Información Med-Line sobre eficacia de omega tres

UTILIDAD DE ÁCIDOS GRASOS OMEGA-3 EN PATOLOGÍA HUMANA. Fuente Medline (http//:www.ncbi.nlm.nim.gov/PubMed/ - Search Terms: “omega-3 acid and

double-blind and trial”)

Hipertensión

Howe PR, Lungershausen YK, Cobiac L, Dandy G, Nestel PJ.Effect of sodium restriction and fish oil supplementation on BP and thrombotic risk factors in patients treated with ACE inhibitors. J Hum Hypertens 1994;8(1):43-9CSIRO Division of Human Nutrition, Adelaide, South Australia.Effects of dietary sodium restriction combined with fish oil supplementation on BP and related risk factors were assessed in hypertensives treated with angiotensin converting enzyme (ACE) inhibitors. After a four week run-in phase, a six week intervention trial was conducted in which four matched groups of 14 patients, taking either captopril or enalapril, were assigned to one of four dietary treatments: low sodium (80 mmol/day) with fish oil (5 g of omega-3 fatty acids per day); normal sodium (150 mmol/day) with fish oil; low sodium with olive oil; normal sodium with olive oil. All subjects adopted a low sodium diet and adjustments of nutrient intake were made by double-blind administration of sodium and oils in supplementary tablets and capsules. BP fell in all treatment groups during intervention. However, the reduction of SBP was 4.2 mmHg greater in subjects on a low sodium intake than in those taking normal sodium. There were no differences in BP between those taking olive oil and those taking fish oil but plasma triglycerides and serum thromboxane production were reduced by 27% and 51%, respectively in the latter. Thus the antihypertensive effect of ACE inhibitors can be augmented by sodium restriction alone but supplementing the diet with fish oil may yield additional cardiovascular benefits.PMID: 8151606

Lungershausen YK, Howe PR. Improved detection of a blood pressure response to dietary intervention with 24-hour ambulatory monitoring. Am J Hypertens 1994; 7(12):1115-7CSIRO Division of Human Nutrition, Adelaide, South Australia. Ambulatory blood pressure (ABP) monitoring was undertaken in 25 hypertensives on beta-blocker monotherapy who completed a double-blind crossover trial to compare the effects of fish oil and corn oil supplements on BP. Clinic BP was measured with a Dinamap monitor on two consecutive days at the end of each treatment phase. ABP was recorded during the intervening 24-h period with a Spacelabs 90207 monitor. Averages of 24-h, daytime, and nighttime ABP readings correlated closely with Dinamap readings. Within-subject BP differences between fish oil and corn oil treatment were similar for Dinamap (3.2 +/- 1.8/2.5 +/- 1.0 mm Hg) and for 24-h ABP (2.5 +/- 1.0/2.3 +/- 0.8 mm Hg), but were more significant with the latter. Thus detection of the antihypertensive effects of dietary intervention can be improved by the use of ABP. PMID: 7702808

Lungershausen YK, Abbey M, Nestel PJ, Howe PR. Reduction of blood pressure and plasma triglycerides by omega-3 fatty acids in treated hypertensives. J Hypertens 1994;12(9):1041-5 CSIRO Division of Human Nutrition, Adelaide, South Australia.OBJECTIVE: To assess the effects of omega-3 (n-3) fatty acid supplementation on blood pressure and plasma lipids in hypertensives treated with diuretics or beta-blockers. DESIGN: Double-blind -controlled cross-over trial consisting of a 4-week run-in phase and two 6-week intervention phases. PATIENTS: A total of 43 patients of either sex taking a beta-blocker only (n = 29), a diuretic only (n = 3) or a beta-blocker plus diuretic (n = 11) for hypertension were recruited from

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general practice. One patient from the latter group was withdrawn. METHODS: Seated blood pressure was measured every 2 weeks in the clinic with a Dinamap. After the run-in phase, participants were randomly assigned to take a supplement of either Omacor (85% n-3 fatty acid concentrate) or corn oil (four 1-g capsules/day) for 6 weeks, after which they crossed over to the other supplement. Fasted blood samples were taken at the end of each phase for lipid analysis. MAIN OUTCOME MEASURES: The within-individual differences in systolic and diastolic pressure and plasma lipids between Omacor and corn oil treatment. RESULTS: Systolic/diastolic blood pressures measured during the run-in phase were normal (132 +/- 2/76 +/- 1 mmHg, n = 42) but decreased further with n-3 fatty acid supplementation. The mean within-individual difference in blood pressure compared with corn oil supplementation was 3.1 +/- 1.0/1.8 +/- 0.6 mmHg (P < 0.01). This was accompanied by a 21% reduction in plasma triglycerides (P < 0.01) and a 15% increase in high-density lipoprotein-2 cholesterol (P < 0.01) but there were no significant differences in total or low-density lipoprotein cholesterol. CONCLUSION: The antihypertensive and hypo-triglyceridaemic effects of n-3 fatty acid supplementation seen in the present study suggest that it may be a useful adjunct to antihypertensive therapy with beta-blockers or diuretics.PMID: 7852747

Zakaria B, Bertsch S. [Low-dose omega-3 fatty acids as lipid lowering agents in the practice. A field study of ambulatory patients in general practice] Fortschr Med 1992 10;110(10):178-82BASICS: Clinical trials have shown that omega-3 fatty acids are also effective at smaller doses than those so far recommended for lowering lipid concentrations. AIMS: Testing this finding in a large number of unselected outpatients. STUDY: Open multicentric trial involving 197 patients with dyslipoproteinemia. Treatment comprised omega-3 fatty acids, 1.1 to 1.4 g per day administered for a period of 12 weeks. RESULTS: After 12 weeks of treatment,

serum triglycerides decreased on average by about 23%, total cholesterol by about 10%, and LDL cholesterol by about 5%. HDL cholesterol rose by an average of 16%. The fish oil preparation (Eicosapen, Nycomed, Munich) was well tolerated; a fishy taste and mild gastrointestinal complaints led to discontinuation of treatment in only four cases. It was also found that the effect of omega-3 fatty acids was appreciably greater in hypertensives than in patients with normal blood pressure--not only on systolic and diastolic blood pressure, but also on serum triglycerides and HDL.PMID: 1577358

Bonaa KH, Bjerve KS, Straume B, Gram IT, Thelle D. Effect of eicosapentaenoic and docosahexaenoic acids on blood pressure in hypertension. A population-based intervention trial from the Tromso study. N Engl J Med 1990 22;322(12):795-801Institute of Community Medicine, University of Tromso, Norway.Studies of whether polyunsaturated fatty acids in fish oil--in particular, eicosapentaenoic and docosahexaenoic acids--lower blood pressure have varied in design and results. We conducted a population-based, randomized, 10-week dietary-supplementation trial in which the effects of 6 g per day of 85 percent eicosapentaenoic and docosahexaenoic acids were compared with those of 6 g per day of corn oil in 156 men and women with previously untreated stable, mild essential hypertension. The mean systolic blood pressure fell by 4.6 mm Hg (P = 0.002), and diastolic pressure by 3.0 mm Hg (P = 0.0002) in the group receiving fish oil; there was no significant change in the group receiving corn oil. The differences between the groups remained significant for both systolic (6.4 mm Hg; P = 0.0025) and diastolic (2.8 mm Hg; P = 0.029) pressure after control for anthropometric, lifestyle, and dietary variables. The decreases in blood pressure were larger as concentrations of plasma phospholipid n-3 fatty acids increased (P = 0.027). Dietary supplementation with fish oil did not change mean blood

