Low serum adrenic acid levels in infants and subsequent food-induced anaphylaxis

Abstract

Background: The dietary fat hypothesis links increases in allergic diseases to reduced consumption of n-3 polyunsaturated fatty acids from fish, for example, eicosapentaenoic acid, and increased intake of n-6 polyunsaturated fatty acids from vegetable oils, for example, arachidonic acid.

Objective: Building upon the "fat hypothesis," we sought to investigate the association between 24 types of serum fatty acid levels in infants and the risk of subsequent food-induced anaphylaxis (FIA) by age 2 years as the primary outcome.

Methods: This study was conducted as a prespecified supplemental analysis within the ABC randomized clinical trial. We measured levels of 24 fatty acids in residual serum samples collected from 268 infants at age 5 to 6 months using gas chromatography-mass spectrometry.

Results: Among the 258 infants, 58 exhibited immediate-type food allergies, whereas 200 showed no food allergy. Of the 58 infants, 12 were diagnosed with FIA, whereas the remaining 46 had nonanaphylactic food allergy. Unexpectedly, among the 24 fatty acids, only adrenic acid, also known as docosatetraenoic acid, which is one of the n-6 polyunsaturated fatty acids, showed significantly lower levels in infants with FIA (median [interquartile range] (wt.%), 0.16 [0.14-0.17]), compared with those with no food allergy (0.19 [0.17-0.21]) (P = .0007). In contrast, adrenic acid levels in infants with nonanaphylactic food allergy were 0.19 [0.16-0.21] (wt.%), which did not differ significantly from those in infants with no food allergy (P = .69).

Conclusions: This study generated a hypothesis suggesting that infants with low serum adrenic acid levels might be at greater risk of subsequent FIA. This unexpected result warrants further investigation.

Keywords: AdA; Anaphylaxis; adrenic acid; docosatetraenoic acid (DTA); food allergy; food-induced anaphylaxis; infants; leukotriene B4; prostaglandin E2.

Fig 1

Flow diagram of study participation.

Fig 2

Serum AdA levels presented as a percentage of serum fat weight [wt. %] (A) and as the serum value in μg/mL (B), and EPA/AA ratios (C) across the 4 food allergy categories.

Fig 3

Association between AA and AdA (A), EPA and AdA (B), EPA and DPA (C), and AA and DPA (D).

Fig 4

Hypothetical mechanisms of FIA triggered in infants with low AdA levels induced by high EPA/AA ratio (A), and not triggered in those with high AdA levels and a balanced EPA/AA ratio (B). PGE2, Prostaglandin E2. “→” means promotion, and “⊣” means inhibition. The solid arrows indicate strong metabolism, whereas the open arrows indicate weak metabolism. The dashed arrow between LTB4 and FIA indicates an unknown mechanism.