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Fish Oil Reviews

(51 References)

Yaqoob, P. (2003). "Lipids and the immune response: from molecular mechanisms to clinical applications." Curr Opin Clin Nutr Metab Care 6(2): 133-50.

            PURPOSE OF REVIEW: This review critically evaluates recent studies investigating the effects of fatty acids on immune and inflammatory responses in both healthy individuals and in patients with inflammatory diseases, with some reference to animal studies where relevant. It examines recent findings describing the cellular and molecular basis for the modulation of immune function by fatty acids. The newly emerging area of diet-genotype interactions will also be discussed, with specific reference to the anti-inflammatory effects of fish oil. RECENT FINDINGS: Fatty acids are participants in many intracellular signalling pathways. They act as ligands for nuclear receptors regulating a host of cell responses, they influence the stability of lipid rafts, and modulate eicosanoid metabolism in cells of the immune system. Recent findings suggest that some or all of these mechanisms may be involved in the modulation of immune function by fatty acids. SUMMARY: Human studies investigating the relationship between dietary fatty acids and some aspects of the immune response have been disappointingly inconsistent. This review presents the argument that most studies have not been adequately powered to take into account the influence of variation (genotypic or otherwise) on parameters of immune function. There is well-documented evidence that fatty acids modulate T lymphocyte activation, and recent findings describe a range of potential cellular and molecular mechanisms. However, there are still many questions remaining, particularly with respect to the roles of nuclear receptors, for which fatty acids act as ligands, and the modulation of eicosanoid synthesis, for which fatty acids act as precursors.


Wen, Z. Y. and F. Chen (2003). "Heterotrophic production of eicosapentaenoic acid by microalgae." Biotechnol Adv 21(4): 273-94.

            Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid that plays an important role in the regulation of biological functions and prevention and treatment of a number of human diseases such as heart and inflammatory diseases. As fish oil fails to meet the increasing demand for purified EPA, alternative sources are being sought. Microalgae contain large quantities of high-quality EPA and they are considered a potential source of this important fatty acid. Some microalgae can be grown heterotrophically on cheap organic substrate without light. This mode of cultivation can be well controlled and provides the possibility to maximize EPA production on a large scale. Numerous strategies have been investigated for commercial production of EPA by microalgae. These include screening of high EPA-yielding microalgal strains, improvement of strains by genetic manipulation, optimization of culture conditions, and development of efficient cultivation systems. This paper reviews recent advances in heterotrophic production of EPA by microalgae with an emphasis on the use of diatoms as producing organisms.


von Schacky, C. (2003). "The role of omega-3 fatty acids in cardiovascular disease." Curr Atheroscler Rep 5(2): 139-45.

            Plant-derived alpha-linolenic acid has been studied in a limited number of investigations. So far, some epidemiologic and a few mechanistic studies suggest a potential of protection from cardiovascular disease, but this potential remains to be proven in intervention studies. In contrast, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are prevalent in fish and fish oils, have been studied in thousands of investigations. A consistent body of evidence has been elaborated in various types of investigations, ultimately demonstrating reduction in total mortality, cardiovascular mortality, and morbidity by ingestion of roughly 1 g/d of EPA plus DHA. Current guidelines, however, do not discern between the omega-3 fatty acids mentioned; in fact, most even do not differentiate polyunsaturated fatty acids at all. Unfortunately, this complicates efficient implementation of an effective means of prophylaxis of atherosclerosis.


Villar, J., M. Merialdi, et al. (2003). "Nutritional interventions during pregnancy for the prevention or treatment of maternal morbidity and preterm delivery: an overview of randomized controlled trials." J Nutr 133(5 Suppl 2): 1606S-1625S.

            This overview assesses the effectiveness of nutritional interventions to prevent or treat maternal morbidity, mortality and preterm delivery. Cochrane systematic reviews and other up-to-date systematic reviews and individual randomized controlled trials were sought. Searches were carried out up to July 2002. Iron and folate supplements reduce anemia and should be included in antenatal care programs. Calcium supplementation to women at high risk of hypertension during pregnancy or low calcium intake reduced the incidence of both preeclampsia and hypertension. Fish oil and vitamins E and C are promising for preventing preeclampsia and preterm delivery and need further testing. Vitamin A and beta-carotene reduced maternal mortality in a large trial; ongoing trials should provide further evaluation. No specific nutrient supplementation was identified for reducing preterm delivery. Nutritional advice, magnesium, fish oil and zinc supplementation appear promising and should be tested alone or together in methodologically sound randomized controlled trials. Anema in pregnancy can be prevented and treated effectively. Considering the multifactorial etiology of the other conditions evaluated, it is unlikely that any specific nutrient on its own, blanket interventions or magic bullets will prevent or treat preeclampsia, hemorrhage, obstructed labor, infections, preterm delivery or death during pregnancy. The few promising interventions for specific outcomes should be tested or reconsidered when results of ongoing trials become available. Until then, women and their families should receive support to improve their diets as a general health rule, which is a basic human right.


Vergili-Nelsen, J. M. (2003). "Benefits of fish oil supplementation for hemodialysis patients." J Am Diet Assoc 103(9): 1174-7.

            A literature review on fish oil supplementation in the population undergoing chronic hemodialysis therapy suggests that supplementation may be beneficial for various challenges to health and well-being prevalent in this population. One study indicated that pruritus symptoms improved with fish oil supplementation, but not with supplementation with two other oils. In a study designed to determine whether fish oils could prevent vascular access graft thrombosis, graft patency rates were approximately 76% in the fish oil and approximately 15% in the placebo group (P>.03). In a pilot study, subjects given fish oil required 16% less erythropoietin and experienced a 3.6% increase in serum albumin levels. Some studies suggest that fish oil supplementation in hemodialysis patients is cardioprotective, with one study finding that "fish eaters" are half as likely to die as "non-fish eaters." Potential risks of supplementation include gastrointestinal distress, prolonged bleeding, and vitamin A toxicity, although the likelihood of serious side effects is probably low. Dietitians are in a position to advise physicians and/or patients regarding appropriate dosages and ways to minimize risks when supplementation seems warranted. Future research could compare the benefits of fish consumption with those of fish oil supplementation and explore the benefits of other n-3 fatty acid sources, such as flaxseed.


Vanschoonbeek, K., M. P. de Maat, et al. (2003). "Fish oil consumption and reduction of arterial disease." J Nutr 133(3): 657-60.

            Fish oil consumption may help to normalize the prethrombotic state and reduce arterial disease. This antithrombotic potential of fish oil, rich in (n-3) polyunsaturated fatty acids (PUFA), has been attributed to a reduction in platelet activation, a lowering of plasma triglycerides and (vitamin K-dependent) coagulation factors and/or a decrease in vascular tone. Most intervention studies have shown only moderate effects of (n-3) PUFA on these hemostatic variables. On the other hand, the usually small prolongation in bleeding time with fish oil does not appear to lead to bruising or hemorrhage, at least in healthy subjects. This contrasts with the increased bleeding risk accompanying the more prominent antihemostatic effects of antiplatelet and anticoagulant drugs. Here we propose that the beneficial effect of (n-3) PUFA diet is related to down-regulation of the mutually positive interactions of platelet activation and coagulation. In addition, we consider the possibility that the dietary effect on hemostatic and lipid factors involves transcription regulation of multiple genes, perhaps in a subject-dependent manner.


Trushina, E. N., O. K. Mustafina, et al. (2003). "[The mechanism of action of polyunsaturated fatty acids on the immune system]." Vopr Pitan 72(3): 35-40.

            This article presents the literature materials about polyunsaturated fatty acids as nutritional immunomodulators.


