This study aimed to explore the potential causal association between PUFA and the risk of intrahepatic cholestasis of pregnancy (ICP) using Mendelian randomisation (MR) analysis. A two-sample MR analysis was conducted utilising large-scale European-based genome-wide association studies summary databases. The primary MR analysis was carried out using the inverse variance-weighted (IVW) method, complemented by other methods such as MR-egger, weighted-median and weighted mode. Sensitivity analysis was also performed to validate the robustness of the findings. Results indicated a 31 % reduced risk of ICP for every 1 standard deviation (sd) increase in n-3 fatty acids levels (OR = 0·69, 95 % CI: 0·54, 0·89, P = 0·004) and in the ratio of n-3 fatty acids to total fatty acids (OR = 0·69, 95 % CI: 0·53, 0·91, P = 0·008). Conversely, there was a 51 % increased risk of ICP for every 1 sd increase in the ratio of n-6 fatty acids to n-3 fatty acids (OR = 1·51, 95 % CI: 1·20, 1·91, P < 0·001) and a 138 % increased risk for every 1 sd increase in the ratio of linoleic fatty acids to total fatty acids (OR = 2·38, 95 % CI: 1·55, 3·66, P < 0·001). The findings suggest that n-3 fatty acids may have a protective effect against the risk of ICP, while n-6 fatty acids and linoleic fatty acids could be potential risk factors for ICP. The supplementation of n-3 fatty acids, as opposed to n-6 fatty acids, could be a promising strategy for the prevention and management of ICP.

This article aims to study the different dietary fat types associated with obesity and coronary indices. A sample of 491 healthy adults was included in a cross-sectional manner. Dietary fats intake, obesity indices (conicity index (CI), body adiposity index (BAI), abdominal volume index (AVI), body roundness index (BRI), and weight-adjusted-waist index (WWI)), and cardiovascular indices (cardiometabolic index (CMI), lipid accumulation product (LAP), and atherogenic index of plasma (AIP)) were calculated and studied. Participants with an acceptable intake of omega-3 had a higher BRI score (1⋅90 ± 0⋅06 v. 1⋅70 ± 0⋅06). Participants with an unacceptable intake of cholesterol had a higher CI (1⋅31 ± 0⋅11 v. 1⋅28 ± 0⋅12; P = 0⋅011), AVI (20⋅24 ± 5⋅8 v. 18⋅33 ± 6⋅0; P < 0⋅001), BRI (2⋅00 ± 1⋅01 v. 1⋅70 ± 1⋅00; P = 0⋅003), WWI (11⋅00 ± 0⋅91 v. 10⋅80 ± 0⋅97; P = 0⋅032), and lower AIP (0⋅46 ± 0⋅33 v. 0⋅53 ± 0⋅33; P = 0⋅024). Total fat, saturated fat (SFA), and polyunsaturated fat (PUFA) intake had a significant moderate correlation with AVI and BRI. The monounsaturated fat (MUFA) intake had a significantly weak correlation with CI, AVI, BRI, WWI, and AIP. Cholesterol and omega-6 had weak correlations with all indices. Similar correlations were seen among male and female participants. The different types of fat intake significantly affected obesity and coronary indices, especially SFA and PUFA, as well as omega-3 and cholesterol. Gender and the dietary type of fat intake have a relationship to influence the indicators of both obesity and coronary indices.

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.

Current studies on inhibitory effects of n-3 PUFA on pro-inflammatory cytokines have inconsistent results. Thus, a meta-analysis of randomised controlled trials was conducted to identify the effects of n-3 PUFA administration on circulating IL-6 and TNF in patients with cancer. Studies that examined the effects of n-3 PUFA administration on circulating IL-6 and TNF in patients with cancer were identified by searching PubMed and EMBASE from January 1975 to February 2021. Differences in n-3 PUFA administration and control conditions were determined by calculating standardised mean differences (SMD) with 95 % CI. Twenty studies involving 971 patients met the inclusion criteria. The overall SMD were 0·485 (95 % CI 0·087, 0·883) for IL-6 and 0·712 (95 % CI 0·461, 0·962) for TNF between n-3 PUFA administration and control conditions. Sources of heterogeneity were not found through subgroup and meta-regression analyses. Publication bias was observed in TNF with a slight contribution to the effect size. n-3 PUFA can reduce circulating IL-6 and TNF levels in patients with cancer. Results supported the recommendation of n-3 PUFA as adjuvant therapy for patients with cancer, possibly excluding head and neck cancer, owing to their anti-inflammatory properties.

