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Eicosapentaenoic acid (EPA) Reviews: 2005
Zhang, L. K. and C. S. Tang (2005). "[Cytochrome P450/epoxyeicosatrienoic acids system and myocardial ischemic-reperfusion injury]." Zhongguo Yi Xue Ke Xue Yuan Xue Bao 27(4): 539-42.
Interests on the effects of cytochrome P450 (CYP450) monooxygenases and epoxyeicosatrienoic acids (EETs) on myocardial ischemic-reperfusion injury has been increased in recent years. The CYP450/EET system may influence the degree of myocardial ischemic-reperfusion injury through "poly-targets", such us oxygen free radical, calcium overload, leukocytes adherence, nitric oxide, ATP-sensitive K+ channels, and mitogen activated protein kinase. The exaggeration or recovery of injury depends on the physical status. Study of factors that affects CYP450/EET, particularly identification of their involvement in cardioprotective signaling and specific roles, will elucidate the mechanisms of myocardial ischemic-reperfusion injury, and find a new way of prevention and treatment. This article will review the relationship between the changes of CYP450/EETs system and myocardial ischemic-reper-
Young, G. and J. Conquer (2005). "Omega-3 fatty acids and neuropsychiatric disorders." Reprod Nutr Dev 45(1): 1-28.
Epidemiological evidence suggests that dietary consumption of the long chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), commonly found in fish or fish oil, may modify the risk for certain neuropsychiatric disorders. As evidence, decreased blood levels of omega-3 fatty acids have been associated with several neuropsychiatric conditions, including Attention Deficit (Hyperactivity) Disorder, Alzheimer's Disease, Schizophrenia and Depression. Supplementation studies, using individual or combination omega-3 fatty acids, suggest the possibility for decreased symptoms associated with some of these conditions. Thus far, however, the benefits of supplementation, in terms of decreasing disease risk and/or aiding in symptom management, are not clear and more research is needed. The reasons for blood fatty acid alterations in these disorders are not known, nor are the potential mechanisms by which omega-3 fatty acids may function in normal neuronal activity and neuropsychiatric disease prevention and/or treatment. It is clear, however, that DHA is the predominant n-3 fatty acid found in the brain and that EPA plays an important role as an anti-inflammatory precursor. Both DHA and EPA can be linked with many aspects of neural function, including neurotransmission, membrane fluidity, ion channel and enzyme regulation and gene expression. This review summarizes the knowledge in terms of dietary omega-3 fatty acid intake and metabolism, as well as evidence pointing to potential mechanisms of omega-3 fatty acids in normal brain functioning, development of neuropsychiatric disorders and efficacy of omega-3 fatty acid supplementation in terms of symptom management.
Woods, M. N. (2005). "Role of n-3 fatty acids in prevention of disease complications in patients with HIV." Nutr Clin Care 8(1): 24-30.
Hypertriglyceridemia and insulin resistance have been seen in patients with HIV. Beneficial effects of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported for these conditions. One study of n-3 fatty acid supplementation in patients with HIV reported a decrease in serum triglyceride levels. These marine fatty acids appear to be working at a number of sites to achieve an improvement in lipid metabolism and insulin sensitivity. There is disagreement about the amount of n-3 fatty acids needed to achieve different effects and about the optimal ratio of dietary n-6 and n-3 fatty acids.
Wong, K. W. (2005). "Clinical efficacy of n-3 fatty acid supplementation in patients with asthma." J Am Diet Assoc 105(1): 98-105.
The rising prevalence of asthma is an alarming health concern. The morbidity and mortality associated with asthma not only disrupts the quality of life, but it also escalates health care costs. Asthma is a chronic inflammatory disease of the respiratory tract. An exaggerated production of the arachidonic acid-derived eicosanoids, leukotrienes, has been implicated as the chemical trigger for inflammation. n-3 fatty acid supplementation has been shown to suppress the synthesis of the n-6 series of leukotrienes by competing and inhibiting the metabolism of arachidonic acid. The results from epidemiological studies suggested that fish consumption was beneficially associated with lung function and prevalence of asthma. The data generated from clinical trials, however, indicated that n-3 fatty acid supplementation did not consistently improve severity of symptoms, lung functions, airway responsiveness, and medication use in asthmatic patients. Future research should focus on the effects of long-term supplementation using weight-based dosages on specific biochemical markers and clinical outcomes. Leading organizations have not included nutrition as part of the management guidelines for asthma. Meanwhile, regular fish consumption at least three times per week should be highly encouraged as part of a well-balanced diet and to meet the adequate intake levels established for n-3 fatty acids.
van Bokhorst-de van der Schueren, M. A. (2005). "Nutritional support strategies for malnourished cancer patients." Eur J Oncol Nurs 9 Suppl 2: S74-83.
A large body of evidence exists, which demonstrates the importance of nutritional support in cancer. The nutritional needs of patients with cancer may differ from those of the healthy population due to hypermetabolism, impaired organ function, increased nutrient losses and therapy-related malnutrition. Patients with cancer often have increased requirements for both macro- and micronutrients due to long periods of undernutrition prior to diagnosis. The aim of nutritional support should be the prevention or reversal of malnutrition, and this should be initiated as early as possible to improve outcomes. Oral supplementation is a simple, non-invasive method of increasing the nutrient intake of those patients who are unable to meet nutritional requirements, despite dietary counselling. Enteral tube feeding is indicated for patients who are unable to meet their nutritional needs by oral intake alone, and has been shown to improve clinical outcomes. Novel approaches in oral supplementation include the use of eicosapentaenoic acid (EPA), a compound under investigation for its role in preventing and treating cancer-associated malnutrition. Individual studies suggest that EPA attenuates cancer-associated wasting and improves immune function. In addition, it has been shown to have anti-tumour effects and improve clinical outcomes. However, results are not consistent for all patient groups and further research is required.
Tisdale, M. J. (2005). "The ubiquitin-proteasome pathway as a therapeutic target for muscle wasting." J Support Oncol 3(3): 209-17.