Terry, P. D., T. E. Rohan, et al. (2003). "Intakes of fish and marine fatty acids and the risks of cancers of the breast and prostate and of other hormone-related cancers: a review of the epidemiologic evidence." Am J Clin Nutr 77(3): 532-43.

            Marine fatty acids, particularly the long-chain eicosapentaenoic and docosahexaenoic acids, have been consistently shown to inhibit the proliferation of breast and prostate cancer cell lines in vitro and to reduce the risk and progression of these tumors in animal experiments. However, whether a high consumption of marine fatty acids can reduce the risk of these cancers or other hormone-dependent cancers in human populations is unclear. Focusing primarily on the results of cohort and case-control studies, we reviewed the current epidemiologic literature on the intake of fish and marine fatty acids in relation to the major hormone-dependent cancers. Despite the many epidemiologic studies that have been published, the evidence from those studies remains unclear. Most of the studies did not show an association between fish consumption or marine fatty acid intake and the risk of hormone-related cancers. Future epidemiologic studies will probably benefit from the assessment of specific fatty acids in the diet, including eicosapentaenoic and docosahexaenoic acids, and of the ratio of these to n-6 fatty acids, dietary constituents that have not been examined individually very often.


Spector, S. L. and M. E. Surette (2003). "Diet and asthma: has the role of dietary lipids been overlooked in the management of asthma?" Ann Allergy Asthma Immunol 90(4): 371-7; quiz 377-8, 421.

            OBJECTIVE: This article discusses the role of diet in the management of asthma. Readers will gain an understanding of how evolution of the western diet has contributed to increased asthma prevalence and how dietary modification that includes management of dietary lipids may reduce symptoms of asthma. DATA SOURCES: Relevant studies published in English were reviewed. STUDY SELECTION: Medline search to identify peer-reviewed abstracts and journal articles. RESULTS: Asthma and obesity, which often occur together, have increased in prevalence in recent years. Studies suggest adaption of a western diet has not only contributed to obesity, but that increased intake of specific nutrients can cause changes in the frequency and severity of asthma. Increased asthma prevalence has also been proposed to arise from increased exposure to diesel particles or lack of exposure to infectious agents or endotoxins during childhood, generating a biased Th2 immune response, and increased cytokine and leukotriene production. Antagonists directed against these pro-inflammatory mediators include anticytokines and antileukotrienes. A reduction in the levels of inflammatory mediators associated with asthma has also been seen with dietary interventions, such as the administration of oils containing gamma-linolenic acid and eicosapentaenoic acid. CONCLUSIONS: Evidence suggests elevated body mass index and dietary patterns, especially intake of dietary lipids, contribute to symptoms of asthma. Dietary modification may help patients manage their asthma as well as contribute to their overall health.


Skerrett, P. J. and C. H. Hennekens (2003). "Consumption of fish and fish oils and decreased risk of stroke." Prev Cardiol 6(1): 38-41.

            Consumption of fish and fish oils was first associated with decreased risk of cardiovascular disease almost 50 years ago. Since then, a number of epidemiologic studies have evaluated whether their consumption is specifically associated with stroke. Ecologic/cross-sectional and case-control studies have generally shown an inverse association between consumption of fish and fish oils and stroke risk. Results from five prospective studies have been less consistent, with one showing no association, one showing a possible inverse association, and three demonstrating a significant inverse association. In the latest and largest of these, the Nurses Health Study, the relative risk of total stroke was lower, although not significantly so, among women who regularly ate fish than among those who did not. A significant decrease in the risk of thrombotic stroke (relative risk, 0.49; 95% confidence interval, 0.26-0.93) was observed among women who ate fish at least two times per week compared with women who ate fish less than once per month, after adjustment for age, smoking, and other cardiovascular risk factors; a nonsignificant decrease was observed among women in the highest quintile of long-chain omega-3 polyunsaturated fatty acid intake. No association was observed between consumption of fish or fish oil and hemorrhagic stroke. These data support the hypothesis that consumption of fish several times per week reduces the risk of thrombotic stroke but does not increase the risk of hemorrhagic stroke.


Ristic, V. and G. Ristic (2003). "[Role and importance of dietary polyunsaturated fatty acids in the prevention and therapy of atherosclerosis]." Med Pregl 56(1-2): 50-3.

            INTRODUCTION: Hyperlipoproteinemia is a key factor in development of atherosclerosis, whereas regression of atherosclerosis mostly depends on decreasing the plasma level of total and LDL-cholesterol. Many studies have reported the hypocholesterolemic effect of linolenic acid. TYPES OF POLYUNSATURATED FATTY ACIDS (PUFA): Linoleic and alpha-linolenic acids are essential fatty acids. The main sources of linoleic acid are vegetable seeds and of alpha-linolenic acid-green parts of plants. alpha-linolenic acid is converted to eicosapentaenoic and docosahexaenoic acid. Linoleic acid is converted into arachidonic acid competing with eicosapentaenoic acid in the starting point for synthesis of eicosanoids, which are strong regulators of cell functions and as such, very important in physiology and pathophysiology of cardiovascular system. Eicosanoids derived from eicosapentaneoic acid have different biological properties in regard to those derived from arachidonic acid, i.e. their global effects result in decreased vasoconstriction, platelet aggregation and leukocyte toxicity. ROLE AND SIGNIFICANT OF PUFA: The n-6 to n-3 ratio of polyunsaturated fatty acids in the food is very important, and an optimal ratio 4 to 1 in diet is a major issue. Traditional western diets present absolute or relative deficiency of n-3 polyunsaturated fatty acids, and a ratio 15-20 to 1. In our diet fish and fish oil are sources of eicosapentaenoic and docosahexaenoic acid. Refined and processed vegetable oils change the nature of polyunsaturated fatty acids and obtained derivates have atherogenic properties.


Parra, J. L. and K. R. Reddy (2003). "Hepatotoxicity of hypolipidemic drugs." Clin Liver Dis 7(2): 415-33.

            Dyslipidemic conditions and their cardiovascular related complications are common. Effective primary and secondary prevention strategies include therapies to lower LDL and total cholesterol and to increase HDL. Further, it seems that there is a need for therapeutic reduction in triglycerides as it emerges as an independent risk factor for CVD. Many clinical trials have been designed to evaluate pharmacologic compounds in the treatment of the dyslipidemias and they seem to have shown a safe profile, both in the experiment phases and in post-marketing observation studies. Nevertheless, sporadic reports of hepatotoxicity with statins and niacin still arise (Table 2). Although routine hepatic biochemical test monitoring is recommended, the cost-effectiveness is questionable because often these reactions are idiosyncratic and may not be identified by this routine screening. The risk/benefit ratio is in favor of using these medications in individuals at risk. There is no evidence to suggest intrinsic hepatotoxic activity as such. Drugs that lower triglycerides such as fibrates, have been observed to improve hepatic biochemical tests, although in small series. This leads to speculation whether treatment with fibrates would be beneficial for non-alcoholic fatty liver disease (NAFLD), a condition that is emerging as one of enormous magnitude.


Olsen, S. F., N. J. Secher, et al. (2003). "The potential benefits of using fish oil in relation to preterm labor: the case for a randomized controlled trial?" Acta Obstet Gynecol Scand 82(11): 978-82.


Okamoto, S., R. Ishisu, et al. (2003). "[Prevention of restenosis after PTCA and patient's QOL]." Nippon Rinsho 61 Suppl 4: 524-8.


Mickleborough, T. and R. Gotshall (2003). "Dietary components with demonstrated effectiveness in decreasing the severity of exercise-induced asthma." Sports Med 33(9): 671-81.

