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Background: Asthma is an inflammatory disease. The potential of omega-6 fatty acids to alleviate asthma symptoms through their anti-inflammatory and immunomodulatory effects has been investigated. However, the association of dietary omega-6 fatty acids in childhood and adolescent asthma remains controversial., Objective: The aim of this study was to evaluate the association between dietary intake of omega-6 fatty acids and asthma in children and adolescents in the United States., Methods: We conducted a cross-sectional analysis of 5045 children and adolescents from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2020. Covariates were adjusted, and multivariate logistic regression, restricted cubic splines, threshold effects, and subgroup analyses were used., Results: Of the 5045 participants, 1000 (19.8%) were identified as having asthma. After adjustment for potential confounders, individuals in the second group (T2, 215.3-377.7 mg/kg/day) had an adjusted odds ratio (OR) of 0.70 (95% CI: 0.57-0.86, P = 0.001) for asthma compared with those in the lowest omega-6 fatty acid intake group (T1, < 215.3 mg/kg/day). Similarly, individuals in the third group (T3, > 377.7 mg/kg/day) had an adjusted OR of 0.59 (95% CI: 0.45-0.78, P < 0.001) for asthma. Furthermore, a non-linear (L-shaped) relationship between omega-6 intake and asthma was observed (P = 0.001), with subgroup analyses confirming the stability of the results. In the threshold analysis, a critical turning point was observed at around 384.2 mg/kg/day (OR = 0.996, 95% CI: 0.995-0.998, P < 0.001)., Conclusion: The consumption of omega-6 fatty acids in the diet showed an L-shaped association with asthma among children and adolescents in the United States. A critical turning point was noted at approximately 384.2 mg/kg/day., (© 2024. The Author(s).)

The effect of diets with various dietary MUFA content and n-6/n-3 ratios, diets 1 (55.33, 1.00), 2 (25.30, 1.00), 3 (55.13, 2.05), 4 (24.92, 2.03), 5 (54.94, 8.06) and 6 (24.91, 8.06) and a control diet with fish oil (FO), diet 7 (33.60, 5.97), was studied on growth and digestive physiology of rainbow trout, Oncorhynchus mykiss. Juveniles, 14.65 g ± 0.17, were fed the experimental diets for eight weeks. Those fish fed diet 1 (55.33, 1.00) had the lowest growth and nutritional indices, while fish fed diet 6 (24.91, 8.06) possessed the highest indices. However, fish fed D7 (33.60, 5.97) was intermediate in this regard. Proximate body composition results revealed no significant differences among various experimental groups (P > 0.05). Fish fed on diet 1 possessed the highest alkaline protease activity, while fish raised on diet 2 showed the lowest enzyme activity (P < 0.05). Fish fed on diets 1, 3 and 4 had the highest lipase activity (P > 0.05). Amylase activity and intestinal parameters did not differ among groups (P > 0.05). MUFA contents of liver and muscle reflected the MUFA contents of the diets; however, liver PUFA contents was not affected by dietary PUFA contents (P < 0.05). However, 18:3n-3 contents of liver decreased as dietary n-6/n-3 ratio increased (P < 0.05). Furthermore, the liver 20:4n-6 contents considerably increased as dietary n-6/n-3 increased to 8.06 (P < 0.05). Muscle 22:6n-3 content of groups 1 to 6 was lower than group 7 (P < 0.05). In conclusion, rainbow trout was considerably capable of de novo synthesis of 22:6n-3. Meanwhile, increasing dietary n-6/n-3 ratio to 8.06 decreased the muscle 22:6n-3 content which requires further considerations regarding fish immune competence and nutritional quality for human consumption., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Linoleic acid (LA), as a part of the wider debate about saturated, omega-6 and omega-3 fatty acids (FAs) and health, continues to be at the center of controversy in the world of fatty acid research. A robust evidence base, however, demonstrates that higher intakes and blood levels of LA are associated with improved cardiometabolic health outcomes. LA lowers total and low-density lipoprotein cholesterol when compared with saturated fatty acids and carbohydrates. Using large prospective datasets, higher blood levels of LA were associated with lower risk of coronary heart disease, stroke and incident type-2 diabetes mellitus compared with lower levels, suggesting that, across the range of typical dietary intakes, higher LA is beneficial. Recent trials of LA-rich oils report favorable outcomes in people with common lipid disorders. However, an LA intake that is too high can impair endogenous synthesis of eicosapentaenoic acid (EPA) from alpha-linolenic acid (ALA), but the threshold at which this becomes clinically relevant is not known. In the absence of a significant intake of EPA and docosahexaenoic acid, an ideal dietary ratio of LA and ALA may be theoretically useful as it provides insight into the likely extent of endogenous EPA synthesis from ALA. Updating dietary reference intakes (DRIs) for LA and ALA is needed; however, there are insufficient data to establish RDAs for these fatty acids. The omega-6 (n-6) to omega-3 (n-3) PUFA ratio is not informative and does not shed meaningful insight about the amount of individual fatty acids in each class needed to confer health benefits., (© 2024. The Author(s).)

The aim of this study was to investigate the effects of a supplement rich in ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) and antioxidant vitamins on physical performance and body composition following a period of high-intensity functional training (HIFT). Nineteen healthy young adults (nine males, ten females) underwent an 8-week HIFT program (3 days·week -1 ) where they were randomized 1:1 into either the supplement group (SG)- n = 10, receiving a 20 mL daily dose of a dietary cocktail formula (Neuroaspis™ PLP10) containing a mixture of ω-3 and ω-6 PUFAs (12,150 mg), vitamin A (0.6 mg), vitamin E (22 mg), and γ-tocopherol (760 mg)-or the placebo group (PG)- n = 9, receiving a 20 mL daily dose of virgin olive oil. Body composition, cardiorespiratory fitness, muscle strength, and muscle endurance were assessed before and after the training period. Body mass did not change, but muscle mass increased by 1.7 ± 1.9% or 0.40 ± 0.53 kg in the SG ( p = 0.021) and decreased by 1.2 ± 1.6% or 0.28 ± 0.43 kg ( p = 0.097) in the PG, compared with baseline. VO 2 max, vertical jump, squat 1RM, bench press 1RM, and muscle endurance increased similarly in both groups. The effects of HIFT on physical performance parameters, muscle damage, and inflammation indices were not affected by the supplementation. In conclusion, HIFT combined with high doses of ω-3 and ω-6 PUFAs and antioxidant vitamins resulted in a small but significant increase in muscle mass and fat reduction compared with HIFT alone.

Objectives: The association between the ingestion of n-3 and n-6 fatty acids and rheumatoid arthritis (RA) remains unclear. To address this, this study utilised data from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2020., Methods: Dietary intake information on n-3 and n-6 fatty acids was gathered through 24-hour interviews about dietary recall and adjusted based on weight. RA patient data was collected using questionnaires. Associations were evaluated using logistic regression and spline analyses. The study included a total of 50,352 participants in a cross-sectional manner., Results: In the adjusted Model 2, higher odds ratios (ORs) of 0.72 (95% CI: 0.60-0.86) and 0.76 (95% CI: 0.62-0.92) were observed for n-3 and n-6 fatty acid intake, respectively, compared to the lowest category., Conclusions: The results suggest a negative correlation between the ingestion of n-3 and n-6 fatty acids and the risk of rheumatoid arthritis in US adults.

Background and Aims: The objective of this research was to explore the associations between dietary PUFAs intake and hyperuricemia risk., Methods and Results: Based on the National Health and Nutrition Examination Survey (NHANES) 2003-2015, all eligible individuals were divided into hyperuricemia and non-hyperuricemia groups based on diagnostic criteria for hyperuricemia (serum uric acid >420 μmol/L for men and >360 μmol/L for women). Multivariate-adjusted logistic regression was employed to explore the relationship between dietary PUFAs intake and hyperuricemia risk. Total PUFAs and their subtypes were modeled to isocalorically replace saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). Higher intake of n-3 PUFAs, n-6 PUFAs, linoleic acid (LA), alpha-linoleic acid (ALA), and non-marine PUFAs intake correlated with decreased hyperuricemia risk, with adjusted odds ratio (OR) and 95% confidence interval (95%CIs) were 0.77 (0.63, 0.93), 0.75 (0.61, 0.92), 0.75 (0.61, 0.91), 0.69 (0.55, 0.87), and 0.73 (0.59, 0.91), respectively. Replacing 5% of total energy intake from SFAs with isocaloric PUFAs was associated with decreased odds of hyperuricemia in men (0.69 (0.57, 0.84)) and in individuals (0.81 (0.71, 0.92)). Similar trends were observed in the substitution of SFAs with non-marine PUFAs in men (0.87 (0.80, 0.94)) and in all individuals (0.92 (0.88, 0.98)). Sensitivity analyses exhibited consistent results with primary analyses., Conclusion: Higher dietary intake of n-3 PUFAs, n-6 PUFAs, LA, ALA, and non-marine PUFAs was associated with decreased hyperuricemia risk. These results support the recommendation to substitute SFAs with PUFAs in diet., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

