Maternal supplementation with n-3 fatty acids affects placental lipid metabolism, inflammation, oxidative stress, the endocannabinoid system, and the neonate cytokine concentrations in dairy cows

Background The placenta plays a crucial role in supporting and influencing fetal development.We compared the effects of prepartum supplementation with omega-3(n-3)fatty acid(FA)sources,flaxseed oil(FLX)and fish oil(FO),on the expression of genes and proteins related to lipid metabolism,inflammation,oxidative stress,and the endocannabinoid system(ECS)in the expelled placenta,as well as on FA profile and inflammatory response of neonates.Late-pregnant Holstein dairy cows were supplemented with saturated fat(CTL),FLX,or FO.Placental cotyledons(n=5)were collected immediately after expulsion,and extracted RNA and proteins were analyzed by RTPCR and proteomic analysis.Neonatal blood was assessed for FA composition and concentrations of inflammatory markers.Results FO increased the gene expression of fatty acid binding protein 4(FABP4),interleukin 10(IL-10),catalase(CAT),cannabinoid receptor 1(CNR1),and cannabinoid receptor 2(CNR2)compared with CTL placenta.Gene expression of ECS-enzyme FA-amide hydrolase(FAAH)was lower in FLX and FO than in CTL.Proteomic analysis identified 3,974 proteins;of these,51–59 were differentially abundant between treatments(P≤0.05,|fold change|≥1.5).Top canonical pathways enriched in FLX vs.CTL and in FO vs.CTL were triglyceride metabolism and inflammatory processes.Both n-3 FA increased the placental abundance of FA binding proteins(FABPs)3 and 7.The abundance of CNR1 cannabinoid-receptor-interacting-protein-1(CNRIP1)was reduced in FO vs.FLX.In silico modeling affirmed that bovine FABPs bind to endocannabinoids.The FLX increased the abundance of inflammatory CD44-antigen and secreted-phosphoprotein-1,whereas prostaglandin-endoperoxide synthase 2 was decreased in FO vs.CTL placenta.Maternal FO enriched neonatal plasma with n-3 FAs,and both FLX and FO reduced interleukin-6 concentrations compared with CTL.Conclusion Maternal n-3 FA from FLX and FO differentially affected the bovine placenta;both enhanced lipid metabolism and modulated oxidative stress,however,FO increased some transcriptional ECS components,possibly related to the increased FABPs.Maternal FO induced a unique balance of pro-and anti-inflammatory components in the placenta.Taken together,different sources of n-3 FA during late pregnancy enhanced placental immune and metabolic processes,which may affect the neonatal immune system.

Comparison of the effects of 3 kinds of oils rich in omega-3 polyunsaturated fatty acids on glycolipid metabolism and lipoprotein subfractions

Dietary omega-3 polyunsaturated fatty acids(ω-3 PUFAs)can be classifi ed into animal-and plant-derivedω-3 PUFAs.Patients with type 2 diabetes(T2DM)are frequently accompanied by dyslipidemia,which is closely related to the high-density lipoprotein(HDL-C)subfractions change.This study aimed to determine the effects of different sourcesω-3 PUFAs on glucolipid metabolism and lipoprotein subfractions in T2DM with dyslipidemia.Ninety T2DM patients with dyslipidemia were randomly assigned to take 3 g/day fi sh oil(FO,containing eicosapentaenoic acid(EPA)and docosahexaenoic acid(DHA)),3 g/day perilla oil(PO,containingα-linolenic acid(ALA)),or 3 g/day blend oil(BO,containing EPA,DHA and ALA)for 3 months.90 patients completed the intervention.There was a significant reduction of glycated hemoglobin(HbA1c)in all the groups.The triglycerides(TG)in the FO group were signifi cantly different with a group×time interaction(P=0.043),which was higher compared with the other two groups.The serum small HDL-C subfractions in the PO group was higher and the serum large HDL-C subfractions in the PO group was lower than those in the BO and FO groups.Plant-derivedω-3 PUFAs are more effective at controlling blood glucose than animal-derivedω-3 PUFAs.However,animal-derivedω-3 PUFAs have a signifi cant lowering effect on TG compared with plant-derivedω-3 PUFAs.Particularly,large HDL-C subfractions after animal-derivedω-3 PUFAs intake were higher than plant-derivedω-3 PUFAs intake;while small HDL-C subfractions were lower.Both the animal-and plant-derivedω-3 PUFAs have practical value in improving glucose and lipids metabolism in T2DM patients with dyslipidemia.

