Protective effect of fish oil supplementation on exercise-induced bronchoconstriction in asthma

BACKGROUND: Previous research has demonstrated that fish oil supplementation has a protective effect on exercise-induced bronchoconstriction (EIB) in elite athletes, which may be attributed to its antiinflammatory properties. Since EIB in asthma involves proinflammatory mediator release, it is feasible that fish oil supplementation may reduce the severity of EIB in asthmatic subjects. STUDY OBJECTIVES: To determine the efficacy of fish oil supplementation on severity of EIB in subjects with asthma. DESIGN: Randomized, double-blind, crossover study. SETTING: Lung function and exercise testing in a university research laboratory.Patients and measurements: Sixteen asthmatic patients with documented EIB entered the study on their normal diet and then received either fish oil capsules containing 3.2 g of eicosapentaenoic acid and 2.0 g of docohexaenoic acid (fish oil diet, n = 8) or placebo capsules (placebo diet, n = 8) daily for 3 weeks. At the beginning of the study (normal diet) and at the end of each treatment phase, the following pre-exercise and postexercise measures were assessed: (1) pulmonary function; (2) induced sputum differential cell count percentage and proinflammatory eicosanoid metabolite (leukotriene C4 [LTC4]-leukotriene E4 [LTE4] and prostaglandin D2 [PGD2]) and cytokine (interleukin [IL]-1beta and tumor necrosis factor [TNF]-alpha) concentrations; and (3) eicosanoid metabolites leukotriene B4 (LTB4) and leukotriene B5 (LTB(5)) generation from activated polymorphonuclear leukocytes (PMNLs). RESULTS: On the normal and placebo diet, subjects exhibited EIB. However, the fish oil diet improved pulmonary function to below the diagnostic EIB threshold, with a concurrent reduction in bronchodilator use. Induced sputum differential cell count percentage and concentrations of LTC4-LTE4, PGD2, IL-1beta, and TNF-alpha were significantly reduced before and following exercise on the fish oil diet compared to the normal and placebo diets. There was a significant reduction in LTB4 and a significant increase in LTB5 generation from activated PMNLs on the fish oil diet compared to the normal and placebo diets. CONCLUSION: Our data suggest that fish oil supplementation may represent a potentially beneficial nonpharmacologic intervention for asthmatic subjects with EIB.     

Inspiratory stridor in elite athletes

STUDY OBJECTIVES: Diagnosis and medical intervention for exercise-induced bronchospasm (EIB) are often based on self-reported symptoms, without spirometric confirmation. Inspiratory stridor (IS), a symptom of vocal cord dysfunction (VCD), is frequently mistaken for EIB wheeze. Athletes with exercise IS that spontaneously resolves on activity cessation are suspect for VCD and may not have EIB. This study estimated IS prevalence in elite athletes and determined its relationship to EIB. Subjects/methods: Three hundred seventy athletes (174 female and 196 male subjects) provided a medical history, and underwent spirometry before and after exercise challenge. Exercise challenges were conducted in cold, dry ambient conditions. EIB positive (EIB +) was defined as a > or = 10% postexercise fall in FEV(1). Athletes were monitored for IS during exercise; 78.4% of the athletes in this study (n = 290) were tested on multiple occasions. RESULTS: EIB was identified in 30% of 370 athletes tested (58 female and 53 male subjects). IS was observed in 5.1% (18 female and 1 male subjects) during exercise and spontaneously resolved in these subjects within 5 min after exercise cessation. Ten IS-positive (IS +) athletes (52.6%) were EIB +, and 8 of these athletes had a previous EIB diagnosis; however, beta(2)-agonist treatment resolved IS in only 2 subjects. Eight of nine IS +/EIB-negative (EIB -) athletes had a previous EIB diagnosis; seven subjects received beta(2)-agonist treatment with no IS resolution. Resting spirometric measurements did not distinguish IS, but postexercise mid-flow (FEF(50)/FIF(50)) ratio > 1.5 was more frequent (33%, p < 0.05) among IS + athletes. The FEF(50)/FIF(50) ratio was higher for IS +/EIB + athletes than for IS -/EIB + athletes (1.97 +/- 1.69 vs 0.81 +/- 0.39, p < 0.05). The postexercise fall in FVC was greater (p < 0.05) for IS +/EIB - athletes (9.2 +/- 5.0%) than for IS-negative (IS -) /EIB - athletes (5.3 +/- 4.3%). No difference in postexercise FEV(1) was identified between IS + and IS - athletes (within EIB + or EIB - groups). CONCLUSIONS: Five percent of athletes were IS +, with EIB comorbidity observed in 53% of these subjects. Misdiagnosis of IS as EIB is common. The lack of a beta(2)-agonist response in combination with postexercise serial spirometry can be useful in excluding solitary IS and confirming EIB diagnosis.     

