Atopic and non-atopic effects of fish oil supplementation during pregnancy.

BACKGROUND: We recently conducted a double-blinded randomised controlled trial showing that fish-oil supplementation during pregnancy reduced the risk of persistent wheeze or asthma in the child by 30%. Here, we explore the mechanisms of the intervention. METHODS: 736 pregnant women were given either placebo or n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in the third trimester in a randomised controlled trial. Deep clinical follow-up of the 695 children in the trial was done at 12 visits until age 6 years, including assessment of genotype at the fatty acid desaturase (FADS) locus, plasma fatty acids, airway DNA methylation, gene expression, microbiome and metabolomics. RESULTS: Supplementation with n-3 LCPUFA reduced the overall risk of non-atopic asthma by 73% at age 6 (relative risk (RR) 0.27 (95% CI 0.06 to 0.85), p=0.042). In contrast, there was no overall effect on asthma with atopic traits (RR 1.42 (95% CI 0.63 to 3.38), p=0.40), but this was significantly modified by maternal FADS genotype and LCPUFA blood levels (interaction p<0.05), and supplementation did reduce the risk of atopic asthma in the subgroup of mothers with FADS risk variants and/or low blood levels of n-3 LCPUFA before the intervention (RR 0.31 (95% CI 0.11 to 0.75), p=0.016). Furthermore, n-3 LCPUFA significantly reduced the number of infections (croup, gastroenteritis, tonsillitis, otitis media and pneumonia) by 16% (incidence rate ratio 0.84 (95% CI 0.74 to 0.96), p=0.009). CONCLUSIONS: n-3 LCPUFA supplementation in pregnancy showed protective effects on non-atopic asthma and infections. Protective effects on atopic asthma depended on maternal FADS genotype and n-3 LCPUFA levels. This indicates that the fatty acid pathway is involved in multiple mechanisms affecting the risk of asthma subtypes and infections. TRIAL REGISTRATION NUMBER: NCT00798226.

Changes in polyunsaturated fatty acids during treatment of malnourished children may be insufficient to reach required essential fatty acid levels - A randomised controlled trial.

BACKGROUND & AIMS: Severe acute malnutrition (SAM) is a global concern. Studies on the impact of ready-to-use therapeutic foods (RUTFs) on polyunsaturated fatty acids (PUFA) are almost non-existent. The aim was to investigate the change in whole-blood PUFA and nutrition and health markers among Cambodian children with SAM after treatment with RUTFs. METHODS: The trial was an 8-week randomised clinical trial of the effectiveness of locally produced fish-based RUTF (L-RUTF) vs standard milk-based RUFT (S-RUTF). Whole-blood fatty acids were analysed using dried blood spots. Nutrition and health markers were assessed using anthropometric assessment and blood samples for markers of inflammation. The trial was conducted at the National Pediatric Hospital, Phnom Penh, Cambodia, with one hundred and twenty-one 6-59-month-old children in treatment for SAM. RESULTS: L-RUTF had a higher content of n-3 PUFA and a higher content of arachidonic acid (AA) and docosahexaenoic acid (DHA), while S-RUTF had the highest content of n-6 PUFA. At baseline, the children presented with a Mead acid level in whole-blood of around 0.08% of total fatty acids (FA%) and an omega-3 index of ∼0.91 ± 0.44. After eight weeks of S-RUTF treatment, linoleic acid (LA), AA, n-6/n-3 PUFA ratio, and Mead acid levels were increased. The L-RUTF intervention did not change the whole-blood PUFAs from baseline. At discharge, the children in the L-RUTF group had a lower n-6/n-3 PUFA ratio than the children in the S-RUTF group, driven by a lower alpha-linolenic acid (ALA) (0.20 vs 0.27 FA%, p = 0.004) and lower LA (15.77 vs 14.21 FA%, p = 0.018) with no significant differences in AA or DHA levels. Weight-for-height z-score at discharge was negatively associated with total PUFA (ß -1.4 FA%, 95%CI. -2.7; -0.1), n-6 LCPUFA (ß -1.3 FA%, 95%CI. -1.3; -0.3), and AA (ß -0.6 FA%, 95%CI. -1.0; -0.2). Age-adjusted height was negatively associated with the Mead acid:AA ratio (ß -1.2 FA%, 95%CI. -2.2; -0.2). No significant change was seen in inflammation markers within groups or between groups during treatment, and n-3 and n-6 PUFAs were not associated with markers of inflammation or haemoglobin status at discharge. CONCLUSION: The trial found that whole-blood markers of PUFA status were low in children at admission and discharge from SAM treatment, indicating that the currently recommended composition of RUTFs are not able to correct their compromised essential fatty acid status. The higher content of DHA and AA in L-RUTF did not give rise to any improvement in PUFA status. No changes in health markers or associations between PUFA and health markers were found. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02907424.

