This document summarizes a presentation on new approaches to food allergy testing. It begins with the presenter's commercial disclosure statements listing companies he has received honoraria from or served on speaker's bureaus for. The presentation then covers the different immunoglobulin antibodies involved in food allergies, specifically IgE, IgG, and IgA. It discusses the mechanisms and downstream effects of these antibodies and food allergy reactions. Finally, it reviews several studies that have found associations between food allergies or sensitivities and conditions like attention-deficit/hyperactivity disorder, depression, anxiety, and autism spectrum disorders.

1. Adjunct Asst. Prof of Psychiatry – Indiana University School of
Medicine Department of Psychiatry
Child, Adolescent, Adult, Functional Neuropsychiatry – Evansville,
Indiana
4rth Annual MMH CONFERENCE – Chicago, IL.
Saturday, September 21, 2013
New Adventures in Food Allergy Testing
Louis B. Cady, MD – CEO & Founder – Cady Wellness InstituteLouis B. Cady, MD – CEO & Founder – Cady Wellness Institute

2. Continuing Medical Education Commercial Disclosure Requirement
for Louis B. Cady, M.D.
I, Louis B. Cady, MD, have the following commercial relationships to
disclose:
•Speaker honoraria received from:
• Immunolaboratories, Great Plains Diagnostic Labs, LABRIX
•Speaker’s bureaus (active) for:
• Forest Pharmaceuticals, Sunovion, Shionogi
•Historical data – speaker’s bureau for Bristol-Myers Squibb,
Celltech, Cephalon, Eli Lilly, Glaxo-Smith Kline, Janssen, McNeil,
Pfizer-Roerig, Sanofi!~aventis, Sepracor, Shire, McNeil, Takeda,
Janssen, Searle, Shire, Takeda, Wyeth-Ayerst

3. IMMUNOLOGY
The forgotten component
of “workups”

4. "What is
food for
one, is to
others bitter
poison.”
Lucretius – 099? B.C.
– 055? A.D.
De rerum natura.

5. “The Three Little Ig’s & Three Stories”
•Ig E
•Ig G
•Ig
xciting
oing along
norant

6. IgE Antibodies: catastrophic reactions vs. sneezes
and itching (checked via skin tests or RAST)
http://pathmicro.med.sc.edu/ghaffar/skintest.jpg

7. http://users.rcn.com/jkimball.ma.ultranet/B
iologyPages/M/MastCell.gif
www.souzaoenterprises.com/A
llergiescomp.jpg
CELLULAR immunity

8. This model of human IgG1 was created
by E. A. Padlan -- "Anatomy of the
Antibody Molecule." Molecular
Immunology 31:169 (1994)
HUMORAL Immunity
“Globulin molecules
capable of attacking the
invading agent.” [Guyton]

9. Actions and downstream effects
• Direct action of antibodies:
– Agglutination, precipitation, neutralization,
lysis
• Downstream effects: complement
activation:
– Lysis, opsonization/phagocytosis, chemotaxis,
agglutination, neutralization of viruses,
INFLAMMATORY EFFECTS

10. The Classical Pathway of Complement Activation
http://www.youtube.com/watch?v=gNvHLStz-VA

11. It can therefore be hypothesized that all the
components of the circulatory humoral system are
participating in this reaction and that Type II, the
cytotoxic, and Type III, the immune-complex type of
immunologic reaction, are the major contributors in
the production of symptoms.
It can therefore be hypothesized that all the
components of the circulatory humoral system are
participating in this reaction and that Type II, the
cytotoxic, and Type III, the immune-complex type of
immunologic reaction, are the major contributors in
the production of symptoms.
Trevino RJ. Laryngoscope. 1981
Nov;91(11):1913-36.

12. De Weck Al. Ann Allergy. 1984
Dec;53(6 Pt 2):583-6.
De Weck Al. Ann Allergy. 1984
Dec;53(6 Pt 2):583-6.
“antigen-IgG complexes generating
anaphylatoxins…”

13. ADHD Diagnosis
DSM-IV (TR)
–SIX Symptoms present
before age 7 years
–Impairment from symptoms
present in 2 or
more settings
–Significant social, academic,
or occupational impairment
–Exclude other mental
disorders
DSM-V
–Symptoms rewritten
slightly
• FIVE only required for
adults