Modification of selected lipoproteins and blood pressure by different dosages of n-3-fatty acids

125 male patients with cardiovascular diseases (51.0 +/- 5.1 years) were treated with supplementary fish oil diet (gelatin capsules 2 g or 6 g PUFA/a day) and arachis oil gelatin capsules, respectively, as well as simultaneous fat- and energy-reduced diet at a moderate body-training during a four-week cure. N-3 PUFA-rich fish oil diet caused a significant decrease of the triglycerides and the Apo B with increase of the HDL2 cholesterol. By addition of reduction diet the effect became clearer by additional ascertained decrease of total and LDL-cholesterol. The blood pressure-reducing effect of n-3 PUFA, but not n-6 PUFA, at test as well as on exertion was present with 2 g and 6 g/a day, however, it was more conspicuous with the higher dosage.     

Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis

OBJECTIVE: To determine the efficacy of fish oil derived (n-3) fatty acid supplementation (3-6 capsules/day) in subjects with rheumatoid arthritis (RA) whose (n-6) fatty acid intake in the background diet was < 10 g/day, compared to olive/corn oil capsule supplement over a 15 week period. METHODS: A placebo controlled, double blind, randomized 15 week study to determine the effect of supplementation on clinical variables in 50 subjects with RA whose background diet was naturally low in (n-6) fatty acids. Fish oil containing 60% (n-3) fatty acids was supplemented at a rate of 40 mg/kg body weight. RESULTS: Analysis of 9 clinical variables indicated there was a significant difference (p < 0.02) between control and treatment groups. Five subjects in the treatment group and 3 in the control group met the American College of Rheumatology 20% improvement criteria. Dietary supplementation resulted in a significant increase in eicosapentaenoic acid in plasma and monocyte lipids in the supplemented group. CONCLUSION: The findings suggest that fish oil supplementation that delivers (n-3) fatty acids at a dose of 40 mg/kg body weight/day, with dietary (n-6) fatty acid intake < 10 g/day in the background diet, results in substantial cellular incorporation of (n-3) fatty acids and improvements in clinical status in patients with RA.     

Effect of polyunsaturated fatty acids of the n-3 and n-6 series on lipid composition and eicosanoid synthesis of platelets and aorta and on immunological induction of atherosclerosis in rabbits

The effect of dietary fish oil (rich in n-3 polyunsaturated fatty acids (PUFA], corn oil (rich in n-6 PUFA) and coconut oil (low in n-3 and n-6 PUFA) on the induction of atherosclerosis by serum sickness in rabbits was investigated over a 12-month period. Dietary fish oil led to a significant increase in the level of eicosapentaenoic acid (EPA) in all platelet phospholipid fractions and to a significant reduction in the level of platelet phosphatidylethanolamine arachidonic acid (AA). In aortic total phospholipids, rabbits given fish oil showed a significant reduction in AA and a significant increase in EPA. Rabbits given fish oil showed significantly lower collagen-induced platelet thromboxane A2 release and aortic production of 6-keto-PGF1 alpha. Serum total immune complex levels and anti-horse serum IgG levels were not influenced by diet. There was a significant reduction in total aortic atherosclerosis in fish oil-fed animals compared with coconut oil fed animals.     

Fat modification in the diabetes diet.

