1. THE BENEFITS OF SOY
FORMULA IN THE
MANAGEMENT of COW’S MILK
ALLERGY
Prof. Ariyanto Harsono MD PhD SpAK
1

2. Pendahuluan
 The process will continue in the lives of babies
 Sensitization to another food proteins would
otherwise occur
Prof DR Dr Ariyanto Harsono SpA(K)
Cow's milk is generally the first
allergen in infants
once responses to cow's milk IgE occurs

3. Prevention is very important
Allergy Prevention:
 Primary
 Secondary
 Tertiary
3
Adjusting Solid Foods to Milk formula used
Other Suplement yang: LCP, vitamines, micronutrient
Soy Formula has a positive effect on immunity and
Allergy

4. Aktivasi
sel-sel
Imuno-
kompeten
•Sel T
•Sel B
•Sel Mast
•Sel
Langer-
hans
Aktivasi
sel-sel
struk-
tural
•Sel
endotel
•Sel
epitel
Aktivasi dan
Rekruitmen
•Sel Mast
•Eosinofil
•Basofil
Pelepasan
mediator
Kerusakan
epitel
Stimulasi
neural
Dilatasi &
peningkatan
permeabilitas
vaskulerl
Bronkokonstriksi
Perbaikan
epitel
•Proliferasi
fibroblast
•Deposisi
kolagen
•Hipertropi/hiper
plasia otot polos
•Ekspansi
vaskuler
Penyempitan
saluran nafas
bawah
Symptom
alergi
Bronkus
hiper-reaktif
A
L
E
R
G
E
N
A B C D E
Airway
remodelling
Primary Prevention Secondary Prevention
Tertiary Prevention
J Allergy Clin Immunol 2005;116:3-14
Prof DR Dr Ariyanto Harsono SpA(K)
4
Imunopathology of allergy

5. Ag
APC MHC-II Th0
IL-12/ IL-1
Th-2
Th.1
IL-1 IL-2, IFN-γ
B-Cell
IL-4
IL-5
SEL PLASMASEL MEMORI
IL-6
IL-10
A
AKTIVAtion of IMMUNOCOMPETENce CELLS by
ANTIGEN
Memory Cells
Prof DR Dr Ariyanto Harsono SpA(K) 5

6. B
ACTIVATION of STRUCTURAL
CELLS
Nature Rev Immunol 2003; 3: 867-78
Eosinophil
Eosinophil
Prof DR Dr Ariyanto Harsono SpA(K) 6

7. C
MEDIATOR RELEASE
Prof DR Dr Ariyanto Harsono SpA(K) 7

8. Granule contents:
Histamine,TNF-α
Proteases, Heparin
Lipid mediators:
Prostaglandins
Leukotrienes
Cytokine production:
Specifically IL-4, IL-13
Prof DR Dr Ariyanto Harsono SpA(K) 8

9. D EFFECT of MEDIATOR RELEASE to TARGET ORGAN
Nature Rev Immunol 2004: 3:234-237
Prof DR Dr Ariyanto Harsono SpA(K) 9

10. Kehamilan = “Th2-disease”
*Anti-oxydants
*Avoid tobacco smoke
Primary Prevention: Gestational age
Prof DR Dr Ariyanto Harsono SpA(K) 10

11. • Exclusive
breastfeeding
• Maternal
hypoallergenic diet
• Delay solid foods
• pHF if not breastfed
Prof DR Dr Ariyanto Harsono SpA(K) 11

12. Primary prevention with Milk
Formula
Partially hydrolyzed
formulas:
pHF FORMULA
Prof DR Dr Ariyanto Harsono SpA(K) 12