14. From:
www.patientmedia.com
(used with permission of
William Esteb)

15. Food Allergies and ADHD in the Literature
• Get “THE THINKER” illustration•Food allergies presumed to be related to ADHD
•Before 1976 – No known relationship between FA and ADD
•1976 – IgE reactivity + food allergies = decreased IQ
•1985 – d/c of antigenic foods = ADHD improvement
•1993 – more confirmation
•1994 – some kids that got better on diet did NOT have IgE
reactivity
•2003 – evidence mounting for non-IgE sensitivities related to food
allergies]
•2002 – 2011 Pelsser LM et al – SIX published papers (European
and Dutch literature, cf: www.pubmed.gov).
•73 papers, at present – 8/03/2013

16. Millman, et al – the groundbreaking
article
• “Allergy & Learning Disabilities in Children” – Annals
of Allergy, 1976 [36:3, 149-160.]
• “The allergic tension-fatigue syndrome observed by Speer”
– “A symptom complex accepted by many allergists.”
• Food allergies established by scratch testing or intradermal
injections
• Positive correlation between [IgE] food
allergies and IQ scores.
–The more the food allergies, the
lower the IQ scores.

17. Oligoantigenic diet (w/o testing)
• “Controlled trial of oligoantigenic treatment in the
Hyperkinetic Syndrome.” Egger et al. Lancet,
March 9, 1985, 540-545.
• No testing performed
• Children empirically placed on restrictive diet.
– Two meats, two carb sources, two fruits, one vegetable,
water, calcium, vitamins.
• No food allergy symptoms were provoked; ADHD
improved.

18. The crossover study – no
distinguishing between IgE and IgG
• “Effects of a few foods diet on ADD.” Carter et al, Archives
of Disease in Childhood, 1993;69:564-568.
• “Few foods” elimination diet
– 59 of 78 children improved.
• “This trial indicates that diet can contribute to behavior
disorders in children and that this effect can be shown in a
double blind, placebo controlled trial.”
• “The ways in which [this] diet worked remain
unclear. Toxic pharmacological, or allergic
mechanisms could be involved, and the
physiological effects of different foods may vary.”

19. Profound cautions
• “Effects of a few foods diet on ADD.” Carter et al, Archives
of Disease in Childhood, 1993;69:564-568 (cont.)
• “The treatment, as applied in this study, has
disadvantages. It is a difficult and exacting
regimen, which puts a considerable strain on
the whole family. It is not yet clear whether modified
diets can also be effective…. It may therefore be possible
to devise a less restricted diet with similar levels of
success.”
• Cady impression: “Shooting in the dark is dangerous.”

20. The appearance of IgG
• “Foods and additives are common causes of
ADHD in children.” Boris, et. al. Annals of Allergy,
vol.. 72, 1994, 462-468.
• “DBPCF” - “double blind placebo controlled
food challenge test”
• 4/19 children who showed improvement
with removal of offending foods were non-
atopic.

21. Pelsser publishes - 2002
• “few foods diet” – {rice, turkey, pear &
lettuce} in 40 children
– 36 boys, 4 girls; 3-7 years of age, all dx with
ADHD}
• Results:
– 25 patients (62%) improved behavior >/= 50%
– 10 (25%) had improved parent/teacher ratings.
– 9 (23%) withdrew from study
Pelsser LM, Buitelaar JK. Favourable effect of a standard elimination diet on
the behavior of young children with attention deficit hyperactivity disorder
(ADHD): a pilot study. Ned Tijdschr Geneeskd. 2002;146(52):2543–2547

22. “IgE and Non IgE Food Allergy”
• Sabra, et al. Annals of Allergy, Asthma, and
Immunology 2003;90 (Suppl 3)71-76.
• “The gastrointestinal tract serves not only a
nutritive function but also is a major immunologic
organ. Although previously thought to be triggered
primarily by an IgE mediated mechanism of injury,
considerable evidence now suggests that non-
IgE mechanisms may also be involved in the
pathogenesis of FA (“food allergy”).