            Exercise-induced asthma (EIA) occurs in up to 90% of individuals with asthma and approximately 10% of the general population without asthma. EIA describes a condition in which vigorous physical activity triggers acute airway narrowing with heightened airway reactivity resulting in reductions in forced expiratory volume in 1 second of greater than 10% compared with pre-exercise values. Treatment of EIA almost exclusively involves the use of pharmacological medications. However, there is accumulating evidence that a dietary excess of salt and omega-6 fatty acids, and a dietary deficiency of antioxidant vitamins and omega-3 fatty acids, can modify the severity of EIA. The modification of these dietary factors has the potential to reduce the incidence and prevalence of this disease. The dietary component most studied to date is dietary salt. Recent studies have supported a role for dietary salt as a modifier of the severity of EIA, suggesting that salt-restrictive diets can reduce the severity of EIA. Since EIA is part of the asthmatic diathesis, it is possible that EIA may serve as a useful model for investigation of potential dietary interventions for reducing airway hyperresponsiveness.


Lee, K. W. and G. Y. Lip (2003). "The role of omega-3 fatty acids in the secondary prevention of cardiovascular disease." Qjm 96(7): 465-80.

            It has long been recognized from epidemiological studies that Greenland Eskimos have substantially reduced rates of acute myocardial infarction (MI) compared with Western controls. From these epidemiological observations, the benefits of fatty fish consumption have been explored in cell culture and animal studies, as well as randomized controlled trials investigating the cardioprotective effects of omega-3 fatty acids. Dietary omega-3 fatty acids seem to stabilize the myocardium electrically, resulting in reduced susceptibility to ventricular arrhythmias, thereby reducing the risk of sudden death. These fatty acids also have potent anti-inflammatory effects, and may also be antithrombotic and anti-atherogenic. Furthermore, the recent GISSI-Prevention study of 11 324 patients showed a marked decrease in risk of sudden cardiac death as well as a reduction in all-cause mortality in the group taking a highly purified form of omega-3 fatty acids, despite the use of other secondary prevention drugs, including beta-blockers and lipid-lowering therapy. The use of omega-3 fatty acids should be considered as part of a comprehensive secondary prevention strategy post-myocardial infarction.


Leaf, A., Y. F. Xiao, et al. (2003). "Prevention of sudden cardiac death by n-3 polyunsaturated fatty acids." Pharmacol Ther 98(3): 355-77.

            This is a review of our present understanding of the mechanism by which the n-3 polyunsaturated fatty acids (PUFA) in fish oils prevent fatal ventricular arrhythmias in animals and cultured heart cells. A brief review of three clinical trials that suggest that these PUFAs prevent sudden cardiac death is also included in order to emphasize the potential importance of these fatty acids in human nutrition. The PUFAs act by stabilizing electrically every cardiac myocyte by modulating conductance of ion channels in the sarcolemma, particularly the fast, voltage-dependent sodium current and the L-type calcium currents, though other ion currents are also affected. Work in progress suggests that the primary site of action of the PUFAs may be on the phospholipid bilayer of the heart cells in the microdomains through which the ion channels penetrate the membrane bilayer in juxtaposition with the ion channels rather than directly on the channel protein itself. These PUFAs then allosterically alter the conformation and conductance of the channels. Both potential benefits and possible adverse effects of the PUFAs in man will be discussed. Knowing that the ion channels have been structurally conserved among all excitable tissues, we tested their effects on the electrophysiology of rat hippocampal CA1 neurons and found that the sodium and calcium ion channels in these neurons were also affected by PUFAs. An attempt to show the place of the PUFAs in human nutrition during the 2-4 million years of our evolution will conclude the review.


Leaf, A., J. X. Kang, et al. (2003). "Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils." Circulation 107(21): 2646-52.


Kroes, R., E. J. Schaefer, et al. (2003). "A review of the safety of DHA45-oil." Food Chem Toxicol 41(11): 1433-46.

            Polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA), are natural constituents of the human diet; however, dietary intakes of these fatty acids are below recommended values. The main dietary source of DHA is fatty fish, with lesser amounts provided by shellfish, marine mammals, and organ meats. The addition to traditional food products of refined oils produced by marine microalgae represents potential sources of supplemental dietary DHA. DHA45-oil is manufactured through a multi-step fermentation and refining process using a non-toxigenic and non-pathogenic marine protist. Comprising approximately 45% DHA, and lesser concentrations of palmitic acid and docosapentaenoic acid, DHA45-oil is intended for use in foods as a dietary source of DHA. The safety of DHA45-oil was evaluated in various genotoxicity and acute, subchronic, and reproductive toxicity studies. DHA45-oil produced negative results in genotoxicity assays and demonstrated a low acute oral toxicity in mice and rats. Dietary administration of DHA45-oil to rats in subchronic and one-generation reproductive studies produced results consistent with those observed in oral studies using high concentrations of omega-3 PUFAs from fish or other microalgal-derived oils. The results of these studies, as well as those of various published metabolic, toxicological, and clinical studies with DHA-containing oils, support the safety of DHA45-oil as a potential dietary source of DHA.


Kris-Etherton, P. M., W. S. Harris, et al. (2003). "Omega-3 fatty acids and cardiovascular disease: new recommendations from the American Heart Association." Arterioscler Thromb Vasc Biol 23(2): 151-2.


Kris-Etherton, P. M., W. S. Harris, et al. (2003). "Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease." Arterioscler Thromb Vasc Biol 23(2): e20-30.


Kastelein, J. (2003). "What future for combination therapies?" Int J Clin Pract Suppl(134): 45-50.

            For most patients who require lipid-lowering treatment, statin monotherapy is the appropriate treatment. However, in those patients where statin monotherapy does not produce optimal lipid levels, the combination of a statin with niacin, a bile acid sequestrant, a fibric acid derivative, a cholesterol absorption inhibitor or a fish oil preparation may provide improved control. The choice of combination therapy depends upon the patient's lipid profile and tolerability of the medication. Combination of a statin with niacin, a bile acid sequestrant or ezetimibe, a cholesterol absorption inhibitor, should be considered for patients with very high low-density lipoprotein cholesterol (LDL-C) levels, while combination with either a fibric acid derivative or a fish oil should be considered for patients with high LDL-C and high triglyceride levels. A number of new lipid-lowering agents are currently in development, including cholesteryl ester transfer protein (CETP) inhibitors, acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitors, ileal bile acid transport (IBAT) inhibitors, microsomal triglyceride transfer protein (MTP) inhibitors and dual peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonists. Introduction of these novel therapies will provide opportunities for developing different combination strategies that may help to optimise lipid profiles in patients who are currently difficult to treat. The introduction of new combinations will require careful study to ensure that the risks of drug interactions and adverse events are minimised.


Julius, U. (2003). "Fat modification in the diabetes diet." Exp Clin Endocrinol Diabetes 111(2): 60-5.