The risk of chronic diseases such as cardiovascular disease, cancer, inflammation, obesity, and autoimmune disease is linked to the quality of dietary fats, with lower intake of saturated and higher intake of n-6 and n-3 polyunsaturated fatty acids (PUFA) considered beneficial to health. This study investigated the effect of supplementing sows' diets with cow's milk biofortified with n-6 or n-3 PUFA, at varying n-6/n-3 ratios (8.26, 7.92, and 2.72) during their growing phase and throughout gestation and lactation on their reproductive performance and immune-inflammatory status. Specifically, we analyzed circulating cholesterol and fatty acid profiles of serum, colostrum and milk, sow body weight, and neonate colostrum intake, Apgar scores, muscle composition, and embryo viability. Analysis of circulating immunoglobulins (Ig), interleukins, and eicosanoids and complement system hemolytic activity were used to evaluate inflammatory and immune responses of sows and piglets. Expression of lipolysis and lipogenic genes in the liver were investigated in sows and piglets, with additional investigation of hypothalamus genes regulating appetite in sows. Feeding sows milk biofortified with n-6 and n-3 PUFA altered serum fatty acid profiles, reduced triglycerides (TG), increased embryo total number, increased early gestation backfat, and reduced colostrum IgG. Piglets of biofortified sow had higher circulating IgA, IgM and TNF-α, and lower IL-10. Sows fed n-3 biofortified milk had higher very low-density lipoproteins (VLDL) and TNF-α in circulation. Offspring from sows fed n-6 versus n-3 biofortified milk had lower IL-10 and expression levels of SREBP-1. N-3 versus n-6 also lowered arachidonic acid (ARA) levels in sow's milk and piglet viability 1. Findings offer insights into the potential health benefits of dietary supplementation with biofortified milk in swine, which serve as good model of diet-nutrition studies of humans, and therefore can potentially be considered in dietary recommendations both human and animal populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Reis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Functional lipids are dietary substances that may have an impact on human health by lowering the risk of chronic illnesses and enhancing the quality of life. Numerous functional lipids have been reported to have potential health benefits in the prevention, management, and treatment of cardiovascular disease, the leading cause of death in the United States. However, there is still insufficient and contradictory information in the literature about their effectiveness and associated mechanisms of action. The objective of this review, therefore, is to evaluate available literature regarding these functional lipids and their health benefits. Various studies have been conducted to understand the links between functional lipids and the prevention and treatment of chronic diseases. Recent studies on phytosterols have reported that CLA, medium-chain triglycerides, and omega-3 and 6 fatty acids have positive effects on human health. Also, eicosanoids, which are the metabolites of these fatty acids, are produced in relation to the ratio of omega-3 to omega-6 polyunsaturated fatty acids and may modulate disease conditions. These functional lipids are available either in dietary or supplement forms and have been proven to be efficient, accessible, and inexpensive to be included in the diet. However, further research is required to properly elucidate the dosages, dietary intake, effectiveness, and their mechanisms of action in addition to the development of valid disease biomarkers and long-term effects in humans.

Background: Depression is a common psychological disorder worldwide, affecting mental and physical health. Previous studies have explored the benefits of polyunsaturated fatty acids (PUFAs) intake in depressive symptoms; however, few studies have focused on the association between all types of fatty acids intake and depressive symptoms. Therefore, we explored the relationship between the intake of different fatty acids intake and the risk of depressive symptoms., Methods: The study was based on the data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES), a large US-based database. We used a nutrient residual model and multi-nutrient density model for the analysis. We calculated the nutrient density and residual in men and women separately, and the fatty acids intake was divided into quartiles based on the sex distribution. The relationship between the depressive symptoms and the intake of different fatty acids was examined using logistic regression; furthermore, we explored the relationships separately in men and women., Results: The intake of monounsaturated fatty acids (MUFAs) and PUFAs, particularly n-3 and n-6 PUFAs, were associated with reduced odds ratios for depressive symptoms. The inverse relationship between the intake of MUFAs, PUFAs, n-3, and n-6 PUFAs and depressive symptoms was stronger in women. The inverse relationship between total fatty acid (TFAs) intake and depressive symptoms existed only in a single model. In contrast, saturated fatty acid (SFAs) intake was not related to depressive symptoms., Conclusion: Consuming MUFAs and PUFAs can counteract the depressive symptoms, especially in women., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Single-nucleotide polymorphisms (SNPs) in fatty acid desaturase (FADS) genes may modify dietary fatty acid requirements and influence cardiometabolic health (CMH)., Objectives: We evaluated the role of selected variants in maternal and offspring FADS genes on offspring CMH at the age of 11 y and assessed interactions of genotype with diet quality and prenatal docosahexaenoic acid (DHA) supplementation., Methods: We used data from offspring (n = 203) born to females who participated in a randomized controlled trial of DHA supplementation (400 mg/d) from midgestation to delivery. We generated a metabolic syndrome (MetS) score from body mass index, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and fasting glucose and identified 6 distinct haplotypes from 5 offspring FADS SNPs. Dietary n-6 (ω-6):n-3 fatty acid ratios were derived from 24-h recall data (n = 141). We used generalized linear models to test associations of offspring diet and FADS haplotypes with MetS score and interactions of maternal and offspring FADS SNP rs174602 with prenatal treatment group and dietary n-6:n-3 ratio on MetS score., Results: Associations between FADS haplotypes and MetS score were null. Offspring SNP rs174602 did not modify the association of prenatal DHA supplementation with MetS score. Among children with TT or TC genotype for SNP rs174602 (n = 88), those in the highest n-6:n-3 ratio tertile (>8.61) had higher MetS score relative to the lowest tertile [<6.67) (Δ= 0.36; 95% confidence interval (CI): 0.03, 0.69]. Among children with CC genotype (n = 53), those in the highest n-6:n-3 ratio tertile had a lower MetS score relative to the lowest tertile (Δ= -0.23; 95% CI: -0.61, 0.16)., Conclusions: There was evidence of an interaction of offspring FADS SNP rs174602 with current dietary polyunsaturated fatty acid intake, but not with prenatal DHA supplementation, on MetS score. Further studies may help to determine the utility of targeted supplementation strategies and dietary recommendations based on genetic profile., (Copyright © 2024. Published by Elsevier Inc.)

Modern agriculture allows for the production of foods that are high in n-6 linoleic acid and low in n-3 α-linolenic acid (LA high /ALA low ), which are suggested to be associated with an increased risk for the onset of anxiety disorders. However, there is not sufficient evidence to understand its underlying brain mechanism. Given that mouse offspring derived from mothers fed a LA high /ALA low diet during gestation and early lactation showed increased anxiety-related behaviors and that rodents exposed to a LA high /ALA low diet are more vulnerable to stress, in this study, we investigated the effects of maternal LA high /ALA low diet consumption on stress-induced anxiety-related behavior and the brain structures involved in the expression of negative emotional states in mouse offspring. In a standard environment, offspring exposed to either the control diet or the LA high /ALA low diet in utero showed similar stay times in the center zone in the open field test. On the other hand, under stressful environments, offspring exposed to the LA high /ALA low diet in utero showed decreased stay times in the center zone compared to those exposed to the control diet. We further found that the number of a subpopulation of pyramidal neurons in the basolateral amygdala, which can regulate negative emotional behaviors, was greater in the offspring exposed to the LA high /ALA low diet compared to those exposed to the control diet. These data suggest that maternal dietary imbalance between n-6 and n-3 polyunsaturated fatty acids confers stress vulnerability to offspring during the process of brain development.

Objective: To examine the causal association between 15 dietary factors and the incidence of colorectal cancer through the application of Mendelian randomization methodology., Methods: The data associated with 15 dietary factors were derived from the IEU OPEN GWAS database, and the colorectal cancer data were sourced from the FinnGen database. The Inverse Variance Weighting method was the principal research method. Sensitivity analyses were implemented to affirm the robustness of the findings. Additionally, we conducted multivariable Mendelian randomization analyses to adjust for the intake of ω-3 and ω-6 polyunsaturated fatty acids., Results: In our research, we observed suggestive causal relationships between genetically predicted water intake and the reduced risk of colorectal cancer (OR = 0.54; 95% CI= 0.31 ∼ 0.93; p  = 0.028); genetically predicted ω-3 PUFA intake (OR = 1.17; 95% CI= 1.05 ∼ 1.30; p  = 0.005) were suggestively associated with the increased risk of colorectal cancer. In the multivariable Mendelian randomization analysis, the effect of ω-3 PUFA intake remains significant after adjusting for the influence of ω-6 PUFA intake. Horizontal pleiotropy was not present in this study., Conclusions: There exists a suggestive causal association between increased water intake and decreased risk of colorectal cancer, while ω-3 PUFA intake are suggestive linked to the increased risk of colorectal cancer.

