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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Additive neurorestorative effects of exercise and docosahexaenoic acid intake in a mouse model of Parkinson’s disease

There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.

The Effects of n-3 Fatty Acids and Bexarotene on Breast Cancer Cell Progression

Breast cancer cell growth can be inhibited in vivo by retinoid X receptor (RXR) specific retinoids. In both animal and cell culture studies, omega-3 fatty acids share growth regulatory effects similar to those of RXR specific retinoids (rexinoids). One synthetic rexinoid, bexarotene (LCD 1069, Targretin), is used clinically to treat cancer patients. Of concern is that some patients are unable to tolerate high doses of such treatment drugs. We hypothesized that n-3 fatty acids and bexarotene may work synergistically to slow breast cancer cell growth. To test our hypothesis, we used MCF-7 human mammary carcinoma cells and an in vitro cell culture model. We investigated the relationship between the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) alone and in conjunction with bexarotene in slowing MCF-7 cell growth. Following a 72 hr incubation with the respective treatments, bexarotene enhanced cell growth (p < 0.05) while DHA showed a strong growth inhibitory effect which was not enhanced by the addition of bexarotene (p < 0.05). EPA alone was not effective in altering cell growth (p < 0.05). Interestingly, when combined with bexarotene, EPA was more effective at slowing cell growth than when cells received EPA alone. Thus, select omega-3 fatty acids alone are more effective than bexarotene in slowing MCF-7 cell progression. However, the use of the RXR-selective retinoids may enhance the growth regulatory mechanisms of the fatty acid EPA.

Fatty Acid Treatment with Pure Omega-3 Eicosapentaenoic Acid Ethyl Ester for Patients with Cardiovascular Diseases: Differences between Branded (EPADEL®) and Generic Products

Background: Omega-3 polyunsaturated fatty acids (PUFAs) have some protective benefits for patients with coronary artery and cerebrovascular diseases. Eicosapentaenoic acid (EPA) drugs are prescribed as branded (B: EPADEL?) or generic products but no data exist concerning the differences in treatment outcomes between these products. Methods and Results: We investigated the differences in the serum levels of EPA, docosahexaenoic acid (DHA) and arachidonic acid (AA), and the EPA/AA ratios through blood sampling six months after daily administration of 1800 mg of EPADEL? and a generic EPA drug was initiated for 96 patients with cardiovascular diseases. All patients received these PUFA treatments while continuing with baseline therapy. After 6 months of administration, EPADEL? produced better results than the generic (G) product (EPA;baseline: 59.4 ± 25.5 μg, B: 215.5 ± 58.8 μg, G: 199.7 ± 63.8 μg, B vs G, p < 0.0005;AA;baseline: 197.4 ± 44.6 μg, B: 158.3 ± 36.3 μg, G: 163.6 ± 38.9 μg, B vs G, p < 0.02, as mean ± SD). Conclusions: There were clear differences between EPA branded and the generic products. Further study is required to determine whether the benefits from the branded product justify the higher price compared to the generic drug cost.

The Impact of Omega-3 Fatty Acid Use on the Risk of Atrial Fibrillation in Patients with Cardiovascular Disease

Fish oils containing omega-3 fatty acids (OM3FA) are widely prescribed in the management of dyslipidemia. An asso-ciation between OM3FA and reduced risk of atrial fibrillation (AF) has been proposed. We examined the impact of OM3FA exposure on the risk of developing AF in patients with cardiovascular disease. Data was obtained from elec-tronic medical records of patients seen by our cardiology service between 2005 and 2007. Patients were excluded if AF developed prior to, or on the day of, OM3FA exposure. A total of 11,360 subjects were eligible for analyses. Subjects exposed to OM3FA were at higher risk for AF. Nearly all AF risk factors were significantly more prevalent in the OM3FA exposed group. As expected, those prescribed OM3FA were also more likely to be prescribed statins, ACE in-hibitors, aspirin, and beta blockers. AF occurred in 8.5% (221/2600) of OM3FA exposed subjects and 23.5% (2054/8760) of those not exposed. After controlling for AF risk factors, OM3FA exposed subjects were 74% less likely to develop AF than those not exposed to OM3FA (odds ratio 0.26, 95%CI 0.22-0.30, p < 0.0001). After controlling for risk factors for AF, OM3FA use is significantly associated with a reduced risk for AF in patients with cardiovascular disease. Potential mechanisms which may explain the ability of OM3FAs to reduce AF include its anti-inflammatory and anti-arrhythmic properties. The optimal dose of OM3FA to prevent AF is unknown and warrants prospective as-sessment in a randomized controlled trial of OM3FAs powered to detect significant differences in AF.