            The modification of dietary fat in the diet of diabetic patients is of interest with respect to metabolic and other consequences of this modification. To begin with the data are reviewed for the use of monounsaturated fatty acids (MUFA) in the diabetes diet. Compared to a carbohydrate-rich diet, glucose concentrations are lower. Blood pressure was also found to be lower. There were no major differences with respect to lipid concentrations. HDL-cholesterol levels tended to be higher after a MUFA-rich diet. In type-1 diabetic patients, the number of circulating big VLDL particles was greater after a MUFA diet than after a carbohydrate-rich diet. Comparisons were also made between diets enriched with MUFA and with polyunsaturated fatty acids (PUFA). With respect to lipid concentrations, different groups observed different effects. While one group saw no differences in fasting lipids, they measured a higher remnant-like particle cholesterol after a diet enriched with MUFA. Another group found higher total and LDL-cholesterol levels after a PUFA-rich diet than after a MUFA-diet. In their study, fasting glucose, insulin and fasting chylomicrons and postprandial chylomicrons and VLDL were higher following the PUFA diet. A MUFA-rich diet increased endothelium-dependent flow-mediated dilatation in the superficial femoral artery. Alpha-linolenic acid appears to be a precursor of eicospentaenoic and docosahexaenoic fatty acids. As a diet rich in n-6 PUFA reduces this conversion, a n-6/n-3 PUFA ratio not exceeding 4 - 6 should be observed. No prospective data are available for alpha-linolenic acid in diabetic patients. The review summarizes the results of the Lyon Diet Heart Study and the Nurses' Health Study. Both studies saw a reduced cardiovascular risk associated with a higher intake of alpha-linolenic acid. Finally, data on the effects of fish oil are given. The latter has a clearly expressed triglyceride-lowering effect. Data with respect to glucose control are heterogeneous. Major studies did not find any influence in glucose concentrations. Hepatic glucose production and peripheral insulin sensitivity remained constant. Evidently, nerve function can be improved by fish oil. Data have been compiled comparing the effects of fish oil with those of olive oil, linseed oil and sunflower oil.


Joy, C. B., R. Mumby-Croft, et al. (2003). "Polyunsaturated fatty acid supplementation for schizophrenia." Cochrane Database Syst Rev(2): CD001257.

            BACKGROUND: Limited evidence supports a hypothesis suggesting that schizophrenic symptoms may be the result of altered neuronal membrane structure and metabolism. This structure and metabolism is dependent on blood plasma levels of certain essential fatty acids and their metabolites. OBJECTIVES: To review the effects polyunsaturated fatty acids for people with schizophrenia. SEARCH STRATEGY: The initial search of 1998 was updated. We searched the Cochrane Schizophrenia Group's Register (July 2002), and authors of included studies and relevant pharmaceutical companies were contacted. SELECTION CRITERIA: All randomised clinical trials of polyunsaturated fatty acid treatment for schizophrenia. DATA COLLECTION AND ANALYSIS: Reviewers, working independently, selected, quality assessed, and extracted relevant data. Analysis was on an intention-to-treat basis. Where possible and appropriate Relative Risk (RR) and their 95% confidence intervals (CI) were calculated and the number needed to treat (NNT) estimated. For continuous data, weighted mean differences (WMD) and their 95% confidence intervals were calculated. Data were inspected for heterogeneity. MAIN RESULTS: Five short small studies (n=313) were included. One small study (n=30) suggested that an omega-3 EFA (ecisapentenoic acid (EPA) enriched oil) may have some antipsychotic properties when compared with placebo, even if not given as a supplement to standard drugs (RR not needing antipsychotic drugs 0.73 CI 0.54 to 1.00; RR less than 25% improvement in PANSS 0.54 CI 0.3 to 0.96, NNT 3 CI 2 to 29). Other studies comparing omega-3 EFA's with placebo as a supplement to antipsychotics were too small to be conclusive. There was a suggestion that people already on antipsychotics when given omega-3 EFA supplementation had greater improvement of mental state compared to those receiving a placebo supplementation but the result were not significant (n=29, 1 RCT, RR <25% improvement in PANSS 0.62 CI 0.37 to 1.05). However, the mental state of both medicated and un-medicated patients was significantly better for those receiving omega-3 EFA supplementation (n=59, 2 RCTs, RR <25% improved on PANSS 0.58 CI 0.39 to 0.85, NNT 3 CI 2-8). Medium term data, however, did not favour either group (n=87, 1 RCT, MD PANSS endpoint -1.0 CI -8.15 to 6.15). All studies had low attrition (<10% total, n=271, 4 RCTs, RR leaving the study early 0.91 CI 0.36 to 2.33). Another study (n=31) comparing two types of omega-3 EFA's, ecisapentenoic acid enriched oil and docosahexanoic acid oil, also found no differences between these two EFA's in measures of mental state. One small (n=16) study investigated the effects of an omega-6 EFA compared with placebo for tardive dyskinesia and found no clear effects. There is not a clear dose response to omega-3 supplementation. Adverse effects seem rare but diarrhoea may be a problem in the medium term. REVIEWER'S CONCLUSIONS: The use of omega-3 polyunsaturated fatty acids for schizophrenia remains experimental and large well designed, conducted and reported studies are indicated and needed.


Iusupova, G. I., T. V. Fedichkina, et al. (2003). "[Sources of lipids in parenteral and enteral nutrition]." Vopr Pitan 72(3): 32-5.

            The review is devoted to sources of lipids in enteral and parenteral nutrition. The role of omega-3 and omega polyunsaturated fatty acids in metabolism of some lipid mediators is examined.


Imazio, M., D. Forno, et al. (2003). "Omega-3 polyunsatured fatty acids role in postmyocardial infarction therapy." Panminerva Med 45(2): 99-107.

            Largely initiated by studies among Eskimos in the early 1970s, great attention has been given to possible effects of omega-3 polyunsatured fatty acids (PUFA) in cardiovascular diseases. A series of positive effects on pathogenetic mechanisms of cardiovascular disease has been discovered from laboratory studies in cell cultures, animal models and in humans. omega-3 PUFA can reduce platelets and leucocytes activities as well as plasma triglycerides. Moreover they can have antiarrhythmic properties. Nowadays patients who experienced myocardial infarction have decreased risk of total and cardiovascular mortality by treatment with omega-3 PUFA (1 g daily). This effect is present irrespective of high or low fish intake or simultaneous intake of other drugs for secondary prevention of coronary heart disease. Mainly on the basis of GISSI Prevention trial results, dietary supplementation with omega-3 PUFA is now recommended as a new component of secondary prevention after myocardial infarction in national and international guidelines.


Holder, H. (2003). "Nursing management of nutrition in cancer and palliative care." Br J Nurs 12(11): 667-8, 670, 672-4.

            Malnutrition is prevalent in patients with cancer. This can have deleterious effects including reduced response to treatment, diminished quality of life, increased length of hospital stay and decreased survival. It is, therefore, imperative that thorough nutritional screening is carried out by nurses on patients' admission and during their hospital stay to detect those who are malnourished or at risk of malnutrition in order to plan their nutritional care effectively. Cancer cachexia is the progressive weight loss and emaciation seen in cancer patients, particularly in advanced disease, which can have a devastating effect on the physical, psychological, social and spiritual aspects of the patient's life. Therefore, the aims of nutritional care are identified depending on the stage of the patient's illness and recommendations made for nursing, pharmacological and nutritional intervention. These include nursing comfort strategies, the use of recommended pharmacological agents and dietary interventions such as experimenting with different foods, textures, portion sizes and nutritional supplements. The use of fish oil-enhanced nutritional supplements and artificial nutritional support is also discussed. Consideration is also given to the legal and ethical aspects of providing nutrition and nutritional support.


Heller, A. R., H. J. Theilen, et al. (2003). "Fish or chips?" News Physiol Sci 18: 50-4.

            Cell membranes are not simply barriers separating intracellular from extracellular space. Rather, they represent a dynamic high-turnover system that adapts to current demands. During inflammation, prostaglandins and leukotrienes are formed from membrane-derived phospholipids. Encouraging improvements in critically ill patients were observed after nutritional replacement of long-chain omega-6 fatty acids with long-chain omega-3-fatty acids, contained in fish oil.


Halsted, C. H. (2003). "Dietary supplements and functional foods: 2 sides of a coin?" Am J Clin Nutr 77(4 Suppl): 1001S-1007S.