Dyslipidaemia, a significant risk factor of CVD, is threatening human health worldwide. PUFA are crucial long-chain fatty acids for TAG synthesis and removal, potentially decreasing dyslipidaemia risk. We examined dyslipidaemia prevalence among 15 244 adults aged ≥ 20 years from National Health and Nutrition Examination Survey 2009–2016. Dyslipidaemia was defined as total cholesterol ≥ 240 mg/dl, or HDL-cholesterol < 40 mg/dl/50 mg/dl for males/females, respectively, or LDL-cholesterol ≥ 160 mg/dl, or TAG ≥ 200 mg/dl, or taking lipid-modifying medications. We measured the daily PUFA intake using a 24-h dietary recall. Demographics, social economics, and lifestyle factors were collected using questionnaires/interviews. Additionally, we measured Se and Hg levels in the whole blood. Logistic regression models were used to examine the association between PUFA and dyslipidaemia. The unweighted and weighted dyslipidaemia prevalences were 72·4% and 71·0 %, respectively. When grouped into tertiles, PUFA intake above 19·524 g/d was associated with an independent 19 % decrease in dyslipidaemia risk (OR = 0·81 (95 % CI 0·71, 0·94)) compared with the lowest tertile (PUFA intake ≤ 12·349 g/d). A threshold inverse association was further determined by the restricted cubic spline analysis. When PUFA intake was increased to its turning point, that is, 19 g/d, the lower nadir risk for dyslipidaemia was obtained (OR = 0·72 (95 % CI 0·56, 0·89)). When the exposure was the sum of α-linolenic acid and octadecatetraenoic acid, the inverse linear association remained. Dietary PUFA intake is a beneficial factor for dyslipidaemia among American adults, independent of many potential confounders, including Hg and Se.

An adequate intake of PUFA plays a vital role in human health. Therefore, it is important to assess PUFA intakes in different populations and validate them with biomarkers, but only a few small studies are in paediatric populations. We calculated the dietary intake of PUFA and their main food sources in children and assessed associations between PUFA intakes and plasma proportions. Dietary intakes of 7-year-old children (n 8242) enrolled in the Avon Longitudinal Study of Parents and Children were calculated from the parental-completed FFQ. Plasma PUFA were measured in 5571 children 8 months later, and 4380 children had complete dietary and plasma data. The association between dietary and plasma PUFA proportions was estimated using Spearman’s correlation coefficients, quintile cross-classification and Cohen’s κ coefficients. Mean total PUFA intake was 13·2 g/d (sd 4·2), contributing 6·5 % of total energy intake; n-6 PUFA contributed 5·2 % and n-3 PUFA 0·7 %. The n-6:n-3 ratio was 7·9:1. Mean intakes of EPA and DHA were 35·7 mg/d and 49·7 mg/d, respectively. Most n-3 and n-6 PUFA intakes were weakly correlated with their respective plasma lipids (0·07 ≤ r ≤ 0·16, P < 0·001). The correlation between dietary and plasma DHA was stronger though (r = 0·34, P < 0·001), supported by a modest level of agreement between quintiles (k = 0·32). The results indicate that the FFQ was able to reasonably rank the long-chain (LC) PUFA, DHA, in this paediatric population. Public health initiatives need to address the suboptimal ratio of n-6:n-3 PUFA and very low n-3 LC-PUFA intakes in school-age children in the UK.

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 10-week feeding trial was conducted to investigate the effect of dietary curcumin (CC) on growth antioxidant responses, fatty acid composition, and expression of lipid metabolism-related genes of large yellow croaker fed a high-fat diet (HFD). Four diets (lipid level at 18 %) were formulated with different levels of curcumin (0, 0·02, 0·04 and 0·06 %). The best growth performance was found in the 0·04 % curcumin group, with the body and hepatic lipid levels lower than the control group (0 % CC). The content of TAG, total cholesterol and LDL-cholesterol was the least in the 0·06 % curcumin group. The lowest malondialdehyde and the highest superoxide dismutase, catalase and total antioxidant capacity were observed in the 0·04 % curcumin group. The 0·04 % curcumin group had higher expression of Δ6fad, elovl5 and elovl4 and showed higher hepatic n-6 and n-3 PUFA. Expression of ppara, cpt1, and aco was significantly increased, while expression of srebp1 and fas was dramatically decreased in curcumin groups compared with the control group. Overall, 0·04 % curcumin supplementation could mitigate the negative effects caused by HFD and promote growth via reducing hepatic lipid deposition, improving antioxidant activity and increasing PUFA of large yellow croaker. To conclude, abnormal hepatic lipid deposition was probably due to increased fatty acid oxidation and reduced de novo synthesis of fatty acids.