Atrophy of skeletal muscle is common to a number of conditions, including cancer, sepsis, AIDS, renal failure, diabetes, severe trauma, and burns. In all cases, protein synthesis in skeletal muscle is depressed, whereas protein degradation is increased through an increase in activity and expression of the ubiquitin-proteasome proteolytic pathway. This pathway is not responsive to simple nutritional intervention. Certain agents, including glucocorticoids, cytokines, proteolysis-inducing factor (PIF), and oxidative stress, are thought to be responsible for the induction of the ubiquitin-proteasome pathway in skeletal muscle in catabolic conditions. Insulin suppresses activation of this pathway, and loss of insulin action in diabetes leads to muscle wasting. Cytokines, PIF, and reactive oxygen species (ROS) are thought to induce proteasome expression through activation of the transcription factor nuclear factor kappa B (NF-kappaB). Targets for therapeutic intervention include antagonists of the inducers of proteasome expression, intracellular signaling pathways leading to activation of NF-kappaB, and the enzymes inducing ubiquitin conjugation to the substrate protein (myosin), as well as the proteasome itself. Anticytokine and anti-PIF antibodies are effective in attenuating muscle protein degradation in certain experimental animal models,and glucocorticoid receptor antagonists are effective in the treatment of sepsis. Agents that inhibit NF-kappaB activation, such as resveratrol, thalidomide, ibuprofen, eicosapentaenoic acid, and beta-hydroxy-beta-methylbutyrate, are effective in the preservation of skeletal muscle mass in cachexia.These results suggest that the ubiquitin-proteasome pathway is an appropriate therapeutic target to prevent muscle wasting.
Smith, W. L. (2005). "Cyclooxygenases, peroxide tone and the allure of fish oil." Curr Opin Cell Biol 17(2): 174-82.
Skepticism about the health benefits of fish oil is largely the result of our incomplete understanding of the biochemistry of omega3 essential fatty acids. Recent work has confirmed the roles of omega3 fatty acids in gene transcription and signal transduction, and has given insight into the effects of eicosapentaenoic acid (EPA) and the EPA/arachidonic acid (AA) ratio on prostanoid (PG) metabolism and function. One pronounced effect of fish-oil-induced increases in EPA/AA ratios is decreased PG formation from AA via cyclooxygenase-1, because EPA inhibits this isoform. In addition, cells lacking endogenous alkyl-peroxide-generating systems and thus having a low 'peroxide tone' cannot oxygenate EPA via cyclooxygenase-1. Platelets, however, which are equipped with a lipoxygenase that can produce an abundance of hydroperoxide from AA, can form small amounts of thromboxane A3 from EPA via cyclooxygenase-1. A second major consequence of elevated EPA/AA ratios is significantly increased production of 3-series PGs, including PGE3, via cyclooxygenase-2. There are four PGE receptor subtypes and at least one of these types--not yet identified--has a significantly different response to PGE3 than to PGE2; this difference may underlie the ability of omega3 fatty acids to mitigate inflammation and tumorigenesis.
Singh, S. P., X. R. Zhou, et al. (2005). "Metabolic engineering of new fatty acids in plants." Curr Opin Plant Biol 8(2): 197-203.
Metabolic engineering of plants to express high levels of new fatty acids that are of nutritional and industrial importance has proven to be highly challenging. Significant advances have been made recently, however, particularly in the development of the first plant oils to contain long-chain polyunsaturated fatty acids, such as arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid. Methods of increasing the accumulation of Delta12-modified fatty acids synthesized by transgenically expressed FAD2-like enzymes have also been investigated. Biochemical analyses of plants that express these introduced fatty-acid metabolic pathways have highlighted the central importance of ensuring the removal of novel fatty acids from their site of synthesis on phosphatidylcholine to enable their further modification, exclusion from membrane lipids and accumulation in seed triacylglycerols.
Singh, M. (2005). "Essential fatty acids, DHA and human brain." Indian J Pediatr 72(3): 239-42.
Essential fatty acids cannot be synthesized in the body but they are required for maintenance of optimal health. There are two classes of polyunsaturated fatty acids (PUFAs)--omega-6 and omega-3. The parent omega-6 fatty acid, linoleic acid (LA) is desaturated in the body to form arachidonic acid while parent omega-3 fatty acid alpha-linolenic acid (ALA) is desaturated by microsomal enzyme system through a series of metabolic steps to form eicosapentaenoic acid (EPA) and decosahexaenoic acid (DHA). But there is a limited metabolic capability during early life to metabolize PUFAs to more active long-chain fatty acids. There is a critical role of EFAs and their metabolic products for maintenance of structural and functional integrity of central nervous system and retina. Most of the brain growth is completed by 5-6 years of age. At birth brain weight is 70% of an adult, 15% brain growth occurs during infancy and remaining brain growth is completed during preschool years. DHA is the predominant structural fatty acid in the central nervous system and retina and its availability is crucial for brain development. It is recommended that the pregnant and nursing woman should take at least 2.6 g of omega-3 fatty acids and 100-300 mg of DHA daily to look after the needs of her fetus and suckling infant. The follow-up studies have shown that infants of mothers supplemented with EFAs and DHA had higher mental processing scores, psychomotor development, eye-hand coordination and stereo acuity at 4 years of age. Intake of EFAs and DHA during preschool years may also have a beneficial role in the prevention of attention deficit hyperactivity disorder (ADHD) and enhancing learning capability and academic performance.
Serhan, C. N. (2005). "Novel eicosanoid and docosanoid mediators: resolvins, docosatrienes, and neuroprotectins." Curr Opin Clin Nutr Metab Care 8(2): 115-21.
PURPOSE OF REVIEW: It is well known that arachidonic acid is the precursor to potent mediators. Many clinical studies suggest that omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid have beneficial actions in human diseases. The molecular basis of these actions remains of interest. RECENT FINDINGS: These demonstrate that eicosapentaenoic acid and docosahexaenoic acid are precursors to potent (nM range) bioactive mediators that possess both anti-inflammatory and protective properties. These mediators were coined resolvins, docosatrienes, and protectins as general classes, since each possesses unique chemical structures that are features of the new chemical classes and are biosynthesized by new pathways. Resolvins, discovered first, were identified during the resolution phase of acute inflammation; hence the term resolution interaction products, because they are also biosynthesized by human cells via cell-cell interactions. Docosatrienes contain conjugated triene structures generated from docosahexaenoic acid as a defining feature. The protectins comprise docosatrienes and resolvins of the D series that are both neuroprotective and anti-inflammatory. Aspirin impacts on these new pathways by triggering formation of their epimers (i.e. R isomers). SUMMARY: In view of the many beneficial actions attributed to omega-3 dietary supplementation, identification of novel potent mediators from omega-3 that are both anti-inflammatory and protective may have wide implications.
Pouwer, F., G. Nijpels, et al. (2005). "Fat food for a bad mood. Could we treat and prevent depression in Type 2 diabetes by means of omega-3 polyunsaturated fatty acids? A review of the evidence." Diabet Med 22(11): 1465-75.
