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Fish Oil

Table of Contents

image Change of fatty acid composition, platelet aggregability and RBC function in elderly subjects with administration of low dose fish oil concentrate and comparison with those in younger subjects
image Inhibition of phagocyte-endothelium interactions by oxidized fatty acids: a natural anti-inflammatory mechanism?
image On the causes of multiple sclerosis
image Multiple sclerosis: vitamin D and calcium as environmental determinants of prevalence (a viewpoint). I.: Sunlight, dietary factors and epidemiology
image Biological effects of fish oils in relation to chronic diseases.
image Red blood cell and adipose tissue fatty acids in mild inactive multiple sclerosis.
image Magnesium taurate and fish oil for prevention of migraine.
image Nonpharmacologic treatment of hypertension.
image Fish oils modulate blood pressure and vascular contractility in the rat and vascular contractility in the primate
image Effects of fish oil, nifedipine and their combination on blood pressure and lipids in primary hypertension.
image Effects of a combination of evening primrose oil (gamma linolenic acid) and fish oil (eicosapentaenoic + docahexaenoic acid) versus magnesium, and versus placebo in preventing pre-eclampsia.
image Microbial infection or trauma at cardiovascular representation area of medulla oblongata as some of the possible causes of hypertension or hypotension.
image Fish oil and other nutritional adjuvants for treatment of congestive heart failure
image Dietary (n-3) fatty acids increase superoxide dismutase activity and decrease thromboxane production in the rat heart.
image Effects of n-3 fatty acids and fenofibrate on lipid and hemorrheological parameters in familial dysbetalipoproteinemia and familial hypertriglyceridemia.
image Repeated fasting and refeeding with 20:5, n-3 Eicosapentaenoic Acid (EPA): A novel approach for rapid fatty acid exchanges and its effect on blood pressure, plasma lipids and hemostasis.
image Interactions between dietary fat, fish, and fish oils and their effects on platelet function in men at risk of cardiovascular disease.
image The protective effects of dietary fish oil on focal cerebral infarction
image Prevalence of essential fatty acid deficiency in patients with chronic gastrointestinal disorders.
image The effect of polyunsaturated fatty acids on the progress of cachexia in patients with pancreatic cancer
image Modulation of antioxidant enzymes and programmed cell death by n-3 fatty acids
image Dietary marine lipids suppress continuous expression of interleukin-1beta gene transcription
image Tissue specific regulation of transforming growth factor beta by omega-3 lipid-rich krill oil in autoimmune murine lupus
image The effects of dietary lipid manipulation on the production of murine T cell-derived cytokines
image Dietary omega-3 lipids delay the onset and progression of autoimmune lupus nephritis by inhibiting transforming growth factor beta mRNA and protein expression
image Fish oil feeding modulates leukotriene production in murine lupus nephritis
image Effects of n-3 and n-6 fatty acids on the activities and expression of hepatic antioxidant enzymes in autoimmune-prone NZBxNZW F1 mice
image Increased TGF-beta and decreased oncogene expression by omega-3 fatty acids in the spleen delays onset of autoimmune disease in B/W mice
image Decreased pro-inflammatory cytokines and increased antioxidant enzyme gene expression by omega-3 lipids in murine lupus nephritis
image Suppression of autoimmune disease by dietary n-3 fatty acids
image Role of omega-3 fatty acids in health and disease
image Dietary marine lipids suppress murine autoimmune disease
image Depression of humoral responses and phagocytic functions in vivo and in vitro by fish oil and eicosapentanoic acid
image The type of dietary fat affects the severity of autoimmune disease in NZB/NZW mice
image Effects of dietary supplementation on autoimmunity in the MRL/lpr mouse: A preliminary investigation
image A fish oil diet rich in eicosapentaenoic acid reduces cyclooxygenase metabolites, and suppresses lupus in MRL-lpr mice
image The protective effect of dietary fish oil on murine lupus
image [Use of the fish oil "Polyen" in pediatric practice]
image The effect on human tumor necrosis factor alpha and interleukin 1beta production of diets enriched in n-3 fatty acids from vegetable oil or fish oil
image Validation of a meta-analysis: The effects of fish oil in rheumatoid arthritis
image n-3 Polyunsaturated fatty acids: Update 1995
image Effects of fish oil supplementation on non-steroidal anti-inflammatory drug requirement in patients with mild rheumatoid arthritis-a double-blind placebo controlled study.
image Association of etretinate and fish oil in psoriasis therapy. Inhibition of hypertriglyceridemia resulting from retinoid therapy after fish oil supplementation.
image Effects of dietary fish oil lipids on allergic and inflammatory diseases.
image Omega-3 fatty acids in health and disease and in growth and development
image The effect of dietary fish oil supplement upon the content of dihomo-gammalinolenic acid in human plasma phospholipids.
image Effects of dietary supplementation with marine fish oil on leukocyte lipid mediator generation and function in rheumatoid arthritis.
image A double-blind placebo controlled trial of Efamol Marine on skin and joint symptoms of psoriatic arthritis.
image Fish-oil fatty acid supplementation in active rheumatoid arthritis. A double-blinded, controlled, crossover study.
image The cardiovascular protective role of docosahexaenoic acid
image Prevention of cardiac arrhythmia by dietary (n-3) polyunsaturated fatty acids and their mechanism of action
image Omega3 fatty acids in the prevention-management of cardiovascular disease Simopoulos A.P.
image Dietary fish oil: Influence on lesion regression in the porcine model of atherosclerosis
image Enhanced capacity of n-3 fatty acid-enriched macrophages to oxidize low density lipoprotein mechanisms and effects of antioxidant vitamins
image Fish oil supplementation in patients with heterozygous familial hypercholesterolemia
image Increased serum level of total homocysteine in CAPD patients: Despite fish oil therapy
image Effects of interaction of RRR-alpha-tocopheryl acetate and fish oil on low-density-lipoprotein oxidation in postmenopausal women with and without hormone-replacement therapy
image Platelets, carotids, and coronaries. Critique on antithrombotic role of antiplatelet agents, exercise, and certain diets.
image [Changes in fatty acid composition, platelet aggregability and RBC function in elderly subjects with administration of low-dose fish oil concentrate and comparison with younger subjects]
image Do fish oils prevent restenosis after coronary angioplasty?
image n-3 fatty acid incorporation into LDL particles renders them more susceptible to oxidation in vitro but not necessarily more atherogenic in vivo.
image Nutrition in inflammatory bowel disease
image Nutrition and gastrointestinal disease
image Dietary fiber and gastrointestinal disease The role of short-chain fatty acid metabolism in colonic disorders
image Nutritional issues in pediatric inflammatory bowel disease
image The starved colon - Diminished mucosal nutrition, diminished absorption, and colitis
image Nutrition and ulcerative colitis
image An enteral formula containing fish oil, indigestible oligosaccharides, gum arabic and antioxidants affects plasma and colonic phospholipid fatty acid and prostaglandin profiles in pigs
image Influence of nutrition in ulcerative colitis - The significance of nutritional care in inflammatory bowel disease
image Influence of intravenous n-3 lipid supplementation on fatty acid profiles and lipid mediator generation in a patient with severe ulcerative colitis
image The role of marine fish oils in the treatment of ulcerative colitis
image Fish oil fatty acid supplementation in active ulcerative colitis: A double-blind, placebo-controlled, crossover study
image Short chain fatty acid rectal irrigation for left-sided ulcerative colitis: A randomised, placebo controlled trial
image Special issues in nutritional therapy of inflammatory bowel disease
image A randomized controlled study of evening primrose oil and fish oil in ulcerative colitis
image Treatment of ulcerative colitis with fish oil supplementation: A prospective 12 month randomised controlled trial
image Incorporation of fatty acids from fish oil and olive oil into colonic mucosal lipids and effects upon eicosanoid synthesis in inflammatory bowel disease
image Fish oil may impede tumour angiogenesis and invasiveness by down-regulating protein kinase C and modulating eicosanoid production
image Fat, fish, fish oil and cancer
image Effect of dietary supplementation with omega-3 fatty acids on MED
image Arachidonic and docosahexanoic acid content of bovine brain myelin: Implications for the pathogenesis of multiple sclerosis
image Summary of the NATO advanced research workshop on dietary omega 3 and omega 6 fatty acids: biological effects and nutritional essentiality.
image Vasorelaxant properties of n-3 polyunsaturated fatty acids in aortas from spontaneously hypertensive and normotensive rats.
image Eicosapentaenoic acid, but not docosahexaenoic acid, increases mitochondrial fatty acid oxidation and upregulates 2,4-dienoyl-CoA reductase gene expression in rats.
image Improvement by eicosanoids in cancer cachexia induced by LLC-IL6 transplantation
image Docosahexaenoic and eicosapentaenoic acids inhibit human lymphoproliferative responses in vitro but not the expression of T cell surface activation markers
image Omega-3 polyunsaturated fatty acids: A potential new treatment of immune renal disease
image Anti-inflammatory properties of docosahexaenoic and eicosapentaenoic acids in phorbol-ester-induced mouse ear inflammation
image Beneficial effect of eicosapentaenoic and docosahexaenoic acids in the management of systemic lupus erythematosus and its relationship to the cytokine network.
image Exposure to the n-3 polyunsaturated fatty acid docosahexaenoic acid impairs alpha1-adrenoceptor-mediated contractile responses and inositol phosphate formation in rat cardiomyocytes
image Omega-3 fatty acids and prevention of ventricular fibrillation.
image N-3 but not N-6 fatty acids reduce the expression of the combined adhesion and scavenger receptor CD36 in human monocytic cells.
image Essential fatty acid metabolism in patients with essential hypertension, diabetes mellitus and coronary heart disease.
image The fatty acid composition of human gliomas differs from that found in nonmalignant brain tissue
image The effect of unsaturated fatty acids on membrane composition and signal transduction in HT-29 human colon cancer cells
image Effect of omega-3 fatty acids on the progression of metastases after the surgical excision of human breast cancer cell solid tumors growing in nude mice
image Suppression of nitric oxide production in lipopolysaccharide-stimulated macrophage cells by omega3 polyunsaturated fatty acids
image Incorporation of long-chain n-3 fatty acids in tissues and enhanced bone marrow cellularity with docosahexaenoic acid feeding in post-weanling Fischer 344 rats
image Demonstration of organotropic effects of chemopreventive agents in multiorgan carcinogenesis models.
image Long-term effects of eicosapentaenoic acid on diabetic peripheral neuropathy and serum lipids in patients with type II diabetes mellitus
image Inhibition of lipolysis and muscle protein degradation by EPA in cancer cachexia
image Comparison of the effectiveness of eicosapentaenoic acid administered as either the free acid or ethyl ester as an anticachectic and antitumour agent
image Kinetics of the inhibition of tumour growth in mice by eicosapentaenoic acid-reversal by linoleic acid
image Anticachectic and antitumor effect of eicosapentaenoic acid and its effect on protein turnover
image Altered fatty acid, cholesterol and Na+/K+ ATPase activity in erythrocyte membrane of rheumatoid arthritis patients.
image Health effects and metabolism of dietary eicosapentaenoic acid.
image [Potential value of eicosapentaenoic acid]
image Low prevalences of coronary heart disease (CHD), psoriasis, asthma and rheumatoid arthritis in Eskimos: are they caused by high dietary intake of eicosapentaenoic acid (EPA), a genetic variation of essential fatty acid (EFA) metabolism or a combination of both?
image Effects of 11-week increases in dietary eicosapentaenoic acid on bleeding time, lipids, and platelet aggregation.
image Cell cycle arrest and induction of apoptosis in pancreatic cancer cells exposed to eicosapentaenoic acid in vivo
image Dietary fats and coronary heart disease
image Eicosapentaenoic acid (C20:5) augments glucose-induced insulin secretion from beta-TC3 insulinoma cells

