Combination of arginine and omega-3 fatty acids enteral nutrition in critically ill and surgical patients: a meta-analysis

Immunonutrients may improve outcomes in critically ill and surgical patients. The objective of this meta-analysis was to determine if the combination of arginine and omega-3 fatty acids impacts infection rate, hospital length of stay and mortality in critically ill or surgical patients. In total, 23 studies met all of the criteria. Immunonutrition with arginine and omega-3 fatty acids was administered either pre- or post-operatively or during intensive care unit stay in seven, ten and six studies, respectively. Infection rate and length of stay were significantly lower in patients receiving immunonutrition compared with the control group. In a subgroup analysis, these differences were maintained in the pre- and post-operative populations, but were not significant in the critically ill population. Mortality was not significantly different between the immunonutrition and control groups.     

Bioequivalence of two omega-3 fatty acid ethyl ester formulations: a case of clinical pharmacology of dietary supplements

AIM

To evaluate the bioequivalence of two omega-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA) ethyl ester preparations, previously shown not to be bioequivalent in healthy subjects, with the objective of providing a guideline for future work in this area.

METHOD

A randomized double-blind crossover protocol was chosen. Volunteers with the lowest blood concentrations of n-3 LC-PUFA were selected. They received the ethyl esters in a single high dose (12 g) and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) blood concentrations were analyzed after fingerprick collection at intervals up to 24 h.

RESULTS

Differently from a prior study, the pharmacokinetic analysis indicated a satisfactory bioequivalence: for the AUC(0,24 h) 90% CI of the ratio between the two formulations were in the range for bioequivalence (for EPA 0.98, 1.04 and for DHA 0.99, 1.04) and the same was true for C_max and t_max (90% CI were 0.95, 1.14 and 1.10, 1.25 for EPA and 0.88, 1.02 and 0.84, 1.24 for DHA).

CONCLUSION

This study shows that, in order to obtain reliable bioequivalence data of products present in the daily diet, certain conditions should be met. Subjects should have low, homogeneous baseline concentrations and not be exposed to food items containing the product under evaluation, e.g. fish. Finally, as in the case of omega-3 fatty acids, selected doses should be high, eventually with appropriate conditions of intake.     

Effects on fibrinolytic activity of corn oil and a fish oil preparation enriched with omega-3-polyunsaturated fatty acids in a long-term study

Summary

In addition to their beneficial effects in reducing platelet responsiveness, it has been a matter of controversy whether polyunsaturated fatty acids impair the fibrinolytic system or not. In a double-blind, parallel clinical trial, 40 subjects were randomized to treatment with 6?g/day of corn oil, or to 6?g/day of a fish oil preparation, enriched with omega-3-polyunsaturated fatty acids (2.0?g/day of omega-3-PUFA). Clinical and fibrinolytic variables were measured before and after 5 months of treatment. In the corn oil group, plasminogen activator inhibitor (PAI-1)decreased significantly but in the cod liver oil group, PAI-1 remained unchanged. Activities and mass concentrations of tissue plasminogen activator (t-PA) were unchanged in both groups. It is concluded that, in the doses given here, both these preparations have small or no effects on the fibrinolytic system.     

Potential effects of omega-3 fatty acids on anemia and inflammatory markers in maintenance hemodialysis patients

Background

Anemia is a common complication among hemodialysis (HD) patients. Although intravenous iron and erythropoiesis-stimulating agents revolutionized anemia treatment, about 10% of HD patients show suboptimal response to these agents. Systemic inflammation and increased serum hepcidin level may contribute to this hyporesponsiveness. Considering the anti-inflammatory properties of omega-3 fatty acids, this study aimed to evaluate potential role of these fatty acids in improving anemia and inflammation of chronic HD patients.

Methods

In this randomized, placebo-controlled trial, 54 adult patients with HD duration of at least 3 months were randomized to ingest 1800 mg of either omega-3 fatty acids or matching placebo per day for 4 months. Anemia parameters including blood hemoglobin, serum iron, transferrin saturation (TSAT), erythropoietin resistance index, and required dose of intravenous iron and erythropoietin, and serum concentrations of inflammatory/anti-inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, C-reactive protein (CRP), hepcidin, ferritin, intact parathyroid hormone (iPTH), and ratios of IL-10 to IL-6 and IL-10 to TNF-α were measured at baseline and after 4 months of the intervention.

Results

45 subjects (25 in the omega-3 and 20 in the placebo group) completed the study. No significant changes were observed in blood hemoglobin, serum iron, TSAT, and required dose of intravenous iron in either within or between group comparisons. Additionally, erythropoietin resistance index as well as required dose of intravenous erythropoietin showed no significant change in the omega-3 group compared to the placebo group. Although a relative alleviation in inflammatory state appeared in the omega-3 group, the mean differences of inflammatory and anti-inflammatory markers between the two groups did not reach statistically significant level except for IL-10-to-IL-6 ratio and serum ferritin level which showed significant changes in favor of omega-3 treatment (P <0.001 and P = 0.003, respectively).