13. Target
Organ
IgE-mediated disorder Non IgE-mediated
disorder
Skin
Gastro-
intestinal
Respiratory
Tract
Multi-
system
Urticaria and angioedema
Atopic Dermatitis
Oral Allergy Syndrome
Gastrointestinal anaphylaxis
Allergic eosinophilic
gastroenteritis
Asthma; Allergic Rhinitis
Food-induced anaphylaxis
Food associated, exercise-
induced anaphylaxis
Atopic Drmatitis
Dermatitis Herpetiformis
Proctocolitis
Enterocolitis
Allergic eosinophilic-GE
Enteropathy syndrome
Celiac Disease
GI Haemorrhage
Heiner Syndrome
Clinical ManifestationE Symptoms
Prof DR Dr Ariyanto Harsono SpA(K)
13

14. VACCINATION
ACTIVATION
ANTIGEN
SPECIFIC
B CELL
GENERATION OF
MEMORY
ACTIVATED
CD4
+
Th-2 CELL IL-4
DIFFERENTIATION
& AFFINITY
MATURATION
ANTIBODY SECRETING
PLASMA CELLS
ANTIGEN
PROCESSING &
PRESENTATION
MHC Class II B CELL IMMUNOGLOBULINE
T CELL RECEPTOR ANTIGEN
B CELL
IL-5,IL-13
Cow’s Milk Protein
Cow’s Milk epitope
Prof DR Dr Ariyanto Harsono SpA(K) 14

15. CE Symptoms
Prof DR Dr Ariyanto Harsono SpA(K)
15
Oral allergy syndrome

16. Prof DR Dr Ariyanto Harsono
SpA(K) 16
Rinitis Alergika

17. Prof DR Dr Ariyanto Harsono
SpA(K) 17
Atopic Dermatitis

18. 18
Prof DR Dr Ariyanto Harsono SpA(K)
Urticaria

19. Prof DR Dr Ariyanto Harsono SpA(K) 19
Quinke’s oedem
Quinke’s oedem

20. Prof DR Dr Ariyanto Harsono SpA(K) 20
Quinke’s oedem

21. Prof DR Dr Ariyanto Harsono
SpA(K)
21
Larynx oedem

22. Prof DR Dr Ariyanto Harsono SpA(K) 22
Fixed Skin Eruption

23. Asthma Prof DR Dr Ariyanto Harsono
SpA(K) 23

24. Arthropathy
Prof DR Dr Ariyanto Harsono SpA(K) 24

25. Vasculitis
Prof DR Dr Ariyanto Harsono SpA(K) 25

26. Otitis Media Serosa
Prof DR Dr Ariyanto Harsono SpA(K) 26

27. Secondary Prevention
Extensively Hydrolyzed Formula
Formula Soy Isolate
27Prof DR Dr Ariyanto Harsono SpA(K)

28. Prevensi Sekunder
Extensively Hydrolyzed Formula
Formula Soy Isolate
28Prof DR Dr Ariyanto Harsono SpA(K)

29. History
• Early 1900 preparation based on “soy-protein”
for treatment of CMPA (in USA)
• Since1960 :composition better adapted to infan
t nutritional needs
• 2000 : infant formula based on soy fulfills
European Directives and legislation for
infant feeding
Prof DR Dr Ariyanto Harsono SpA(K) 29

30. Soy protein isolate instead of soy-cereal
• Previously: soy concentrate (protein content 70 %)
Now : isolate (95% protein) Dupuy et al,1994
• Addition of + methionine, + carnitine, + taurine,
+Fe, +Zn, +Ca, + P Heating to destroy « anti--
protease activity » for over 90 %
Prof DR Dr Ariyanto Harsono SpA(K) 30

31. WHO Committee on Nutrition / AAP:
Indications of Soy Infant Formula
Cow's milk allergy (CMA)
• For ages 6-12 months->
• For ages 0-6 months (necessary doctor
decisions in accordance with ESPGHAN
2010 Guideline)
Lactose intolerance
galactosemia
family Vegetarian
Prof DR Dr Ariyanto Harsono
SpA(K)
31

32. Other indications for soy infant
formula
• Cultural: traditional dietary habits
• Economic
• Religious (sometimes pork enzymes used
to hydrolyse in eHF?)
• Philosophical
Prof DR Dr Ariyanto Harsono SpA(K) 32

