Preventing-Food-Allergy-by-Early-Food-Introduc_2025_The-Journal-of-Allergy-a.pdf

Clinical Commentary Review
Preventing Food Allergy by Early Food 
Introduction: East Meets West With the Lack 
Dual-Allergen Exposure Theory
Kiwako Yamamoto-Hanada, MD, PhDa, Jennifer J. Koplin, PhDb,c, Marion Groetch, MS, RDNd, George du Toit, MDe,f, 
and Yukihiro Ohya, MD, PhDa,g,h
Tokyo and Aichi, Japan; Brisbane, Queensland; and Parkville, Victoria, Australia; New York, 
NY; and London, United Kingdom
Food allergy (FA) is a growing global health concern with 
prevalence varying by region, influenced by genetic, 
environmental, and cultural factors. Eczema represents the 
strongest early-life risk factor, which supporting the Lack dual- 
allergen exposure hypothesis in which disrupted skin barriers 
facilitate sensitization, whereas timely oral exposure promotes 
tolerance. Over recent decades, prevention strategies have 
shifted from allergen avoidance to early introduction, 
particularly after the Learning Early About Peanut Allergy 
study. Although early egg introduction has been associated with 
a reduced risk of egg allergy in some studies, others have 
reported no significant effect. In contrast, early peanut 
introduction has strong preventive effects in Western countries 
with high peanut allergy prevalence, but it appears less 
impactful in Japan, where peanut consumption and prevalence 
are low. The role of early cow’s milk introduction remains 
inconclusive, although recent Japanese data suggest possible 
benefit from small daily intake. Effective eczema management, 
including proactive anti-inflammatory therapy, may be crucial, 
because moisturizers alone are insufficient for FA prevention. 
Sustained and regular allergen intake after early introduction is 
likely to support long-term tolerance further. Prevention 
strategies must also account for cultural feeding practices, 
family dietary habits, and regional epidemiology, because these 
factors shape feasibility and public health relevance. Supporting 
a smooth transition to family foods, such as encouraging infants 
to share family meals without unnecessary restrictions, may help 
sustain tolerance and promote healthy eating patterns. 
Collaboration between Eastern and Western medical 
communities will be essential to harmonize evidence with 
cultural practices and develop effective, personalized FA 
prevention strategies worldwide.
Ó 2025 The Authors. 
aAllergy Center, National Center for Child Health and Development, Tokyo, Japan
bChild Health Research Centre, University of Queensland, Brisbane, Queensland, 
Australia
cCentre for Food and Allergy Research, Murdoch Children’s Research Institute, 
Parkville, Victoria, Australia
dElliot and Roslyn Jaffe Food Allergy Institute, Division of Allergy and Immu­
nology, Department of Pediatrics, Kravis Children’s Hospital, Icahn School of 
Medicine at Mount Sinai, New York, NY
eDepartment of Women and Children’s Health (Paediatric Allergy), School of Life 
Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, 
London, United Kingdom
fChildren’s Allergy Service, Evelina London Children’s Hospital, Guy’s and St 
Thomas’ Hospital, London, United Kingdom
gDepartment of Occupational and Environmental Health, Graduate School of 
Medical Sciences, Nagoya City University, Aichi, Japan
hDivision of General Allergy, Bantane Hospital, Fujita Health University, Aichi, 
Japan
Conflicts of interest: K. Yamamoto-Hanada has received research funding as an 
investigator from the Japan Agency for Medical Research and Development 
(AMED) for the Prevention of Allergy via Cutaneous Intervention study, and as 
principal investigator from AMED and Otsuka Pharmaceutical for the DIFENSE 
study; has also received research funding outside the submitted work from 
AMED, the Japan Society for the Promotion of Science (grant number 
23K28010), the National Center for Child Health and Development, the Nip­
ponham Foundation for the Future of Food, the Urakami Foundation for Food and 
Food Culture Promotion, Alcare, Bee Case, Fam’s Baby, Kao, Natural Science, 
Otsuka Pharmaceutical, and Takano; has served as a speaker outside the sub­
mitted work for AbbVie, Bee Case, Eli Lilly, Maruho, Meiji, Otsuka Pharma­
ceutical, Pfizer, Pierre Fabre Japan, Regeneron, Sanofi, Santen, Sun Pharma, and 
Takano; and has served as a consultant outside the submitted work for AbbVie, 
Bee Case, Otsuka Pharmaceutical, Sanofi, and Santen. J.J. Koplin receives 
research funding from the National Health and Medical Research Council of 
Australia and has received a research award from the Stallergenes Greer Foun­
dation, paid to her institution, outside the submitted work. M. Groetch receives 
royalties from UpToDate and the Academy of Nutrition and Dietetics and 
consulting fees from Food Allergy Research & Education; serves on the Medical 
Advisory Board of International Food Protein Induced Enterocolitis Syndrome, as 
a senior advisor to Food Allergy Research & Education, as a health sciences 
advisor for American Partnership for Eosinophilic Disorders; and on the editorial 
board of the Journal of Food Allergy; and has no commercial interests to disclose. 
