Do infants of breast-feeding mothers benefit from additional long-chain PUFA from fish oil? A 6-year follow-up.

Fish-oil supplements are marketed as enhancing intelligence and cognitive performance. However, empirical data concerning the utility of these products in healthy term infants are mixed, particularly with respect to lasting effects into childhood. We evaluated whether fish-oil supplementation during infancy leads to better neurocognitive/behavioural development at 6 years. We conducted a double-blind randomised controlled trial of supplementation with n-3 long-chain PUFA in 420 healthy term infants. Infants received either fish oil (containing at least 250 mg DHA and at least 60 mg EPA) or placebo (olive oil) daily from birth to 6 months of age. Neurodevelopmental follow-up was conducted at a mean age of 6 years (sd 7 months), whereby 335 children were assessed for language, executive functioning, global intelligence quotient and behaviour. No significant differences were observed between the groups for the main neurocognitive outcomes. However in parent-report questionnaire, fish-oil supplementation was associated with negative externalising (P = 0·035, d = 0·24) and oppositional/defiant behaviour (P = 0·006, d = 0·31), particularly in boys (P = 0·01, d = 0·45; P = 0·004, d = 0·40). Our results provide evidence that fish-oil supplementation to predominantly breast-fed infants confers no significant cognitive or behavioural benefit to children at 6 years.

Can polymorphisms in the fatty acid desaturase (FADS) gene cluster alter the effects of fish oil supplementation on plasma and erythrocyte fatty acid profiles? An exploratory study.

PURPOSE: The enzymes encoded by fatty acid desaturases (FADS) genes determine the desaturation of long-chain polyunsaturated fatty acids (LCPUFA). We investigated if haplotype and single nucleotide polymorphisms (SNPs) in FADS gene cluster can influence LCPUFA status in infants who received either fish oil or placebo supplementation. METHODS: Children enrolled in the Infant Fish Oil Supplementation Study (IFOS) were randomly allocated to receive either fish oil or placebo from birth to 6 months of age. Blood was collected at 6 months of age for the measurement of fatty acids and for DNA extraction. A total of 276 participant DNA samples underwent genotyping, and 126 erythrocyte and 133 plasma fatty acid measurements were available for analysis. Twenty-two FADS SNPs were selected on the basis of literature and linkage disequilibrium patterns identified from the HapMap data. Haplotype construction was completed using PHASE. RESULTS: For participants allocated to the fish oil group who had two copies of the FADS1 haplotype consisting of SNP minor alleles, DHA levels were significantly higher compared to other haplotypes. This finding was not observed for the placebo group. Furthermore, for members of the fish oil group only, the minor homozygous carriers of all the FADS1 SNPs investigated had significantly higher DHA than other genotypes (rs174545, rs174546, rs174548, rs174553, rs174556, rs174537, rs174448, and rs174455). CONCLUSIONS: Overall results of this preliminary study suggest that supplementation with fish oil may only significantly increase DHA in minor allele carriers of FADS1 SNPs. Further research is required to confirm this novel finding.

Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy.

PURPOSE: Impaired GABAergic inhibition has been implicated in the pathophysiology of epilepsy. The possibility of a paradoxical excitatory effect of GABA in epilepsy has been suggested, but has not been investigated in vivo. We investigated pre- and post-synaptic GABAergic mechanisms in patients with idiopathic generalised epilepsy (IGE). METHOD: In 10 patients and 12 control subjects we explored short- and long-interval intracortical inhibition (SICI, LICI; post-synaptic GABAA and GABAB-mediated respectively) and long-interval intracortical facilitation (LICF; pre-synaptic disinhibition) using transcranial magnetic stimulation. RESULTS: While post-synaptic GABAB-mediated inhibition was unchanged in IGE (p=0.09), LICF was reduced compared to controls (controls: 141±17% of baseline; untreated patients: 107±12%, p=0.2; treated patients: 79±10%, p=0.003). GABAA-mediated inhibition was reduced in untreated patients (response amplitude 56±4% of baseline vs. 26±6% in controls, p=0.004) and normalised with treatment (37±12%, p=0.5 vs. controls). When measured during LICI, GABAA-mediated inhibition became excitatory in untreated IGE (response amplitude 120±10% of baseline, p=0.017), but not in treated patients. CONCLUSION: Pre- and post-synaptic GABA-mediated inhibitory mechanisms are altered in IGE. The findings lend in vivo support to evidence from experimental models and in vitro studies of human epileptic brain tissue that GABA may have a paradoxical excitatory role in ictogenesis.

Does docosahexaenoic acid supplementation in term infants enhance neurocognitive functioning in infancy?

The proposal that dietary docosahexaenoic acid (DHA) enhances neurocognitive functioning in term infants is controversial. Theoretical evidence, laboratory research and human epidemiological studies have convincingly demonstrated that DHA deficiency can negatively impact neurocognitive development. However, the results from randomized controlled trials (RCTs) of DHA supplementation in human term-born infants have been inconsistent. This article will (i) discuss the role of DHA in the human diet, (ii) explore the physiological mechanisms by which DHA plausibly influences neurocognitive capacity, and (iii) seek to characterize the optimal intake of DHA during infancy for neurocognitive functioning, based on existing research that has been undertaken in developed countries (specifically, within Australia). The major observational studies and RCTs that have examined dietary DHA in human infants and animals are presented, and we consider suggestions that DHA requirements vary across individuals according to genetic profile. It is important that the current evidence concerning DHA supplementation is carefully evaluated so that appropriate recommendations can be made and future directions of research can be strategically planned.