Effects of storage practices on long-chain polyunsaturated fatty acids and lipid peroxidation of preterm formula milk.

BACKGROUND: Preterm formula milk (FM) is often prepared in advance, potentially affecting nutritional quality. Long-chain polyunsaturated fatty acids (LCPUFAs), important for brain and immune system function, are prone to lipid peroxidation, which correlates with comorbidities of prematurity. The effects of clinical storage practices on LCPUFA content and lipid peroxidation of preterm FM were investigated. METHODS: UK liquid and powder preterm FM (2017) (from two manufacturers) were subjected to routine storage conditions (liquid: refrigeration ≤10 h; powder: weekly preparation in accordance with the manufacturer's instructions and refrigeration ≤24 h for 4 weeks). LCPUFA content, thiobarbituric acid reactive substances and 4-hydroxy-2-nonenal (HNE) content were analysed. RESULTS: Storage did not significantly decrease LCPUFA content. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition recommended LCPUFA intake, whereas in utero accretion rates could not be achieved with both FM brands (liquid and powder). Lipid peroxidation was evident on opening, with 6× higher levels in powder. No effect of ≤10-h refrigeration on peroxidation was seen in liquid FM. In powder FM, it increased over refrigeration (HNE opening: 6.5-9.7 µg mL-1 versus day 28, 24 h: 16.6-36.5 µg mL-1 ) with a significant interaction between storage time and refrigeration (P = 0.015), with higher HNE at 4 h on days 0, 7, 14 and 21 (all P < 0.05). CONCLUSIONS: The results suggest that preterm FM and storage conditions do not support in utero accretion rates for LCPUFAs. Although the results suggest different susceptibility of liquid and powder FM to peroxidation upon refrigeration, they are too preliminary to make specific recommendations. We suggest minimising storage time of fresh and prepared powder FM, wherever possible.

Extremely preterm infants receiving standard care receive very low levels of arachidonic and docosahexaenoic acids.

BACKGROUND & AIMS: Adequate supply of arachidonic (ARA) and docosahexaenoic (DHA) acids is essential for brain development, and extremely preterm infants may be at risk of deficiency. Current levels of ARA and DHA given to extremely preterm infants and the amounts available for accretion have not been established, although recent evidence suggests DHA intake is at a level likely to lead to severe deficits. This study quantified the omega-6 and omega-3 polyunsaturated fatty acid (PUFA) intakes from all sources in the first six weeks of life of preterm infants in standard care. In addition, the relationship between blood levels of circulating cytokines and PUFAs was explored. METHODS: Single centre longitudinal study with omega-6 and omega-3 PUFA intake data analysed from all sources for 17 infants born <28 weeks gestation. At six weeks of age the infants' whole-blood fatty acid levels were measured along with a range of cytokines and chemokines analysed by Luminex® multiplex array. RESULTS: ARA intake was significantly below international recommendations in weeks 1-5 (all p < 0.05), and DHA intake was significantly below recommendations in week 1 (p < 0.0001). The amounts of ARA and DHA available for accretion were significantly below estimated accretion rates in all weeks (all p < 0.001). Mean ARA and DHA intakes were correlated with their respective blood levels (r = 0.568, p = 0.017 and r = 0.704, p = 0.002). There were significant relationships between MIP-1ß and blood DHA levels (rs = 0.559, p = 0.02) and between RANTES and omega-6:omega-3 PUFA ratio (rs = -0.498, p = 0.042). CONCLUSIONS: This study establishes that extremely preterm infants receive insufficient intakes of ARA and DHA. Moreover, blood fatty acid levels may provide a useful measure of intake, where establishing sufficient consumption could have clinical importance. There may also be important interactions between long-chain PUFA status and markers of inflammation, which requires further study.

Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways.

Emerging evidence suggests a complex interplay between the endocannabinoid system, omega-3 fatty acids and the immune system in the promotion of brain self-repair. However, it is unknown if all omega-3 fatty acids elicit similar effects on adult neurogenesis and if such effects are mediated or regulated by interactions with the endocannabinoid system. This study investigated the effects of DHA and EPA on neural stem cell (NSC) fate and the role of the endocannabinoid signalling pathways in these effects. EPA, but not DHA, significantly increased proliferation of NSCs compared to controls, an effect associated with enhanced levels of the endocannabinoid 2-arachidonylglycerol (2-AG) and p-p38 MAPK, effects attenuated by pre-treatment with CB1 (AM251) or CB2 (AM630) receptor antagonists. Furthermore, in NSCs derived from IL-1ß deficient mice, EPA significantly decreased proliferation and p-p38 MAPK levels compared to controls, suggesting a key role for IL-1ß signalling in the effects observed. Although DHA similarly increased 2-AG levels in wild-type NSCs, there was no concomitant increase in proliferation or p-p38 MAPK activity. In addition, in NSCs from IL-1ß deficient mice, DHA significantly increased proliferation without effects on p-P38 MAPK, suggesting effects of DHA are mediated via alternative signalling pathways. These results provide crucial new insights into the divergent effects of EPA and DHA in regulating NSC proliferation and the pathways involved, and highlight the therapeutic potential of their interplay with endocannabinoid signalling in brain repair.

