The objective of this study is to establish a methodological proposal in order to carry out qualitative systematic reviews and apply these findings to a review of Omega-3 Fatty Acids with respect to health and illness. Based on a methodological proposal, a general protocol was developed to provide a sound basis for the preparation of the reviews in this journal supplement. A systematic technique was proposed in order to revise the existing scientific literature on Omega-3 Fatty Acids, with particular emphasis on aspects relating to health and illness. The aim of qualitative systematic reviews is to collate and summarise the results of the primary studies reviewed which will be carried out through a descriptive synthesis. It can be concluded that systematic reviews provide a summary of the existing primary documents on a specific scientific question. The detailed and explicit methods used lead to the identification, critical evaluation and synthesis of the scientific literature. Furthermore, both bias and random effects are reduced, resulting in more reliable data from which to draw conclusions and make recommendations to support decision-making.

Dietary fat and its effects on health and disease has attracted interest for research and Public Health. Since the 1980s many bodies and organizations have published recommendations regarding fat intake. In this paper different sets of recommendations are analyzed following a systematic review process to examine dietary reference intakes, nutritional goals and dietary guidelines for fat and fatty acids. A literature search was conducted in relevant literature databases along a search for suitable grey literature reports. Documents were included if they reported information on either recommended intake levels or dietary reference values or nutritional objectives or dietary guidelines regarding fat and/or fatty acids and/or cholesterol intake or if reported background information on the process followed to produce the recommendations. There is no standard approach for deriving nutrient recommendations. Recommendations vary between countries regarding the levels of intake advised, the process followed to set the recommendations. Recommendations on fat intake share similar figures regarding total fat intake, saturated fats and trans fats. Many sets do not include a recommendation about cholesterol intake. Most recent documents provide advice regarding specific n-3 fatty acids. Despite efforts to develop evidence based nutrient recommendations and dietary guidelines that may contribute to enhance health, there are still many gaps in research. It would be desirable that all bodies concerned remain transparent about the development of dietary recommendations. In order to achieve this, the type of evidence selected to base the recommendations should be specified and ranked. Regular updates of such recommendations should be planned.

Omega 3 fatty acids can be obtained from several sources, and should be added to the daily diet to enjoy a good health and to prevent many diseases. Worldwide, general population use omega-3 fatty acid supplements and enriched foods to get and maintain adequate amounts of these fatty acids. The aim of this paper was to review main scientific evidence regarding the public health risks and benefits of the dietary sources of omega-3 fatty acids. A systematic literature search was performed, and one hundred and forty-five articles were included in the results for their methodological quality. The literature described benefits and risks of algal, fish oil, plant, enriched dairy products, animal-derived food, krill oil, and seal oil omega-3 fatty acids.

Over the last few decades n-3 long chain polyunsaturated fatty acid status became of special interest for scientists. Biochemical measures on the n-3 fatty acid status vary depending on body compartment assessed and measures chosen. Plasma phospholipids and red blood cell membrane phospholipids are mainly used as n-3 fatty acid status marker. The conventional analysis of phospholipid fatty acids involves lipid extraction and consecutive chromatographic separation of phospholipids from other lipid fractions, which is time-consuming and costly. In recent years, different investigators have tried to overcome these limitations by using other biological markers or by modifying the analytical procedures used to assess n-3 fatty acid status. The aim of this systematic review was to provide an overview on these novel analytical methods developed for the fatty acid quantification by gas chromatography, highlights the methodological limitations, and discusses advantages or disadvantages of the biological markers used. Seventeen papers were identified that fulfilled the inclusion criteria. New opportunities arise from sensitive and precise high-throughput methodologies for assessment of plasma total lipid and plasma glycerophospholipid fatty acids, as well as cheek cell fatty acid composition.