The n-3 PUFA, EPA and DHA, play an important role in human health. As the intake of EPA and DHA from the diet is often inadequate, supplementation of those fatty acids is recommended. A novel source of n-3 PUFA is Calanus finmarchicus oil (CO) which contains fatty acids mainly bound in wax esters. To date, no data are available on the effects of long-term intake of this marine oil on n-3 PUFA blood levels. Therefore, the aim of this study was to evaluate the effect of CO on the n-3 PUFA blood levels using the omega-3 index (O3I). The data originate from a larger randomised controlled trial. For this analysis, samples from seventy-two participants (59·2 (sd 6·2) years, BMI 27·7 (sd 5·28) kg/m2) were analysed. Of those, thirty-six performed 2×/week exercise and received 2 g of CO, which provided 124 mg stearidonic acid (SDA), 109 mg EPA and 87 mg DHA daily (EXCO group), while the other group performed exercise only (EX group) and served as a control for this analysis. The O3I increased from 6·07 (sd 1·29) % at baseline to 7·37 (sd 1·10) % after 12 weeks within the EXCO group (P < 0·001), while there were no significant changes in the EX group (6·01 (sd 1·26)–6·15 (sd 1·32) %, P = 0·238). These data provide first evidence that wax ester-bound n-3 PUFA from CO can significantly increase the O3I despite relatively low EPA + DHA amounts. Further, the effects of exercise could be excluded.

To induce diet-induced obesity (DIO) in rodents, diets high in saturated fat and/or carbohydrates are commonly used. In the laboratory, standardised diets evolved over time without paying particular attention to the effect of fat composition on metabolic alterations. In the present study, customised high-fat diets (HFD) enriched with a combination of lard and different concentrations of New Zealand green-lipped mussel (Perna canaliculus) oil or MSC Hoki (Macruronus novaezelandiae, blue grenadier) liver oil, important sources of n-3 PUFA, in comparison with a solely lard-based diet, were fed to lean and DIO male C57BL/6 mice and their effects on metabolic parameters were monitored. Intriguingly, an isoenergetic HFD containing 63 % of total fat in the form of mussel oil and only 28 % in the form of lard attenuated HFD-induced body weight gain after 1 and 4 weeks, respectively. Consistently, changing a lard-enriched HFD to the mussel oil diet reduced body weight markedly even after mice had been exposed to the former diet for 10 months. The weight-reducing effect of the diet was not caused by altered energy intake or expenditure, but was associated with reduced visceral fat mass. Collectively, these data suggest a novel weight-reducing potential of green-lipped mussel oil.

In this systematic review, we critically evaluated human clinical trials that assessed the effects of dietary fat quality on metabolic endotoxaemia. The studies were selected from three databases (PubMed, Scopus and Cochrane Library), and the keywords were defined according to the Medical Subject Headings indexing terminology. Two authors searched independently, according to the pre-defined selection criteria. Quality and risk assessment of bias for each selected study were also evaluated. The results of the included studies demonstrated associations between higher SFA intake and increased postprandial lipopolysaccharide (LPS) concentrations. On the other hand, after the consumption of PUFA, bloodstream LPS concentrations were lower. However, in none of the long-term studies, the consumption of dietary fats did not seem to exert effects on LPS concentration. Hence, SFA seem to act as a risk factor for transient increase in endotoxaemia, while PUFA demonstrated exerting a protective effect. Taken together, the evidence suggests that the dietary fatty acid profile may influence bloodstream endotoxin concentrations through modulation of factors such LPS clearance, alkaline phosphatase activity, bile acid metabolism, intestinal permeability and intestinal microbiota composition.