G. du Toit received funding as investigator on the LEAP Studies, performed as a 
project of the Immune Tolerance Network, an international clinical research 
consortium headquartered at the Benaroya Research Institute and supported by 
the National Institute of Allergy and Infectious Diseases of the National Institutes 
of Health. Y. Ohya has received research funding as principal investigator from 
the Ministry of Health, Labour, and Welfare for the Prevention of Egg Allergy 
With Tiny Amount Intake study and from AMED for the Prevention of Allergy 
via Cutaneous Intervention study; has also received research funding from Fam’s 
and, outside the submitted work, from AMED, the Japan Society for the Pro­
motion of Science and the National Center for Child Health and Development; 
has received honoraria as a speaker outside the submitted work from AbbVie, Eli 
Lilly, Ikeda Mohando, Kyorin, Maruho, Otsuka Pharmaceutical, Pfizer, Pierre 
Fabre Japan, Regeneron, Sanofi, Santen, and Sun Pharma; and has received 
consultation fees outside the submitted work from AbbVie, Bee Case, Kao, 
Kyowahakko Kirin, Leo Pharma, Maruho, Otsuka Pharmaceutical, and Sanofi.
Received for publication September 13, 2025; revised October 14, 2025; accepted 
for publication October 16, 2025.
Available online ■■
Corresponding author: Yukihiro Ohya, MD, PhD, Department of Occupational and 
Environmental Health, Graduate School of Medical Sciences, Nagoya City 
University, 1 Kawasumi, Mizuho-cho, Mizuho-ku Nagoya 467-8601, Japan. 
E-mail: ohyayuk@med.nagoya-cu.ac.jp. 
2213-2198
Ó 2025 The Authors. Published by Elsevier Inc. on behalf of the American 
Academy of Allergy, Asthma & Immunology. This is an open access article under 
the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
https://doi.org/10.1016/j.jaip.2025.10.036
1
Food allergy (FA) is a growing global health concern with inconclusive, although recent Japanese data suggest inevitable
Abbreviations used 
ASCIA- Australasian Society of Clinical Immunology and Allergy
BSACI- British Society for Allergy & Clinical Immunology
EAACI- European Academy of Allergy & Clinical Immunology
ED- Eliciting dose
FA- Food allergy
SPADE- Strategy for Prevention of Milk Allergy by Daily Ingestion 
of Infant Formula in Early Infancy
Published by Elsevier Inc. on behalf of the American Acad­
emy of Allergy, Asthma & Immunology. This is an open 
access article under the CC BY-NC-ND license (http:// 
creativecommons.org/licenses/by-nc-nd/4.0/). (J Allergy 
Clin Immunol Pract 2025;■:■-■) 
Key words: Food allergy; Early allergen introduction; Atopic 
dermatitis; Dual-allergen exposure hypothesis; Eczema man­
agement; Peanut; Egg; Cultural differences; Allergy prevention; 
East—West comparison 
INTRODUCTION
The epidemiology of food allergy (FA) varies globally, 
influenced by genetic, environmental, and dietary factors.1-5 A 
meta-analysis estimated the global FA prevalence at 4.3% (95% 
CI, 3.8-4.7), with rates of 4.2% in Asia, 3.2% in the Americas, 
4.8% in Europe, 1.6% in Africa, and 7.5% in Oceania.3 Milk 
and egg were historically the most common, particularly in in­
fants and young children.3 However, peanut and nut allergies 
are increasingly prevalent, particularly in urbanized regions.4,6
Key risk factors in early childhood include male sex and a 
family history of allergic disease. Eczema is recognized as the 
strongest risk factor,3,7 underscoring the importance of skin 
barrier dysfunction and early immune dysregulation. The Lack 
dual-allergen exposure theory8 was originally proposed as a hy­
pothesis but is now widely regarded as an established theory 
supported by multiple random controlled trials,9-15 confirming 
its validity. It proposes that sensitization primarily occurs 
through a disrupted, inflamed skin barrier, particularly in in­
fants with eczema, whereas early oral exposure promotes toler­
