
  • Hadjivassiliou et al, Lancet 347 369-371 (1996)
  • IgG and IgA gliadin antibodies occur in 2 of
    Italian school children
  • Catassi et al, Lancet 343 200-203 (1994)

192
Cows Milk Allergy and IDDM
  • Children with IDDM have IgG against a peptide
    fraction of bovine serum albumen that cross-react
    with a pancreatic beta-cell surface protein
  • Adults with recent-onset IDDM show excessive
    T-cell proliferation in response to beta-casein,
    compared to normal and auto-immune controls

193
DIAGNOSIS OF FOOD ALLERGY
  • History
  • atopic disease
  • multisystem complaints
  • fluctuations
  • provocations
  • - rough skin, red ears, geographic tongue
  • Skin tests, IgE (total/food specific)
  • Dietary elimination/challenge
  • symptom change
  • gut permeability change

194
D-XYLOSE ABSORPTION DECREASES AFTER FOOD ALLERGEN
CONSUMPTION
  • In children with cows milk protein enteropathy
    (diarrhea, pain), 1 hour blood d-xylose was
    significantly higher on a milk-free diet than 4
    days after starting a milk-containing diet
  • Morin et at, Lancet i 1102-1104 (1979)

195
(No Transcript)
196
Elimination Diets
  • Elemental
  • Oligoantigenic
  • Avoid commonest allergens milk, wheat, corn,
    soy, eggs, citrus, nuts, fish
  • Gluten and/or casein-free
  • Yeast and mold-free
  • Low-salicylate

197
Technique of Food Elimination
  • Obtain baseline measure of target symptoms or
    signs
  • Complete avoidance of all food/drink containing
    test components for 5-14 days
  • Instruct patients/parents in foods that can or
    should be eaten and in monitoring of symptoms

198
Food Challenge Techniques
  • If there is no change in target parameters,
    return to usual diet en bloc and observe for
    exacerbation
  • If improvement is observed, introduce foods
    singly, one every 1-2 days, 2-6 challenges for
    each food delayed reactions are common
  • If symptoms occur, hold challenges until clear
  • Avoid suspected symptom provokers
  • Re-challenge with these after completion

199
TREATMENT OF FOOD ALLERGY
  • Symptomatic pharmacotherapy
  • Dietary avoidance
  • Pre-prandial cromolyn 800-1600 mg/day
  • Intestinal repair
  • Probiotics
  • Counseling nutritional, psychological
  • Induction of oral tolerance

200
Detoxification
  • Leo Galland M.D.
  • Foundation for Integrated Medicine

201
OUR BODIES DETOXIFY
  • Exogenous, foreign substances
  • Endogenous, internally created substances

202
ENDOGENOUS SUBSTANCES
  • Gut toxins
  • bacteria
  • parasites
  • yeast
  • Hormones
  • Bile acids
  • Metabolic intermediates

203
EXOGENOUS SUBSTANCES
  • Xenobiotics
  • herbicides
  • pesticides
Write a Comment
User Comments (0)
About PowerShow.com