N-3 polyunsaturated fatty acids (n-3 PUFAs) delivered by fish oil supplements alter the number and functions of circulating extracellular vesicles (EVs), but consumption of oily fish does not reproduce this effect. In order to assess the effects of fish oil supplements and oily fish, at a level achievable in the diet, on EV numbers, composition and procoagulant activity in healthy human volunteers, forty-two healthy subjects were assigned to one of three treatment groups: (i) fish oil supplements plus white fish meals, (ii) control supplements plus oily fish meals or (iii) control supplements plus white fish meals for 12 weeks in a randomized, double-blind, placebo-controlled, parallel trial; circulating EVs were enumerated and their procoagulant activity assessed using thrombin generation and fibrinolysis assays. Our results showed that fish oil supplements decreased circulating EV numbers and reduced EV-stimulated thrombin generation, but the consumption of oily fish at half the dose of EPA had no effect on either EV number or thrombogenic capacity. Consumption of both oily fish and fish oil supplements increased the EPA and DHA contents of EVs and the proportion of EPA in circulating EVs was strongly associated with EV-stimulated thrombin generation. This study revealed that the additional 1 g/d EPA delivered in the fish oil supplements is required to decrease the numbers and thrombogenic capacity of EVs, since oily fish at a level achievable in the diet had no effect. Increasing EPA intake beyond current guidelines for oily fish consumption may therefore be required for cardiovascular benefits relating to EVs.

Epidemiological and clinical trial evidence indicates that n-6 polyunsaturated fatty acid (PUFA) intake is cardioprotective. Nevertheless, claims that n-6 PUFA intake promotes inflammation and oxidative stress prevail. This narrative review aims to provide health professionals with an up-to-date evidence overview to provide the requisite background to address patient/client concerns about oils containing predominantly unsaturated fatty acids (UFA), including MUFA and PUFA. Edible plant oils, commonly termed vegetable oils, are derived from vegetables, nuts, seeds, fruits and cereal grains. Substantial variation exists in the fatty acid composition of these oils; however, all are high in UFA, while being relatively low in saturated fatty acids (SFA), except for tropical oils. Epidemiological evidence indicates that higher PUFA intake is associated with lower risk of incident CVD and type 2 diabetes mellitus (T2DM). Additionally, replacement of SFA with PUFA is associated with reduced risk of CVD and T2DM. Clinical trials show higher intake of UFA from plant sources improves major CVD risk factors, including reducing levels of atherogenic lipids and lipoproteins. Importantly, clinical trials show that increased n-6 PUFA (linoleic acid) intake does not increase markers of inflammation or oxidative stress. Evidence-based guidelines from authoritative health and scientific organisations recommend intake of non-tropical vegetable oils, which contain MUFA and n-6 PUFA, as part of healthful dietary patterns. Specifically, vegetable oils rich in UFA should be consumed instead of rich sources of SFA, including butter, tallow, lard, palm and coconut oils.

This review will provide an overview of the immune system and then describe the effects of frailty, obesity, specific micronutrients and the gut microbiota on immunity and susceptibility to infection including data from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic where relevant. A key role for the immune system is providing host defence against pathogens. Impaired immunity predisposes to infections and to more severe infections and weakens the response to vaccination. A range of nutrients, including many micronutrients, play important roles in supporting the immune system to function. The immune system can decline in later life and this is exaggerated by frailty. The immune system is also weakened with obesity, generalised undernutrition and micronutrient deficiencies, which all result in increased susceptibility to infection. Findings obtained during the SARS-CoV-2 pandemic support what was already known about the effects of ageing, frailty and obesity on immunity and susceptibility to infection. Observational studies conducted during the pandemic also support previous findings that multiple micronutrients including vitamins C, D and E, zinc and selenium and long-chain n-3 fatty acids are important for immune health, but whether these nutrients can be used to treat those already with coronavirus disease discovered in 2019 (COVID-19), particularly if already hospitalised, is uncertain from current inconsistent or scant evidence. There is gut dysbiosis in patients with COVID-19 and studies with probiotics report clinical improvements in such patients. There is an inverse association between adherence to a healthy diet and risk of SARS-CoV-2 infection and hospitalisation with COVID-19 which is consistent with the effects of individual nutrients and other dietary components. Addressing frailty, obesity and micronutrient insufficiency will be important to reduce the burden of future pandemics and nutritional considerations need to be a central part of the approach to preventing infections, optimising vaccine responses and promoting recovery from infection.