The aims of the present study were to review the validity of dietary methods used to measure the usual long chain (LC) omega-3 polyunsaturated fatty acid (n-3 PUFA) intake of a population and to assess the usefulness of different biomarkers of n-3 PUFA in healthy humans. Two systematic literature searches were conducted until May 2011 to update previous systematic reviews. The first literature search aimed to find studies validating the methodology used for measuring the dietary intake of n-3 PUFA. The second search aimed to find human intervention studies in which n-3 PUFA status changed after 2 weeks of n-3 PUFA supplementation. Sixteen studies were identified for inclusion in the first review. Correlation coefficients between fatty acids in subcutaneous fat or blood lipids and dietary intake of n-3 PUFA from different questionnaires were similar. Subcutaneous fat has been reported as the best reference method for some authors, and these studies showed moderate correlation coefficients with no dietary intake method being superior to any other. As for the evaluation of biomarkers of docosahexaenoic acid (DHA, 22 : 6 n-3) and eicosapentaenoic acid (EPA, 20 : 5n-3) status in response to supplementation, the new search reaffirmed and reinforced the evidence supporting that plasma phospholipid DHA, erythrocyte DHA, and platelet DHA were all effective and robust biomarkers of DHA status. Our findings only confirmed earlier studies and did not provide evidence for reaching new conclusions.

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.

The aim of this review is to evaluate the effects of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) supplementation in pregnant and lactating women and infants during postnatal life, on the visual acuity, psychomotor development, mental performance and growth of infants and children. Eighteen publications (11 sets of randomized control clinical trial [RCTs]) assessed the effects of the n-3 LCPUFA supplementation during pregnancy on neurodevelopment and growth, in the same subjects at different time points; 4 publications (2 data sets from RCTs) addressed physiological responses to n-3 LCPUFA supplementation during pregnancy & lactation and 5 publications (3 data sets from RCTs) exclusively during lactation. Some of these studies showed beneficial effects of docosahexaenoic acid (DHA) supplementation during pregnancy and/or lactation especially on visual acuity outcomes and some on long-term neurodevelopment; a few, showed positive effects on growth. There were also 15 RCTs involving term infants who received infant formula supplemented with DHA, which met our selection criteria. Many of these studies claimed a beneficial effect of such supplementation on visual, neural, or developmental outcomes and no effects on growth. Although new well designed and conducted studies are being published, evidence from RCTs does not demonstrate still a clear and consistent benefit of n-3 LCPUFA supplementation during pregnancy and/or lactation on term infants growth, neurodevelopment and visual acuity. These results should be interpreted with caution due to methodological limitations of the included studies.

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.

A systematic review to identify studies reporting the effects of n-3 long chain polyunsaturated fatty acids (LCPUFA) intake, during pregnancy and postnatally, on infants and young children's body composition was performed. A structured search strategy was performed in the MEDLINE (PubMed), EMBASE, and LILACS databases. Inclusion and exclusion criteria were defined according to the research question. Only those studies addressing the relationship between n-3 LCPUFA exposure during the perinatal period and later adiposity measured in terms of weight, height, body mass index (BMI), skinfold thickness and/or circumferences were included regardless of the study design. Studies quality was scored and were thereafter categorised into those reporting on maternal intake of n-3 LCPUFA during pregnancy or lactation (6 publications) or on infant's n-3 LCPUFA intake (7 publications). Two studies showed inverse associations between maternal n-3 LCPUFA intake and children's later body composition (lower adiposity, BMI or body weight), two showed direct associations and no effects were observed in the remaining two studies. Among those studies focusing on n-3 LCPUFA intake through enriched infant formulas; three observed no effect on later body composition and two showed higher weight and adiposity with increased amounts of n-3 LCPUFA. Reversely, in two studies weight and fat mass decreased. In conclusion, reported body composition differences in infants and young children were not clearly explained by perinatal n-3 LCPUFA intake via supplemented formulas, breastfeeding or maternal intakes of n-3 LCPUFA during pregnancy and lactation. Associated operational mechanisms including n-3 LCPUFA doses and sources applied are not sufficiently explained and therefore no conclusions could be made.

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.

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.

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.