AIMS: Evidence strongly suggests that depression is a common complication of Type 2 diabetes mellitus. However, there is considerable room to improve the effectiveness of pharmacological antidepressant agents, as in only 50-60% of the depressed subjects with diabetes does pharmacotherapy lead to remission of depression. The aim of the present paper was to review whether polyunsaturated fatty acids (PUFA) of the omega-3 family could be used for the prevention and treatment of depression in Type 2 diabetes. METHODS: MEDLINE database and published reference lists were used to identify studies that examined the associations between omega-3 PUFA and depression. To examine potential side-effects, such as on glycaemic control, studies regarding the use of omega-3 supplements in Type 2 diabetes were also reviewed. RESULTS: Epidemiological and clinical studies suggest that a high intake of omega-3 PUFA protects against the development of depression. There is also some evidence that a low intake of omega-3 is associated with an increased risk of Type 2 diabetes, but the results are less conclusive. Results from randomized controlled trials in non-diabetic subjects with major depression show that eicosapentaenoic acid is an effective adjunct treatment of depression in diabetes, while docosahexanoic acid is not. Moreover, consumption of omega-3 PUFA reduces the risk of cardiovascular disease and may therefore indirectly decrease depression in Type 2 diabetes, via the reduction of cardiovascular complications. CONCLUSIONS: Supplementation with omega-3 PUFA, in particular eicosapentaenoic acid, may be a safe and helpful tool to reduce the incidence of depression and to treat depression in Type 2 diabetes. Further studies are now justified to test these hypotheses in patients with Type 2 diabetes.
Plat, J. and R. P. Mensink (2005). "Food components and immune function." Curr Opin Lipidol 16(1): 31-7.
PURPOSE OF REVIEW: Enhancing immune function or alternatively dampening inflammatory processes by specific food components has received a lot of interest. The purpose of this review is to summarize recent findings with the emphasis on underlying mechanisms. RECENT FINDINGS: Dietary beta-glucans are relatively new candidates in the field of immune modulation by diet. In-vitro and animal studies suggest that beta-glucans shift inflammatory profiles to a Th1 type, which may enhance resistance against bacterial and parasitic infections. Regarding polyunsaturated fatty acids, there is evidence that n-3 fatty acids from fish oils (eicosapentaenoic acid and docosahexaenoic acid) dampen inflammatory responses. Whether eicosapentaenoic acid or docosahexaenoic acid is responsible for this phenomenon remains controversial. It is also inconclusive whether the plant-derived n-3 fatty acid alpha-linolenic acid has the same antiinflammatory effects as observed for fish oils. Saturated fatty acids may activate toll-like receptors and consequently the inflammatory pathway. The effect of total fat intake is controversial, since high-fat diets have been found to suppress immune function, while also improving intestinal barrier function. Finally, Gingko biloba was found to lower nuclear factor kappaB and activator protein 1 activation, possibly due to its high content of polyphenols. SUMMARY: In this review we discuss the nutritional components able to enhance immune function or show antiinflammatory effects. It can be concluded that diet certainly has the potential to direct immune responses. Apart from studies on fish oils, however, evidence from human studies is limited.
Peet, M. and C. Stokes (2005). "Omega-3 fatty acids in the treatment of psychiatric disorders." Drugs 65(8): 1051-9.
The importance of omega-3 fatty acids for physical health is now well recognised and there is increasing evidence that omega-3 fatty acids may also be important to mental health. The two main omega-3 fatty acids in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have important biological functions in the CNS. DHA is a major structural component of neuronal membranes, and changing the fatty acid composition of neuronal membranes leads to functional changes in the activity of receptors and other proteins embedded in the membrane phospholipid. EPA has important physiological functions that can affect neuronal activity. Epidemiological studies indicate an association between depression and low dietary intake of omega-3 fatty acids, and biochemical studies have shown reduced levels of omega-3 fatty acids in red blood cell membranes in both depressive and schizophrenic patients.Five of six double-blind, placebo-controlled trials in schizophrenia, and four of six such trials in depression, have reported therapeutic benefit from omega-3 fatty acids in either the primary or secondary statistical analysis, particularly when EPA is added on to existing psychotropic medication. Individual clinical trials have suggested benefits of EPA treatment in borderline personality disorder and of combined omega-3 and omega-6 fatty acid treatment for attention-deficit hyperactivity disorder. The evidence to date supports the adjunctive use of omega-3 fatty acids in the management of treatment unresponsive depression and schizophrenia. As these conditions are associated with increased risk of coronary heart disease and diabetes mellitus, omega-3 fatty acids should also benefit the physical state of these patients. However, as the clinical research evidence is preliminary, large, and definitive randomised controlled trials similar to those required for the licensing of any new pharmacological treatment are needed.
Okuyama, H. (2005). "[Need to change the direction of cholesterol-related medication--a problem of great urgency]." Yakugaku Zasshi 125(11): 833-52.
The cholesterol hypothesis implies that reducing the intake of saturated fatty acids and cholesterol and increasing that of polyunsaturated fatty acid are effective in lowering serum total cholesterol (TC), and thereby reducing the incidence of coronary heart disease (CHD). However, these dietary recommendations are essentially ineffective in reducing TC in the long run, but rather increase mortality rates from CHD and all causes. The reported "apparent relative risk of high TC in CHD mortality" (the ratio of mortality at the highest/lowest TC levels) varied several-fold among populations studied. The incidence of familial hypercholesterolemia (FH) in a population was proposed to be a critical factor in the observed variability, which could be accounted for by assuming that 1) the high CHD mortality rate in high-TC groups is mainly a reflection of the incidence and severity of FH, and 2) high TC is not a causative factor of CHD in non-FH cases. This interpretation is supported by recent observations that high TC is not positively associated with high CHD mortality rates among general populations more than 40-50 years of age. More importantly, higher TC values are associated with lower cancer and all-cause mortality rates among these populations, in which relative proportions of FH are likely to be low (circa 0.2%). Although the effectiveness of statins in preventing CHD has been accepted in Western countries, little benefit seems to result from efforts to limit dietary cholesterol intake or to TC values to less than approximately 260 mg/dl among the general population and the elderly. Instead, an unbalanced intake of omega6 over omega3 polyunsaturated fats favors the production of eicosanoids, the actions of which lead to the production of inflammatory and thrombotic lipid mediators and altered cellular signaling and gene expression, which are major risk factors for CHD, cancers, and shorter longevity. Based on the data reviewed here, it is urgent to change the direction of current cholesterol-related medication for the prevention of CHD, cancer, and all-cause mortality.
Oh, R. (2005). "Practical applications of fish oil (Omega-3 fatty acids) in primary care." J Am Board Fam Pract 18(1): 28-36.