N-3 long-chain PUFA (LC-PUFA) and probiotics are generally considered to induce health benefits. The objective was to investigate (1) the impact of fish oil and/or probiotics on serum fatty acids (sFA), (2) the interaction of sFA with low-grade inflammation and (3) the relation of sFA to the onset of gestational diabetes mellitus (GDM). Pregnant women with overweight/obesity were allocated into intervention groups with fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo in early pregnancy (fish oil: 1·9 g DHA and 0·22 g EPA, probiotics: Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 CFU, each daily). Blood samples were collected in early (n 431) and late pregnancy (n 361) for analysis of fatty acids in serum phosphatidylcholine (PC), cholesteryl esters (CE), TAG and NEFA with GC and high-sensitivity C-reactive protein and GlycA by immunoassay and NMR spectroscopy, respectively. GDM was diagnosed according to 2 h 75 g oral glucose tolerance test. EPA in PC, CE and TAG and DHA in PC, CE, TAG and NEFA were higher in fish oil and fish oil + probiotics groups compared with placebo. EPA in serum NEFA was lower in women receiving probiotics compared with women not receiving. Low-grade inflammation was inversely associated with n-3 LC-PUFA, which were related to an increased risk of GDM. Fish oil and fish oil + probiotics consumption increase serum n-3 LC-PUFA in pregnant women with overweight/obesity. Although these fatty acids were inversely related to inflammatory markers, n-3 LC-PUFA were linked with an increased risk for GDM.

PUFA modulate immune function and have been associated with the risk of childhood atopy and asthma. We investigated the effect of maternal fat intake in mice on PUFA status, elongase and desaturase gene expression, inflammatory markers and lung function in the offspring. C57BL/6J mice (n 32) were fed either standard chow (C, 20·4 % energy as fat) or a high-fat diet (HFD, 39·9 % energy as fat) for 4 weeks prior to conception and during gestation and lactation. At 21 d of age, offspring were weaned onto either the HFD or C, generating four experimental groups: C/C, C/HF, HF/C and HF/HF. Plasma and liver fatty acid composition were measured by GC and gene expression by quantitative PCR. Lung resistance to methacholine was assessed. Arachidonic acid concentrations in offspring plasma and liver phospholipids were increased by HFD; this effect was greater in the post-natal HFD group. DHA concentration in offspring liver phospholipids was increased in response to HFD and was higher in the post-natal HFD group. Post-natal HFD increased hepatic fatty acid desaturase (FADS) 2 and elongation of very long-chain fatty acid 5 expression in male offspring, whereas maternal HFD elevated expression of FADS1 and FADS2 in female offspring compared with males. Post-natal HFD increased expression of IL-6 and C-C motif chemokine ligand 2 (CCL2) in perivascular adipose tissue. The HFD lowered lung resistance to methacholine. Excessive maternal fat intake during development modifies hepatic PUFA status in offspring through regulation of gene expression of enzymes that are involved in PUFA biosynthesis and modifies the development of the offspring lungs leading to respiratory dysfunction.

A glyceride mixture of monoglyceride, diglyceride and TAG increases solubilisation and enhances emulsification of n-3 fatty acid (FA)-containing lipids in the stomach. This allows for better access of digestive enzymes, pivotal for the release of bioactive n-3 FA. The objective was to compare the effect of a glyceride formulation and an ethyl ester formulation of EPA + DHA on concentrations of EPA and DHA in plasma following single dosing. We conducted a double-blind crossover trial in which twenty healthy adults aged 50–70 years consumed a single dose (2·8 g EPA + DHA) of each EPA + DHA formulation without a meal in random order separated by a 2-week washout period. EPA and DHA were measured in plasma total lipid over the following 12 h. EPA and DHA in plasma total lipid increased over 12 h with both formulations. A 10-fold greater Δ concentration of EPA, 3-fold greater Δ concentration of DHA and 5-fold greater Δ concentration of EPA + DHA were seen with the glyceride-EPA + DHA. The time at which the maximal concentrations of n-3 FA occurred was 4 h earlier for EPA, 1 h earlier for DHA and 2 h earlier for EPA + DHA when consuming glyceride-EPA + DHA. A mixture of monoglyceride, diglyceride and TAG results in greater and faster incorporation of EPA and DHA into blood plasma lipid in the absence of a fatty meal. This may provide benefit to individuals on a low-fat diet or with digestive impairments and could result in greater efficacy in clinical trials using n-3 FA.