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Depression of humoral responses and phagocytic functions in vivo and in vitro by fish oil and eicosapentanoic acid

Virella G, Kilpatrick JM, Rugeles MT, Hyman B, Russell R.
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston 29425

Clin Immunol Immunopathol (USA), 1989, 52/2 (257-270)

 

Previous studies have demonstrated that eicosapentanoic acid (EPA) has anti-inflammatory properties in both humans and experimental animals and may also depress humoral immunity in experimental animals. Our investigations showed that the addition of eicosapentanoic acid to human peripheral blood mononuclear cell cultures inhibited B cell responses to mitogenic stimulation and depressed the expression of interleukin 2 receptors in pokeweed mitogen-stimulated lymphocytes. Neutrophils were also affected in their ability to release the contents of primary and secondary granules, particularly when stimulated with antigen-antibody complexes. Similar depressions of B cell responses and neutrophil functions were observed in a normal volunteer who ingested 6 g/day of a commercially available fish oil extract (equivalent to 2.1 g of EPA/day) during a 6-week period. Phagocytosis, enzymatic release, circulating immunoglobulin levels, and the response to tetanus toxoid both in vivo and in vitro were depressed during ingestion of fish oil. Most parameters showed a trend toward normalization 6 weeks after the suspension of fish-oil supplementation. These effects of fish oil extracts and EPA on phagocytosis and humoral responses may be advantageously used in the therapy of chronic inflammatory diseases and autoimmune diseases but could be a cause for concern when these compounds are used for longer periods of time and with minimal medical supervision for the prophylaxis of atherosclerosis.

 

The type of dietary fat affects the severity of autoimmune disease in NZB/NZW mice

Alexander NJ, Smythe NL, Jokinen MP

Am J Pathol (USA), 1987, 127/1 (106-121)

 

The type of dietary fat dramatically affects the onset of autoimmune disease in lupus-prone female New Zealand Black/New Zealand White Fsub 1 (B/W) mice. Disease development was strikingly slowed in mice fed a diet containing quantities of omega-3 fatty acids (fish oil, FO). By 10 months of age, 94% of the FO mice were still living, whereas all the mice fed a saturated fat diet (lard, L) were dead. Those mice fed a corn oil (CO) diet were intermediate with 35% alive at the 10-month time evaluation. Long after the L and CO groups had succumbed to glomerulonephritis, the FO group had negligible proteinuria. Both B and T cell function, particularly antibody production and resultant circulating immune complex (CIC) levels, were modified by the type of dietary fat. FO mice exhibited lower levels of anti-ds-DNA and lower levels of CICs than L or CO mice. B/W antibody response to a T-independent antigen (DNP-Dextran) was enhanced at 8 months of age in FO mice, whereas it was suppressed in L mice. T-dependent (sheep red blood cell) responses at that time period were reduced in all the diet groups, a reflection of the reduced numbers of accessory T cells as determined by FACS analysis. The natural killer (NK) response to YAC-1 cells decreased in the L group from 5 to 9 months of age but remained unchanged in the CO and FO groups. Severe glomerulonephritis was the most common histopathologic finding in the L and CO groups. Arteritis was found in the spleens of nearly all the L and CO mice. Arteritis of the heart, colon and intestine, stomach, kidney, and liver were also seen principally in the L. mice. In contrast, most FO mice had minimal to mild glomerulonephritis and no or minimal arteritis in the spleen. It is likely omega-3 fatty acids of fish oil reduce immune-complex-induced glomerulonephritis through production of prostaglandin metabolites with attenuated activity and/or through altering cell membrane structure and fluidity, which may, in turn, affect the responsiveness of immune cells.