Inflammation is part of the normal host response to infection and injury. Eicosanoids, cytokines, chemokines, adhesion molecules and other inflammatory molecules are frequently produced during this process. Numerous studies in humans have documented the inflammation-limiting properties of omega-3 fatty acids, but only a few have been randomised clinical trials. The aim of this study was to perform a systematic search of randomised clinical trials on omega-3 fatty acids and inflammatory biomarkers in all subjects including healthy and ill persons up to February 2011 using PubMed and LILACS databases, defined by a specific equation using MeSH terms and limited to randomised clinical trials; there was no any a priori decision to include some diseases and not others. The quality of each publication was validated by using the JADAD scale and the CONSORT checklist. Inflammatory biomarkers were considered as primary outcomes. Twenty-six publications of the last 10 years were selected. Studies included healthy subjects and patients with cardiovascular disease and other chronic and acute diseases; all reported the number of subjects, type of study, type and doses of omega-3 fatty acids, main outcomes and major inflammatory biomarkers. Dietary omega-3 fatty acids are associated with plasma biomarker levels, reflecting lower levels of inflammation and endothelial activation in cardiovascular disease and other chronic and acute diseases, including chronic renal disease, sepsis and acute pancreatitis. However, further research is required before definitive recommendations can be made about the routine use of omega-3 fatty acids in critically ill patients or with neurodegenerative or chronic renal disease.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of the joints and bones. The n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (ARA) is the precursor of inflammatory eicosanoids which are involved in RA. Some therapies used in RA target ARA metabolism. Marine n-3 PUFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) found in oily fish and fish oils decrease the ARA content of cells involved in immune responses and decrease the production of inflammatory eicosanoids from ARA. EPA gives rise to eicosanoid mediators that are less inflammatory than those produced from ARA and both EPA and DHA give rise to resolvins that are anti-inflammatory and inflammation resolving, although little is known about these latter mediators in RA. Marine n-3 PUFAs can affect other aspects of immunity and inflammation relevant to RA, including dendritic cell and T cell function and production of inflammatory cytokines and reactive oxygen species, although findings for these outcomes are not consistent. Fish oil has been shown to slow the development of arthritis in animal models and to reduce disease severity. A number of randomised controlled trials of marine n-3 PUFAs have been performed in patients with RA. A systematic review included 23 studies. Evidence is seen for a fairly consistent, but modest, benefit of marine n-3 PUFAs on joint swelling and pain, duration of morning stiffness, global assessments of pain and disease activity, and use of non-steroidal anti-inflammatory drugs.

Metabolic syndrome (MS) is characterised by accumulation of CVD risk factors. The use of very long chain n-3 polyunsaturated fatty acids (VLC n3 PUFA) could potentially benefit MS by reducing risk factors. To better understand the possible VLC n3 PUFA benefits, the literature was systematically reviewed for randomised controlled trials (RCT) that published effects of VLC n3 PUFA on MS patients. 17 RCT fulfilled the inclusion criteria and were analysed for relevance to the research question. The available RCT convincingly show that the administration of VLC n3 PUFA doses > 1 g for at least 3 months produces a significant reduction of triglycerides ranging from 7 % to 25 %. These results confirm the hypotriglyceridemic effect of VLC n3 PUFA in MS patients. The triglyceride lowering may produce further benefits by reducing the % of pro-atherogenic small dense LDL particles (sdLDL) and also perhaps by ameliorating the inflammatory process associated with MS. High doses of VLC n3 PUFA ( ≥ 3 g/day) may produce further TAG reductions but could raise other risk factors such as LDL-C. No clear effects were found on other MS markers. The combination of VLC n3 PUFA plus a statin may be useful to prevent the occurrence of coronary events. More studies are needed using different amounts of VLC n3 PUFA, time lengths, dietary backgrounds and different profiles of MS patients before clear recommendations can be made.

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.

Introduction: Cardiovascular disease remains the commonest health problem in developed countries, and residual risk after implementing all current therapies is still high. The use of marine omega-3 fatty acids (DHA and EPA) has been recommended to reduce cardiovascular risk by multiple mechanisms. Objectives: To update the current evidence on the influence of omega-3 on the rate of cardiovascular events. Review Methods: We used the MEDLINE and EMBASE databases to identify clinical trials and randomized controlled trials of omega-3 fatty acids (with quantified quantities) either in capsules or in dietary intake, compared to placebo or usual diet, equal to or longer than 6 months, and written in English. The primary outcome was a cardiovascular event of any kind and secondary outcomes were all-cause mortality, cardiac death and coronary events. We used RevMan 5·1 (Mantel-Haenszel method). Heterogeneity was assessed by the I2 and Chi2 tests. We included 21 of the 452 pre-selected studies. Results: We found an overall decrease of risk of suffering a cardiovascular event of any kind of 10 % (OR 0·90; [0·85–0·96], p = 0·001), a 9 % decrease of risk of cardiac death (OR 0·91; [0·83–0·99]; p = 0·03), a decrease of coronary events (fatal and non-fatal) of 18 % (OR 0·82; [0·75–0·90]; p < 1 × 10− 4), and a trend to lower total mortality (5 % reduction of risk; OR 0·95; [0·89–1·02]; p = 0·15. Most of the studies analyzed included persons with high cardiovascular risk. Conclusions: marine omega-3 fatty acids are effective in preventing cardiovascular events, cardiac death and coronary events, especially in persons with high cardiovascular risk.