Different n-6/n-3 polyunsaturated fatty acid ratios affect postprandial metabolism in normal and hypertriglyceridemic rats

Postprandial metabolism plays major roles in many pathological conditions.The n-6/n-3 polyunsaturated fatty acid(PUFA)ratio is closely related to various physiological disorders.This study aimed to investigate the effects of high fat meals with different n-6/n-3 PUFA ratios on postprandial metabolism in normal control(NC)and hypertriglyceridemia(HTG)rats.The postprandial response of triglyceride(TG)in HTG groups was higher than that in NC groups after different n-6/n-3 PUFA ratio meals.The HTG groups showed higher postprandial total cholesterol(TC)responses than NC groups after 1:1 and 20:1 ratio meals.The 5:1 n-6/n-3 PUFA ratio elicited lower postprandial responses of tumor necrosis factorα(TNF-α)than 1:1 and 10:1 ratios in HTG groups.The postprandial malondialdehyde(MDA)response was lower after a 5:1 n-6/n-3 PUFA ratio meal than 1:1 and 20:1 ratio meals in HTG groups.The 1:1 ratio resulted in a lower postprandial reactive oxygen species(ROS)level than 5:1 and 10:1 n-6/n-3 PUFA ratios in NC groups.The results showed that a low n-6/n-3 PUFA ratio improved postprandial dysmetabolism induced by a high fat meal in NC and HTG rats.A high n-6/n-3 PUFA ratio increased the difference in postprandial metabolism between NC and HTG rats.

Development and Production of Omega-3 Fatty Acids-Enriched Foods is an Important Dietary Strategy to Improve People's Nutritional and Health Status

Both Omega-6 and Omega-3 fatty acids are essential nutrients important for cellular structure and function but cannot be synthesized by the human body and must be obtained from food.These two classes of fatty acids are metabolically and functionally different and antagonistically regulate many physiological and pathological processes.Thus,the relative balance between Omega-6 and Omega-3 fatty acids are critical for good health.However,today’s diet contains too much Omega-6 but too little Omega-3,leading to a severe imbalance with a very high Omega-6/Omega-3 ratio(>10)in most people.Many lines of evidence suggest that this imbalance is a key factor contributing to the development of modern chronic diseases.A growing number of studies ranging from laboratory research to clinical trials have shown that balancing the tissue ratio of Omega-6/Omega-3 fatty acids by increasing tissue levels of Omega-3 fatty acids and/or decreasing the content of Omega-6 fatty acids are very beneficial for the prevention and treatment of many life-threating chronic diseases as well as for health promotion of the general public.Therefore,development and production of foods rich in Omega-3-fatty acids should be considered as a key health program to balance essential fat intake and thereby improve the nutritional and health status of all people.

A randomized controlled trial of omega-3 fatty acids in dry eye syndrome

AIM:To evaluate the role of dietary supplementation of omega-3 fatty acids in dry eye syndrome.METHODS:A prospective,interventional,placebo controlled,double blind randomized trial was done at two referral eye centers.Two hundred and sixty-four eyes of patients with dry eye were randomized to receive one capsule(500mg)two times a day containing 325mg EPA and 175mg DHA for 3 months(omega-3 group).The omega-3 group was compared to a group of patients(n=254)who received a placebo(placebo group).There were 4 patient visits(at baseline,1 month,2 months and3 months).On each visit,recording of corrected distance visual acuity(CDVA),slit lamp examination and questionnaire based symptom evaluation and scoring was done.A symptomatic score of 0-6 was mild,6.1-12moderate and 12.1-18 severe dry eye.Response to intervention was monitored by routine tear function tests like Schirmer I test,tear film break-up time(TBUT),Rose Bengal staining and most notably,conjunctival impression cytology.RESULTS:Sixty-five percent of patients in the omega-3group and 33%of patients in placebo group had significant improvement in symptoms at 3 months(P=0.005).There was a significant change in both Schirmer’s test value and TBUT values in the omega-3group(P【0.001),both comparisons.However,there was a larger drift in TBUT values in omega-3 than the placebo group,in comparison to Schirmer’s test values.The mean TBUT score was 2.54±2.34 in the omega-3group and 0.13±0.16 in placebo group,respectively.The mean reduction in symptom score in omega-3 group was 2.02±0.96 as compared to 0.48±0.22 in placebogroup(P【0.001).Despite a slight increase mean score,the Schirmer scores did not correlate well with symptomatic improvement.CONCLUSION:Omega-3 fatty acids have a definite role for dry eye syndrome.The benefit seems to be more marked in conditions such as blepharitis and meibomian gland disease.The role of omega fatty acids in tear production and secretion needs further evaluation.

