The benefits of soy formmula in the management of cma

THE BENEFITS OF SOY FORMULA IN THE

MANAGEMENT of COW’S MILK ALLERGY

Prof. Ariyanto Harsono MD PhD SpAK

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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

Prevention is very important

Allergy Prevention: Primary

Secondary Tertiary


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Adjusting Solid Foods to Milk formula used

Other Suplement yang: LCP, vitamines, micronutrient

Soy Formula has a positive effect on immunity and Allergy

Aktivasi sel-selImuno-kompeten•Sel T•Sel B•Sel Mast•Sel Langer- hans

Aktivasi sel-selstruk-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/hiperplasia otot polos•Ekspansi vaskuler

Penyempitan saluran nafas bawah

Symptom alergi

Bronkus hiper-reaktif

ALERGEN

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

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

AAKTIVAtion of IMMUNOCOMPETENce CELLS by ANTIGEN

Memory Cells


http://images.google.com/imgres?imgurl=http://www.uiowa.edu/~cemrf/archive/confocal/confocalimages/images/Human%2520Dendritic%2520Cell,%2520Karla%2520Daniels,%2520Biological%2520Sciences.jpg&imgrefurl=http://www.uiowa.edu/~cemrf/archive/confocal/confocalimages/pages/Human%2520Dendritic%2520Cell,%2520Karla%2520Daniels,%2520Biological%2520Sciences.htm&h=346&w=350&sz=15&tbnid=nl5wFa22oyMJ:&tbnh=114&tbnw=115&start=1&prev=/images?q=dendritic+cell&hl=id&lr=&sa=G

http://images.google.com/imgres?imgurl=http://www.diabetes-research.org/Images/t-cell.jpg&imgrefurl=http://www.diabetes-research.org/immuno_research.htm&h=256&w=317&sz=41&tbnid=aFk2u2OGnrcJ:&tbnh=91&tbnw=112&start=21&prev=/images?q=T+cell&start=20&hl=id&lr=&sa=N

http://images.google.com/imgres?imgurl=http://www.diabetes-research.org/Images/t-cell.jpg&imgrefurl=http://www.diabetes-research.org/immuno_research.htm&h=256&w=317&sz=41&tbnid=aFk2u2OGnrcJ:&tbnh=91&tbnw=112&start=21&prev=/images?q=T+cell&start=20&hl=id&lr=&sa=N

BACTIVATION of STRUCTURAL CELLS

Nature Rev Immunol 2003; 3: 867-78

Eosinophil

Eosinophil


CMEDIATOR RELEASE


Granule contents:Histamine,TNF-Proteases, Heparin Lipid mediators:

ProstaglandinsLeukotrienes

Cytokine production:Specifically IL-4, IL-13


D EFFECT of MEDIATOR RELEASE to TARGET ORGANNature Rev Immunol 2004: 3:234-237


Kehamilan = “Th2-disease”

*Anti-oxydants

*Avoid tobacco smoke

*Probiotics last trimester of gestation

Primary Prevention: Gestational age


• Exclusive breastfeeding

• Maternal hypoallergenic diet

• Delay solid foods• pHF if not breastfed


Primary prevention with Milk Formula

Partially hydrolyzed formulas:

pHF FORMULA


Target Organ

IgE-mediated disorder Non IgE-mediated disorder

Skin

Gastro-intestinal

Respiratory Tract Multi-system

Urticaria and angioedemaAtopic Dermatitis

Oral Allergy SyndromeGastrointestinal anaphylaxisAllergic eosinophilic gastroenteritis Asthma; Allergic Rhinitis

Food-induced anaphylaxisFood associated, exercise-induced anaphylaxis

Atopic DrmatitisDermatitis Herpetiformis

ProctocolitisEnterocolitisAllergic eosinophilic-GEEnteropathy syndromeCeliac DiseaseGI Haemorrhage