            Dietary supplements are used by more than one-half of the adult US population. In contrast to pharmaceuticals, dietary supplements may be sold in the United States with little regulation other than listing of ingredients and the potential health benefits. By contrast, herbal products in Germany are carefully regulated by the same standards as drugs, and efforts are under way to standardize their regulation in the entire European Union. Most herbal users do not inform their physicians that they are taking these supplements, and most physicians do not inquire. Although some herbal products have clinically proven benefits, it is increasingly apparent that many contain potentially toxic substances, particularly in relation to interactions with drugs. Hence, it is essential that practicing physicians develop a working knowledge of herbals-specifically, about claims for their usage and potential or proven efficacies and toxicities-and that they incorporate such knowledge into the evaluation and management of their patients. By contrast, functional foods-integral components of the diet that are understood to contribute added health benefits-are the subject of intense and widespread research in food and nutritional science. Examples include many polyphenolic substances, carotenoids, soy isoflavones, fish oils, and components of nuts that possess antioxidant and other properties that decrease the risk of vascular diseases and cancer. Practicing physicians are advised to stay abreast of these emerging findings in order to best advise their patients on the value of health-promoting diets in disease prevention.


Ghosh, S. and R. J. Playford (2003). "Bioactive natural compounds for the treatment of gastrointestinal disorders." Clin Sci (Lond) 104(6): 547-56.

            Many healthy subjects and patients are taking natural bioactive products for the prevention and treatment of multiple conditions, including gastrointestinal disorders. Based on current evidence, the scientific validity of the use of many of these commercial compounds by the general public is severely limited, with quality control and regulatory issues continuing to be a concern. Nevertheless, there is sufficient preliminary data to warrant further research of these products in order to identify novel compounds for potential clinical use in addition to performing formal randomized controlled clinical trials of the commercial preparations.


Fugh-Berman, A. and F. Kronenberg (2003). "Complementary and alternative medicine (CAM) in reproductive-age women: a review of randomized controlled trials." Reprod Toxicol 17(2): 137-52.

            PURPOSE: Complementary and alternative medicine (CAM) therapies are widely used in the general population. This paper reviews randomized controlled trials of CAM therapies for obstetrical and gynecologic conditions and presents therapies that are likely to be used by women of reproductive age and by pregnant women. DATA SOURCES: Sources included English-language papers in MEDLINE 1966-2002 and AMED (1985-2000) and the authors' extensive holdings. STUDY SELECTION: Randomized controlled clinical trials of CAM therapies for obstetric and gynecologic conditions. DATA EXTRACTION: Clinical information was extracted from the articles and summarized in tabular form or in the text.DATA SYNTHESIS: Ninety-three trials were identified, 45 of which were for pregnancy-related conditions, 33 of which were for premenstrual syndrome, and 13 of which were for dysmenorrhea. Data support the use of acupressure for nausea of pregnancy and calcium for PMS. Preliminary studies indicate a role for further research on Vitamin B6 or ginger for nausea and vomiting of pregnancy; calcium, magnesium, Vitamin B6, or chaste-tree berry extract for PMS; and a low-fat diet, exercise, or fish oil supplementation for dysmenorrhea. CONCLUSIONS: Limited evidence supports the efficacy of some CAM therapies. Exposure of women of reproductive age to these therapies can be expected.


Forbes, A. (2003). "Alternative immunomodulators." Eur J Gastroenterol Hepatol 15(3): 245-8.

            There is now a large number of potential immunomodulatory agents that may be of value in inflammatory bowel disease. The newer immunosuppressants, such as tacrolimus and mycophenolate, probably offer little more than providing comparable alternatives to more established agents, and fish oil and other eicosanoid modulators are probably not especially potent if effective. The biological agents, however, bring a more novel and potentially powerful approach. Natalizumab, and targeted mucosal delivery of interleukin-10 already show considerable promise.


Dubnov, G. and E. M. Berry (2003). "Omega-6/omega-3 fatty acid ratio: the Israeli paradox." World Rev Nutr Diet 92: 81-91.


Dorchy, H. (2003). "Dietary management for children and adolescents with diabetes mellitus: personal experience and recommendations." J Pediatr Endocrinol Metab 16(2): 131-48.

            Diet has traditionally played an important role in diabetic therapy. Over the years, various diets have been proposed, often without scientific evidence. One of the main errors was (is) to speculate that there exists a direct linear correlation between the injection of x units of insulin and the utilization of y grams of glucose. If this were true, one should give more insulin to practice physical activity. In reality, it is the reverse. Dietary recommendations issued over the last few years are the same for diabetic and non-diabetic individuals in order to avoid degenerative diseases. In many countries, the intake of fat is too high, and that of complex carbohydrates too low. The so-called 'Mediterranean diet', in combination with appropriate insulin therapy, may be optimal. This consists mainly of fiber-rich complex carbohydrates (grain), vegetables, fruits, fish, and olive oil. Explanations of this diet should focus on quality rather than quantity of foodstuffs, and should be given by a multidisciplinary team. Prescription of a highly rigid diet has proved ineffective in producing adequate metabolic control, and increases the risk of deviations from the diet. In our experience, the proper use of the two-injection regimen, in countries where the meal schedule allows correct allocation of diet, may lead to 'intensive conventional therapy' and good metabolic control. It is inadequate to systematically assign the multiple-insulin injection regimen to intensified insulin therapy, and the 'conventional' two-injection regimen to a non-intensified insulin therapy. The proper use of the basal-bolus regimen, with increased flexibility in daily life and dietary freedom, cannot always be applied successfully before adolescence. The adjustment of insulin dosage is more complicated than in the twice-daily injection regimen because dose alteration cannot be made only according to sliding scales based on the glycemia measured immediately before the insulin injection. The simplistic use of these non-physiological sliding scales is the main error in the multiple daily insulin injection regimen. The use of fast-acting insulin analogs in the basal-prandial regimen improves post-prandial glycemia at the expense of an increase in pre-prandial glucose levels, if the period between two meals, and therefore two injections, exceeds 3-4 hours, because of the short duration of action. If there are 4-6 or 7 hours between two meals, it is better to use a rapid-acting insulin. Avoid dogmatism--only objective results (good glycosylated hemoglobin and lipid levels, as well as good quality of life) are important.


de Lorgeril, M. and P. Salen (2003). "Dietary prevention of coronary heart disease: focus on omega-6/omega-3 essential fatty acid balance." World Rev Nutr Diet 92: 57-73.


Cottrell, D. A., B. J. Marshall, et al. (2003). "Therapeutic approaches to dyslipidemia in diabetes mellitus and metabolic syndrome." Curr Opin Cardiol 18(4): 301-8.

            Type 2 diabetes mellitus and the closely related metabolic syndrome are associated with significant risk for cardiovascular disease. Recent evidence suggests that both conditions are increasing in epidemic proportions. Dyslipidemia is characterized by increased triglyceride-rich lipoproteins; low high-density lipoprotein cholesterol; small, dense low-density lipoprotein particles; increased postprandial lipemia; and abnormal apolipoprotein A1 and B metabolism. All these lipoprotein disturbances accelerate atherosclerosis in these patients. It is likely that many patients will need combinations of lipid-modifying therapy to achieve American Diabetes Association (ADA), Adult Treatment Panel III, and American Heart Association (AHA)/American College of Cardiology (ACC) guidelines to help prevent cardiovascular disease and death.


Corpet, D. E. and F. Pierre (2003). "Point: From animal models to prevention of colon cancer. Systematic review of chemoprevention in min mice and choice of the model system." Cancer Epidemiol Biomarkers Prev 12(5): 391-400.

