The role of polyunsaturated fatty acids in the development of allergic diseases

Introduction. The steady increase in the prevalence and severity of allergic diseases worldwide necessitates the search for new pathogenetic mechanisms and preventive strategies. In addition to genetic predisposition, environmental factors, particularly the nature of nutrition during critical periods of early ontogenesis, have a significant impact on the development of the immune response and the risk for atopy. Polyunsaturated fatty acids (PUFAs) play a central role in this process, and the imbalance between the consumption of pro-inflammatory omega-6 and anti-inflammatory ω-3 PUFAs is considered a key factor in the epidemiology of allergic diseases. The aim. To systematize current data on the role and mechanisms of the effect of long-chain PUFA on the risk of development and course of allergic diseases, as well as to assess the potential for their use in prevention and therapy, taking into account genetic features of metabolism.

Materials and methods. The analysis of data from epidemiological, observational, and intervention studies, as well as systematic reviews, devoted to the study of the relationship between the consumption of PUFAs (both with food and in the form of supplements) during pregnancy, lactation, and early childhood with markers of immune response and clinical outcomes of allergic diseases. Special attention is paid to the role of polymorphisms of genes of the FADS cluster (FADS1, FADS2), encoding desaturase enzymes, in the modulation of the effects of PUFAs.

Results. The biological effects of ω-6 (arachidonic acid, ArA) and ω-3 (eicosapentaenoic acid, EPA and docosahexaenoic acid, DHA) PUFA were established to be opposite. ARA metabolites (prostaglandins, leukotrienes) provoke and support allergic inflammation, promote the polarization of the Th2-type immune response and IgE synthesis. On the contrary, ω-3 PUFAs compete with arcs for enzymes, suppressing the synthesis of pro-inflammatory eicosanoids and promoting the formation of specialized resolving mediators (SRM) that resolve inflammation and promote the formation of immune tolerance. Taking ω-3 PUFA supplements during pregnancy and lactation has been shown to be associated with a reduced risk of atopic dermatitis, sensitization to food allergens (especially egg white) and bronchial asthma in children, and the effects can persist for many years. The enrichment of infant formula with PUFA brings their immunomodulatory properties closer to those of breast milk. The effectiveness of PUFA interventions significantly depends on the genetic profile. Carriers of minor alleles of polymorphisms of the FADS genes are characterized by reduced desaturase activity, which leads to lower baseline concentrations of PUFA (especially ARA) and, as a result, to a greater susceptibility to the positive effects of supplementation of ω-3 PUFA and to a potentially lower risk of developing allergies mediated by reduced synthesis of proinflammatory mediators. The “genotype-diet” interaction is a critical factor: dietary interventions (for example, breastfeeding, increased consumption of fish) demonstrate the most pronounced protective effect in carriers of certain genotypes. At the same time, the data from individual studies are contradictory, which may be due to differences in research design, dosages, initial nutritional status of participants and their genetic background.

Conclusion. Long-chain PUFA play a fundamental role in the modulation of immune processes underlying the pathogenesis of allergic diseases. ω-3 PUFA supplementation during the perinatal period and early childhood demonstrates significant potential for the primary prevention of atopy. However, further large-scale prospective studies are required to develop personalized recommendations, taking into account the genetic characteristics of PUFA metabolism (primarily, the FADS cluster polymorphisms), which will allow identifying target populations, optimal doses, timing, and duration of interventions to maximize their clinical effectiveness.

Contribution:
Mukhortykh V.A., Larkova I.A. — creation of the concept, construction of sections of the work;
Mukhortykh V.A., Larkova I.A., Tarmaeva N.A. — work with literature sources, analysis and generalization of the data obtained, writing the text;
Revyakina V.A. — editing the text.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Acknowledgment. The research work on the preparation of the manuscript was carried out using funds from a subsidy for the implementation of a state assignment within the framework of the Fundamental Scientific Research Program (FGMF-2025-0003).

Conflict of interest. The authors declare no conflict of interest.

Received: November 06, 2025
Accepted: November 27, 2025
Published: December 25, 2025

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