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n3-PUFA impact health in several ways, including cardiovascular protection and anti-inflammatory effects, but the underlying mechanisms are not fully understood. In this exploratory study involving 31 healthy subjects, we aimed to investigate the effects of 12 weeks of fish-oil supplementation (1500 mg EPA+DHA/day) on the physical properties of multiple blood cell types. We used deformability cytometry (DC) for all cell types and Laser-assisted Optical Rotational Red Cell Analysis (Lorrca) to assess red blood cell (RBC) deformability. We also investigated the correlation between changes in the physical properties of blood cells and changes in the Omega-3 Index (O3I), defined as the relative content of EPA+DHA in RBCs. Following supplementation, the mean±SD O3I increased from 5.3 %±1.5 % to 8.3 %±1.4 % (p < 0.001). No significant changes in RBC properties were found by both techniques. However, by DC we observed a consistent pattern of physical changes in lymphocytes, neutrophils and monocytes. Among these were significant increases in metrics correlated with the cells' deformability resulting in less stiff cells. The results suggest that leukocytes become softer and have an increased ability to deform under induced short-term physical stress such as hydrodynamic force in the circulation. These changes could impact immune function since softer leukocytes can potentially circulate more easily and could facilitate a more rapid response to systemic inflammation or infection. In conclusion, fish-oil supplementation modulates some physical properties of leukocyte-subfractions, potentially enhancing their biological function. Further studies are warranted to explore the impact of n3-PUFA on blood cell biology, particularly in disease states associated with leukocyte dysregulation.

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The growing interest in Omega-3 fatty acids as diagnostic markers or new therapeutic approaches also for COVID-19 disease, led us to investigate the presence of potential correlations between Omega-3 fatty acids' levels in whole blood and days of hospitalization or admission to the paediatric intensive care unit (PICU) in 51 children with MIS-C diagnosis following SARS-CoV-2 infection. A statistically significant negative correlation was observed between days of hospitalization and docosapentaenoic acid (22:5n-3,DPA), docosahexaenoic acid (DHA) and total Omega-3 FA levels. Dividing the study group into quartiles according to Omega-3-Index (O3I), no statistically significant difference was observed with respect to the PICU admission rate. In contrast, the number of days of hospitalization in Q4 (O3I ≥ 2.51 %) was different from the number observed in groups Q1-3 (O3I < 2.51 %), with subjects showing higher O3I needing shorter hospitalizations than the subjects with lower O3I. According to previous study investigating O3I in adults affected by Sars-cov-2 we explored the levels of this nutrients in children with MIS-C. Our exploratory study shows that high DPA, DHA and O3I levels could be effective in reducing the length of hospitalization.

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BACKGROUND: During pregnancy, the demand for omega-3 fatty acids, notably docosahexaenoic acid (DHA), escalates for both maternal and foetal health. Insufficient levels can lead to complications and can affect foetal development. This study investigated omega-3 status and its relation to dietary intake in pregnant Latvian women, along with its impact on gestational duration and newborn birth weight. METHODS: The study comprised 250 pregnant and postpartum women with a mean age of 31.6 ± 4.8 years. Nutrition and omega-3 supplementation data were collected through a questionnaire covering 199 food items and 12 supplements. Fatty acids in erythrocyte membrane phospholipids were analysed via gas chromatography with flame ionization detection. RESULTS: The median omega-3 fatty acid intake, including eicosapentaenoic acid (EPA) and DHA from diet and supplements, was 0.370 g/day, which is deemed sufficient. However, the median weekly fish intake (126.0 g) and daily nut/seed intake (7.4 g) were insufficient. The median omega-3 supplement intake was 1.0 g/day. No correlation between omega-3 supplement intake and the omega-3 index was observed. There was a weak correlation between the DHA intake from fish and the omega-3 index (r = 0.126, p = 0.047), while a significant correlation between the total EPA and DHA intake from various sources and the omega-3 index was noted (r = 0.163, p = 0.01). Most women (61.6%) had an omega-3 index < 4%, while 34.8% had an index between 4 and 8%, and only 3.6% had an index > 8%. Notably, significant differences in EPA levels and the omega-3 index were found among respondents with differing infant birth weights (p < 0.05). CONCLUSIONS: The omega-3 intake during pregnancy adheres to the established guidelines, although fish consumption remains insufficient. A preconception evaluation of the omega-3 index is advocated to optimize prenatal intake. The indications suggest potential correlations between EPA levels, the omega-3 index, and infant birth weight.