Neurological benefits of omega-3 fatty acids.

The central nervous system is highly enriched in long-chain polyunsaturated fatty acid (PUFA) of the omega-6 and omega-3 series. The presence of these fatty acids as structural components of neuronal membranes influences cellular function both directly, through effects on membrane properties, and also by acting as a precursor pool for lipid-derived messengers. An adequate intake of omega-3 PUFA is essential for optimal visual function and neural development. Furthermore, there is increasing evidence that increased intake of the long-chain omega-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may confer benefits in a variety of psychiatric and neurological disorders, and in particular neurodegenerative conditions. However, the mechanisms underlying these beneficial effects are still poorly understood. Recent evidence also indicates that in addition to the positive effects seen in chronic neurodegenerative conditions, omega-3 PUFA may also have significant neuroprotective potential in acute neurological injury. Thus, these compounds offer an intriguing prospect as potentially new therapeutic approaches in both chronic and acute conditions. The purpose of this article is to review the current evidence of the neurological benefits of omega-3 PUFA, looking specifically at neurodegenerative conditions and acute neurological injury.

A combination of intravenous and dietary docosahexaenoic acid significantly improves outcome after spinal cord injury.

Previous studies have shown that omega-3 polyunsaturated fatty acids such as alpha-linolenic acid and docosahexaenoic acid (DHA) are neuroprotective in models of spinal cord injury (SCI) in rodents. However, the mechanism of action underlying these effects has not been elucidated, and the optimum treatment regime remains to be defined. We have therefore carried out a detailed analysis of the effects of DHA in adult rats subject to thoracic compression SCI. Saline or DHA (250 nmol/kg) was administered intravenously (i.v.) 30 min after compression. After injury, the saline group received a standard control diet for 1 or 6 weeks, whereas DHA-injected animals received either a control or a DHA-enriched diet (400 mg/kg/day) for 1 or 6 weeks. Other groups received a DHA-enriched diet only for 1 week following injury, or received acute DHA (250 nmol/kg; i.v.) treatment delayed up to 3 h after injury. We also assessed oxidative stress and the inflammatory reaction at the injury site, neuronal and oligodendrocyte survival and axonal damage and the locomotor recovery. At 24 h, lipid peroxidation, protein oxidation, RNA/DNA oxidation and the induction of cyclooxygenase-2 were all significantly reduced by i.v. DHA administration. At 1 week and 6 weeks, macrophage recruitment was reduced and neuronal and oligodendrocyte survival was substantially increased. Axonal injury was reduced at 6 weeks. Locomotor recovery was improved from day 4, and sustained up to 6 weeks. Rats treated with a DHA-enriched diet in addition to the acute DHA injection were not significantly different from the acute DHA-treated animals at 1 week, but at 6 weeks showed additional improvements in both functional and histological outcomes. DHA treatment was ineffective if the acute injection was delayed until 3 h post-injury, or if the DHA was administered for 1 week solely by diet. Our results in a clinically relevant model of SCI show that significant neuroprotection can be obtained by combining an initial acute i.v. injection of DHA with a sustained dietary supplementation. Given that the safety and tolerability of preparations enriched in omega-3 fatty acids is already well-documented, such a combined DHA treatment regime deserves consideration as a very promising approach to SCI management.

Dietary enrichment with omega-3 polyunsaturated fatty acids reverses age-related decreases in the GluR2 and NR2B glutamate receptor subunits in rat forebrain.

Ageing is associated with a decrease in the brain content of omega-3 polyunsaturated fatty acids (PUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and with decreased neuroplasticity. The glutamate receptor subunits GluR2 and NR2B play a significant role in forebrain synaptic plasticity. We investigated GluR2 and NR2B in the aged prefrontal cortex, hippocampus and striatum, and tested if treatment with a preparation containing EPA and DHA can reverse age-related changes. The study compared adult and old (3-4 and 24-26 month) rats, and the latter were fed a standard diet or a diet supplemented for 12 weeks with omega-3 PUFA at 270mg/kg/day (ratio EPA to DHA 1.5:1). Ageing was associated with decreases in the GluR2 and NR2B subunits in all structures. These decreases were fully reversed by omega-3 PUFA supplementation. Age-related changes in the phospholipid PUFA content were also seen. Decreases in DHA were mostly corrected by supplementation. This study supports the neuroprotective effect of omega-3 fatty acids in brain ageing, and illustrates specific mechanisms underlying this effect.