The health benefits of the long-chain omega-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been known for over 50 years and underpin the UK population recommendation to consume >450 mg EPA + DHA per day. These recommendations, last revised in 2004, are based mainly on epidemiological evidence. Much research has been conducted in the interim. Most randomised controlled trials (RCT) use doses of EPA + DHA of 840 mg/d or more. For anti-inflammatory, triacylglycerol-lowering and anti-hypertensive effects, >1.5 g EPA + DHA per day is needed. Cognitive benefits are also likely to require these higher intakes. Farmed salmon now contains considerably less EPA + DHA relative to farmed fish of 20 years ago, meaning one portion per week will no longer provide the equivalent of 450 mg EPA + DHA per day. Oily fish alone can only provide a fraction of the EPA + DHA required to meet global needs. Furthermore, there is low global oily fish consumption, with typical intakes of <200 mg EPA + DHA per day, and limited intakes in vegans and vegetarians. Therefore, there is an urgent need for affordable, acceptable, alternative EPA + DHA sources, including vegan/vegetarian friendly options, such as bio-enriched poultry, red meat and milk products; fortified foods; enriched oilseeds (for example, genetically modified Camelina sativa); algae and algal oils; and approaches which enhance endogenous EPA/DHA synthesis. In this narrative review, we suggest that current EPA + DHA intake recommendations are too low, consider EPA/DHA from a holistic health-sustainability perspective and identify research, policy and knowledge mobilisation areas which need attention.

Accumulation of exogenous fatty acids such as the long-chain n-11 MUFA cetoleic acid (CA, C22:1n-11) may induce functional changes, through direct effects or by affecting the amounts of other fatty acids through changes in catabolic and anabolic processes including desaturation of fatty acids or by other processes. The primary aim of this study was to investigate if dietary CA was absorbed and accumulated in a TAG-rich tissue for storage (white adipose tissue), a stable phospholipid-rich tissue (brain), metabolically active tissues (liver and skeletal muscle) or circulating in the blood (blood cells) and metabolised. Secondary aims included investigating any effects on the levels of EPA and DHA. Eighteen male Zucker diabetic Sprague Dawley (ZDSD) rats were fed diets with herring oil (HERO) containing 0·70 % CA or anchovy oil (ANCO) devoid of CA, or a control diet with soyabean oil for 5 weeks. The HERO and ANCO diets contained 0·35 and 0·37 wt% EPA + DHA, respectively. Data were analysed using one-way ANOVA. CA from dietary HERO was absorbed, and CA and two chain-shortened metabolites were found in blood cells, liver, white adipose tissue (WAT) and muscle, but n-11 MUFAs were not found in the brain. The concentrations of EPA and DHA were similar in liver lipids (TAG, cholesteryl esters and NEFA) as well as in WAT, muscle and brain from rats fed the HERO or ANCO diets. To conclude, CA was taken up by tissues but did not affect levels of EPA and DHA in this diabetic rat model.

In its 2023 revision of the social cost of carbon, the U.S. Environmental Protection Agency values people’s lives on the basis of their willingness to pay for them, without applying any distributional weights. It justifies this proposal on grounds of the Kaldor–Hicks criterion, which avoids interpersonal comparisons of wellbeing. But this criterion was discredited 70 years ago. Interpersonal comparisons of wellbeing cannot truly be avoided, and they should be used to determine distributional weights. One way of doing so is to identify as a numeraire a good that brings equal wellbeing to each person. A healthy life year is a reasonable, though only approximate, candidate for such a good. This article presents the point of view of a philosopher, regarding the practice of economists from outside the discipline.

This review aims to critically evaluate the efficacy of long-chain ո-3 PUFA ingestion in modulating muscle protein synthesis (MPS), with application to maintaining skeletal muscle mass, strength and function into later life. Ageing is associated with a gradual decline in muscle mass, specifically atrophy of type II fibres, that is exacerbated by periods of (in)voluntary muscle disuse. At the metabolic level, in otherwise healthy older adults, muscle atrophy is underpinned by anabolic resistance which describes the impaired MPS response to non-pharmacological anabolic stimuli, namely, physical activity/exercise and amino acid provision. Accumulating evidence implicates a mechanistic role for n-3 PUFA in upregulating MPS under stimulated conditions (post-prandial state or following exercise) via incorporation of EPA and DHA into the skeletal muscle phospholipid membrane. In some instances, these changes in MPS with chronic ո-3 PUFA ingestion have translated into clinically relevant improvements in muscle mass, strength and function; an observation evidently more prevalent in healthy older women than men. This apparent sexual dimorphism in the adaptive response of skeletal muscle metabolism to EPA and DHA ingestion may be related to a greater propensity for females to incorporate ո-3 PUFA into human tissue and/or the larger dose of ingested ո-3 PUFA when expressed relative to body mass or lean body mass. Future experimental studies are warranted to characterise the optimal dosing and duration of ո-3 PUFA ingestion to prescribe tailored recommendations regarding n-3 PUFA nutrition for healthy musculoskeletal ageing into later life.