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pressure in the subjects who ate fish three or more times a week as part of their usual diet, or in those who had a base-line concentration of plasma phospholipid n-3 fatty acids above 175.1 mg per liter. We conclude that eicosapentaenoic and docosahexaenoic acids reduce blood pressure in essential hypertension, depending on increases in plasma phospholipid n-3 fatty acids.PMID: 2137901

Hiperlipidemia

Conquer JA, Holub BJ. Supplementation with an algae source of docosahexaenoic acid increases n- fatty acid status and alters selected risk factors for heart disease in vegetarian subjects. J Nutr 1996;126(12):3032-9Department of Human Biology and Nutritional Sciences, University of Guelph, Ontario, Canada.The purpose of this double-blind study was to investigate the influence of dietary supplementation with an algae source of docosahexaenoic acid [DHA; 22:6(n-3)], devoid of any eicosapentaenoic acid [EPA; 20:5(n-3)], on serum/platelet DHA status, the estimated retroconversion of DHA to EPA, and risk factors for heart disease in vegetarian subjects. Healthy vegetarians (12 male, 12 female) consumed nine capsules daily of either DHA (1.62 g/d) or corn oil for 6 wk. Consumption of DHA capsules increased DHA levels in serum phospholipid by 246% (from 2.4 to 8.3 g/100 g fatty acids) and in platelet phospholipid by 225% (from 1.2 to 3.9 g/100 g fatty acids). EPA levels increased in serum phospholipid by 117% (from 0.57 to 1.3 g/100 g fatty acids) and in platelet phospholipid by 176% (0.21 to 0.58 g/100 g fatty acids) via metabolic retroconversion; the estimated extent of DHA retroconversion to EPA was 11.3 and 12.0%, based on the serum and platelet analyses, respectively. Arachidonic acid [AA; 20:4(n-6)] levels in serum and platelet phospholipids decreased moderately during the trial period (DHA group) as did both docosapentaenoic acids [22:5(n-6) and 22:5(n-3)]. Although no

significant changes were found in the total and LDL-cholesterol levels with DHA supplementation, the total cholesterol:HDL-cholesterol ratio showed a moderate decrease over time as did the LDL-cholesterol:HDL-cholesterol ratio and serum triglyceride concentrations. DHA supplementation did not alter the various thrombogenic factors measured. In conclusion, DHA supplementation markedly enhanced the DHA status (of serum and platelets), provided for the formation of substantial EPA, and lowered the total and LDL-cholesterol:HDL-cholesterol ratiosPMID: 9001371

Mueller BA, Talbert RL, Tegeler CH, Prihoda TJ. The bleeding time effects of a single dose of aspirin in subjects receiving omega-3 fatty acid dietary supplementation. J Clin Pharmacol 1991; 31(2):185-90Department of Pharmacy Practice, School of Pharmacy and Pharmacol Sciences, Purdue University, West Lafayette, Indiana.Dietary supplementation with omega-3 fatty acids reduces platelet aggregation in subjects who usually eat a diet low in these fatty acids. Aspirin also has an antiplatelet effect. The clinical effects of the concomitant administration of these agents were examined in this double-blind controlled crossover trial. Twelve healthy adults were randomized to supplement their diet for 21 days with 8 g of omega-3 fatty acids or identical-looking olive oil capsules. At the end of each treatment period, bleeding times were obtained before and after the administration of one 325-mg aspirin tablet. Overall, percent change in bleeding time after omega-3 fatty acid supplementation was significantly prolonged compared with olive oil supplementation before aspirin administration but not after. Bleeding times were influenced significantly by the order of randomization in the two treatment groups. Changes in post-aspirin bleeding time varied in subjects after they received olive oil. Post-aspirin bleeding times after omega-3 fatty acid supplementation were prolonged compared with baseline values but not significantly prolonged when compared with those after olive oil administration. The authors

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concluded that the concomitant administration of a single dose of aspirin does not prolong bleeding time in subjects who eat a diet enriched by omega-3 fatty acids versus a diet enriched by olive oil.PMID: 2010565

Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, Berglund L, Osmundsen K. Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovasc Risk 1997;4(5-6):385-91Department of Medicine, University of Kansas Medical Center, Kansas City, USA.BACKGROUND: Severe hypertriglyceridemia is a risk factor for acute pancreatitis, therefore decreasing serum triglyceride concentrations is an important component of risk management. Omega-3 fatty acids are well known hypotriglyceridemic agents, but their efficacy in severe forms of the disorder is not well documented. Our objective was to examine the effects of Omacor, a drug composed of 85% omega-3 fatty acid ethyl esters. METHODS: Forty-two patients with triglyceride concentrations between 5.65 and 22.60 mmol/l (500 and 2000 mg/dl) were studied in a prospective, double-blind, placebo-controlled trial of Omacor (4 g/day for 4 months). RESULTS: Compared with baseline values, Omacor significantly reduced mean triglyceride concentrations by 45% (P<0.00001), cholesterol by 15% (P< 0.001), very-low-density lipoprotein cholesterol by 32% (P< 0.0001) and cholesterol:high density lipoprotein (HDL) cholesterol ratio by 20% (P=0.0013), and increased HDL cholesterol by 13% (P=0.014) and low-density lipoprotein cholesterol by 31% (P=0.0014). The placebo had no effect on these parameters. Omacor was well tolerated and no patient discontinued medication because of side effects. CONCLUSIONS: Four capsules of Omacor per day markedly decreased triglyceride concentrations in patients with severe hypertriglyceridemia. The availability of a potent and safe omega-3 fatty acid preparation for this patient population should diminish the risk for acute pancreatitis, and may also reduce the long-term risk for cardiovascular disease.PMID: 9865671

Stalenhoef AF, de Graaf J, Wittekoek ME, Bredie SJ, Demacker PN, Kastelein JJ. The effect of concentrated n-3 fatty acids versus gemfibrozil on plasma lipoproteins, low density lipoprotein heterogeneity and oxidizability in patients with hypertriglyceridemia. Atherosclerosis 2000; 153(1):129-38541 Department of Internal Medicine, University Hospital Nijmegen, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. [email protected] evaluated in a double-blind randomized trial with a double-dummy design in 28 patients with primary hypertriglyceridemia, the effect of gemfibrozil (1200 mg/day) versus Omacor (4 g/day), a drug containing the n-3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), on lipid and lipoprotein levels, low density lipoprotein (LDL) subfraction profile and LDL oxidizability. Both Omacor and gemfibrozil therapy resulted in a similar significant decrease in serum triglyceride (TG), very low density lipoprotein (VLDL) triglyceride and VLDL cholesterol concentrations and an increase in high density lipoprotein (HDL) and LDL cholesterol concentrations. The increase in LDL cholesterol was due to a significant increase in cholesterol content of the relatively buoyant LDL subfractions LDL1, LDL2 and LDL3, whereas the relative contribution of the dense LDL subfractions LDL4 and LDL5 to total LDL tended to decrease. So, both therapies resulted in a more buoyant LDL subfraction profile, reflected by a significant increase of the value of parameter K (+10.3% on Omacor vs. +26.5% on gemfibrozil therapy, gemfibrozil vs Omacor P>0.05). Cu(2+)-induced oxidation of LDL was measured by continuous monitoring of conjugated dienes. After 12 weeks of Omacor treatment LDL appeared more prone to oxidative modification in vitro than LDL after gemfibrozil treatment, as measured by the significantly decreased lag time, preceding the onset of the lipid peroxidation. In both groups the rate of oxidation did not change with therapy. The amount of dienes formed during oxidation increased significantly on Omacor