23. Pelsser publishes (again)- 2011
• “Impact of Nutrition Study on Children with ADHD”
• 100 children, 4-8 years of age with ADHD
– Open label phase – 5 weeks of a restricted elimination
diet (“diet group”) OR healthy control diet (50 kids each)
– THEN – 4 week double-blind crossover challenge of “diet
group” responders
• Challenge responders:
– With either HIGH or LOW IgG reactivity (per testing):
• increase of 20.8 point on ADHD [ARS] rating scale (p<0.0001)
• 11.6% increase of a Conner’s score (p<0.0001)
• After challenge – 63% of children relapsed
Pelsser LM, Frankena K, Toorman J, et al. Effects of a restricted elimination
diet on the behaviour of children with attention-deficit hyperactivity disorder
(INCA study): a randomised controlled trial. Lancet. 2011;377(9764):494–503

24. What does a 20.8 point increase in ARS
mean???
Number crunching:
•9 symptoms of
inattentiveness & 9 of
hyper/impuls = 18.
•Lichert scale {0 – 3}
•Max score = 18 *3 = 54
points
•20.8 points = 39% of
range.
• Assume little Johnny has dropped from 45 to 18 in phase II of study (40%
drop which was required.)
• Increase from 18 +20.8 points = 39 points = 2.16 X increase in sxs.

25. • Drug examples:
– Fluoxetine at 80 mg (max dose) gets
increased to 172.8 mg
– LiCO3 gets increased from 1200 mg/d to
2,592mg of Li+/day
– LIPITOR – goes from 80 mg to 172.8 mg
Well, what does a 2.16 X effect mean?
• My favorite: a speeding ticket for 75 mph in a
70 mph zone gets increased to going 162 mph!!

26. FROM HYPERNESS TO
HEADACHES
…and joint pains,
migraines, brain fog,
irritable bowel
syndrome, asthma,
fatigue, misc. aches
and pains

27. www.pubmed.com search August 2, 2013
Correlations found between food allergy & :
• ADHD (73 citations)
• Depression (80 citations)
• Anxiety (109 citations)
• Acute psychosis (1 citation)
• Autism (43 citations)
• Schizophrenia (20 citations)

28. Mechanisms of behavioral, atopic, and other
reactions to artificial food colors in children
[Stevens LJ et al. Nutr. Rev. 2013 May; 71(5):268-81]
• “… a subgroup of children (with or without
ADHD) react adversely to challenges with
AFC’s.”
• “Children with ADHD show EXCESS
inattention, impulsivity, and hyperactivity.”
• “Studies using at least 50 mg of AFC’s
showed a greater % of children who reacted
to the challenge.”

29. Neltner, T. JAMA Internal Medicine
August 7, 2013
Neltner, T. JAMA Internal Medicine
August 7, 2013
In a previous study, Neltner and his colleagues estimated that
about 43 percent of the 10,000 or so additives allowed in food
were on the FDA's GRAS list, with other additives approved
through other means or not submitted to the FDA.
Manufacturers made their own safety
determinations for about 1,000 additives without
ever notifying the agency.
In a previous study, Neltner and his colleagues estimated that
about 43 percent of the 10,000 or so additives allowed in food
were on the FDA's GRAS list, with other additives approved
through other means or not submitted to the FDA.
Manufacturers made their own safety
determinations for about 1,000 additives without
ever notifying the agency.

30. Millichap & Yee. Vol 129, no. 2 Feb 1 2012 – pp 330-
337
Full article:
• Diets reviewed:
– Sugar restricted. Additive/preservative free,
elimination diet and FATTY ACID SUPPLEMENTS
• NOTABLE: “ADHD-associated Western diet”
high in fat and refined sugars
• ADHD-free [sic] healthy diet: {fiber, folate, and
omega 3 fatty acids.
• Multiple cits. on + results with IgG elimination

31. Millichap & Yee. Loc. Cit.
• Other findings:
– Strong results with Omega 3 & 6 supplementation.
• (doses of 300 – 600 omega 3 and 30-60 mg Omega 6/d)
– Benefits of zinc supplementation
• (optimal dose of d-amphetamine was 37% lower with zinc
than with placebo)
– Children are more sensitive to reactive
hypoglycemia than adults: AVOID SUGAR LOAD.
– Unusually low ferritin levels {18.4ng/ml, mean}
correlated with baseline inattention, hyperactivity
and impulsivity.
• Also correlated with dose of d-amphetamine required.

