Allergy Modulation by N-3 Long Chain Polyunsaturated Fatty Acids and Fat Soluble Nutrients of the Mediterranean Diet

Abstract

The Mediterranean diet, containing valuable nutrients such as n-3 long chain poly-unsaturated fatty acids (LCPUFAs) and other fat-soluble micronutrients, is known for its health promoting and anti-inflammatory effects. Its valuable elements might help in the battle against the rising prevalence of non-communicable diseases (NCD), including the development of allergic diseases and other (chronic) inflammatory diseases. The fat fraction of the Mediterranean diet contains bioactive fatty acids but can also serve as a matrix to dissolve and increase the uptake of fat-soluble vitamins and phytochemicals, such as luteolin, quercetin, resveratrol and lycopene with known immunomodulatory and anti-inflammatory capacities. Especially n-3 LCPUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derived from marine oils can target specific receptors or signaling cascades, act as eicosanoid precursors and/or alter membrane fluidity and lipid raft formation, hereby exhibiting anti-inflammatory properties. Beyond n-3 LCPUFAs, fat-soluble vitamins A, D, E, and K1/2 have the potential to affect pro-inflammatory signaling cascades by interacting with receptors or activating/inhibiting signaling proteins or phosphorylation in immune cells (DCs, T-cells, mast cells) involved in allergic sensitization or the elicitation/effector phase of allergic reactions. Moreover, fat-soluble plant-derived phytochemicals can manipulate signaling cascades, mostly by interacting with other receptors or signaling proteins compared to those modified by fat-soluble vitamins, suggesting potential additive or synergistic actions by applying a combination of these nutrients which are all part of the regular Mediterranean diet. Research concerning the effects of phytochemicals such as polyphenols has been hampered due to their poor bio-availability. However, their solubility and uptake are improved by applying them within the dietary fat matrix. Alternatively, they can be prepared for targeted delivery by means of pharmaceutical approaches such as encapsulation within liposomes or even unique nanoparticles. This review illuminates the molecular mechanisms of action and possible immunomodulatory effects of n-3 LCPUFAs and fat-soluble micronutrients from the Mediterranean diet in allergic disease development and allergic inflammation. This will enable us to further appreciate how to make use of the beneficial effects of n-3 LCPUFAs, fat-soluble vitamins and a selection of phytochemicals as active biological components in allergy prevention and/or symptom reduction.

Epithelial barrier hypothesis: Effect of the external exposome on the microbiome and epithelial barriers in allergic disease

“…Especially, in western countries, as a result of the widespread consumption of fast food, the increased use of predominantly n‐6 containing vegetable oils is proposed to be one of the main factors in the increase of asthma 217 . High n‐6/n‐3 ratio and n‐6‐derived AA metabolites induce asthma by causing airway inflammation and bronchoconstriction 218,219 . In contrast, n‐3 fatty acids have beneficial effects by reducing airway inflammation and severity of bronchoconstriction and are also sources of pro‐resolving mediators that have been shown to reduce airway inflammation 220,221 .…”

“…217 High n‐6/n‐3 ratio and n‐6‐derived AA metabolites induce asthma by causing airway inflammation and bronchoconstriction. 218 , 219 In contrast, n‐3 fatty acids have beneficial effects by reducing airway inflammation and severity of bronchoconstriction and are also sources of pro‐resolving mediators that have been shown to reduce airway inflammation. 220 , 221 Furthermore, maternal intake of n‐3 fatty acids during pregnancy has been shown to have protective effects against asthma in children.…”

The External Exposome and Allergies: From the Perspective of the Epithelial Barrier Hypothesis

“…Although there are limited and some conflicting data, consumption of processed/fast food has been reported to increase the risk of AD (108). A high n-6/n-3 fatty acid ratio induces asthma by causing airway inflammation and bronchoconstriction (109). Contrary to n-6 fatty acids, n-3 fatty acids mainly exert a protective effect on allergic diseases by reducing the inflammatory response, mostly through proresolving mediators (110).…”

Pathogenesis, diagnosis, dietary management, and prevention of gastrointestinal disorders in the paediatric population

“…Due to their effects on neurodevelopment and immune response, there is also a growing interest in the role of long-chain polyunsaturated fatty acids (LCPUFA) added in milk formulas. The n-3 LCPUFA supplementation during pregnancy has shown a reduced risk of egg sensitization in the first year of life and a reduced risk of developing atopic eczema [ 22 ]. Milk formulas with added LCPUFA could influence the risk of developing allergies in children [ 23 ].…”