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Background Plasma trimethylamine N-oxide (TMAO) has drawn much attention as a marker of several chronic diseases. Data on the relation between diet and TMAO are discordant and few human intervention studies have assessed causality for this association. Objectives We aimed to evaluate the effects on plasma TMAO of diets based on foods rich in polyphenols (PP) and/or long-chain n–3 fatty acids (LCn3) or whole-grain cereals (WGCs), in individuals at high cardiometabolic risk. Methods An ancillary study was performed within 2 randomized controlled trials, aimed at evaluating the medium-term effects on cardiometabolic risk factors of diets naturally rich in PP and/or LCn3 (Etherpaths Project) or WGCs (HealthGrain Project). Results In the Etherpaths study (n = 78), the changes in TMAO (8-wk minus baseline) were statistically significant for the diets rich in LCn3 (+1.15 ± 11.58 μmol/L) (P = 0.007), whereas they were not for the diets rich in PP (−0.14 ± 9.66 μmol/L) (P  = 0.905) or their interaction (P  = 0.655) (2-factor ANOVA). In the HealthGrain Study (n  = 48), the TMAO change (12-wk minus baseline) in the WGC group (+0.94 ± 3.58 μmol/L) was significantly different from that in the Refined Cereal group (−1.29 ± 3.09 μmol/L) (P  = 0.037). Considering the pooled baseline data of the participants in the 2 studies, TMAO concentrations directly correlated with LCn3, EPA (20:5n–3), and protein intake, but not SFAs, fiber, MUFAs, and PP intake. Among food groups, TMAO directly correlated with the intake of fish, vegetables, and whole-grain products, but not meat, processed meat, and dairy products. Conclusions Diets rich in LCn3 of marine origin or WGCs significantly increased plasma TMAO concentration. These changes mirrored the direct associations between TMAO concentrations and intakes of fish and WGCs, suggesting that TMAO reflects intakes of these healthy foods and, therefore, it is not a universally valid biomarker of cardiometabolic risk independent of the background diet. These trials were registered at clinicaltrials.gov as NCT01154478 and NCT00945854. [ABSTRACT FROM AUTHOR]

Long-chain n -3 PUFA (LC n -3 PUFA) prevent, in rodents, insulin resistance (IR) induced by a high-fat and/or fructose diet but not IR induced by glucocorticoids. In humans, contrasting effects have also been reported. We investigated their effects on insulin sensitivity, feed intake (FI) and body weight gain in genetically insulin resistant male obese (fa/fa) Zucker (ZO) rats during the development of obesity. ZO rats were fed a diet supplemented with 7 % fish oil (FO) + 1 % corn oil (CO) (wt/wt) (ZO FO ), while the control group was fed a diet containing 8 % fat from CO (wt/wt) (ZO CO ). Male lean Zucker (ZL) rats fed either FO (ZL FO ) or CO (ZL CO ) diet were used as controls. FO was a marine-derived TAG oil containing EPA 90 mg/g + DHA 430 mg/g. During an oral glucose tolerance test, glucose tolerance remained unaltered by FO while insulin response was reduced in ZO FO only. Liver insulin sensitivity (euglycaemic-hyperinsulinaemic clamp + 2 deoxyglucose) was improved in ZO FO rats, linked to changes in phosphoenolpyruvate carboxykinase expression, activity and glucose-6-phosphatase activity. FI in response to intra-carotid insulin/glucose infusion was decreased similarly in ZO FO and ZO CO . Hypothalamic ceramides levels were lower in ZO FO than in ZO CO . Our study demonstrates that LC n -3 PUFA can minimise weight gain, possibly by alleviating hypothalamic lipotoxicity, and liver IR in genetically obese Zucker rats.