Several meta-analyses investigating the efficacy of n-3 PUFA in alleviating depression symptoms have reported conflicting findings. In the present study, we aimed to perform an umbrella meta-analysis to provide a definite conclusion. A comprehensive systematic search of PubMed, Scopus, Embase, Web of Science and Cochrane Central Library was performed up to June 2021. Meta-analysis studies evaluating the effects of n-3 PUFA on depression symptoms were included. The quality of the included meta-analyses was assessed using AMSTAR questionnaire. Out of 101 studies, twenty-two studies with twenty-six effect sizes (ES) were eligible for inclusion. Sixteen ES showed significant improving effect of n-3 supplementation on depression symptoms among which eleven ES had small ES. The other studies observed no significant effect. Available evidence suggests that n-3 PUFA (EPA, DHA) supplementation could be considered as an effective add-on therapeutic approach in relieving depression symptoms.

The social cost of greenhouse gases is important in many regulatory impact analyses. However, calculations of the social cost of greenhouse gases are highly complex and periodically revisited. We offer seven recommendations to improve current estimates. These include recommendations to use both country-level and global measures of the social cost of greenhouse gases, to use country-specific values for monetizing climate damages, to represent uncertainties by reporting distributions instead of using only central values, and to conduct a temporal distributional analysis that shows the magnitudes of climate damages across generations. We also provide recommendations for the discount rates that should be used when estimating the social cost of greenhouse gases, and the appropriate discount rates for regulatory impact analyses that include the social cost of greenhouse gases.

The relationship between erythrocyte membrane n-3 PUFA and breast cancer risk is controversial. We aimed to examine the associations of erythrocyte membrane n-3 PUFA with odds of breast cancer among Chinese women by using a relatively large sample size. A case–control study was conducted including 853 newly diagnosed, histologically confirmed breast cancer cases and 892 frequency-matched controls (5-year interval). Erythrocyte membrane n-3 PUFA were measured by GC. Logistic regression and restricted cubic spline were used to quantify the association between erythrocyte membrane n-3 PUFA and odds of breast cancer. Erythrocyte membrane α-linolenic acid (ALA), docosapentaenoic acid (DPA) and total n-3 PUFA were inversely and non-linearly associated with odds of breast cancer. The OR values (95 % CI), comparing the highest with the lowest quartile (Q), were 0·57 (0·43, 0·76), 0·43 (0·32, 0·58) and 0·36 (0·27, 0·49) for ALA, DPA and total n-3 PUFA, respectively. Erythrocyte membrane EPA and DHA were linearly and inversely associated with odds of breast cancer ((EPA: ORQ4 v. Q1 (95 % CI) = 0·59 (0·45, 0·79); DHA: ORQ4 v. Q1 (95 % CI) = 0·50 (0·37, 0·67)). The inverse associations were observed between ALA and odds of breast cancer in postmenopausal women, and between DHA and oestrogen receptor+ breast cancer. This study showed that erythrocyte membrane total and individual n-3 PUFA were inversely associated with odds of breast cancer. Other factors, such as menopause and hormone receptor status, may warrant further investigation when examining the association between n-3 PUFA and odds of breast cancer.