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

Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma

BACKGROUND: Previous research has shown that diet can modify the bronchoconstrictor response to exercise in asthmatic subjects. OBJECTIVE: Determine the effect of ascorbic acid supplementation on pulmonary function and several urinary markers of airway inflammation in asthmatic subjects with exercise-induced bronchoconstriction (EIB). METHODS: Eight asthmatic subjects with documented EIB participated in a randomized, placebo controlled double-blind crossover trial. Subjects entered the study on their usual diet and were placed on either 2 weeks of ascorbic acid supplementation (1500 mg/day) or placebo, followed by a 1-week washout period, before crossing over to the alternative diet. Pre- and post-exercise pulmonary function, asthma symptom scores, fraction of exhaled nitric oxide (FENO), and urinary leukotriene (LT) C4-E4 and 9alpha, 11beta-prostagladin (PG) F2] were assessed at the beginning of the trial (usual diet) and at the end of each treatment period. Results: The ascorbic acid diet significantly reduced (p < 0.05) the maximum fall in post-exercise FEV1 (-6.4 +/- 2.4%) compared to usual (-14.3 +/- 1.6%) and placebo diet (-12.9 +/- 2.4%). Asthma symptoms scores significantly improved (p<0.05) on the ascorbic acid diet compared to the placebo and usual diet. Post-exercise FENO, LTC4-E4 and 9alpha, 11beta-PGF2 concentration was significantly lower (p<0.05) on the ascorbic acid diet compared to the placebo and usual diet. CONCLUSION: Ascorbic acid supplementation provides a protective effect against exercise-induced airway narrowing in asthmatic subjects.     

Consumption of eicosapentaenoic acid and docosahexaenoic acid impair murine interleukin-12 and interferon-gamma production in vivo

In mice, individual dietary omega-3 polyunsaturated fatty acids n-3 (PUFA) were found to be sufficient to effect the changes in circulating interleukin (IL)-12 and interferon (IFN)-gamma levels that were previously seen in fish oil-fed mice. Weanling female C3H mice were fed one of five experimental diets. All five diets met all known nutritional requirements for mice and differed only in the fat source. After 4 weeks, mice were challenged with live Listeria monocytogenes or sterile PBS. Twenty-four hours after infection, n-3 PUFA-fed mice had significantly lower circulating IL-12 p70 and IFN-gamma than mice fed the control diet (P<.01). In addition, splenic cytokine mRNA for IL-12 p40, tumor necrosis factor-alpha, and IL-1beta were lower in infected mice fed n-3 PUFA-containing diets than in mice fed the olive oil ethyl esters control diet. The reduction of IL-12 and IFN-gamma production by n-3 PUFA may have important implications for host infectious disease resistance.     

Comparative effects of feeding different fats on fatty acid composition of major individual phospholipids of rat hearts

Comparative effects of feeding dietary linoleic (corn oil), oleic (olive oil), alpha-linolenic (soybean oil) and polyunsaturated fatty acids (fish oil) on lipid content and fatty acid composition of major individual phospholipids of rat hearts were examined. Feeding different diets did not result in lipid accumulation in the heart. Total triglyceride, nonesterified fatty acid, cholesteryl ester and phospholipid levels of heart tissue were not affected by the type of dietary fatty acid. However, heart free cholesterol levels decreased in both animals fed the olive and the fish oil diets. The percentage of individual phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and cardiolipin (CL) did not modify by changes in the dietary fat composition. Heart tissue from animals fed on olive oil were enriched with 18:1 (n-9 + n-7) fatty acid in all phospholipid fractions. Animals fed corn oil contained higher proportions of 18:2 (n-6) for PC, PE and CL, and the ingestion of the soybean oil diet increased 18:2 (n-6) for PC and CL in the same proportion as the ingestion of the corn oil diet. The levels of 22:6 (n-3) were increased in the fish oil-fed group, accompanied by both a decrease in total (n-6) fatty acids and an increase in total (n-3) fatty acids in the three phospholipid fractions. The 20:5 (n-3) was only detected in these animals. These results show that olive oil is as effective as fish oil in reducing heart cholesterol content and support earlier works suggesting the role of fish oil in preventing cardiovascular disease.     

Dietary Omega-3 Polyunsaturated Fatty Acid Supplementation and Airway Hyperresponsiveness in Asthma