The efficacy of n-3 polyunsaturated fatty acids (PUFAs) in improving outcomes in a renal ischemia-reperfusion injury (IRI) model has previously been reported. However, the underlying mechanisms remain poorly understood and few reports demonstrate how dietary n-3 PUFAs influence the composition of membrane phospholipids in the kidney. Additionally, it has not been elucidated whether perilla oil (PO), which is mainly composed of the n-3 alpha-linolenic acid, mitigates renal IRI. In this study, we investigated the effect of dietary n-3 PUFAs (PO), compared with an n-6 PUFA-rich soybean oil (SO) diet, on IRI-induced renal insufficiency in a rat model. Levels of membrane phospholipids containing n-3 PUFAs were higher in the kidney of PO-rich diet-fed rats than the SO-rich diet-fed rats. Levels of blood urea nitrogen and serum creatinine were significantly higher in the ischemia-reperfusion group than the sham group under both dietary conditions. However, no significant differences were observed in blood urea nitrogen, serum creatinine, or histological damage between PO-rich diet-fed rats and SO-rich diet-fed rats. In the kidney of PO-rich diet-fed rats, levels of arachidonic acid and arachidonic acid-derived pro-inflammatory lipid mediators were lower than SO-rich diet-fed rats. Eicosapentaenoic acid and eicosapentaenoic acid-derived lipid mediators were significantly higher in the kidney of PO-rich than SO-rich diet-fed rats. These results suggest that dietary n-3 PUFAs alter the fatty acid composition of membrane phospholipids and lipid mediators in the kidney; however, this does not attenuate renal insufficiency or histological damage in a renal IRI model., Competing Interests: Declaration of competing interest The authors declare no conflicts of interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Studies evaluating effects of prenatal polyunsaturated fatty acid (PUFA) intake on childhood asthma reveal mixed results. Inconsistencies may result from not accounting for important modifying factors such as maternal asthma or child sex., Objective: To evaluate whether associations between prenatal PUFA intake and childhood asthma are modified by prenatal active maternal asthma or child sex in 412 mother-child dyads., Methods: Energy-adjusted prenatal dietary and supplement intakes of omega-3 (n-3) and omega-6 (n-6) PUFAs were estimated using the Block98 Food Frequency Questionnaire, administered during pregnancy. Mothers reported asthma in children followed prospectively to 4.0 plus or minus 1.7 years. Generalized additive models with smooth terms for PUFA (n-3, n-6, n-6/n-3 ratio) effects were used to investigate associations between PUFAs and child asthma, without prespecifying the form of these relationships, including effect modification by active maternal asthma or child sex., Results: Among mothers (40% Black, 31% Hispanic), 22% had active asthma in pregnancy; 17.5% of children developed asthma. Lower maternal n-3 PUFA intake was significantly associated with risk of childhood asthma (P = .03), in particular among children of mothers with active asthma and low n-3 PUFA intake (P = .01). This inverse association was more apparent in girls (P = .01) compared with boys (P = .30), regardless of maternal asthma status. For n-6 PUFA and the n-6/n-3 ratio, there was a lower risk of childhood asthma in the midrange of intake and increased risk at higher intake (n-6 PUFA P = .10, n-6/n-3 ratio P = .13)., Conclusion: Consideration of factors that modify effects of prenatal PUFA intake on childhood asthma has implications for designing intervention strategies tailored to impact those at greatest risk., (Copyright © 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The effects of saturated fat intake on obesity and cardiovascular health remain inconclusive, likely due in part to their varied nature and interactions with other nutrients. Investigating the synergistic effects of different saturated fat sources with other dietary lipid components will help establish more accurate nutritional guidelines for dietary fat intake. Over the past two decades, zebrafish (Danio rerio) have been established as an attractive model system to address questions regarding contributions of dietary lipid intake to diet-induced obesity in humans. The goal of the present study was to assess interactions of three different saturated fat sources (milk fat, palm oil, and coconut oil) with sex and total dietary lipid intake on weight gain and body composition in adult zebrafish. Larvae were raised on live feeds until 28 days post fertilization, and then fed a formulated maintenance diet until three months of age. An eight-week feeding trial was then initiated, in which zebrafish were fed nine experimental low- and high-fat diets varying in saturated fatty acid and long-chain polyunsaturated fatty acid content, in addition to a low-fat and high-fat control diet. At termination of the feeding trial, each treatment was evaluated according to body mass, moisture content, and adiposity. Sex and diet significantly interacted in their effects on body mass (P = 0.026), moisture content (P = 0.044), and adiposity (P = 0.035). The influence of saturated fat source on body mass was observed to be dependent on intake of total dietary lipid. In females, all three saturated fat sources had similar effects on adiposity. From these observations, we hypothesize that impacts of saturated fat intake on energy allocation and obesity-related phenotypes are influenced by both sex and intake of other dietary lipid components. Our results suggest that current nutritional guidelines for saturated fat intake may need to be re-evaluated and take sex-specific recommendations into consideration., Competing Interests: The authors have declared that no competing interests exist.

Senile plaque formation as a consequence of amyloid-β peptide (Aβ) aggregation constitutes one of the main hallmarks of Alzheimer's disease (AD). This pathology is characterized by synaptic alterations and cognitive impairment. In order to either prevent or revert it, different therapeutic approaches have been proposed, and some of them are focused on diet modification. Modification of the ω-6/ω-3 fatty acids (FA) ratio in diets has been proven to affect Aβ production and senile plaque formation in the hippocampus and cortex of female transgenic (TG) mice. In these diets, linoleic acid is the main contribution of ω-6 FA, whereas alpha-linoleic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) are the contributors of ω-3 FA. In the present work, we have explored the effect of ω-6/ω-3 ratio modifications in the diets of male double-transgenic APPswe/PS1ΔE9 (AD model) and wild-type mice (WT). Amyloid burden in the hippocampus increased in parallel with the increase in dietary ω-6/ω-3 ratio in TG male mice. In addition, there was a modification in the brain lipid profile proportional to the ω-6/ω-3 ratio of the diet. In particular, the higher the ω-6/ω-3 ratio, the lower the ceramides and higher the FAs, particularly docosatetraenoic acid. Modifications to the cortex lipid profile was mostly similar between TG and WT mice, except for gangliosides (higher levels in TG mice) and some ceramide species (lower levels in TG mice).

Folate cannot prevent all neural tube defects (NTD), indicating that other pathogeneses still exist except for the folate deficiency. Maternal diabetes mellitus during pregnancy can increase the risk of offspring NTD. Our previous study showed that polyunsaturated fatty acids (PUFA) were lower in the placenta of human NTD cases than in healthy controls, and the supplementation of fish oil (rich in long-chain (LC) n-3 PUFA, mainly C20:5n-3 and C22:6n-3) had a better prevention effect against sodium valproate induced NTD than corn oil (rich in C18:2n-6) and flaxseed oil (rich in C18:3n-3). The aim of the present study was to investigate whether PUFA could prevent diabetes-induced NTD in mice. Streptozotocin (STZ)-induced diabetic pregnant mice were fed with a normal diet (DMC), a diet containing a low dose of fish oil (DMLn-3), a diet containing a high dose of fish oil (DMHn-3) or a diet rich in corn oil (DMn-6). Healthy pregnant mice were fed with a normal diet (HC). Compared with the DMC group, the rate of NTD was significantly lower in the DMHn-3 group (4.44% vs. 12.50%), but not in the DMLn-3 (11.11%) or DMn-6 group (12.03%). The NTD rate in the DMHn-3 group was comparable with that in the HC group (1.33%) ( p = 0.246), and lower than that in the DMn-6 group ( p = 0.052). The NTD rate in DMLn-3 and DMn-6 groups was significantly higher than that in the HC group. No significant difference was observed in NTD rate between DMLn-3 and DMHn-3 groups, and between DMLn-3 and DMn-6 groups. Compared with the HC group, the DMC group had a significantly lower C22:6n-3 in both serum and embryos. Fish oil supplementation ameliorated neuroepithelial cell apoptosis, and the apoptotic rate was comparable between DMHn-3 and HC groups. Although the apoptotic rate was significantly lower in the DMn-6 group than the DMC group, it was still much higher than that in the HC group. The proteins P53 and Bax in embryos were higher, while the proteins Bcl-2 and Pax3 were lower in the DMC group than in the HC group. The disturbance of Pax3, P53 and Bax induced by diabetes was abolished in DMLn-3, DMHn-3 and DMn-6 groups. Importantly, Bcl-2 in embryos was restored to the normal level only in the DMHn-3 group but not in the DMLn-3 or DMn-6 group. In conclusion, LC n-3 PUFA enriched fish oil has a protective effect against NTD in diabetes induced by STZ through improving neuroepithelial cell apoptosis, and the mechanism may be by increasing the anti-apoptosis protein Bcl-2 independently of Pax3 and P53.

Supplementing palmitic acid (C16 : 0) in combination with modifying the dietary n-6:n-3 fatty acid (FA) ratio may benefit energy metabolism and milk responses of dairy cows. Twelve Holstein cows (70 (sd 11) days in milk) were used in a replicated 4 × 4 Latin square and allocated to four low-fibre diets (18·5 % forage neutral-detergent fibre) supplemented with no FA (CON), or 2·4 % C16 : 0-enriched supplement (PAL), 2·4 % mixture (2:1) of C16 : 0 and n-6 FA (PW6), and mixture (2:1) of C16 : 0 and n-3 FA (PW3). The dietary ratio of n-6:n-3 was increased with PW6 (10:1) and decreased with PW3 (2·8:1), whereas PAL alone made no change in the ratio (about 7:1). Compared with CON, all FA-supplemented treatments increased milk yield. However, feed and energy intakes were higher in PAL than PW3 or PW6, resulting in greater feed efficiency for PW3 and PW6 than PAL. Dietary FA supplements decreased milk protein concentration but tended to increase protein yield. Compared with CON and FA mixtures, PAL increased milk fat content and tended to increase milk SFA and atherosclerotic index. The concentration of milk n-3 FA was similar between CON and PW3. Feeding PAL increased milk energy output and decreased energy partitioning towards body reserves (-4·2 %), while this measure was positive for other treatments. Blood TAG and NEFA concentrations, but not β-hydroxybutyrate, were increased by FA-supplemented treatments. Feeding C16 : 0 combined with either n-6 or n-3 FA enhanced feed efficiency, alleviated the negative impacts on body energy reserves, but lowering the dietary n-6:n-3 ratio improved the FA profile of milk.

Osteoarthritis (OA), the most common form of arthritis, is characterized by cartilage destruction, and its incidence is much higher in the osteoporotic population. There is increasing evidence that the occurrence and development of OA are modulated by the dietary intake of polyunsaturated fatty acids (PUFA). This study investigated the effects of dietary PUFA, including n-3/n-6 PUFA proportion and the molecular form of n-3 PUFA, on OA using osteoporotic osteoarthritis dual model mice, where phospholipid type n-3 PUFA were specifically examined. The results revealed that a low proportion of n-6/n-3 PUFA in diets from 1 : 1 to 6 : 1 significantly improved the cartilage structure and inhibited articular cartilage polysaccharide loss. Furthermore, the low proportion n-6/n-3 PUFA diets inhibited the NF-κB signaling pathway by activating G-protein coupled receptor 120 (GPR120) to reduce inflammation and inhibit catabolism. Antarctic krill (Euphausia superba) oil (AKO), rich in phospholipid-type n-3 PUFA, had a better effect on OA than linseed oil (plant-derived n-3 PUFA), which may be due to peroxisome proliferator-activated receptor-gamma (PPAR γ). These findings suggested that the low proportion n-6/n-3 PUFA diets, particularly with AKO, alleviated inflammation and inhibited articular cartilage degeneration. Therefore, dietary intervention can be a potential treatment for OA.