 

Effects of dietary supplementation on autoimmunity in the MRL/lpr mouse: A preliminary investigation

Godfrey DG, Stimson WH, Watson J, Belch JF, Sturrock RD

Ann Rheum Dis (UK), 1986, 45/12 (1019-1024)

 

The effects of dietary fatty acid supplementation on various disease parameters in the spontaneously autoimmune MRL-mp-lpr/lpr mouse model of systemic lupus erythematosus before onset of disease were investigated. A fat deficient diet was supplemented with the following oils: olive oil, sunflower oil, evening primrose oil (EPO), fish oil, and a fish oil/EPO mixture. The mice receiving a diet enriched with EPO showed an increase in survival, as did those receiving a fish oil/EPO mixture. These results, taken together with those of the other parameters monitored, suggest that EPO may be of benefit in alleviating the murine form of the disease.

 

A fish oil diet rich in eicosapentaenoic acid reduces cyclooxygenase metabolites, and suppresses lupus in MRL-lpr mice

Kelley VE, Ferretti A, Izui S, Strom TB

J Immunol (USA), 1985, 134/3 (1914-1919)

 

Dietary supplementation of fish oil as the exclusive source of lipid suppresses autoimmune lupus in MRL-lpr mice. This marine oil diet decreases the lymphoid hyperplasia regulated by the lpr gene, prevents an increase in macrophage surface Ia expression, reduces the formation of circulating retroviral gp70 immune complexes, delays the onset of renal disease, and prolongs survival. We show that a fatty acid component uniquely present in fish oil but not in vegetable oil decreases the quantity of dienoic prostaglandin E, thromboxane B, and prostacyclin normally synthesized by multiple tissues, including kidney, lung, and macrophages, and promotes the synthesis of small amounts of trienoic prostaglandin in autoimmune mice. We suggest that this change in endogenous cyclooxygenase metabolite synthesis directly suppresses immunologic and/or inflammatory mediators of murine lupus.

 

The protective effect of dietary fish oil on murine lupus

Robinson DR, Prickett JD, Polisson R, Steinberg AD, Levine L

Prostaglandins (USA), 1985, 30/1 (51-75)

 

Dietary marine lipids markedly reduce the sensitivity of glomerulonephritis and its associated mortality in inbred strains of mice developing autoimmune disease, a model for human systemic lupus erythematosus. We report here the influence of varying the dose of menhaden oil and the timing of its administration on the mortality of female (NZB x NZW) Fsub 1 mice. After ingesting 25 wt% menhaden oil (MO) forperiods of 1.5 weeks to 12 months, there was a stable content of tissue n-3 fatty acids, with total n-3 fatty acids of 28% and 35% in spleen and liver, respectively. The extent of protection from mortality was dependent on the dose of MO with marked protection at doses of 11 to 25%, marginal protection at 5.5% and no protection at 2.5% MO. Delay in the institution of MO until ages 5 or 7 months still resulted in large reductions of mortality. Conversely, institution of a MO diet from 6 weeks until ages 5 to 7 months followed by a change to beef tallow resulted in little protection. Serum levels of 4 cyclooxygenase products were reduced ranging from 26 to 76% in mice fed MO diets, compared to mice fed beef tallow, based on radioimmunoassay. The degree of reduction in mortality on different doses of MO was correlated best with tissue levels of C22:5, and levels of C20:5 and C22:6 were similar at high and low doses of MO, suggesting that levels of 22:5 may be related to the protective effects of marine lipids on autoimmune disease.

 

[Use of the fish oil "Polyen" in pediatric practice]

Ladodo KS, Levachev MM, Naumova VI, Balabolkin II, Kutafina EK, Gorelova ZhIu, Netrebenko OK, Garankina TI, Korf II, Kulakova SN, Karagodina ZV

Vopr Pitan (Russia) 1996, (2) p22‑5

 

The effects of supplementation of basic diets with 'Polyen' in daily doses of 2.5‑4.0 g during 30‑40 days together with antioxidants were studied in patients with kidney diseases (diet No7, n = 14), different allergies (hypoallergenic diet, n = 37) and in control children (n = 12). It was shown positive dynamics in fatty acid contents in plasma and red blood cell membranes, in humoral and cell immunity indicators and in improving of clinical symptoms of diseases. 'Polyen' is recommended for wide use in pediatric practice.

 

The effect on human tumor necrosis factor alpha and interleukin 1beta production of diets enriched in n‑3 fatty acids from vegetable oil or fish oil

GE Caughey, E Mantzioris, RA Gibson, LG Cleland and MJ James
Rheumatology Unit, Royal Adelaide Hospital, Australia

American Journal of Clinical Nutrition (USA), 1996, 63/1 (116‑122)

 

The effect of a flaxseed oil‑based diet on tumor necrosis factor alpha (TNFalpha) and interleukin 1 beta (IL‑1beta) synthesis was examined in healthy volunteers. Use of flaxseed oil in domestic food preparation for 4 wk inhibited TNFalpha and IL‑1 beta production by similar 30%. Fish‑oil supplementation (9 g/d) continued for a further 4 wk; TNFalpha and IL‑1beta synthesis were inhibited by 74% and 80%, respectively. There was a significant inverse exponential relation between TNFalpha or IL‑1beta synthesis and mononuclear cell content of eicosapentaenoic acid (EPA), an n=3 fatty acid derived from ingested EPA (fish oil) or metabolism of ingested alpha‑linolenic acid (flaxseed oil). Cytokine production decreased as cellular EPA increased to similar1% of total fatty acids. Further increases in EPA content did not result in further decreases in cytokine production. The results indicate that vegetable oils rich in n=3 fatty acids inhibit TNFalpha and IL‑1beta synthesis.

 

Validation of a meta-analysis: The effects of fish oil in rheumatoid arthritis

Fortin PR, Lew RA, Liang MH, Wright EA, Beckett LA, Chalmers TC, Sperling RI.
Department of Rheumatology and Immunology, Brigham and Women's Hospital, Boston, Massachusetts, USA

Journal of Clinical Epidemiology (USA), 1995, 48/11 (1379-1390)

 

The purpose of this study was to validate the results of a meta-analysis showing the efficacy of fish oil in rheumatoid arthritis with the results of a re-analysis of the complete primary data set. A Medline search yielded seven published papers. Three additional trials were found by contacting authorities in the field. Inclusion criteria included (1) a double-blind, placebo-controlled study, (2) use of at least one of seven predetermined outcome measures, (3) results reported for both placebo and treatment groups at baseline and follow-up, (4) randomization, and (5) parallel or cross-over design. Papers were scored for quality. Demographic and outcomes variables were collected. For the re-analysis of the primary data, the same variables were abstracted for the 395 individual patients randomized. The meta-analysis demonstrated that dietary fish oil supplementation for 3 months significantly reduced tender joint count (rate difference (RD) (95% CI) = -2.9 (-3.8 to -2.1) (p = 0.001)) and morning stiffness (RD (95% CI) = -25.9 (-44.3 to -7.5) (p < 0.01)) as compared with heterogeneous dietary control oils. The re-analysis of the primary data confirmed a significant reduction in tender joint count (p = 0.001) and in morning stiffness (p < 0.02) in the parallel analysis that ignored interaction terms. The analyses that included an nteraction term between site and treatment gain confirmed a significant reduction in tender joint count. The results for morning stiffness were similar to the meta-analysis, but did not quite reach statistical significance (p = 0.052-0.083). The relative improvements in the other outcome variables did not reach statistical significance. Use of fish oil improved the number of tender joints and duration of morning stiffness at 3 months as analyzed by both meta- and mega-analysis. The fuller mega-analysis confirmed the results of the meta-analysis. The advantages of mega-analysis were as follows: (1) the ability to analyze the homogeneity of the patient populations, (2) the ability to make clinically sensible adjustments in the form of the comparison, and (3) the ability to examine subsets of the data.