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In 2016, the first worldwide n3 PUFA status map was published using the Omega-3 Index (O3I) as standard biomarker. The O3I is defined as the percentage of EPA + DHA in red blood cell (RBC) membrane FAs. The purpose of the present study was to update the 2016 map with new data. In order to be included, studies had to report O3I and/or blood EPA + DHA levels in metrics convertible into an estimated O3I, in samples drawn after 1999. To convert the non-RBC-based EPA + DHA metrics into RBC we used newly developed equations. Baseline data from clinical trials and observational studies were acceptable. A literature search identified 328 studies meeting inclusion criteria encompassing 342,864 subjects from 48 countries/regions. Weighted mean country O3I levels were categorized into very low ≤4%, low >4-6%, moderate >6-8%, and desirable >8%. We found that the O3I in most countries was low to very low. Notable differences between the current and 2016 map were 1) USA, Canada, Italy, Turkey, UK, Ireland and Greece (moving from the very low to low category); 2) France, Spain and New Zealand (low to moderate); and 3) Finland and Iceland (moderate to desirable). Countries such as Iran, Egypt, and India exhibited particularly poor O3I levels.

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There is an increasing body of evidence supporting a link between low intakes of ω-3 long-chain polyunsaturated fatty acids (LCPUFA) and numerous diseases and health conditions. However, few people are achieving the levels of fish/seafood or eicosapentaenoic acid and docosahexaenoic acid intake recommended in national and international guidelines. Knowledge of a person's ω-3 LCPUFA status will benefit the interpretation of research results and could be expected to lead to an increased effort to increase intake. Dietary intake survey methods are often used as a surrogate for measuring ω-3 PUFA tissue status and its impact on health and functional outcomes. However, because individuals vary widely in their ability to digest and absorb ω-3 PUFA, analytical testing of biological samples is desirable to accurately evaluate ω-3 PUFA status. Adipose tissue is the reference biospecimen for measuring tissue fatty acids, but less-invasive methods, such as measurements in whole blood or its components (e.g., plasma, serum, red blood cell membranes) or breast milk are often used. Numerous commercial laboratories provide fatty acid testing of blood and breast milk samples by different methods and present their results in a variety of reports such as a full fatty acid profile, ω-3 and ω-6 fatty acid profiles, fatty acid ratios, as well as the Omega-3 Index, the Holman Omega-3 Test, OmegaScore, and OmegaCheck, among others. This narrative review provides information about the different ways to measure ω-3 LCPUFA status (including both dietary assessments and selected commercially available analytical tests of blood and breast milk samples) and discusses evidence linking increased ω-3 LCPUFA intake or status to improved health, focusing on cardiovascular, neurological, pregnancy, and eye health, in support of recommendations to increase ω-3 LCPUFA intake and testing.

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Background: Frequent soccer heading negatively affects brain health. Omega-3 fatty acids are neuroprotective against head impacts. A biomarker of omega-3 tissue status, red blood cell (RBC) omega-3 content is reduced during soccer activity. However, whether these changes are associated with frequent heading impacts is unknown. Aim: Explore the association between soccer heading frequencies and RBC omega-3 status. Methods: A prospective cohort study in collegiate women soccer players (n = 16). Players' RBC omega-3 status, Omega-3 Index, and self-reported gameplay header frequencies collected during a competitive season. Results: Mean Omega-3 Index (i.e., pre/postseason) was low (3.95 ± 0.44%). Postseason Omega-3 Index negatively correlated (r = -0.545, p = 0.029) with heading frequencies. Change in Omega-3 Index negatively correlated (r = -0.663, p = 0.005) with average headers per game. Conclusion: RBC omega-3 status is negatively influenced by frequent soccer heading throughout a competitive season which may have concerning implications for player brain health.