ance. Supporting this, various food allergens have been detected 
in the environment,16-18 and environmental peanut exposure 
such as peanut proteins in household dust has been linked to 
increased sensitization in children with eczema.19
Lifestyle and environmental changes may further explain 
rising FA prevalence.20 The epithelial barrier hypothesis21 and 
hygiene hypothesis22 highlight how pollution, Westernized di­
ets, smaller family size, and reduced microbial exposure can 
impair immune tolerance. Some observational studies suggested 
that early antacid use might increase allergy risk. However, a 
recent systematic review did not find a significant association for 
FA, leaving the evidence inconclusive.23
International guidelines (eg, the Joint CSACI, the American 
Academy of Allergy, Asthma & Immunology and ACAAI,24 the 
British Society for Allergy & Clinical Immunology (BSACI),25
the Australasian Society of Clinical Immunology and Allergy 
(ASCIA),26 the European Academy of Allergy & Clinical 
Immunology (EAACI),27 the Asia Pacific Association of Pedi­
atric Allergy, Respirology & Immunology,28 and the Japanese 
Society of Pediatric Allergy and Clinical Immunology29
emphasize early allergen introduction as a key strategy for pre­
venting FA; some guidelines also recommend eczema care.29 A 
2023 systematic review30 noted inconsistencies across guidelines 
and emphasized the need for harmonization. Although these 
principles are globally relevant, cultural and dietary differences 
between the East and West require regionally adapted 
approaches.
HISTORICAL PERSPECTIVES ON FA PREVENTION
Approaches to FA prevention have evolved over recent de­
cades, shaped by cultural practices and emerging evidence. In 
Western countries, guidelines in the 1990s and early 2000s 
recommended allergen avoidance, especially for infants at high 
risk.31 However, around 2008, recommendations32 began 
shifting away from delayed introduction, and after the 2015 
Learning Early About Peanut Allergy study,9 guidelines more 
strongly endorsed early introduction of allergenic foods.
A pivotal observational study published in 2008, led by du 
Toit and Lack,33 compared peanut allergy prevalence between 
Jewish children in Israel and the United Kingdom. The study 
found a markedly lower rate of peanut allergy in Israel, where 
early peanut consumption was common. This key finding laid 
the groundwork for the Learning Early About Peanut Allergy 
randomized trial (RCT), which confirmed that early introduc­
tion of peanut can prevent peanut allergy in infants at high risk.
As a result, organizations such as the BSACI,25 ASCIA,26
CSACI and ACAAI,24 and EAACI27 now recommend introducing 
allergenic foods in infancy. Whereas the EAACI highlights intro­
duction at around 4 to 6 months, the American Academy of Al­
lergy, Asthma & Immunology, ASCIA, and BSACI recommend 
introduction from around 6 months, with the BSACI noting that 
infants at greater risk may benefit from introduction from 4 
months. Similarly, the US Dietary Guidelines state that “If an in­
fant has severe eczema, egg allergy, or both (conditions that increase 
the risk of peanut allergy), age-appropriate, peanut-containing 
foods should be introduced as early as age 4 to 6 months.”34
In contrast, complementary feeding in Eastern countries often 
begins with rice porridge and vegetables, whereas peanuts and 
nuts are not commonly used as complementary foods during 
infancy. However, as dietary habits in many Eastern countries 
gradually westernize, there is a growing trend toward incorpo­
rating Western evidence into prevention strategies. Guidelines 
from organizations such as the Japanese Society of Pediatric Al­
lergy and Clinical Immunology29 increasingly integrate global 
evidence while adapting to cultural and dietary contexts.