Variants in the human genes of fatty acid (FA) desaturase 1 (FADS1), 2 (FADS2) and 3 (FADS3) are associated with PUFA blood levels. We explored if maternal prenatal supplementation and children’s genetic variation in seventeen SNP of the FADS1, FADS2 and FADS3 gene cluster influence twenty-one of the most relevant cheek cells’ derived FA in glycerophospholipids (GPL-FA). The study was conducted in 147 Spanish and German mother–children pairs participating in the Nutraceuticals for a Healthier Life (NUHEAL) study at 8, 9 and 9·5 years. Linear and mixed model longitudinal regression analyses were performed. Maternal fish-oil (FO) or FO+5-methyltetrahydrofolate (5-MTHF) supplementation during pregnancy was associated with a significant decrease of arachidonic acid (AA) concentrations in cheek cell GPL in the offspring, from 8 to 9·5 years; furthermore, maternal FO+5-MTHF supplementation was associated with higher n-6 docosapentaenoic acid concentrations in their children at age 8 years. FADS1 rs174556 polymorphism and different FADS2 genotypes were associated with higher concentrations of linoleic and α-linolenic acids in children; moreover, some FADS2 genotypes determined lower AA concentrations in children’s cheek cells. It is suggested an interaction between type of prenatal supplementation and the offspring genetic background driving GPL-FA levels at school age. Prenatal FO supplementation, and/or with 5-MTHF, seems to stimulate n-3 and n-6 FA desaturation in the offspring, increasing long-chain PUFA concentrations at school age, but depending on children’s FADS1 and FADS2 genotypes. These findings suggest potential early nutrition programming of FA metabolic pathways, but interacting with children’s FADS polymorphisms.

CVD remains the greatest cause of death globally, and with the escalating prevalence of metabolic diseases, including type-2 diabetes, CVD mortality is predicted to rise. While the replacement of SFA has been the cornerstone of effective dietary recommendations to decrease CVD risk since the 1980s, the validity of these recommendations have been recently challenged. A review of evidence for the impact of SFA reduction revealed no effect on CVD mortality, but a significant reduction in risk of CVD events (7–17%). The greatest effect was found when SFA were substituted with PUFA, resulting in 27% risk reduction in CVD events, with no effect of substitution with carbohydrate or protein. There was insufficient evidence from randomised controlled trials to conclude upon the impact of SFA replacement with MUFA on CVD and metabolic outcomes. However, there was high-quality evidence that reducing SFA lowered serum total, and specifically LDL-cholesterol, a key risk factor for CVD, with greatest benefits achieved by replacing SFA with unsaturated fats. The exchange of SFA with either PUFA or MUFA, also produced favourable effects on markers of glycaemia, reducing HbA1c, a long-term marker of glycaemic control. In conclusion, the totality of evidence supports lowering SFA intake and replacement with unsaturated fats to reduce the risk of CVD events, and to a lesser extent, cardiometabolic risk factors, which is consistent with current dietary guidelines.

As only limited evidence is available for potential benefits of n-3 PUFA supplementation in patients with peripheral arterial disease (PAD), we studied the effects of 4 g n-3 PUFA on endothelial function and inflammatory markers. Seventy patients with stable PAD classified as Rutherford stage 2 or 3 and good control of cardiovascular factors were randomised to receive either 4 g n-3 PUFA or placebo daily for 3 months in a double-blind fashion. Primary endpoint was endothelial function assessed by flow-mediated vasodilation (FMD). In addition, ankle–brachial index, maximum and pain-free walking distances were determined. Lipid parameters including the omega-3 index reflecting n-3 PUFA intake as well as pro-inflammatory, endothelial and platelet activation markers were measured over the same time interval. After 3 months of treatment with 4 g n-3 PUFA daily, a significant improvement of FMD was observed compared with placebo (n-3 PUFA, median Δ 3·7 (interquartile range (IQR) –1·8, 7·1) % v. placebo, Δ –0·5 (IQR –6·5, 3·0) %, P = 0·01 between the groups). After a 3-month washout period, this benefit was not sustained (n-3 PUFA, median Δ 0·6 (IQR –2·2, 5·6) % v. placebo, Δ –0·9 (IQR –6·6, 6·7) %, P = 0·20). In response to n-3 PUFA, an improvement of lipid parameters with a pronounced increase in the omega-3 index was seen. No changes were found for other parameters. In conclusion, in patients with PAD, 4 g/d n-3 PUFA improved cardiovascular risk in PAD patients, which needs testing in large-scale trials.