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The Omega-3 Index (O3I) reflects eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content in erythrocytes. While the O3I is associated with numerous health outcomes, its widespread use is limited. We investigated whether urinary metabolites could be used to non-invasively monitor the O3I in an exploratory analysis of a previous placebo-controlled, parallel arm randomized clinical trial in males and females (n = 88) who consumed either ~3 g/d olive oil (OO; control), EPA, or DHA for 12 weeks. Fasted blood and first-void urine samples were collected at baseline and following supplementation, and they were analyzed via gas chromatography and multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS), respectively. We tentatively identified S-carboxypropylcysteamine (CPCA) as a novel urinary biomarker reflecting O3I status, which increased following both EPA and DHA (p < 0.001), but not OO supplementation, and was positively correlated to the O3I (R = 0.30, p < 0.001). Additionally, an unknown dianion increased following DHA supplementation, but not EPA or OO. In ROC curve analyses, CPCA outperformed all other urinary metabolites in distinguishing both between OO and EPA or DHA supplementation groups (AUC > 80.0%), whereas the unknown dianion performed best in discriminating OO from DHA alone (AUC = 93.6%). Candidate urinary biomarkers of the O3I were identified that lay the foundation for a non-invasive assessment of omega-3 status.

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The aim of the study was to perform a comprehensive fundamental analysis of the factors of inflammation, oxidative stress, fibrosis, myocardial dysfunction, ischemia and omega-3 index associated with postoperative atrial fibrillation (POAF) after coronary artery bypass graft (CABG) surgery in patients with coronary artery disease. The study involved 158 patients who were admitted to the hospital to undergo CABG surgery. Patients were divided into two groups: group 1 comprised 111 patients without POAF (82% males, median age-62.0 (56.0; 66.0) years), and group 2 comprised 47 patients with POAF (84.4% males, median age-65.0 (61.0; 70.0) years). POAF occurred 5.2 (2.0; 7.0) days after CABG. In all the patients, we evaluated laboratory tests before and 3-4 days after CABG. All the patients also underwent echocardiography. According to results of multifactorial regression analysis, the odds ratio of POAF development for left atrial diameter >41 mm was 4.3 (95% confidence interval (CI) 2.0-9.7, p < 0.001), interleukin (IL)-6 postoperative levels >22.07 pg/mL-3.0 (95% CI 1.4-8.2, p = 0.006), IL-8 postoperative levels >9.67 pg/mL-2.3 (95% CI 1.2-7.3, p = 0.006), superoxide dismutase postoperative levels in plasma >1100.5 U/g-3.2 (95% CI 1.4-9.2, p = 0.03), glutathione postoperative levels ≤0.194 micromole/g of hemoglobin-1.9 (95% CI 1.2-6.3, p < 0.001), glutathione peroxidase postoperative levels ≤17.36 millimole/g of hemoglobin-2.2 (95% CI 1.1-8.2, p < 0.001), glutathione reductase postoperative levels ≤2.99 millimole/g of hemoglobin-2.3 (95% CI, 1.1-5.7, p < 0.001), malondialdehyde postoperative levels >1.25 micromole/g of hemoglobin-2.0 (95% CI, 1.2-7.9, p < 0.001), NO postoperative levels in plasma >36.4 micromole/L-1.5 (95% CI, 1.1-5.9, p < 0.001) and omega-3 index ≤1.59%-2.6 (95% CI 1.5-9.1, p < 0.001). Our study showed that increased left atrial diameter, high postoperative levels of inflammatory factors, oxidative stress, fibrosis indicators and omega-3 index were associated with POAF in patients who underwent CABG.

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Aim: Cardiovascular diseases (CVDs) represent the major cause of morbidity and mortality worldwide including Libya, where they account for 43% of all deaths. Sphingolipids are involved in the pathology of numerous diseases including cardiovascular diseases and are proposed as potential biomarkers of cardiovascular health that could be more effective compared to traditional clinical biomarkers. The aim of this study was to determine the sphingolipid content in the erythrocyte membrane of Libyan migrant and Serbian resident women. In addition, to examine if sphingolipid levels could be used as a novel indicator of cardiovascular risk, we evaluated possible correlations with some well-established biomarkers of cardiovascular health.Materials and Methods: A total of 13 Libyan and 15 Serbian healthy women participated in the study. The high-performance version thin-layer chromatography (HPTLC) using the image analysis tool JustTLC was applied for quantification of erythrocytes' sphingolipids.Results: Lower mean values of erythrocytes' sphingolipids and cholesterol concentrations were found in the group of Libyan emigrants compared to Serbian resident women. Besides, in this group of apparently healthy women (n = 28), the sphingolipid content of erythrocytes was inversely related to the Omega-3 index (r =-0.492, p = 0.008) and directly linked to vitamin D status (r = 0.433, p = 0.021) and membrane cholesterol levels (r = 0.474, p = 0.011).Conclusion: The erythrocytes' sphingolipid levels should be measured/assessed as an additional biomarker of CV health, by applying a simple and routine method. Still, further investigation in a larger population-specific context is warranted.

