Modulation of DNA methylation states and infant immune system by dietary supplementation with ω-3 PUFA during pregnancy in an intervention study

Am J Clin Nutr. 2013 Aug;98(2):480-7. doi: 10.3945/ajcn.112.052241. Epub 2013 Jun 12.


Background: Early-life exposures to tobacco smoke and some dietary factors have been identified to induce epigenetic changes in genes involved in allergy and asthma development. Omega-3 (n-3) polyunsaturated fatty acid (PUFA) intake during pregnancy could modulate key cytokines and T helper (Th) cell maturation; however, little is known about the mechanism by which ω-3 PUFA could have a beneficial effect in preventing inflammatory disorders.

Objective: We sought to test whether prenatal dietary supplementation with ω-3 PUFA during pregnancy may modulate epigenetic states in the infant immune system.

Design: This study was based on a randomized intervention trial conducted in Mexican pregnant women supplemented daily with 400 mg docosahexaenoic acid (DHA) or a placebo from 18 to 22 wk of gestation to parturition. We applied quantitative profiling of DNA methylation states in Th1, Th2, Th17, and regulatory T-relevant genes as well as LINE1 repetitive elements of cord blood mononuclear cells (n = 261).

Results: No significant difference in promoter methylation levels was shown between ω-3 PUFA-supplemented and control groups for the genes analyzed; however, ω-3 PUFA supplementation was associated with changes in methylation levels in LINE1 repetitive elements (P = 0.03) in infants of mothers who smoked during pregnancy. Furthermore, an association between the promoter methylation levels of IFNγ and IL13 was modulated by ω-3 PUFA supplementation (P = 0.06).

Conclusions: Our results indicate that maternal supplementation with ω-3 PUFA during pregnancy may modulate global methylation levels and the Th1/Th2 balance in infants. Therefore, the epigenetic mechanisms could provide attractive targets for prenatal modulation and prevention of inflammatory disorders and potentially other related diseases in childhood and adulthood.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • DNA Methylation / drug effects*
  • Dietary Supplements*
  • Double-Blind Method
  • Epigenesis, Genetic
  • Fatty Acids, Omega-3 / administration & dosage*
  • Fatty Acids, Omega-3 / blood
  • Female
  • Humans
  • Immune System / drug effects*
  • Infant
  • Interferon-gamma / blood
  • Interferon-gamma / genetics
  • Interleukin-13 / blood
  • Interleukin-13 / genetics
  • Linear Models
  • Mexico
  • Multivariate Analysis
  • Pregnancy
  • Prenatal Nutritional Physiological Phenomena*
  • Promoter Regions, Genetic
  • Sequence Analysis, DNA
  • Th1-Th2 Balance / drug effects
  • Young Adult


  • Fatty Acids, Omega-3
  • Interleukin-13
  • Interferon-gamma