Heiner Syndrome

Clinical ManifestationE Symptoms

Prof DR Dr Ariyanto Harsono SpA(K)13

VACCINATION

ACTIVATIONANTIGEN SPECIFIC

B CELL

GENERATION OF MEMORY

ACTIVATED CD4

+ Th-2 CELL IL-4

DIFFERENTIATION

& AFFINITYMATURATION

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


CE Symptoms


Oral allergy syndrome


Rinitis Alergika


Atopic Dermatitis

18Prof DR Dr Ariyanto Harsono SpA(K)

Urticaria


Quinke’s oedem

Quinke’s oedem


Quinke’s oedem


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Larynx oedem


Fixed Skin Eruption

AsthmaProf DR Dr Ariyanto Harsono

SpA(K) 23

ArthropathyProf DR Dr Ariyanto Harsono SpA(K) 24

Vasculitis


Otitis Media Serosa


Secondary Prevention

Extensively Hydrolyzed Formula

Formula Soy Isolate


Prevensi Sekunder

Extensively Hydrolyzed Formula

Formula Soy Isolate


History

• Early 1900 preparation based on “soy-protein” for treatment of CMPA (in USA)

• Since1960 :composition better adapted to infant nutritional needs

• 2000 : infant formula based on soy fulfills European Directives and legislation for infant feeding


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 %


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 intolerancegalactosemiafamily Vegetarian


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Other indications for soy infant formula

• Cultural: traditional dietary habits

• Economic

• Religious (sometimes pork enzymes used to hydrolyse in eHF?)

• Philosophical


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 ER because their structure resembles that of the endogenous hormone 17-estradiol.

J. Clin. Invest. 2006 116:16-19


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 116:16-19Prof DR Dr Ariyanto Harsono SpA(K)

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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


H2O


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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


• 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


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



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 controlsbone age, urinary markers of bone metabolism, serum levels of bone alkaline phosphatase, osteocalcin17beta- 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


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 formulaAfter 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

Goal of Secondary Prevention


1. Morbidity

2. Quality of life

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.


J Allergy Clin Immunol 2005;115:1109-17.

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


J Allergy Clin Immunol 2005;115:1109-17.

Eur Respir J 1997;10:6-12.

Arachidonic Acid (ARA)

Phospholiphase A

Cyccloxygenase Lipoxygenase

Prostaglandine

TXA

Prostacyclin

Leukotriene A

Leukotriene B

Leukotriene C

Omega-3, DHAecosapantaenoic acid

HETE,5-HETE, PAF

PGD2/E2

PGD3 LTC4

LTC5


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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


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


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LC-PUFA and immune response

ARA DHA

Prostaglandine D2/E2LtC4

Push B cells to produce IgE

Th1 Response

pro-inflammatory anti-inflammatory

Antagonizes ARALTC5/PGD3/Prostacycline

Prostaglandine E2


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SeleniumEssential 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.


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Vitamin DVitamin D helps build and maintain bone Vitamin D is a fat soluble vitamin serves as an important biological regulator of calcium and phosphorus metabolismVit D deficiency can cause ricketsAAP Recommendations whole milk infant formula must meet IU/100 Vit D 40 kcal (258 IU / L)


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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)


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


• 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.

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.


Pediatrics: 1998 :101(1) : 148 -153


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

Growth in Infants Fed Soy Formulas


From the nutritional point of view, formulas based on soy-protein have in comparison with cow milk based formula (eHF):

•no advantages

•no disadvantages


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 growthProf DR Dr Ariyanto Harsono SpA(K)

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Prof Dr Ariyanto Harsono dr SpAK

CURICULUM VITAE

Tempat /tgl lahir : Kediri, 3- JuliAgama : Islam

Status Perkawinan: MenikahPendidikan

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, 1990-1991Jabatan sekarang : Guru Besar Ilmu Kesehatan

Anak, Dep IKA FK UNAIR/RSU Dr.Soetomo, Surabaya.

Konsultan Alergi/Imunologi: 1992

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Thank YouProf DR Dr Ariyanto Harsono

SpA(K)62

The benefits of soy formmula in the management of cma

Education

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