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treatment, but not on gemfibrozil treatment. Plasma thiobarbituric acid reactive substances were higher after Omacor and lower after gemfibrozil treatment, although not significantly. We conclude that both Omacor and gemfibrozil have favorable effects on lipid and lipoprotein concentrations and the LDL subfraction profile. However, Omacor increased the susceptibility of LDL to oxidation, whereas gemfibrozil did not affect the resistance of LDL to oxidative modification in vitro. The clinical relevance of these changes remains to be established in the light of other postulated favorable effects of n-3 fatty acids on the course of cardiovascular disease.PMID: 11058707

Stark KD, Park EJ, Maines VA, Holub BJ. Effect of a fish-oil concentrate on serum lipids in postmenopausal women receiving and not receiving hormone replacement therapy in a placebo-controlled, double-blind trial. Am J Clin Nutr 2000;72(2):389-94 Department of Human Biology and Nutritional Sciences, University of Guelph, Canada.BACKGROUND: n-3 Fatty acid supplementation lowered serum triacylglycerol concentrations in studies in which most of the subjects were male. The effects of n-3 fatty acid supplementation in postmenopausal women receiving and not receiving hormone replacement therapy (HRT) have received little attention. OBJECTIVE: We sought to determine the effects of a fish-oil-derived n-3 fatty acid concentrate on serum lipid and lipoprotein risk factors for cardiovascular disease in postmenopausal women receiving and not receiving HRT, with an emphasis on serum triacylglycerol concentrations and the ratio of triacylglycerol to HDL cholesterol. DESIGN: Postmenopausal women (n = 36) were grouped according to exogenous hormone use and were randomly allocated to receive 8 capsules/d of either placebo oil (control) or n-3 fatty acid-enriched oil (supplement). The supplement provided 2.4 g eicosapentaenoic acid (EPA) plus 1.6 g docosahexaenoic acid (DHA) daily. Serum lipids and the fatty acid composition of

serum phospholipids were determined on days 0 and 28. RESULTS: Supplementation with n-3 fatty acids was associated with 26% lower serum triacylglycerol concentrations (P < 0.0001), a 28% lower overall ratio of serum triacylglycerol to HDL cholesterol (P < 0.01), and markedly greater EPA and DHA concentrations in serum phospholipids (P < 0.05). CONCLUSIONS: These results show that supplementation with a fish-oil-derived concentrate can favorably influence selected cardiovascular disease risk factors, particularly by achieving marked reductions in serum triacylglycerol concentrations and triacylglycerol:HDL cholesterol in postmenopausal women receiving and not receiving HRT. This approach could potentially reduce the risk of coronary heart disease by 27% in postmenopausal women.PMID: 10919932

Ateroesclerosis

von Schacky C, Angerer P, Kothny W, Theisen K, Mudra H. The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1999;130(7):554-62University of Munich, Germany. [email protected]: Epidemiologic studies, studies of mechanisms of action, and many animal studies indicate that dietary intake of omega-3 fatty acids has antiatherosclerotic potential. Few trials in humans have examined this potential. OBJECTIVE: To determine the effect of dietary intake of omega-3 fatty acids on the course of coronary artery atherosclerosis in humans. DESIGN: Randomized, double-blind, placebo-controlled, clinically controlled trial. SETTING: University preventive cardiology unit. PATIENTS: 223 patients with angiographically proven coronary artery disease. INTERVENTION: Fish oil concentrate (55% eicosapentaenoic and docosahexaenoic acids) or a placebo with a fatty acid composition resembling that of the average European diet, 6 g/d for 3 months and then 3 g/d for 21 months.

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MEASUREMENTS: The results of standardized coronary angiography, done before and after 2 years of treatment, were evaluated by an expert panel (primary end point) and by quantitative coronary angiography. Patients were followed for clinical and laboratory status. RESULTS: Pairs of angiograms (one taken at baseline and one taken at 2 years) were evaluated for 80 of 112 placebo recipients and 82 of 111 fish oil recipients. At the end of treatment, 48 coronary segments in the placebo group showed changes (36 showed mild progression, 5 showed moderate progression, and 7 showed mild regression) and 55 coronary segments in the fish oil group showed changes (35 showed mild progression, 4 showed moderate progression, 14 showed mild regression, and 2 showed moderate regression) (P = 0.041). Loss in minimal luminal diameter, as assessed by quantitative coronary angiography, was somewhat less in the fish oil group (P > 0.1). Fish oil recipients had fewer cardiovascular events (P = 0.10); other clinical variables did not differ between the study groups. Low-density lipoprotein cholesterol levels tended to be greater in the fish oil group. CONCLUSION: Dietary intake of omega-3 fatty acids modestly mitigates the course of coronary atherosclerosis in humans.PMID: 10189324

Brude IR, Drevon CA, Hjermann I, Seljeflot I, Lund-Katz S, Saarem K, Sandstad B, Solvoll K, Halvorsen B, Arnesen H, Nenseter MS. Peroxidation of LDL from combined-hyperlipidemic male smokers supplied with omega-3 fatty acids and antioxidants. Arterioscler Thromb Vasc Biol 1997;17(11):2576-88Institute for Nutrition Research, University of Oslo, Norway.The effects of marine omega-3 polyunsaturated fatty acids (FAs) and antioxidants on the oxidative modification of LDL were studied in a randomized, double-blind, placebo-controlled trial. Male smokers (n = 41) with combined hyperlipidemia were allocated to one of four groups receiving supplementation with omega-3 FAs (5 g eicosapentaenoic acid and

docosahexaenoic acid per day), antioxidants (75 mg vitamin E, 150 mg vitamin C, 15 mg beta-carotene, and 30 mg coenzyme Q10 per day), both omega-3 FAs and antioxidants, or control oils. LDL and human mononuclear cells were isolated from the patients at baseline and after 6 weeks of supplementation. LDL was subjected to cell-mediated oxidation by the patients' own mononuclear cells, as well as to Cu(2+)-catalyzed and 2,2'-azobis-(2-amidinopropane hydrochloride) (AAPH)-initiated oxidation. Extent of LDL modification was measured as lag time, the formation rate of conjugated dienes (CDs), the maximum amount of CDs formed, formation of lipid peroxides, and the relative electrophoretic mobility of LDL on agarose gels. Dietary supplementation with omega-3 FAs increased the concentration of total omega-3 FAs in LDL and reduced the concentration of vitamin E in serum. The omega-3 FA-enriched LDL particles were not more susceptible to Cu(2+)-catalyzed, AAPH-initiated, or autologous cell-mediated oxidation than control LDL. In fact, enrichment with omega-3 FAs significantly reduced the formation rate of CDs when LDL was subjected to AAPH-induced oxidation. Supplementation with moderate amounts of antioxidants significantly increased the concentration of vitamin E in serum and increased the resistance of LDL to undergo Cu(2+)-catalyzed oxidation, measured as increased lag time, reduced formation of lipid peroxides, and reduced relative electrophoretic mobility compared with control LDL. Supplementation with omega-3 FAs/antioxidants showed oxidizability of LDL similar to that of control LDL and omega-3 FA-enriched LDL. In conclusion, omega-3 FAs neither rendered the LDL particles more susceptible to undergo in vitro oxidation nor influenced mononuclear cells' ability to oxidize autologous LDL, whereas moderate amounts of antioxidants protected LDL against oxidative modification.PMID: 9409230