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Optimal dietary intake of omega-3 long-chain polyunsaturated fatty acids (n3-LCPUFAs) is critical to human health across the lifespan. However, omega-3 index (O3I) determination is not routinely assessed due to complicated procedures for n3-LCPUFA analysis from the phospholipid (PL) fraction of erythrocytes. Herein, a high-throughput method for lipidomics based on multisegment injection-nonaqueous capillary electrophoresis-mass spectrometry was applied to identify circulating PLs as surrogate biomarkers of O3I in two randomized placebo-controlled trials. An untargeted lipidomic data workflow using a subgroup analysis of serum extracts from sunflower oil versus high-dose fish oil (FO)-supplemented participants revealed that ingested n3-LCPUFAs were primarily distributed as their phosphatidylcholines (PCs) relative to other PL classes. In both high-dose FO (5.0 g/day) and EPA-only trials (3.0 g/day), PC (16:0_20:5) was the most responsive PL, whereas PC (16:0_22:6) was selective to DHA-only supplementation. We also demonstrated that the sum concentration of both these PCs in fasting serum or plasma samples was positively correlated to the O3I following FO (r = 0.708, P = 1.02 × 10-11, n = 69) and EPA- or DHA-only supplementation (r = 0.768, P = 1.01 × 10-33, n = 167). Overall, DHA was more effective in improving the O3I (ΔO3I = 4.90 ± 1.33%) compared to EPA (ΔO3I = 2.99 ± 1.19%) in young Canadian adults who had a poor nutritional status with an O3I (3.50 ± 0.68%) at baseline. Our method enables the rapid assessment of the O3I by directly measuring two circulating PC species in small volumes of blood, which may facilitate screening applications for population and precision health.

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Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal morbidity and mortality. Although therapeutic hypothermia is an effective treatment, substantial chronic neurological impairment often persists. The long-chain omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, offer therapeutic potential in the post-acute phase. To understand how PUFAs are affected by HIE and therapeutic hypothermia we quantified for the first time the effects of HIE and therapeutic hypothermia on blood PUFA levels and lipid peroxidation. In a cross-sectional approach, blood samples from newborns with moderate to severe HIE, who underwent therapeutic hypothermia (sHIE group) were compared to samples from newborns with mild HIE, who did not receive therapeutic hypothermia, and controls. The sHIE group was stratified into cerebral MRI predictive of good (n = 10), or poor outcomes (n = 10; nine developed cerebral palsy). Cell pellets were analyzed for fatty acid content, and plasma for lipid peroxidation products, thiobarbituric acid reactive substances and 4-hydroxy-2-nonenal. Omega-3 Index (% DHA + EPA) was similar between control and HIE groups; however, with therapeutic hypothermia there were significantly lower levels in poor vs. good prognosis sHIE groups. Estimated Δ-6 desaturase activity was significantly lower in sHIE compared to mild HIE and control groups, and linoleic acid significantly increased in the sHIE group with good prognosis. Reduced long-chain omega-3 PUFAs was associated with poor outcome after HIE and therapeutic hypothermia, potentially due to decreased biosynthesis and tissue incorporation. We speculate a potential role for long-chain omega-3 PUFA interventions in addition to existing treatments to improve neurologic outcomes in sHIE.

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Numerous studies have described associations between the omega-3 index (defined as the RBC percentage of EPA and DHA) and mental conditions, but no risk stratification or target value has gathered consensus so far. This narrative review aims to summarize the published data on the association between omega-3 index and mental illness and to contribute to the concept of an omega-3 index in the field of mental health. The bibliographic searches have been carried out in PubMed, Scopus and Web of Science databases to find relevant English language original research studies related to that association. The study search and selection process were registered in a PRISMA flow. Thirty-six studies were included in this review examining the links between omega-3 index and postpartum depression (3), major depression (15), major depression and bipolar disorder (1), bipolar disorder (4), schizophrenia and major depression (1), schizophrenia and other psychosis (5) and dementia (7). Thirty of these studies found either significant differences in omega-3 index between patients and controls or inverse relationships between omega-3 index and disease severity. The published evidence is compelling enough to suggest omega-3 index as a risk factor for some psychiatric diseases, specifically, major depression, postpartum depression, psychosis, and dementia. In occidental populations, we propose a risk threshold of (a) 4-5% in major depression and dementia, (b) 5% in postpartum depression, and (c) 4% for psychosis transition.