BACKGROUND: Fish oil (Omega-3 fatty acids) has been studied for more than 30 years. However, recent concerns of mercury and environmental toxins have clouded fish oil's potential clinical benefits. This article aims to review practical, evidence-based applications of fish oil for the primary care physician. METHODS: PubMed search using key words 'fish oil,' 'docosahexaenoic,' and 'eicosapentaenoic' in title/abstract. Limited to human clinical trials. Articles were further scanned for relevant sources. RESULTS: For secondary prevention of cardiovascular disease, 1 g of fish oil has shown to reduce overall and cardiovascular mortality, myocardial infarction, and sudden cardiac death. Higher doses may be used for its potent triglyceride-lowering effects and for patients with rheumatoid arthritis to reduce nonsteroidal anti-inflammatory use. Omega-3 fatty acid supplementation of infant formula has shown benefit in infant neural growth and development. With the potential health benefits of fish, women of childbearing age should be encouraged to eat 1 to 2 low-mercury fish meals per week. CONCLUSIONS: Fish oil has numerous practical applications for the primary care physician. Understanding the diverse clinical research of Omega-3 fatty acids and fish oil is important in determining its role in primary care practices.
Noseda, G. (2005). "[Fats and oils (including omega3, omega6)]." Ther Umsch 62(9): 625-8.
Saturated fatty acids contribute essentially to atherogenesis, especially to coronary artery disease. In contrast, the protective effect of monounsaturated fatty acids such as oleic acid, contained in olive oil and as a constituent of a Mediterranean diet is very well shown epidemiologically. There is a modest beneficial effect on the clinical manifestation of coronary heart disease when saturated fatty acids of animal provenience are partially replaced by omega 6 fatty acids (linoleic acid). However, studies with the addition of omega-3-fatty acids in the diet (fish oil rich in eicosapentaenoic and docosaexaenoic acid and rape seed oil rich in alpha linolenic acid) demonstrate a significant decrease of sudden cardiac death and non fatal myocardial infarction. Long-chain omega-3-fatty acids have a direct antiarrhythmic effect on myocytes. The reduction of non-fatal myocardial infarctions during consumption of diets rich in long chain omega-3-fatty acids could at least in part be attributed to inhibitory effects on platelet aggregation and thus on thrombus formation and to a stabilization of atherosclerotic plaques.
Moyad, M. A. (2005). "An introduction to dietary/supplemental omega-3 fatty acids for general health and prevention: part I." Urol Oncol 23(1): 28-35.
The correction of a subtle nutritional deficiency that may reduce the risk of a future chronic disease is indeed a challenge. However, some specific examples in the past, such as the addition of folic acid to prevent neural tube defects and calcium and vitamin D to prevent osteoporosis, should provide some encouragement that some conditions can be prevented with the appropriate addition of a deficient compound. One of the most intriguing current and future impacts on public health may come from a greater intake of omega-3 fatty acids such as alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). The omega-3 fatty acids continue to accumulate research that suggests that may prevent a variety of diverse chronic diseases and potentially some acute clinical scenarios. In Part 1 of this manuscript the potential for these compounds to prevent certain cardiovascular conditions are discussed. In Part 2 the potential for an impact in arthritis, numerous areas of cancer research, depression, maternal and child health, neurological diseases, osteoporosis, and other medical disciplines are also briefly covered. The future appears bright for these agents, but specifically which conditions, who qualifies, testing, frequency, adequate sources, future trials and numerous other questions need to be addressed and answered before the potential impact can catch up to the recent hype.
Moyad, M. A. (2005). "An introduction to dietary/supplemental omega-3 fatty acids for general health and prevention: part II." Urol Oncol 23(1): 36-48.
The correction of a subtle nutritional deficiency that may reduce the risk of a future chronic disease is indeed a challenge. However, some specific examples in the past, such as the addition of folic acid to prevent neural tube defects and calcium and vitamin D to prevent osteoporosis, should provide some encouragement that some conditions can be prevented with the appropriate addition of a deficient compound. One of the most intriguing current and future impacts on public health may come from a higher intake of omega-3 fatty acids, such as alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). The omega-3 fatty acids continue to accumulate research that suggests that they may prevent a variety of diverse chronic diseases and potentially some acute clinical scenarios. In the first part of this article, the potential for these compounds to prevent certain cardiovascular conditions are discussed. In the second part, the potential for an impact in arthritis, numerous areas of cancer research, depression, maternal and child health, neurologic diseases, osteoporosis, and other medical disciplines are also briefly covered. The future appears bright for these agents, but specifically which conditions, who qualifies, testing, frequency, adequate sources, future trials, and numerous other questions need to be addressed and answered before the potential impact can catch up to the recent hype.
Morimoto, K. C., A. L. Van Eenennaam, et al. (2005). "Endogenous production of n-3 and n-6 fatty acids in mammalian cells." J Dairy Sci 88(3): 1142-6.
Polyunsaturated fatty acids (PUFA) are important components of mammalian diets, and the beneficial effects of n-3 PUFA on human development and cardiovascular health have been well documented. Caenorhabditis elegans is one of the few animals known to be able to produce linoleic (LA, 18:2n-6) and alpha-linolenic (ALA, 18:3n-3) essential fatty acids. These essential PUFA are generated by the action of desaturases that successively direct the conversion of monounsaturated fatty acids (MUFA) to PUFA. The cDNA coding sequences of the C. elegans Delta(12) and n-3 fatty acid desaturases were each placed under the control of separate constitutive eukaryotic promoters and simultaneously introduced into HC11 mouse mammary epithelial cells by adenoviral transduction. Phospholipids from transduced cells showed a significant decrease in the ratios of both MUFA:PUFA and n-6:n-3 fatty acids relative to control cultures. The fatty acid profile of transduced cellular phospholipids revealed significant decreases in MUFA and arachidonic acid (20:4n-6), and increases in LA, ALA, and eicosapentaenoic acid (20:5n-3). The fatty acid composition of triacylglycerols derived from transduced cells was similarly, but less dramatically, affected. These results demonstrate the functionality of C. elegans fatty acid desaturase enzymes in mammalian cells. Expression of these desaturases in livestock might act to counterbalance the saturating effect that rumen microbial biohydrogenation has on the fatty acid profile of ruminant products, and allow for the development of novel, land-based dietary sources of n-3 PUFA.
Mickleborough, T. D. (2005). "Dietary omega-3 polyunsaturated fatty acid supplementation and airway hyperresponsiveness in asthma." J Asthma 42(5): 305-14.
