Long chain N-3 polyunsaturated fatty acids in the prevention of allergic and cardiovascular disease

The diet is considered to have a major impact on human health. Dietary lipids including long chain polyunsaturated fatty acids (LCPUFA) possess potent immunomodulatory activities. Over the last decades the incidence of inflammatory disorders including allergic and cardiovascular diseases (CVD) has been rising. This phenomenon is associated with deficiencies in N-3 LCPUFA, found in fatty fish, and increased content of N-6 LCPUFA in the Western diet. LCPUFA act via different mechanisms including membrane fluidity, raft composition, lipid mediator formation, signaling pathways and transmembrane receptors. N-3 LCPUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce the development of allergic disease by affecting both the innate and adaptive immune system involved in the initiation and persistence of allergic disease. Fish oil has been shown to be effective in the primary prevention of allergic disease in infants at risk when supplemented during pregnancy and lactation. Subtle effects of N-3 LCPUFA on the outcome of the immune response may underlie these protective effects. This review describes the currently reported effects of LCPUFA on dendritic cells, T cells, B cells and mast cells. Also CVD are positively affected by N-3 LCPUFA. Populations consuming high amounts of oily fish are protected against CVD. Moreover N-3 LCPUFA are effective in the secondary prevention of cardiovascular events. Amongst other effects, EPA and DHA have been shown to suppress endothelial cell activation hereby reducing adhesion molecule expression and endothelial cell - leukocyte interactions. This review describes the mechanistic basis of the preventive role for N-3 LCPUFA in allergic disease and CVD.     

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.     

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

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 consumpton 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.     

A multi-country economic evaluation of low-dose aspirin in the primary prevention of cardiovascular disease

BACKGROUND: Low-dose aspirin (acetylsalicylic acid) is standard care in patients with a history of cardiovascular disease (CVD). The use of low-dose aspirin in primary prevention is not yet fully established, although meta-analyses and US and European guidelines support its use in people at increased risk of CVD. The primary objective of this study was to assess the economic consequences of the use of low-dose aspirin in the primary prevention of CVD in four European countries (UK, Germany, Spain and Italy). METHODS: Based on results (benefits and harms) reported in meta-analyses, a state-transition model was developed to predict the cost effectiveness of low-dose aspirin in the primary prevention of CVD. The model consists of five health states: no history of CVD, history of stroke, history of myocardial infarction (MI), history of stroke and MI, and death. A 10-year time horizon and 1-year cycles were used. Secondary prevention data were derived from the aspirin arm of the CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events) study.Direct costs from the public healthcare payer's perspective were used (euro, 2003 values). Effects were expressed in life-years (LY) and QALYs gained. Quality weights were obtained from published data.Country-specific discounting was applied on effects and costs (3.5% for the UK, 5% for Germany and 3% for Spain and Italy). Univariate sensitivity analysis and Monte Carlo simulation were performed to assess uncertainty in the results. RESULTS: For patients with an annual risk of coronary heart disease (CHD) of 1.5%, the model resulted in 10-year savings with low-dose aspirin of on average euro 201 (95% CI 81, 331), euro 281 (95% CI 141, 422), euro 797 (95% CI 301, 1331) and euro 427 (95% CI 122, 731) per patient in the UK, Germany, Spain and Italy, respectively. Average total cost was almost 3- to 4-fold higher in Spain and Italy than in the UK and Germany. Savings (non-significant) start in the first year of treatment in all countries.Sensitivity analyses on cost of complications, utility, discounting, stroke rate and gastrointestinal bleeding rate showed the robustness of the results. From an annual risk of CHD of 0.236% for the UK, 0.324% for Germany, 0.244% for Spain and 0.560% for Italy, low-dose aspirin was cost saving compared with placebo. Monte Carlo analysis showed aspirin dominance in about 97% of cases for the three studied annual risks of CHD (0.6%, 1.0% and 1.5%) in the UK, Germany and Spain. In Italy, aspirin dominance in > 95% of cases was seen at annual risks of 1% and 1.5%. CONCLUSIONS: Administering low-dose aspirin to patients with an annual risk of CHD of > or = 1% appears to be significantly cost saving from the healthcare payer's perspective in all countries analysed. Sensitivity analyses (CHD risk and bleedings) suggested the results were robust.     