Sex differences in hippocampal-dependent memory and the hippocampal lipidome in adolescent rats raised on diets with or without DHA.

Recent studies suggest the effects of DHA supplementation on human memory may differ between females and males during infancy, adolescence, and early adulthood, but the underlying mechanisms are not clear. As a result, this study sought to examine the spatial memory and brain lipidomic profiles in female and male adolescent rats with or without a DHA-enriched diet that began perinatally with the supplementation of dams. Spatial learning and memory were examined in adolescent rats using the Morris Water Maze beginning at 6 weeks of age and animals were sacrificed at 7 weeks of age to permit isolation of brain tissue and blood samples. Behavioral testing showed that there was a significant diet x sex interaction for two key measures of spatial memory (distance to zone and time spent in the correct quadrant during the probe test), with female rats benefiting the most from DHA supplementation. Lipidomic analyses suggest levels of arachidonic acid (ARA) and n-6 docosapentaenoic acid (DPA) containing phospholipid species were lower in the hippocampus of DHA supplemented compared with control animals, and principal component analyses revealed a potential dietary treatment effect for hippocampal PUFA. Females fed DHA had slightly more PE P-18:0_22:6 and maintained levels of PE 18:0_20:4 in the hippocampus in contrast with males fed DHA. Understanding how DHA supplementation during the perinatal and adolescent periods changes cognitive function in a sex-specific manner has important implications for determining the dietary requirements of DHA. This study adds to previous work highlighting the importance of DHA for spatial memory and provides evidence that further research needs to consider how DHA supplementation can cause sex-specific changes.

PLAAT1 Exhibits Phosphatidylcholine:Monolysocardiolipin Transacylase Activity.

Tissue-specific cardiolipin fatty acyl profiles are achieved by remodeling of de novo synthesized cardiolipin, and four remodeling enzymes have thus far been identified. We studied the enzyme phospholipase A and acyltransferase 1 (PLAAT1), and we report the discovery that it has phosphatidylcholine (PC):monolysocardiolipin (MLCL) transacylase activity. Subcellular localization was analyzed by differential centrifugation and immunoblotting. Total levels of major phospholipids, and the fatty acyl profile of cardiolipin, were analyzed in HEK293 cells expressing murine PLAAT1 using gas chromatography. Apparent enzyme kinetics of affinity-purified PLAAT1 were calculated using radiochemical enzyme assays. This enzyme was found to localize predominantly to the endoplasmic reticulum (ER) but was detected at low levels in the mitochondria-associated ER matrix. Cells expressing PLAAT1 had higher levels of total cardiolipin, but not other phospholipids, and it was primarily enriched in the saturated fatty acids myristate, palmitate, and stearate, with quantitatively smaller increases in the n-3 polyunsaturated fatty acids linolenate, eicosatrienoate, and eicosapentanoate and the monounsaturated fatty acid erucate. Affinity-purified PLAAT1 did not catalyze the transacylation of MLCL using 1-palmitoyl-2-[14C]-linoleoyl-PC as an acyl donor. However, PLAAT1 had an apparent Vmax of 1.61 µmol/min/mg protein and Km of 126 µM using [9,10-3H]-distearoyl-PC as an acyl donor, and 0.61 µmol/min/mg protein and Km of 16 µM using [9,10-3H]-dioleoyl-PC. PLAAT1 is therefore a novel PC:MLCL transacylase.