Conclusion

Omega-3 fatty acids relatively improved systemic inflammation of chronic HD patients without any prominent benefits on anemia. However, future well-designed studies on larger number of patients may determine utility of omega-3 fatty acids in HD patients with respect to inflammation and anemia.     

辛伐他汀加omega-3脂肪酸治疗冠心病及其等危症合并混合性血脂异常随机双盲对照研究

目的评价辛伐他汀与国产omega-3脂肪酸合用在冠心病及其等危症合并混合性血脂异常患者调脂治疗中的疗效和安全性。方法用随机双盲安慰剂平行对照的试验方法,冠心病及其等危症合并混合性血脂异常患者经6-12周辛伐他汀10或20mg治疗后,低密度脂蛋白胆固醇已达标(LDL-C<2.6mmol·L-1)或接近达标(LDL-C<3.4 mmol·L-1),但甘油三酯(TG)水平在2.26-5.64 mmol·L-1,加用omega-3脂肪酸每日3g或安慰剂,治疗2月,40例患者完成试验,每组患者20名。结果Omega-3脂肪酸组治疗后,TG、总胆固醇(TC)、非高密度脂蛋白胆固醇(Non-HDL-C)较基线分别显著降低1.06±O,74(31.1％),0.35±0.58(6.3％),0.44±0.58 mmol·L-1(10.4％)(P<0.05);Omega-3脂肪酸组较安慰剂组TG降低更明显(P<0.05)。加用Omega-3脂肪酸组治疗2个月后,较基线单用辛伐他汀显著增加30％的Non-HDL-C达标率(P<0.05)及25％的全面达标率(P<0.05)。Omega-3脂肪酸组TG基线值与TG下降幅度呈显著正相关(P<0.05)。两组间药物不良反应无统计学差异。结论辛伐他汀加用国产omega-3脂肪酸调脂治疗冠心病及其等危症合并混合性血脂异常患者安全、有效。     

Omega-3 polyunsaturated fatty acids for major depressive disorder

Introduction: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) are not synthesized by the human body; they must be derived from dietary sources and they have been known to be involved with neurological, cardiovascular, cerebrovascular, autoimmune and metabolic diseases, and cognitive disorder as well as mood disorders.

Areas covered: A number of epidemiological and preclinical studies have proven the potential benefit and critical role of omega-3 PUFA in the development and management of major depressive disorder (MDD). In addition, recently independent clinical trials and meta-analyses have also provided superidority of omega-3 PUFA over placebo as monotherapy or augmentation agent in the treatment of MDD. This article presents a brief overview of the evidence to date about the clinical application and biological mechanisms of omega-3 PUFA in the treatment of MDD.

Expert opinion: Given the potential action mechanism, clinical benefits and currently available clinical trial data, omega-3 PUFAs may deserve greater attention and wider application for treatment of MDD. However, the practical utility of omega-3 PUFA as one of promising alternative agent for treatment of MDD still have many questions unresolved to be fully addressed in near future.     

The mechanism of action of omega-3 fatty acids in secondary prevention post-myocardial infarction

ABSTRACT

Background: Omega-3 fatty acids from fish and fish oils can protect against coronary heart disease (CHD), which is still the most common cause of death in the Western economies. Evidence from epidemiological and case cohort studies indicate that consumption of fatty fish and omega-3 fatty acids reduces the risk of cardiovascular mortality.

Objective: This article briefly reviews the evidence regarding omega-3 fatty acids and CHD and outlines the mechanisms through which omega-3 fatty acids might confer cardiac benefits over and above the standard secondary prevention strategies.

Conclusion: The conclusion reached is that omega-3 fatty acids play a significant role in secondary prevention post-myocardial infarction. The mechanisms through which two of these omega-3 fatty acids, eicosapentaenoic acid and docosahexanoic acid, exert their action appear to be distinct and adjuvant to the available standard secondary prevention therapies. The role to be played by the administration of a newly licensed 90% concentrate EPA + DHA formulation (1?g/day capsule: Omacor) is explored.     