Asthma prevalence continues to increase despite the progress that has been made in the treatment options for asthma. Alternative treatment therapies that reduce the dose requirements of pharmacological interventions would be beneficial, and could potentially reduce the public health burden of this disease. There is accumulating evidence that dietary modification has potential to influence the severity of asthma and reduce the prevalence and incidence of this condition. A possible contributing factor to the increased incidence of asthma in Western societies may the consumption of a pro-inflammatory diet. In the typical Western diet, 20-25-fold more omega (n)-6 polyunsaturated fatty acids (PUFA) than n-3 PUFA are consumed, which results in the release of pro-inflammatory arachidonic acid metabolites. Eicosapentaenoic acid and docosahexaenoic acid are n-3 PUFA derived from fish oil that competitively inhibit n-6 PUFA arachidonic acid (AA) metabolism and this reduce the generation of pro-inflammatory 4-series leukotrienes (LTs) and 2-series prostaglandins (PGs) and production of cytokines from inflammatory cells. These data are consistent with the proposed pathway by which dietary intake of n-3 PUFA modulates lung disease. This article will review the existing information concerning the relationship between n-3 PUFA supplementation and airway hyperresponsiveness in asthma. It includes studies assessing the efficacy of n-3 PUFA supplementation in exercise-induced bronchoconstriction. This review will also address the question as to whether supplementing the diet with n-3 PUFA represents a viable alternative treatment regimen for asthma.
Matthan, N. R., H. Jordan, et al. (2005). "A systematic review and meta-analysis of the impact of omega-3 fatty acids on selected arrhythmia outcomes in animal models." Metabolism 54(12): 1557-65.
Epidemiological studies and clinical trials report the beneficial effects of fish or fish oil consumption on cardiovascular disease outcomes including sudden death. We performed a systematic review of the literature on controlled animal studies that assessed the effects of omega-3 fatty acids on selected arrhythmia outcomes. On the basis of predetermined criteria, 27 relevant animal studies were identified; 23 of these were feeding studies, and 4 were infusion studies. Across species, fish oil, eicosapentaenoic acid, and/or docosahexaenoic acid appear to have beneficial effects on ventricular tachycardia (VT) and fibrillation (VF) in ischemia- but not reperfusion-induced arrhythmia models; no effect on the incidence of death and infarct size; and inconsistent results with regard to arrhythmia score, VF threshold, ventricular premature beats or length of time in normal sinus rhythm, compared to omega-6, monounsaturated, or saturated fatty acids, and no treatment controls. In a meta-analysis of 13 studies using rat models, fish oil but not alpha-linolenic acid supplementation showed a significant protective effect for ischemia- and reperfusion-induced arrhythmias by reducing the incidence of VT and VF. It is not known whether omega-3 fatty-acid supplementation has antiarrhythmic effects in other disease settings not related to ischemia.
La Guardia, M., S. Giammanco, et al. (2005). "Omega 3 fatty acids: biological activity and effects on human health." Panminerva Med 47(4): 245-57.
Polyunsaturated fatty acids (PUFAs) have an important role in human diet, both for the prevention and the therapy of different pathologies. In this review, a critical evaluation of PUFAs dietary sources and biological functions in human organism has been done. In particular, the efficacy of omega-3 fatty acids in the improvement of the lipidic pattern and in the excitability of myocardium has been analyzed, and, therefore, their usefulness in the prevention of cardiovascular diseases and postinfarction arrhythmias. As PUFAs are precursors of prostaglandins and leucotriens, which are involved in phlogosis and immune response, a diet rich in fish oil reduces the production of PGE2 involved in many phlogosis events. Moreover, an increase in the eicosapentaenoic acid (EPA) intake leads to a reduction in the production of inflammatory cytokines (interleukin 1, 2, 6 and tumor necrosis factor); so, it is important to use omega-3 in chronic inflammatory diseases, as the rheumatoid arthritis. It seems that omega-3 could prevent the onset of hormone-dependent tumours (i.e. breast and prostatic cancer); in vitro observations, in fact, have shown that the PG of the series 2, derived from omega-6, have a carcinogenic action; instead, the anticancer effect of omega-3 could derive from their effect in antagonizing the formation of such PG; it can be useful, therefore, to increase the dietary omega-3/omega-6 ratio. Moreover, the effects of omega-3 on the anatomic and functional central nervous system development and of their possible therapeutical use in some psychiatric pathologies were evaluated.
Jatoi, A. (2005). "Fish oil, lean tissue, and cancer: is there a role for eicosapentaenoic acid in treating the cancer anorexia/weight loss syndrome?" Crit Rev Oncol Hematol 55(1): 37-43.
Eicosapentaenoic acid is an omega-3 fatty acid, a group of fatty acids characterized by a double bond that sits three carbons down from the n terminal of the molecule. Derived from dark, rich fish, eicosapentaenoic acid has received increasing attention as a therapy for the cancer anorexia/weight loss syndrome. Multiple studies, including laboratory and preliminary clinical studies suggest this fish oil derivative may benefit cancer patients. Recently, however, three large comparative studies suggest that eicosapentaenoic acid is relatively ineffective for treating this syndrome. In view of these recent results, the goals of this review are as follows: (1) to provide background on the mandate for further study of the cancer-associated anorexia/weight loss syndrome; (2) to review the preliminary data that have suggested that eicosapentaenoic acid is a promising agent for treating this syndrome; (3) to review the methodology and findings of the more recent, definitive clinical trials; (4) to discuss and speculate on why the earlier positive findings drew conclusions that are discrepant from the results of more recent comparative clinical studies.
Inoue, H. (2005). "[Endogenous ligands for PPARs]." Nippon Rinsho 63(4): 578-83.
Peroxisome proliferator-activated receptors (PPARs), a family of three nuclear receptors/transcription factors, are widely recognized as molecular targets for drugs against lifestyle related disease. In spite of intensive search for natural ligands, no truly endogenous ligand has been identified as yet. Rather, these results have lead to the suggestion that PPAR may act as various lipid sensors. Namely, the ligand binding modes of PPARs would be similar to those of odorant receptors or substrate-binding modes of drug-metabolizing enzyme P450 family. In this brief review, free fatty acids, lipid mediators in arachidonate cascade and polyphenolic compounds such as resveratrol will be discussed as natural ligands for PPARs.
Harrison, N. and B. Abhyankar (2005). "The mechanism of action of omega-3 fatty acids in secondary prevention post-myocardial infarction." Curr Med Res Opin 21(1): 95-100.
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.
Harris, W. S. (2005). "Extending the cardiovascular benefits of omega-3 Fatty acids." Curr Atheroscler Rep 7(5): 375-80.
The cardiovascular benefits of omega (n)-3 fatty acids (FA) become clearer with each passing year. Although useful in large doses for lowering serum triglyceride levels, the primary benefits are likely to arise from smaller, nutritional intakes of eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA). Doses of less than 1 g/d appear to reduce risk for fatal coronary heart disease events, perhaps by stabilizing the myocardium and reducing risk for fatal arrhythmias. New evidence points to a possible benefit on atrial fibrillation, particularly in the immediate post-cardiac surgery setting. Studies in women with coronary heart disease now suggest that plaque progression may be slowed by increased intakes of oily fish, even in women with diabetes. The relative importance of the n-6 FA linoleic acid (LA), the short-chain n-3 FA alpha linolenic acid (ALA), and the long-chain n-3 FAs EPA and DHA is becoming clearer. If intakes of the latter are adequate (perhaps over 250 mg/d), then there appears to be little need to consume more ALA or less LA.