33. Phytoestrogen
Biological consequences of soy-rich diets
have been attributed to the presence of
soy isoflavones, which are members of the
phytoestrogen family.
Phytoestrogens are plant-derived,
estrogen-like compounds capable of
interacting with the estrogen receptors ER
and ERβ because their structure
resembles that of the endogenous
hormone 17β-estradiol.
J. Clin. Invest. 2006 116:16-19
Prof DR Dr Ariyanto Harsono SpA(K) 33

34. Phytoestrogen...
Four groups of phenolic compounds are classified
as phytoestrogens:
isoflavones,
stilbenes,
coumestans, and
lignans.
The main isoflavones, found mostly in soybeans,
are:
 genistein,
 daidzein, and
 glycitein.
J. Clin. Invest. 2006 116:16-19
Prof DR Dr Ariyanto Harsono SpA(K)
34

35. Phytoestrogen...
Several epidemiological studies have
concluded that phytoestrogens confer:
cardioprotection by downregulating
cardiovascular disease risk markers,
consistent improvement in endothelial
function
antioxidant activity. J. Clin. Invest. 2006 116:16-19
Prof DR Dr Ariyanto Harsono SpA(K) 35

36. H2O
Prof DR Dr Ariyanto Harsono
SpA(K)
36

37. Phytoestrogen...
Soy product consumption has been
associated with the following:
reduced serum cholesterol levels via
reductions in total and low-density
lipoprotein levels;
vasodilatory activity under certain
conditions
enhanced activity of certain antioxidant
enzymes to increase antioxidant activities.
J. Clin. Invest. 2006 116:16-19
Prof DR Dr Ariyanto Harsono
SpA(K) 37

38. • symptoms of menopause
• Prevention of obesity
• Soy intake is related to a lower body mass
index in adult women
Maskarinec G. Eur J Nutr 2008;;47:138-
ˇ44
Prof DR Dr Ariyanto Harsono SpA(K) 38

39. Prof DR Dr Ariyanto Harsono SpA(K) 39

40. A high intake of Soy and Isoflavones may
be associated with a reduced prevalence
of allergic Rhinitis
J Allergy Clin Immunol 2005;115:1176-83
Prof DR Dr Ariyanto Harsono SpA(K) 40

41. Prof DR Dr Ariyanto Harsono SpA(K) 41
Soy protein formulas in children: no hormonal effects in long-term feeding.
48 children (mean age 37 months (range 7--96 months) 27
boys, 21 girls) soy > 6 months 18 controls
bone age, urinary markers of bone metabolism, ␣
serum levels of bone alkaline phosphatase, osteocalcin
17beta--oestradiol, intact parathyroid hormone
girls: no signs/symptoms of precocious puberty
boys: no gynecomastia
bone age within the normal range bone alkaline
phosphatase, osteocalcin, 17beta--oestradiol, intact
parathyroid hormone, urinary levels of the markers of bone
metabolism all within normal values.
Giampietro PG;; J Pediatr Endocrinol Metab. 2004
;;17:191--6

42. Prof DR Dr Ariyanto Harsono SpA(K) 42
Soy protein infant formulae and follow-ˇon formulae:
a commentary by the ESPGHAN Committee on Nutrition.
Before 6 months
 Soy not recommended
 Extensive protein hydrolysates recommended
 if eHF not tolerated: amino-ˇacid based formula
After 6 months
 Soy can be used if tolerance first established
 Benefit: acceptability, cost…..
Giampietro PG;; J Pediatr Endocrinol Metab. 2004 ;17:191--6
J Pediatr Gastroenterol Nutr. 2006;;42:352-ˇ61

43. Prof DR Dr Ariyanto Harsono SpA(K)
43

44. Goal of Secondary Prevention
Prof DR Dr Ariyanto Harsono SpA(K) 44
1. Morbidity
2. Quality of life

45. Other Milk supplement
* Lipid-soluble vitamin E has a capacity of
defense against oxidant-induced
membrane injury. Studies have
consistently demonstrated beneficial
associations between dietary vitamin E
and ventilatory function, and few have
demonstrated beneficial association with
asthma and atopy.
Prof DR Dr Ariyanto Harsono SpA(K) 45
J Allergy Clin Immunol 2005;115:1109-17.