 

n-3 Polyunsaturated fatty acids: Update 1995

Endres S, De Caterina R, Schmidt EB, Kristensen SD.
Medizinische Klinik, Klinikum Innenstadt der Ludwig-Maximilians-Universitat, Munich, Germany

European Journal of Clinical Investigation (United Kingdom), 1995, 25/9

 

Epidemiologic and biochemical studies have suggested an anti-inflammatory effect of n-3 fatty acids. Beneficial therapeutic effects reported from small patient groups need to be confirmed in large-cohort controlled clinical trials. There is a growing number of clinical trials of n-3 fatty acid supplementation in disease. Clinical benefits have been moderate in patients with rheumatoid arthritis and with arterial hypertension. Clearly negative results have been reported during the past 2 years for patients with lupus nephritis and for patients with psoriasis or with atopic dermatitis. Such trials have now been completed. For patients with coronary artery disease following coronary angioplasty, earlier results of a large meta-analysis; could not be confirmed. For patients with IgA-nephropathy and for patients following kidney transplantation, a clear benefit was seen in patients receiving fish oil. These promising results are currently pursued in follow-up phase III clinical trials.

 

Effects of fish oil supplementation on non-steroidal anti-inflammatory drug requirement in patients with mild rheumatoid arthritis—a double-blind placebo controlled study.

Lau CS, Morley KD, Belch JJ.
Department of Medicine, Ninewells Hospital, Dundee, Scotland

Br J Rheumatol (England) Nov 1993, 32 (11) p982-9

 

Maxepa contains eicosapentaenoic acid (EPA) (171 mg/capsule) and docosahexaenoic acid (DHA) (114 mg/capsule). EPA acts as an alternative substrate to arachidonate, leading to the formation of the less proinflammatory prostaglandins (‘3’ series) and leukotrienes (‘5’ series). If Maxepa has anti-inflammatory properties it could be expected to reduce the requirement for NSAIDs in patients with RA. This has not been investigated nor has Maxepa therapy been studied over a full 1-yr period. Sixty-four patients with stable RA requiring NSAID therapy only were studied. Patients received either 10 Maxepa or air-filled placebo capsules per day for 12 months. All then received placebo capsules for a further 3 months. Patients were reviewed at 3-monthly intervals. NSAID requirement at entry visit for each patient was assigned as 100%. Patients were instructed to slowly reduce their NSAID dosage providing there was no worsening of their symptoms. Clinical and laboratory parameters of RA activity were also measured. There was a significant reduction in NSAID usage in patients on Maxepa when compared with placebo from month 3 [mean (95% C.I. for mean) requirement--71.1 (55.9-86.2)% and 89.7 (73.7-105.7)%, respectively]. This effect reached its maximum at month 12 [40.6 (24.5-56.6)% and 84.1 (62.7-105.5)%, respectively] and persisted to month 15 [44.7 (27.6-61.8)% and 85.8 (60.5-111.1)%, respectively] (P < 0.001, ANOVA). These patients were able to reduce their NSAID requirement without experiencing any deterioration in the clinical and laboratory parameters of RA activity.

 

Association of etretinate and fish oil in psoriasis therapy. Inhibition of hypertriglyceridemia resulting from retinoid therapy after fish oil supplementation.

Frati C, Bevilacqua L, Apostolico V.
Department of Dermatology, Frosinone Hospital, Rome, Italy

Acta Derm Venereol Suppl (Stockh) (NORWAY) 1994, 186 p151-3

 

We studied the main papers concerning treatment with fish oil (EPA and DHA) of patients with psoriasis vulgaris, psoriatic arthritis and pustular psoriasis. In our investigation, 25 patients with psoriasis vulgaris evidenced a statistically significant increase in triglyceride serum levels, compared with controls. 10 of these patients underwent therapy with etretinate 0.75-1.0 mg/kg daily for 2 months followed by 2-3 months of etretinate 0.35-0.50 mg/kg daily associated with fish oil 1.5 g (EPA and DHA) daily. According with several authors, fish oil is able not only to produce good clinical results, but also to minimize the side effects of retinoid therapy, especially hypertriglyceridemia.

 

Effects of dietary fish oil lipids on allergic and inflammatory diseases.

Lee TH, Arm JP, Horton CE, Crea AE, Mencia-Huerta JM, Spur BW.
Department of Allergy and Allied Respiratory Disorders, U.M.D.S., Guy's Hospital, London, U.K

Allergy Proc (United States) Sep-Oct 1991, 12 (5) p299-303

 

Fish oil is rich in the polyunsaturated N-3 fatty acids, eicosapentaenoic (EPA) and docosahexaenoic acids (DCHA). EPA competes with arachidonic acid (AA) for metabolism by the cyclooxygenase and lipoxygenase pathways. Selective metabolites derived from EPA have reduced biological activities as compared with the AA-derived counterparts. Dietary supplementation with EPA led to incorporation of EPA into membrane phospholipids, an inhibition of 5-lipoxygenase pathway activity, and a reduction of the elaboration of platelet-activating factor. Neutrophil chemotaxis and the capacity of these cells to adhere to endothelial cells are substantially attenuated. This suggests that EPA has anti-inflammatory potential. Clinical trials in rheumatoid arthritis, psoriasis, atopic dermatitis, and bronchial asthma have shown beneficial effects. Whether the benefit obtained clinically is sufficient to replace or significantly reduce any clinical condition remains to be answered.

 

Omega-3 fatty acids in health and disease and in growth and development

AP Simopoulos
Center for Genetics, Nutrition and Health, Washington, DC 20009

Am J Clin Nutr (United States) Sep 1991, 54 (3) p438-63

 

Several sources of information suggest that man evolved on a diet with a ratio of omega 6 to omega 3 fatty acids of approximately 1 whereas today this ratio is approximately 10:1 to 20-25:1, indicating that Western diets are deficient in omega 3 fatty acids compared with the diet on which humans evolved and their genetic patterns were established. Omega-3 fatty acids increase bleeding time; decrease platelet aggregation, blood viscosity, and fibrinogen; and increase erythrocyte deformability, thus decreasing the tendency to thrombus formation. In no clinical trial, including coronary artery graft surgery, has there been any evidence of increased blood loss due to ingestion of omega 3 fatty acids. Many studies show that the effects of omega 3 fatty acids on serum lipids depend on the type of patient and whether the amount of saturated fatty acids in the diet is held constant. In patients with hyperlipidemia, omega 3 fatty acids decrease low-density-lipoprotein (LDL) cholesterol if the saturated fatty acid content is decreased, otherwise there is a slight increase, but at high doses (32 g) they lower LDL cholesterol; furthermore, they consistently lower serum triglycerides in normal subjects and in patients with hypertriglyceridemia whereas the effect on high-density lipoprotein (HDL) varies from no effect to slight increases. The discrepancies between animal and human studies most likely are due to differences between animal and human metabolism. In clinical trials eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the form of fish oils along with antirheumatic drugs improve joint pain in patients with rheumatoid arthritis; have a beneficial effect in patients with ulcerative colitis; and in combination with drugs, improve the skin lesions, lower the hyperlipidemia from etretinates, and decrease the toxicity of cyclosporin in patients with psoriasis. In various animal models omega 3 fatty acids decrease the number and size of tumors and increase the time elapsed before appearance of tumors. Studies with nonhuman primates and human newborns indicate that DHA is essential for the normal functional development of the retina and brain, particularly in premature infants. Because omega 3 fatty acids are essential in growth and development throughout the life cycle, they should be included in the diets of all humans. Omega-3 and omega 6 fatty acids are not interconvertible in the human body and are important components of practically all cell membranes. Whereas cellular proteins are genetically determined, the polyunsaturated fatty acid (PUFA) composition of cell membranes is to a great extent dependent on the dietary intake.

 

The effect of dietary fish oil supplement upon the content of dihomo-gammalinolenic acid in human plasma phospholipids.