Effects of n-3 polyunsaturated fatty acids on depressive symptoms,anxiety and emotional state in patients with acute myocardial infarction

BackgroundOur aim was to assess whether an early introduced n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation affects depression symptoms, anxiety and emotional state in patients with acute myocardial infarction (AMI) and no history of mental disorders.MethodsFifty two patients with AMI were enrolled into the study and randomized to the study group (group P; n = 26; standard therapy + n-3 PUFA1 g daily) or the control group (group C; n = 26; standard therapy). The following psychological tests were used at the baseline (3rd day of AMI) and after one month (30 ± 1 days): Beck Depression Inventory (BDI), State-Trait Anxiety Inventory in a specific situation (STAI-S) and as a general trait (STAI-T), Emotional State Questionnaire (ESQ).ResultsThe baseline characteristics, pharmacotherapy and BDI, STAI-S/T and ESQ were similar between both groups. The mean test scores assessed for all patients (group P and C) during the one-month observation were significantly lower for BDI (p = 0.04), STAI-T (p = 0.03), STAI-S (p = 0.01) and harm/loss emotions (p = 0.005). After adjusting for age, sex, body mass index, coronary artery disease severity, ejection fraction, serum troponin level and the baseline tests results, n-3 PUFAintervention revealed additional significant decrease in BDI (p = 0.046), STAI-S (p = 0.03) and harm/loss emotions (p = 0.04).ConclusionsOur study provides novel and preliminary observations – n-3 PUFAsupplementation reveals additional decreasing effects on depressive and anxiety symptoms in early post-MI patients.     

n-3多不饱和脂肪酸的研究进展

目的综述n-3多不饱和脂肪酸的最新研究进展。方法查阅文献，进行整理和归纳。结果及结论n-3多不饱和脂肪酸有广泛的生物学活性及广阔的应用前景。     

The role of n-3 polyunsaturated fatty acids in the prevention and treatment of cardiovascular disease

Growing evidence has suggested an important role of n-3 polyunsaturated fatty acids in reducing risk of cardiovascular disease in the general population and patients with preexisting heart disease. In particular, several long-term epidemiologic studies have found an inverse association between fish consumption and risk of coronary heart disease or stroke. Two secondary prevention trials have found that increasing fish consumption or fish oil supplementation significantly reduced coronary death among patients with existing myocardial infarction. In addition, epidemiologic and clinical studies have suggested that alpha-linolenic acid (ALA), a short-chain n3-3 fatty acid from plant sources, may have similar cardiac benefits as long-chain n-3 fatty acids from fish. Potential mechanisms through which n-3 polyunsaturated fatty acids protect against CVD include their antiarrhythmic and antithrombotic effects, and improving insulin sensitivity and endothelial function. (c) 2001 Prous Science. All rights reserved.     

n-3 polyunsaturated fatty acids and the prevention of colorectal cancer: molecular mechanisms involved

Increasing evidence supports the hypothesis that nutrition habits play a critical role in the incidence and growth of colorectal cancer. Among dietary factors, fish-derived n-3 polyunsaturated fatty acids (PUFAs) have gained particular interest, since epidemiological studies have shown a reduced incidence of this cancer in populations consuming high levels of fish. Also a variety of experimental studies and different clinical trials substantiated the beneficial role of n-3 PUFAs. Such an anti-neoplastic activity has been related to the regulatory effects exhibited by n-3 PUFAs on cell proliferation and apoptosis. Anti-angiogenic and anti-metastatic effects have been also reported for these fatty acids. Finally, it has been suggested that they may act as adjuvant therapeutic agents sensitizing tumors, including colon cancer, to different anti-neoplastic drugs. Several molecular mechanisms have been hypothesized to explain their anti-neoplastic action and, in particular, the modulating effect on the expression of several proteins involved in the regulation of cell cycle and apoptosis, such as Bcl-2, Bax, c-Myc seem to play a central role. Their inhibitory action has been also recently suggested for the molecular pathways driven by COX-2 and beta-catenin, known to play a major role in the development and progression of colon cancer. The aim of the present review is to analyze the anti-neoplastic effect of n-3 PUFAs towards colon cancer, and examine the molecular mechanisms involved.     

n-3多不饱和脂肪酸在慢性肾脏疾病中的应用

数十年来的动物研究支持鱼油中的主要成分n-3多不饱和脂肪酸(n-3PUFA)在肾脏疾病治疗中的有效性,在一些人类肾小球疾病如IgA肾病中n-3PUFA也被证实有益,但临床试验结果并不一致。n-3PUFA应用能否成为肾脏疾病的一种新的治疗手段,仍需进一步的大规模临床研究。     

n-3系多烯酸摄取量的探讨

n-3系多烯酸具有防治心血管疾病、促进脑组织及视网膜的正常生长发育等生理作用,因此越来越引起人们摄取的兴趣。从目前的膳食结构来看,摄取n-3系多烯酸是十分必要的。如何正确的摄取,以充分发挥n-3系多烯酸对人体的健康作用及避免不良反应是人们摄取及开发这方面的保健食品和药物时值得注意的问题。     