Macrolipidomic Profiling of Vegetable Oils: The Analysis of Sunflower Oils with Different Oleic Acid Content.

Conventional breeding techniques and genetic modifications have made it possible to alter the composition of vegetable oils. In recent years, the field of lipidomics has rapidly evolved due to technological developments in mass spectrometry. "Macrolipidomics" is an approach dedicated to detailed characterization of the most abundant lipids of a sample and has the potential to be useful for the profiling of commercial seed oils. Seed oils are composed largely of triacylglycerols (TAG) with various fatty acyls that can result in a number of isobaric and isomeric TAG species in each sample. Comprehensive methods for fatty acyl TAG characterization are still scarce. In this chapter, we describe the steps required to process and analyze different sunflower oils with altered oleic acid content to generate quantitative data for discrete fatty acyl species of TAG molecules. We utilized a dual ultra-high-performance liquid chromatography (UHPLC) serial coupling setup and untargeted tandem mass spectrometry (MS/MS) to quantitate 23 common TAG species in three sunflower oils containing 40% (low), 60% (mid), and 85% (high) oleic acid by weight.

Dietary Reference Intakes based on chronic disease endpoints: outcomes from a case study workshop for omega 3's EPA and DHA.

Given the focus on developing Dietary Reference Intakes (DRIs) based on chronic disease risk reduction and recent research for omega-3 long chain PUFA since the last DRI review, the Canadian Nutrition Society convened a panel of stakeholders for a 1-day workshop in late 2019. Attendees discussed the new NASEM guidelines for establishing DRI values based on chronic disease risk endpoints and the strength of current evidence for EPA and DHA as it relates to the new guidelines. Novelty: Summarizes evidence and expert opinions regarding the potential for reviewing DRI values for EPA and DHA and cardiovascular disease risk and early development.

Fish oil supplementation in cancer patients. Capsules or nutritional drink supplements? A controlled study of compliance.

BACKGROUND & AIMS: Fish-oil, rich in Omega-3 long chain polyunsaturated fatty acids (n-3 LC PUFAs), may in high doses inhibit the development or progression of cancer cachexia. However, poor compliance to oral nutritional supplements is a well-known problem. We aimed to investigate acceptability and compliance to a nutritional drink with fish-oil compared to an equivalent dose of fish-oil administered as capsules in patients receiving chemotherapy for GI tract cancers. Moreover, we aimed to investigate, if there was a difference between a nutritional drink or capsules with respect to nutritional status and side effects. Finally, we aimed to examine, if n-3 LC PUFAs affect leukocyte and platelet counts, and markers of dose-limiting toxicities of chemotherapy. METHODS: We consecutively included 41 patients with advanced cancer in the controlled study. Patients were allocated (not randomized) to ingest either 10 capsules/day for four weeks or 400 mL/day of a nutritional drink with same dose of n-3 LC PUFA dose. Compliance was assessed by daily self-registration and n-3 LC PUFAs in whole blood. Side effects were assessed by 10 cm visual analog scales. RESULTS: Compliance and daily consumption of n-3 LC PUFAs were 96.4% (94.1-99.3) and 4.8 (4.7-4.9) g/day in the capsule group and 80.8 (55.4-93.6) % and 4.0 (2.8-4.7) g/day in the group, respectively (p ≤ 0.02). We found no differences between the groups with respect to changes in whole blood n-3 LC PUFAs, weight, nutritional status, acceptability or side effects. However, in the capsule group the whole blood n-3 LC PUFAs correlated negatively with the increase in nausea (rs = -0.39, p = 0.05), but not in the nutritional drink group. Nausea, reduced appetite and loose stools were of greatest importance for the deviations from recommended doses. The number of capsules had a negative impact on acceptability and compliance, whereas this was mainly related to taste and texture in the nutritional drink group. No changes in median thrombocyte or leukocyte blood counts were observed. CONCLUSIONS: Fish oil in capsules appeared to result in better compliance compared to a nutritional drink with an equivalent dose of n-3 LC PUFAs. However, capsules and the drink did not differ with respect to the effect on nutritional status or side effects. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT03751384.

