N-3 polyunsaturated fatty acids effectively protect against neural tube defects in diabetic mice induced by streptozotocin.

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.

The effects of dietary saturated fat source on weight gain and adiposity are influenced by both sex and total dietary lipid intake in zebrafish.

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.

Diets with Higher ω-6/ω-3 Ratios Show Differences in Ceramides and Fatty Acid Levels Accompanied by Increased Amyloid-Beta in the Brains of Male APP/PS1 Transgenic Mice.

Senile plaque formation as a consequence of amyloid-ß peptide (Aß) 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 Aß 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).

Dietary intake of n-3 polyunsaturated fatty acids alters the lipid mediator profile of the kidney but does not attenuate renal insufficiency.

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.

Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial.

OBJECTIVE: To determine whether dietary interventions that increase n-3 fatty acids with and without reduction in n-6 linoleic acid can alter circulating lipid mediators implicated in headache pathogenesis, and decrease headache in adults with migraine. DESIGN: Three arm, parallel group, randomized, modified double blind, controlled trial. SETTING: Ambulatory, academic medical center in the United States over 16 weeks. PARTICIPANTS: 182 participants (88% women, mean age 38 years) with migraines on 5-20 days per month (67% met criteria for chronic migraine). INTERVENTIONS: Three diets designed with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and linoleic acid altered as controlled variables: H3 diet (n=61)-increase EPA+DHA to 1.5 g/day and maintain linoleic acid at around 7% of energy; H3-L6 diet (n=61)-increase n-3 EPA+DHA to 1.5 g/day and decrease linoleic acid to ≤1.8% of energy; control diet (n=60)-maintain EPA+DHA at <150 mg/day and linoleic acid at around 7% of energy. All participants received foods accounting for two thirds of daily food energy and continued usual care. MAIN OUTCOME MEASURES: The primary endpoints (week 16) were the antinociceptive mediator 17-hydroxydocosahexaenoic acid (17-HDHA) in blood and the headache impact test (HIT-6), a six item questionnaire assessing headache impact on quality of life. Headache frequency was assessed daily with an electronic diary. RESULTS: In intention-to-treat analyses (n=182), the H3-L6 and H3 diets increased circulating 17-HDHA (log ng/mL) compared with the control diet (baseline-adjusted mean difference 0.6, 95% confidence interval 0.2 to 0.9; 0.7, 0.4 to 1.1, respectively). The observed improvement in HIT-6 scores in the H3-L6 and H3 groups was not statistically significant (-1.6, -4.2 to 1.0, and -1.5, -4.2 to 1.2, respectively). Compared with the control diet, the H3-L6 and H3 diets decreased total headache hours per day (-1.7, -2.5 to -0.9, and -1.3, -2.1 to -0.5, respectively), moderate to severe headache hours per day (-0.8, -1.2 to -0.4, and -0.7, -1.1 to -0.3, respectively), and headache days per month (-4.0, -5.2 to -2.7, and -2.0, -3.3 to -0.7, respectively). The H3-L6 diet decreased headache days per month more than the H3 diet (-2.0, -3.2 to -0.8), suggesting additional benefit from lowering dietary linoleic acid. The H3-L6 and H3 diets altered n-3 and n-6 fatty acids and several of their nociceptive oxylipin derivatives in plasma, serum, erythrocytes or immune cells, but did not alter classic headache mediators calcitonin gene related peptide and prostaglandin E2. CONCLUSIONS: The H3-L6 and H3 interventions altered bioactive mediators implicated in headache pathogenesis and decreased frequency and severity of headaches, but did not significantly improve quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT02012790.

Consumption of Monounsaturated Fatty Acids Is Associated with Improved Cardiometabolic Outcomes in Four African-Origin Populations Spanning the Epidemiologic Transition.

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.

Beneficial Effects of a Specially Designed Home Meal Replacement on Cardiometabolic Parameters in Individuals with Obesity: Preliminary Results of a Randomized Controlled Clinical Trial.

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).

A low proportion n-6/n-3 PUFA diet supplemented with Antarctic krill (Euphausia superba) oil protects against osteoarthritis by attenuating inflammation in ovariectomized mice.

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.

Maternal active asthma in pregnancy influences associations between polyunsaturated fatty acid intake and child asthma.

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.

Methodology for altering omega-3 EPA+DHA and omega-6 linoleic acid as controlled variables in a dietary trial.

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.

Changes in lipoprotein particle subclasses, standard lipids, and apolipoproteins after supplementation with n-3 or n-6 PUFAs in abdominal obesity: A randomized double-blind crossover study.

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.

Associations of Dietary ω-3, ω-6 Fatty Acids Consumption with Sleep Disorders and Sleep Duration among Adults.

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.

Effects of Omega-3 Polyunsaturated Fatty Acids and Their Metabolites on Haemostasis-Current Perspectives in Cardiovascular Disease.

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.

Superovulatory response and embryo quality in Boer does following dietary supplementation with different sources of omega-3 and omega-6 fatty acids during the breeding season.

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.

Dietary low ratio of n-6/n-3 polyunsaturated fatty acids improve type 2 diabetes mellitus via activating brown adipose tissue in male mice.

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, ß-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.

Association Between Dietary Fish and PUFA Intake in Midlife and Dementia in Later Life: The JPHC Saku Mental Health Study.

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.

Microbiota, a New Playground for the Omega-3 Polyunsaturated Fatty Acids in Cardiovascular Diseases.

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.

Metabolically healthy obesity: is there a link with polyunsaturated fatty acid intake and status?

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.

Increasing dietary n-6 fatty acids while keeping n-3 fatty acids stable decreases EPA in polar lipids of farmed Atlantic salmon (Salmo salar).

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.

Effect of supplementing palmitic acid and altering the dietary ratio of n-6:n-3 fatty acids in low-fibre diets on production responses of dairy cows.

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 ß-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.