n－3多烯脂肪酸在创伤感染中的作用

为探讨ｎ－３多烯脂肪酸在创伤感染中所起的作用，采用盲肠结扎穿孔诱发大鼠脓毒血症，食道插管灌入液体鱼油治疗。研究结果，术前接受４ｗｋ鱼油治疗组与脓毒症组比较，前者动物枯否细胞释放的细胞因子，炎性介质及氧自由基产物明显减少，膜磷脂成分及花生四烯酸含量明显增加；同时观察到肝细胞膜脂流动性明显升高，相变温度明显降低，内皮素含量明显减少。提示，ｎ－３多烯脂肪酸有调节创伤感染动物巨噬细胞的生物学功能，减轻肝细胞和血管内皮细胞损伤的作用。     

n-3系多烯酸摄取量的探讨

n-3系多烯酸具有防治心血管疾病、促进脑组织及视网膜的正常生长发育等生理作用,因此越来越引起人们摄取的兴趣.从目前的膳食结构来看,摄取n-3系多烯酸是十分必要的.如何正确的摄取,以充分发挥n-3系多烯酸对人体的健康作用及避免不良反应是人们摄取及开发这方面的保健食品和药物时值得注意的问题.     

n－3多烯脂肪酸在创伤感染中的作用

为探讨ｎ－３多烯脂肪酸在创伤感染中所起的作用，采用盲肠结扎穿孔诱发大鼠脓毒血症，食道插管灌入液体鱼油治疗。研究结果，术前接受４ｗｋ鱼油治疗组与脓毒症组比较，前者动物枯否细胞释放的细胞因子，炎性介质及氧自由基产物明显减少，膜磷脂成分及花生四烯酸含量明显增加；同时观察到肝细胞膜脂流动性明显升高，相变温度明显降低，内皮素含量明显减少。提示，ｎ－３多烯脂肪酸有调节创伤感染动物巨噬细胞的生物学功能，减轻肝细胞和血管内皮细胞损伤的作用。     

Primary and secondary prevention of atrial fibrillation with statins and polyunsaturated fatty acids: review of evidence and clinical relevance

Atrial fibrillation (AF) is an increasingly common arrhythmia that now stands at epidemic proportion, with more than 2.3 million people affected in the USA and over 4.5 million people affected in Western Europe. AF is an expression of underlying heart disease and is increasingly associated with hypertension, congestive heart failure, and ischemic heart disease. It is also a progressive disease secondary to continuous structural remodeling of the atria, which relates to AF itself, to changes associated with aging and to progression of the underlying heart disease. Traditionally, AF has been addressed only after it has already presented with pharmacological and nonpharmacological therapies designed for rhythm or rate control (secondary prevention). Although secondary prevention is the most feasible approach at present, the concept of primary prevention of AF with therapies aimed at preventing the development of substrate and correcting the risk factors for AF has emerged as a strategy, which is likely to produce a larger effect in the general population. Recent experiments provided new insights into AF pathophysiology, which generated background for new mechanism-based therapies. Agents targeting inflammation, oxidative injury, atrial myocyte metabolism, extracellular matrix remodeling, and fibrosis have theoretical advantages as novel therapeutic strategies. In this respect, drugs that are not traditionally antiarrhythmic such as angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, aldosterone antagonists, statins, and omega-3 polyunsaturated fatty acids have shown an antiarrhythmic potential in addition to any treatment effect on the underlying disease. These agents are thought to have an advantage of targeting both the occurrence and progression of the substrate for AF, thus, providing primary and secondary prevention of the arrhythmia. Although first experimental and hypothesis-generating small clinical studies or retrospective analyses have been encouraging, several larger, properly designed, prospective trials have not confirmed earlier observations. This review provides a contemporary evidence-based insight into the possible preventative and reverse remodeling role of statins and polyunsaturated fatty acids in AF.     