Whole-blood PUFA and associations with markers of nutritional and health status in acutely malnourished children in Cambodia.

OBJECTIVE: To measure fatty acid composition, particularly whole-blood PUFA content, in acutely malnourished children and identify associations with markers of nutritional and health status. DESIGN: PUFA were assessed in dried blood spots obtained from a cross-sectional study. Nutritional and health status were assessed by anthropometry, haemoglobinopathies, inflammation and blood counts. SETTING: Cambodia. PARTICIPANTS: The study was conducted with 174 children aged 0·5-18 years with acute malnutrition. RESULTS: Among total fatty acids (FA), the relative percentage of total PUFA was 20 % FA, with 14 % of the children having very low PUFA (mead acid (MA):arachidonic acid (AA) >0·02, n-6 docosapentaenoic acid:DHA >0·2 and total n-6:n-3 PUFA >10·5). Wasting was not associated with any PUFA. Stunting and low height were consistently positively associated with total PUFA and positively with n-6 PUFA. Height was positively associated with n-3 long-chain PUFA (LCPUFA). The presence of haemoglobinopathies or inflammation was positively associated with MA:AA, but not total PUFA. Elevated blood platelet counts were positively correlated with linoleic acid and appeared to be influenced by anaemia (P = 0·010) and inflammation (P = 0·002). Monocyte counts were high during inflammation (P = 0·052) and correlated positively with n-6 LCPUFA and n-3 LCPUFA. CONCLUSIONS: Children with acute malnutrition or stunting had low PUFA, while elevated platelets and monocytes were associated with high PUFA. In acutely malnourished children, inflammation could lead to elevated blood cell counts resulting in increased whole-blood PUFA which does not reflect dietary intake or nutritional status.

Applications of Innovative Lipidomic Methods for Blood Lipid Biomarkers.

Assessing dietary intake is critical for understanding the relationship between diet and health. Fatty acid blood biomarkers have been particularly useful in determining dietary intakes and assessing the risk of chronic disease. However, fatty acid analysis involves the removal of fatty acids from their complex lipid structures resulting in a loss of potentially useful biological information. "Lipidomics" involves the use of mass spectrometry to identify lipids in their native form. Lipidomic approaches present challenges as an alternative to fatty acid analysis. This includes different types of lipidomic approaches and a lack of consensus on the lipids reported in different studies. Distinguishing between macrolipidomic approaches to characterize highly abundant lipids and microlipidomic approaches examining low abundant bioactive lipids and the use of brutto, medio, genio, and infinio to describe the level of information of lipidomic data can provide clarity to the field. Using lipidomic measurements for understanding docosahexaenoic acid metabolism during pregnancy will also be examined.

DHA Cycling Halves the DHA Supplementation Needed to Maintain Blood and Tissue Concentrations via Higher Synthesis from ALA in Long-Evans Rats.