Asthma prevalence continues to increase despite the progress that has been made in the treatment options for asthma. Alternative treatment therapies that reduce the dose requirements of pharmacological interventions would be beneficial, and could potentially reduce the public health burden of this disease. There is accumulating evidence that dietary modification has potential to influence the severity of asthma and reduce the prevalence and incidence of this condition. A possible contributing factor to the increased incidence of asthma in Western societies may the consumption of a pro-inflammatory diet. In the typical Western diet, 20–25-fold more omega (n)-6 polyunsaturated fatty acids (PUFA) than n-3 PUFA are consumed, which results in the release of pro-inflammatory arachidonic acid metabolites. Eicosapentaenoic acid and docosahexaenoic acid are n-3 PUFA derived from fish oil that competitively inhibit n-6 PUFA arachidonic acid (AA) metabolism and this reduce the generation of pro-inflammatory 4-series leukotrienes (LTs) and 2-series prostaglandins (PGs) and production of cytokines from inflammatory cells. These data are consistent with the proposed pathway by which dietary intake of n-3 PUFA modulates lung disease. This article will review the existing information concerning the relationship between n-3 PUFA supplementation and airway hyperresponsiveness in asthma. It includes studies assessing the efficacy of n-3 PUFA supplementation in exercise-induced bronchoconstriction. This review will also address the question as to whether supplementing the diet with n-3 PUFA represents a viable alternative treatment regimen for asthma.     

Dietary Omega-3 Polyunsaturated Fatty Acid Supplementation and Airway Hyperresponsiveness in Asthma

Asthma prevalence continues to increase despite the progress that has been made in the treatment options for asthma. Alternative treatment therapies that reduce the dose requirements of pharmacological interventions would be beneficial, and could potentially reduce the public health burden of this disease. There is accumulating evidence that dietary modification has potential to influence the severity of asthma and reduce the prevalence and incidence of this condition. A possible contributing factor to the increased incidence of asthma in Western societies may the consumption of a pro-inflammatory diet. In the typical Western diet, 20-25-fold more omega (n)-6 polyunsaturated fatty acids (PUFA) than n-3 PUFA are consumed, which results in the release of pro-inflammatory arachidonic acid metabolites. Eicosapentaenoic acid and docosahexaenoic acid are n-3 PUFA derived from fish oil that competitively inhibit n-6 PUFA arachidonic acid (AA) metabolism and this reduce the generation of pro-inflammatory 4-series leukotrienes (LTs) and 2-series prostaglandins (PGs) and production of cytokines from inflammatory cells. These data are consistent with the proposed pathway by which dietary intake of n-3 PUFA modulates lung disease. This article will review the existing information concerning the relationship between n-3 PUFA supplementation and airway hyperresponsiveness in asthma. It includes studies assessing the efficacy of n-3 PUFA supplementation in exercise-induced bronchoconstriction. This review will also address the question as to whether supplementing the diet with n-3 PUFA represents a viable alternative treatment regimen for asthma.     

The Gruppo Italiano per lo Studio della Sopravvivenza nell’infarto miocardio (GISSI)-Prevenzione trial on fish oil and vitamin E supplementation in myocardial infarction survivors

A recent large-scale, open-label, randomized, controlled trial in 11,324 myocardial infarction (MI) survivors has shown low-dose fish oil, but not vitamin E, to reduce significantly the cumulative rate of all-cause death, nonfatal MI, and nonfatal stroke. Neither intervention significantly reduced the other primary endpoint, the cumulate rate of cardiovascular death, nonfatal MI, and nonfatal stroke. Analysis of secondary endpoints indicated that the benefits of the 875 mg fish oil capsules containing 850 to 882 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as ethyl esters was in reducing mortality and not in a reduction of nonfatal MI. It was a safe intervention. The internal validity and external validity of the data was examined and the findings placed in clinical perspective. Important questions remain about the benefits of increased plant sources of n-3 polyunsaturated fatty acids (PUFA) for those who cannot obtain or consume fish. Also the benefits of diet versus fish oil supplementation haven’t been determined precisely. Although it seems reasonable to increase sources of n-3 PUFA in the diet for those at high risk of coronary heart disease, current data do not support a policy of promoting fish oil capsules for secondary prevention of coronary heart disease.     

Dietary n-3 polyunsaturated fatty acid and status of immunocompetent cells involved in innate immunity in female rats

The aim of this study was to estimate the contributions of dietary n-3 polyunsaturated fatty acid (PUFA), a representative dietary immunosuppressant, to the activity of both alveolar macrophages (AM) and natural killer (NK) cells, and compare them to those of n-6 PUFA. Twelve 5-week-old female Sprague-Dawley rats were divided into two dietary groups, one fed a 10% fat diet for 9 weeks enriched with n-3 PUFA (n-3 diet) and the other an n-6 PUFA (n-6 diet). AM reduced the release of nitric oxide, monocyte chemoattractant protein 1 and tumor necrosis factor alpha in the rats fed the n-3 diet, compared with rats fed the n-6 diet. NK cell activity was reduced by consumption of the n-3 diet. This study suggests that consumption of n-3 PUFA can ameliorate pulmonary inflammatory disorders which are affected by the reduction of not only proinflammatory cytokines but also chemokine released from AM.     