Cleland LG, Gibson RA, Neumann M, French JK.
Rheumatology Unit, Royal Adelaide Hospital, North Terrace, Australia

Prostaglandins Leukot Essent Fatty Acids (Scotland) May 1990, 40 (1) p9-12

 

Patients (n = 23) with definite or classical rheumatoid arthritis were given 18 g/day fish oil in gelatin capsules which provided 3.2 g/day EPA and 2.0 g/day DHA. The treatment period was 12 weeks followed by a 4 week washout period. Fish oil supplementation to the diet resulted in a substantial increase in the content of EPA and DHA in each of the plasma fractions examined (PL, TG, and CE). Little change was seen in the AA level of the TG and CE fractions but a modest decrease in AA was seen in PL. However the intake of fish oil caused a significant depression in the content of DGLA in the PL (p less than 0.005) and CE (p less than 0.01) fractions relative to baseline values. All changes had reverted to near baseline levels 4 weeks after dietary intervention. Since DGLA is the precursor of PGE1, which has been shown to be anti-inflammatory, our findings suggest that the anti-inflammatory effects of fish oil consumption could be mitigated by an associated reduction in DGLA.

 

Effects of dietary supplementation with marine fish oil on leukocyte lipid mediator generation and function in rheumatoid arthritis.

Sperling RI, Weinblatt M, Robin JL, Ravalese J 3rd, Hoover RL, House F, Coblyn JS, Fraser PA, Spur BW, Robinson DR, et al.
Department of Medicine, Harvard Medical School, Boston, Massachusetts.

Arthritis Rheum (United States) Sep 1987, 30 (9) p988-97

 

Twelve patients with active rheumatoid arthritis supplemented their usual diet with 20 gm of Max-EPA fish oil, daily, for 6 weeks. Following this supplementation, the ratio of arachidonic acid to eicosapentaenoic acid in the patients’ neutrophil cellular lipids decreased from 81:1 to 2.7:1, and the mean generation of leukotriene B4 (with calcium ionophore stimulation) significantly declined by 33%. The mean neutrophil chemotaxis to both leukotriene B4 and FMLP significantly increased toward the normal range at week 6. The generation of 5-lipoxygenase products by calcium ionophore-stimulated monocytes was not significantly suppressed, but a significant decline (37%) in platelet-activating factor generation was noted at week 6. The modulation of these measures of leukocyte inflammatory potential suggests that fish oil supplementation may have an antiinflammatory effect.

 

A double-blind placebo controlled trial of Efamol Marine on skin and joint symptoms of psoriatic arthritis.

Veale DJ, Torley HI, Richards IM, O'Dowd A, Fitzsimons C, Belch JJ, Sturrock RD.
University Department of Medicine, Ninewells Hospital and Medical School, Dundee

Br J Rheumatol (England) Oct 1994, 33 (10) p954-8

 

Fish oil may be beneficial in the treatment of psoriasis and in RA. We examined the potential benefit of Efamol Marine, a combination of evening primrose oil and fish oil in the treatment of 38 patients with PsA. Patients with PsA were entered in a double-blind placebo controlled study and received either 12 Efamol Marine capsules or 12 placebo capsules daily for 9 months. All patients received placebo capsules for a further 3 months. At month 3 of the study patients were asked to reduce their intake of NSAIDs and maintain that decrease provided there was no worsening of their joint symptoms. Clinical assessments of skin and joint disease severity and activity were performed at 0, 1, 3, 6, 9 and 12 months. All measures of skin disease activity including severity, percentage body affected and itch were unchanged by Efamol Marine. The NSAID requirement remained the same between both treatment groups. In addition, there was no change demonstrated in the activity of arthritis as measured by duration of morning stiffness. Ritchie articular index, number of active joints, ESR and CRP. However, a rise in serum TXB2 was observed in the active group during the placebo phase; in addition a fall in leukotriene B4 production occurred during the active phase period followed by a marked rise during the placebo phase suggesting some laboratory documented anti-inflammatory effect. In conclusion, this study suggests that Efamol Marine may alter prostaglandin metabolism in patients with PsA, although it did not produce a clinical improvement and did not allow reduction in NSAID requirement. A larger dose of essential fatty acid may be needed to produce a clinical benefit.

 

Fish-oil fatty acid supplementation in active rheumatoid arthritis. A double-blinded, controlled, crossover study.

Kremer JM, Jubiz W, Michalek A, Rynes RI, Bartholomew LE, Bigaouette J, Timchalk M, Beeler D, Lininger L.

Ann Intern Med (United States) Apr 1987, 106 (4) p497-503

 

Study Objective: to determine the efficacy of fish-oil dietary supplements in active rheumatoid arthritis and their effect on neutrophil leukotriene levels. Design: nonrandomized, double-blinded, placebo-controlled, crossover trial with 14-week treatment periods and 4-week washout periods. Setting: academic medical center, referral-based rheumatology clinic. Patients: forty volunteers with active, definite, or classical rheumatoid arthritis. Five patients dropped out, and two were removed for noncompliance. Interventions: treatment with nonsteroidal anti-inflammatory drugs, slow-acting antirheumatic drugs, and prednisone was continued. Twenty-one patients began with a daily dosage of 2.7 g of eicosapaentanic acid and 1.8 g of docosahexenoic acid given in 15 MAX-EPA capsules (R.P. Scherer, Clearwater, Florida), and 19 began with identical-appearing placebos. The background diet was unchanged. Measurements and Main Results: the following results favored fish oil placebo after 14 weeks: mean time to onset of fatigue improved by 156 minutes (95% confidence interval, 1.2 to 311.0 minutes), and number of tender joints decreased by 3.5 (95% Cl, -6.0 to -1.0). Other clinical measures favored fish oil as well but did reach statistical significance. Neutrophil leukotriene B4 production was correlated with the decrease in number of tender joints (Spearman rank correlation r=0.53; p less than 0.05). There were no statistically significant differences in hemoglobin level, sedimentation rate, or presence of rheumatoid factor or in patient-reported adverse effects. An effect from the fish oil persisted beyond the 4-week washout period. Conclusions: fish-oil ingestion results in subjective alleviation of active rheumatoid arthritis and reduction in neutrophil leukotriene B4 production. Further studies are needed to elucidate mechanisms of action and optimal dose and duration of fish-oil supplementation.

 

The cardiovascular protective role of docosahexaenoic acid

McLennan P, Howe P, Abeywardena M, Muggli R, Raederstorff D, Mano M, Rayner T, Head R.
CSIRO Division of Human Nutrition, Adelaide, South Australia, Australia

European Journal of Pharmacology (Netherlands), 1996, 300/1‑2 (83‑89)

 

Dietary fish oils rich in n‑3 polyunsaturated fatty acids can modulate a diverse range of factors contributing to cardiovascular disease. This study examined the relative roles of eicosapentaenoic acid (20:5 n‑3; EPA) and docosahexaenoic acid (22:6 n‑3; DHA) which are the principal n‑3 polyunsaturated fatty acids regarded as candidates for cardioprotective actions. At low dietary intakes (0.4‑1.1% of energy (%en)), docosahexaenoic acid but not eicosapentaenoic acid inhibited ischaemia‑induced cardiac arrhythmias. At intakes of 3.9‑10.0%en, docosahexaenoic acid was more effective than eicosapentaenoic acid at retarding hypertension development in spontaneously hypertensive rats (SHR) and inhibiting thromboxane‑like vasoconstrictor responses in aortas from SHR. In stroke‑prone SHR with established hypertension, docosahexaenoic acid (3.9‑10.0%en) retarded the development of salt‑loading induced proteinuria but eicosapentaenoic acid alone was ineffective. The results demonstrate that purified n‑3 polyunsaturated fatty acids mimic the cardiovascular actions of fish oils and imply that docosahexaenoic acid may be the principal active component conferring cardiovascular protection.