For a better understanding of these differences, Table I35-38
compares infant complementary feeding practices between the 
East and West. For example, early peanut introduction39 and the 
use of commercial baby foods40 are common in Australia, whereas 
in Japan, early introduction of certain nuts is promoted in 
specialized allergy clinics.41 These data illustrate diverse feeding 
practices and the need for culturally sensitive allergy prevention 
strategies, although evidence remains heterogeneous.30
KEY EVIDENCE SUPPORTING EARLY 
INTRODUCTION
We performed a meta-analysis of RCTs9-14,42-50 evaluating 
the early introduction of major allergenic foods (egg, milk, and 
peanut) and their effects on FA incidence (Figures 1-4). This 
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analysis builds on and updates the previously published sys­
tematic reviews and meta-analyses by Scarpone et al,51 incor­
porating recent evidence including an additional RCT by the 
Strategy for Prevention of Milk Allergy by Daily Ingestion of 
Infant Formula in Early Infancy (SPADE) study13 on cow’s 
milk allergy prevention. All included studies were stratified by 
geographic region (Western vs Eastern countries). Scarpone et al 
did not conduct subgroup analyses by geographic regions, and 
the current review provides these results. We analyzed findings 
using fixed- and random-effects models and calculated risk ratios 
(RRs) and 95% CIs.
Our pooled analysis demonstrated that early allergen intro­
duction significantly reduces FA risk (Figures 1, A-C). For any 
allergenic foods combined, early introduction yielded a pooled 
random-effects RR of 0.49 (95% CI, 0.33-0.74; I2 = 49%; n =
4 studies10-12,42) (Figure 1, A), consistent with findings reported 
in the systematic review by Scarpone et al.51 Subgroup analyses 
confirmed consistent protective effects in the West (random- 
effects RR = 0.53 [0.33-0.85]; I2 = 59%; n = 3 studies11,12,42) 
in Figure 1, B and the East (RR = 0.37 [0.16—0.83]; n = 1 
study10) in Figure 1, C.
Regarding milk (Figure 2, A-C), the overall effect of early 
introduction was not statistically significant (pooled random- 
effects RR =
0.64 [0.26-1.56]; I2 =
55%; n =
7 
studies10,12,13,42-45) and exhibited substantial heterogeneity 
(Figure 2, A). Subgroup analysis revealed reduced heterogeneity 
in the four Western studies12,42-44 (Figure 2, B), where no sig­
nificant effect was detected, suggesting consistency in outcomes 
across these trials. In contrast, the Eastern subgroup of three 
studies10,13,45 (Figure 2, C) showed high heterogeneity, indi­
cating variability in study design, population characteristics, and 
implementation of early milk introduction protocols. However, 
the SPADE study (Japan)13 suggested that daily ingestion of 
small amounts of milk formula combined with breastfeeding 
from age 1 month might reduce milk allergy risk in the general 
population (RR = 0.12 [0.03-0.52]). Intervention methods for 
milk varied across studies, and it was suggested that the pre­
ventive effect may differ depending on the amount and timing 
of intake. In addition, the study by Katz et al,52 although 
observational in design, concluded that “early exposure to cow’s 
milk protein as a supplement to breast-feeding might promote 
tolerance.” This finding supports the hypothesis that early 
introduction of cow’s milk protein could be beneficial, although 
further randomized controlled trials are needed to confirm this 
effect.
Egg introduction demonstrated the most consistent preven­
tive effect across subgroups among allergens with a pooled 
random-effects RR of 0.59 (95% CI, 0.46-0.76; I2 = 6%; n = 9 
TABLE I. Comparison of infant complementary feeding practices: East vs West29-32
Aspect
East (Asia)
West (Europe/North America, including Australia)
Typical ingredients
Rice, vegetables, tofu, fish, fermented foods 
(eg, miso, natto)
Potatoes, meat, dairy products, fruits, 
vegetables, grains
Cooking methods
Boiling, steaming, minimal seasoning
Blending, pureeing, microwaving, often using 
commercial baby food
Flavor profile
Mild, natural flavors, often based on family meals
Varied flavors, sometimes sweetened or seasoned
Weaning style
Spoon-feeding, gradual texture progression 
(puree →mashed →solid)
Baby-led weaning increasingly popular: finger foods 
from age 6 mo, skipping pureed foods altogether.