Effects of dietary ratio of n-6 to n-3 polyunsaturated fatty acids on immunoglobulins, cytokines, fatty acid composition, and performance of lactating sows and suckling piglets

This experiment was conducted to investigate the effects of dietary ratios of n-6：n-3 polyunsaturated fatty acids （PUFA） on the performance of lactating sows and their piglets. Thirty pregnant Landrace sows were assigned to one of three treatments from d 108 of gestation until weaning （26-29 d） and were fed diets containing different ratios of n-6：n-3 PUFA including 3：1,9：1 and 13：1. The effects on sow and litter production traits were examined together with an assessment of sow body condition. No differences were detected among the treatments for the daily feed intake of sows or changes in sow weight and back-fat levels during lactation （P 〉 0.05）. Litter size at d 14 and d 21 were tended to increase in 3：1 treatment compared with 9：1 and 13：1 treatments （P 〈 0.10）. Litter weight gain （1.77 kg/d） from d 0 to d 14 was tended to increase in 9：1 groups compared with the other two treatments （P 〈 0.10）. A significant difference was observed for the content of a -linolenic acid, total n-3 PUFA, and the ratio of n-6：n-3 PUFA in the colostrum, milk, and piglets plasma （P 〈 0.01）. The effects of different ratios of n-6：n-3 PUFA in sow diets on colostrum, milk and piglet plasma immunoglobulin concentrations are studied. No difference was observed among treatments in the concentrations of IgM, and IgA in colostrum （P 〉 0.05）. A great significant difference for IgG concentration was observed among 3 group in colostrum. A great significant difference for IgA, and IgM （P〈 0.01） concentrations in piglet plasma at d14 and a significant difference for IgG（P 〈 0.05） was observed at d14. Furthermore, at d 21 of lactation, piglet plasma IgG and IgA concentration were greater in 3：1 compared with 13：1 group （P 〈 0.01）. In summary, the current study demonstrated that altering the ratio of n-6：n-3 PUFA in lactating sow diet had an effect on the immune component including immunoglobulin and cytokines, and it tended to increase the litter average daily gain and improve the immune status of piglets when dietary ratio of n-6：n-3 PUFA was 9：1.

Omega-3 polyunsaturated fatty acids promote liver regeneration after 90% hepatectomy in rats

AIM:To evaluate the effectiveness of omega-3 polyunsaturated fatty acid(ω-3 PUFA) administration on liver regeneration after 90% partial hepatectomy(PH) in rats.METHODS:ω-3 PUFAs were intravenously injected in the ω-3 PUFA group before PH surgery.PH,sparing only the caudate lobe,was performed in both the control and the ω-3 PUFA group.Survival rates,liver weight/body weight ratios,liver weights,HE staining,transmission electron microscope imaging,nuclearassociated antigen Ki-67,enzyme-linked immunosorbent assay and signal transduction were evaluated to analyze liver regeneration.RESULTS:All rats in the control group died within 30 h after hepatectomy.Survival rates in the ω-3 PUFA group were 20/20 at 30 h and 4/20 1 wk after PH.Liver weight/body weight ratios and liver weights increased significantly in the ω-3 PUFA group.The structure of sinusoidal endothelial cells and space of Disse was greatly restored in the ω-3 PUFA group compared to the control group after PH.In the ω-3 PUFA group,interleukin(IL)-4 and IL-10 levels were significantly increased whereas IL-6 and tumor necrosis factor-levels were dramatically decreased.In addition,activation of protein kinase B(Akt) and of signal transducer and activator of transcription 3 signaling pathway were identified at an earlier time after PH in the ω-3 PUFA group.CONCLUSION:Omega-3 polyunsaturated fatty acids may prevent acute liver failure and promote liver regeneration after 90% hepatectomy in rats.

Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease （NAFLD） has been recognized as a major health burden. It is the most important cause of chronic liver disease and a major in- dependent cardiovascular risk factor. Lacking a definite treatment for NAFLD, a specific diet and an increase in physical activity represent the most commonly used therapeutic approaches. In this review, major literature data about the use of omega-3 polyunsaturated fatty ac- ids （n-3 PUFAs） as a potential treatment of NAFLD have been described, n-3 PUFAs, besides having a beneficial impact on most of the cardio-metabolic risk factors （hy- pertension, hyperlipidemia, endothelial dysfunction and atherosclerosis） by regulating gene transcription factors [i.e., peroxisome proliferator-activated receptor （PPAR） cz, PPARy, sterol regulatory element-binding protein-i, carbohydrate responsive element-binding protein], im- pacts both lipid metabolism and on insulin sensitivity. In addition to an enhancement of hepatic beta oxidation and a decrease of the endogenous lipid production, n-3 PUFAs are able to determine a significant reduction of the expression of pro-inflammatory molecules （tumor necrosis factor-~ and interleukin-6） and of oxygen reac- tive species. Further strengthening the results of the in vitro studies, both animal models and human interven- tion trials, showed a beneficial effect of n-3 PUFAs on the severity of NAFLD as expressed by laboratory pa- rameters and imaging measurements. Despite available results provided encouraging data about the efficacy of n-3 PUFAs as a treatment of NAFLD in humans, well- designed randomized controlled trials of adequate size and duration, with histological endpoints, are needed to assess the long-term safety and efficacy of PUFA, as well as other therapies, for the treatment of NAFLD and non-alcoholic steatohepatitis patients. It is worthwhile to consider that n-3 PUFAs cannot be synthesized by the human body and must be derived from exogenous sources （fish oil, flaxseeds, olive oil） which are typical foods of the Mediterranean diet, known for its beneficial effects in preventing obesity, diabetes and, in turn, cardiovascular events. According to these data, it is important to consider that most of the beneficial effects of n-3 PUFAs can also be obtained by an equilibrate nutrition program.

Role of omega-3 polyunsaturated fatty acids,citrus pectin,and milk-derived exosomes on intestinal barrier integrity and immunity in animals

The gastrointestinal tract of livestock and poultry is prone to challenge by feedborne antigens,pathogens,and other stress factors in the farm environment.Excessive physiological inflammation and oxidative stress that arises firstly disrupts the intestinal epithelial barrier followed by other components of the gastrointestinal tract.In the present review,the interrelationship between intestinal barrier inflammation and oxidative stress that contributes to the pathogenesis of inflammatory bowel disease was described.Further,the role of naturally existing immunomodulatory nutrients such as the omega-3 polyunsaturated fatty acids,citrus pectin,and milk-derived exosomes in preventing intestinal barrier inflammation was discussed.Based on the existing evidence,the possible molecular mechanism of these bioactive nutrients in the intestinal barrier was outlined for application in animal diets.

Effects of the Ratio of n-6∶n-3 Polyunsaturated Fatty Acids in the Maternal Diet on Immunoglobulins,Fatty Acid Composition,and Performance of Lactating Sows and Suckling Piglets under Conditions of Low Maternal Energy Intake

This experiment was conducted to investigate the effects of different ratios of n-6 ∶ n-3 polyunsaturated fatty acids （PUFA） in sow diets on the performance of lactating sows and their piglets at low digestible energy intakes. Twenty-one pregnant Landrace sows were assigned to one of three diets from day 108 of gestation until weaning （26 to 29 d） ,containing n-6∶n-3 PUFA ratios of 3 ∶1,8 ∶1 and 11 ∶1. The effects on sow and litter production traits and on sow body condition were examined. There were no differences among treatments in daily feed intakes or in changes in sow weight and back-fat levels during lactation. Litter size,litter weight at birth and weaning and litter average daily weight gain were also unaffected by treatment. As expected, large differences were observed in n-6 and n-3 fatty acids in the colostrum and plasma of sows and piglets （P 〈 0. 01） . The ratio of n6 ∶ n-3 PUFA the diet was positively correlated with those in colostrum,sow plasma and piglet plasma （R 2= 0. 55,0. 80 and 0. 80,respectively） . Sow plasma insulin and IGF-I levels at weaning were unaffected by the treatments. Plasma leptin （P 〈 0. 05） concentrations were increased in sows fed the diet with a n-6∶n-3 ratio of 8 ∶ 1. Immunoglobulin concentrations in colostrum were not altered by dietary treatment. Plasma IgG concentrations at d 14 were highest in piglets from sows fed the 8 ∶ 1 ratio of n-6∶n-3. Furthermore,this group had the highest IgA concentrations at day 21 of lactation compared with the other two groups （P 〈 0. 05） . In summary,our study demonstrated that at low digestible energy levels,altering the ratio of n-6 ∶ n-3 PUFA in the diets for lactating sows affected immune components and the fatty acid composition of lactating sows and their piglets. Further studies are needed to examine whether higher levels of fat supplementation than those used in the present study （1. 5%） can successfully enhance performance.