Long-chain omega-3 PUFAs, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are of increasing interest because of their favorable effect on cardiometabolic risk. This study explores the association between omega 6 and 3 fatty acids intake and cardiometabolic risk in four African-origin populations spanning the epidemiological transition. Data are obtained from a cohort of 2500 adults aged 25-45 enrolled in the Modeling the Epidemiologic Transition Study (METS), from the US, Ghana, Jamaica, and the Seychelles. Dietary intake was measured using two 24 h recalls from the Nutrient Data System for Research (NDSR). The prevalence of cardiometabolic risk was analyzed by comparing the lowest and highest quartile of omega-3 (EPA+ DHA) consumption and by comparing participants who consumed a ratio of arachidonic acid (AA)/EPA + DHA ≤4:1 and >4:1. Data were analyzed using multiple variable logistic regression adjusted for age, gender, activity, calorie intake, alcohol intake, and smoking status. The lowest quartile of EPA + DHA intake is associated with cardiometabolic risk 2.16 (1.45, 3.2), inflammation 1.59 (1.17, 2.16), and obesity 2.06 (1.50, 2.82). Additionally, consuming an AA/EPA + DHA ratio of >4:1 is also associated with cardiometabolic risk 1.80 (1.24, 2.60), inflammation 1.47 (1.06, 2.03), and obesity 1.72 (1.25, 2.39). Our findings corroborate previous research supporting a beneficial role for monounsaturated fatty acids in reducing cardiometabolic risk.

We aimed to investigate if a home meal replacement (HMR), designed with a low ω-6/ω-3 fatty acid ratio, improves cardiometabolic parameters, including metabolic syndrome (MetS) in obese individuals. We conducted a monocentric, controlled, randomized crossover trial. The HMR contains higher protein and fat content, lower carbohydrate content, and a lower ω6FA/ω3FA ratio than the regular diet. Sixty-four participants were randomized into two groups and switched to the other group following a 4-week intervention. While subjects in the HMR group were provided three HMRs daily, those in the control group were requested to maintain their regular dietary pattern. We conducted paired t-tests, repeated measures analysis of variance, and McNemar tests before and after the intervention. Body mass index (BMI) and weight were lower in the HMR group after adjusting for age, sex, and total energy intake and significantly changed in the between-group differences. The waist circumference, systolic blood pressure, triglycerides, triglyceride-glucose index, and triglyceride to high-density lipoprotein cholesterol ratio were reduced in the HMR group (all p < 0.05). The percentage of subjects with MetS significantly decreased from 39.1% at baseline to 28.1% post-intervention ( p = 0.035). Using the HMR for 4 weeks reduced the BMI, weight, and MetS prevalence in individuals with obesity. This trial was registered at clinicaltrials.gov (NCT04552574).

Background & Aims: Increasing dietary intake of n-3 EPA+DHA and lowering dietary n-6 LA is under investigation as a therapeutic diet for improving chronic pain syndromes as well as other health outcomes. Herein we describe the diet methodology used to modulate intake of n-3 and n-6 PUFA in a free living migraine headache population and report on nutrient intake, BMI and diet acceptability achieved at week 16 of the intensive diet intervention and week 22 follow-up time-point., Methods: A total of 178 participants were randomized and began one of three diet interventions: 1) a high n-3 PUFA, average n-6 PUFA (H3) diet targeting 1500 mg EPA+DHA/day and 7% of energy (en%) from n-6 linoleic acid (LA), 2) a high-n-3 PUFA, low-n-6 PUFA (H3L6) targeting 1500 mg EPA+DHA/day and <1.8 en% n-6 LA or 3) a Control diet with typical American intakes of both EPA+DHA (<150 mg/day) and 7 en% from n-6 LA. Methods used to achieve diet change to week 16 include diet education, diet counseling, supply of specially prepared foods, self-monitoring and access to online diet materials. Only study oils and website materials were provided for the follow-up week 16 to week 22 periods. Diet adherence was assessed by multiple 24 h recalls administered throughout the trial. Diet acceptability was assessed in a subset of participants at 4 time points by questionnaire., Results: At week 16 H3 and H3L6 diet groups significantly increased median n-3 EPA+DHA intake from 48 mg/2000 kcals at baseline to 1484 mg/2000 kcals (p < 0.0001) and from 44 mg/2000 kcals to 1341 mg/2000 kcals (p < 0.0001), respectively. In the Control group, EPA+DHA intake remained below the typical American intake with baseline median at 60 mg/2000 kcals and 80 mg/2000 kcals (p = 0.6) at week 16. As desired, LA intake was maintained in the H3 and Control group with baseline median of 6.5 en% to 7.1 en% (p = 0.4) at week 16 and from 6.5 en% to 6.8 en% (p = 1.0) at week 16, respectively. In the H3L6 group, n-6 LA decreased from 6.3 en% at baseline to 3.2 en% (p < 0.0001) at week 16. There were no significant changes in BMI or diet acceptability throughout the trial or between diet groups., Conclusions: We find this diet method to be acceptable to research participants and successful in altering dietary n-3 EPA+DHA with and without concurrent decreases in n-6 LA. If n-6 LA of less than 3 en% is desired, additional techniques to limit LA may need to be employed., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Marine-derived omega-3 (n-3) polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lower circulating levels of triacylglycerols (TAGs), and the plant-derived omega-6 (n-6) PUFA linoleic acid (LA) may reduce cholesterol levels. Clinical studies on effects of these dietary or supplemental PUFAs on other blood fat fractions are few and have shown conflicting results. This study aimed to determine effects of high-dose supplemental n-3 (EPA + DHA) and n-6 (LA) PUFAs from high-quality oils on circulating lipoprotein subfractions and standard lipids (primary outcomes), as well as apolipoproteins, fatty acids, and glycemic control (secondary outcomes), in females and males with abdominal obesity., Methods: This was a randomized double-blind crossover study with two 7-wk intervention periods separated by a 9-wk washout phase. Females (n = 16) were supplemented with 3 g/d of EPA + DHA (TAG fish oil) or 15 g/d of LA (safflower oil), while males (n = 23) received a dose of 4 g/d of EPA + DHA or 20 g/d of LA. In fasting blood samples, we investigated lipoprotein particle subclasses by nuclear magnetic resonance spectroscopy, as well as standard lipids, apolipoproteins, fatty acid profiles, and glucose and insulin. Data were analyzed by linear mixed-effects modeling with 'subjects' as the random factor., Results: The difference between interventions in relative change scores was among the lipoprotein subfractions significant for total very-low-density lipoproteins (VLDLs) (n-3 vs. n-6: -38%∗ vs. +16%, p < 0.001; ∗: significant within-treatment change score), large VLDLs (-58%∗ vs. -0.91%, p < 0.001), small VLDLs (-57%∗ vs. +41%∗, p < 0.001), total low-density lipoproteins (LDLs) (+5.8%∗ vs. -4.3%∗, p = 0.002), large LDLs (+23%∗ vs. -2.1%, p = 0.004), total high-density lipoproteins (HDLs) (-6.0%∗ vs. +3.7%, p < 0.001), large HDLs (+11%∗ vs. -5.3%, p = 0.001), medium HDLs (-24%∗ vs. +6.2%, p = 0.030), and small HDLs (-9.9%∗ vs. +9.6%∗, p = 0.002), and among standard lipids for TAGs (-16%∗ vs. -2.6%, p = 0.014), non-esterified fatty acids (-19%∗ vs. +5.5%, p = 0.033), and total cholesterol (-0.28% vs. -4.4%∗, p = 0.042). A differential response in relative change scores was also found for apolipoprotein (apo)B (+0.40% vs. -6.0%∗, p = 0.008), apoA-II (-6.0%∗ vs. +1.5%, p = 0.001), apoC-II (-11%∗ vs. -1.7%, p = 0.025), and apoE (+3.3% vs. -3.8%, p = 0.028)., Conclusions: High-dose supplementation of high-quality oils with n-3 (EPA + DHA) or n-6 (LA) PUFAs was followed by reductions in primarily TAG- or cholesterol-related markers, respectively. The responses after both interventions point to changes in the lipoprotein-lipid-apolipoprotein profile that have been associated with reduced cardiometabolic risk, also among people with TAG or LDL-C levels within the normal range., Registration: Registered under ClinicalTrials.gov Identifier: NCT02647333., Clinical Trial Registration: Registered at https://clinicaltrials.gov/ct2/show/NCT02647333., Competing Interests: Conflict of interest All the authors declare to have no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The relationship between ω-3 and ω-6 fatty acids consumption and sleep disorders or duration are controversial. Therefore, we used the data of the National Health and Nutrition Examination Survey 2007-2016 in this cross-sectional study to explore their relationships. ω-3 and ω-6 fatty acids consumption was assessed using two 24 h dietary recall interviews. Sleep disorders and sleep duration were based on self-reported data. Logistic regression models and restricted cubic spline analyses were used. Compared with tertile one, the odds ratios (ORs) and 95% confidence intervals (CIs) of sleep disorders for the second tertile of ω-6 fatty acid intake and the highest tertile of ω-6:ω-3 ratio were 1.30 (1.04-1.62) and 1.36 (1.08-1.70), respectively. Inverse U-shaped and linear dose-response relationships were observed between dietary ω-6 fatty acid intake and ω-6:ω-3 ratio and sleep disorders, respectively. In addition, ω-3 fatty acid consumption was adversely related to sleep disorders in men and the OR (95% CI) was 0.68 (0.49-0.95). Compared with normal sleep duration, ω-3 fatty acid consumption was negatively related to very short, short, and long sleep duration risk. The relative risk ratios (RRRs) were 0.53 (0.35-0.81), 0.79 (0.67-0.93), and 0.81 (068-0.98), respectively. The RRR of very short sleep for ω-6 fatty acid consumption was 0.57 (0.45-0.73). Our study indicates that ω-6 fatty acid consumption and the ω-6:ω-3 ratio are positively associated with the risk of sleep disorders, while the negative association between ω-3 fatty acids and sleep disorders may exist only in men. Furthermore, ω-3 and ω-6 fatty acid consumption are negatively related to the risk of non-normal sleep duration.

