High dietary omega-6 fatty acids contribute to reduced docosahexaenoic acid in the developing brain and inhibit secondary neurite growth

Brain Res. 2008 Oct 27;1237:136-45. doi: 10.1016/j.brainres.2008.07.107. Epub 2008 Aug 5.


Docosahexaenoic acid (DHA, 22:6omega-3) is a major polyunsaturated fatty acid in the brain and is required in large amounts during development. Low levels of DHA in the brain are associated with functional deficits. The omega-3 fatty acids are essential nutrients and their metabolism and incorporation in developing brain depends on the composition of dietary fat. We assessed the importance of the intake of the omega-3 fatty acid, 18:3omega-3 and the balance with the omega-6 fatty acid, 18:2omega-6, and the effects of dietary arachidonic acid (20:4omega-6) and DHA in milk diets using the piglet as a model of early infant nutrition. Piglets were fed (% energy) 1.2% 18:2omega-6 and 0.05% 18:3omega-3 (deficient), 10.7% 18:2omega-6 and 1.1% 18:3omega-3 (contemporary), 1.2% 18:2omega-6 and 1.1% 18:3omega-3 (evolutionary), or the contemporary diet with 0.3% 20:4omega-6 and 0.3% DHA (supplemented) from birth to 30 days of age. Our results show that a contemporary diet, high in 18:2omega-6 compromises DHA accretion and leads to increased 22:4omega-6 and 22:5omega-6 in the brain. However, an evolutionary diet, low in 18:2omega-6, supports high brain DHA. DHA supplementation effectively increased DHA, but not the intermediate omega-3 fatty acids, 20:5omega-3 and 22:5omega-3. Using primary cultures of cortical neurons, we show that 22:5omega-6 is efficiently acylated and preferentially taken up over DHA. However, DHA, but not 22:5omega-6 supports growth of secondary neurites. Our results suggest the need to consider whether current high dietary omega-6 fatty acid intakes compromise brain DHA accretion and contribute to poor neurodevelopment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Arachidonic Acid
  • Brain* / drug effects
  • Brain* / growth & development
  • Brain* / metabolism
  • Dietary Supplements*
  • Docosahexaenoic Acids / metabolism*
  • Fatty Acids, Omega-6 / administration & dosage*
  • Male
  • Neurites / drug effects*
  • Neurites / physiology
  • Neurons / cytology
  • Swine
  • Tissue Distribution


  • Fatty Acids, Omega-6
  • Docosahexaenoic Acids
  • Arachidonic Acid