Background: Intervention studies have shown that long-chain (LC) n-3 PUFA intake can prolong gestation but the dose-time-effect relations remain unresolved.Objectives: We examined the effect on gestation duration of 2 doses of supplemental LC n-3 PUFAs.Methods: We undertook a 3-group parallel randomized controlled trial in areas of China with low (median: 2.1 g/d) and higher (14.3 g/d) fish intake. Unselected women (median: age, 26.2 y; BMI, 20. kg/m2) were randomly assigned at midgestation to take four 0.72-g identical gelatin capsules per day until the last day of the preterm period (<259 days of gestation), when they were asked to stop. Capsules contained fish oil [high fish oil (HFO) group (60% w/w LC n-3 PUFAs)], a 1:3 mixture of fish oil to olive oil [low fish oil (LFO) group (20%)], or olive oil [control (CON) group (0%)], providing 2.0, 0.5, and 0 g/d of LC n-3 PUFAs, respectively. Habitual fish intake was recorded at baseline. Hazard rate ratios (HRRs) for spontaneous delivery <259 days of gestation and <273 days of gestation across groups were estimated by Cox regression.Results: Among 5531 women randomly assigned, 92.5% were included in analyses (1706/1825, 1695/1851, and 1717/1855, respectively). The groups were similar with respect to hazard rates <259 days of gestation [HRR: 1.04 (95% CI: 0.70, 1.53) for LFO compared with CON and 0.90 (95% CI: 0.60, 1.35) for HFO compared with CON], hazard rates <273 days of gestation [HRR: 1.00 (95% CI: 0.86, 1.18) and 0.91 (95% CI: 0.77, 1.07), respectively], and mean gestation durations [differences: 0.2 d (95% CI: -0.5, 0.8) and 0.6 d (95% CI: -0.06, 1.2), respectively]. Inspection of pregnancy survival curves suggested that LC n-3 PUFAs delayed delivery in low fish consumers by 5-10 d and that this effect ceased rapidly after stopping taking the capsules.Conclusion: This trial could not substantiate that fish oil prevents preterm birth in Chinese women, possibly because statistical power was too low. This trial was registered at clinicaltrials.gov as NCT02770456. [ABSTRACT FROM AUTHOR]

Background First Nations (FNs) populations in Canada experience a disproportionally higher rate of obesity and type 2 diabetes (T2D) compared to the general population. Recent data suggest that a high consumption of fish may help prevent T2D. On the other hand, fish might also be a potential source of environmental contaminants which could potentially be a risk factor for T2D. Objective To investigate the potential associations between self-reported T2D and consumption of locally-harvested fish, dietary long-chain omega-3 fatty acids (n-3FAs) and persistent organic pollutants intake among adult FNs living on reserve in Ontario. Design Data from the First Nations Food Nutrition and Environment Study, which included a cross-sectional study of 1429 Ontario FNs adults living in 18 communities across 4 ecozones in 2012 were analyzed. Social and lifestyle data were collected using household interviews. The consumption of locally-harvested fish was estimated using a traditional food frequency questionnaire along with portion size information obtained from 24hr recalls. Fish samples were analyzed for the presence of contaminants including dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyls (PCBs). Dietary intakes of DDE and PCBs were estimated using community-specific levels of DDE/PCBs in fish species. Multiple logistic regression models adjusted for potential covariates including age, gender, body mass index, physical activity, total energy intake, smoking, and education were developed. Results The prevalence of T2D in Ontario FNs was 24.4%. A significant positive association between fish consumption of one portion per week and more and T2D compared to no fish consumption was found (OR=2.5 (95% CI: 1.38–4.58). Dietary DDE and PCBs intake was positively associated with T2D (OR=1.09 (95%CI: 1.05–1.75) for DDE and OR=1.07 (95%CI: 1.004–1.27) for PCBs) per unit increase in DDE/PCBs while n-3-FAs intake, adjusted for DDE/PCBs intake, showed an inverse effect against T2D among older individuals (OR=0.86 (95% CI: 0.46–0.99). Conclusion Our results support previous findings that exposure to DDE and PCBs may increase the risk of T2D. Elevated levels of contaminants in fish may counteract with potentially beneficial effects of n-3FAs from fish consumption. However, the overall health benefits of high consumption of fish with a high n-3 FAs content may outweigh the adverse effect of contaminants. [ABSTRACT FROM AUTHOR]