Cultural influence
Strong reliance on family traditions and elders’ advice
Influenced by pediatric guidelines and modern 
parenting trends
Introduction age
Around 6 mo (World Health Organization guideline), 
sometimes slightly earlier
Around 6 mo (World Health Organization 
guideline) complementary foods are 
recommended; however, most introduce 
complementary foods before age 6 mo.
Use of commercial food
Less common, homemade meals preferred
More common, wide variety of commercial 
baby food available
Nutritional focus
Balanced with rice and vegetables, 
emphasis on digestion
Emphasis on iron-rich foods 
(for the predominantly breastfed infant) 
and variety
Peanuts
Peanut are not commonly used as complementary foods. 
Although early introduction is being studied, national 
guidelines often do not explicitly recommend it. 
Whole peanuts should not be given to children aged <6 
y owing to choking hazards, as recommended by 
consumer safety authorities in Japan.
Early introduction (around 4-6 mo) of peanut is 
increasingly recommended based on the LEAP 
study,26 especially for allergy prevention 
in high-risk infants. 
Ground peanut and other infant-safe forms of peanut 
are advised, because whole peanuts are a choking 
hazard to children aged <4 y in the American 
Academy of Pediatrics guidelines.
Tree nuts
Tree nuts are not commonly used as complementary 
foods. Although early introduction is being studied, 
national guidelines often do not explicitly 
recommend it. 
Whole tree nuts should not be given to children aged <6 
y owing to choking hazards, as recommended by 
consumer safety authorities in Japan.
Introduce potentially allergenic foods such as infant- 
safe forms of tree nuts together with other 
complementary foods around age 6 mo in the 
United States.34
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Whole peanuts should be given to children aged <6 in high-risk infants.
studies10,12,14,42,46-50) (Figure 3, A), benefiting both Western 
(RR = 0.67 [0.51-0.88]; I2 = 0%; n = 7 studies12,42,46-50) 
(Figure 3, B) and Eastern (RR = 0.28 [0.14-0.54]; I2 = 0%; 
n = 2 studies10,14) populations (Figure 3, C). Introduction of 
well-cooked egg seems to be safer than raw, pasteurized egg for 
the prevention of egg allergy. Two Japanese RCTs (Natsume 
201714 and Nishimura 202210) provided strong support for 
early egg introduction with a small protein dose of heated-egg 
powder in infants with eczema whose eczema was well- 
controlled. In both studies, early egg introduction was con­
ducted in the context of active eczema treatment, ensuring good 
control throughout the intervention period. This approach 
underscores the importance of managing skin inflammation 
before and during allergenic food introduction to reduce the risk 
of allergic sensitization.
Peanut introduction was also significantly protective (pooled 
random-effects RR = 0.32 [0.18-0.56]; I2 = 21%; n = 4 
studies9,10,12,42) (Figure 4, A), driven by a significant effect in 
Western data (pooled random-effects RR = 0.31 [0.17-0.56]; 
I2 = 45%; n = 3 studies9,12,42) (Figure 4, B). Conversely, the 
single study in the East (Japan)10 did not observe a protective 
effect of early peanut introduction in infants with eczema 
(Figure 4, C), although the RR of 0.48 [0.04-5.21]is similar to 
that in the West, with wide CIs owing to the small sample size. 
Egg allergy is the most common, whereas the prevalence of 
peanut allergy is low in Japan,53 which suggests that other 
cultural or dietary factors may influence these outcomes. On a 
global scale, Japan’s per capita peanut consumption is remark­
ably low, amounting to less than one tenth that in the United 
States.54
These findings indicate that although the early introduction of 
allergenic foods reduces FA risk, its magnitude differs between 
regions. Early egg introduction shows consistent preventive ef­
fects, whereas benefits of early peanut introduction are evident in 
Western countries with high prevalence, but are less pronounced 
in Japan. Kojima et al53 reported only 0.2% peanut allergy at 4 
years in a Japanese cohort, and early ingestion was not significantly 
protective. In Israel, where peanuts are commonly introduced 
early in infancy and widely consumed, the prevalence of peanut 
allergy is also low.33 Thus, early introduction may be most 
beneficial for foods with both high consumption and high allergy 
prevalence. The effect of milk introduction remains inconclusive 
and may depend on timing, dose, and concurrent breastfeeding. 