Long-chain omega-3 polyunsaturated fatty acid (LC n-3 PUFA) supplements, rich in eicosapentaenoic acid and/or docosahexaenoic acid, are increasingly being recommended within athletic institutions. However, the wide range of doses, durations and study designs implemented across trials makes it difficult to provide clear recommendations. The importance of study design characteristics in LC n-3 PUFA trials has been detailed in cardiovascular disease research, and these considerations may guide LC n-3 PUFA study design in healthy cohorts. This systematic review examined the quality of studies and study design considerations used in evaluating the evidence for LC n-3 PUFA improving performance in physically trained adults. SCOPUS, PubMed and Web of Science electronic databases were searched to identify studies that supplemented LC n-3 PUFA in physically trained participants. Forty-six (n = 46) studies met inclusion. Most studies used a randomised control design. Risk of bias, assessed using the design-appropriate Cochrane Collaboration tool, revealed that studies had a predominant judgment of ‘some concerns’, ‘high risk’ or ‘moderate risk’ in randomised controlled, randomised crossover or non-randomised studies, respectively. A custom five-point quality assessment scale demonstrated that no study satisfied all recommendations for LC n-3 PUFA study design. This review has highlighted that the disparate range of study designs is likely contributing to the inconclusive state of outcomes pertaining to LC n-3 PUFA as a potential ergogenic aid. Further research must adequately account for the specific LC n-3 PUFA study design considerations, underpinned by a clear hypothesis, to achieve evidence-based dose, duration and composition recommendations for physically trained individuals.

Information on the Omega-3 Index (O3I) in the United Kingdom (UK) is scarce. The UK-Biobank (UKBB) contains data on total plasma n3-PUFA% and DHA% measured by NMR. The aim of our study was to create an equation to estimate the O3I (eO3I) from these data. We first performed an inter-laboratory experiment with 250 random blood samples in which the O3I was measured in erythrocytes by GC, and total n3 % and DHA% were measured in plasma by NMR. The best predictor of eO3I included both DHA% and a derived metric, the total n3 %–DHA%. Together these explained 65 % of the variability (r = 0·832, P < 0·0001). We then estimated the O3I in 117 108 UKBB subjects and correlated it with demographic and lifestyle variables in multivariable-adjusted models. The mean eO3I was 5·58 % (sd 2·35 %) in this UKBB cohort. Several predictors were significantly correlated with eO3I (all P < 0·0001). In general order of impact and with directionality (–, inverse and +, direct): oily-fish consumption (+), fish oil supplement use (+), female sex (+), older age (+), alcohol use (+), smoking (–), higher waist circumference and BMI (–), lower socioeconomic status and less education (–). Only 20·5 % of eO3I variability could be explained by predictors investigated, and oily fish consumption accounted for 7·0 % of that. With the availability of the eO3I in the UKBB cohort, we will be in a position to link risk for a variety of diseases with this commonly used and well-documented marker of n3-PUFA biostatus.

The present study evaluated the effects of increasing the dietary levels of EPA and DHA in Atlantic salmon (Salmo salar) reared in sea cages, in terms of growth performance, welfare, robustness and overall quality. Fish with an average starting weight of 275 g were fed one of four different diets containing 10, 13, 16 and 35 g/kg of EPA and DHA (designated as 1·0, 1·3, 1·6 and 3·5 % EPA and DHA) until they reached approximately 5 kg. The 3·5 % EPA and DHA diet showed a significantly beneficial effect on growth performance and fillet quality compared with all other diets, particularly the 1 % EPA and DHA diet. Fish fed the diet containing 3·5 % EPA and DHA showed 400–600 g higher final weights, improved internal organ health scores and external welfare indicators, better fillet quality in terms of higher visual colour score and lower occurrence of dark spots and higher EPA and DHA content in tissues at the end of the feeding trial. Moreover, fish fed the 3·5 % EPA and DHA diet showed lower mortality during a naturally occurring cardiomyopathy syndrome outbreak, although this did not reach statistical significance. Altogether, our findings emphasise the importance of dietary EPA and DHA to maintain good growth, robustness, welfare and fillet quality of Atlantic salmon reared in sea cages.

Atlantic salmon were fed diets containing graded levels of EPA + DHA (1·0, 1·3, 1·6 and 3·5 % in the diet) and one diet with 1·3 % of EPA + DHA with reduced total fat content. Fish were reared in sea cages from about 275 g until harvest size (about 5 kg) and were subjected to delousing procedure (about 2·5 kg), with sampling pre-, 1 h and 24 h post-stress. Delousing stress affected plasma cortisol and hepatic mRNA expression of genes involved in oxidative stress and immune response, but with no dietary effects. Increasing EPA + DHA levels in the diet increased the trace mineral levels in plasma and liver during mechanical delousing stress period and whole body at harvest size. The liver Se, Zn, Fe, Cu, and Mn and plasma Se levels were increased in fish fed a diet high in EPA + DHA (3·5 %) upon delousing stress. Furthermore, increased dietary EPA + DHA caused a significant increase in mRNA expression of hepcidin antimicrobial peptide (HAMP), which is concurrent with downregulated transferrin receptor (TFR) expression levels. High dietary EPA + DHA also significantly increased the whole-body Zn, Se, and Mn levels at harvest size fish. Additionally, the plasma and whole-body Zn status increased, respectively, during stress and at harvest size in fish fed reduced-fat diet with less EPA + DHA. As the dietary upper limits of Zn and Se are legally added to the feeds and play important roles in maintaining fish health, knowledge on how the dietary fatty acid composition and lipid level affect body stores of these minerals is crucial for the aquaculture industry.