The objective of the present study was to assess the fatty acid composition of horse-meat available at the retail market in northern Spain. Horse steaks ( Longissimus thoracis et lumborum muscle; n = 82) were purchased from butcher-shops and large grocery stores throughout six northern regions of Spain in two different seasons. Fat content differed significantly among regions (1.12 to 2.77%). Samples with higher intramuscular fat content presented the highest percentages of total monounsaturated fatty acids and the lowest contents of dimethylacetal and polyunsaturated fatty acids (PUFA), while the opposite was found in the leanest samples. A high variability was observed in the muscle and subcutaneous n-3 PUFA content. Overall, total n-3 PUFA content ranged between 1.17% and 18.9% in muscle fat and between 1.52% and 27.9% in backfat. Interestingly, almost 5% of surveyed loins from horse carcasses (4 out of 82) contained over 300 mg of linolenic acid per 100 g of meat which could have been marketed as a “source” of n-3 FAs according to Commission Regulation (EU) No 116/2010. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate how long-term dietary intake of long-chain n-3 polyunsaturated fatty acids (LCn-3 PUFAs), estimated by repeated food frequency questionnaires (FFQs) over 15 years, is correlated with LCn-3 PUFAs in adipose tissue (AT). Methods: Subcutaneous adipose tissue was obtained in 2003-2004 (AT-03) from 239 randomly selected women, aged 55-75 years, after completion of a 96-item FFQ (FFQ-03). All participants had previously returned an identical FFQ in 1997 (FFQ-97) and a 67-item version in 1987-1990 (FFQ-87). Pearson product-moment correlations were used to evaluate associations between intake of total and individual LCn-3 PUFAs as estimated by the three FFQ assessments and AT-03 content (% of total fatty acids). Results: FFQ-estimated mean relative intake of LCn-3 PUFAs (% of total fat intake) increased between all three assessments (FFQ-87, 0.55 ± 0.34; FFQ-97, 0.74 ± 0.64; FFQ-03, 0.88 ± 0.56). Validity, in terms of Pearson correlations between FFQ-03 estimates and AT-03 content, was 0.41 (95 % CI 0.30-0.51) for total LCn-3 PUFA and ranged from 0.29 to 0.48 for individual fatty acids; lower correlation was observed among participants with higher percentage body fat. With regard to long-term intake estimates, past dietary intake was also correlated with AT-03 content, with correlation coefficients in the range of 0.21-0.33 and 0.21-0.34 for FFQ-97 and FFQ-87, respectively. The correlations were improved by using average estimates from two or more FFQ assessments. Exclusion of fish oil supplement users (14 %) did not alter the correlations. Conclusion: These data indicate reasonable validity of FFQ-based estimates of long-term (up to 15 years) LCn-3 PUFA intake, justifying their use in studies of diet-disease associations. [ABSTRACT FROM AUTHOR]