Promising results from the SPADE study13 in Japan warrant 
further research to assess whether similar protective effects occur 
in Western populations. Region-specific strategies considering 
epidemiology and dietary habits are needed, although definitive 
trials are constrained by ethics.
THE ROLE OF ECZEMA MANAGEMENT IN FOOD 
ALLERGY PREVENTION
According to the dual-allergen exposure theory, proactive 
management of atopic dermatitis55 is expected to reduce FA 
FIGURE 1. (A) All food introductions in the West and the East. (B) All food introductions in the West. (C) All food introductions in the 
East. RR, relative risk.
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development. An observational study in Japan indicated that 
early intervention for eczema,56 including proactive treatment 
targeting both clinical symptoms and subclinical inflammation, 
may decrease the risk of allergic sensitization.
The Phase 3 Prevention of Allergy via Cutaneous Interven­
tion study in Japan demonstrated that early targeted eczema 
treatment, such as proactive therapy with topical corticosteroids 
combined with skin barrier care, may reduce the risk of hen’s 
egg allergy in children with early-onset eczema.15,57 However, 
the authors cautioned that the enhanced treatment protocol 
should be modified before being considered for routine practice, 
owing to potential adverse effects such as significantly reduced 
growth in the aggressively treated group. A follow-up Prevention 
of Allergy via Cutaneous Intervention-ON (PACI-ON) cohort 
is currently investigating the long-term outcomes of this inter­
vention.58 Ongoing studies, including the Stopping Eczema and 
Allergy Study59 (emollient therapy combined with topical cor­
ticosteroids) in the United States and United Kingdom and the 
DIFENSE study60 (topical phosphodiesterase-4 inhibitors) in 
Japan, are expected to provide further robust evidence on 
whether intensive skin management can effectively prevent FA 
development.
These findings emphasize the potential benefit of integrating 
early eczema management, particularly proactive therapy 
addressing subclinical inflammation, with timely allergenic food 
introduction as complementary strategies for FA prevention. 
Importantly, skin barrier reinforcement with moisturizers alone 
has not demonstrated sufficient preventive efficacy by systematic 
reviews.61,62 This underscores the necessity of focusing eczema 
treatment on underlying inflammation rather than barrier repair 
alone.63
Staphylococcus aureus colonization is linked to higher rates of 
food allergen sensitization and may delay tolerance acquisition, 
emphasizing the role of microbial factors alongside eczema 
management in early allergen introduction.64
Infants with early-onset eczema,65,66 uncontrolled eczema,67
or persistent eczema68 are at risk for FA. In the Prevention of 
Egg Allergy With Tiny Amount Intake study, infants who 
consumed eggs from an early age but had poorly controlled 
eczema still developed egg allergy. This suggests that early and 
FIGURE 2. (A) Milk introduction in the West and the East. (B) Milk introduction in the West. (C) Milk introduction in the East. RR, relative 
risk.
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regular oral allergen intake alone may not be sufficient to pre­
vent FA.
IMPLEMENTATION IN CLINICAL PRACTICE: EAST 
VERSUS WEST
Lack dual-allergen exposure theory and its clinical 
implications
The dual-allergen exposure theory underscores the critical 
importance of effective eczema management combined with the 
timely oral introduction of allergenic foods in preventing IgE- 
mediated FA. Infants with atopic dermatitis have increased 
susceptibility to percutaneous sensitization to allergens. Conse­
quently, integrated management strategies that address both 
eczema and dietary interventions are likely essential to mitigate 
IgE-mediated FA risk. From a biological perspective, the 
fundamental mechanisms underlying allergy prevention, such as 
oral tolerance induction, may be similar between Eastern and 
Western populations. However, the effectiveness of early 
introduction strategies may differ depending on local and family 
dietary habits and the prevalence of specific FAs. Current evi­
dence regards cow’s milk allergy prevention and eczema man­
agement primarily derived from Eastern populations, whereas 
evidence about peanut allergy prevention is primarily derived 
from Western populations. Thus, although the biological basis 
appears consistent, regional factors may influence the practical 
outcomes of prevention strategies. Early introduction of aller­
genic foods, even in small amounts, followed by regular and 
sustained ingestion of sufficient amounts of allergenic protein, 
can induce oral immune tolerance and thus prevent the devel­
opment of IgE-mediated FA. Early introduction may be asso­
ciated with an increased incidence of food protein-induced 
enterocolitis syndrome69 in some cases (the condition remains 
rare), but FA prevention specifically targets immediate-type 
FIGURE 3. (A) Egg introduction in the West and the East. (B) Egg introduction in the West. (C) Egg introduction in the East. RR, relative 
risk.