46.  Water-soluble vitamin C provides anti-oxidant
capacity primarily by scavenging oxygen free
radicals and suppressing macrophage secretion
of super oxide anions, therefore play a role in
preventing mucosal shedding caused by
mediators released from eosinophils and
oxydants.
 n-3 polyunsaturated fatty acid (Omega-3),
eicosapantaenoic acid, and docahexaenoic acid
might have contributed to the decrease in
asthma and atopic disease morbidity.
Micronutrents: Fe, Zn, Se
Prof DR Dr Ariyanto Harsono SpA(K) 46
J Allergy Clin Immunol 2005;115:1109-17.
Eur Respir J 1997;10:6-12.

47. Arachidonic Acid (ARA)
Phospholiphase A
Cyccloxygenase Lipoxygenase
Prostaglandine
TXA
Prostacyclin
Leukotriene A
Leukotriene B
Leukotriene C
Omega-3, DHA
ecosapantaenoic
acid
HETE,5-HETE, PAF
PGD2/E2
PGD3 LTC4
LTC5
47

48. Prof DR Dr Ariyanto Harsono SpA(K) 48
IMMUNOMODULATORY AND
IMMUNOSUPRESSIVE EFFECTS OF PUFAs
PUFAs modulate :
1. Cytokine production
2. Lymphocyte proliferation
3. Surface molecule expression
4. Phagocytosis and apoptosis
5. Inhibit natural killer (NK)cell activity

49. Prof DR Dr Ariyanto Harsono SpA(K) 49
 N-3 PUFA are better than n-6 PUFA
 The ratio of n-3 to n-6 may be an
important factor in modulating
inflammation
 Increasing the ratio of n-3 to n-6 
antiinflammatory effect especially with
atopic disease

50. Prof DR Dr Ariyanto Harsono
SpA(K)
50
LC-PUFA and immune response
ARA DHA
Prostaglandine D2/E2
LtC4
Push B cells to produce IgE
Th1 Response
pro-inflammatory anti-inflammatory
Antagonizes ARA
LTC5/PGD3/Prostacycline
Prostaglandine E2

51. Prof DR Dr Ariyanto Harsono
SpA(K)
51
Selenium
Essential trace mineral that plays a role in the body's
defense as an anti-oxidant and helps scavenge free
radicals that can cause tissue damage
Selenium concentrations in breast milk during
lactation and decreased greatly influenced by maternal
diet.
Infants who received soy formula with added selenium
may benefit from the addition of selenium to maintain
optimum levels of selenium.

52. Prof DR Dr Ariyanto Harsono
SpA(K)
52
Vitamin D
Vitamin D helps build and maintain bone
Vitamin D is a fat soluble vitamin serves as an important
biological regulator of calcium and phosphorus
metabolism
Vit D deficiency can cause rickets
AAP Recommendations whole milk infant formula must
meet IU/100 Vit D 40 kcal (258 IU / L)

53. Prof DR Dr Ariyanto Harsono
SpA(K)
53
Calcium and Phosphorus
–Has an important function collectively they build bones and teeth.
–Promotes nerve function and muscle
–activation of the enzyme helps convert food into energy
–Up until 1980 because of erratic absorption of minerals stabilita
suspension and the presence of excessive soy phytates 
Consequently several studies have shown that poor bone
mineralization between infants who received cow's milk formula
compared to infants receiving soy formula
–Formulations of soy formula has been improved, so that the
concentration of calcium and phosphorus in serum and bone
mineralization in infants who receive formula milk formula milk
cows and donkeys
–The ratio of calcium and phosphorus in the latest standard is 1.3:
1 (ESPGHAN 2010)

