Table 7  Main studies on the link between the omega-3 fatty acids supplementation and respiratory infections/illness in pediatric age.
Study  Author  Study Population  Omega-3 Fatty Acids (dosage)  Results
Infants fed docosahexaenoic acid- and arachidonic acid-supplemented formula have decreased incidence of bronchiolitis/bronchitis the first year of life.  Pastor et al., 2006 [214]  InfantsRCT  DHA (17 mg/100 kcal)  Reduced incidence of bronchiolitis/bronchitis in the DHA+ group at 5 months (p = 0.0001), 7 months (p = 0.01), and 9 months (p = 0.01)
Fish oil n-3 polyunsaturated fatty acids selectively affect plasma cytokines and decrease illness in Thai schoolchildren: a randomized, double-blind, placebo-controlled intervention trial.  Thienprasert et al., 2009 [221]  Children (9–12 years)RCT  EPA (200 mg) + DHA (1 g)  Fewer episodes (p = 0.014) and shorter duration (p = 0.024) of illness in fish oil group. TGF-β1 concentration was lower in fish oil group (p < 0.001).
Enteral Omega-3 Fatty Acid, γ-Linolenic Acid, and Antioxidant Supplementation in Acute Lung Injury.  Rice et al., 2011 [222]  Adults within 48 h of ARI onsetRCT  EPA (6.84 g) + DHA (3.40 g) daily  Not improving in the primary end point of ventilator-free days in patients with acute lung injury.
Prenatal Docosahexaenoic Acid Supplementation and Infant Morbidity: Randomized Controlled Trial.  Imhoff-Kunsch et al., 2011 [213]  Pregnant woman; a total of more of 800 infants were included in the trial.RCT  DHA (400 mg)  At 1 month: shorter duration of cough, phlegm, and wheezing, respectively (p < 0.001). At 3 months: 14% less time ill (p < 0.0001). At 6 months: shorter duration of fever, nasal secretion, difficulty breathing, rash, and “other illness,” respectively (all p < 0.05).
A Phase II Randomized Placebo-Controlled Trial of Omega-3 Fatty Acids for the Treatment of Acute Lung Injury.  Stapleton et al., 2011 [223]  Adults within 48 h of ARI onsetRCT  EPA (9.75 g) + DHA (6.75 g) daily  Not reduction of biomarkers of pulmonary or systemic inflammation in patients with ALI.
Respiratory hospitalisation of infants supplemented with docosahexaenoic acid as preterm neonates.  Atwell et al., 2012 [215]  Infants born <33 weeks’ gestationRCT  High DHA (∼1%) vs. standard DHA (∼0.3%) in breast milk or formula  Not reduced hospitalisation for LRTI problems in the first 18 months.
The effect of a 1-year multiple micronutrient or n-3 fatty acid fortified food intervention on morbidity in Indian school children.  Thomas et al., 2012 [217]  Children (6–10 years)RCT  α-linolenic acid (900 mg) + DHA (100 mg) vs. α-linolenic acid (140 mg)  Significantly fewer episodes of URTI/child/year (relative risk (RR) = 0.88, 95% confidence interval (CI): 0.79, 0.97) in high consuming n-3 fatty acids group.Significantly shorter duration/episode of URTI (RR = 0.81, 95% CI: 0.78, 0.85), LRTI (RR = 0.91, 95% CI: 0.85, 0.97) in high consuming n-3 fatty acids group.
Effects of Growing-Up Milk Supplemented with Prebiotics and LCPUFAs on Infections in Young Children.  Chatchatee et al., 2014 [218]  Children (11–29 months)RCT  Growing-up milk with addition of 19.2 mg/100 mL of n-3 LCPUFAs (EPA + DHA, 4:6)  Decreased risk of developing at least 1 infection (p = 0.03) in the active group.Trend toward a reduction (p = 0.07) in the total number of infections in the active group.
N–3 Long-chain PUFAs reduce respiratory morbidity caused by iron supplementation in iron-deficient South African schoolchildren: a randomized, double-blind, placebo-controlled intervention  Malan et al., 2015 [219]  Children (6–11 years) with iron-deficiencyRCT  EPA (80 mg) + DHA (420) + placebo vs Fe + EPA/DHAvs Fe + placebovs placebo + placebo  Iron supplementation increased morbidity (p = 0.001), mostly respiratory.Increase in morbidity caused by iron supplementation was prevented (p = 0.009) by DHA/EPA.
Fish Oil–Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring  Bisgaard et al., 2016 [216]  Pregnant women at 24 weeks of gestation; a total of 695 children were included in the trial.RCT  2.4 g of n−3 LCPUFA (55% EPA and 37% DHA) daily  Lower risk of persistent wheeze or asthma in the treatment group (p = 0.035).Reduced risk of infections of the lower respiratory tract (p = 0.033) in the treatment group
ARI, acute respiratory infection; CI, confidence interval; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; LCPUFA, long-chain polyunsaturated fatty acid; LRTI, lower respiratory tract infection; PUFA, polyunsaturated fatty acid; RCT, randomized controlled trial; RR, relative risk; TGF, transforming growth factor; URTI, upper respiratory tract infection.