 

Prevention of cardiac arrhythmia by dietary (n‑3) polyunsaturated fatty acids and their mechanism of action

Nair SS, Leitch JW, Falconer J, Garg ML

Journal of Nutrition (USA), 1997, 127/3 (383‑393)

 

The role of marine fish oil (n‑3) polyunsaturated fatty acids in the prevention of fatal ventricular arrhythmia has been established in experimental animals. Prevention of arrhythmias arising at the onset of ischemia and reperfusion is important because if untreated, they result in sudden cardiac death. Animals supplemented with fish oils in their diet developed little or no ventricular fibrillation after ischemia was induced. Similar effects have also been observed in cultured neonatal cardiomyocytes. Several mechanisms have been proposed and studied to explain the antiarrhythmic effects of fish oil polyunsaturated fatty acids, but to date, no definite mechanism has been validated. The sequence of action of these mechanisms and whether more than one mechanism is involved is also not clear. Some of the mechanisms suggested to explain the antiarrhythmic action of fish oils include the incorporation and modification of cell membrane structure by (n‑3) polyunsaturated fatty acids, their direct effect on calcium channels and cardiomyocytes and their role in eicosanoid metabolism. Other mechanisms that are currently being investigated include the role of (n‑3) polyunsaturated fatty acids in cell signalling mediated through phosphoinositides and their effect on various enzymes and receptors. This article reviews these mechanisms and the antiarrhythmic studies using (n‑3) polyunsaturated fatty acids.

 

Omega3 fatty acids in the prevention‑management of cardiovascular disease

Simopoulos A.P.

Center for Genetics, Nutrition and Health, Washington, DC 20009, USA

Canadian Journal of Physiology and Pharmacology (Canada), 1997, 75/3 (234‑239)

 

Epidemiologic studies show that populations who eat fish versus those who do not have a reduced death rate from cardiovascular disease. Experimental studies have shown that omega‑3 fatty acids affect the function of cells involved in atherothrombosis in numerous ways, including the modification of eicosanoid products in the cyclooxygenase and lipoxygenase pathways, the reduced synthesis of cytokines and platelet‑derived growth factor, and alterations of leukocyte and endothelial cell properties. Intervention studies in patients with restenosis, myocardial infarction, and cardiac arrhythmias with omega‑3 fatty acid supplementation have been addressed in several clinical studies. The ingestion of omega‑3 fatty acids following one episode of myocardial infarction appears to decrease the rate of cardiac death. These effects of omega‑3 fatty acids appear to be due to their antiarrhythmic properties. In fact, fish oil has been shown to reduce ventricular arrhythmias and to be more beneficial than currently used pharmacologic agents. The dose, duration, and mechanisms involved in the prevention and management of cardiovascular disease following omega‑3 fatty acid ingestion or supplementation need to be investigated by double blind controlled clinical trials.

 

Dietary fish oil: Influence on lesion regression in the porcine model of atherosclerosis

Barbeau ML, Klemp KF, Guyton JR, Rogers KA.
Department of Anatomy and Cell Biology, University of Western Ontario (London), Canada

Arteriosclerosis, Thrombosis, and Vascular Biology (USA), 1997, 17/4 (688‑694)

 

We examined the influence of dietary fish oil on lesion regression in a porcine model of atherogenesis. Thirty‑two female Yucatan miniature pigs were fed an atherogenic diet for 8 months. A no‑regression group (n=8) was killed to determine the extent of atherosclerosis at 8 months. Three regression groups were switched to normal minipig chow supplemented with either MaxEPA fish oil (FO group, n=8), a control oil with the ratio of polyunsaturated to monounsaturated to saturated fatty acid matched to that of the fish oil (CO group, n=8), or no oil supplement (NO group, n=8) for a further 4 months. Plasma cholesterol levels reached between 15 and 20 mmol/L during the atherogenic phase and returned to normal (2 mmol/L) within 2 months of the beginning of the regression diet. Compared with the NO group, fish oil supplementation during the regression phase caused a decrease in VLDL and HDL cholesterol and an increase in LDL cholesterol. Similarly, the control oil also caused a decrease in VLDL cholesterol; however, in contrast to the FO group, HDL cholesterol increased and LDL cholesterol was unchanged. FO LDL, which had decreased levels of 20:4 (n‑6 fatty acid) and increased levels of 18:3, 20:5, and 22:6 (n‑3 fatty acids), was shown to be twice as susceptible to copper‑mediated oxidation as CO LDL particles. Morphological examination of the major blood vessels revealed a significant reduction in lesion area in the ascending and thoracic aorta as well as the carotid artery after the regression diet; however, there was no significant difference between the fish oil and control oil groups in any of the vessels measured. Therefore, despite increased LDL, decreased HDL and an increased susceptibility to in vitro oxidation of LDL, fish oil supplementation of a regression diet did not influence lesion regression.

 

Enhanced capacity of n‑3 fatty acid‑enriched macrophages to oxidize low density lipoprotein mechanisms and effects of antioxidant vitamins

Suzukawa M, Abbey M, Clifton P, Nestel PJ.
CSIRO, Division of Human Nutrition, Adelaide, Australia

Atherosclerosis (Ireland), 1996, 124/2 (157‑169)

 

We have investigated possible mechanisms by which n‑3 fatty acid‑enriched macrophages enhance the oxidation of low density lipoprotein (LDL), and the ability of antioxidant vitamins to prevent this. Macrophages were enriched with n‑3 fatty acids (eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid) following incubation with fish oil. These macrophages produced large amount of TEARS in medium containing metals, and showed enhanced capacity to oxidize LDL (3‑4 fold increase compared to control cells) and to accumulate the modified LDL. 5,8,11,14‑eicosatetraynoic acid (ETYA, 15‑lipoxygenase inhibitor) and superoxide dismutase (SOD) did not inhibit the enhanced capacity of n‑3 fatty acid‑enriched cells to oxidize LDL. However antioxidants, (vitamin E‑enriched macrophages or vitamin C in the medium), inhibited this enhanced capacity. Medium conditioned by n‑3 fatty acid‑enriched cells had pro‑oxidant effects on metal‑initiated LDL oxidation. We conclude that n‑3 fatty acid‑enriched macrophages display increased oxidant capacity which is not inhibited by ETYA or SOD, and that antioxidant vitamins inhibit the enhanced capacity to oxidize LDL.

 

Fish oil supplementation in patients with heterozygous familial hypercholesterolemia

Balestrieri GP, Maffi V, Sleiman I, Spandrio S, Di Stefano O, Salvi A, Scalvini T.
Clinica Medica, Universita, Brescia

Recenti Progressi in Medicina (Italy), 1996, 87/3 (102‑105)

 

Familial hypercholesterolemia is associated with premature coronary heart disease. In patients with familial hypercholesterolemia, monotherapy with hydroxymethylglutaryl coenzyme A reductase inhibitors rarely achieves the goal of desirable low‑density lipoprotein levels. Epidemiological studies suggest that populations with a high dietary intake of marine n3 fatty acids are protected against coronary heart disease. Hepatic synthesis and secretion of very low density lipoproteins are reduced during fish oil supplementation while other effects on lipid and lipoprotein metabolism are controversial. Fourteen patients affected by familial heterozygous hypercholesterolemia on chronic treatment with simvastatin were enrolled in a double blind, placebo controlled, randomized cross‑over trial that evaluated the effect of fish oil ethyl ester (Esapent, 5.1 g/day) on lipid and lipoprotein serum concentrations. Total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, apoprotein B, apoprotein AI, lipoprotein (a) did not show any significant variation during the four week treatment period with fish oil ethyl ester. The present data suggest that the possible favourable influence of fish oil on the progression of atherosclerosis in these high‑risk patients might involve mechanisms which are different from lipid metabolism.