Inflammation is a normal part of the immune response and should be self-limiting. Excessive or unresolved inflammation is linked to tissue damage, pathology and ill health. Prostaglandins and leukotrienes produced from the n-6 fatty acid arachidonic acid are involved in inflammation. Fatty acids may also influence inflammatory processes through mechanisms not necessarily involving lipid mediators. The n-3 fatty acids EPA and DHA possess a range of anti-inflammatory actions. Increased content of EPA and DHA in the membranes of cells involved in inflammation has effects on the physical nature of the membranes and on the formation of signalling platforms called lipid rafts. EPA and DHA interfere with arachidonic acid metabolism which yields prostaglandins and leukotrienes involved in inflammation. EPA gives rise to weak (e.g. less inflammatory) analogues and both EPA and DHA are substrates for the synthesis of specialised pro-resolving mediators. Through their effects on early signalling events in membranes and on the profile of lipid mediators produced, EPA and DHA alter both intracellular and intercellular signals. Within cells, this leads to altered patterns of gene expression and of protein production. The net result is decreased production of inflammatory cytokines, chemokines, adhesion molecules, proteases and enzymes. The anti-inflammatory and inflammation-resolving effects of EPA and DHA are relevant to both prevention and treatment of human diseases that have an inflammatory component. This has been widely studied in rheumatoid arthritis where there is good evidence that high doses of EPA + DHA reduce pain and other symptoms.

EPA and DHA are required for normal cell function and can also induce health benefits. Oily fish are the main source of EPA and DHA for human consumption. However, food choices and concerns about the sustainability of marine fish stocks limit the effectiveness of dietary recommendations for EPA + DHA intakes. Seed oils from transgenic plants that contain EPA + DHA are a potential alternative source of EPA and DHA. The present study investigated whether dietary supplementation with transgenic Camelina sativa seed oil (CSO) that contained EPA and DHA was as effective as fish oil (FO) in increasing EPA and DHA concentrations when consumed as a dietary supplement in a blinded crossover study. Healthy men and women (n 31; age 53 (range 20–74) years) were randomised to consume 450 mg/d EPA + DHA provided either as either CSO or FO for 8 weeks, followed by 6 weeks washout and then switched to consuming the other test oil. Fasting venous blood samples were collected at the start and end of each supplementation period. Consuming the test oils significantly (P < 0·05) increased EPA and DHA concentrations in plasma TAG, phosphatidylcholine and cholesteryl esters. There were no significant differences between test oils in the increments of EPA and DHA. There was no significant difference between test oils in the increase in the proportion of erythrocyte EPA + DHA (CSO, 12 %; P < 0·0001 and FO, 8 %; P = 0·02). Together, these findings show that consuming CSO is as effective as FO for increasing EPA and DHA concentrations in humans.

The aim of the present paper is to review the effects of non-digestible oligosaccharides (NDO) on immunity, focusing on their microbiota-independent mechanisms of action, as well as to explore their potential beneficial role in inflammatory bowel diseases (IBD). IBD are chronic, inflammatory conditions of the gastrointestinal tract. Individuals with IBD have an aberrant immune response to commensal microbiota, resulting in extensive mucosal inflammation and increased intestinal permeability. NDO are prebiotic fibres well known for their role in supporting intestinal health through modulation of the gut microbiota. NDO reach the colon intact and are fermented by commensal bacteria, resulting in the production of SCFA with immunomodulatory properties. In disease states characterised by increased gut permeability, prebiotics may also bypass the gut barrier and directly interact with intestinal and systemic immune cells, as demonstrated in patients with IBD and in infants with an immature gut. In vitro models show that fructooligosaccharides, inulin and galactooligosaccharides exert microbiota-independent effects on immunity by binding to toll-like receptors on monocytes, macrophages and intestinal epithelial cells and by modulating cytokine production and immune cell maturation. Moreover, animal models and human supplementation studies demonstrate that some prebiotics, including inulin and lactulose, might reduce intestinal inflammation and IBD symptoms. Although there are convincing preliminary data to support NDO as immunomodulators in the management of IBD, their mechanisms of action are still unclear and larger standardised studies need to be performed using a wider range of prebiotics.