The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from seafood sources (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant sources (alpha-linolenic acid, ALA) and risk of type 2 diabetes mellitus (DM) remains unclear. We systematically searched multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of DM. Data were independently extracted in duplicate by 2 investigators, including multivariate-adjusted relative risk (RR) estimates and corresponding 95 % CI. Generalized least-squares trend estimation was used to assess dose–response relationships, with pooled summary estimates calculated by both fixed-effect and random-effect models. From 288 identified abstracts, 16 studies met inclusion criteria, including 18 separate cohorts comprising 540 184 individuals and 25 670 cases of incident DM. Consumption of fish and/or seafood was not significantly associated with DM (n = 13 studies; RR per 100 g/d = 1·12, 95 % CI = 0·94, 1·34); nor were consumption of EPA+DHA (n = 16 cohorts; RR per 250 mg/d = 1·04, 95 % CI = 0·97, 1·10) nor circulating levels of EPA+DHA biomarkers (n = 5 cohorts; RR per 3 % of total fatty acids = 0·94, 95 % CI = 0·75, 1·17). Both dietary ALA (n = 7 studies; RR per 0·5 g/d = 0·93, 95 % CI = 0·83, 1·04) and circulating ALA biomarker levels (n = 6 studies; RR per 0·1 % of total fatty acid = 0·90, 95 % CI = 0·80, 1·00, P = 0·06) were associated with non-significant trend towards lower risk of DM. Substantial heterogeneity (I2~80 %) was observed among studies of fish/seafood or EPA+DHA and DM; moderate heterogeneity ( < 55 %) was seen for dietary and biomarker ALA and DM. In unadjusted meta-regressions, study location (Asia vs. North America/Europe), mean BMI, and duration of follow-up each modified the association between fish/seafood and EPA+DHA consumption and DM risk (P-interaction ≤ 0·02 each). We had limited statistical power to determine the independent effect of these sources of heterogeneity due to their high collinearity. The overall pooled findings do not support either major harms or benefits of fish/seafood or EPA+DHA on development of DM, and suggest that ALA may be associated with modestly lower risk. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation.

Experimental models showed consistently a modulation of carcinogenesis by omega 3 polyunsaturated fatty acids (ω3 PUFA). Fish intake is often described as part of a beneficial dietary pattern. However, observational epidemiological studies on the relationship between ω3 PUFA reported conflicting results. The objective of this systematic review is to determine whether there exists any progress in the evaluation of the causal relationship between dietary ω3 PUFA and cancers since the previous FAO/OMS expert consultation and whether it is possible to propose preventive and/or adjuvant therapeutic recommendations. Prospective and case-control observational studies published since 2007 and meeting validity criteria were considered together with RCT. Experimental studies are mentioned to provide for biological plausibility. When evaluating the level of evidence, a portfolio approach was used, weighted by a hierarchy giving higher importance to prospective studies followed by RCT if any. There is a probable level of evidence that ALA per se is neither a risk factor nor a beneficial factor with regards to cancers. Observational studies on colorectal, prostate and breast cancers only provided limited evidence suggesting a possible role of LC-ω3PUFA in cancer prevention because insufficient homogeneity of the observations. Explanation for heterogeneity might be the inherent difficulties associated with epidemiology (confounding and dietary pattern context, measurement error, level of intake, genetic polymorphism). The role of LC-ω3PUFA as adjuvant, might be considered of possible use, in view of the latest RCT on lung cancers even if RCT on other cancers still need to be undertaken.