Given the evidence of the health benefits of plant-based diets and long-chain n-3 (ω-3) fatty acids, there is keen interest in better understanding the role of α-linolenic acid (ALA), a plant-derived n-3 fatty acid, on cardiometabolic diseases and cognition. There is increasing evidence for ALA largely based on its major food sources (i.e., walnuts and flaxseed); however, this lags behind our understanding of long-chain n-3 fatty acids. Meta-analyses of observational studies have shown that increasing dietary ALA is associated with a 10% lower risk of total cardiovascular disease and a 20% reduced risk of fatal coronary heart disease. Three randomized controlled trials (RCTs) [AlphaOmega trial, Prevención con Dieta Mediterránea (PREDIMED) trial, and Lyon Diet Heart Study] all showed benefits of diets high in ALA on cardiovascular-related outcomes, but the AlphaOmega trial, designed to specifically evaluate ALA effects, only showed a trend for benefit. RCTs have shown that dietary ALA reduced total cholesterol, LDL cholesterol, triglycerides, and blood pressure, and epidemiologic studies and some trials also have shown an anti-inflammatory effect of ALA, which collectively account for, in part, the cardiovascular benefits of ALA. A meta-analysis reported a trend toward diabetes risk reduction with both dietary and biomarker ALA. For metabolic syndrome and obesity, the evidence for ALA benefits is inconclusive. The role of ALA in cognition is in the early stages but shows promising evidence of counteracting cognitive impairment. Much has been learned about the health benefits of ALA and with additional research we will be better positioned to make strong evidence-based dietary recommendations for the reduction of many chronic diseases., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Salmon provides long-chain (LC) n-3 PUFA and Se, which are well recognised for their health benefits. The n-3 and Se status of the New Zealand population is marginal. The objective of the present study was to compare the effects of consuming salmon v. supplementation with salmon oil on LC n-3 and Se status. Healthy volunteers (n 44) were randomly assigned to one of four groups consuming 2 × 120 g servings of salmon/week or 2, 4 or 6 salmon oil capsules/d for 8 weeks. Linear regression analysis predictive models were fitted to the capsule data to predict changes in erythrocyte LC n-3 levels with intakes of LC n-3 from capsules in amounts equivalent to that consumed from salmon. Changes in Se status (plasma Se and whole-blood glutathione peroxidase) were compared between the groups consuming salmon and capsules (three groups combined). Salmon, 2, 4 and 6 capsules provided 0·82, 0·24, 0·47 and 0·69 g/d of LC n-3 fatty acids. Salmon provided 7 μg/d and capsules < 0·02 μg/d of Se. The predictive model (r2 0·31, P = 0·001) showed that increases in erythrocyte LC n-3 levels were similar when intakes of 0·82 g/d LC n-3 from salmon or capsules (1·92 (95 % CI 1·35, 2·49) v. 2·32 (95 % 1·76, 2·88) %) were consumed. Plasma Se increased significantly more with salmon than with capsules (12·2 (95 % CI 6·18, 18·12) v. 1·57 (95 % CI − 2·32, 5·45) μg/l, P = 0·01). LC n-3 status was similarly improved with consumption of salmon and capsules, while consuming salmon had the added benefit of increasing Se status. This is of particular relevance to the New Zealand population that has marginal LC n-3 and Se status. [ABSTRACT FROM PUBLISHER]

Abstract: The protective cardiovascular effect of long-chain n-3 fatty acids has been firmly established in populations with high fish consumption, like those from Mediterranean countries. The current fish consumption in a representative sample from Catalonia, a Mediterranean region, and its relationship with plasma concentrations of eicosapentaenoic (EPA) and docosahexaenoic (DHA) and some classical cardiovascular disease risk factors was evaluated. Mean fish and seafood intake was 78.5±51.4g/day. Mean plasma concentrations of EPA and DHA were respectively 0.48% and 1.99% of total fatty acids. Consumption of marine foods among the Catalan population, the main source of n-3 fatty acids, appears to beneficially affect some cardiovascular disease risk factors. Our results show that both EPA and DHA are negatively associated with triacylglycerol (TG) concentrations and the ratio of total cholesterol (TC) to HDL-cholesterol. Furthermore, EPA but not DHA has a beneficial effect on plasma HDL-cholesterol among the Catalan population. There were no significant associations between long-chain n-3 fatty acids and LDL-cholesterol, TC, glucose, insulin or blood pressure. Oily fish intake, which is richest in EPA and DHA, is currently at an order of only 1 serving per week in the Catalan population and its increase should therefore be promoted. [Copyright &y& Elsevier]

The effects of an n-3 PUFA-enriched diet on cardiac cell membrane phospholipid fraction compositions and associated protein kinase-C (PKC) translocation modification have never been studied in higher mammals. This is of importance since membrane fatty acid composition has been shown to influence PKC signalling pathways. In the present study, we have tested whether the incorporation of n-3 PUFA in cardiac membrane phospholipids correlated with changes in the fatty acid composition of diacylglycerols (DAG) and led to a differential translocation of PKC isoforms. Two groups of five dogs were fed the standard diet supplemented with palm oil or fish oil for 8 weeks. Dogs fed a fish oil-enriched diet showed a preferential incorporation of EPA and, to a lesser extent, of DHA, at the expense of arachidonic acid, in the circulating TAG, plasma phospholipids, erythrocyte phospholipids and cardiomyocyte phospholipid fractions. Analysis of 1,2-DAG fatty acid composition also indicated a preferential enrichment of EPA compared with DHA. Associated with these results, a reduction in the expression of PKC-?? and PKC-?? isoforms in the particulate fractions was observed whereas no effect was seen for PKC-?? and PKC-??. We conclude that a fish oil-enriched diet induces a modification in fatty acid composition of cardiac membrane phospholipids, associated with a differential translocation of PKC isoforms. These results can be explained by the production of structurally different DAG that may participate in some of the protective effects of n-3 PUFA against various chronic diseases. [ABSTRACT FROM PUBLISHER]

