The omega-3 index, the percentage of EPA plus DHA in erythrocytes (measured by standardised analysis), represents a human body's status in EPA and DHA. An omega-3 index is measured in many laboratories around the world; however, even small differences in analytical methods entail large differences in results. Nevertheless, results are frequently related to the target range of 8–11 %, defined for the original and scientifically validated method (HS-Omega-3 Index®), raising ethical issues, and calling for standardisation. No human subject has an omega-3 index <2 %, indicating a vital minimum. Thus, the absence of EPA and DHA cannot be tested against presence. Moreover, clinical events correlate with levels, less with the dose of EPA and DHA, and the bioavailability of EPA and DHA varies inter-individually. Therefore, the effects of EPA and DHA are difficult to demonstrate using typical drug trial methods. Recent epidemiologic data further support the relevance of the omega-3 index in the cardiovascular field, since total mortality, cardiovascular mortality, cardiovascular events such as myocardial infarction or stroke, or blood pressure all correlate inversely with the omega-3 index. The omega-3 index directly correlates with complex brain functions. Compiling recent data supports the target range for the omega-3 index of 8–11 % in pregnancy. Many other potential applications have emerged. Some, but not all health issues mentioned have already been demonstrated to be improved by increasing intake of EPA and DHA. Increasing the omega-3 index into the target range of 8–11 % with individualised doses of toxin-free sources for EPA and DHA is tolerable and safe.

Population ageing affects the entire world population. Also at world level one can observe a sharp increase in the proportion of older people. The challenge posed by population ageing translates into ensuring that the extra years of life will be as good as possible, free from high-cost dependency. Omega-3 fatty acids are now generally recognized as potential key nutrients to prevent the pathological conditions associated to the aging process. Ageing physiological process, its association with quality of life and the impact of omega-3 fatty acids intake and/or status is the focus of the present review. This report deals with the effects of omega-3 fatty acids on normal aging of older adults ( ≥  65 years) mainly on the effects such as nutritional status itself, cognition, bone health, muscle tonus, and general health status. The preliminary broad search of the literature on the effects of omega-3 fatty acids on normal aging yielded 685 citations. Forty two full text papers were checked for inclusion and thirty six studies were finally included in this review. It may be concluded that paradoxically even though the elderly population is the largest one, the number of studies and the methodology employed clearly lacks of sufficient evidence to establish definite conclusions on the effects of omega-3 fatty acids on aging metabolism without pathological conditions and on quality of life.

Epidemiological and clinical studies suggest that consumption of omega (ω-3) polyunsaturated fatty acids (PUFA) contributes to the reduction of cardiovascular mortality through different mechanisms including modulation of cellular metabolic functions, gene expression and beneficial effects on lipid profile or blood pressure. The aim of the study is to review the effects of ω-3 PUFA supplemented as fish oil or blue fish in blood pressure. The analysis of different studies suggests that high doses ω-3 PUFA ( ≥  3 g/day) produces a small but significant decrease in blood pressure, especially systolic blood pressure, in older and hypertensive subjects; however, the evidence is not consistent among different studies. ω-3 polyunsaturated fatty acids consumption might have a place in the control of patients with mild hypertension before starting drug treatment and of those who prefer changes of lifestyles like diet.

Some epidemiological evidence suggests that diets high in omega 3 fatty acids (n-3 FAs) may be beneficial for skeletal health. The aim of this systematic review was to determine if randomized controlled trials (RCTs) support a positive effect of n-3 FAs on osteoporosis. A systematic search was performed in PubMed and EMBASE databases. We included RCTs with skeletal outcomes conducted in adults or children (> = 1 year old) using n-3 FA fortified foods, diets or supplements alone or in combination with other vitamins/minerals, versus placebo. Primary outcomes were incident fracture at any site and bone mineral density (BMD) in g/cm2. Secondary outcomes included bone formation or resorption markers and bone turnover regulators. A total of 10 RCTs met inclusion criteria. Effect sizes with 95 % confidence intervals were estimated to compare studies across various treatments and outcome measures. No pooled analysis was completed due to heterogeneity of studies and small sample sizes. No RCTs included fracture as an outcome. Four studies reported significant favorable effects of n-3 FA on BMD or bone turnover markers. Of these, three delivered n-3 FA in combination with high calcium foods or supplements. Five studies reported no differences in outcomes between n-3 FA intervention and control groups; one study included insufficient data for effect size estimation. Strong conclusions regarding n-3 FAs and bone disease are limited due to the small number and modest sample sizes of RCTs, however, it appears that any potential benefit of n-3 FA on skeletal health may be enhanced by concurrent administration of calcium.