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Higher levels of omega-3 fatty acids in red blood cell membranes (omega-3 index or O3I) and cardiorespiratory fitness (CRF) are each associated with reduced cognitive impairment, but little research has examined the relationship between O3I and cognitive function while accounting for CRF. We analyzed cross-sectional data from 5,464 healthy men and women aged 55-85 years who had preventive medical examinations between 2009 and 2023. Primary exposures included O3I (<4.0%, 4.0-7.9%, or ≥ 8.0%) and age- and sex-based CRF quintile (1 = low, 2-3 = moderate, 4-5 = high). Cognitive impairment was defined as a Montreal Cognitive Assessment score of ≤ 25. We used Poisson regression to estimate relative risks (RR) of cognitive impairment, controlling for covariates. O3I < 4% was associated with increased cognitive impairment relative to ≥ 8.0% (RR, 1.21; 95% CI, 1.01-1.44) in a partially adjusted model. This association did not remain statistically significant in the fully adjusted model which included CRF. Low versus high CRF was associated with cognitive impairment (RR, 1.28; 95% CI, 1.07-1.53), independent of O3I and clinical biomarkers. The interaction between CRF and O3I was not significant (P = 0.8). In joint association analysis, risk of cognitive impairment was elevated with lower omega-3 index or CRF or both. Additional research is needed to fully understand the association between O3I and cognitive function at varying CRF levels.

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Omega-3 polyunsaturated fatty acids (n-3 PUFA) have unique properties which benefit athlete populations. The literature investigating NCAA collegiate, rugby sevens and German endurance athletes indicates suboptimal n-3 PUFA dietary intake and biological status. The aims of this study were: (i) to explore the dietary intakes and FA profiles of elite level, team-based, female athletes and (ii) to understand perceived barriers towards achieving n-3 dietary guidelines. A total of 35 athletes (24.8 ± 4.5 years) completed both a questionnaire and a finger prick test. All the participants reported consuming fish and seafood over the previous six months however only nine athletes consumed ≥ 2 servings of fish per week. Four participants reported using an n-3 supplement. The mean omega-3 index (O3I; including supplementers) was below target levels of >8% (5.19 ± 0.86%). O3I was significantly higher (p < 0.001) in those consuming ≥ 2 servings of fish per week and/or supplements (5.91 ± 0.81%) compared with those who did not (4.82 ± 0.63%). The main barriers reported by those not consuming two servings of fish per week were sensory (n = 11; 42%), cooking skills (n = 10; 38%) and knowledge of n-3 benefits (n = 7; 27%). The current study shows that elite level female athletes present with suboptimal n-3 dietary intake and O3I due to their food preferences, cooking skills and n-3 knowledge.

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The inclusion of omega-3 fatty acids in our dietary intake is important for performance and recovery and may reduce the risk of various health issues. Studies have shown the omega-3 fatty acid status of US service members is low. The purpose of this study was to evaluate whether offering fish and omega-3-enhanced foods would increase the Omega-3 Index (O3I). We hypothesize cadets will increase O3I with enhanced omega-3 options more than fish alone. Food service venues at 3 US service academies offered fish and other omega-3 foods to cadets for 12 weeks. Questionnaires were used to collect information on the dietary habits and omega-3 food intake of participants. The O3I of each participant was measured at baseline, mid- (6 weeks), and after data collection (12 weeks) time points. Following the 12 weeks, we found a significant increase in O3I. More specifically, the intake of other omega-3 foods, smoothies (3 per week) and toppings (3 per week), increased O3I in cadets. This study identified a strategy encouraging omega-3 food intake and improving O3I among cadets. These results help us understand how we can more effectively impact military service member nutrition for optimal health and performance.