32. Association of atopic and non-atopic asthma
with emotional symptoms in school children
• Cross sectional data on asthma and allergic
diseases at 10 year follow-up of two birth cohorts.
– Atopic = “asthma ever and + IgE test”
– Non-atopic = “asthma ever and NEGATIVE IgE”
• “Non atopic asthma was associated with about 3-
fold higher likelihood of emotional symptoms
compared to children with no asthma.” [OR = 2.90,
CI 95% = 1.46-5.73]
• Atopic asthma – not associated with emotional
symptoms [OR 1.35]
Kohlboeck G et al. Pediatr Allergy Immuno. 2013 May; 24(3):230-
6

33. Serological tests in gluten sensitivity
(nonceliac gluten intolerance)
• “Gluten sensitivity” noted to be recently identified
as a new clinical entity included in spectrum of
gluten-related disorders.
• Study - Sera from 78 patients with GS + 80 patients with
celiac disease was retrospectively analyzed for:
– immunoglobulin (Ig)G/IgA antigliadin antibodies
– IgG deamidated gliadin peptide antibodies
– IgA tissue transglutaminase antibodies (tTGA)
– IgA endomysial antibodies (EmA)
Volta U, et al. J Clin Gastroenterol. 2012 Sep;46(8);680-5.

34. Serological tests in gluten sensitivity
(nonceliac gluten intolerance)
• Patients with GS had intestinal and extraintestinal
symptoms
– Abdominal pain, bloating, diarrhea, constipation
– “foggy mind,” tiredness, eczema/skin rash, headache,
joint/muscle pain, numbness of legs/arms, depression,
and anemia
• NORMAL or MILDLY ABNORMAL small intestinal
mucosa
• CONCLUSIONS: “The serological pattern of GS is
characterized by IgG AGA positivity in more than
half of the cases.”
Volta U, et al. J Clin Gastroenterol. 2012 Sep;46(8);680-5.

35. “Is a subtype of autism an allergy of
the brain?”
Theoharides, TC. Clin Ther. 2013 May; 3595):584-91.
• Methods – PubMed search since 1995:
associations between autism/ASD’s and
“allergy, atopy, brain, corticotropin-releasing
hormone, cytokines, eczema, food allergy,
food intolerance, gene mutation,
inflammation, mast cells, mitochondria”…
[etc.]
• “Children with ASD…present with food and
skin allergies that involve mast cells (IgE).”

36. “Is a subtype of autism an allergy of
the brain?”
Theoharides, TC. Clin Ther. 2013 May; 3595):584-91.
• “Activation of brain mast cells by
allergic, environmental, immune,
NEUROHORMONAL, stress, TOXIC
TRIGGERS, especially in those areas
associated with behavior and language,
lead to focal brain allergies and
subsequent focal encephalitis.”

37. Food allergy and autism spectrum
disorders: is there a link?
Jyonouchi H. Curr Allergy Asthma Rep. 2009 May;9(3):194-201
• “ Our previous studies indicated a high
prevalence of non-IgE mediated FA in
young children with ASD’s.”
• “…non-IgE-mediated FA may
account for some but not all GI
symptoms observed in children
with ASDs.”

38. Anxiety & depression in patients with self-
reported food hypersensitivity
• 130 consecutive patients and 75 random healthy
volunteers
– Completed the Hospital Anxiety and Depression Scale
(HADS)
• 57% of patients fulfilled a DSM-IV criteria for at
least one psychiatric disorder.
– Anxiety disorders – 34%
– Depression – 16%
• Food hypersensitivity rarely confirmed by
provocation tests. (Non IgE)
• 81% of patients had irritable bowel syndrome
Lillestol K et al. Gen Hosp Psychiatry. 2010 Jan-Feb; 32(1):42-8.

39. IgG food allergies in IBS
• 150 outpatients with IBS randomized to diet
excluding all IgG reactive items or a sham diet
(excluding the same number of foods but not the
ones to which they had antibodies)
– 25% reduction in IBS symptoms in fully compliant
patients
– 10% reduction in moderately compliant
• “Food elimination based on IgG antibodies
may be effective in reducing IBS symptoms
and is worthy of further medical research.”
Atkinson, W et al. Food elimination based on IgG antibodies in irritable bowel
syndrome: a randomised controlled trial. Gut. 2004 Oct;53(10):1459-64.

40. Gluten – one of the ultimate “bad
boys” in food sensitivities
• Headaches
• Tearing up your gut
• Depression
• Suicide*
– * Untreated celiac
disease and
attempted suicide.
Lancet, September
1995. Pelligrino et al

41. Gluten and neurologic disease
• “More recent studies have emphasized that
a wider spectrum of neurologic syndromes
may be the presenting extraintestinal
manifestation of gluten sensitivity with or
without intestinal pathology.”
– -Bushara, KO. Neurologic presentation of
celiac disease – Gastroenterology. 2005 Apr;
128(4 Suppl 1):592-7.