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reactions, and food protein-induced enterocolitis syndrome 
represents a distinct non IgE—mediated mechanism.
In infants with early-onset eczema, percutaneous sensitization 
often precedes oral exposure and is associated with elevate specific IgE 
levels.70 Effective eczema treatment can reduce IgE levels,71,72 which 
reinforces the need to manage skin inflammation before comple­
mentary feeding. Strategies aimed at reducing the degree of sensiti­
zation are important, because higher sensitization levels increase the 
risk of symptom elicitation and lower the threshold of allergen 
exposure to trigger a reaction.73,74 In this population, pre-challenge 
risk assessment and supervised oral food challenge may ensure safe 
allergen introduction. Although routine prescreening with skin or 
specific IgE testing is not recommended, in-office introduction re­
mains an option for families who prefer it. As guidelines increasingly 
move from recommending routine prescreening, this approach re­
mains controversial and warrants further study.
Eczema, particularly early-onset and more severe forms, is a 
well-established risk factor for FA, but most infants worldwide do 
not have eczema. Importantly, cases of FA still develop in these 
infants at low risk. Therefore, consistent with recent Australian as 
well as US and Canadian consensus guidelines,24 timely intro­
duction of allergenic foods is recommended for all infants irre­
spective of eczema status, to promote immune tolerance.
Regular and sustained allergenic food intake
Recent research highlights that regular intake of allergenic 
foods is crucial to prevent FA. Studies13,75 show that regular 
consumption of cow’s milk after early introduction helps pre­
vent cow’s milk allergy, whereas discontinuation or intermittent 
exposure may increase allergy risk.76,77 An observational study 
showed that egg consumption two or more times per week 
during late infancy is associated with a decreased risk of devel­
oping egg allergy in later childhood.78 Similarly, Abrams et al79
reported that early introduction followed by regular consump­
tion of allergenic foods (eg, a few times a week) significantly 
reduces the risk of developing allergies.
Eliciting dose and allergen-specific considerations
In infants aged 12 months or younger with FA, eliciting doses 
(EDs) predicted to provoke objective reactions in 5% of allergic 
individuals were estimated at 28.6 mg for egg white protein, 6.1 
mg for milk protein, and 27.7 mg for wheat protein.80 These 
ED values are higher than those observed in older children and 
tend to decrease with age. Table II provides approximate ex­
amples of typical food portions corresponding to the ED values 
for egg, milk, and wheat proteins in infants.
Notably, ED values vary across allergens, and nuts and pea­
nuts show much lower EDs predicted to provoke objective re­
actions in 5% of allergic individuals (Table III).83 Taken 
together, these findings suggest that initial allergenic protein 
doses for infant introduction should be small, especially for 
infants with eczema or elevated IgE levels who are at high risk. 
Subsequently, gradual dose escalation can occur based on 
tolerance.
FIGURE 4. (A) Peanut introduction in the West and the East. (B) Peanut introduction in the West. (C) Peanut introduction in the East. RR, 
relative risk.
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Commercial allergen introduction products
In the United States and Japan, many commercial products 
are marketed for the early introduction of allergenic foods.84
However, most lack proven preventive effects, may contain less 
protein than indicated, and have occasionally triggered allergic 
reactions, including bodily responses to the natural food after 
using such products. This highlights the need to verify the 
products’ allergen-specific protein content.85 Their use, espe­
cially in infants at high risk, should occur only under profes­
sional supervision.
CULTURAL AND REGIONAL VARIATIONS: EAST 
VERSUS WEST
Food allergy prevention strategies must reflect cultural, 
environmental, and family dietary differences between Eastern 
and Western populations. Dietary customs, prevalent allergens, 
food preparation methods, and the timing and frequency of 
allergen introduction necessitate region-specific guidelines.