Grynberg, A. (2005). "Hypertension prevention: from nutrients to (fortified) foods to dietary patterns. Focus on fatty acids." J Hum Hypertens 19 Suppl 3: S25-33.
Diet affects significantly the incidence and severity of cardiovascular diseases and fatty acid intake, in its qualitative as well as quantitative aspects, and influences several risk factors including cholesterol (total, LDL and HDL), triglycerides, platelet aggregation and blood pressure, as evidenced in the 2001 WHO report. This review focuses on the qualitative concern of lipid intake, the various classes of fatty acids of the lipid fraction of the diet, saturated, monounsaturated and polyunsaturated, and their effects on blood pressure. Saturated fat have a bad file and several experimental studies in the rat showed a progressive increase in blood pressure in response to a highly saturated diet. Moreover, a highly saturated diet during gestation led to offspring which, when adults, presented a gender-related hypertension. The mechanism of this effect may be related to the polyunsaturated/saturated ratio (p/s). During the past 20 years, trans fatty acids have been suspected of deleterious health effects, but the investigations have shown that these fatty acids display a biological behaviour close to that of saturated fatty acids (SFA). Moreover, epidemiological investigations did not confirm the relationship between trans fatty acids and cardiovascular pathology. Polyunsaturated fatty acids have been shown to exert a positive action on hypertension. This effect could be attributed to the alteration of the p/s, but mainly to the omega3 polyunsaturated fatty acids (PUFAs). The comparison of several animal models led to the conclusion that long-chain omega3 PUFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) can prevent the increase in blood pressure and reduce established hypertension, but the efficient dose remains an object of discussion. Moreover, the two long-chain omega3 PUFAs, EPA and DHA, display specific effects, which vary with the aetiology of hypertension, because their mechanism of action is different. DHA acts on both blood pressure and heart function (heart rate and ECG) and interferes with the adrenergic function. Conversely, EPA, which is not incorporated in cardiac phospholipids, has no effect on the heart and its mechanism of action is largely unknown. Although it is accepted by the scientific community that the intake of EPA and DHA needs to be increased, we will have to discover new ways to do it, since marine products are the main source of these fatty acids, and this source is not inexhaustible.
Gordon, J. N., S. R. Green, et al. (2005). "Cancer cachexia." Qjm 98(11): 779-88.
Cancer cachexia is a severe debilitating disorder for which there are currently few therapeutic options. It is driven by the release of pro-inflammatory cytokines and cachectic factors by both host and tumour. Over the past few years, basic science advances have begun to reveal the breadth and complexity of the immunological mechanisms involved, and in the process have uncovered some novel potential therapeutic targets. The effectiveness of thalidomide and eicosapentaenoic acid at attenuating weight loss in clinical trials also provides a further rationale for modulating the immune response. We are now entering an exciting period in cachexia research, and it is likely that the next few years will see effective new biological therapies reach clinical practice.
Filburn, C. R. and D. Griffin (2005). "Canine plasma and erythrocyte response to a docosahexaenoic acid-enriched supplement: characterization and potential benefits." Vet Ther 6(1): 29-42.
Results of this study confirm that dietary supplementation in dogs with a natural source of omega-3 fatty acids (salmon oil), with a docosahexaenoic acid:eicosapentaenoic acid (DHA:EPA) ratio of 1.5:1, increases plasma and red blood cell levels of these fatty acids. Supplementation with this DHA-enriched oil improves the long-chain polyunsaturated fatty acid omega-6:omega-3 (n-6:n-3) ratio, which may benefit dogs of all ages. Studies describing some of the neurologic, renal, cardiovascular, immune, and musculoskeletal effects of elevated blood levels of n-3 fatty acids, especially DHA, are reviewed. The importance of providing an enriched source of DHA, instead of its shorter precursors, is emphasized.
Deans, C. and S. J. Wigmore (2005). "Systemic inflammation, cachexia and prognosis in patients with cancer." Curr Opin Clin Nutr Metab Care 8(3): 265-9.
PURPOSE OF REVIEW: Cachexia remains an important cause of morbidity and mortality among cancer patients. The mechanisms underlying this syndrome remain unclear and are almost certainly multifactorial. Evidence from animal models suggests a compelling link between cachexia and inflammation, and a variety of pro-inflammatory cytokines play an integral role. This review summarizes current thinking relating to inflammation, cachexia and prognosis in cancer patients, with particular emphasis on studies relating to recent therapeutic advances. RECENT FINDINGS: Pro-inflammatory cytokines induce the acute phase protein response, a key marker of systemic inflammation. Recent evidence has also implicated other tumour-derived mediators, such as proteolysis-inducing factor and parathyroid hormone-related peptide. In addition, systemic inflammation has been found in association with many malignancies, and has been correlated with weight loss, hypermetabolism, anorexia, and adverse prognosis. Treatments such as fish oil, monoclonal antibodies, and non-steroidal anti-inflammatory drugs, have all been utilized to attenuate systemic inflammation and influence weight loss. Recent clinical studies have suggested that eicosapentaenoic acid and cyclo-oxygenase 2 inhibitors promote weight gain and downregulate the acute phase protein response. SUMMARY: Pro-inflammatory processes are clearly implicated in the hypermetabolism and weight loss associated with cancer-associated cachexia. In addition, the presence of systemic inflammation is now clearly linked with adverse prognosis in patients with cancer, which cannot be fully explained by the association with weight loss. Systemic inflammation remains an important area for novel therapeutic targets in combating cachexia, and eicosapentaenoic acid and cyclo-oxygenase 2 inhibitors appear to be efficacious in the armory against cachexia.
Das, U. N. (2005). "Long-chain polyunsaturated fatty acids, endothelial lipase and atherosclerosis." Prostaglandins Leukot Essent Fatty Acids 72(3): 173-9.