BACKGROUND: Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) recommendations are frequently stated at 500 mg/d; however, adherence to these recommendations would result in a large global commercial EPA/DHA production deficit. Previously, our laboratory demonstrated that acute DHA intake in rats can increase the capacity for synthesis-secretion of n-3 (ω-3) polyunsaturated fatty acids (PUFAs). OBJECTIVE: We aimed to investigate the utility of a dietary DHA cycling strategy that employs 2 wk of repeated DHA feeding for a total of 3 cycles over 12 wk. METHODS: Male Long-Evans rats were fed a 10% fat diet by weight comprised of either 1) a 2-wk, 2% α-linolenic acid (ALA, DHA-ALA group 18:3n-3) diet followed by a 2-wk, 2% DHA + 2% ALA diet over 3 consecutive 4-wk periods ("DHA cycling," DHA-ALA group); 2) a 2% DHA + 2% ALA diet (DHA group) for 12 wk; or 3) a 2% ALA-only diet (ALA group) for 12 wk. At 15 wk old, blood and tissue fatty acid concentrations and liver mRNA expression and 13C-DHA natural abundances were determined. RESULTS: DHA concentrations in plasma, erythrocytes, and whole blood between the DHA-ALA group and the DHA groups were not different (P ≥ 0.05), but were 72-110% higher (P < 0.05) than in the ALA group. Similarly, DHA concentrations in liver, heart, adipose, and brain were not different (P ≥ 0.05) between the DHA-fed groups, but were at least 62%, 72%, 320%, and 68% higher (P < 0.05) than in the ALA group in liver, heart, adipose, and skeletal muscle, respectively. Compound-specific isotope analysis indicated that 310% more liver DHA in the DHA-ALA group compared with the DHA group is derived from dietary ALA, and this was accompanied by a 123% and 93% higher expression of elongation of very long-chain (Elovl)2 and Elovl5, respectively, in the DHA-ALA group compared with the ALA group. CONCLUSIONS: DHA cycling requires half the dietary DHA while achieving equal blood and tissue DHA concentrations in rats. Implementation of such dietary strategies in humans could reduce the gap between global dietary n-3 PUFA recommendations and commercial production.

Effect of complementary food with small amounts of freshwater fish on whole blood n-3 fatty acids in Cambodian infants age 6-15 months.

The impact of freshwater fish consumption on the status of long-chain n-3 fatty acids (n-3 LCPUFA) in infants in landlocked, low-income populations is unknown. We used secondary data from a randomized, single-blinded, controlled trial to evaluate the impact of daily consumption of complementary food products with small amounts of freshwater fish on whole blood n-3 LCPUFA in Cambodian infants. Infants (n = 419), received daily, one of four food products for 9 months. Two products contained freshwater fish: WinFood (10% fish by dry weight) and WinFood-L (12% fish by dry weight), while two products were non-fish-based: corn-soy blends (CSB+ and CSB++). Whole blood fatty acids and breastfeeding status were assessed at baseline and endline of the intervention. The WinFood products contributed to an estimated maximum intake of 86.5 mg/day n-3 LCPUFA. There was no difference in whole blood n-3 LCPUFA among the four intervention groups or between the fish-based and the non-fish-based groups (p ≥ 0.142). At endline, 71% of the children were still breastfed. Interaction analyses indicated a lower ratio of n-6/n-3 PUFA in non-breastfed infants in the WinFood groups compared to the CSB groups (pinteraction = 0.026). Thus, a high intake of n-3 LCPUFA from breastmilk may have blurred a potential impact of small amounts of freshwater fish effect on n-3 LCPUFA status in Cambodian infants.

Two weeks of docosahexaenoic acid (DHA) supplementation increases synthesis-secretion kinetics of n-3 polyunsaturated fatty acids compared to 8 weeks of DHA supplementation.

Docosahexaenoic acid (DHA, 22:6n-3) must be consumed in the diet or synthesized from n-3 polyunsaturated fatty acid (PUFA) precursors. However, the effect of dietary DHA on the metabolic pathway is not fully understood. Presently, 21-day-old Long Evans rats were weaned onto one of four dietary protocols: 1) 8 weeks of 2% ALA (ALA), 2) 6 weeks ALA followed by 2 weeks of 2% ALA + 2% DHA (DHA), 3) 4 weeks ALA followed by 4 weeks DHA and 4) 8 weeks of DHA. After the feeding period, 2H5-ALA and 13C20-eicosapentaenoic acid (EPA, 20:5n-3) were co-infused and blood was collected over 3 h for determination of whole-body synthesis-secretion kinetics. The synthesis-secretion coefficient (ml/min, means ± SEM) for EPA (0.238±0.104 vs. 0.021±0.001) and DPAn-3 (0.194±0.060 vs. 0.020±0.008) synthesis from plasma unesterified ALA, and DPAn-3 from plasma unesterified EPA (2.04±0.89 vs. 0.163±0.025) were higher (P<.05) after 2 weeks compared to 8 weeks of DHA feeding. The daily synthesis-secretion rate (nmol/d) of DHA from EPA was highest after 4 weeks of DHA feeding (843±409) compared to no DHA (70±22). Liver gene expression of ELOVL2 and FADS2 were lower (P<.05) after 4 vs. 8 weeks of DHA. Higher synthesis-secretion kinetics after 2 and 4 weeks of DHA feeding suggests an increased throughput of the PUFA metabolic pathway. Furthermore, these findings may lead to novel dietary strategies to maximize DHA levels while minimizing dietary requirements.