54. Prof DR Dr Ariyanto Harsono
SpA(K) 54
Iron
Has an important role for the development of the
brain in the early stages of life.
Iron deficiency can cause anemia , can harm brain
tissue.
The AAP recommends that infant formulas
fortified with iron 4 mg - 12 mg / L

55. Prof DR Dr Ariyanto Harsono
SpA(K) 55
• Zinc
• Plays an important role in growth, brain and immunity
development
• Zinc plays an important role in normal growth,
neurotransmitter in motor function
• Zinc supplementation in infant formula may help
reduce the duration and severity of diarrhea.
• Mild zinc deficiency has a characteristic growth is
slower than normal.

56. The health implications of soy
infant formula
• Soy formula composition meets US Food and Drug Administration
and AAP guidelines for vitamin, mineral, and electrolyte content and
provides 67 kcal/dL:Soy isolate protein plus L-methionine, L-
carnitine, and taurine provide 2.45 to 2.8 grams per 100 kilocalories.
• Fat consisting mostly of vegetable oils provides 5.02 to 5.46 grams
per 100 kilocalories.
• Carbohydrate, consisting of corn maltodextrin, corn syrup solids,
and sucrose, provides 10.26 to 10.95 grams per 100 kilocalories.
• Soy formulas contain 20% more calcium and phosphorus than cow's
milk formulas and are fortified with iron and zinc because of
phosphorus, iron, and zinc binding.
Prof DR Dr Ariyanto Harsono
SpA(K) 56
Pediatrics: 1998 :101(1) : 148 -153

57. Prof DR Dr Ariyanto Harsono
SpA(K) 57
Numerous studies have documented normal growth
and development in term neonates fed methionine-
supplemented isolated soy protein-based formulas.
 Average energy intakes in infants receiving soy
protein formulas also are equivalent to those
achieved with cow milk formula.
 The serum albumin concentration, as a marker of
nutritional adequacy is normal,
 Bone mineralization also is equivalent to that
documented with cow milk-based formula.
 Additional studies confirm that soy protein formulas
do not interfere with the normal immune responses to
oral immunization with polio vaccine.Pediatrics: 1998 :101(1) : 148 -153

58. Growth in Infants Fed Soy Formulas
Prof DR Dr Ariyanto Harsono SpA(K) 58

59. From the nutritional point of view, formulas
based on soy-protein have in comparison
with cow milk based formula (eHF):
•no advantages
•no disadvantages
Prof DR Dr Ariyanto Harsono SpA(K) 59

60. Conclusion
 Primary prevention with hypo-allergenic formula
should be started from the first trimester of life, do
not wait for the symptoms of allergy. Food additives
should also hypo-allergenic
 Secondary prevention using advanced hydrolyzed
formula or formula Soy Isolate
 Other nutritional supplements: omega-3,
ecosapentaenoic acid, DHA plays a role in immune
modulation of inflammatory mediators
 Anti-oxidants: Vitamin A, C, E
Vit D
 Micronutrients: Fe, Zn, Se
 In the full-term infants fed on Soy Formula going
good growth
Prof DR Dr Ariyanto Harsono SpA(K)
60

61. Prof Dr Ariyanto Harsono dr SpAK
CURICULUM VITAE
Tempat /tgl lahir : Kediri, 3- Juli
Agama : Islam
Status Perkawinan: Menikah
Pendidikan
S-1: Lulus Dokter : FK UNAIR, 1972
S-2: Spesialis Anak : FK UNAIR, 1982
S-3: Program Pascasarjana UNAIR, 2004
Pendidikan tambahan : Sertifikat “Fellowship on Food Allergy”,
Academisch Ziekenhuis Utrecht, Nederland, 1990-1991
Jabatan sekarang : Guru Besar Ilmu Kesehatan Anak,
Dep IKA FK UNAIR/RSU Dr.Soetomo, Surabaya.
Konsultan Alergi/Imunologi: 1992
61

62. Thank You
Prof DR Dr Ariyanto Harsono
SpA(K)
62