Background: Previous acute studies suggest the Glu298Asp polymorphism (rs1799983) may influence vascular reactivity in response to long-chain n-3 PUFA intake. However, the effects of this genotype on postprandial vascular function after meals rich in SFAs, n-6 PUFAs, and MUFAs are unclear., Objectives: This study determined the impact of the Glu298Asp polymorphism on changes in vascular function and cardiometabolic risk biomarkers in response to sequential meals of varying fat composition., Methods: In a randomized, double-blind, crossover, acute study, 32 postmenopausal women (mean ± SD age: 58 ± 5 y; BMI: 25.9 ± 4.1 kg/m2) consumed mixed meals (breakfast: 0 min, 50 g fat; lunch: 330 min, 30 g fat) containing SFAs, n-6 PUFAs, or MUFAs on 3 occasions. Blood samples for cardiometabolic disease risk markers and real-time measures of vascular reactivity [including flow-mediated dilatation (FMD; primary outcome)] were collected/performed before and regularly for 480 min after breakfast. Participants were retrospectively genotyped for the Glu298Asp (rs1799983) polymorphism. Data were analyzed using linear mixed models., Results: For the postprandial %FMD response, a test fat × genotype interaction was observed for the AUC (P = 0.019) but not incremental AUC (IAUC), with the AUC being ∼24% greater after MUFA- than after SFA- and n-6 PUFA-rich meals in the Glu298 homozygotes (P ≤ 0.026). Test fat × genotype interactions were also evident for postprandial insulin (P ≤ 0.005), with the MUFA-rich meals demonstrating significantly higher AUC (12.8%/14.9%), IAUC (14.6%/20.0%), and maximum concentration (20.0%/34.5%) than the SFA- and n-6 PUFA-rich meals, respectively, in Asp298 carriers (P < 0.05). Genotype did not influence other study outcome measures in response to the test fats., Conclusions: Our findings suggest the Glu298Asp polymorphism may represent a potential determinant of the inter-individual variability in postprandial responsiveness of %FMD and insulin to acute meal fat composition in postmenopausal women. Further studies are required to confirm these observations.This trial was registered at clinicaltrials.gov as NCT02144454., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The purpose of this study was to determine effects of various sources of omega-3 and omega-6 fatty acids on ovarian response and embryo quality in Boer does when there was a superovulation treatment regimen imposed. Pluriparous does were randomly assigned to be treated with 300 g of one of four experimental supplements containing linseed oil (LO), soybean oil (SO), palm oil (PO), or a control supplement without fatty acids (CO), for 15 days. Does were fitted with a controlled internal drug release (CIDR) device containing 0.3 g progesterone for 7 days. At 48 h before CIDR withdrawal, does were treated with 80 mg follicle-stimulating hormone (FSH) administered at 12 h intervals. Embryos were collected 7 days after the last natural mating. Estrous response and interval between CIDR withdrawals to estrous onset were similar between treatments (P > 0.05). Number of ovulations was similar for does in the different groups (10.0, 9.2, 7.0, and 7.0, in LO, SO, PO, and CO, respectively; P > 0.05). There was premature luteal regression in does of the SO, PO, and CO groups, except in LO group. The LO-treated does had a larger (P < 0.05) mean number of ova/embryos recovered than does of SO, PO, and CO groups (7.2, 2.0, 0.2, 0.2, respectively) and transferable embryos (5.1, 1.4, 0.2, 0.2, respectively). These results indicate that including LO in supplements may be a feasible strategy for preventing premature luteal regression and improving embryo quality in goats treated to induce follicular super-stimulation for induction of superovulation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The ratio n-6/n-3 polyunsaturated fatty acids (PUFA) has been caused widespread discussion. However, the best ratio and mechanism of n-6/n-3 PUFA in type 2 diabetes mellitus (T2DM) are largely unknown. This study investigated the effects of different ratio of n-6/n-3 PUFA diets on brown adipose tissue (BAT) and T2DM in mice. Results showed that compared with high ratio of n-6/n-3 PUFA (50:1) diet, lower ratio of n-6/n-3 PUFA (1:1 and 5:1) diets significantly increased BAT mass by 67.55% and 60.49%, decreased the fasting blood glucose (24.87% and 20.64%), total cholesterol (32.9% and 23.84%), triglyceride (33.51% and 29.62%), low-density lipoprotein cholesterol (19.23% and 17.38%), and increased glucose tolerance by 21.99% and 15.52%. Further, qRT-PCR analyses indicated that lower ratio of n-6/n-3 PUFA diets activated BAT, increased the expression of Ucp1, β-3AR, PPAR-γ, cAMP, GLU1, HSL, LPL, and PGC-1α, further improved lipid and glucose metabolism in T2DM mice. In conclusion, this study substantiated that the lower ratio of n-6/n-3 PUFA (1:1 and 5:1) improve symptoms associated with T2DM via activating BAT. PRACTICAL APPLICATION: Dietary ratio of n-6/n-3 polyunsaturated fatty acids is essential for the improvement of chronic diseases. Our current study showed that 1:1 or 5:1 ratio of n-6/n-3 polyunsaturated fatty acids had better efficiency for type 2 diabetes mellitus via activating brown adipose tissue when compared with 1:50. This finding provided useful guidance for the daily diet of patients with diabetes., (© 2021 Institute of Food Technologists®.)

The beneficial effects of long-chain polyunsaturated omega-3 fatty acids (omega-3 PUFAs) in cardioprotection are widely known and generally accepted. In this literature review, we have focused on the known and postulated mechanisms of action of omega-3 PUFAs and their metabolites on various components of the haemostatic system, in particular on blood platelets and endothelium. We have also made an attempt to provide a comprehensive review of epidemiological studies with particular regard to clinical trials. Notably, the results of these studies are contradictory, and some of them failed to report the beneficial effects of taking or supplementing omega-3 PUFAs in the diet. A potential explanation, in our opinion, could be the need to use higher doses of omega-3 PUFAs and a proper ratio of omega-3 and omega-6 PUFAs. An additional problem which is difficult to solve is the use of a proper neutral placebo for interventional studies. Despite some controversies regarding the beneficial effects of supplementation of omega-3 PUFAs in cardiovascular disease, our review suggests that a promising aspect of future studies and applications is to focus on the anti-thrombotic properties of these compounds. An argument supporting this assumption is the recent use of omega-3 PUFAs as a supporting tool for the treatment of COVID-19 complications.

Several cardioprotective mechanisms attributed to Omega-3 polyunsaturated fatty acids (PUFAs) have been studied and widely documented. However, in recent years, studies have supported the concept that the intestinal microbiota can play a much larger role than we had anticipated. Microbiota could contribute to several pathologies, including cardiovascular diseases. Indeed, an imbalance in the microbiota has often been reported in patients with cardiovascular disease and produces low-level inflammation. This inflammation contributes to, more or less, long-term development of cardiovascular diseases. It can also worsen the symptoms and the consequences of these pathologies. According to some studies, omega-3 PUFAs in the diet could restore this imbalance and mitigate its harmful effects on cardiovascular diseases. Many mechanisms are involved and included: (1) a reduction of bacteria producing trimethylamine (TMA); (2) an increase in bacteria producing butyrate, which has anti-inflammatory properties; and (3) a decrease in the production of pro-inflammatory cytokines. Additionally, omega-3 PUFAs would help maintain better integrity in the intestinal barrier, thereby preventing the translocation of intestinal contents into circulation. This review will summarize the effects of omega-3 PUFAs on gut micro-biota and the potential impact on cardiac health.

There is an increased use of vegetable oils containing n-6 fatty acids (FA) in aquafeeds, and several trials indicate that there might be an increased requirement of EPA and DHA for Atlantic salmon when they are fed higher dietary n-6 FA. With a limited supply of EPA and DHA for production of aquafeeds, it is important to know how to efficiently use these FA to maintain growth and health of the fish. In the present trial, three diets containing equal amounts of n-3 FA (about 7·7 % of total FA) and different n-6:n-3 FA ratios (about 1, 2 and 6), as well as one diet with n-6:n-3 FA ratio at about 1 but twice as much n-3 FA, were fed to Atlantic salmon. Despite constant dietary n-3, increasing dietary n-6 led to significantly reduced n-3 in tissue polar lipids. Interestingly, EPA was significantly reduced while DHA was not. Maintaining a stable n-3 content in the polar lipids when increasing dietary n-6 FA was only obtained by simultaneously increasing the dietary n-3 content and with this maintaining the same n-6:n-3 FA ratio. Polar lipid n-6 FA in tissues thus primarily reflected the dietary n-6:n-3 FA ratio and not the absolute dietary n-6 FA content. Neutral lipids, on the other hand, reflected the dietary absolute levels of both n-3 and n-6 FA. This study indicates that a better use of dietary EPA is achieved by keeping the dietary n-6:n-3 FA ratio low.

Background: The relationship between midlife dietary habits and risk of dementia remains unclear., Objective: To investigate the association between dietary fish and n-3 polyunsaturated fatty acid (PUFA) consumption in midlife and risk of dementia in later life., Methods: This population-based cohort study assessed food frequency (average intake in 1995 and 2000) and cognition (2014-2015) in 1,127 participants (aged 45-64 in 1995). We used logistic regression analyses to calculate odds ratios (ORs) for dementia and mild cognitive impairment (MCI) diagnoses for consumption quartiles of fish, PUFA-rich fish, total n-3 PUFAs, total n-6 PUFAs, types of PUFAs, and n-3/n-6 PUFA ratio. Estimated ORs were adjusted for age; sex; education; smoking status; alcohol consumption frequency; physical activity; histories of cancer, myocardial infarction, and diabetes mellitus; and depression., Results: Significantly reduced risks of dementia over non-dementia (MCI plus cognitively normal) were observed in the second (OR = 0.43 (95% CI = 0.20-0.93)), third (OR = 0.22 (95% CI = 0.09-0.54)), and highest quartiles (OR = 0.39 (95% CI = 0.18-0.86)) for fish; the third (OR = 0.39 (95% CI = 0.16-0.92)) and highest quartiles (OR = 0.44 (95% CI = 0.19-0.98)) for eicosapentaenoic acid (EPA); the second (OR = 0.39 (95% CI = 0.18-0.84)), third (OR = 0.30 (95% CI = 0.13-0.70)), and highest quartiles (OR = 0.28 (95% CI = 0.12-0.66)) for docosahexaenoic acid (DHA); and the third (OR = 0.36 (95% CI = 0.16-0.85)) and highest quartiles (OR = 0.42 (95% CI = 0.19-0.95)) for docosapentaenoic acid (DPA)., Conclusion: High intake of fish in midlife might aid in preventing dementia.

