Combining a high DHA multi-nutrient supplement with aerobic exercise: protocol for a randomised controlled study assessing mobility and cognitive function in older women.

There is a complex interplay between cognition and gait in older people, with declines in gait speed coexisting with, or preceding cognitive decline. Omega-3 fatty acids, B vitamins, vitamin E, phosphatidylserine, and Ginkgo Biloba show promise in preserving mobility and cognitive function in older adults. Exercise benefits mobility and there is evidence suggesting positive interactions between exercise and omega-3 fatty acids on physical and cognitive function in older adults. Non-frail or pre-frail females aged ≥60 years are included in a randomized placebo controlled study. Intervention groups are: high DHA multi-nutrient supplement and exercise, placebo supplement and exercise, high DHA multi-nutrient supplement, and placebo supplement. Dietary supplementation is 24 weeks. The exercise intervention, two cycle ergometer classes per week, is for the final 12 weeks. The primary outcome is habitual walking speed, secondary outcomes include gait variables under single and dual task, five times sit to stand, verbal and spatial memory, executive function, interference control and health related quality of life. Blood fatty acids, serum homocysteine, dietary intake, physical activity, and verbal intelligence are measured to assess compliance and control for confounding factors. The study is registered at www.clinicaltrials.gov (NCT03228550)

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-1β 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

Long‐Chain Polyunsaturated Fatty Acids and Lipid Peroxidation Products in Donor Human Milk in the United Kingdom: Results From the LIMIT 2‐Centre Cross‐Sectional Study

Background: Donor human milk is increasingly used as alternative to mother’s own milk to feed preterm infants, however, it may provide less long-chain polyunsaturated fatty acid (LCPUFA), and more oxidised lipids, which may be detrimental for preterm infant health and development. Levels have not been reported for donor human milk in the U.K. Methods: Donor human milk (n=19) from two neonatal units, milk from preterm mothers from a neonatal unit (n=10), and term mothers from the community (n=11) were analysed for fatty acid, malondialdehyde, 4-hydroxy-2-nonenal, and hexanal content. Study registration: NCT03573531 Results: Donor human milk had significantly lower absolute LCPUFA content compared to term milk (P<0.001) and significantly lower omega-3 PUFAs than preterm milk (P<0.05), although relative LCPUFA composition did not differ. Exclusive donor human milk feeding leads to significantly lower fat (3.7 vs. 6.7 g/d) and LCPUFA (DHA: 10.6 vs. 16.8 mg/d; ARA: 17.4 vs. 25.2 mg/d) intake than recommended by ESPGHAN, and provides only 17.3% and 43.1% of the in utero accreted ARA and DHA. Donor human milk also had the highest proportion of lipid peroxidation. Conclusions: This study confirms that donor human milk in the U.K. has insufficient levels of LCPUFAs for preterm infants. It demonstrates for the first time that donor human milk has the highest level of lipid peroxidation, compared to preterm or term milk. This has important implications for preterm infant nutrition, as exclusive donor human milk feeding might not be suitable long-term, and may contribute to the development of major preterm neonatal morbidities

The dynamic dimerization of the yeast ADP/ATP carrier in the iunner mitochondrial membrane is affected by conserved cysteine residues

The ADP/ATP carrier (AAC) that facilitates the translocation of ATP made in mitochondria is inserted at the inner mitochondrial membrane by the TIM10-TIM22 protein import system. Here we addressed the state of the AAC precursor during insertion (stage IV of import) and identified residues of the carrier important for dimerization. By a combination of (i) import of a mix of His-tagged and untagged versions of AAC either 35S-labeled or unlabeled, (ii) import of a tandem covalent dimer AAC into wild-type mitochondria, and (iii) import of monomeric AAC into mitochondria expressing only the tandem covalent dimer AAC, we found that the stage IV intermediate is a monomer, and this stage is probably the rate-limiting step of insertion in the membrane. Subsequent dimerization occurs extremely rapidly (within less than a minute). The incoming monomer dimerizes with monomeric endogenous AAC suggesting that the AAC dimer is very dynamic. Conserved Cys residues were found not to affect insertion significantly, but they are crucial for the dimerization process to obtain a functional carrier