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Recent scientific studies in the field of health and nutrition have unanimously affirmed the importance of consuming the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), because of their cardioprotective properties. Fatty acid profiling in erythrocyte membranes allows the omega-3 index, which is a recognized indicator of the risk of developing cardiovascular disease, to be calculated. One consequence of the upward trend in healthy lifestyles and longevity is an increase in the number of studies into the omega-3 index, which requires a reliable method for the quantitative analysis of fatty acids. This article describes the development and validation of a sensitive and reproducible liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for the quantitative analysis of 23 fatty acids (in the form of fatty acid methyl esters, FAMEs) in 40 µl of whole blood and erythrocytes. The list of acids includes saturated, omega-9 unsaturated, omega-6 unsaturated and omega-3 unsaturated fatty acids as well as their trans-isomers. The limit of quantitation was 250 ng ml-1 for C12:0, C16:0 and C18:0; and 62.5 ng ml-1 for other FAMEs, including EPA, DHA and trans-isomers of FAME C16:1, C18:1 and C18:2 n-6. Sample preparation for fatty acid (FA) esterification/methylation with boron trifluoride-methanol (BF3) has been optimized. Chromatographic separation has been carried out on a C8 column in gradient mode using a mixture of acetonitrile, isopropanol and water with the addition of 0.1% formic acid and 5 mM ammonium formate. As a result, the problem of separating the cis- and trans-isomers of FAME C16:1, C18:1 and C18:2 n-6 has been solved. The electrospray ionization mass spectrometry (ESI-MS) detection of FAMEs, in the form of ammonium adducts, has been optimized for the first time, which has made the method more sensitive that when the protonated species are used. This method has been applied to 12 samples from healthy subjects that consumed omega-3 supplements and has proven to be a reliable tool for determining the omega-3 index.

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Purpose: To evaluate effectiveness of omega-3 fatty acid supplements in relieving dry eye symptoms and signs in symptomatic visual display terminal users (VDT). Methods: A randomized controlled study was done; eyes of 470 VDT users were randomized to receive four capsules twice daily for 6 months (O3FAgroup), each containing 180 mg of eicosapentaenoic acid and 120 mg docosahexaenoic acid. The O3FA group was compared with another group (n = 480) who received four capsules of a placebo (olive oil) twice daily. Patients were evaluated at baseline, 1, 3, and 6 months, respectively. The primary outcome was improvement in omega-3 index (a measure of EPA and DHA ratio in RBC membrane). Secondary outcomes were improvement dry eye symptoms, Nelson grade on conjunctival impression cytology, Schirmer test values, tear film breakup time (TBUT), and tear film osmolarity. Means of groups (pre-treatment, 1, 3, and 6-months) were compared with repeated measure analysis of variance. Results: At baseline, 81% patients had low omega-3 index. In the O3FA group, a significant increase in omega-3 index, improvement in symptoms, reduction in tear film osmolarity, and increase in Schirmer, TBUT, and goblet cell density was observed. These changes were not significant in the placebo group. Improvement in test parameters was significantly (P < 0.001) better in patients with low omega3 index (<4%) subgroup. Conclusion: Dietary omega-3 fatty acids are effective for dry eye in VDT users; omega-3 index appears to be the predictor to identify potential dry eye patients who are likely to benefit from oral omega-3 dietary intervention.

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BACKGROUND: The role of nutritional status and the risk of contracting and/or experiencing adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are unclear. Preliminary studies suggest that higher n-3 PUFA intakes are protective. OBJECTIVES: This study aimed to compare the risk of 3 coronavirus disease 2019 (COVID-19) outcomes (testing positive for SARS-CoV-2, hospitalization, and death) as a function of the baseline plasma DHA levels. METHODS: The DHA levels (% of total fatty acids [FAs]) were measured by nuclear magnetic resonance. The 3 outcomes and relevant covariates were available for 110,584 subjects (hospitalization and death) and for 26,595 ever-tested subjects (positive for SARS-CoV-2) in the UK Biobank prospective cohort study. Outcome data between 1 January, 2020, and 23 March, 2021, were included. The Omega-3 Index (O3I) (RBC EPA + DHA%) values across DHA% quintiles were estimated. The multivariable Cox proportional hazards models were constructed, and linear (per 1 SD) relations with the risk of each outcome were computed as HRs. RESULTS: In the fully adjusted models, comparing the fifth to the first DHA% quintiles, the HRs (95% confidence intervals) for testing positive, being hospitalized, and dying with COVID-19 were 0.79 (0.71, 0.89, P < 0.001), 0.74 (0.58, 0.94, P < 0.05), and 1.04 (0.69-1.57, not significant), respectively. On a per 1-SD increase in DHA% basis, the HRs for testing positive, hospitalization, and death, were 0.92 (0.89, 0.96, P < 0.001), 0.89 (0.83, 0.97, P < 0.01), and 0.95 (0.83, 1.09), respectively. The estimated O3I values across DHA quintiles ranged from 3.5% (quintile 1) to 8% (quintile 5). CONCLUSIONS: These findings suggest that nutritional strategies to increase the circulating n-3 PUFA levels, such as increased consumption of oily fish and/or use of n-3 FA supplements, may reduce the risk of adverse COVID-19 outcomes.