            The Apc(Min/+) mouse model and the azoxymethane (AOM) rat model are the main animal models used to study the effect of dietary agents on colorectal cancer. We reviewed recently the potency of chemopreventive agents in the AOM rat model (D. E. Corpet and S. Tache, Nutr. Cancer, 43: 1-21, 2002). Here we add the results of a systematic review of the effect of dietary and chemopreventive agents on the tumor yield in Min mice. The review is based on the results of 179 studies from 71 articles and is displayed also on the internet http://corpet.net/min.(2) We compared the efficacy of agents in the Min mouse model and the AOM rat model, and found that they were correlated (r = 0.66; P < 0.001), although some agents that afford strong protection in the AOM rat and the Min mouse small bowel increase the tumor yield in the large bowel of mutant mice. The agents included piroxicam, sulindac, celecoxib, difluoromethylornithine, and polyethylene glycol. The reason for this discrepancy is not known. We also compare the results of rodent studies with those of clinical intervention studies of polyp recurrence. We found that the effect of most of the agents tested was consistent across the animal and clinical models. Our point is thus: rodent models can provide guidance in the selection of prevention approaches to human colon cancer, in particular they suggest that polyethylene glycol, hesperidin, protease inhibitor, sphingomyelin, physical exercise, epidermal growth factor receptor kinase inhibitor, (+)-catechin, resveratrol, fish oil, curcumin, caffeate, and thiosulfonate are likely important preventive agents.


Colin, A., J. Reggers, et al. (2003). "[Lipids, depression and suicide]." Encephale 29(1): 49-58.

            Polyunsatured fatty acids are made out of a hydrocarbonated chain of variable length with several double bonds. The position of the first double bond (omega) differentiates polyunsatured omega 3 fatty acids (for example: alpha-linolenic acid or alpha-LNA) and polyunsatured omega 6 fatty acids (for example: linoleic acid or LA). These two classes of fatty acids are said to be essential because they cannot be synthetised by the organism and have to be taken from alimentation. The omega 3 are present in linseed oil, nuts, soya beans, wheat and cold water fish whereas omega 6 are present in maize, sunflower and sesame oil. Fatty acids are part of phospholipids and, consequently, of all biological membranes. The membrane fluidity, of crucial importance for its functioning, depends on its lipidic components. Phospholipids composed of chains of polyunsatured fatty acids increase the membrane fluidity because, by bending some chains, double bonds prevent them from compacting themselves perfectly. Membrane fluidity is also determined by the phospholipids/free cholesterol ratio, as cholesterol increases membrane viscosity. A diet based on a high proportion of essential polyunsatured fatty acids (fluid) would allow a higher incorporation of cholesterol (rigid) in the membranes to balance their fluidity, which would contribute to lower blood cholesterol levels. Brain membranes have a very high content in essential polyunsatured fatty acids for which they depend on alimentation. Any dietary lack of essential polyunsatured fatty acids has consequences on cerebral development, modifying the activity of enzymes of the cerebral membranes and decreasing efficiency in learning tasks. EPIDEMIOLOGICAL DATA: The prevalence of depression seems to increase continuously since the beginning of the century. Though different factors most probably contribute to this evolution, it has been suggested that it could be related to an evolution of alimentary patterns in the Western world, in which polyunsatured omega 3 fatty acids contained in fish, game and vegetables have been largely replaced by polyunsatured omega 6 fatty acids of cereal oils. Some epidemiological data support the hypothesis of a relation between lower depression and/or suicide rates and a higher consumption of fish. These data do not however prove a relation of causality. CHOLESTEROL AND DEPRESSION: Several cohort studies (on nondepressed subjects) have assessed the relationship between plasma cholesterol and depressive symptoms with contradictory results. Though some results found a significant relationship between a decrease of total cholesterol and high scores of depression, some other did not. Studies among patients suffering from major depression signalled more constantly an association between low cholesterol and major depression. Besides, some trials showed that clinical recovery may be associated with a significant increase of total cholesterol. CHOLESTEROL AND SUICIDAL BEHAVIOR: The hypothesis that a low cholesterol level may represent a suicidal risk factor was discovered accidentally following a series of epidemiological studies which revealed an increase of the suicidal risk among subjects with a low cholesterol level. Though some contradictory studies do exist, this relationship has been confirmed by several subsequent cohort studies. These findings have challenged the vast public health programs aimed at promoting the decrease of cholesterol, and even suggested to suspend the administration of lipid lowering drugs. Recent clinical studies on populations treated with lipid lowering drugs showed nevertheless a lack of significant increase of mortality, either by suicide or accident. In addition, several controlled studies among psychiatric patients revealed a decrease of the concentrations of plasma cholesterol among patients who had attempted suicide in comparison with other patients. POLYUNSATURATED FATTY ACID AND DEPRESSION: In major depression, all studies revealed a significant decrease of the polyunsaturated omega 3 fatty acids and/or an increase of the omega 6/omega 3 ratio in plasma and/or in the membranes of the red cells. In addition, two studies found a higher severity of depression when the level of polyunsaturated omega 3 fatty acids or the ratio omega 3/omega 6 was low. Parallel to these modifications, other biochemical perturbations have been reported in major depression, particularly an activation of the inflammatory response system, resulting in an increase of the pro-inflammatory cytokines (interleukins: IL-1b, IL-6 and interferon g) and eicosanoids (among others, prostaglandin E2) in the blood and the CSF of depressed patients. These substances cause a peroxidation and, consequently a catabolism of membrane phospholipids, among others those containing polyunsaturated fatty acids. The cytokines and eicosanoids derive from polyunsaturated fatty acids and have opposite physiological functions according to their omega 3 or omega 6 precursor. Arachidonic acid (omega 6) is, among others, precursor of pro-inflammatory prostaglandin E2 (PGE2), whereas polyunsaturated omega 3 fatty acids inhibit the formation of PGE2. It has been shown that a dietary increase of polyunsaturated omega 3 fatty acids reduced strongly the production of IL-1 beta, IL-2, IL-6 and TNF-alpha (tumor necrosis factor-alpha). In contrast, diets with a higher supply of linoleic acid (omega 6) increased significantly the production of pro-inflammatory cytokines, like TNF-alpha. Therefore, polyunsaturated omega 3 fatty acids could be associated at different levels in the pathophysiology of major depression, on the one hand through their role in the membrane fluidity which influences diverse steps of neurotransmission and, on the other hand, through their function as precursor of pro-inflammatory cytokines and eicosanoids disturbing neurotransmission. In addition, antidepressants could exhibit an immunoregulating effect by reducing the release of pro-inflammatory cytokines, by increasing the release of endogenous antagonists of pro-inflammatory cytokines like IL-10 and, finally, by acting like inhibitors of cyclo-oxygenase. THERAPEUTIC USE OF FATTY ACIDS: Data available concerning the administration of supplements of DHA (docosahexanoic acid) or other polyunsaturated fatty acids omega 3 are limited. In a double blind placebo-controlled study on 30 patients with bipolar disorder, the addition of polyunsaturated omega 3 fatty acids was associated with a longer period of remission. Moreover, nearly all the other prognosis measures were better in the omega 3 group. Very recently, a controlled trial showed the benefits of adding an omega 3 fatty acid, eicosopentanoic acid, among depressed patients. After 4 weeks, six of the 10 patients receiving the fatty acid were considered as responders in comparison with only one of the ten patients receiving placebo. CONCLUSIONS: Some epidemiological, experimental and clinical data favour the hypothesis that polyunsaturated fatty acids could play a role in the pathogenesis and/or the treatment of depression. More studies however are needed in order to better precise the actual implication of those biochemical factors among the various aspects of depressive illness.


Cleland, L. G., M. J. James, et al. (2003). "The role of fish oils in the treatment of rheumatoid arthritis." Drugs 63(9): 845-53.