The aim of this study was to compare dietary intake and status of polyunsaturated fatty acids (PUFA) in plasma and erythrocyte phospholipids metabolically healthy and unhealthy, and obese and nonobese persons. Metabolic health status in 171 participants was defined according to criteria for metabolic syndrome. Obese and nonobese metabolically unhealthy persons (MUHO and MUHNO) had higher energy intake of n -6 PUFA (7.82 ± 1.03 and 7.49 ± 0.86) and lower intake of n -3 PUFA (0.60 ± 0.12 and 0.62 ± 0.11) compared to obese and nonobese metabolically healthy persons (MHO and MHNO) (5.92 ± 0.63 and 5.72 ± 0.67; 1.20 ± 0.07 and 1.22 ± 0.09, respectively) and a higher n -6/ n -3 PUFA ratio. The plasma level of n -6 PUFA was lower in the MUHO and MUHNO groups (38.49 ± 3.71 and 38.53 ± 2.19) compared to MHNO (40.90 ± 2.43), while n -3 PUFA status was lower in obese than in nonobese persons (3.58 ± 0.79 and 3.50 ± 1.02 vs. 4.21 ± 0.80 and 4.06 ± 1.15). The MHO group had a higher eicosapentaenoic/arachidonic acid ratio and estimated desaturase (SCD16, D6D) and elongase activity in plasma phospholipids compared to MHNO. The low intake of n -3 PUFA is directly associated with metabolic risk factors. These results indicated that obesity is closely associated with low levels of n -3 PUFA in plasma phospholipids, suggesting that dietary modifications including n -3 PUFA supplementation appear to be suitable therapeutic strategy in obese persons.

A high-carbohydrate diet (HCD) is a well-established experimental model of accelerated liver fatty acid (FA) deposition and inflammation. In this study, we evaluated whether canola oil can prevent these physiopathological changes. We evaluated hepatic FA accumulation and inflammation in mice fed with a HCD (72.1% carbohydrates) and either canola oil (C group) or soybean oil (S group) as a lipid source for 0, 7, 14, 28, or 56 days. Liver FA compositions were analyzed by gas chromatography. The mRNA expression of acetyl-CoA carboxylase 1 (ACC1) was measured as an indicator of lipogenesis. The mRNA expression of F4/80, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-10, as mediators of liver inflammation, were also measured. The C group stored less n-6 polyunsaturated FAs (n-6 PUFAs) and had more intense lipid deposition of monounsaturated FAs (MUFAs), n-3 PUFAs, and total FAs. The C group also showed higher ACC1 expression. Moreover, on day 56, the C group showed higher expressions of the inflammatory genes F4/80, TNF-α, IL-1β, and IL-6, as well as the anti-inflammatory IL-10. In conclusion, a diet containing canola oil as a lipid source does not prevent the fatty acid accumulation and inflammation induced by a HCD.

Due to the aging population in the world, neurodegenerative diseases have become a serious public health issue that greatly impacts patients' quality of life and adds a huge economic burden. Even after decades of research, there is no effective curative treatment for neurodegenerative diseases. Polyunsaturated fatty acids (PUFAs) have become an emerging dietary medical intervention for health maintenance and treatment of diseases, including neurodegenerative diseases. Recent research demonstrated that the oxidized metabolites, particularly the cytochrome P450 (CYP) metabolites, of PUFAs are beneficial to several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease; however, their mechanism(s) remains unclear. The endogenous levels of CYP metabolites are greatly affected by our diet, endogenous synthesis, and the downstream metabolism. While the activity of omega-3 (ω-3) CYP PUFA metabolites and omega-6 (ω-6) CYP PUFA metabolites largely overlap, the ω-3 CYP PUFA metabolites are more active in general. In this review, we will briefly summarize recent findings regarding the biosynthesis and metabolism of CYP PUFA metabolites. We will also discuss the potential mechanism(s) of CYP PUFA metabolites in neurodegeneration, which will ultimately improve our understanding of how PUFAs affect neurodegeneration and may identify potential drug targets for neurodegenerative diseases.

Prospective observational studies support the use of long-chain omega-3 polyunsaturated fatty acids (PUFAs) in the primary prevention of atherosclerotic cardiovascular disease; however, randomised controlled trials, have often reported neutral findings. There is a long history of debate about the potential harmful effects of a high intake of omega-6 PUFAs, although this idea is not supported by prospective observational studies or randomised controlled trials. Health effects of PUFAs might be influenced by Δ-5 and Δ-6 desaturases, the key enzymes in the metabolism of PUFAs. The activity of these enzymes and modulation by variants in encoding genes (FADS1-2-3 gene cluster) are linked to several cardiometabolic traits. This Review will further consider non-genetic determinants of desaturase activity, which have the potential to modify the availability of PUFAs to tissues. Finally, we discuss the consequences of altered desaturase activity in the context of PUFA intake, that is, gene-diet interactions and their clinical and public health implications., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We studied the influence of experimentally induced DM1, in combination with different dietary n6:n3 polyunsaturated fatty acid (PUFA) ratios on different types of nerve fibers in rat myocardium, in order to reveal whether protective/unfavorable effects of different PUFAs on myocardial function in diabetic patients could be a (partial) repercussion of their effect on the changes in cardiac innervation. The control group (c) and diabetic group (stz) were fed with an n6/n3 ratio of ≈7; the diet of the stz+n6 group had an n6/n3 ratio ≈60, while the diet for the stz+DHA group contained 2.5% of fish oil (containing 16% eicosapentaenoic acid-EPA and 19% docosahexaenoic acid-DHA), n6/n3 ratio of ≈1. DM1 was induced by i.p. injection of streptozotocin (55 mg/kg) and rats were euthanized 30 days after induction. Immunohistochemistry was used for the detection and quantification of different types of neuronal fibers in the cardiac septum. We found changes in cardiac innervations characteristics for the initial phase of experimental DM1, which manifested as an increase in total number and area density of all neuronal fibers, measured by Pgp9.5 immunoreactivity. By detailed analysis, we found that this increase consisted mostly of heavy myelinated NF200 immunoreactive fibers and TH immunoreactive sympathetic fibers, while the density of ChAT immunoreactive parasympathetic fibers decreased. In the deep (middle) part of the myocardium, where rare fibers (of all studied types) were found, significant differences were not found. Surprisingly, we found a more consistent protective effect of n6 PUFAs, in comparison to n3 PUFAs supplementation. These results may provide a better understanding of the potential impacts of different PUFA ratios in the diet of diabetic patients on cardiac innervation and genesis and outcome of diabetic autonomic cardiomyopathy.

The objective of this study was to compare the effect of contrasting sources of dietary n-6 and n-3 PUFA on expression of genes related to lipid metabolism in dairy cows. During 63 days, fifteen lactating cows were assigned to a control or basal diet containing no added lipid (n = 5 cows); and treatment diets supplemented with SO (n = 5 cows; unrefined soybean oil; 2.9% of DM) or FO (n = 5 cows; fish oil manufactured from salmon oil; 2.9% of DM). Plasma for fatty acid (FA) analysis and milk somatic cells (MSC) were obtained from all cows at the beginning of the study (day 0) and on days 21, 42 and 63. Plasma was used to determine FA transport dynamics. Compared with control and FO, plasma from SO had increased contents of C18:1 cis-9, C18:1 trans-11, C18:2 cis-9, trans-11 and total monounsaturated FA. On the other hand, compared with control and SO, FO increased plasma contents of C20:3 n-3, C20:3 n-6, C20:4 n-6, C20:5 n-3, C22:6 n-3 and total polyunsaturated FA. Moreover, plasma C18:3 n-3 and C20:5 n-3 increased over time for all diets. Compared with control, SO downregulated ACACA, INSIG1, and DGAT1, whereas FO downregulated ACACA, PPARGC1, LPIN1 and FABP3 on day 63, in MSC. At different time-points, SO and FO downregulated genes related to synthesis and intracellular transport of FA, synthesis of triglycerides, and transcription factors.

Objective: To investigate the effect of Apolipoprotein E (APOE) genotype on the association between dietary polyunsaturated fat (PUFA), cognitive function, and cerebral glutamate. Methods: A participant sample of 122 middle-aged adults were grouped according to APOE genotype (ϵ4 carrier or ϵ4 non-carrier) and asked to record dietary intake for three consecutive days. All participants also underwent neuropsychological testing and a proton magnetic resonance spectroscopy ( 1 H MRS) scan to assess glutamate in the posterior cingulate cortex. Results: Multiple regression analyses revealed a significant interaction between APOE genotype and PUFA intake on memory performance, F (1,113) = 6.749, p  = .016. Greater PUFA intake was associated with better memory performance in healthy middle-aged adults who were APOE ϵ4 non-carriers, but not for ϵ4 carriers. Furthermore, there was a significant interaction between APOE genotype and PUFA intake on cerebral glutamate, in that dietary PUFA was associated with greater cerebral glutamate in APOE ϵ4 carriers, but not for ϵ4 non-carriers, F (1,114) = 5.173, p  = .025. Conclusions: The findings suggest that PUFA action on the brain differs according to APOE polymorphism and points towards cerebral glutamate as a potential marker of genetic risk for Alzheimer's disease (AD). Early treatment consisting of PUFA supplementation that is tailored to APOE genotype may be an important intervention for the prevention of cognitive decline.