 

Increased serum level of total homocysteine in CAPD patients: Despite fish oil therapy

Holdt B, Korten G, Knippel M, Lehmann JK, Claus R, Holtz M, Hausmann S.
University of Rostock, Germany

Peritoneal Dialysis International (Canada), 1996, 16/SUPPL. 1(S246‑S249)

 

It has been shown that serum total homocysteine (HC) is a risk factor for vascular disease which characterizes endothelial damage. The incidence of vascular disease is increased in continuous ambulatory peritoneal dialysis (CAPD) patients. Our aim was to investigate: (1) whether concentration of HC correlates with atherosclerotic and inflammatory events, and (2) if fish oil therapy can retard the disturbance In lipid metabolism which promotes atherosclerosis. Fourteen patients with various degrees of impaired peritoneal clearance and lipid metabolism were observed. In all patients the serum HC was elevated. Seven patients were treated with fish oil for three months. The results indicate an average increase of HC (+18%), total cholesterol (+6.6%), aggregation of erythrocytes (+9%), and an average decrease of dialysate‑to‑plasma creatinine (D/P) ratio (‑7%), deformability of erythrocytes (‑8%), and normalization of elevated soluble interleukin‑2 receptor (sIL‑2R) values. Regression analysis of all data demonstrated a significant correlation between HC and parameters of lipid metabolism and hemorheology. There were no significant correlations between HC and peritoneal function and serum cytokine levels. We conclude that the treatment in CAPD patients with fish oil did not improve the lipid metabolism disturbances in atherosclerosis and peritoneal function. Elevated HC confirms the progression of the disease.

 

Effects of interaction of RRR‑alpha‑tocopheryl acetate and fish oil on low‑density‑lipoprotein oxidation in postmenopausal women with and without hormone‑replacement therapy

Wander RC, Du SH, Ketchum SO, Rowe KE.
Department of Nutrition and Food Management, Oregon State University, Corvallis 97331, USA

American Journal of Clinical Nutrition (USA), 1996, 63/2 (184‑193)

 

We evaluated the effects of RRR‑alpha‑tocopheryl acetate (alpha‑tocopheryl acetate) and hormone‑replacement therapy (HRT) on the oxidative susceptibility of low‑density lipoprotein (LDL) in postmenopausal women consuming a fish oil supplement. The independent effect of fish oil was also assessed. Forty‑eight women, equally divideed in a double‑blind cross over trial. Each of the four periods lasted 5 wk and was followed by a 4‑wk washout interval. During each period all subjects were given a 15‑g supplement of fish oil and either 0 (placebo), 100, 200, or 400 mg alpha‑tocopheryl acetate daily. LDL resistance to oxidative modification was assessed by calculating lag time, propagation rate, and maximum production of conjugated dienes. Supplementation with fish oil and placebo shortened lag time and slowed propagation rate in women both using and not using HRT. After subjects consumed fish oil, supplementation with alpha‑tocopheryl acetate in creased plasma and LDL alpha‑tocopherol contents significantly and lengthened lag time (at even the lowest concentration) but had no significant effect on propagation rate or maximum production compared with values measured after consumption of fish oil alone. Women not using HRT had faster propagation rates and higher maximum production than women using HRT; after supplementation with fish oil and alpha‑tocopheryl acetate these differences prevailed. Supplements as low as 100 mg alpha‑tocopheryl acetate/d increase the resistance of LDL to oxidation when fish oil supplements are used. HRT and fish oil supplements may independently affect LDL oxidative susceptibility.

 

Platelets, carotids, and coronaries. Critique on antithrombotic role of antiplatelet agents, exercise, and certain diets.

Eichner ER

Am J Med (United States) Sep 1984, 77 (3) p513-23

 

“Antiplatelet” drugs and certain life styles seem to have an “antithrombotic” effect that may help protect against stroke and heart attack. This review of the experience with aspirin, dipyridamole, and sulfinpyrazone offers new interpretations of some of the major clinical trials, suggests guidelines for use of antiplatelet drugs, and integrates novel observations on diet and exercise into the “thromboxane- prostacyclin balance” hypothesis. It is argued that the Canadian stroke study showed that aspirin protects men with transient ischemic attacks from coronary death as well as from stroke, that type II errors may have been made in some clinical trials, that aspirin protects women as well as men, that aspirin benefits patients who have had a heart attack, that the effect of aspirin in angina varies with the type of angina, that the dose of aspirin used may not be critical, that guidelines for use of dipyridamole and sulfinpyrazone are still inconclusive, and that exercise and fish oil supplements may be “antithrombotic.” (100 Refs.)

 

[Changes in fatty acid composition, platelet aggregability and RBC function in elderly subjects with administration of low-dose fish oil concentrate and comparison with younger subjects]

Terano T, Kobayashi S, Tamura Y, Yoshida S, Hirayama T.
Second Department of Internal Medicine, Chiba University, School of Medicine

Ronen Igakkai Zasshi (Japan) Aug 1994, 31 (8) p596-603

 

Anti-thrombotic and anti-atherogenic effects of eicosapentaenoic acid (EPA) through the modulation of various cell functions related to thrombogenesis have been reported recently. We previously reported that the administration of EPA at low doses could more effectively elevate the plasma EPA concentration in elderly subjects than in younger ones. Magnetic resonance imaging examination of the brain often reveals lacunar lesions in elderly subjects without any signs or symptoms of cerebrovascular diseases. In this study we clarified the effect of administration of low doses of fish oil concentrate on platelet and RBC function in elderly subjects, compared with younger subjects. Thirty six elderly subjects (mean age 78) without any signs or symptoms of cerebrovascular diseases, all receiving the same diet in the same lodging house for the aged, were divided into 3 groups. Different amounts of fish oil concentrate (0.25-0.5 g/day of EPA) were administered to the 3 groups, daily for more than 1 month. Changes of plasma fatty acid composition, platelet aggregability, whole blood viscosity and RBC deformability was examined before and after EPA administration. One month after EPA treatment, the plasma EPA content had increased dose dependently, with suppression of platelet aggregation and improvement of RBC function. In younger subjects receiving the same amount of EPA, the elevation of plasma EPA was less than that observed in the elderly. In summary, low dose EPA administration can improve the function of platelet and RBC to an anti-thrombotic state and would be useful to prevent the occurrence of cerebrovascular diseases in elderly subjects without any side effects.

 

Do fish oils prevent restenosis after coronary angioplasty?

Leaf A, Jorgensen MB, Jacobs AK, Cote G, Schoenfeld DA, Scheer J, Weiner BH, Slack JD, Kellett MA, Raizner AE, et al.
Massachusetts General Hospital, Charlestown 02129

Circulation (United States) Nov 1994, 90 (5) p2248-57

 

BACKGROUND—The omega-3 polyunsaturated fatty acids derived from fish oils have been shown to modulate many factors believed to affect the pathogenesis of atherosclerosis. Because certain features of restenosis following angioplasty mimic some of the early changes of atherogenesis, some researchers have suggested that fish oil might prevent restenosis following angioplasty. We report the effects of omega-3 fatty acids on the rate of restenosis following percutaneous intraluminal coronary angioplasty (PTCA). METHODS AND RESULTS—From August 1989 through September 1992, 551 patients were randomized to start receiving a daily dietary supplement of ten 1.0-g capsules containing 80.6% ethyl esters of omega-3 fatty acids providing 4.1 g eicosapentaenoic acid (EPA) and 2.8 g docosahexaenoic acid (DHA) for 6 months or an equal amount of an ethyl ester of corn oil. Four hundred seventy subjects who were well matched for risk factors completed successful angioplasty of one or multiple lesions in native coronary vessels and constituted the study cohort, of whom 447 were evaluable at 6 months after PTCA. The criteria for restenosis were that the quantitative coronary angiography at 6 months show a > 30% increase in narrowing at the stenosis site or loss of at least half of the gain achieved at the time of PTCA and final restenosis with < 50% luminal diameter remaining. In 93% of the patients, the end point was determined by angiography and in all except 1% of these by quantitative coronary angiography. Compliance with the fish oil supplement was good as judged by incorporation of EPA and DHA in plasma and red blood cell phospholipids. The restenosis rate among analyzable patients was 46% for corn oil and 52% for fish oil (P = .37). The addition of 200 mg alpha-tocopherol for all subjects during the study had no effect on restenosis rates. CONCLUSIONS—This was the largest of such trials to date, and a supplement of 8 g/d of omega-3 fatty acids failed to prevent the usual high rate of restenosis after PTCA. No adverse effects were attributable to this large daily supplement of omega-3 fatty acids.