Role of perinatal long-chain omega-3 fatty acids in cortical circuit maturation:Mechanisms and implications for psychopathology

Accumulating translational evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid(DHA) plays a role in the maturation and stability of cortical circuits that are impaired in different recurrent psychiatric disorders. Specifically, rodent and cell culture studies find that DHA preferentially accumulates in synaptic and growth cone membranes and promotes neurite outgrowth, dendritic spine stability, and synaptogenesis. Additional evidence suggests that DHA may play a role in microglia-mediated synaptic pruning, as well as myelin development and resilience. In nonhuman primates n-3 fatty acid insufficiency during perinatal development leads to widespread deficits in functional connectivity in adult frontal cortical networks compared to primates raised on DHA-fortified diet. Preterm delivery in non-human primates and humans is associated with early deficits in cortical DHA accrual. Human preterm birth is associated with longstanding deficits in myelin integrity and cortical circuit connectivity and increased risk for attention deficit/hyperactivity disorder(ADHD), mood, and psychotic disorders. In general, ADHD and mood and psychotic disorders initially emerge during rapid periods of cortical circuit maturation and are characterized by DHA deficits, myelin pathology, and impaired cortical circuit connectivity. Together these associations suggest that early and uncorrected deficits in fetal brain DHA accrual may represent a modifiable risk factor for cortical circuit maturation deficits in psychiatric disorders, and could therefore have significant implications for informing early intervention and prevention strategies.

Omega-3 fatty acids and mental health

Nutrition plays a key role in brain development,mental health,and psychiatric disorders.The role of omega-3 polyunsaturated fatty acids in physical health is well established,and their role in mental health is becoming increasingly evident.Omega-3 fatty acids are involved in a wide range of physiological functions that are related to neurogenesis,neurotransmission,and neuroinflammation;therefore,they play fundamental roles in the development,functioning,and aging of the brain.In humans,dietary deficiencies of omega-3 fatty acids are associated with an increased risk of developing various psychiatric disorders,including depression,bipolar disorder,schizophrenia,dementia,attention-deficit/hyperactivity disorder,and autism.In particular,eicosapentaenoic and docosahexaenoic acid have been linked to the maintenance of mental health,and their deficits have been implicated in the pathophysiology of mental disorders.This may be mediated by the modulation of inflammatory processes and their direct effects on neuronal membrane fluidity and receptor function.However,randomized clinical trials that have investigated the therapeutic effects of omega-3 fatty acids have yielded inconclusive results,thereby limiting the use of these nutrients in psychiatric practice.High-quality clinical trials should be conducted to examine the efficacy of omega-3 fatty acids in preventing and treating mental disorders.The undesirable side effects of omega-3 fatty acid supplementation should also be considered.These effects may become apparent after many years of administration,and therefore,they may not be detected in most cases.

EFFECTS OF SIMVASTAIN COMBINED WITH OMEGA-3 FATTY ACIDS ON HIGH SENSITIVE C-REACTIVE PROTEIN, LIPIDEMIA, ANDFIBRINOLYSIS IN PATIENTS WITH MIXED DYSLIPIDEMIA

Objective To evaluate the effects of simvastatin combined with omega-3 fatty acids on high sensitive C-reactive protein(HsCRP), lipidemia, and fibrinolysis in coronary heart disease (CHD) and CHD risk equivalent patients with mixed dyslipi-demia. Methods A randomized, double-blind placebo controlled and parallel group trial was conducted. Patients with CHD and CHD risk equivalents with mixed dyslipidemia were treated with 10 or 20 mg simvastatin for 6-12 weeks. Following with the treatment of patients whose low-density lipoprotein cholesterol (LDL-ch) reaching goal level (< 100 mg/dL) or close to the goal (< 130 mg/dL), while triglyceride (TG) ≥200 mg/dL and < 500 mg/dL, was combined with omega-3 fatty acids (3 g/d) or a placebo for 2 months. The effects of the treatment on HsCRP, total cholesterol (TC), LDL-ch, high-density lipoprotein cholesterol (HDL-ch), TG, lipoprotein (a) [LP (a)], apolipoprotein A1 (apoA1), apolipoprotein B (apoB), plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (tPA) were investigated. Forty patients finished the study with each group consisting of twenty patients. Results (1) There were significant reductions of HsCRP, TG, TC, and TC/HDL-ch, which decreased by 2.16 ±2.77 mg/L (38.5%), 94.0 ±65.4 mg/dL (31.1%), 13.3 ±22.3 mg/dL (6.3%), 0.78 ±1.60 respectively in the omega-3 fatty acids group (P< 0.01, < 0.001, < 0.05, < 0.05) compared to the baseline. HsCRP and triglyceride reduction were more significant in omega-3 fatty acids group compared to the placebo group (P=0.021 and 0.011 respectively). (2) In the omega-3 fatty acids group, the values and percentage of TG reduction had a significantly positive relation with HsCRP reduction (r=0.51 and 0.45, P=0.021 and 0.047 respectively). Conclusion In CHD and CHD risk equivalent patients with mixed dyslipidemia, dyslipidemia’s therapeutic effect using simvastatin and omega-3 fatty acids may result from not only the combination of lipid adjustment, but also enhancement of their own nonlipid influences.