A high-cholesterol, n-3 polyunsaturated fatty acid diet causes different responses in rats and hamsters

This study was designed to investigate the response to a high-cholesterol, n-3 polyunsaturated fatty acid (PUFA) or n-6 PUFA diet in rats and hamsters. Animals were fed n-3 or n-6 PUFA with a cholesterol-free diet, or with a diet enriched with cholesterol (0.5%, w/w) for 2 weeks. In rats and hamsters fed a cholesterol-free diet, plasma cholesterol, triglycerides and very-low-density lipoprotein (VLDL)-triglyceride levels in n-3 PUFA group were significantly lower than those in n-6 PUFA group. In contrast, when diets were supplemented with 0.5% cholesterol, the plasma cholesterol- and triglyceride-lowering effect of dietary n-3 PUFA disappeared. In hamsters fed with the atherogenic diet (0.5% dietary cholesterol) for 2 weeks, n-3 PUFA induced hypercholesterolemia more than n-6 PUFA, the increase being in the VLDL and low-density lipoprotein (LDL) fractions. Our data thus indicate that elevation of VLDL- and LDL-cholesterol in hamsters by n-3 PUFA, compared with n-6 PUFA, is dependent on 0.5% dietary cholesterol supplementation. In rats, on the other hand, dietary n-3 PUFA did not induce hypercholesterolemia more than n-6 PUFA when 0.5% cholesterol was supplemented. Although the effects of n-3 PUFA on plasma cholesterol, triglycerides and VLDL-triglycerides were similar in hamsters and rats, the interactive effects of n-3 PUFA and cholesterol on plasma and lipoprotein cholesterol levels differed in the two species. It was also found that plasma triglycerides, cholesterol and lipoprotein cholesterol levels in hamsters are higher than in rats in the presence and absence of dietary cholesterol. In addition, cholesterol feeding induces hypertriglyceridemia and hypercholesterolemia only in hamsters. Moreover, liver triglyceride concentrations increased in rats fed a cholesterol-rich diet and hepatic triglyceride levels of the n-3 PUFA-fed rats were significantly lower than those in the n-6 PUFA-fed rats in the presence and absence of dietary cholesterol. However, triglycerides did not accumulate in the liver in hamsters fed a cholesterol-rich diet and hepatic triglyceride levels of the n-3 PUFA-fed hamsters were not significantly different from those in the n-6 PUFA-fed hamsters in the presence and absence of dietary cholesterol. Therefore, these studies confirm marked species differences in response to the interactive effects of dietary n-3 PUFA and cholesterol.     

Effects of dietary saturated,monounsaturated and n-3 fatty acids on fasting lipoproteins,LDL size and post-prandial lipid metabolism in healthy subjects

BACKGROUND: The influence of the quality of dietary fat on some aspects of lipid metabolism-i.e. lipoprotein concentrations, post-prandial lipids and LDL size-is not completely understood, especially in healthy individuals. OBJECTIVES: Aim of this study was to evaluate the effects of different types of dietary fat (monounsaturated vs. saturated fatty acids, and n-3 or placebo supplementation) on fasting lipoproteins, LDL size and post-prandial lipids in healthy people. DESIGN: One hundred and sixty-two individuals were randomly assigned to follow two isoenergetic diets, one rich in saturated fatty acids (SFA diet) and the other in monounsaturated fatty acids (MUFA diet). Each group was further randomised to receive supplementation with fish oil (3.6 g/day) or placebo. RESULTS: The type of diet significantly affected LDL cholesterol and triacylglycerol content, which was higher with the SFA diet and lower with the MUFA diet. The changes between the two diets were statistically significant for cholesterol (P<0.01) and triacylglycerol (P<0.03). VLDL cholesterol and triacylglycerol were significantly reduced and LDL cholesterol significantly increased by fish oil supplementation. Plasma triacylglycerol was significantly lower in those taking n-3 fatty acids, also 1 and 3 h after a test-meal. Neither type of diet nor n-3 supplementation affected LDL size. CONCLUSIONS: A moderate substitution of saturated fatty acids with monounsaturated fatty acids has beneficial effects on lipid metabolism also in healthy individuals. A moderate supplementation of long-chain n-3 fatty acids in healthy individuals reduces both fasting and post-prandial triacylglycerol concentrations but increases LDL cholesterol, irrespective of the type of diet.     