Omega-3 polyunsaturated fatty acids and cognition in a college-aged population

The cognitive influences of omega-3 polyunsaturated fatty acids (n-3 PUFA) remain unclear throughout the life span. Dietary n-3 PUFA appear cognitively beneficial prenatally and neuroprotective at later age; however, researchers using supplementation designs have reported disparate findings across age groups. Few studies have examined the cognitive impact of n-3 PUFA during young adulthood. This study assessed the cognitive effects of fish oil supplementation at college age, hypothesizing benefits on affect, executive control, inhibition, and verbal learning and memory. College-aged participants were assigned to active (n = 20, 5 men; age = 19.9, sage = 1.8) or placebo (n = 21, 7 men; age = 20.4, sage = 1.6) treatments, receiving fish oil (480 mg DHA/720 mg EPA) or coconut oil, respectively. Both groups completed four weeks of supplementation. At baseline and posttreatment, the researchers administered the Rey Auditory Verbal Learning Test (RAVLT; Lezak, 1995), Stroop Color and Word Test (SCWT; Golden & Freshwater, 2002), Trail Making Test (TMT; Corrigan & Hinkeldey, 1987; Gaudino, Geisler, & Squires, 1995; Lezak, 1995), and Positive and Negative Affect Schedule (PANAS; Watson, Clark, & Tellegen, 1988). Repeated-measures ANOVAs indicated no benefits of fish oil on the SCWT, RAVLT Stages 1 to 5, or PANAS. An interaction occurred between condition and time of measurement (i.e., baseline and posttreatment) on RAVLT Stages 6 and 7, and placebo significantly improved TMT performance over fish oil. The benefits of n-3 PUFA on RAVLT performance derived more from depreciated placebo performance than improved performance due to fish oil. The placebo gain on TMT performance likely derived from a learning effect. Together, these results present limited cognitive benefits of n-3 PUFA at college age; however, the treatment may have been subtherapeutic, with a larger sample needed to generalize these results.     

急性心肌梗死后患者二级预防的研究

目的 通过观察对急性心肌梗死（AMI）患者定期复诊、督导规范二级预防用药,与未干预的AMI患者后二级预防对比,对AMI患者出院进行管理的作用进行分析.方法 选取急性ST段抬高心肌梗死并接受再灌注治疗患者622例.观察组患者225例为进行冠心病二级预防用药督导,督促定期复查者;不能坚持上述情况而分散就医、未规律服药,未定期复诊者394例为对.照组.比较随访1年时两组复查时血压、心率、心功能情况.结果 随访1年观察组与对照组患者的收缩压分别为（113±19）mm Hg（1 mm Hg=0.133 kPa）与（118±18）mm Hg（P=0.040）;舒张压分别为（72±14）mm Hg与（75±16）mm Hg（P=0.015）.观察组患者的血压的较对照组有所降低.随访1年时2组患者的心率分别为（70±14）次/min与（77±19）次/min（P=0.000）.观察组患者的心率较对照组有所减慢.出院后1年随访,结果显示观察组患者较对照组左心室舒张末期内径[分别为（50.6±5.3）mm与（58.8±5.8）mm,P=0.020]、左心室收缩末期内径[分别为（34.9±7.1）mm比（38.8±6.2）mm,P=0.011]有所减小;左心室射血分数[分别为（56.5±10.8）%与（50.3±11.6）%,P=0.0024]有所提高,两组之间的差异有统计学意义.结论 对急性心肌梗死患者出院后进行冠心病二级预防健康教育有积极意义.     

ω-3不饱和脂肪酸临床应用新进展

总结了ω3不饱和脂肪酸作用机制及临床应用。ω-3不饱和脂肪酸可用于治疗或辅助治疗多种疾病，尤其是在心血管疾病、高脂血症、风湿性关节炎、抑郁症及营养免疫等方面疗效肯定，且安全性高，不良反应少，是目前临床上集治疗与营养支持为一体的药物。     

Dietary n-3 polyunsaturated fatty acids and the paradox of their health benefits and potential harmful effects

There is some evidence to support the toxicity of polyunsaturated fatty acids (PUFAs) and their oxidative products, suggesting their involvement in the pathogenesis of different chronic diseases, including cancer. It has been shown that products of PUFA oxidation may exert a carcinogenic action by forming mutagenic adducts with DNA. However, a large amount of evidence accumulated over several decades has indicated the beneficial effects of administration of n-3 PUFAs in the prevention and therapy of a series of diseases. In particular, there is much evidence that n-3 PUFAs exert anti-inflammatory and antineoplastic effects, whereas n-6 PUFAs promote inflammation and carcinogenesis. In our tissues, both of the two classes of PUFAs can be converted into bioactive products, incorporated into membrane phospholipids or bound to membrane receptors, where they may alter, often in opposite ways, transduction pathways and affect important biological processes, such as cell death and survival, inflammation, and neo-angiogenesis. In the present review, we intend to shed light on the paradox of the coexisting healthy and toxic effects of n-3 PUFAs, focusing on their possible pro-oxidant cytotoxic and carcinogenic effect, in order to understand if their increased intake, recommended by a number of health agencies worldwide and promoted by nutraceutical producers, may or may not represent a hazard to human health.