神经干细胞治疗小儿脑瘫现状与进展

他汀类药物应用于高脂血症患者及心脑血管疾病的一二级预防,越来越多的研究表明,他汀类在降脂、抗炎、保护血管内皮、稳定动脉粥样硬化斑块、抗心律失常同时,还会影响患者的血糖水平。因此,全面了解他汀类药物的作用,指导临床用药意义重大。     

辛伐他汀加用Omega-3脂肪酸对混合性血脂异常患者高敏C反应蛋白、血脂及纤溶的影响

目的:评价辛伐他汀加用Omega-3脂肪酸对冠心病及冠心病等危症合并混合性血脂异常患者高敏C反应蛋白(HsCRP)、血脂及纤溶的影响.方法:采用随机、双盲、安慰剂平行对照方法,40例冠心病及冠心病等危症合并混合性血脂异常患者经6～12周辛伐他汀10mg或20mg治疗后,分为试验组(n=20)和对照组(n=20),分别加用Omega-3脂肪酸3g*d-1或安慰剂,治疗2个月,观察治疗前后对HsCRP、血脂及纤溶的影响.结果:试验组治疗后HsCRP、三酰甘油(TG)、总胆固醇(TC)、TC/高密度脂蛋白胆固醇(HDL-C)较基线分别降低(2.16±2.77)(38.5%),(94.0±65.4)(31.1%),(13.3±22.3)mmol*L-1(6.3%)和(0.78±1.60)mg*dL-1(P分别<0.01,<0.001,<0.05,<0.05),对照组HsCRP及TG降低更为显著(P分别为0.021及0.011).试验组TG降低的数值及百分数分别与HsCRP降低的数值及百分数呈显著正相关(r分别为0.51和0.45,P分别为0.021和0.047).结论:辛伐他汀加用Omega-3脂肪酸增加二者的调脂优势和非调脂优势.     

Epigenetic regulation of gene expression and M2 macrophage polarization as new potential omega-3 polyunsaturated fatty acid targets in colon inflammation and cancer

Introduction: It has become increasingly clear that dietary habits may affect the risk/progression of chronic diseases with a pathogenic inflammatory component, such as colorectal cancer. Considerable attention has been directed toward the ability of nutritional agents to target key molecular pathways involved in these inflammatory-related diseases.

Areas covered: ω-3 Polyunsaturated fatty acids (PUFA) and their oxidative metabolites have attracted considerable interest as possible anti-inflammatory and anti-cancer agents, especially in areas such as the large bowel, where the influence of orally introduced substances is high and tumors show deranged PUFA patterns. On this basis, we have analyzed pre-clinical findings that have recently revealed new insight into the molecular pathways targeted by ω-3 PUFA.

Expert opinion: The findings analyzed herein demonstrate that ω-3 PUFA may exert beneficial effects by targeting the epigenetic regulation of gene expression and altering M2 macrophage polarization during the inflammatory response. These mechanisms need to be better explored in the large bowel, and further studies could better clarify their role and the potential of dietary interventions with ω-3 PUFA in the large bowel. The epigenomic mechanism is discussed in view of the potential of ω-3 PUFA to enhance the efficacy of other agents used in the therapy of colorectal cancer.     

Lipidomics reveals the dynamics of lipid profile altered by omega-3 polyunsaturated fatty acid supplementation in healthy people

Glycerophospholipids (GPs) and sphingolipids (SPs) are important lipid components in the body and play biological functions. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are important nutrients, and their supplements are commonly used for preventing some diseases. However, the effect of n-3 PUFAs on the human glycerophospholipidome and sphingolipidome is unclear. We used targeted lipidomics to study the GP and SP profile of healthy individuals after supplementation with n-3 PUFAs for 3, 7, 14 and 21 days. Fuzzy c-means clustering was used to cluster the lipid species into six classes reflecting different changed-content patterns after n-3 PUFA supplementation. Among the species with significantly changed content, lysophospholipids were the most sensitive; their content started to increase on day 3. The content of phosphatidylserines increased at a later stage. The content of most of the phosphatidylcholines and alkylphosphatidylcholines decreased on day 21. A correlation network analysis of lipid species suggested that some enzymes involved in the metabolism of lysophospholipids and phosphatidylserines were regulated by n-3 PUFAs. Levels of creatine kinase-MB (CK-MB), urea, glucose, triglycerides and total bilirubin were altered by n-3 PUFA at 21 days. Correlation analysis revealed that the level of CK-MB was negatively correlated with those of species in lysophosphatidic acid, lysophosphatidylcholine, lysophosphatidylethanolamine and phosphatidylserine classes, which were increased by n-3 PUFA supplementation. With the analysis in this work, we demonstrated the regular pattern of n-3 PUFAs on GP and SP metabolism, which provides a pharmacological basis for n-3 PUFAs for clinical application.     