Portugal has high fish/seafood consumption, which may have both risks and benefits. This study aims to quantify the net health impact of hypothetical scenarios of fish/seafood consumption in the Portuguese population using a risk–benefit assessment methodology. Consumption data from the National Food, Nutrition and Physical Activity Survey 2015–2016 (n 5811) were used to estimate the mean exposure to methylmercury and EPA + DHA in the current and the alternative scenarios considered. Alternative scenarios (alt) were modelled using probabilistic approaches to reflect substitutions from the current consumption in the type of fish/seafood (alt1: excluding predatory fishes; alt2: including only methylmercury low-level fishes) or in the frequency of weekly fish/seafood consumption (alt3 to alt6: 1, 3, 5 or 7 times a week, replacing fish/seafood meals with meat or others). The overall health impact of these scenarios was quantified using disability-adjusted life years (DALY). In the Portuguese population, about 11 450 DALY could be prevented each year if the fish/seafood consumption increased to a daily basis. However, such a scenario would result in 1398 extra DALY considering the consumption by pregnant women and the respective risk on fetal neurodevelopment. Our findings support a recommendation to increase fish/seafood consumption up to 7 times/week. However, for pregnant women and children, special considerations must be proposed to avoid potential risks on fetal neurodevelopment due to methylmercury exposure.

With growing and ageing populations, the incidence of dementia is expected to triple globally by 2050. In the absence of effective drugs to treat or reverse the syndrome, dietary approaches which prevent or delay disease onset have considerable population health potential. Prospective epidemiological studies and mechanistic insight from experimental models strongly support a positive effect of a high fish and long chain n-3 fatty acid (EPA and DHA) intake on a range of cognitive outcomes and dementia risk, with effect sizes equivalent to several years of ageing between the highest and lowest consumers. As reviewed here, an effect of EPA and DHA on neuroinflammation and oxylipin production is likely to in part mediate the neurophysiological benefits. However, randomised controlled trials (RCTs) with EPA and DHA supplementation have produced mixed findings. Insight into the likely modulators of response to intervention and factors which should be considered for future RCTs are given. Furthermore, the impact of APOE genotype on disease risk and response to EPA and DHA supplementation is summarised. The prevalence of dementia is several-fold higher in APOE4 females (about 13% Caucasian populations) relative to the general population, who are emerging as a subgroup who may particularly benefit from DHA intervention, prior to the development of significant pathology.

EPA and DHA are essential for maternal and fetal health, but epidemiological data are sparse in China. We examined the trends of EPA alone and a combination of EPA plus DHA in pregnant and lactating women in three distinct geographic regions in China and explored their potential influencing factors. A total of 1015 healthy women during mid-pregnancy, late pregnancy or lactation were recruited from Weihai (coastland), Yueyang (lakeland) and Baotou (inland) cities of China between May and July of 2014. Maternal EPA and DHA concentrations (percentage of total fatty acids) in plasma and erythrocytes were measured by capillary GC. Adjusted EPA plus DHA concentrations in both plasma and erythrocytes significantly declined from mid-pregnancy (2·92 %, 6·95 %) to late pregnancy (2·20 %, 6·42 %) and lactation (2·40 %, 6·29 %) (Ptrend < 0·001); and both concentrations were highest in coastland, followed by lakeland, and lowest in inland (P < 0·001). Regarding EPA alone, the concentrations were higher in women during lactation or late pregnancy and in women in coastland and inland areas. Moreover, concentrations of EPA or EPA plus DHA were higher in women with older age, higher education, higher annual family income per capita and higher dietary intake of marine aquatic product and mutton. In lactating women, erythrocyte EPA concentration was higher in those having breast-feeding partially v. exclusively. In conclusion, maternal plasma and erythrocyte concentrations of EPA plus DHA or EPA alone differed with geographic regions, physiological periods and maternal characteristics, indicating a need of population-specific health strategies to improve fatty acids status in pregnant and lactating women.