Alterations of attention and impulsivity in the rat following a transgenerational decrease in dietary omega-3 fatty acids

Polyunsaturated fatty acids(PUFAs),particularly the omega-3 PUFAs,are thought to be involved in neuronal processes,to play a role in neurodevelopmental disorders and to be important for the integrity of central nervous system functioning.The present study investigated the effects of nutritional omega-3 PUFAs on attentional functions and impulsive behavior in Wistar rats.For this purpose,female Wistar rats were fed an omega-3 deficient diet over several generations,and the dams of the seventh generation were randomly assigned to two diet groups and fed an omega-3 deficient or an omega-3 sufficient diet.In addition,a group of previously untreated dams was fed an omega-3 sufficient diet.The male offspring of these three diet groups were tested using an established paradigm for the assessment of attention and impulsive behavior,i.e.a modified version of the five-choice-serial-reaction-time task(5CSRTT).The present data show that the deficiency of omega-3 PUFAs over generations led to substantial changes in attentional processes and impulsive behaviors.The impairments associated with an omega-3 deficiency were partly corrected by treatment with the omega-3 sufficient diet in the last generation of the omega-3 deficient group which showed substantial improvements in attention parameters.While there were no significant effects of dietary modifications on psychomotor activity levels,there was some evidence for changes in impulsive behavior.In conclusion,transgenerational dietary changes in the availability of omega-3 PUFAs led to changes in attentional processes and impulsive behavior in rats,supporting the hypothesis that omega-3 PUFAs play a role in cognitive and behavioral processes.The present findings offer a promising approach in the investigation of the role of omega-3 PUFAs in a variety of cognitive and behavioral domains.

The Relationships between Erythrocyte Membrane n-6 to n-3 Polyunsaturated Fatty Acids Ratio and Blood Lipids and C-reactive Protein in Chinese Adults:An Observational Study

Objective To investigate the relationships between erythrocyte membrane n-6：n-3 PUFAs ratio and blood lipids and high sensitivity C-reactive protein （hs-CRP）. Methods The Chinese and a observational study consisted of a population-based cross-sectiona subsequent 1-year follow-up study of 171 subjects with the fasting cholesterol of 5.13-8.00 mmol/L. study of 456 plasma total Results In the cross-sectional analysis, plasma low-density lipoprotein cholesterol （LDL-c） had a significant and negative association with the erythrocyte membrane n-6：n-3 PUFAs ratio （P for trend=0.019） after adjusting for sex, age and total PUFA percentage. In the follow-up study, 171 subjects were categorized into quartiles by the changes of n-6：n-3 ratio in erythrocyte membrane （△=month 12-month 0）. In the top quartile whose ratios of n-6：n-3 increased by an average of 1.25 during the follow-up, the LDL-c-lowering extent was 3.3 times of that in the lowest quartile whose ratios of n-6：n-3 decreased by an average of 1.13 （-1.07 mmol/L v.s. -0.32 mmol/L）. The hsCRP decreased by 0.11 mg/dL in the lowest quartile while increasing by 0.10 mg/dL in the top quartile （P for difference=0.052）. Conclusion Our results suggested that the balance between n-6 and n-3 fatty acids may optimize the cardiovascular benefits from dietary PUFAs.

Combined Add-on Supplementation of Omega-3 Fatty Acids, Vitamin E, Vitamin A, Copper, and Selenium in Rheumatoid Arthritis