OBJECTIVES/GOALS: This study aimed to investigate the mechanistic effects of fish oil (âμ-3 fatty acids) or evening primrose oil (âμ-6 fatty acids) supplementation on platelet reactivity in postmenopausal women. METHODS/STUDY POPULATION: Postmenopausal women were recruited from the Ann Arbor community and the University of Michigan Medicine Center. All subjects were recruited under study protocols approved by the University of Michigan IRB between November 2015 and March 2017. We conducted a randomized, double-blind, two-period crossover trial, consisting of a 60-day supplementation period followed by a 14-day washout period in between and at the end of the study. Subjects were treated daily in random order with 2g of fish oil supplement and 2g of evening primrose oil. Blood was drawn at baseline, post-supplementation, and after washout. The effects of fatty acid supplementation on platelet aggregation, dense granule secretion and activation of basal integrin âºIIbÎ23 were assessed following supplementation and washout period. RESULTS/ANTICIPATED RESULTS: The study started with 90 postmenopausal women. A total of 78 subjects completed the study, with 12 subjects dropping out due to non-compliance and medical reasons. Supplementation with fish oil attenuated the thrombin receptor PAR4-induced platelet aggregation, whereas primrose oil supplementation attenuated aggregation mediated by PAR4 or collagen. Supplementation with âμ-3 or âμ-6 fatty acids decreased platelet dense granule secretion and attenuated basal levels of integrin âºIIbÎ23 activation. Post-washout following supplementation with primrose oil, the thrombin receptor PAR1-induced platelet aggregation was similarly attenuated. For either treatment, the observed effects post supplementation on dense granule secretion and basal integrin activation were sustained after the washout. DISCUSSION/SIGNIFICANCE: Postmenopausal women are at increased risk for a cardiovascular event due to platelet hyperactivity. This study indicates that supplementation with âμ-3 and âμ-6 fatty acids may offer significant protection for postmenopausal women against cardiovascular diseases and occlusive thrombotic events by reducing platelet reactivity.

A number of studies are investigating the role of n-3 polyunsaturated fatty acids in children with metabolic inborn errors, while the effects on visual and brain development in premature infants and neonates are well known. However, their function incertain chronic neurological, inflammatory and metabolic disorders is still under study. Standards should be established to help identify the need of docosahexaenoic acid supplementation in conditions requiring a restricted diet resulting in an altered metabolism system, and find scientific evidence on the effects of such supplementation. This study reviews relevant published literature to propose adequate n-3 intake or supplementation doses for different ages and pathologies. The aim of this review is to examine the effects of long chain polyunsaturated fatty acids supplementation in preventing cognitive impairment or in retarding its progress, and to identify nutritional deficiencies, in children with inborn errors of metabolism. Trials were identified from a search of the Cochrane and MEDLINE databases in 2011. These databases include all major completed and ongoing double-blind, placebo-controlled, randomized trials, as well as all studies in which omega-3 supplementation was administered to children with inborn errors, and studies assessing omega-3 fatty acids status in plasma in these pathologies. Although few randomized controlled trials met the inclusion criteria of this review, some evidenced that most of children with inborn errors are deficient in omega-3 fatty acids, and demonstrated that supplementation might improve their neural function, or prevent the progression of neurological impairment. Nontheless, further investigations are needed on this issue.

In animal studies, n-3 PUFA have been shown to influence body composition and to reduce the accumulation of body fat, thereby affecting body weight homeostasis. In addition, it has been suggested that an additional supply of n-3 PUFA during pregnancy or lactation, or both, would have a beneficial effect on birth weight and infant growth and development. The purpose of the present study was to systematically review interventional clinical trials on the effects of dietary n-3 PUFA supplementation on body weight in adult subjects and in infants whose mothers were supplemented with these fatty acids during pregnancy and/or lactation. A systematic search, focused on n-3 PUFA and body weight, and limited to controlled clinical trials, was performed in different databases. The quality of all included studies was assessed against set criteria, and results of eligible trials were compared. There were few studies targeting this topic. In adults, all of the five studies included, except for one, show no change in body weight by dietary supplementation with n-3 PUFA. Within those trials conducted in pregnant and/or lactating women in which a main outcome was birth weight or growth in infancy, two showed a modest increase in birth weight and the rest showed no effect. None of the trials showed an effect of maternal n-3 PUFA supplementation on infant's weight at the short term. However, it should be noted that a number of limitations, including a variety of experimental designs, type and doses of n-3 PUFA, and high attrition rates, among others, make impossible to draw robust conclusions from this review.

Pregnancy is associated with a reduction in maternal serum docosahexaenoic acid (DHA, 22:6 n-3) percentage and its possible depletion in the maternal store. Since the synthesis of long chain polyunsaturated fatty acids (LCPUFA) in the fetus and placenta is low, both the maternal LCPUFA status and placental function are critical for their supply to the fetus. Maternal supplementation with DHA up to 1 g/d or 2·7 g n-3 LCPUFA did not have any harmful effect. DHA supplementation in large studies slightly the enhanced length of gestation (by about 2 days), which may increase the birth weight by about 50 g at delivery. However no advice can be given on their general using to avoid preterm deliveries in low or high risk pregnancies. Several studies, but not all, reported improvements of the offspring in some neurodevelopmental tests as a result of DHA supplementation during gestation, or, at least, positive relationships between maternal or cord serum DHA percentages and cognitive skills in young children. The effect seems more evident in children with low DHA proportions, which raises the question of how to identify those mothers who might have a poor DHA status and who could benefit from such supplementation. Most studies on the effects of n-3 LCPUFA supplementation during pregnancy on maternal depression were judged to be of low-to-moderate quality, mainly due to small sample sizes and failure to adhere to Consolidated Standards of Reporting Trials guidelines. In contrast, the effects of n-3 LCPUFA supplementation on reducing allergic diseases in offspring are promising.