Vitamin E supplementation modulates the biological effects of omega-3 fatty acids in naturally aged rats

Omega-3 fatty acids are well-known class of nutraceuticals with established health benefits. Recently, the oxidation products of these fatty acids are gaining attention, as they are likely to disturb body redox balance. Therefore, the efficacy of omega-3 fats under conditions of diminished antioxidant status, such as aging, is always a concern. Present study assessed the effects of omega-3 fats (DHA and EPA) together with or without vitamin-E in naturally aged rats. It was found that in omega-3 fats alone consumed rats the lipid profile was improved, while in omega-3 fat with vitamin-E-consumed group (OMVE), the hepato protective and antioxidant properties were pronounced, especially the redox status of brain tissue. It is possible that vitamin-E might have reduced the peroxidation of omega-3 fats, thereby allowing their synergistic effects. Hence, the use of vitamin-E along with omega-3 fat may be beneficial under aged conditions.     

Role of omega-6 and omega-3 fatty acids in fetal programming

Maternal nutrition plays a critical role in fetal development and can influence adult onset of disease. Linoleic acid (LA) and alpha-linolenic acid (ALA) are major omega-6 (n-6) and n-3 polyunsaturated fatty acids (PUFA), respectively, that are essential in our diet. LA and ALA are critical for the development of the fetal neurological and immune systems. However, in recent years, the consumption of n-6 PUFA has increased gradually worldwide, and elevated n-6 PUFA consumption may be harmful to human health. Consumption of diets with high levels of n-6 PUFA before or during pregnancy may have detrimental effects on fetal development and may influence overall health of offspring in adulthood. This review discusses the role of n-6 PUFA in fetal programming, the importance of a balance between n-6 and n-3 PUFAs in the maternal diet, and the need of further animal models and human studies that critically evaluate both n-6 and n-3 PUFA contents in diets.     

The induction of apoptosis in pre-malignant keratinocytes by omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is inhibited by albumin

The long chain omega-3 polyunsaturated fatty acids (PUFA) have been reported to exert anti-cancer effects. At this study we tested the effect of the omega-3 PUFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on pre-malignant keratinocytes growth in the well-characterised human pre-malignant epidermal cell line, HaCaT and attempted to identify a PUFA serum antagonist. Both EPA and DHA inhibited HaCaT growth and induced apoptosis. At the 10% (v/v) foetal bovine serum (FBS) medium, limited growth inhibition (3–20% for 50 μM DHA and EPA respectively) and negligible apoptosis were observed with PUFA use. However, at 3% (v/v) FBS medium, 30–50 μM of PUFA caused impressive levels of growth inhibition (82–83% for 50 μM DHA and EPA respectively) and increase of apoptosis (8–19% increase in 72 h). None of the numerous serum growth factors present in FBS or the antioxidant n-tert-butyl-α-phenylnitrone could inhibit the PUFA-induced cytotoxicity. In contrast, bovine and human albumin (0.1–0.3%, w/v) significantly antagonized the growth inhibitory and apoptosis-inducing effects of PUFA. In conclusion, we have shown for the first time that omega-3 PUFA inhibit the growth and induce apoptosis of pre-malignant keratinocytes and identified albumin as a major antagonistic factor in serum that could limit their effectiveness at pharmacologically-achievable doses.     

Benefits and risks of fish consumption Part I. A quantitative analysis of the intake of omega-3 fatty acids and chemical contaminants

In recent years, and based on the importance of fish as a part of a healthy diet, there has been a notable promotion of fish consumption. However, the balance between health benefits and risks, due to the intake of chemical contaminants, is not well characterized. In the present study, edible samples of 14 marine species were analyzed for the concentrations of omega-3 fatty acids, as well as a number of metals and organic pollutants. Daily intakes were specifically determined for a standard adult of 70 kg, and compared with the tolerable/admissible intakes of the pollutants, if available. Salmon, mackerel, and red mullet were the species showing the highest content of omega-3 fatty acids. The daily intakes of cadmium, lead, and mercury through fish consumption were 1.1, 2.0, and 9.9 μg, respectively. Dioxins and furans plus dioxin-like polychlorinated biphenyls (PCBs) intake was 38.0 pg WHO-TEQ/day, whereas those of polybrominated diphenyl ethers (PBDEs), polychlorinated diphenyl ethers (PCDEs), polychlorinated naphthalenes (PCNs) and hexachlorobenzene (HCB) were 20.8, 39.4, 1.53, and 1.50 ng/day, respectively. In turn, the total intake of 16 analyzed polycyclic aromatic hydrocarbons (PAHs) was 268 ng/day. The monthly fish consumption limits for human health endpoints based on the intake of these chemical contaminants were calculated for a 70 years exposure. In general terms, most marine species here analyzed should not mean adverse health effects for the consumers. However, the type of fish, the frequency of consumption, and the meal size are essential issues for the balance of the health benefits and risks of regular fish consumption.