For example, infants born in Australia with parents born in 
East Asia had approximately threefold higher rates of peanut 
sensitization and allergy compared with those with Australian- 
born parents,86 illustrating complex gene—environment in­
teractions. In Australia, infants who developed FA despite 
allergen introduction by 6 months were more likely to have 
Asian-born parents and early-onset moderate to severe eczema.87
Furthermore, earlier introduction of peanut was associated with 
a reduced risk of peanut allergy in infants with Australian-born 
parents, but not in those with Asian-born parents.39 In a na­
tionally representative survey of the US population, the preva­
lence of FA was found to be higher among Asian, Hispanic, and 
non-Hispanic Black individuals compared with non-Hispanic 
White individuals.88 Personalized management of allergic dis­
eases requires integration of patients’ genetic predisposition and 
relevant environmental exposures.
In Japan, most infants with eczema are sensitized to egg by 6 
months. This makes egg allergy the most common FA and 
emphasizes the importance of early egg introduction. In 
contrast, peanut sensitization is rare by 1 year, which suggests 
that early peanut introduction may be less critical. Nevertheless, 
evidence from other countries indicates that early nut intro­
duction could be beneficial if it is culturally acceptable.89
However, data from Australia showing a low prevalence of 
cashew sensitization and allergy in those with early introduction 
highlight the potential benefits of early nut introduction if it is 
culturally acceptable.90
IgE sensitization alone does not confirm FA, yet strict 
avoidance diets are still often recommended by primary 
FIGURE 5. Summary of preventing food allergy by early food introduction: East meets West.
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physicians and specialists, potentially delaying tolerance. Proper 
evaluation, including oral food challenges, can prevent unnec­
essary avoidance and support safe early introduction. The 
number of families who do not reintroduce foods after an oral 
food challenge remains high, underscoring the need for high- 
quality data to support families in implementing safe reintro­
duction.91 Education for health care professionals, caregivers, 
and the public is also essential to promote evidence-based 
practices in eczema control, allergen introduction, and avoid­
ance of unnecessary food restrictions.92-94
CONCLUSION
Ultimately, region-specific strategies are needed that build on 
the dual-allergen exposure theory, now evolved from hypothesis 
through accumulating trial evidence, integrating early allergen 
introduction with proactive eczema management, tailored dietary 
guidance, and cultural sensitivity. Supporting a smooth transition 
to family foods, encouraging children to eat the same meals as their 
family while avoiding unnecessary restrictions, can help sustain 
tolerance and foster healthy eating habits. Collaboration between 
Eastern and Western medical communities can support person­
alized prevention, especially for culturally diverse populations.
Acknowledgments
We sincerely thank Yue Kakizaki for her skillful illustration 
work in the preparation of Figure 5.
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TABLE II. Example food amounts of 30 mg of protein
Allergen
Example food amount of ∼30 mg protein
Hen’s egg
1/200th of a whole egg
Milk
1 mL liquid milk 
0.8 g yogurt*
Wheat
0.3 g wheat flour 
1 cup of small elbow macaroni†
0.56 g udon (cooked)‡
*About 0.729-0.850 g based on 170 g yogurt containing 6 or 7 g protein (depending 
on the fat content).
†This is based on the classic size of elbow noodles in the United States.81
‡Cooked udon noodles are about 5.31% protein based on the US Department of 
Agriculture FoodData Central.82
TABLE III. Food-allergenic population eliciting dose83
Food item
Eliciting dose 
(amount of protein) 
predicted to provoke 
objective reactions 
in 5% of allergic 
individuals, mg (95% CI)
Food quantity
Cashew
1.6 (0.4-9.4)
0.008 g
Hen’s egg
2.4 (1.3-5.3)
0.02 g
Fish
15.6 (4.6-102)
0.078 g
Hazel
4.7 (1.7-15.7)
0.035 g
Milk
3.1 (1.6-6.6)
0.09 mL
Peanut
3.9 (2.8-7.1)
0.116 g
Sesame
4.2 (0.6-57.7)
0.021 g
Shrimp
429 (94.0-1,854)
2.1 g
Walnut
1.2 (0.1-13.0)
0.008 g
Wheat
9.3 (3.9-24.9)
0.36 g
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