            Fish oils are a rich source of omega-3 long chain polyunsaturated fatty acids (n-3 LC PUFA). The specific fatty acids, eicosapentaenoic acid and docosahexaenoic acid, are homologues of the n-6 fatty acid, arachidonic acid (AA). This chemistry provides for antagonism by n-3 LC PUFA of AA metabolism to pro-inflammatory and pro-thrombotic n-6 eicosanoids, as well as production of less active n-3 eicosanoids. In addition, n-3 LC PUFA can suppress production of pro-inflammatory cytokines and cartilage degradative enzymes.In accordance with the biochemical effects, beneficial anti-inflammatory effects of dietary fish oils have been demonstrated in randomised, double-blind, placebo-controlled trials in rheumatoid arthritis (RA). Also, fish oils have protective clinical effects in occlusive cardiovascular disease, for which patients with RA are at increased risk.Implementation of the clinical use of anti-inflammatory fish oil doses has been poor. Since fish oils do not provide industry with the opportunities for substantial profit associated with patented prescription items, they have not received the marketing inputs that underpin the adoption of usual pharmacotherapies. Accordingly, many prescribers remain ignorant of their biochemistry, therapeutic effects, formulations, principles of application and complementary dietary modifications. Evidence is presented that increased uptake of this approach can be achieved using bulk fish oils. This approach has been used with good compliance in RA patients. In addition, an index of n-3 nutrition can be used to provide helpful feedback messages to patients and to monitor the attainment of target levels.Collectively, these issues highlight the challenges in advancing the use of fish oil amid the complexities of modern management of RA, with its emphasis on combination chemotherapy applied early.


Cleland, L. G., M. J. James, et al. (2003). "Omega-6/omega-3 fatty acids and arthritis." World Rev Nutr Diet 92: 152-68.


Christon, R. A. (2003). "Mechanisms of action of dietary fatty acids in regulating the activation of vascular endothelial cells during atherogenesis." Nutr Rev 61(8): 272-9.

            Dietary long chain omega-3 polyunsaturated fatty acids from fish oil appear to be clearly efficient in regulating endothelial dysfunction (or activation), which is the first stage of atherogenesis. Studies on endothelial cells in vitro have shown that the main dietary PUFA and oleic acid may prevent endothelium activation either by inhibiting the expression of adhesion molecules or by improving the nitric oxide production. Saturated fatty acids and also linoleic acid do not inhibit endothelium activation. The mechanisms involved in this inhibition could be related to endothelial cell membrane characteristics or redox status. However, these findings need to be confirmed in vivo.


Chiarla, C., I. Giovannini, et al. (2003). "[Use of unconventional lipid substrates in parental nutrition]." Clin Ter 154(2): 135-40.

            In addition to the classic soybean oil fat emulsion, developed more than 40 years ago and still widely used, emulsions with other lipid substrates are available today for parenteral nutrition; these substrates implement the benefits offered by soybean oil when mixed with it in given proportions. Soybean oil triglycerides are rich in linoleic acid, a long chain omega-6 polyunsaturated fatty acid, which is essential and is an indispensable component of parenteral nutrition. However, very high doses of omega-6 polyunsaturated fatty acids should be avoided, particularly in some critical illnesses. Medium chain triglycerides, long well known to nutritionists and dietitians for their easy intestinal absorption, have become available in parenteral nutrition emulsions in a mixture with soybean oil. Medium chain triglycerides are completely and readily used for energy production and do not interfere significantly in the production of inflammatory mediators, in the composition of cell membranes and in body organ and system functions. Omega-3 polyunsaturated fatty acids, essential fatty acids derived from fish oil, permeate cell structure and affect cell activity with different mechanisms, playing also an important role in the modulation of inflammatory processes. Omega-3 emulsions in parenteral nutrition are currently added as a supplement to other fat emulsions. Knowledge of these "non-conventional" fat emulsions is being continuously improved by investigative work and clinical experience.


Chen, W. J. and S. L. Yeh (2003). "Effects of fish oil in parenteral nutrition." Nutrition 19(3): 275-9.

            OBJECTIVE: Fish oil is a rich source of omega-3 fatty acids (FAs), especially eicosapentaenoic acid and docosahexaenoic acid. The existing data suggest that eicosapentaenoic acid and docosahexaenoic acid are the active agents in fish oil. A number of clinical trials have shown that dietary fish oil supplementation has antiatherogenic properties and immunomodulation effects. Fish oils are not used widely in parenteral nutrition because fish oil emulsions have not been commercially available until very recently. Studies concerning the use of fish oil in parenteral route are rare. METHODS: We reviewed the effect of parenteral fish oil infusion on lipid metabolism and immune response in normal and disease conditions. RESULTS: Studies showed that the main effects of parenteral infusion of fish oil are: 1) incorporation of omega-3 FAs into cellular membranes of many cell populations that consequently influence the disease process of some disease conditions, 2) an effect on eicosanoid metabolism leading to a decrease in platelet aggregation and thrombosis, 3) amelioration of the severity of diet-induced hepatic steatosis, 4) less accumulation of lipid peroxidation products in liver tissue, and 5) immunomodulation effects and therapeutic benefits in animal disease models or various disease conditions of humans. Most of these studies suggested that parenteral infusion of omega-3 FAs have clinical beneficial effects comparable to those of dietary administration. However, different effects of omega-3 and omega-6 FAs in some situations has been reported. For example, plasma triacylglycerol levels were not lowered after fish oil infusion in normal or diabetic rats when compared with those of safflower oil or soybean oil infusion. The reason for the difference remain unclear. CONCLUSION: The metabolic and immunologic effects of parenteral use of omega-3 FAs requires further evaluation, especially in some disease conditions.


Chajes, V. and P. Bougnoux (2003). "Omega-6/omega-3 polyunsaturated fatty acid ratio and cancer." World Rev Nutr Diet 92: 133-51.


Calder, P. C. (2003). "Long-chain n-3 fatty acids and inflammation: potential application in surgical and trauma patients." Braz J Med Biol Res 36(4): 433-46.

            Lipids used in nutritional support of surgical or critically ill patients have been based on soybean oil, which is rich in the n-6 fatty acid linoleic acid (18:2n-6). Linoleic acid is the precursor of arachidonic acid (20:4n-6). In turn, arachidonic acid in cell membrane phospholipids is the substrate for the synthesis of a range of biologically active compounds (eicosanoids) including prostaglandins, thromboxanes, and leukotrienes. These compounds can act as mediators in their own right and can also act as regulators of other processes, such as platelet aggregation, blood clotting, smooth muscle contraction, leukocyte chemotaxis, inflammatory cytokine production, and immune function. There is a view that an excess of n-6 fatty acids should be avoided since this could contribute to a state where physiological processes become dysregulated. One alternative is the use of fish oil. The rationale of this latter approach is that fish oil contains long chain n-3 fatty acids, such as eicosapentaenoic acid. When fish oil is provided, eicosapentaenoic acid is incorporated into cell membrane phospholipids, partly at the expense of arachidonic acid. Thus, there is less arachidonic acid available for eicosanoid synthesis. Hence, fish oil decreases production of prostaglandins like PGE2 and of leukotrienes like LTB4. Thus, n-3 fatty acids can potentially reduce platelet aggregation, blood clotting, smooth muscle contraction, and leukocyte chemotaxis, and can modulate inflammatory cytokine production and immune function. These effects have been demonstrated in cell culture, animal feeding and healthy volunteer studies. Fish oil decreases the host metabolic response and improves survival to endotoxin in laboratory animals. Recently clinical studies performed in various patient groups have indicated benefit from this approach.


Cajaraville, M. P., I. Cancio, et al. (2003). "Peroxisome proliferation as a biomarker in environmental pollution assessment." Microsc Res Tech 61(2): 191-202.

