Effects of omega 3 supplementation on the placenta: A translational integrative review

Abstract

Introduction

Maternal obesity and placental damage are associated with adverse stages of pregnancy, such as pre-eclampsia.

Maternal obesity and placental damage are associated with adverse stages of pregnancy, such as pre-eclampsia.

Objective

To analyze the scientific evidence on the influence of omega 3 (n-3) fatty acid supplementation during pregnancy and its impact on the placenta in experimental (rodent) and clinical models, demonstrating concordances, disagreements, and translational gaps.

To analyze the scientific evidence on the influence of omega 3 (n-3) fatty acid supplementation during pregnancy and its impact on the placenta in experimental (rodent) and clinical models, demonstrating concordances, disagreements, and translational gaps.

Methods

The search was conducted in the MEDLINE/PubMed, LILACS, and Cochrane Library databases between July and August 2025. Original peer-reviewed studies, rodent experiments, and specific clinical trials (RCTs) were included. The risk of bias was assessed using the SYRCLE RoB tool (experimental) and Cochrane RoB 2 (RCT).

The search was conducted in the MEDLINE/PubMed, LILACS, and Cochrane Library databases between July and August 2025. Original peer-reviewed studies, rodent experiments, and specific clinical trials (RCTs) were included. The risk of bias was assessed using the SYRCLE RoB tool (experimental) and Cochrane RoB 2 (RCT).

Results

Sixteen experimental studies and eight RCTs were included. Translational convergence was identified in the increase of n-3 levels and the n-3:n-6 ratio in maternal plasma and placenta, although ideal concentrations remain as gaps. There was convergence in the increased mRNA expression of FATP1 and FATP4 genes in the placenta of healthy pregnant women and obese mice, optimizing fetal lipid transport, but the expression of FABP1, FATP2, and CD36 showed discrepancies. Both studies demonstrated increased gene expression of IL10 and reduced IL6, IL8, TNFA, and TLR4 in placentas associated with obesity. However, the increased PPARG distribution in rodents is not replicated in human placentas. n3 normalized the expression and protein concentrations of VEGF in rodents, restoring angiogenic balance, a parameter not analyzed in any RCT. Heterogeneity was observed in n-3 doses in both studies, as well as in the onset of supplementation. None of the studies presented a low risk of bias in all categories evaluated.

Sixteen experimental studies and eight RCTs were included. Translational convergence was identified in the increase of n-3 levels and the n-3:n-6 ratio in maternal plasma and placenta, although ideal concentrations remain as gaps. There was convergence in the increased mRNA expression of FATP1 and FATP4 genes in the placenta of healthy pregnant women and obese mice, optimizing fetal lipid transport, but the expression of FABP1, FATP2, and CD36 showed discrepancies. Both studies demonstrated increased gene expression of IL10 and reduced IL6, IL8, TNFA, and TLR4 in placentas associated with obesity. However, the increased PPARG distribution in rodents is not replicated in human placentas. n3 normalized the expression and protein concentrations of VEGF in rodents, restoring angiogenic balance, a parameter not analyzed in any RCT. Heterogeneity was observed in n-3 doses in both studies, as well as in the onset of supplementation. None of the studies presented a low risk of bias in all categories evaluated.

Conclusion

Supplementation with n-3, in experimental models, is positive for placental health, through the optimization of lipid transport, resolution of inflammation and oxidative stress. However, in human RCTs, the available evidence remains inconclusive. The discrepancies reveal that the clinical efficacy of n-3 supplementation depends on overcoming methodological flaws and transitioning to a protective nutrition paradigm, based on the genetic and metabolic stratification of pregnant women.

Supplementation with n-3, in experimental models, is positive for placental health, through the optimization of lipid transport, resolution of inflammation and oxidative stress. However, in human RCTs, the available evidence remains inconclusive. The discrepancies reveal that the clinical efficacy of n-3 supplementation depends on overcoming methodological flaws and transitioning to a protective nutrition paradigm, based on the genetic and metabolic stratification of pregnant women.