42. “UBO’s on MRI” – the gluten
connection
• 10 patients – had headaches.
– MRI
– UBO’s
• 6 – unsteady, 4 gait ataxia
• 90% response rate to gluten free diet.

43. Observant pediatricians and
depressed parents – with celiac dz

44. Corvaglia, et al 1999
• 3 adult patients found with undiagnosed/untreated
celiac disease
• Found by pediatricians who noted family history
when child’s medical history obtained.
• Celiac disease diagnosis was MADE in childhood,
but diet was stopped due to no more GI
symptoms.
• In all three patients, depressive symptoms
improved with gluten free diet.

45. Does it have to be celiac/gluten to
mess up your head?
“According to the results obtained, serum IgG
antibodies to common food should be investigated
in patients with migraine.”
“According to the results obtained, serum IgG
antibodies to common food should be investigated
in patients with migraine.”

46. Jonez, HD Calif Med. 1953 November; 79(5): 376–380.
• http://www.ncbi.nlm
.nih.gov/pmc/article
s/PMC1521914/pdf
/califmed00209-
0035.pdf

47. Practicum

48. Photos deleted for syllabus materials. The
presenter has permission to use the patient’s
photos during the live presentation only.

49. Criticality of removing IgG antigens
(+ complete, holistic approach)
RX: dairy free diet (+IgG test); D3 5000 IU/d; Armour thyroid,
Testosterone cypionate 100 mg IM q wk, MVI, Zinc, DHEA 50 mg
(photo shot 15
months after tx)
(permission granted to use photos & data)
Photos deleted for syllabus materials. The
presenter has permission to use the patient’s
photos during the live presentation only.

50. Photos deleted for syllabus materials. The
presenter has permission to use the patient’s
photos during the live presentation only.

51. Just one more: Rusty- 6/28/11 “The
kid that wouldn’t poop.”
• 11 year old male 5th
grader with dx of ADHD and
Speech Apraxia; problems with reading, writing, oral
expressive language, math, sequencing
• Medical:
– Hx of “lazy bowel”
• “He doesn’t go more than once in two weeks.”
• Dietary: likes cheese, chicken nuggets, ice cream, Coke, pizza.
Used to like cottage cheese.
– GI sxs refractory to pediatric interventions
• Dx 1: ADD: 6/9 sxs of inattentiveness ON RX.
• Dx 2:“Probable severe IgG food sensitivity with
obvious stool retention problems”

52. Dairy IgG sensitivity suspected.
Testing/Results:
• Pediatrician ordered IgE RAST = NEGATIVE
• 7/25/11 – no change. 2 BM’s in one month.
– IgG Testing previously ordered. (Mom resistant
and delayed due to cost. Finally done after this
appt). RESULTS……

53. Milk = 5+
“The kid who wouldn’t poop.”

54. The kid that wouldn’t poop, concl.
• 8/15/11 – milk/wheat stopped.
• Constipation and fecal retention
totally eliminated within 1 week.
• Follow-up: “He won’t follow the
diet.” Mom wimped out. Now
constipated again.

55. What to be looking for…
• Obvious GI problems
• Meds not working.
• Chiro adjustments don’t
“hold.”
• Atypical presentations
• KNOWN associations
(autism)
• Symptoms varying with diet
• Excess ABX use (candida)
• Lack of normal progression
in treatment

56. Diagnostic challenges & IgG food
sensitivities - opportunities exist
• “Tough cases”
• Weird, multiple symptoms
• Headaches
• GI symptoms, food cravings, or both
• ADHD and “bipolar” type symptoms
• Processing issues (no pills available!)
• Headaches resistant to standard
chiropractic and medical tx
• Fatigue, “brain fog”, temper fits

57. Personal collection - Louis B. Cady, M.D.

58. Louis B. Cady, M.D. www.cadywellness.com
www.facebook.com/cadywellness www.tms-relief.com
Office: 812-429-0772 E-mail: lcady@cadywellness.com
4727 Rosebud Lane – Suite F ~ Interstate Office Park Newburgh, IN 47630 (USA)
TWITTER FEEDS: @LouisCadyMD @TMS4depression
Once more…. 
Where to “get the slides” -
Syllabus
www.slideshare.net/lcady
md
Cady Wellness Institute
app.