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Enfermedad coronaria

Deslypere JP. Influence of supplementation with N-3 fatty acids on different coronary risk factors in men--a placebo controlled study. Verh K Acad Geneeskd Belg 1992;54(3):189-216Department of Endocrinology, University Hospital, Gent.Recent epidemiological studies have shown some beneficial health effects of the long chain (n-3) polyunsaturated fatty acids found in fatty fish. Although the results of these studies are often ambiguous and inconclusive, they have prompted many intervention trials to study the effects of n-3 fatty acids (FA) on the cardiovascular risk profile. However screening of the literature revealed that many of the beneficial effects of fish (oil) were obtained in intervention studies which had several serious shortcomings in their design. Therefore we started a placebo controlled randomised trial with increasing doses of n-3FA (respectively 0; 1.12; 2.24 and 3.37 g n-3 FA/day) and in order to have a maximum compliance this study was done in healthy monks. Fifty eight subjects took the fish oil capsules during 12 months and were thereafter followed for another 6 months. We couldn't detect any effect of n-3 FA supplementation on total cholesterol, HDL cholesterol, LDL cholesterol, apo A1, Lp(a), HbA1C, glucose, fibrinogen, factor VIII, antithrombin III, plasminogen activator inhibitor, tissue plasminogen activator and von Willebrand factor concentration, on bleeding time or on systolic or diastolic blood pressure. A pronounced significant dose dependent decrease of triglyceride levels was seen, while a slight but statistical significant decrease of apo-B levels was observed in the highest fish oil dose. As the importance of triglycerides in the pathogenesis of atherosclerosis is still under discussion, the clinical relevance of these finding is not clear at the moment. It seems therefore improbable that the anti-atherosclerotic action of n-3 FA is due to an effect on the lipid, apoprotein, coagulation or fibrinolysis parameters as measured in our study. Hence further research must be focused on other

parameters (prostaglandins) which can be influenced by n-3 FA and which probably play an equally important role in the atherosclerotic process.PMID: 1413984

Christensen JH, Gustenhoff P, Korup E, Aaroe J, Toft E, Moller JM, Rasmussen K, Dyerberg J, Schmidt EB. [n-3 polyunsaturated fatty acids, heart rate variability and ventricular arrhythmias in post-AMI-patients. A clinical controlled trial] Ugeskr Laeger 1997;159(37):5525-9 Aalborg Sygehus, medicinsk endokrinologisk afdeling.There is evidence for an antiarrhythmic effect of n-3 polyunsaturated fatty acids (n-3 PUFA) in animals. The aim of the present study was to investigate the effect of dietary n-3 PUFA on ventricular arrhythmias and heart rate variability (HRV) in patients with a previous myocardial infarction. Fifty-five patients were randomized to receive either 5.2 g of n-3 PUFA daily for 12 weeks or placebo in a double blind, placebo-controlled study. Prior to randomization a 24-hour Holter recording was obtained, and this was repeated at the end of the study. The major end-points were the number of ventricular extrasystoles (VE)/24 hours and the 24-hour HRV. A non-significant decrease in VE/24 hours was found in both the n-3 PUFA group and among controls after dietary supplementation, whereas HRV significantly increased after n-3 PUFA compared to both baseline values (p = 0.04) and to controls (p = 0.01). The present study therefore supports the hypothesis that n-3 PUFA may have an anti-arrhythmic effect in humans.PMID: 9312922

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Salonen R, Nikkari T, Seppanen K, Venalainen JM, Ihanainen M, Rissanen V, Rauramaa R, Salonen JT. Effect of omega-3 fatty acid supplementation on platelet aggregability and platelet produced thromboxane. Thromb Haemost 1987; 57(3):269-72Kuopio Research Institute of Exercise Medicine, Finland.We investigated the sustained effect of 12-week supplementation of 2.880 g/day of omega-3 fatty acids on platelet aggregability, platelet produced thromboxane B2 concentration and serum fatty acid composition in a double-blind controlled trial in 44 healthy mildly overweight eastern Finnish men recruited from a representative population sample. The supplementation was discontinued seven days before the biochemical measurements. Body weight, alcohol consumption and dietary composition remained constant during the study. Even though the percentage of eicosapentaenoic acid (20:5 omega 3) in total serum lipids increased by 37% (p less than 0.01) and that of dihomo-gamma-linolenic acid (20:3 omega 6) decreased by 18% (p less than 0.01) more in the omega-3 supplemented than placebo group during supplementation, there were no significant differences in the changes in either the ADP induced platelet aggregation or in vitro platelet produced thromboxane B2 concentration between the groups. These data suggest that omega-3 fatty acids have no detectable sustained effect either on ADP induced platelet aggregation or on thromboxane produced by the platelets in vitro.PMID: 3660329

Durrington PN, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, France M. An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart 2001 May;85(5):544-8 University Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK. [email protected]: Omega-3 fatty acids, such as those present in fish oil, have been reported to prolong life in myocardial infarction survivors. These fatty acids can decrease serum triglyceride concentrations, but so far the doses used in trials examining their effects on coronary end points have had only minimal triglyceride lowering effects. OBJECTIVE: To examine the triglyceride lowering effectiveness, safety, and tolerability of Omacor, a concentrate of omega-3, long chain, polyunsaturated fatty acids from fish oil (84% of the total as opposed to an average of 35% in fish oil) over one year in patients with established coronary heart disease (CHD) and persisting hypertriglyceridaemia, despite receiving simvastatin in doses similar to those employed in the Scandinavian simvastatin survival study. SUBJECTS AND METHODS: 59 patients with CHD, receiving simvastatin 10-40 mg daily with serum triglycerides > 2.3 mmol/l, were randomised to receive Omacor 2 g twice a day or placebo for 24 weeks in a double blind trial. Forty six patients accepted the offer of active treatment for a further 24 weeks in an open phase of the trial. RESULTS: There was a sustained significant decrease in serum triglycerides by 20-30% (p < 0.005) and in very low density lipoprotein (VLDL) cholesterol by 30-40% (p < 0.005) in patients receiving active Omacor at three, six, and 12 months compared either to baseline or placebo. Omacor did not have any deleterious effect on low density or high density lipoprotein cholesterol or on biochemical and haematological safety tests. There was no

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adverse effect on glycaemic control in patients with diabetes, who showed a decrease in serum triglyceride, which was at least as great as in non-diabetic patients. One patient receiving placebo died of acute myocardial infarction. Three patients withdrew from the trial (two on placebo and one on active treatment). Omacor was generally well tolerated. CONCLUSION: Omacor was found to be a safe and effective means of lowering serum triglycerides over one year in patients with CHD and combined hyperlipidaemia, whose triglycerides remained elevated despite simvastatin treatment.PMID: 11303007