            Peroxisome proliferators comprise a heterogeneous group of compounds known for their ability to cause massive proliferation of peroxisomes and liver carcinogenesis in rodents. In recent years it has become evident that other animals may be threatened by peroxisome proliferators, in particular aquatic organisms living in coastal and estuarine areas. These animals are exposed to a variety of pollutants of industrial, agricultural and urban origin which are potential peroxisome proliferators. Both laboratory and field studies have shown that phthalate ester plasticizers, PAHs and oil derivatives, PCBs, certain pesticides, bleached kraft pulp and paper mill effluents, alkylphenols and estrogens provoke peroxisome proliferation in different fish or bivalve mollusc species. The response appears to be mediated by peroxisome-proliferator activated receptors, members of the nuclear receptor family, recently cloned in fish. Based on these results it is proposed that peroxisome proliferation could be used as a biomarker of exposure to a variety of pollutants in environmental pollution assessment. This is illustrated by a case study in which mussels, used worldwide as sentinels of environmental pollution, were transplanted from reference to contaminated areas and vice versa. In mussels native to an area polluted with PAHs and PCBs, peroxisomal acyl-CoA oxidase (AOX) activity and peroxisomal volume density were 2-3 fold and 5-fold higher, respectively, compared to the reference site. When animals were transplanted to the polluted station, with increased concentration of organic xenobiotics, a concomitant significant increase of AOX was recorded. Conversely, in animals transplanted to the cleaner station, AOX activity and peroxisomal volume density decreased significantly. These results indicate that peroxisome proliferation is a rapid (i.e., two days) and reversible response to pollution in mussels. Before peroxisome proliferation can be implemented as a biomarker in biomonitoring programs, a well-defined protocol should be established and validated in intercalibration and quality assurance programmes. Furthermore, the influence of biotic and abiotic factors, some of which are known to affect peroxisome proliferation (season, tide level, interpopulation and interindividual variability), should be taken into consideration. The possible hepatocarcinogenic effects as well as the potential adverse effects on reproduction, development, and growth of peroxisome proliferators are unknown in aquatic organisms, thus providing a challenge for future investigations.


Bistrian, B. R. (2003). "Clinical aspects of essential fatty acid metabolism: Jonathan Rhoads Lecture." JPEN J Parenter Enteral Nutr 27(3): 168-75.

            The clinical implications of the metabolism of the 2 essential fatty acids, linoleic and alpha-linolenic acid, are most clearly related to the membrane phospholipid concentrations of their elongation and desaturation products, arachidonic, eicosapentaenoic, and docosahexaenoic acid. Levels of these very long chain polyunsaturated fatty acids can be altered by diet, prematurity, and disease which can affect growth (nutritional repletion) and the intensity and character of systemic inflammation as well as cognitive and visual function in infants.


Bhatnagar, D. and P. N. Durrington (2003). "Omega-3 fatty acids: their role in the prevention and treatment of atherosclerosis related risk factors and complications." Int J Clin Pract 57(4): 305-14.

            Fatty acids are an important source of energy which can have an influence on serum lipids. Omega-3 and omega-6 fatty acids, both polyunsaturated fatty acids, have been advocated as replacement for saturated fat. Omega-3 fatty acids, derived from fish and certain green plants, lower serum triglycerides, but they have also been shown to have a direct effect on myocardial contractility, blood pressure, platelet function, coagulation factors, cell-mediated immunity and markers of inflammation. Recently available clinical trial data, including those using the concentrated omega-3 fatty acid preparation Omacor, indicate that omega-3 fatty acids are valuable in preventing sudden death following myocardial infarction. Studies indicate that omega-3 fatty acids are just as effective as, or have a benefit superior to, statins in secondary prevention. Omacor is also useful in the treatment of hypertriglyceridaemia, both as monotherapy and in combination with statins.


Barrett, P. H. and G. F. Watts (2003). "Kinetic studies of lipoprotein metabolism in the metabolic syndrome including effects of nutritional interventions." Curr Opin Lipidol 14(1): 61-8.

            Nutritional interventions may favourably regulate dyslipoproteinemia and, hence, decrease cardiovascular disease risk. Lipoprotein kinetic studies afford a powerful approach to understanding and defining the mechanisms by which such interventions modulate lipoprotein metabolism. Stable isotope tracers and compartment models are now commonly employed for such studies. We review the recent application of tracer methodologies to the study of dyslipoproteinemia in the metabolic syndrome. We also focus on the effects of nutritional intervention studies that have addressed the effects of weight loss, n-3 fatty acids, plant sterols and alcohol on very low density lipoprotein, LDL and HDL metabolism. The potential for statin treatment as an adjunct to dietary modification is also discussed. New tracer methodologies are discussed, specifically those referring to reverse cholesterol transport. The nutritional interventions discussed in this review are readily transferable into clinical preventive practice. The potential benefits to be gained by weight loss and fish oil supplementation in the metabolic syndrome extend beyond their specific and positive effects on lipoprotein metabolism. Furthermore, recent developments in tracer methodologies afford new tools for probing the in-vivo pathways of lipoprotein metabolism in future studies.


Asberg, A. (2003). "Interactions between cyclosporin and lipid-lowering drugs: implications for organ transplant recipients." Drugs 63(4): 367-78.

            Dyslipidaemia is more frequent in solid organ transplant recipients than in the general population, primarily as a result of immunosuppressive drug treatment. Both cyclosporin and corticosteroids are associated with dyslipidaemic adverse effects. In order to reduce the overall cardiovascular risk in these patients, lipid-lowering drugs have become widely used, especially HMG-CoA reductase inhibitors (statins). Cyclosporin, as well as most statins (lovastatin, simvastatin, atorvastatin and pravastatin) are metabolised by cytochrome P450 (CYP)3A4, so a bilateral pharmacokinetic interaction between these drugs is theoretically possible. However, results from several studies show that statins do not induce increased systemic exposure of cyclosporin. A small (but not clinically relevant) reduction in systemic exposure of cyclosporin has actually been shown in many studies. Cyclosporin-treated patients on the other hand show several-fold higher systemic exposure of all statins, both those that are metabolised by CYP3A4 and fluvastatin (metabolised by CYP2C9). Therefore, the mechanism for this interaction does not seem to be solely caused by inhibition of CYP3A4 metabolism, but it is probably also a result of inhibition of statin-transport in the liver, at least in part. Other lipid-lowering drugs, such as fibric acid derivatives, bile acid sequestrants, probucol, fish oils and orlistat are also used in solid organ transplant recipients. Most of them do not interact with cyclosporin, but there are reports indicating that both probucol and orlistat may reduce cyclosporin bioavailablility to a clinically relevant degree. There is no information on possible interaction effects of cyclosporin on the pharmacokinetics of lipid-lowering drugs other than statins, but it is not likely that any clinical relevant interference exists with fish oil, orlistat, probucol or bile acid sequestrants.


Alonso, A., M. A. Martinez-Gonzalez, et al. (2003). "[Fish omega-3 fatty acids and risk of coronary heart disease]." Med Clin (Barc) 121(1): 28-35.

            A great amount of evidence from epidemiological studies and clinical trials supports a protective effect against coronary heart disease for fish consumption and intake of marine omega-3 fatty acids. Biological pathways for this risk reduction include membrane stabilization in the cardiac myocite, inhibition of platelet aggregation, favourable modifications of the lipid profile, decrease in blood pressure and reduction of the inflammatory response of the endothelium. Results from epidemiological studies suggest a threshold effect for the consumption of fish and omega-3 fatty acids. Risk reduction is especially important for cardiac sudden death. Nevertheless, protection against non-fatal coronary heart disease has also been observed. Recently published studies have shown that mercury intake, present in high concentrations in fish, could counteract the beneficial effect from fish consumption.


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