The effects of dietary fatty acid supplementation on endothelial function and vascular tone in healthy subjects

OBJECTIVE: Evaluation of the effects of supplementation of n-3 and n-6 fatty acids on vascular tone and endothelial function in healthy men and women aged 40 to 65 years. METHODS: In a double-blind, randomised, placebo controlled study, 173 healthy volunteers took one of six oil supplements for 8 months. Supplements were placebo, oleic acid rich sunflower oil, evening primrose oil, soya bean oil, tuna fish oil, and tuna/evening primrose oil mix. Endothelium-dependent and independent vascular responses were measured in the forearm skin using laser Doppler imaging following iontophoretic applications of acetylcholine and sodium nitroprusside, respectively. RESULTS: Acetylcholine, but not sodium nitroprusside responses were significantly improved after tuna oil supplementation (P=0.02). Additionally, there were significant positive correlations between acetylcholine responses and n-3 fatty acid levels in the plasma and erythrocyte membrane phospholipids after tuna oil supplementation. No significant changes in vascular response were seen after supplementation with any of the other oils. CONCLUSIONS: Fish oil supplementation has a beneficial effect on endothelial function, even in normal healthy subjects. Modification of the diet by an increase of 6% in eicosapentaenoic acid and 27% in docosahexaenoic acid (equivalent to eating oily fish 2-3 times/week) might have significant beneficial effects on cardiovascular function and health.     

Pilot study of the effects of n-3 polyunsaturated fatty acids on exhaled nitric oxide in patients with stable asthma.

BACKGROUND: The anti-inflammatory effects of n-3 polyunsaturated fatty acids (n-3 PUFA) have been demonstrated both in vitro and in vivo. The results of epidemiological studies suggest that fish consumption has a beneficial effect on lung function and prevalence of asthma. However, data from intervention trials have not revealed a beneficial effect of n-3 PUFA supplementation in patients with established disease. OBJECTIVE: To study the effects of short-term n-3 PUFA supplementation in addition to maintenance therapy on exhaled nitric oxide in asthmatic patients. METHODS: A double-blind, placebo-controlled trial was undertaken in 20 women with asthma. Patients received either a combination of eicosapentaenoic acid and docosahexaenoic acid plus 10 mg vitamin E or placebo twice daily for 2 weeks. The primary outcome measure was the fraction of exhaled nitric oxide (FeNO) and the secondary outcomes were asthma control (score on theAsthma Control Questionnaire [ACQI) and lung function (forced expiratory volume in 1 second [FEV1]). RESULTS: No significant differences were observed in FeNO, ACQ score, or FEV1 between patients receiving n-3 PUFA supplementation and those receiving placebo. CONCLUSIONS: Short-term dietary supplementation with n-3 PUFA in women with stable asthma was not associated with statistically significant changes in FeNO, asthma control, or lung function.     

Beneficial effects of long-chain n-3 fatty acids included in an energy-restricted diet on insulin resistance in overweight and obese European young adults

AIMS/HYPOTHESIS: Epidemiological research indicates that long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) improve insulin resistance. The aim of this study was to investigate the effects of seafood consumption on insulin resistance in overweight participants during energy restriction. METHODS: In this 8 week dietary intervention, 324 participants (20-40 years, BMI 27.5-32.5 kg/m(2), from Iceland, Spain and Ireland) were randomised by computer to one of four energy-restricted diets (-30E%) of identical macronutrient composition but different LC n-3 PUFA content: control (n = 80; no seafood; single-blinded); lean fish (n = 80; 150 g cod, three times/week); fatty fish (n = 84; 150 g salmon, three times/week); (4) fish oil (n = 80; daily docosahexaenoic/eicosapentaenoic acid capsules, no other seafood; single-blinded). Fasting glucose, insulin, adiponectin, plasma triacylglycerol and fatty acids in erythrocyte membrane were measured at baseline and endpoint. Insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). Linear models with fixed effects and covariates were used to investigate the effects of seafood consumption on fasting insulin and HOMA-IR at endpoint in comparison with the control group. RESULTS: Of the participants, 278 (86%) completed the intervention. Fish oil intake was a significant predictor of fasting insulin and insulin resistance after 8 weeks, and this finding remained significant even after including weight loss, triacylglycerol reduction, increased LC n-3 PUFA in membranes or adiponectin changes as covariates in the statistical analysis. Weight loss was also a significant predictor of improvements. CONCLUSIONS/INTERPRETATION: LC n-3 PUFA consumption during energy reduction exerts positive effects on insulin resistance in young overweight individuals, independently from changes in body weight, triacylglycerol, erythrocyte membrane or adiponectin. Trial registration: ClinicalTrials.gov NCT00315770.     