Sanders TA, Hochland MC.A comparison of the influence on plasma lipids and platelet function of supplements of omega 3 and omega 6 polyunsaturated fatty acids. Br J Nutr 1983;50(3):521-9A randomized double-blind crossover trial was carried out to compare the influence on plasma lipid concentrations, platelet thromboxane B2 production and platelet aggregation induced by ADP, collagen and U46619 (a prostaglandin endoperoxide analogue), of a daily 10 g supplement of a fish-oil concentrate (MaxEPA), which provided (g): 1.7 20:5 omega 3, 0.3 22:5 omega 3 and 1.2 22:6 omega 3, taken for 2 weeks by ten healthy subjects, with one of vegetable oil providing 3.4 18:2 omega 6. A lower response to platelet aggregation induced by 0.5 micrograms collagen/ml but not by other aggregating agents was observed following both types of supplement. Platelet thromboxane B2 production induced by collagen also tended to be lower following the supplements. Plasma total cholesterol concentrations were unaffected by the supplements. The MaxEPA but not the vegetable-oil supplement lowered the concentration of plasma triglycerides and increased that of high-density-lipoprotein-cholesterol.PMID: 6639916

Bairati I, Roy L, Meyer F. Double-blind, randomized, controlled trial of fish oil supplements in prevention of recurrence of stenosis after coronary angioplasty. Circulation 1992; 85(3):950-6Department of Social and Preventive Medicine, Faculty of Medicine, Laval University, Quebec City, Ste-Foy, Canada.BACKGROUND. Previous studies suggest that recurrence of coronary stenosis after percutaneous transluminal coronary angioplasty (PTCA) might be prevented with dietary supplements rich in omega-3 fatty acids. The purpose of the present study was to evaluate this hypothesis. In addition, the relation between usual dietary consumption of omega-3 fatty acids and restenosis was assessed. METHODS AND RESULTS. A double-blind, randomized, controlled trial was conducted in which 205 patients undergoing a first PTCA received 15 capsules per day containing 1 g of either fish oil (2.7 g/day of eicosapentaenoic acid, 1.8 g/day of docosahexaenoic acid) or olive oil. The treatment was started 3 weeks before PTCA and continued for 6 months thereafter. Dietary intake was assessed by food frequency questionnaire. At 6 months after PTCA, patients underwent a control angiography. All angiographic lesions were measured by quantitative computer analysis. Four criteria were used to define restenosis. Restenosis occurred less often in the fish oil group (22.0-35.6% depending on the definition) than in the control group (40.0-53.3%). After controlling for other risk factors of restenosis, the association of fish oil supplementation with a lower frequency of restenosis was statistically significant (p = 0.03) for three of four definitions. After adjustment, a dietary intake of omega-3 fatty acids of more than 0.15 g/day was also associated with a lower frequency of restenosis (p less than or equal to 0.03). CONCLUSIONS. This trial documented the protective effect of fish oil supplements on the recurrence of coronary stenosis 6 months after PTCA. The study results suggest that a dietary intervention could be useful in preventing restenosis.PMID: 1537131

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Jula A, Marniemi J, Huupponen R, Virtanen A, Rastas M, Ronnemaa T. Effects of diet and simvastatin on serum lipids, insulin, and antioxidants in hypercholesterolemic men: a randomized controlled trial. JAMA 2002 6;287(5):598-605Research and Development Centre of the Social Insurance Institution, Peltolantie 3, FIN-20720 Turku, Finland. [email protected]: Limited information exists on the interaction between diet and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and the interaction's effect on serum lipid and lipoprotein levels, insulin sensitivity, and circulating antioxidant vitamin and provitamin levels OBJECTIVE: To evaluate the separate and combined effects of diet and simvastatin therapy on serum levels of lipids, lipoproteins, antioxidants, and insulin. DESIGN, SETTING, AND PARTICIPANTS: Randomized, controlled crossover trial conducted from August 1997 to June 1998 in 120 previously untreated hypercholesterolemic men aged 35 to 64 years who were recruited from the community in Turku, southwestern Finland. INTERVENTIONS: After a 4- to 6-week placebo run-in period, participants were randomly allocated to a habitual diet (n = 60) or dietary treatment group (n = 60), and each of these groups was further randomized in a double-blind crossover fashion to receive simvastatin (20 mg/d) or placebo, each for 12 weeks (n = 30 in each group). The main goals of the dietary treatment were to reduce energy intake from saturated plus trans-unsaturated fats to no more than 10% by replacing them partly with monounsaturated and polyun-saturated fats rich in omega-3 fatty acids and to increase intake of fruits, vegetables, and dietary fiber. MAIN OUTCOME MEASURES: Changes in levels of total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol; triglycerides; apolipoprotein B; insulin; glucose; and antioxidants at week 12 of each treatment period, compared among the 4 groups. RESULTS: Dietary treatment decreased levels of total cholesterol by 7.6% (P<.001), LDL cholesterol by 10.8% (P<.001), HDL cholesterol by 4.9% (P =.01),

apolipoprotein B by 5.7% (P =.003), serum insulin by 14.0% (P =.02), and alpha-tocopherol by 3.5% (P =.04). Simvastatin decreased levels of total cholesterol by 20.8%, LDL cholesterol by 29.7%, triglycerides by 13.6%, apolipoprotein B by 22.4%, alpha-tocopherol by 16.2%, beta-carotene by 19.5%, and ubiquinol-10 by 22.0% (P<.001 for all) and increased levels of HDL cholesterol by 7.0% (P<.001) and serum insulin by 13.2% (P =.005). Glucose levels remained unchanged in all groups. The effects of dietary treatment and simvastatin were independent and additive. CONCLUSIONS: A modified Mediterranean-type diet rich in omega-3 fatty acids efficiently potentiated the cholesterol-lowering effect of simvastatin, counteracted the fasting insulin-elevating effect of simvastatin, and, unlike simvastatin, did not decrease serum levels of beta-carotene and ubiquinol-10.PMID: 11829698

Yam D, Bott-Kanner G, Genin I, Shinitzky M, Klainman E.[The effect of omega-3 fatty acids on risk factors for cardiovascular diseases Harefuah 2001; 140(12):1156-8, 1230Weizmann Institute of Science, Givatayim, Israel.Cardiovascular disease (CVD) is associated with dyslipidemia and frequently with insulin resistance, both of which are in general no alleviated by antilipidemic drugs. Our objective was to examine whether a dietary supplement containing omega-3 fatty acids (n-3 FA) can reduce the levels of serum lipids, fasting insulin and glucose in documented CVD patients treated by statins or bezafibrates. In a double-blind placebo-controlled trial of parallel design, 52 patients, age 69.2 years +/- 3.6 treated by antilipidemic drugs, were randomly assigned to receive daily 7 gr of a dietary concentrated supplement containing 67% n-3 FA (185 mg EPA and 465 mg/g DHA) in a form of spread (Yamega Ltd, Israel) or olive oil spread (placebo) and recommended to reduce the consumption of omega-6 fatty acids for 12 weeks. The average values +/- SD before and after dietary supplementations were compared. RESULTS: 44 patients (23 in the n-3 FA group) completed the study. In the n-3FA