This study assessed the molecular mechanism of EPA or DHA protection against intestinal porcine epithelial cell line 1 (IPEC-1) cell damage induced by deoxynivalenol (DON). The cells were divided into six groups, including the CON group, the EPA group, the DHA group, the DON group, the EPA + DON group and the DHA + DON group. RNA sequencing was used to investigate the potential mechanism, and qRT-PCR was employed to verify the expression of selected genes. Changes in ultrastructure were used to estimate pathological changes and endoplasmic reticulum (ER) injury in IPEC-1 cells. Transferrin receptor 1 (TFR1) was tested by ELISA. Fe2+ and malondialdehyde (MDA) contents were estimated by spectrophotometry, and reactive oxygen species (ROS) was assayed by fluorospectrophotometry. RNA sequencing analysis showed that EPA and DHA had a significant effect on the expression of genes involved in ER stress and iron balance during DON-induced cell injury. The results showed that DON increased ER damage, the content of MDA and ROS, the ratio of X-box binding protein 1s (XBP-1s)/X-box binding protein 1u (XBP-1u), the concentration of Fe2+ and the activity of TFR1. However, the results also showed that EPA and DHA decreased the ratio of XBP-1s/XBP-1u to relieve DON-induced ER damage of IPEC-1 cells. Moreover, EPA and DHA (especially DHA) reversed the factors related to iron balance. It can be concluded that EPA and DHA reversed IPEC-1 cell damage induced by DON. DHA has the potential to protect IPEC-1 cells from DON-induced iron imbalance by inhibiting ER stress.

Aspirin (acetylsalicylic acid, ASA) is inexpensive and is established in preventing cardiovascular disease (CVD) and colorectal adenomas. Omega-3 (n3) polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have also shown benefit in preventing CVD. The combination could be an effective preventative measure in patients with such diseases. ASA and n3 PUFA reduced the risk of CVD in ASA-resistant or diabetic patients. EPA- and DHA-deficient patients also benefited the most from n3 PUFA supplementation. Synergistic effects between ASA and EPA and DHA are ‘V-shaped’ such that optimal ASA efficacy is dependent on EPA and DHA concentrations in blood. In colorectal adenomas, ASA (300 mg/d) and EPA reduced adenoma burden in a location- and subtype-specific manner. Low doses of ASA (75–100 mg/d) were used in CVD prevention; however, ultra-low doses (30 mg/d) can also reduce thrombosis. EPA-to-DHA ratio is also important with regard to efficacy. DHA is more effective in reducing blood pressure and modulating systemic inflammation; however, high-dose EPA can lower CVD events in high-risk individuals. Although current literature has yet to examine ASA and DHA in preventing CVD, such combination warrants further investigation. To increase adherence to ASA and n3 PUFA supplementation, combination dosage form may be required to improve outcomes.

The present study aimed to evaluate the effects of different supplemental fat sources (soyabean oil (SBO) as a source of n-6 fatty acid (FA) and fish oil (FO) as a source of n-3 FA) in the starter feed of milk-fed dairy calves during the hot season. Forty Holstein calves (3 d of age; 39·67 kg of body weight; ten calves per group) were randomly assigned to the experimental treatments as follows: (1) starter feed supplemented with no fat source (CON), (2) starter feed supplemented with 3 % SBO (DM basis), (3) starter feed supplemented with 3 % FO (DM basis) and (4) starter feed supplemented with an equal mixture of SBO and FO (1·5 % each, DM basis). The milk feeding schedule was constant for treatments and all calves were weaned on day 65 of age. Results show that calves had greater starter intake, average daily gain and body length when fed SBO compared with the other treatments. However, feed efficiency was increased and inflammatory indicators (TNF-α, serum amyloid A and haptoglobin) concentrations were reduced in the calves fed FO compared with the other treatments. In summary, it was revealed that SBO rich in n-6 FA improved starter intake and growth performance, while FO rich in n-3 FA could improve the immune function of calves. Due to the current experimental condition, an equal mixture of SBO and FO (1·5 % each, DM basis) can be recommended to have an optimum growth performance and immune function while the calves are reared under the heat conditions.