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BACKGROUND: This study developed and validated an integrated metric that enhances understanding of linkages between agro-ecological and socio-economic factors that are important for explaining nutritional wellbeing in relation to fish consumption; especially among adolescent girls who are at risk of nutritional deficiency in Bangladesh. Currently, there is no metric that takes account of environmental, cultural and economic contexts when considering fish consumption and dietary health from a policy perspective. METHODS: The study was designed as a bi-seasonal survey, repeated in the same population of adolescent girls recruited during the dry and wet seasons. Sampling was stratified by five settings (four aqua-agroecological zones and one processing plant community), with 60 girls recruited in each. Associations between candidate predictors (salinity, diet diversity, religion, socio-economic status and women's autonomy score) and dependent variables representing nutritional outcomes (anthropometry, omega-3 index and micronutrient levels) were explored in multivariable regressions. The fitted model with its predictors was validated, and a risk score derived from responses to a few short questions on religion, salinity zone, female autonomy, diet diversity and tilapia consumption. RESULTS: The omega-3 index showed the clearest distinction between seasons, by salinity and religion. Higher female autonomy, religion (being Hindu rather than Muslim), geographical location (living in a high or mid-saline area), and a higher dietary diversity were the strongest predictors of whole blood omega-3 index. The c-index for the prognostic model was 0.83 and 0.76 in the wet and dry season respectively, indicating good predictive accuracy. There appeared to be a clear trend in risk scores differentiating between those 'chronically at risk' and those 'never at risk'. CONCLUSIONS: Observational data on different aquaculture-ecozones defined by salinity enabled us to establish linkages between seasonal fish intake, religion, diet diversity, female autonomy and nutritional wellbeing. The purpose of the metric is to reveal these specific linkages in practice. This tool should improve targeting of timely, preventative and cost-effective nutritional interventions to adolescent girls most at-risk from low omega-3 levels in communities where seafood is produced.

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Long-chain polyunsaturated fatty acids (LCPUFA) are important for brain development and functioning and with that, possibly school performance. Several cross-sectional studies have shown significant positive associations between fish consumption, an important source of LCPUFA and school grades in adolescents. The effect of LCPUFA supplementation on school grades in adolescents has not been investigated yet. The goal of the current study was to investigate (I) the associations between the Omega-3 Index (O3I) at baseline and after 12 months respectively and school grades and (II) the effect of one year krill oil supplementation (source of LCPUFA) on school grades in adolescents with a low O3I at baseline. A double-blind randomised placebo-controlled trial with repeated measurements was executed. Participants received either 400 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day for the first three months in Cohort 1 and the nine months thereafter 800 mg EPA + DHA per day, Cohort 2 started immediately with 800 mg EPA + DHA per day,or a placebo. The O3I was monitored with a finger prick at baseline, three, six and twelve months. Subject grades for English, Dutch and math were collected, a standardised mathematics test was executed at baseline and at 12 months. Data was analysed with (I) explorative linear regressions to investigate associations at baseline and follow-up and (II) mixed model analyses separately for each of the subject grades and the standardised mathematics test to investigate the effect of supplementation after 12 months. The krill oil group had a small significant increase in the mean O3I at all time points. However, very few participants achieved the intended target O3I range of 8-11%. At baseline a significant association between baseline O3I and English grade was show, additionally a trend for an association with Dutch grade was shown. After 12 months no significant associations were found. Additionally, there was no significant effect of krill oil supplementation on subject grades or standardised mathematics test score. In this study, no significant effect of krill oil supplementation on subject grades or standardised mathematics test performance was found. However, as many participants dropped out and/or were non-adherent, results should be interpreted with caution.

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