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group we observed a significant decrease (p < 0.05) of total cholesterol (12.2%). LDL-cholesterol (16.8%), triglycerides (36.1%), insulin in hyperinsulinemic subjects (> 20 microunits/ml) (34.9%), and no significant changes in HDL-cholesterol and glucose. No hyperglycemia was detected. In the olive oil group we observed a significant decrease (p < 0.05) in the LDL-cholesterol values of 15.5% and no significant changes in the other parameters. No side effects were reported during the study in any of the participants. Our findings demonstrate that the incorporation of the dietary supplement containing EPA and DHA omega-3 fatty acids reduces significantly the above risk factors for CVD.PMID: 11789299

Enfermedad bipolar

Freeman MP. Omega-3 fatty acids in psychiatry: a review. Ann Clin Psychiatry 2000;12(3):159-65University of Cincinnati College of Medicine, Biological Psychiatry Program, OH 45267-0559, USA.Omega-3 fatty acids are long-chain, polyunsaturated fatty acids found in plant and marine sources. Unlike saturated fats, which have been shown to have negative health consequences, omega-3 fatty acids are polyunsaturated fatty acids that have been associated with many health benefits. Omega-3 fatty acids may prove to be efficacious in a number of psychiatric disorders. Mood disorders have been associated with abnormalities in fatty acid composition. Several lines of evidence suggest that diminished omega-3 fatty acid concentrations are associated with mood disorders. Clinical data are not yet available regarding omega-3 fatty acids in the treatment of major depression. However, one double-blind treatment trial has been conducted in bipolar disorder. Also, substantial evidence does exist supporting a potential role of omega-3 fatty acids in schizophrenia, although treatment data are needed. A case has been reported in which a patient with schizophrenia was successfully treated with omega-3 fatty acids. Controlled studies are necessary to explore the potential treatment of

schizophrenia with omega-3 fatty acids. Omega-3 fatty acids may also be helpful in the treatment of dementia. Furthermore, omega-3 fatty acids may prove to be a safe and efficacious treatment for psychiatric disorders in pregnancy and in breastfeeding.PMID: 10984006

Stoll AL, Severus WE, Freeman MP, Rueter S, Zboyan HA, Diamond E, Cress KK, Marangell LB.Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry 1999; 56(5):407-12Brigham and Women's Hospital, Department of Psychiatry, Harvard Medical School, Boston, Mass, USA. [email protected]: Omega3 fatty acids may inhibit neuronal signal transduction pathways in a manner similar to that of lithium carbonate and valproate, 2 effective treatments for bipolar disorder. The present study was performed to examine whether omega3 fatty acids also exhibit mood-stabilizing properties in bipolar disorder. METHODS: A 4-month, double-blind, placebo-controlled study, comparing omega3 fatty acids (9.6 g/d) vs placebo (olive oil), in addition to usual treatment, in 30 patients with bipolar disorder. RESULTS: A Kaplan-Meier survival analysis of the cohort found that the omega3 fatty acid patient group had a significantly longer period of remission than the placebo group (P= .002; Mantel-Cox). In addition, for nearly every other outcome measure, the omega3 fatty acid group performed better than the placebo group. CONCLUSION: Omega3 fatty acids were well tolerated and improved the short-term course of illness in this preliminary study of patients with bipolar disorder.PMID: 10232294

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Enfermedad intestinal inflamatoria

Aslan A, Triadafilopoulos G. Fish oil fatty acid supplementation in active ulcerative colitis: a double-blind, placebo-controlled, crossover study. Am J Gastroenterol 1992 Apr;87(4):432-7 Gastroenterology Section, Veterans Affairs Medical Center, Martinez, California.Arachidonic acid metabolites formed by both the cyclooxygenase and lipoxygenase pathways may contribute to the clinical diarrhea and colitis of inflammatory bowel disease. Patients with active ulcerative colitis have increased levels of leukotriene B4 in their rectal mucosa, and these levels tend to correlate with severity of the disease. In this study, we evaluated the efficacy of ingestion of fish oil n-3-omega-fatty acids, inhibitors of leukotriene synthesis, in the treatment of ulcerative colitis. Eleven patients with ulcerative colitis of mild to moderate severity were studied in a 8-month, double-blind, placebo-controlled, crossover trial of dietary supplementation with fish oil, which provided about 4.2 g of omega-3- fatty acids per day. A disease activity index based on patient symptoms and sigmoidoscopic appearance was used to assess efficacy. Mucosal leukotriene B4 production was measured by radioimmunoassay. Mean disease activity index declined 56% for patients receiving fish oil and 4% for patients on placebo (p less than 0.05). There were no statistically significant differences in histopathologic scores or colonic mucosal leukotriene B4 levels. All patients tolerated fish oil ingestion and showed no alteration in routine blood studies. No patient worsened; anti-inflammatory drugs could be reduced or eliminated in eight patients (72%) while receiving fish oil. We conclude that fish oil dietary supplementation results in clinical improvement of active mild to moderate ulcerative colitis but is not associated with significant reduction in mucosal leukotriene B4 production, compared with placebo therapy. Further studies are needed to elucidate the mechanism of action and optimal dose and duration of fish oil supplementation in ulcerative colitis.

PMID: 1553930

Salomon P, Kornbluth AA, Janowitz HD. Treatment of ulcerative colitis with fish oil n--3-omega-fatty acid: an open trial. J Clin Gastroenterol 1990 Apr;12(2):157-61 Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029-6574.We evaluated the efficacy of fish oil n--3-omega-fatty acids, inhibitors of leukotriene synthesis, in the treatment of ulcerative colitis. An open trial of 10 patients with mild to moderate ulcerative colitis who had either failed (n = 9) or refused (n = 1) conventional therapy was performed. Patients received 15 MAX-EPA capsules containing a total of 2.7 g of eicosapentanoic acid in three divided doses daily for 8 weeks. The activity of ulcerative colitis and response to therapy was based upon daily stool diaries, sigmoidoscopy, and symptomatic response. All patients tolerated the fish oil and showed no alteration in routine blood studies. Seven patients had moderate to marked improvement; steroid dose could be reduced in four of the five patients on prednisone. Three patients had little or no improvement. No patient worsened. These results of our open study appear to justify a double-blind trial of this dietary supplement in ambulatory patients with ulcerative colitis. PMID: 2109004

Otros

James MJ, Cleland LG. Dietary n-3 fatty acids and therapy for rheumatoid arthritis. Semin Arthritis Rheum 1997; 27(2):85-97Rheumatology Unit, Royal Adelaide Hospital, Australia.OBJECTIVE: To examine the potential for dietary n-3 fats to be component of therapy for rheumatoid arthritis (RA). METHODS: Studies of encapsulated fish oil use in RA were reviewed and critiqued, and possible biochemical mechanisms for fish oil effects were examined. The potential for use of n-3 fats was evaluated within a dietary framework rather than a quasi-