Objectives: The present study evaluated the effects of a combined nutritional supplement, containing omega-3 fatty acids (ω-3 FA) and different antioxidative micronutrients on nutrient status and disease activity in patients with rheumatoid arthritis (RA). Methods: The study was conducted as a double-blind, randomised placebo-controlled trial. A hundred patients with defined RA were allocated to the verum or placebo group. During a period of twelve weeks they were given three capsules of their specific study supplementation every day. The daily dosage of ω-3 FA was 1.35 g (thereof 900 mg eicosapentaenoic acid, EPA), 90 mg vitamin E, 600 μg vitamin A, 3 mg copper, and 75 μg selenium, or soy oil (placebo), respectively. Outcome variables were the changes in DAS 28, the number of tender and swollen joints, morning stiffness, and supply with different nutrients (e.g. serum concentration of EPA, AA and vitamin E), as well as blood lipid levels. Results: Sixty-four participants were included in this analysis: 30 receiving verum and 34 placebo. After twelve weeks of intervention, little but not significant improvements were observed in the DAS 28 and other clinical factors. Subgroup analysis revealed that the effect was much more pronounced in patients who were at least at a moderate activity of illness. Regarding the nutritional status, the serum concentration of EPA (P < 0.001), vitamin E (P < 0.01), SOD (P < 0.05), and GPx (P < 0.001) increased significantly, while AA (P < 0.001) decreased after supplementation. The concentration of triglycerides decreased significantly in the verum group (P < 0.05) but not in the placebo group. Conclusions: A twelve week add-on supplementation of a combined food supplement (ω-3 FA + antioxidants) effected modest but not significant changes in the clinical parameters in RA. Though vitamin E, SOD and GPx improved significantly, equivalent to an increased antioxidant defence. This supplementation was dedicated to enhance the nutritional status of critical nutrients in RA, especially with regard to an increased risk of cardiovascular disease in these patients.

Plasma Phospholipid Omega-3 Fatty Acids and Freshwater Fish Consumption in the Brazilian Amazon

Background: Amazonian riverside communities consume large quantities of freshwater fish, comparable to marine fish consumption of Inuit, Scandinavian and Japanese populations. Few studies have considered the relation of high freshwater fish consumption and intake of omega-3 fatty acids (FA). Objective: The objective of the present study was to determine the profile of the concentrations of plasma phospholipid FAs and its relation with freshwater fish intake in 12 riverside communities in the Tapajós River basin (State of Pará, Brazilian Amazon). Design: This cross-sectional study included 333 adults (15 - 86 years old). Fish meal frequency was determined using a 7-day interview-administered dietary recall questionnaire. Fish were categorized as piscivorous and non-piscivorous fish on trophic level. Plasma phospholipid FAs were measured by capillary gas-liquid chromatography. Results: Participants consumed 5 to 6 fish meals a week, with twice as many non-piscivorous fish than piscivorous fish (4.4 fish/week vs 2.2 fish/week, respectively). The omega-3 FA levels in plasma phospholipids were low (EPA + DHA = 31.21 mg/L;%EPA + DHA = 2.59%). Omega-3 FAs increased with frequency of fish intake, and particularly with piscivorous fish, controlling for sociodemographic, anthropometric and lifestyle characteristics. DHA levels were greater in women than in men. Conclusions: Omega-3 FA in this Amazonian population increased with fish consumption, but although they consumed freshwater fish almost daily, the concentrations of omega-3 FA were relatively low and comparable to fish-eater communities for which fish is not a dietary mainstay. It is possible that nutrients present in marine, but not in certain freshwater fish species, may facilitate absorption of omega-3 FA. Sex and/or gender differences must be taken into account when assessing the relationship between fish consumption and plasma phospholipid omega-3 FA levels.

Antidiabetic Effects of Omega-3 Polyunsaturated Fatty Acids: From Mechanism to Therapeutic Possibilities

Diabetes mellitus (DM) is chronic disease characterized by hyperglycemia and insulin resistance caused by dysfunction of pancreatic β cells. Over the past few decades, epidemiological studies have suggested that dietary long-chain polyunsaturated fatty acids such as docosahexaenoic acid and eicosapentaenoic acid decrease the risk of metabolic diseases including DM. The mechanisms underlying the therapeutic efficacy of dietary long-chain polyunsaturated fatty acids in treating DM have been partly revealed. In this review, the authors describe the antidiabetic effects of long-chain polyunsaturated fatty acids and also discuss their possibilities as therapeutics for DM in the light of recent findings.