Who's afraid of n-6 polyunsaturated fatty acids? Methodological considerations for assessing whether they are harmful

N-6 fatty acids are essential for normal growth, development and health, and so extreme care is necessary before deciding that they are harmful. Theoretical and epidemiological evidence suggests the involvement of n-6 polyunsaturated fatty acids (PUFAs) in disease progression or prevention; however, n-6 function cannot be considered in isolation but needs to be seen as part of the complex of nutrient interactions with n-3 fatty acids (which compete for the same enzymatic pathways) and antioxidants. Insulin sensitivity might be the common factor relating disease to fatty acid metabolism both within and between the fatty acid pathways. High linoleate to arachidonate concentrations have been observed in insulin resistance, diabetic complications and some tumours, but these are multifactorial processes that include many lifestyle determinants and it is therefore wrong to condemn only n-6 fatty acids in their etiology. The results based on the criteria for assessing diet and disease are still insufficient to declare n-6 fatty acids a serious health risk; at most, the verdict should be "not proven". The question may never be conclusively answered not only because prospective dietary intervention trials (unlike those with n-3 fish oil capsules) are fraught with dosage and compliance problems, but also because of high background linoleate consumption. Tissue fatty acid composition may be a suitable biomarker for PUFA intake but there are many theoretical and methodological problems concerning other suitable markers because of the multiplicity of their biological effects. Before making evidence-based dietary recommendations, future research should consider: 1) how n-3 and n-6 dietary PUFAs affect the physiological balance (dose-response) of their derivatives such as eicosanoids and the newly-discovered fatty acid amides; 2) the metabolic interactions between n-6 and n-3 fatty acid pathways (including gene-nutrient effects); 3) the need for antioxidant cover (quantity and quality); 4) prospective intervention trials.     

Influence of n-3 polyunsaturated fatty acids on soluble cellular adhesion molecules as biomarkers of cardiovascular risk in young healthy subjects

Background and aimSerum levels of soluble cellular adhesion molecules (CAMs) and blood lipid parameters have been used as markers of inflammatory processes associated with cardiovascular disease (CVD) events. The present study evaluated the effects of the intake of n-3 polyunsaturated fatty acids (PUFAs) in fish and fish oil within energy-restricted diets, on soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1).Methods and resultsTwo hundred and seventy-five healthy European subjects aged between 20 and 40 years, were randomized to one of four hypocaloric dietary groups: control (sunflower oil capsules, no seafood), lean fish (3 × 150 g portions of cod/week), fatty fish (3 × 150 g portions of salmon/week), fish oil ((docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) capsules, no seafood)). Diets rich in lean fish significantly decreased ICAM-1 levels, around 5% from baseline to endpoint (p < 0.05), and had no effect on VCAM-1 levels. No significant differences were observed in sICAM-1 levels after the intervention with fatty fish or fish oils. On the other hand, these two seafood based diets were responsible for a significant increase of VCAM-1 levels [fatty fish; 16.1% and fish oil; 21.9%] respectively (p < 0.05).ConclusionsCAMs as inflammatory biomarkers in young and healthy subjects are not conclusive for the evaluation of CVD risk. Hypocaloric fish diets had a different effect on CAMs, being lean fish responsible for the highest decrease in ICAM-1. On the other hand, VCAM-1 results allow speculation that a low dose of n-3 PUFA may be anti-inflammatory contrarily to a high dose which can have a pro-inflammatory effect. CAMs mechanism is complex and affected by multiple factors such as lifestyle, gender, and n-3 dose and source.