Background: Recent literature suggests that the Western diet's imbalance between high ω-6 (n-6) and low ω-3 (n-3) PUFA intake contributes to fatty liver disease in obese youth., Objectives: We tested whether 12 wk of a low n-6:n-3 PUFA ratio (4:1) normocaloric diet mitigates fatty liver and whether the patatin-like containing domain phospholipase 3 (PNPLA3) rs738409 variant affects the response., Methods: In a single-arm unblinded study, obese youth 9-19 y of age with nonalcoholic fatty liver disease were treated with a normocaloric low n-6:n-3 PUFA ratio diet for 12 wk. The primary outcome was change in hepatic fat fraction (HFF%), measured by abdominal MRI. Metabolic parameters included alanine aminotransferase (ALT), lipids, measures of insulin sensitivity, and plasma oxidized linoleic acid metabolites (OXLAMs). Outcomes were also analyzed by PNPLA3 rs738409 genotype. Wilcoxon's signed rank test, the Mann-Whitney U test, and covariance pattern modeling were used., Results: Twenty obese adolescents (median age: 13.3 y; IQR: 10.5-16.4 y) were enrolled and 17 completed the study. After 12 wk of dietary intervention, HFF% decreased by 25.8% (P = 0.009) despite stable weight. We observed a 34.4% reduction in ALT (P = 0.001), 21.9% reduction in triglycerides (P = 0.046), 3.28% reduction in LDL cholesterol (P = 0.071), and a 26.3% improvement in whole body insulin sensitivity (P = 0.032). The OXLAMs 9-hydroxy-octadecandienoic acid (9-HODE) (P = 0.011), 13-HODE (P = 0.007), and 9-oxo-octadecadienoic acid (9-oxoODE) (P = 0.024) decreased after 12 wk. HFF% declined in both the not-at-risk (CC/CG) and at-risk (GG) PNPLA3 rs738409 genotype groups, with significant (P = 0.016) HFF% reduction in the GG group. Changes in 9-HODE (P = 0.023), 9-oxoODE (P = 0.009), and 13-oxoODE (P = 0.003) differed between the 2 genotype groups over time., Conclusions: These data suggest that, independently of weight loss, a low n-6:n-3 PUFA diet ameliorates the metabolic phenotype of adolescents with fatty liver disease and that response to this diet is modulated by the PNPLA3 rs738409 genotype.This trial was registered at clinicaltrials.gov as NCT01556113., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

The increasing prevalence of obesity and its effects on our society warrant intensifying basic animal research for understanding why habitual intake of highly palatable foods has increased due to recent global environmental changes. Here, we report that pregnant mice that consume a diet high in omega-6 (n-6) polyunsaturated fatty acids (PUFAs) and low in omega-3 (n-3) PUFAs (an n-6 high /n-3 low diet), whose n-6/n-3 ratio is approximately 120, induces hedonic consumption in the offspring by upregulating the midbrain dopaminergic system. We found that exposure to the n-6 high /n-3 low diet specifically increases the consumption of palatable foods via increased mesolimbic dopamine release. In addition, neurodevelopmental analyses revealed that this induced hedonic consumption is programmed during embryogenesis, as dopaminergic neurogenesis is increased during in utero access to the n-6 high /n-3 low diet. Our findings reveal that maternal consumption of PUFAs can have long-lasting effects on the offspring's pattern for consuming highly palatable foods.

Lupus is a systemic autoimmune disease typified by uncontrolled inflammation, disruption of immune tolerance, and intermittent flaring - events triggerable by environmental factors. Preclinical and clinical studies reveal that consumption of the marine ω-3 highly unsaturated fatty acids (HUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) might be used as a precision nutrition intervention to lessen lupus symptoms. The anti-inflammatory and pro-resolving effects of ω-3 HUFAs are inextricably linked to their presence in membrane phospholipids. The ω-3 HUFA score, calculated as [100 × (ω-3 HUFAs/(ω-3 HUFAs + ω-6 HUFAs))] in red blood cells (RBCs), and the Omega-3 Index (O3I), calculated as [100 × ((DHA+EPA)/total fatty acids)] in RBCs, are two biomarkers potentially amenable to relating tissue HUFA balance to clinical outcomes in individuals with lupus. Using data from three prior preclinical DHA supplementation studies, we tested the hypothesis that the ω-3 HUFA score and the O3I inversely correlate with indicators of autoimmune pathogenesis in the cSiO 2 -triggered lupus flaring model. The three studies employed both low and high fat rodent diets, as well as more complex diets emulating the U.S. dietary pattern. The ω-3 HUFA scores in RBCs were comparatively more robust than the O3I at predicting HUFA balances in the kidney, liver, spleen, and lung. Importantly, increases in both the ω-3 HUFA score (>40%) and the O3I (>10%) were strongly associated with suppression of cSiO 2 -triggered (1) expression of interferon-regulated genes, proinflammatory cytokine production, leukocyte infiltration, and ectopic lymphoid structure development in the lung, (2) pulmonary and systemic autoantibody production, and (3) glomerulonephritis. Collectively, these findings identify achievable ω-3 HUFA scores and O3I thresholds that could be targeted in future human intervention studies querying how ω-3 HUFA consumption influences lupus and other autoimmune diseases., (Copyright © 2020 Wierenga, Strakovsky, Benninghoff, Rajasinghe, Lock, Harkema and Pestka.)

Previous studies on the association between polyunsaturated fatty acids (PUFAs) and cancer have focused on n-3 PUFAs. To investigate the association between intake or blood levels of n-6 PUFAs and cancer, we searched the PubMed and Embase databases up to March 2020 and conducted a meta-analysis. A total of 70 articles were identified. High blood levels of n-6 PUFAs were associated with an 8% lower risk of all cancers (relative risk (RR) = 0.92; 95% confidence interval (CI): 0.86-0.98) compared to low blood levels of n-6 PUFAs. In the subgroup analyses by cancer site, type of n-6 PUFAs, and sex, the inverse associations were strong for breast cancer (RR = 0.87; 95% CI: 0.77-0.98), linoleic acid (LA) (RR = 0.91; 95% CI: 0.82-1.00), and women (RR = 0.88; 95% CI: 0.79-0.97). In the dose-response analysis, a 2% and 3% decrease in the risk of cancer was observed with a 5% increase in blood levels of n-6 PUFAs and LA, respectively. Thus, there was no significant association between n-6 PUFA intake and the risk of cancer. The pooled RR of cancer for the highest versus lowest category of n-6 PUFA intake was 1.02 (95% CI: 0.99-1.05). Evidence from prospective studies indicated that intake of n-6 PUFAs was not significantly associated with risk of cancer, but blood levels of n-6 PUFAs were inversely associated with risk of cancer.

Omega-3 and omega-6 polyunsaturated fatty acids are synthesized from the essential fatty acids alpha-linolenic acid and linoleic acid, respectively. They are pivotal components of all mammalian cells and were found to be useful in prevention and treatment of a variety of health problems owing to their anti-inflammatory and anti-microbial properties. Omega-3 and omega-6 polyunsaturated fatty acids are further metabolized to anti-inflammatory mediators, such as lipoxins, resolvins, and protectins. Moreover, these polyunsaturated fatty acids were found to have in vivo and in vitro protective efficacies against some parasitic infections. Therefore, dietary intake of polyunsaturated fatty acids should be encouraged because of their considerable beneficial effects., Competing Interests: Declaration of Competing Interest The authors don't have any conflict or funding source to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Current evidence on associations between intakes of linoleic acid (LA), the predominant n-6 (ω-6) fatty acid, and mortality is inconsistent and has not been summarized by a systematic review and meta-analysis., Objective: The aim was to perform a systematic review and meta-analysis of prospective cohort studies to examine associations between LA intake and mortality., Methods: We conducted a comprehensive search of MEDLINE and EMBASE databases through 31 July 2019 for prospective cohort studies reporting associations of LA (assessed by dietary surveys and/or LA concentrations in adipose tissue or blood compartments) with mortality from all causes, cardiovascular disease (CVD), and cancer. Multivariable-adjusted RRs were pooled using random-effects meta-analysis., Results: Thirty-eight studies reporting 44 prospective cohorts were identified; these included 811,069 participants with dietary intake assessment (170,076 all-cause, 50,786 CVD, and 59,684 cancer deaths) and 65,411 participants with biomarker measurements (9758 all-cause, 6492 CVD, and 1719 cancer deaths). Pooled RRs comparing extreme categories of dietary LA intake (high vs low) were 0.87 (95% CI: 0.81, 0.94; I2 = 67.9%) for total mortality, 0.87 (95% CI: 0.82, 0.92; I2 = 3.7%) for CVD mortality, and 0.89 (95% CI: 0.85, 0.93; I2 = 0%) for cancer mortality. Pooled RRs for each SD increment in LA concentrations in adipose tissue/blood compartments were 0.91 (95% CI: 0.87, 0.95; I2 = 64.1%) for total mortality, 0.89 (95% CI: 0.85, 0.94; I2 = 28.9%) for CVD mortality, and 0.91 (95% CI: 0.84, 0.98; I2 = 26.3%) for cancer mortality. Meta-regressions suggested baseline age and dietary assessment methods as potential sources of heterogeneity for the association between LA and total mortality., Conclusions: In prospective cohort studies, higher LA intake, assessed by dietary surveys or biomarkers, was associated with a modestly lower risk of mortality from all causes, CVD, and cancer. These data support the potential long-term benefits of PUFA intake in lowering the risk of CVD and premature death., (Copyright © The Author(s) 2020.)

Purpose: We aimed to assess the association between the dietary intake of fish-derived omega-3 polyunsaturated fatty acids and the risk of colorectal cancer among Swedish women., Materials and Methods: A total of 48,233 women with information on dietary intake were included in the analysis. Participants were followed for incident colorectal cancer until 31 December 2012. Cox proportional hazard models were used to assess the association between baseline fatty acid intake and colorectal cancer risk. All analyses were stratified by colon and rectal cancers., Results: During a median of 21.3 years of follow-up, a total of 344 colorectal cancer cases were ascertained. Although there was no overall association between omega-3 fatty acid intake and colorectal cancer risk, high intake of fish-derived docosahexaenoic acid was associated with reduced risk of rectal cancer (hazard ratios for the third and the highest quartiles were 0.59 (95% confidence interval [CI], 0.37 to 0.96) and 0.62 (95% CI, 0.39 to 0.98), respectively)., Conclusion: In conclusion, we found only limited support for an association between omega-3 polyunsaturated fatty acids and colorectal cancer in a large Swedish cohort of middle-aged women.