Analytical Method To Detect and Quantify Avocatin B in Hass Avocado Seed and Pulp Matter.

Avocatin B, an avocado-derived compound mixture, was demonstrated recently to possess potent anticancer activity by selectively targeting and eliminating leukemia stem cells. Avocatin B is a mixture of avocadene and avocadyne, two 17-carbon polyhydroxylated fatty alcohols (PFAs), first discovered in avocado seeds; their quantities in avocado pulp are unknown. Analytical methods to detect avocado seed PFAs have utilized NMR spectroscopy and GC-MS; both of these lack quantitative capacity and accuracy. Herein, we report a sensitive LC-MS method for the quantitation of avocadene and avocadyne in avocado seed and pulp. The method has a reliable and linear response range of 0.1-50 µM (0.03-17.2 ng/µL) for both avocadene and avocadyne ( r2 > 0.990) with a lower limit of quantitation (LLOQ) of 0.1 µM. The intra- and interassay accuracy and precision of the quality control (QC) samples at LLOQ showed ≤18.2% percentage error and ≤14.4% coefficient of variation (CV). The intra- and interassay accuracy and precision for QC samples at low and high concentrations were well below 10% error and CV. This method was successfully applied to quantify avocadene and avocadyne in total lipid extracts of Hass avocado pulp and seed matter.

Effect of Micronutrient Powder Addition on Sensory Properties of Foods for Older Adults.

Micronutrient fortification can improve nutrient intake of older adults in long-term care. However, previous studies indicate that micronutrient fortification can alter food sensory attributes and, potentially, consumer liking. Others have found no effect of fortification on liking. This research investigates the effect of micronutrient powder addition on the sensory properties of selected foods commonly served in long-term care. A micronutrient powder containing 9 vitamins and 3 minerals was added to tomato soup and oatmeal at different levels. Using projective mapping, changes in sensory properties were observed with powder addition. Descriptive analysis, used to quantify these changes, showed that both the tomato soup and oatmeal had reduced flavor as the amount of added micronutrient powder increased. Oatmeal also showed changes in texture with fortification. Consumer liking scores for tomato soup showed that micronutrient addition affected liking when 100% of a daily dose was added into the soup. Addition of 50% of the daily dose did not affect liking. Oatmeal liking did not differ between fortified and unfortified samples. PRACTICAL APPLICATION: Results from this research can be used to decide whether a micronutrient powder of selected vitamins and minerals can be added to foods served to older adults in long-term care. Although sensory properties of the foods will be altered, fortification of both tomato soup and oatmeal with the developed powder is possible without reducing consumer liking to the point where it is disliked.

Associations between omega-3 fatty acids, selenium content, and mercury levels in wild-harvested fish from the Dehcho Region, Northwest Territories, Canada.

To better understand the risks and benefits of eating wild-harvested fish from the Northwest Territories, Canada, levels of total mercury (HgT) and selenium (Se) and composition of omega-3 fatty acid (n-3 FA) were measured in muscle tissue of fish harvested from lakes in the Dehcho Region, Northwest Territories, Canada. Average HgT levels ranged from 0.057 mg/kg (cisco) to 0.551 mg/kg (northern pike), while average n-3 FA concentrations ranged from 101 mg/100 g (burbot) to 1,689 mg/100 g (lake trout). In contrast to HgT and n-3 FA, mean Se concentrations were relatively similar among species. Consequently, species such as lake whitefish, cisco, and longnose sucker displayed the highest nutrient levels relative to HgT content. Levels of HgT tended to increase with fish size, while Se and n-3 FA levels were typically not associated with fork length or fish weight. Interestingly, HgT concentration was occasionally inversely related to tissue nutrient content. Significant negative correlations were observed between Hg and n-3 FA for lake trout, northern pike, and walleye. There were also significant negative correlations between Hg and Se noted for lake whitefish, cisco, and northern pike. Samples with the highest nutritional content displayed, on occasion, lower levels of HgT. This study provides valuable information for the design of probabilistic models capable of refining public health messaging related to minimizing Hg risks and maximizing nutrient levels in wild-harvested fish in the Canadian subarctic.

Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring.

BACKGROUND: Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contributing factor to the increasing prevalence of wheezing disorders. We assessed the effect of supplementation with n-3 LCPUFAs in pregnant women on the risk of persistent wheeze and asthma in their offspring. METHODS: We randomly assigned 736 pregnant women at 24 weeks of gestation to receive 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day. Their children formed the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort and were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children's lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization. RESULTS: A total of 695 children were included in the trial, and 95.5% completed the 3-year, double-blind follow-up period. The risk of persistent wheeze or asthma in the treatment group was 16.9%, versus 23.7% in the control group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.97; P=0.035), corresponding to a relative reduction of 30.7%. Prespecified subgroup analyses suggested that the effect was strongest in the children of women whose blood levels of eicosapentaenoic acid and docosahexaenoic acid were in the lowest third of the trial population at randomization: 17.5% versus 34.1% (hazard ratio, 0.46; 95% CI, 0.25 to 0.83; P=0.011). Analyses of secondary end points showed that supplementation with n-3 LCPUFA was associated with a reduced risk of infections of the lower respiratory tract (31.7% vs. 39.1%; hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.033), but there was no statistically significant association between supplementation and asthma exacerbations, eczema, or allergic sensitization. CONCLUSIONS: Supplementation with n-3 LCPUFA in the third trimester of pregnancy reduced the absolute risk of persistent wheeze or asthma and infections of the lower respiratory tract in offspring by approximately 7 percentage points, or one third. (Funded by the Lundbeck Foundation and others; ClinicalTrials.gov number, NCT00798226 .).

Micronutrient Food Fortification for Residential Care: A Scoping Review of Current Interventions.

PURPOSE: Malnutrition is common in residential care environments, primarily due to poor intake. Micronutrient deficiency, although poorly investigated to date, is also reported to be high. Improving the nutrient density of consumed foods is a potential mechanism to promote increased nutrient intake. A scoping review was conducted to: (1) explore the evidence on micronutrient food fortification strategies, (2) identify candidate nutrients and food vehicles for successful food fortification, and (3) identify gaps for future research. METHODS: The scoping review framework of Arksey and O'Malley was used. A comprehensive search strategy of 4 electronic databases (MEDLINE, EMBASE, CINAHL, and Web of Science) was completed. Two reviewers were involved in screening and data extraction for all selected articles. RESULTS: A total of 4394 relevant articles were identified for screening, and application of inclusion/exclusion criteria resulted in 6 food fortification studies (8 citations; 1 study had 3 citations). Overall, vitamin D (n = 5 studies) and calcium (n = 4 studies) were the most common micronutrients fortified; milk products, margarine, bread, and pureed foods were fortification vehicles. Most studies fortified below the RDA recommendation and did not include clinical outcomes. Samples were small and intervention periods were short (3-6 months). CONCLUSIONS: Fortification is a viable strategy for improving the nutrient density of foods consumed in residential care. Although disparate, this literature suggests the potential for further undertaking of fortification to prevent micronutrient deficiencies among residents and future research should consider multinutrient preparations and clinical outcomes.

Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults.

