Study Reviews

DHA shows a protective effect against neonatal hyperbilirubinemia encephalopathy

  • 06/08/2018

Bilirubin (a derivative of haemoglobin) is a highly toxic pigment for biological systems, particularly the central nervous system. Bilirubin encephalopathy (hyperbilirubinemia encephalopathy or bilirubin-induced brain dysfunction) is a severe complication of neonatal jaundice and is associated with high degrees of disability and mortality in newborns.

While low levels of UCB can have a neuroprotective effect (helping balance nitric oxide concentrations and neutralising cytotoxic radicals, such as reactive oxygen or nitrogen species), excessive levels have neurotoxic effects mediated by different mechanisms (altering the cell and mitochondrial membrane, inducing myelin loss, stimulating release of proinflammatory cytokines and promoting apoptosis, among others).

Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been shown to have protective effects against neurodegeneration and apoptosis; and docosahexaenoic acid (DHA), in particular, has been shown to reduce unconjugated bilirubin-induced activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPC) in vitro in neonatal hyperbilirubinemia.

The authors of this study used a murine model to investigate the neuroprotective effects of n-3 PUFA against UCB both in vitro and in vivo. The results show that DHA reduced the rate of UCB-induced apoptosis and increased the antioxidative enzyme activity of SOT and CAT; it also improved neuronal morphology. DHA did not reduce the bilirubin serum concentration but it did reduce the damage it caused. These observation provide a theoretical basis for potential clinical treatment of bilirubin encephalopathy in newborns.


Hao W, Song J, Li G. Neuroprotective Effect of ω-3 Polyunsaturated Fatty Acids on Bilirubin Encephalopathy In Vitro and In Vivo. Med Sci Monit. 2018;24:2631-8.

Campistol J, Gálvez H, García Cazorla A, Málaga I, Iriondo M, Cusí V. Disfunción neurológica inducida por bilirrubina (Neurological dysfunction induced by bilirrubin). Neurologia. 2012;27:202-11.