Endothelial lipase (EL), a new member of the lipase gene family, was recently cloned and has been shown to have a significant role in modulating the concentrations of plasma high-density lipoprotein levels (HDL). EL is closely related to lipoprotein and hepatic lipases both in structure and function. It is primarily synthesized by endothelial cells, functions at the cell surface, and shows phospholipase A1 activity. Overexpression of EL decreases HDL cholesterol levels whereas blocking its action increases concentrations of HDL cholesterol. Pro-inflammatory cytokines suppress plasma HDL cholesterol concentrations by enhancing the activity of EL. On the other hand, physical exercise and fish oil (a rich source of eicosapentaenoic acid and docosahexaenoic acid) suppress the activity of EL and this, in turn, enhances the plasma concentrations of HDL cholesterol. Thus, EL plays a critical role in the regulation of plasma HDL cholesterol concentrations and thus modulates the development and progression of atherosclerosis. The expression and actions of EL in specific endothelial cells determines the initiation and progression of atherosclerosis locally explaining the patchy nature of atheroma seen, especially, in coronary arteries. Both HDL cholesterol and EPA and DHA enhance endothelial nitric oxide (eNO) and prostacyclin (PGI2) synthesis, which are known to prevent atherosclerosis. On the other hand, pro-inflammatory cytokines augment free radical generation, which are known to inactivate eNO and PGI2. Thus, interactions between EL, pro- and anti-inflammatory cytokines, polyunsaturated fatty acids, and the ability of endothelial cells to generate NO and PGI2 and neutralize the actions of free radicals may play a critical role in atherosclerosis.
Das, U. N. (2005). "Essential fatty acids and acquired immunodeficiency syndrome." Med Sci Monit 11(6): RA206-211.
Acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV) that is characterized by profound immunodeficiency, opportunistic infections and Kaposi's sarcoma. As yet no effective therapy is available for AIDS, though retroviral drugs are able to prolong life and contain HIV proliferation to some extent. I propose that essential fatty acids (EFAs) and their metabolites could be useful in the prevention and management of AIDS. Linoleic acid (LA) and arachidonic acid (AA) inactivate enveloped viruses, linolenic acid-enriched macrophages are markedly tumoricidal, EFAs activate macrophages and neutrophils and induce free radical generation; and cytokines bring about some of their actions by inducing the release of EFAs; gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA) prevent genetic damage and have tumoricidal actions as well; and are relatively non-toxic when administered orally or parentarally over long periods of time. In view of this, I suggest that further studies with regard to the role of GLA, AA, EPA and/or docosahexaenoic acid (DHA) in the pathobiology of AIDS needs to be performed. It is also proposed that possible use of these fatty acids in the prevention and treatment of AIDS needs serious consideration.
Das, U. N. (2005). "Pathophysiology of metabolic syndrome X and its links to the perinatal period." Nutrition 21(6): 762-73.
It is proposed that metabolic syndrome X is initiated in the perinatal period as a low-grade systemic inflammatory condition. Increased consumption of energy-dense diets by pregnant women and lactating mothers suppresses the activities of Delta-6 and Delta-5 desaturases not only in maternal tissues but also in fetal liver and the placenta, resulting in decreased plasma and tissue concentrations of long-chain polyunsaturated fatty acids omega-6 arachidonic acid (AA), omega-3 eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). EPA, DHA, and AA have negative feedback control on tumor necrosis factor-alpha and IL-6 synthesis. Hence, EPA, DHA, and AA deficiencies induced by an energy-dense diet increase generation of tumor necrosis factor-alpha and interleukin-6, markers of inflammation that in turn decrease production of endothelial nitric oxide and adiponectin to induce insulin resistance in maternal and fetal tissues. Increased concentrations of tumor necrosis factor-alpha and interleukin-6 enhance expression and activity of 11beta-hydroxysteroid dehydrogenase type 1 enzyme, which produces abdominal obesity, insulin resistance, hyperlipidemia, hyperphagia, and hyperleptinemia, characteristic features of metabolic syndrome X. Continued consumption of an energy-dense diet in childhood aggravates these molecular events. This implies that supplementation of long-chain polyunsaturated fatty acids (especially AA, EPA, and DHA in appropriate ratios) from the perinatal period through adulthood could prevent, arrest, or postpone development of metabolic syndrome X.
Das, U. N. (2005). "COX-2 inhibitors and metabolism of essential fatty acids." Med Sci Monit 11(7): RA233-7.
Selective COX-2 inhibitors increase the risk of myocardial infarction and stroke that is attributed to their ability to inhibit prostacyclin (PGI2), lipoxins, resolvins, and endothelial nitric oxide (eNO) but not platelet COX-1 derived thromboxane A2 (TXA2). In contrast, aspirin blocks both COX-1 and COX-2 enzymes that, in turn, increases intracellular concentrations of dihomo-gamma-linolenic acid (DGLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and reduced formation of eicosanoids. On the other hand, such an increase is much less with specific COX-2 inhibitors since they do not block the formation of eicosanoids through COX-1 pathway. DGLA, AA and EPA form precursors to PGE1, PGI2, and PGI3 respectively, which are potent vasodilators and platelet anti-aggregators, and thus aid in the prevention of thrombus formation. EPA has anti-arrhythmic action, and EPA, DHA (docosahexaenoic acid), DGLA, and PGE1 have anti-inflammatory actions as well. EPA, DHA, and AA augment eNO formation that has anti-atherosclerotic action. Hence, combining EFAs with COX-2 inhibitors will prevent thrombotic cardiovascular events.
Das, U. N. (2005). "Can COX-2 inhibitor-induced increase in cardiovascular disease risk be modified by essential fatty acids?" J Assoc Physicians India 53: 623-7.
Selective COX-2 inhibitors increase the risk of myocardial infarction and stroke. This has been attributed to their ability to inhibit endothelial COX-2 derived prostacyclin (PGI2) but not platelet COX-1 derived thromboxane A2 (TXA2). On the other hand, aspirin blocks both COX-1 and COX-2 enzymes without decreasing PGI2 but blocks TXA2 synthesis that explains its beneficial action in the prevention of coronary heart disease (CHD). The inhibitory action of aspirin on COX-1 and COX-2 enzymes enhances the tissue concentrations of dihomo-gamma-linolenic acid (DGLA), arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). These fatty acids form precursors to PGE1, PGI2, PGI3, lipoxins (LXs), and resolvins that have anti-inflammatory actions. In contrast, increase in the concentrations of DGLA, AA, EPA, and DHA is much less with specific COX-2 inhibitors since they do not block the formation of eicosanoids through COX-1 pathway. COX-2 inhibitors interfere with the formation of LXs and resolvins that have neuroprotective and cardioprotective actions. EPA and PGI2 have anti-arrhythmic action. EPA, DHA, and AA augment eNO formation that prevents atherosclerosis. This suggests that COX-2 inhibitors increase cardiovascular and stroke risk by interfering with the formation of eNO, PGI2, LXs, and resolvins and implies that combining EFAs with COX-2 inhibitors could prevent these complications.