Intake of the plant-derived n-3 fatty acid α-linolenic acid (ALA) has been associated with anti-atherosclerotic properties. However, information on the association between ALA intake and development of peripheral artery disease (PAD) is lacking. In this follow-up study, we investigated the association between dietary intake of ALA and the rate of PAD among middle-aged Danish men and women enrolled into the Danish Diet, Cancer and Health cohort between 1993 and 1997. Incident PAD cases were identified through the Danish National Patient Register. Intake of ALA was assessed using a validated FFQ. Statistical analyses were performed using Cox proportional hazard regression allowing for separate baseline hazards among sexes and adjusted for established risk factors for PAD. During a median of 13·6 years of follow-up, we identified 950 valid cases of PAD with complete information on covariates. The median energy-adjusted ALA intake within the cohort was 1·76 g/d (95 % central range: 0·94–3·28). In multivariable analyses, we found no statistically significant association between intake of ALA and the rate of PAD (P = 0·339). Also, no statistically significant associations were observed in analyses including additional adjustment for co-morbidities and in sex-specific analyses. In supplemental analyses with additional adjustment for potential dietary risk factors, we found a weak inverse association of PAD with ALA intake above the median, but the association was not statistically significant (P = 0·314). In conclusion, dietary intake of ALA was not consistently associated with decreased risk of PAD.

EPA and DHA are important components of cell membranes. Since humans have limited ability for EPA and DHA synthesis, these must be obtained from the diet, primarily from oily fish. Dietary EPA and DHA intakes are constrained by the size of fish stocks and by food choice. Seed oil from transgenic plants that synthesise EPA and DHA represents a potential alternative source of these fatty acids, but this has not been tested in humans. We hypothesised that incorporation of EPA and DHA into blood lipids from transgenic Camelina sativa seed oil (CSO) is equivalent to that from fish oil. Healthy men and women (18–30 years or 50–65 years) consumed 450 mg EPA + DHA from either CSO or commercial blended fish oil (BFO) in test meals in a double-blind, postprandial cross-over trial. There were no significant differences between test oils or sexes in EPA and DHA incorporation into plasma TAG, phosphatidylcholine or NEFA over 8 h. There were no significant differences between test oils, age groups or sexes in postprandial VLDL, LDL or HDL sizes or concentrations. There were no significant differences between test oils in postprandial plasma TNFα, IL 6 or 10, or soluble intercellular cell adhesion molecule-1 concentrations in younger participants. These findings show that incorporation into blood lipids of EPA and DHA consumed as CSO was equivalent to BFO and that such transgenic plant oils are a suitable dietary source of EPA and DHA in humans.

We conducted a systematic review of randomised controlled trials (RCT) of increased intake of arachidonic acid (ARA) on fatty acid status and health outcomes in humans. We identified twenty-two articles from fourteen RCT. Most studies were conducted in adults. These used between 80 and 2000 mg ARA per d and were of 1–12 weeks duration. Supplementation with ARA doses as low as 80 mg/d increased the content of ARA in different blood fractions. Overall there seem to be few marked benefits for adults of increasing ARA intake from the typical usual intake of 100–200 mg/d to as much as 1000 mg/d; the few studies using higher doses (1500 or 2000 mg/d) also report little benefit. However, there may be an impact of ARA on cognitive and muscle function which could be particularly relevant in the ageing population. The studies reviewed here suggest no adverse effects in adults of increased ARA intake up to at least 1000–1500 mg/d on blood lipids, platelet aggregation and blood clotting, immune function, inflammation or urinary excretion of ARA metabolites. However, in many areas there are insufficient studies to make firm conclusions, and higher intakes of ARA are deserving of further study. Based on the RCT reviewed, there are not enough data to make any recommendations for specific health effects of ARA intake.

Arachidonic acid (ARA) and DHA, supplied primarily from the mother, are required for early development of the central nervous system. Thus, variations in maternal ARA or DHA status may modify neurocognitive development. We investigated the relationship between maternal ARA and DHA status in early (11·7 weeks) or late (34·5 weeks) pregnancy on neurocognitive function at the age of 4 years or 6–7 years in 724 mother–child pairs from the Southampton Women’s Survey cohort. Plasma phosphatidylcholine fatty acid composition was measured in early and late pregnancy. ARA concentration in early pregnancy predicted 13 % of the variation in ARA concentration in late pregnancy (β=0·36, P<0·001). DHA concentration in early pregnancy predicted 21 % of the variation in DHA concentration in late pregnancy (β=0·46, P<0·001). Children’s cognitive function at the age of 4 years was assessed by the Wechsler Preschool and Primary Scale of Intelligence and at the age of 6–7 years by the Wechsler Abbreviated Scale of Intelligence. Executive function at the age of 6–7 years was assessed using elements of the Cambridge Neuropsychological Test Automated Battery. Neither DHA nor ARA concentrations in early or late pregnancy were associated significantly with neurocognitive function in children at the age of 4 years or the age of 6–7 years. These findings suggest that ARA and DHA status during pregnancy in the range found in this cohort are unlikely to have major influences on neurocognitive function in healthy children.