Objectives To test the earlier suggested hypothesis that intake of long-chain n-3 fatty acids from fish oil may delay the timing of spontaneous delivery and to test if alpha-linolenic acid, provided as flax oil capsules, shows the same effect. Design Randomised controlled trial including women reporting low dietary fish intake. The women were allocated in the proportions of 1:1:1:1:1:1:2 into six treatment groups and a control group, respectively, from week 17–27 of gestation. The treatment groups received fish oil, in various doses, or flax oil, and the control group did not receive any treatment. Setting The Danish National Birth Cohort. Sample A total of 3098 women allocated into six treatment groups and one control group. Methods The six intervention groups were offered fish oil capsules in doses of 0.1, 0.3, 0.7, 1.4 and 2.8 g of eicosapentaenoic acid and docosahexaenoic acid per day or 2.2 g of alpha-linolenic acid (ALA) per day from week 17–27 of gestation until delivery. Main outcome measures Timing of spontaneous delivery. Results No differences in timing of spontaneous delivery was detected in the fish oil groups or the flax oil group, compared with the control group. The difference in timing of spontaneous delivery in the group receiving the highest fish oil dose compared with the control group was 0.8 days (95% CI: –2.3 to 1.0). Only a minority of the women in the intervention groups took capsules until delivery. Conclusion Possible explanations for these findings include no true effect of n-3 fatty acids on spontaneous delivery or a quick-acting effect not detectable in this trial. [ABSTRACT FROM AUTHOR]

Abstract: Milk fat secretion and profiles of conjugated linoleic acids (CLA) and trans-18:1 isomers in milk fat due to a ruminal or duodenal supply of fish oil (FO; EPA=22% of total fatty acids, DHA=7%) were evaluated using six lactating Holstein cows with cannulas in their rumen and duodenum. Cows were fed a control diet based on corn silage (66% of DM), or the control plus 300mL FO/d into the rumen (FO-R) or duodenum (FO-D) for 4 weeks in a replicated 3×3 Latin square design. Dry matter intake was higher with the control (19.8kg/d), intermediate with FO-D (18.0kg/d), and lower with FO-R (16.2kg/d). Yield of milk (22.7kg/d), lactose (1.09kg/d), or crude protein (0.70kg/d) was not affected by treatments. Content of crude protein, true protein, and casein was lower in response to FO-R compared with the control. Despite similar jugular concentration compared with the control, jugular–mammary venous difference for β-OH-butyrate was 54% lower with FO-R or FO-D. Milk fat content and yield were lowest with FO-R (25g/kg, 567g/d) compared with FO-D (32g/kg, 737g/d) or the control (35g/kg, 783g/d). Percentage of trans5-, trans6+7+8-, trans9-, trans10-, trans11-, trans12-, and trans13+14-18:1 in milk fat was greater due to FO-R (0.05, 0.44, 0.48, 1.8, 9.2, 0.70, and 0.82%, respectively) compared with the control or FO-D (0.02, 0.22, 0.19, 0.27, 1.1, 0.35, and 0.40%). Although 18:0 and cis9-18:1 percentage was markedly lower in response to FO-R, percentage of cis11-, cis13-, and cis15-18:1 was greater compared with the control or FO-D. Cis9,trans11-CLA (87–95% of total CLA) averaged 3.2% in response to FO-R compared with 0.51% for control or FO-D. Trans10,cis12-18:2 was not detected. Among non-conjugated 18:2 isomers, cis9,cis12-18:2 was lower but cis9,trans13-, trans9,cis12-, and trans11,cis15-18:2 greater when FO-R was compared with the control or FO-D. There was high correlation (r=0.94–0.99) among data obtained by GLC versus HPLC for most trans-18:1 isomers and cis9,trans11-18:2, suggesting GLC alone with our chromatographic conditions provided adequate separation of isomers. Milk 20:5n-3 (EPA) and 22:6n-3 (DHA) were 0.08 and 0.04% with the control, increased to 0.36 and 0.17% with FO-R, and were 1.47 and 0.47% with FO-D. Data indicate, ruminal supply of FO led to hydrogenation of EPA and DHA and enhanced percentage of various trans-18:1, cis-18:1, non-conjugated 18:2, and cis9,trans11-18:2 in milk fat. Combined increases in trans-18:1 along with reduced availability of 18:0 for endogenous synthesis of cis9-18:1 may play a key role in reduced milk fat synthesis in cows fed fish oil. [Copyright &y& Elsevier]