Studies reporting blood levels of the omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were systematically identified in order to create a global map identifying countries and regions with different blood levels. Included studies were those of healthy adults, published in 1980 or later. A total of 298 studies met all inclusion criteria. Studies reported fatty acids in various blood fractions including plasma total lipids (33%), plasma phospholipid (32%), erythrocytes (32%) and whole blood (3.0%). Fatty acid data from each blood fraction were converted to relative weight percentages (wt.%) and then assigned to one of four discrete ranges (high, moderate, low, very low) corresponding to wt.% EPA+DHA in erythrocyte equivalents. Regions with high EPA+DHA blood levels (>8%) included the Sea of Japan, Scandinavia, and areas with indigenous populations or populations not fully adapted to Westernized food habits. Very low blood levels (≤4%) were observed in North America, Central and South America, Europe, the Middle East, Southeast Asia, and Africa. The present review reveals considerable variability in blood levels of EPA+DHA and the very low to low range of blood EPA+DHA for most of the world may increase global risk for chronic disease.

Changes in whole-blood PUFA and their predictors during recovery from severe acute malnutrition.

Children with severe acute malnutrition (SAM) with complications require in-patient management including therapeutic feeding. Little attention has been given to the effects of these feeds on the essential fatty acid status of children with SAM. The objective of this study was to describe changes in the PUFA composition in whole blood in children with SAM during treatment and to determine predictors of change. This prospective study took place in a paediatric nutrition rehabilitation unit in Kampala, Uganda, and assessed whole-blood fatty acid composition of children with SAM at admission, transition, discharge and follow-up (8 and 16 weeks). ANCOVA was used to identify predictors of change in whole-blood PUFA. The study included 120 children with SAM and twenty-nine healthy control children of similar age and sex. Among the SAM children, 38 % were female and 64 % had oedema. Whole-blood n-6 PUFA proportions increased from admission to follow-up, except for arachidonic acid, which decreased by 0·79 (95 % CI 0·46, 1·12) fatty acid percentage (FA%) from admission to transition and 0·10 (95 % CI 0·23, 0·44) FA% at discharge. n-3 Long-chain (LC) PUFA decreased by 0·21 (95 % CI 0·03, 0·40) FA% at discharge and 0·22 (95 % CI 0·01, 0·42) FA% at 8 weeks of follow-up. This decrease was greater in children from families with recent fish intake and those with nasogastric tube feeding. Current therapeutic feeds do not correct whole-blood levels of LCPUFA, particularly n-3 LCPUFA, in children with SAM. Increased attention is needed to the contents of n-3 LCPUFA in therapeutic feeds.

Essential fatty acid composition and correlates in children with severe acute malnutrition.

BACKGROUND: Severe acute malnutrition (SAM) is a common condition in children living in low-income countries and may be associated with reduced polyunsaturated fatty acids (PUFA) blood levels. The purpose of this study was to describe whole blood fatty acid composition and correlates of PUFA in children admitted with SAM. METHODS: We conducted a cross-sectional study among children admitted with SAM at Mulago National Referral Hospital and healthy controls. Whole blood fatty acid composition was measured and correlated with clinical data such as oedema, levels of haemoglobin, C-reactive protein and HIV-infection status. Multiple linear regression analyses were used to identify correlates of PUFA. RESULTS: The relative contribution of saturated fatty acid to the fatty acids in whole blood (FA%) were lower in 108 children with SAM compared to 24 well-nourished controls whereas most monounsaturated fatty acids were higher in children with SAM. Total and all n-6 PUFA including linoleic (18:2n-6, LA) and arachidonic acid (20:4n-6, AA), as well as total n-3 PUFA and docosahexaenoic acid (22:6n-3, DHA) were lower in children with SAM. The n-6:n-3 PUFA ratio was also lower in the children with SAM. Haemoglobin was a positive correlate of AA, n-3 docosapentaenoic acid (22:5n-3, n-3 DPA), DHA, total n-6 long chain (LC) PUFA and total n-3 LCPUFA. HIV infected children had 0.87 (0.47; 1.58) %-points less n-6 LCPUFA and 0.61 (0.03; 1.19) %-points less AA than the un-infected children. CONCLUSION: Children with SAM presented with lower FA% of LCPUFA. HIV infection and low haemoglobin were also associated with lower FA% of LCPUFA, which may be related to lower numbers of blood cells. Nutrition rehabilitation interventions need to pay more attention to the intake of PUFA.