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pharmaceutical framework. RESULTS: There is consistent evidence from double-blind, placebo-controlled clinical trials that dietary n-3 fats, supplied as fish oil, can have beneficial effects in RA. The beneficial effects appear modest, but their size and extent may have been moderated by common trial design factors such as high n-6 polyunsaturated fat diets and concurrent antiinflammatory drug use. Mechanisms for the clinical effects of n-3 fats in RA may involve their ability to suppress production of inflammatory mediators, including n-6 eicosanoids and proinflammatory cytokines. Suppression of n-6 eicosanoid and cytokine production will be possible using foodstuffs that are rich in n-3 fats and poor in n-6 fats. CONCLUSIONS: There are many overlapping biochemical effects of n-3 fatty acids and antiinflammatory pharmaceuticals that could explain the clinical actions of n-3 fats in RA. They suggest that there is the potential for complementarity between drug therapy and dietary choices that increase intake of n-3 fats and decrease intake of n-6 fats. In particular, there is the potential for drug-sparing effects. Future studies with n-3 fats in RA need to address the fat composition of the background diet and the issue of concurrent drug use.PMID: 9355207

Astorga G, Cubillos A, Masson L, Silva JJ. [Active rheumatoid arthritis: effect of dietary supplementation with omega-3 oils. A controlled double-blind trial] Rev Med Chil 1991 Mar;119(3):267-72Departamento de Medicina (Seccion Reumatologia), Facultad de Medicina, Universidad de Chile, Santiago.We evaluated the effect of dietary supplementation with eicosapentaenoic acid in 8 patients with active rheumatoid arthritis. An appropriate placebo was given in a randomized double blind fashion to 8 control subjects. After 12 weeks of therapy a significant improvement in prehensile function was detected in patients receiving active treatment, other clinical parameters remaining unchanged. No significant side effects were detected. A larger trial may help define a possible

therapeutic role for omega-3 fatty acids in patients with rheumatoid arthritis.PMID: 1842119 [PubMed - indexed for MEDLINE]

Nielsen GL, Faarvang KL, Thomsen BS, Teglbjaerg KL, Jensen LT, Hansen TM, Lervang HH, Schmidt EB, Dyerberg J, Ernst E. The effects of dietary supplementation with n-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized, double blind trial. Eur J Clin Invest 1992 Oct;22(10):687-91 Department of Rheumatology, Aalborg Hospital, Copenhagen, Denmark.STUDY OBJECTIVE: To determine the effect of dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) on disease variables in patients with rheumatoid arthritis. DESIGN: Multicenter, randomized, placebo controlled, double blind. SETTING: Three Danish hospital Departments of Rheumatology. PATIENTS: Fifty-one patients with active rheumatoid arthritis. INTERVENTION: Random allocation to 12 weeks of treatment with either six n-3 PUFA capsules (3.6 g) or six capsules with fat composition as the average Danish diet. MAIN RESULTS: Significant improvement of morning stiffness and joint tenderness. No significant effect on the four other assessed clinical parameters. No serious side effects. CONCLUSIONS: Dietary supplementation with n-3 PUFA in patients with rheumatoid arthritis improved two out of six patient reported disease parameters. Further studies are needed to clarify the more precise role of n-3 PUFA in the treatment of rheumatoid arthritis.PMID: 1459173

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Kjeldsen-Kragh J, Lund JA, Riise T, Finnanger B, Haaland K, Finstad R, Mikkelsen K, Forre O. Dietary omega-3 fatty acid supplementation and naproxen treatment in patients with rheumatoid arthritis. J Rheumatol 1992 Oct;19(10):1531-6Department of General Practice, University of Oslo, Norway.In a controlled, double blind, clinical trial we tested the effect of dietary omega-3 fatty acid supplementation with and without naproxen and placebo, respectively, in 67 patients with active rheumatoid arthritis. The patients were randomized into 3 groups that received the following treatment: Group 1, corn oil ("placebo omega-3 fatty acids"), 7 g/day for 16 weeks, and naproxen, 750 mg/day for 10 weeks followed by a stepwise reduction to 0 mg/day during the following 3 weeks; Group 2, -3 fatty acids, 3.8 g of eicosapentaenoic acid plus 2.0 g of docosahexaenoic acid, and naproxen, 750 mg/day for 16 weeks; and Group 3, omega-3 fatty acids as Group 2 and naproxen as Group 1. At the end of the trial, patients in Group 2 had improved with respect to duration of morning stiffness and global assessment by physician and patient. In Groups 1 and 3 there was a significant deterioration for most of the variables measured. However, for duration of morning stiffness the deterioration was significantly less pronounced in Group 3 compared with Group 1. These effects might be ascribed to the dietary omega-3 fatty acid supplementation.PMID: 1464864

Wander RC, Du SH, Ketchum SO, Rowe KE. alpha-Tocopherol influences in vivo indices of lipid peroxidation in postmenopausal women given fish oil. J Nutr 1996 Mar;126(3):643-52Department of Nutrition and Food Management, Oregon State University, Corvallis, 97331-5103, USA.Although diets containing fish have been shown to be therapeutically valuable, the vitamin E requirement when large

quantities of (n-3) fatty acids are consumed is not known. Additionally, as estrogens may function as an antioxidant, the requirement may be modified in postmenopausal women using hormone replacement therapy (HRT). Consequently, the purpose of this study was to measure the impact of graduated doses of RRR-alpha-tocopheryl acetate (TA) on in vivo indices of lipid peroxidation in postmenopausal women with and without hormone replacement therapy when given a supplement of fish oil. Forty-eight postmenopausal women, half receiving (+HRT) and half not receiving (-HRT) hormone replacement therapy, participated in a four-period, double-blind crossover trial. Each period lasted 5 wk followed by a 4-wk washout interval. During each period, the subjects consumed a 15-g supplement of fish oil and either 0, 100, 200, or 400 mg TA/d in a balanced, single square dosing order. Plasma levels of (n-3) fatty acids were significantly higher after fish oil supplementation; alpha-tocopherol concentration of plasma was significantly higher at each level of supplementation compared with the level without supplementation. Urinary excretion of thiobarbituric acid reactive substances (TBARS) and malondialdehyde, measured as the thiobarbituric-malondialdehyde adduct (TRA-MDA adduct), and the plasma concentration of the adduct were significantly greater after the fish oil supplement. Although urinary TBARS decreased linearly as the dose of TA increases (P < or = 0.05), urinary and plasma concentrations of TBA-MDA adduct did not. This study suggests that the evaluation of highly unsaturated fatty acids as oxidative stressors requires several measures of assessment.PMID: 8598549

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Mendez-Sanchez N, Gonzalez V, Aguayo P, Sanchez JM, Tanimoto MA, Elizondo J, Uribe M. Fish oil (n-3) polyunsaturated fatty acids beneficially affect biliary cholesterol nucleation time in obese women losing weight. J Nutr 2001; 131(9):2300-3Department of Biomedical Research, Medica Sur Clinic and Foundation, Mexico City, Mexico. [email protected] has been reported that intake of (n-3) polyunsaturated fatty acids PUFA) reduces the risk of coronary heart disease and decreases biliary cholesterol saturation in the bile of gallstone patients. We investigated the effect of n-3 PUFA on cholesterol saturation index (CSI) and nucleation time (NT) in obese subjects who were losing weight. This was a double-blind, placebo-controlled clinical trial. Obese women (n = 35) with a body mass index (BMI) > or = 30 kg/m(2), with no prior history of gallstones or cholecystectomy by ultrasound were first studied to ensure absence of stones or biliary sludge. The women were then assigned to a hypocaloric regimen [5.02 MJ (1200 kcal)/d] and to receive 1200 mg/d of ursodeoxycholic acid (UDCA), 11.3 g/d of (n-3) PUFA or a placebo for 6 wk. BMI, CSI and NT were recorded at baseline and at the end of the experimental period. BMI decreased 5.75 +/- 2.7%/mo (range, 1.5-12.42%/mo) during the experiment. The CSI did not change in any of the groups. Cholesterol NT decreased significantly in the UDCA and placebo groups, but not in the (n-3) PUFA group. None of the women had developed gallstones at 6 wk. These results suggest that (n-3) PUFA maintain the CSI and NT in obese women during rapid weight loss, which probably results in the prevention of cholesterol gallstone formation.PMID: 11533270