We determined if long-chain n-3 fatty acids fed as part of a: (1) high polyunsaturated fat diet (currently recommended by several health agencies) or (2) low polyunsaturated fat diet (representative of that consumed by a large segment of the North American population) improved antitumor immune defense and inhibited tumor growth. Rats were fed one of four semi-purified diets (20% w/w fat) for 21 days pre- and 17 days post- R3230AC mammary tumor implantation. The polyunsaturated to saturated fatty acid (P/S) ratio was either 1 (high P/S diet) or 0.35 (low P/S diet). At each P/S ratio, diets provided long-chain n-3 fatty acids at 0 or 5% w/w of total fat. Long-chain n-3 fatty acids fed in a high P/S diet did not affect tumor growth or host immune responses. In contrast, feeding long-chain n-3 fatty acids in a low P/S diet increased natural killer cell cytotoxicity, splenocyte nitric oxide and interleukin-2 production, and the proportion of activated (CD25+) CD8+ and CD28+ cells, but did not significantly inhibit tumor growth. For both P/S diets, tumor cells from rats fed long-chain n-3 fatty acids had a higher n-3 content and n-3/n-6 ratio in phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol. Furthermore, the magnitude of increase in n-3 fatty acid incorporation into tumor phospholipids was greater when fed in a low P/S diet. We demonstrated that the dietary P/S ratio significantly influences the effect of long-chain n-3 fatty acids on host immune responses and n-3 fatty acid incorporation into tumor cells. These findings warrant further consideration when designing dietary recommendations. [ABSTRACT FROM AUTHOR]

Long-chain n-3 PUFA (n-3 LCPUFA) are known to reduce blood pressure (BP), heart rate and vagal tone, but potential stress-mitigating effects of n-3 LCPUFA are not well investigated. We explored the effects of oily fish consumption on long-term stress and the stress response in schoolchildren. Healthy 8-9-year-old children were randomised to receive about 300 g/week of oily fish or poultry for 12 weeks (199 randomised, 197 completing). At baseline and endpoint, we measured erythrocyte n-3 LCPUFA, hair cortisol and the response to a 1-min cold pressor test (CPT) on saliva cortisol, BP and continuous electrocardiogram recordings. Post-intervention hair cortisol did not differ between the groups, but sex-specificity was indicated (Psex × group = 0·074, boys: -0·9 (95 % CI -2·9, 1·0) ng/g, girls: 0·7 (95 % CI -0·2, 1·6) ng/g). Children in the fish group tended to be less prone to terminate CPT prematurely (OR 0·20 (95 % CI 0·02, 1·04)). Mean heart beat interval during CPT was 18·2 (95 % CI 0·3, 36·6) ms longer and high frequency power increased (159 (95 % CI 29, 289) ms2) in the fish v. poultry group. The cardiac autonomic response in the 10 min following CPT was characterised by a sympathetic peak followed by a parasympathetic peak, which was most pronounced in the fish group. This exploratory study does not support a strong effect of oily fish consumption on stress but indicates that oily fish consumption may increase vagal cardiac tone during the physiological response to CPT. These results warrant further investigation.