Impact of postoperative omega-3 fatty acid-supplemented parenteral nutrition on clinical outcomes and immunomodulations in colorectal cancer patients

AIM: To investigate the effect of omega-3 fatty acid parenteral supplementation postoperatively on clinical outcomes and immunomodulation in colorectal cancer patients. METHODS: Forty-two patients undergoing radical colorectal cancer resection with an indication for total parenteral nutrition postoperatively were enrolled in this prospective, double-blind, randomized, controlled study. Patients received total parenteral nutrition supplemented with either soybean oil (LCT; Intralipid, Fresenius-Kabi, SO group, n = 21) or a combination of omega-3 fish oil and soybean oil (LCT:fish oil = 5:1, fish oil; Omegaven, Fresenius-Kabi, FO group, n = 21), up to a total of 1.2 g lipid/kg per day for 7 d postoperatively. A same volume calorie and nitrogen was administrated. Routine blood test, biochemistry, systemic levels of IL-6 and TNF-α, percentage of CD3+, CD4+, and CD8+ lymphocytes were evaluated preoperatively and on postoperative d 1 and 8. Patient outcome was evaluated considering mortality during the hospital stay, length of postoperative hospital stay, and occurrence of infectious complications. RESULTS: Both lipid regimens were well tolerated. No differences between the two groups were noticed in demographics, baseline blood test, biochemistry, serum levels of IL-6 and TNF-α, percentage of CD4+, CD8+ lymphocytes, and ratios of CD4+/CD8+. Compared with those on postoperative d 1, serum IL-6 levels onpostoperative d 8 were significantly depressed in the FO group than in the reference group (-44.43 ± 30.53 vs -8.39 ± 69.08, P = 0.039). Simultaneously, the ratios of CD4+/CD8+ were significantly increased in the FO group (0.92 ± 0.62 vs 0.25 ± 1.22, P = 0.035). In addition, depression of serum TNF-α levels (-0.82 ± 2.71 vs 0.27 ± 1.67, P = 0.125) and elevation of CD3+ and CD4+ lymphocyte percentage (12.85 ± 11.61 vs 3.84 ± 19.62, P = 0.081, 17.80 ± 10.86 vs 9.66 ± 17.55, P = 0.084, respectively) were higher in the FO group than in the reference group. Patients in the FO group trended to need a shorter postoperative hospital stay (17.45 ± 4.80 d vs 19.62 ± 5.59 d, P = 0.19). No statistically significant difference was found when stratified to mortality and occurrence of infectious complications. CONCLUSION: Postoperative supplementation of omega-3 fatty acids may have a favorable effect on the outcomes in colorectal cancer patients undergoing radical resection by lowering the magnitude of inflammatory responses and modulating the immune response.

Omega-3 fatty acid improves the clinical outcome of hepatectomized patients with hepatitis B virus(HBV)-associated hepatocellular carcinoma

Omega-3 fatty acid supplemented total parenteral nutrition improves the clinical outcome of patients undergoing certain operations; however, its benefits for patients with hepatitis type B virus (HBV)-associated hepatocellular carcinoma (HCC) who have undergone hepatectomy are still not clear. The aim of this study was to evaluate the effect of omega-3 fatty acid supplemented total parenteral nutrition on the clinical outcome of patients with HBV- associated HCC who underwent hepatectomy at our institution. A total of 63 patients with HBV-associated HCC who underwent hepatectomy were included in this study. These patients were randomly assigned to receive stand- ard total parenteral nutrition (the control group, n = 31) or omega-3 fatty acid supplemented total parenteral nutri- tion (the omega-3 fatty acid group, n = 32) for at least 5 d. The study endpoints were the occurrence of infection- related complications, recovery of liver function and length of hospital stay. The results showed that the omega-3 fatty acid group had a lower infection rate (omega-3 fatty acid, 19.4% vs control, 43.8%, P 〈 0.05), a better liver function after hepatectomy: alanine transaminase (omega-3 fatty acid, 48.23__+ 18.48 U/L vs control, 73.34 q-40.60 U/L, P 〈 0.01), aspartate transaminase (omega-3 fatty acid, 35.77_ 14.56 U/L vs control, 50.53 4-24.62 U/L, P 〈 0.01), total bilirubin (omega-3 fatty acid, 24.29___7.40 mmol/L vs control, 28. 374-8.06 mmol/L, P 〈 0.05) and a shorter length of hospital stay (omega-3 fatty acid, 12.71 ___2.58 d vs control, 15.91 ___3.23 d, P 〈 0.01). The serum contents of IL-6 (omega-3 fatty acid, 23.98___5.63 pg/mL vs control, 35.55___7.5 pg/mL, P 〈 0.01) and TNF-a (ome- ga-3 fatty acid, 4.43___1.22 pg/mL vs control, 5.96___1.58 pg/mL, P 〈 0.01) after hepatectomy were significantly lower in the omega-3 fatty acid group than those of the control group. In conclusion, administration of omega-3 fatty acid may reduce infection rate and improve liver function recovery in HBV-associated HCC patients after hepatectomy. This improvement is associated with suppressed production of proinflammatory cytokines in these patients.