Campos, F. G., A. G. Logullo Waitzberg, et al. (2005). "Diet and colorectal cancer: current evidence for etiology and prevention." Nutr Hosp 20(1): 18-25.
The etiology of colorectal cancer (CRC) involves the interaction of cell molecular changes and environmental factors, with a great emphasis on diet components. But the paths connecting lifestyle characteristicas and the colorectal carcinogenesis remain unclear. Several risk factors are commonly found in western diets, such as high concentrations of fat and animal protein, as well as low amounts of fiber, fruits and vegetables. A large number of experimental studies have found a counteractive effect of fiber on neoplasia induction, especially in relation to fermentable fiber (wheat bran and cellulose). Epidemiological correlation studies have also indicated that a greater ingestion of vegetables, fruit, cereal and seeds is associated to a lower risk for colorectal neoplasia. Moreover, beneficial properties of fiber (especially from vegetable sources) were documented in more than half of case-control studies. Nevertheless, recent epidemiological data from longitudinal and randomized trials tended not to support this influence. Future research should evaluate what sources of fiber provide effective anti-neoplasic protection, carrying out interventional studies with specific fibers for longer periods. Red meat, processed meats, and perhaps refines carbohydrates are also implicated in CRC risk. Recommendantions to decrease red meat intake are well accepted, although the total amount and composition of specific fatty acids may have distinct roles in this setting. Current evidence favors the substitution of long and medium-chain fatty acids and arachidonic acid for short-chain fatty acids and eicosapentaenoic acid. Excess boy weight and excess energy intake inducing hyperinsulinemia have been also associated to CRC, as well as personal habits such as physical inactivy, high alcohol consumption, smoking and low consumption of folate and methionine. Thus, current recommendations for decreasing the risk of CRC include dietary measures such as increased plant food intake; the consumption of whole grains, vegetables and fruits; and reduced red meat intake.
Calder, P. C. (2005). "Polyunsaturated fatty acids and inflammation." Biochem Soc Trans 33(Pt 2): 423-7.
The n-6 polyunsaturated fatty acid, arachidonic acid, is a precursor of prostaglandins, leukotrienes and related compounds that have important roles as mediators and regulators of inflammation. Consuming increased amounts of long chain n-3 polyunsaturated fatty acids (found in oily fish and fish oils) results in a partial replacement of the arachidonic acid in cell membranes by eicosapentaenoic and docosahexaenoic acids. This leads to decreased production of arachidonic acid-derived mediators. This alone is a potentially beneficial anti-inflammatory effect of n-3 fatty acids. However, n-3 fatty acids have a number of other effects that might occur downstream of altered eicosanoid production or are independent of this. For example, they result in suppressed production of pro-inflammatory cytokines and can modulate adhesion molecule expression. These effects occur at the level of altered gene expression.
Burdge, G. C. and P. C. Calder (2005). "Conversion of alpha-linolenic acid to longer-chain polyunsaturated fatty acids in human adults." Reprod Nutr Dev 45(5): 581-97.
The principal biological role of alpha-linolenic acid (alphaLNA; 18:3n-3) appears to be as a precursor for the synthesis of longer chain n-3 polyunsaturated fatty acids (PUFA). Increasing alphaLNA intake for a period of weeks to months results in an increase in the proportion of eicosapentaenoic acid (EPA; 20:5n-3) in plasma lipids, in erythrocytes, leukocytes, platelets and in breast milk but there is no increase in docosahexaenoic acid (DHA; 22:6n-3), which may even decline in some pools at high alphaLNA intakes. Stable isotope tracer studies indicate that conversion of alphaLNA to EPA occurs but is limited in men and that further transformation to DHA is very low. The fractional conversion of alphaLNA to the longer chain n-3 PUFA is greater in women which may be due to a regulatory effect of oestrogen. A lower proportion of alphaLNA is used for beta-oxidation in women compared with men. Overall, alphaLNA appears to be a limited source of longer chain n-3 PUFA in humans. Thus, adequate intakes of preformed long chain n-3 PUFA, in particular DHA, may be important for maintaining optimal tissue function. Capacity to up-regulate alphaLNA conversion in women may be important for meeting the demands of the fetus and neonate for DHA.
Asano, M. and N. Yamada (2005). "[Dyslipidemia management in patients with impaired glucose tolerance]." Nippon Rinsho 63 Suppl 2: 538-42.
Arita, M., C. B. Clish, et al. (2005). "The contributions of aspirin and microbial oxygenase to the biosynthesis of anti-inflammatory resolvins: novel oxygenase products from omega-3 polyunsaturated fatty acids." Biochem Biophys Res Commun 338(1): 149-57.
Resolvins (Rvs) are oxygenated products derived from omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid that carry potent protective bioactions present in resolving inflammatory exudates. Resolvin E1 (RvE1) is biosynthesized in vivo from EPA via transcellular biosynthetic routes during cell-cell interactions, and thus RvE1 is formed in vivo during multicellular responses such as inflammation and microbial infections. RvE1 protects tissues from leukocyte-mediated injury and counterregulates proinflammatory gene expression. These newly identified Rvs may underlie the beneficial actions of omega-3 PUFAs especially in chronic disorders where unresolved inflammation is a key mechanism of pathogenesis. Here, we present an overview of the biosynthesis of RvE1, with a focus on the aspirin-triggered and microbial P450-initiated pathways. The generation of RvE1 and its actions appear to dampen acute leukocyte responses and facilitate the resolution of inflammation.
Argiles, J. M. (2005). "Cancer-associated malnutrition." Eur J Oncol Nurs 9 Suppl 2: S39-50.
Malnutrition is a common problem among patients with cancer, affecting up to 85% of patients with certain cancers (e.g. pancreas). In severe cases, malnutrition can progress to cachexia, a specific form of malnutrition characterised by loss of lean body mass, muscle wasting, and impaired immune, physical and mental function. Cancer cachexia is also associated with poor response to therapy, increased susceptibility to treatment-related adverse events, as well as poor outcome and quality of life. Cancer cachexia is a complex, multifactorial syndrome, which is thought to result from the actions of both host- and tumour-derived factors, including cytokines involved in a systemic inflammatory response to the tumour. Early intervention with nutritional supplementation has been shown to halt malnutrition, and may improve outcome in some patients. However, increasing nutritional intake is insufficient to prevent the development of cachexia, reflecting the complex pathogenesis of this condition. Nutritional supplements containing anti-inflammatory agents, for example the polyunsaturated fatty acid (PUFA) eicosapentanoic acid (EPA), have been shown to be more beneficial to malnourished patients than nutritional supplementation alone. EPA has been shown to interfere with multiple mechanisms implicated in the pathogenesis of cancer cachexia, and in clinical studies, has been associated with reversal of cachexia and improved survival.