Background & Aim: Lifestyle changes focusing on diet and exercise remain the cornerstone of the treatment of non-alcoholic fatty liver disease (NAFLD). The present co-twin control study of monozygotic (MZ) twin pairs was designed to identify nutritional factors potentially involved in the pathogenesis of NAFLD., Methods: Cross-sectional study of 50 MZ twin pairs (age range: 23-36 years), of which ten pairs were discordant for liver fat (liver fat percentage of one twin ≤5% and his/her co-twin >5% and a difference between co-twins of >5%) as determined by magnetic resonance spectroscopy. Nutrient intake was calculated from 3-day food records., Results: Among the ten liver fat-discordant twin pairs, the n-6: n-3 ratio was significantly higher in the twins with higher liver as compared to their co-twins with lower liver fat (6.6:1 vs. 3.2:1, p-value = 0.005). In multiple regression analysis of within-pair differences including all 50 twin pairs, a higher n-6: n-3 ratio was significantly associated with a higher liver fat percentage within MZ twin pairs after adjustment for body mass index, energy intake and other covariates (standardized beta = 0.43, p-value = 0.001)., Conclusions: Our findings suggest that the n-6: n-3 ratio is a promising dietary agent for the prevention and treatment of NAFLD. Clinical trials are required to better understand causal relationships and required doses., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Multiple sclerosis (MS) is a common demyelinating disease of the central nervous system. Although the exact pathogenesis remains unknown, the leading theory is that it results from immune system dysregulation. Approved disease-modifying therapy appears to modulate the immune system to improve MS-related outcomes. There is substantial interest in the ability of dietary interventions to influence MS-related outcomes. This is an update of the Cochrane Review 'Dietary interventions for multiple sclerosis' (Farinotti 2003; Farinotti 2007; Farinotti 2012)., Objectives: To assess the effects of dietary interventions (including dietary plans with recommendations for specific whole foods, macronutrients, and natural health products) compared to placebo or another intervention on health outcomes (including MS-related outcomes and serious adverse events) in people with MS., Search Methods: On 30 May 2019, we searched CENTRAL, MEDLINE, Embase, and Web of Science. We also searched ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (ICTRP), and Networked Digital Library of Theses and Dissertations (NDLTD). We checked reference lists in identified trials and requested information from trial authors to identify any additional published or unpublished data., Selection Criteria: We included any randomized controlled trial (RCT) or controlled clinical trial (CCT) examining the effect of a dietary intervention versus placebo or another intervention among participants with MS on MS-related outcomes, including relapses, disability progression, and magnetic resonance imaging (MRI) measures., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. Planned primary outcomes were number of participants experiencing relapse and change in disability progression, according to a validated disability scale at the last reported follow-up. Secondary outcomes included MRI activity, safety, and patient-reported outcomes. We entered and analysed data in Review Manager 5., Main Results: We found 41 full-text articles examining 30 trials following full-text review. Participants were adults with MS, defined by established criteria, presenting to MS clinics in Europe, North America, and the Middle East. Study design varied considerably, although all trials had at least one methodological issue leading to unknown or high risk of bias. Trials examined: supplementation to increase polyunsaturated fatty acids (PUFAs) (11 trials); a variety of antioxidant supplements (10 trials); dietary programmes (3 trials); and other dietary supplements (e.g. acetyl L-carnitine, biotin, creatine, palmitoylethanolamide, probiotic, riboflavin) (6 trials). In three trials comparing PUFAs with monounsaturated fatty acids (MUFAs), the evidence was very uncertain concerning difference in relapses (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.88 to 1.20; 3 studies, 217 participants; 75% in the PUFA group versus 74% in the MUFA group; very low-certainty evidence). Among four trials comparing PUFAs with MUFAs, there may be little to no difference in global impression of deterioration (RR 0.85, 95% CI 0.71 to 1.03; 4 studies, 542 participants; 40% in the PUFA group versus 47% in the MUFA group; low-certainty evidence). In two trials comparing PUFAs with MUFAs (102 participants), there was very low-certainty evidence for change in disability progression. None of the PUFA versus MUFA trials examined MRI outcomes. In one trial comparing PUFAs with MUFAs (40 participants), there were no serious adverse events; based on low-certainty evidence. In two trials comparing different PUFAs (omega-3 versus omega-6), there may be little to no difference in relapses (RR 1.02, 95% CI 0.62 to 1.66; 2 studies, 129 participants; 30% in the omega-3 versus 29% in the omega-6 group; low-certainty evidence). Among three trials comparing omega-3 with omega-6, there may be little to no difference in change in disability progression, measured as mean change in Expanded Disability Status Scale (EDSS) (mean difference (MD) 0.00, 95% CI -0.30 to 0.30; 3 studies, 166 participants; low-certainty evidence). In one trial comparing omega-3 with omega-6, there was likely no difference in global impression of deterioration (RR 0.99, 95% CI 0.51 to 1.91; 1 study, 86 participants; 29% in omega-3 versus 29% in omega-6 group; moderate-certainty evidence). In one trial comparing omega-3 with omega-6 (86 participants), there was likely no difference in number of new T1- weighted gadolinium-enhancing lesions, based on moderate-certainty evidence. In four trials comparing omega-3 with omega-6, there may be little to no difference in serious adverse events (RR 1.12, 95% CI 0.38 to 3.31; 4 studies, 230 participants; 6% in omega-3 versus 5% in omega-6 group; low-certainty evidence). In four trials examining antioxidant supplementation with placebo, there may be little to no difference in relapses (RR 0.98, 95% CI 0.59 to 1.64; 4 studies, 345 participants; 17% in the antioxidant group versus 17% in the placebo group; low-certainty evidence). In six trials examining antioxidant supplementation with placebo, the evidence was very uncertain concerning change in disability progression, measured as mean change of EDSS (MD -0.19, 95% CI -0.49 to 0.11; 6 studies, 490 participants; very low-certainty evidence). In two trials examining antioxidant supplementation with placebo, there may be little to no difference in global impression of deterioration (RR 0.99, 95% 0.50 to 1.93; 2 studies, 190 participants; 15% in the antioxidant group versus 15% in the placebo group; low-certainty evidence). In two trials examining antioxidant supplementation with placebo, the evidence was very uncertain concerning difference in gadolinium-enhancing lesions (RR 0.67, 95% CI 0.09 to 4.88; 2 studies, 131 participants; 11% in the antioxidant group versus 16% in the placebo group; very low-certainty evidence). In three trials examining antioxidant supplementation versus placebo, there may be little to no difference in serious adverse events (RR. 0.72, 95% CI 0.17 to 3.08; 3 studies, 222 participants; 3% in the antioxidant group versus 4% in the placebo group; low-certainty evidence)., Authors' Conclusions: There are a variety of controlled trials addressing the effects of dietary interventions for MS with substantial variation in active treatment, comparator, and outcomes of interest. PUFA administration may not differ when compared to alternatives with regards to relapse rate, disability worsening, or overall clinical status in people with MS, but evidence is uncertain. Similarly, at present, there is insufficient evidence to determine whether supplementation with antioxidants or other dietary interventions have any impact on MS-related outcomes., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Adjusting ω-3/ω-6 polyunsaturated fatty acids (PUFAs) ratio in high-fat diet is one potential mean to improve metabolic syndrome; however, underlying mechanisms remain unclear. Four groups of mice were fed 60% kcal diets with saturated fatty acids, three different ω-3/ω-6 PUFAs ratios (low, middle and high) for 12 weeks, respectively. Body weight, atherosclerosis marker, insulin signal index and level of lipid accumulation in liver were significantly lowered in High group compared with saturated fatty acids group and Low group at week 12. Expressions of p-mTOR and raptor were inhibited by high ω-3 PUFAs. Importantly, ω-3 PUFAs intake up-regulated mitochondrial electron transport chain and tricarboxylic acid cycle pathway through metabolomics analysis in liver. Mitochondrial complexes activities were raised, fumaric acid was reduced and oxidative stress was alleviated in High group. We conclude that consuming long-term high-fat diet with same calories but high ω-3/ω-6 PUFAs ratio relieves metabolic syndrome by regulating mTORC1 pathway to enhance mitochondrial function., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Diet may have immunomodulatory effects in persons with multiple sclerosis (PwMS) and studies suggest that diet may be considered a complementary treatment to control the progression of the disease. The role of nutrition in MS and related symptoms have been reported by several studies but remains controversial., Objective: To explore the association between dietary intake and physical capacity and fatigue in PwMS., Methods: An explorative cross-sectional pilot study was conducted, in which 23 ambulatory PwMS were enrolled. Dietary intake was assessed using a 4-day food record. Outcome variables included a 6-Minute Walk Test (6MWT), a VO 2max test, and self-reported questionnaires assessing fatigue severity (Fatigue Severity Scale, FSS) and impact (Modified Fatigue Impact Scale, MFIS). Associations between variables were determined using simple and multiple regression analyses., Results: In the simple but not the multiple (adjusted for sex and age) regression analyses the carbohydrate intake (% of total energy intake) was positively associated with physical capacity (i.e. the 6MWT and VO 2max test), whereas fat intake (% of total energy intake) was inversely associated with physical capacity. In the multiple regression analyses the absolute intake of ω-3 and vitamin D showed trends towards a positive association with the MFIS physical subscale and VO 2max , respectively., Conclusion: Although not consistent across analyses, these findings suggest that better physical capacity most often is associated with a diet rich in carbohydrates and reduced fat content. Further research and randomized controlled trials are required to fully assess the role and the efficacy of diet quality and content on physical capacity in PwMS., Competing Interests: Declaration of Competing Interest MTA has no competing interests. ML-C has received teaching honorary from Novartis. UD has received research support, travel grants, and/or teaching honorary from Biogen Idec, Merck Serono, Almirall, Bayer Schering, Novartis, and Sanofi Aventis and was the principal investigator in a study (ACTIMS) sponsored by Biogen Idec., (Copyright © 2019 Elsevier B.V. All rights reserved.)