 

n-3 fatty acid incorporation into LDL particles renders them more susceptible to oxidation in vitro but not necessarily more atherogenic in vivo.

Whitman SC, Fish JR, Rand ML, Rogers KA.
Department of Anatomy, University of Western Ontario, London, Canada.

Arterioscler Thromb (United States) Jul 1994, 14 (7) p1170-6

 

The hypothesis that n-3 fatty acid incorporation into low- density lipoprotein (LDL) particles renders them more susceptible to oxidative modification and possibly more atherogenic was tested using two groups of female Yucatan miniature swine (10 animals per group) fed an atherogenic diet for 8 months. As a supplement to the atherogenic diet, the first group received a daily oral dose of the fish oil (FO) concentrate MaxEPA, rich in n-3 fatty acids, while the second group received the same dosage of a control oil (CO) low in n-3 fatty acids but with the same ratio of polyunsaturated to monounsaturated to saturated fatty acids as MaxEPA. At 8 months, the animals were killed and perfusion fixed, and all major vessels were removed for morphological assessment of atherosclerotic lesion area. Before fixation, blood samples were collected from all 20 pigs, and LDL ( d = 1.019 to 1.063 g/mL) was separated from the plasma by ultracentrifugation. A series of in vitro oxidative modification reactions were carried out by incubating the LDL with a copper sulfate solution. The susceptibility of each LDL preparation to oxidation was determined by measuring both the formation of conjugated dienes and the relative mobility of each sample in an agarose gel. The incorporation of n-3 fatty acids into LDL particles decreased the lag phase by 30%, resulting in an increased mobility of FO-LDL (compared with CO-LDL) when incubated for 0.5 to 12 hours, but at longer incubation times (18 to 24 hours), the extent of modification between the two groups became equal.(ABSTRACT TRUNCATED AT 250 WORDS)

 

Nutrition in inflammatory bowel disease

Steinhart A.H.; Greenberg G.R.

Canada

Current Opinion in Gastroenterology (USA), 1997, 13/2 (140‑145)

 

Nutrition is an important aspect of the inflammatory bowel diseases (IBDs), ulcerative colitis and Crohn's disease. Components of the diet and the nutritional status of an individual patient may impact on IBD, and the diseases themselves may in turn impact on nutritional status. In this review we highlight recent advances in the field of nutrition and IBD. A topic of particular interest over the past year is the effect of nutrients, particularly fish oils and glutamine, on gut inflammation and permeability, bacterial translocation, and cytokine profiles in humans and in experimental models of IBD. It appears that fish oil may be a useful therapeutic agent in the management of Crohn's disease. Over the past year, data from previous trials of enteral feeds for the treatment of Crohn's disease have been summarized in three meta‑analyses, and further clinical experience with the long‑term use of enteral feeds in pediatric patients has been published. Significant interest continues in the abnormalities of colonocyte metabolism in ulcerative colitis and the role of diminished short‑chain fatty acid production or use in the pathogenesis of ulcerative colitis. Several additional reports on the use of topical short‑chain fatty acid enemas for the treatment of distal ulcerative colitis have appeared in the literature.

 

Nutrition and gastrointestinal disease

O'Keefe S.J.D.

Gastrointestinal Clinic, Groote Schuur Hospital, Observatory 7925, Cape Town South Africa

Scandinavian Journal of Gastroenterology, Supplement (Norway), 1996, 31/220 (52‑59)

 

Nutrition and intestinal function are intimately interrelated. The chief purpose of the gut is to digest and absorb nutrients in order to maintain life. Consequently, chronic gastrointestinal (GI) disease commonly results in malnutrition and increased morbidity and mortality. For example, studies have shown that 50‑70% of adult patients with Crohn's disease were weight‑depleted and 75% of adolescents growth‑retarded. On the other hand, chronic malnutrition impairs digestive and absorptive function because food and nutrients are not only the major trophic factors to the gut but also provide the building blocks for digestive enzymes and absorptive cells. For example, recent studies of ours have shown that a weight loss of greater than 30% accompanying a variety of diseases was associated with a reduction in pancreatic enzyme secretion of over 80%, villus atrophy and impaired carbohydrate and fat absorption. Finally, specific nutrients can induce disease, for example, gluten‑sensitive enteropathy, whilst dietary factors such as fibre, resistant starch, short‑chain fatty acids, glutamine and fish oils may prevent gastrointestinal diseases such as diverticulitis, diversion colitis, ulcerative colitis, colonic adenomatosis and colonic carcinoma. The role of dietary antigens in the aetiology of Crohn's disease is controversial, but controlled studies have suggested that elemental diets may be as effective as corticosteroids in inducing a remission in patients with acute Crohn's disease. In conclusion, nutrition has both a supportive and therapeutic role in the management of chronic gastrointestinal diseases. With the development of modern techniques of nutritional support, the morbidity and mortality associated with chronic GI disease can be reduced. On the other hand, dietary manipulation may be used to treat or prevent specific GI disorders such as coeliac disease, functional bowel disease, Crohn's disease and colonic neoplasia. The future development of nutria‑pharmaceuticals is particularly attractive in view of their low cost and wide safety margins.

 

Dietary fiber and gastrointestinal disease  The role of short‑chain fatty acid metabolism in colonic disorders

Rabassa A.A.; Rogers A.I.

Veterans Administration Medical Center, 1201 NW 16th Street, Miami, FL 33125 USA

Am J Gastroenterol (USA), 1992, 87/4 (419‑423)

 

During the past decade it has become evident that colonic mucosal metabolism is more complex than previously suspected. Luminal short‑chain fatty acids (SCFAs) are recognized as an essential fuel source for colonocytes, particularly in the distal colon. Their absence may explain the development of diversion colitis; however, this has not been confirmed by clinical trials. The histologic, endoscopic, and metabolic similarities between diversion colitis and ulcerative colitis suggest that a nutritional SCFA deficiency state may play a role in the pathogenesis of these disorders. Diversion colitis and continent urinary diversion, utilizing distal and proximal colon reservoirs, provide in vivo models to study normal colonic mucosa in circumstances of reduced intraluminal SCFA concentrations and altered luminal effluent. Further studies utilizing these models would enhance our understanding of the regional differences in mucosal cell metabolism and adaptability and, hopefully, provide therapeutic alternatives for the management of colonic disorders. The welfare of colonic mucosa, as it relates to SCFA metabolism, awaits another exciting decade of investigation.

 

Nutritional issues in pediatric inflammatory bowel disease

Seidman E.; LeLeiko N.; Ament M.; Berman W.; Caplan D.; Evans J.; Kocoshis S.; Lake A.; Motil K.; Sutphen J.; Thomas D.

Division of Gastroenterology, Hopital Ste‑Justine, 3175 Cote Ste‑Catherine Road, Montreal, Que. H3T 1C5 Canada

J Pediatr Gastroenterol Nnutr (USA), 1991, 12/4 (424‑438)

 

Malnutrition, characterized by weight loss, growth failure and micronutrient depletion, are prominent features of inflammatory bowel disease (IBD) in the pediatric age group. Accurate evaluation of the patient's nutritional status and appropriate nutritional support, whether enteral or parenteral, constitute integral parts of the management of the growing child with IBD. Over the past two decades, a number of studies have supported the potential use of nutritional therapy to induce remission and to control disease activity in symptomatic Crohn's disease. More recently, preliminary studies on the use of dietary supplements of marine‑oil‑derived omega‑3 fatty acids have also indicated a beneficial effect in IBD patients. In parallel with these clinical trials, scientific research has recently focused on the concept that specific dietary alterations can modulate the immune response. Components of the diet that may have particular relevance to mucosal immunity and the pathogenesis of IBD include polyunsaturated fatty acids, nucleotides, and amino acids such as glutamine and arginine. Future research in the interactions between specific nutrients and the immune system will likely increase our understanding of the causes of IBD, as well as enhance the development of novel nutritional therapies for IBD patients.