Oily fish and other sources of long-chain n-3 polyunsaturated fatty acids (n-3 LCPs) have been proposed as protective against dementia and age related cognitive impairment. The basic mechanisms underlying these proposed benefits have been postulated and experimental studies supporting the plausibility of the putative effects have been published. Observational epidemiological and case control studies also largely support a protective role of fish consumption on cognitive function with advancing age, albeit with important unexplained heterogeneity in findings. In this review we report the findings of the latest Cochrane review on the benefits of n-3 LCP supplementation on cognitive function among cognitively healthy older people and expand the review by including trials conducted with individuals with prevalent poor cognitive function or dementia. We identified seven relevant trials, four among cognitively healthy older people, and three among individuals with pre-existing cognitive decline or dementia, and overall conclude that there is no evidence to support the routine use of n-3 LCPs supplements for the prevention, or amelioration, of cognitive decline in later life. We identified several challenges in the design of intervention studies for the prevention of dementia and cognitive decline in older people that require careful consideration especially in recruitment and retention in long-term trials. Whether the lack of agreement in findings from mechanistic and observational data and from intervention studies reflects a real absence of benefit on cognitive function from n-3 LCP supplementation, or whether it reflects intrinsic limitations in the design of published studies remains open to question.

Omega-3 fatty acid supplementation studies are inconclusive. We performed two intervention studies. The first study (Berger et al 2007) was a double blind, placebo-controlled randomized trial comparing 2 g Ethyl-eicosapentaenoic acid (EPA) versus placebo in addition to antipsychotic medication in 79 first episode psychosis patients. Mixed model analysis suggests that EPA augmented first episode psychosis patients respond quicker compared to placebo for time to response (p = 0.06). Post hoc analysis for cumulative response rates confirm a higher response rate at week 6 (42.9% versus 17.6% for all subjects, p = .036; 54,2% versus 17.2% for non-affective psychosis, p = .008) that was not significant anymore at week 12 (potential ceiling effect). In the second study (Amminger et al, 2010) using 840 mg EPA and 700 mg docosahexaenoic acid per day as sole treatment in 81 prodromal adolescents only 1 of 38 UHR adolescents (2.6%) in the EPA/DHA group compared to 8 of 38 (21.1%) prodromal adolescents in the placebo group met exit criteria for psychotic disorder (Chi-square Fisher's exact test =6.2, df = 1, p = 0.028; OR = 9.9). The change from baseline on the PANSS total symptom score (p = 0.006), and the GAF score (p = 0.025) were also significant between the treatment groups showing a clinically relevant advantage of EPA/DHA over placebo. Stage of illness may be more relevant for the use of the benign treatments such as omega-3 fatty acids in emerging psychosis and explain previous inconclusive findings. Research designs for future omega-3 fatty acid intervention trials and potential pitfalls will be discussed.

This review summarises findings from studies in companion animals with chronic diseases receiving omega-3 supplementation. Investigated conditions included dermatopathies (dogs n = 7), osteoarthritis (dogs n = 7, cats n = 2), cardiovascular diseases (dogs n = 7), dyslipidaemias (dogs n = 1), gastroenteropathies (dogs n = 2), chronic kidney disease (dogs n = 2, cats n = 3), cognitive impairment (dogs n = 4, cats n = 1), and behavioural disorders (dogs n = 3). When possible, dosages were standardised to mg/kg using available data on food intake and EPA/DHA concentrations. The minimum and maximum ranges of EPA and DHA, along with their ratios, were as follows: for dermatology 0·99–43 mg/kg EPA and 0·66–30 mg/kg DHA (ratio 1·4–3·4); for osteoarthritis 48–100 mg/kg EPA and 20–32 mg/kg DHA (ratio 1·5–3·4); cardiology 27–54·2 mg/kg EPA and 18–40·6 mg/kg DHA (ratio 1·3–1·5); dyslipidaemia 58·8 mg/kg EPA and 45·4 mg/kg DHA (ratio 1·3); cognition (1/5 studies) 225 mg/kg EPA and 90 mg/kg DHA (ratio 2·5); behaviour (1/3) 31 mg/kg EPA and 45 mg/kg DHA (ratio 0·7). Nephrology and oncology studies lacked sufficient data for calculation. Gastrointestinal diseases do not appear to benefit from omega-3 supplementation, likely due to inflammation-related malabsorption, although few adverse effects were reported in dogs. Other enteropathy studies were low-quality (case reports/series). The lowest omega-6/omega-3 ratio with anti-inflammatory effect was 1:3·75, and the highest was 5·5:1. In conclusion, the reviewed EPA and DHA doses appear effective for atopic dermatitis, osteoarthritis, cardiac disease, hyperlipidaemia, and cognitive and behavioural disorders. Further research is needed to clarify efficacy in gastrointestinal and oncological conditions.