Hodge L, Salome CM, Hughes JM, Liu-Brennan D, Rimmer J, Allman M, Pang D, Armour C, Woolcock AJ. Effect of dietary intake of omega-3 and omega-6 fatty acids on severity of asthma in children. Eur Respir J 1998 Feb;11(2):361-5Institute of Respiratory Medicine, Royal Prince Alfred Hospital, Sydney, Australia.We assessed the clinical and biochemical effects in asthmatic children of fish oil supplementation and a diet that increases omega-3 and reduces omega-6 fatty acids. Thirty nine asthmatic children aged 8-12 yrs participated in a double-blind, randomized, controlled trial for 6 months during which they received fish oil capsules plus canola oil and margarine (omega-3 group) or safflower oil capsules plus sunflower oil and margarine (omega-6 group). Plasma fatty acids, stimulated tumour necrosis factor alpha (TNFalpha) production, circulating eosinophil numbers and lung function were measured at baseline and after 3 and 6 months of dietary modification. Day and night symptoms, peak flow rates and medication use were recorded for 1 week prior to laboratory visits. Plasma phospholipid omega-3 fatty acids were significantly greater in the omega-3 group at 3 and 6 months compared to the omega-6 group (p<0.001). In the omega-3 group TNFalpha production fell significantly compared with baseline (p=0.026), but the magnitude of change between groups did not reach significance (p=0.075). There were no significant changes in clinical outcome measures. Dietary enrichment of omega-3 fatty acids over 6 months increased plasma levels of these fatty acids, reduced stimulated tumour necrosis factor alpha production, but had no effect on the clinical severity of asthma in these children.PMID: 9551739

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Makrides M, Neumann MA, Jeffrey B, Lien EL, Gibson RA. A randomized trial of different ratios of linoleic to alpha-linolenic acid in the diet of term infants: effects on visual function and growth. Am J Clin Nutr 2000 Jan;71(1):120-9Department of Paediatrics & Child Health, Flinders University of South Australia and Flinders Medical Centre, Bedford Park (Adelaide), Australia.BACKGROUND: There are nutritional recommendations that the ratio of linoleic to alpha-linolenic acid (LA:ALA) in formula for term infants be between 5:1 and 15:1. These recommendations were made in the absence of data on functional or clinical outcomes. OBJECTIVE: We compared the fatty acid status, visual evoked potential (VEP) acuity, and growth of term infants fed formula containing an LA:ALA of 10:1 or 5:1 with those of a breast-fed reference cohort. DESIGN: Formula-fed infants were allocated randomly in a double-blind fashion to receive formula with an LA:ALA of either 10:1 (16.9:1.7; n = 36) or 5:1 (16.3:3.3; n = 37) from near birth to 34 wk of age. Increased ALA was attained by replacing soy oil with low-erucic acid cannola oil. A parallel group of breast-fed infants was also recruited. Infant growth and fatty acid status were assessed at 6, 16, and 34 wk of age. VEP acuity was assessed at 16 and 34 wk. RESULTS: Infants fed the 5:1 formula had greater docosahexaenoic acid (DHA) concentrations in plasma and erythrocyte phospholipids than did infants fed the 10:1 formula, but DHA concentrations of infants fed the 5:1 formula remained less than those in breast-fed infants. The VEP acuity of all formula-fed and breast-fed infants was not significantly different at 16 and 34 wk of age. At birth, infants fed the 5:1 formula were heavier, were longer, and had a greater head circumference than infants assigned to the 10:1 formula group; this differential was maintained throughout the trial. The rate of gain in weight, length, and head circumference was not significantly different between the 2 formula-fed groups, although breast-fed infants had lower weight and length gains than did formula-fed infants between 16 and 34 wk of age. CONCLUSION: Lowering the

LA:ALA in formula from 10:1 to 5:1 by using low-erucic acid canola oil resulted in a modest increase in plasma DHA but had no effect on VEP acuity or growth rate.PMID: 10617956

Hoffman DR, Birch EE, Birch DG, Uauy R, Castaneda YS, Lapus MG, Wheaton DH. Impact of early dietary intake and blood lipid composition of long-chain polyunsaturated fatty acids on later visual development. J Pediatr Gastroenterol Nutr 2000 Nov;31(5):540-53Retina Foundation of the Southwest, and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75231, USA. [email protected]: In contrast to human milk, current infant formulas in the United States do not contain omega3 and omega6 long-chain polyunsaturated fatty acids. This may lead to suboptimal blood lipid fatty acid profiles and to a measurable diminution of visual function in developing term infants. The need for docosahexaenoic acid and arachidonic acid supplementation in the infant diet was evaluated in a double-blind, randomized clinical trial. METHODS: Healthy term infants were randomized to diets of (1) commercial formula, (2) docosahexaenoic acid-enriched formula (0.35% of total fatty acids), or (3) docosahexaenoic acid- (0.36%) and arachidonic acid- (0.72%) enriched formula. Eighty-seven infants completed the 17-week nutritional trial, and 58 were observed until 52 weeks of life. A reference group was exclusively breast fed for at least 17 weeks (n = 29). Outcome measures included electroretinographic responses, visual evoked potentials, and blood fatty acid analysis in infants at birth and at 6, 17, and 52 weeks of age. RESULTS: Commercial formula-fed infants had 30% to 50% lower content of docosahexaenoic acid in total red blood cell lipids during the 17-week feeding trial compared with breastfed infants. Significant differences persisted at the 1-year follow-up. Arachidonic acid content was consistently reduced in the commercial formula group by 15% to 20%. Infants fed long-chain polyunsaturated fatty acid-

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enriched formulas had docosahexaenoic acid and arachidonic acid blood lipid profiles resembling those of human milk-fed infants. Infants receiving this enriched formula had more mature electroretinographic responses than commercial formula-fed infants at 6 weeks of age. Human milk-fed and docosahexaenoic acid-enriched formula-fed infants had better visual acuity than commercial formula-fed infants at both 17 and 52 weeks of age. Early (17-week) fatty acid profiles in blood lipids were correlated

with later (52-week) visual function development in study infants. CONCLUSIONS: Results from this clinical trial demonstrate that long-chain polyunsaturated fatty acid supplementation of formula in term infants produces blood lipid fatty acid profiles that are similar to those observed in breast-fed infants. This supplementation leads to better visual function later in life (i.e., 1 year of age) than that shown by infants fed commercial formula.PMID: 11144440

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