Regulation of cellular differentiation and apoptosis by fatty acids and their metabolites.

We have reviewed the literature regarding the effects of fatty acids and their metabolites on cellular differentiation and apoptosis. Results obtained in different studies have been variable, but some generalizations can be made. Differentiation was increased by incubation of cells with arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), or leukotriene D4 (LTD4). Effects of these agents on differentiation could be magnified with the simultaneous addition of other differentiation-inducing agents like dimethylsulfoxide or retinoic acid. AA and gamma-linolenic acid increased apoptosis while the effects of n-3 fatty acids (EPA and DHA) and of eicosanoids varied from stimulation to inhibition. These inconsistencies are attributed to the differences in methods used to evaluate differentiation and apoptosis, concentrations of fatty acids and serum, exposure time and the cell models used. Studies using the physiological concentrations of the fatty acids and standardized experimental conditions need to be conducted to establish effects of fatty acids and their metabolites on these cellular processes.     

Highly unsaturated (n-3) fatty acids, but not alpha-linolenic, conjugated linoleic or gamma-linolenic acids, reduce tumorigenesis in Apc(Min/+) mice

We showed previously that dietary eicosapentaenoic acid [EPA, 20:5(n-3)] is antitumorigenic in the APC:(Min/+) mouse, a genetic model of intestinal tumorigenesis. Only a few studies have evaluated the effects of dietary fatty acids, including EPA and docosahexaenoic acid [DHA, 22:6(n-3)], in this animal model and none have evaluated the previously touted antitumorigenicity of alpha-linolenic acid [ALA, 18:3(n-3)], conjugated linoleic acid [CLA, 77% 18:2(n-7)], or gamma-linolenic acid [GLA, 18:3(n-6)]. Stearidonic acid [SDA, 18:4(n-3)], the Delta6-desaturase product of ALA, which is readily metabolized to EPA, has not been evaluated previously for antitumorigenic efficacy. This study was undertaken to evaluate the antitumorigenicity of these dietary fatty acids (ALA, SDA, EPA, DHA, CLA and GLA) compared with oleic acid [OA, 18:1(n-9)] at a level of 3 g/100 g in the diets of APC:(Min/+) mice and to determine whether any alterations in tumorigenesis correspond to alterations in prostaglandin biosynthesis. Tumor multiplicity was significantly lower by approximately 50% in mice fed SDA or EPA compared with controls, whereas less pronounced effects were observed in mice fed DHA (P: = 0.15). ALA, CLA and GLA were ineffective at the dose tested. Although lower tumor numbers coincided with significantly lower prostaglandin levels in SDA- and EPA-fed mice, ALA and DHA supplementation resulted in equally low prostaglandin levels, despite proving less efficacious with regard to tumor number. Prostaglandin levels did not differ significantly in the CLA and GLA groups compared with controls. These results suggest that SDA and EPA attenuate tumorigenesis in this model and that this effect may be related in part to alterations in prostaglandin biosynthesis.     

不同膳食脂肪酸对大鼠乳腺癌组织脂肪酸组成和脂代谢基因表达的影响

目的探讨不同膳食脂肪酸组成影响大鼠乳腺癌发生、发展的可能分子机制。方法用8种不同膳食脂肪酸组成(SFA、MUFA、n-6PUFA、n-3PUFA、1∶1n-6/n-3、5∶1n-6/n-3、10∶1n-6/n-3、1∶2∶1S/M/P其中n-6/n-31∶1)喂养SD雌性大鼠,并在大鼠乳腺癌模型的基础上,用气相色谱内标法观察大鼠乳腺组织脂肪酸组成改变,RT-PCR分析组织脂代谢调控基因(FAS、COX-2和5-LOX)的表达。结果在不同膳食脂肪酸构成中,只有1∶1n-6/n-3能有效抑制大鼠乳腺癌的发生。不同膳食脂肪酸构成可导致大鼠乳腺组织脂肪酸组成发生相应变化,且各组间的脂肪酸含量有显著差异。高乳腺癌诱发的SFA、MUFA、n-6PUFA、5∶1n-6/n-3、10∶1n-6/n-3和1∶2∶1S/M/P喂养组乳腺组织含有较多的C18∶1、C18∶2和C20∶4,而EPA和DHA含量极少。无或低乳腺癌诱发的n-3PUFA和1∶1n-6/n-3喂养组乳腺组织EPA和DHA明显增多,C20∶4含量显著减少。RT-PCR结果显示1∶1n-6/n-3低诱癌组较相应对喂组上调FAS、COX-2和5-LOXmRNA表达力度明显弱于其它高乳腺癌诱发组。结论不同膳食脂肪酸组成能明显改变大鼠乳腺组织脂肪酸组成,进而影响脂代谢基因FAS、COX-2和5-LOX表达,可能是大鼠乳腺癌发生的分子机制之一。     

Dietary n-3 polyunsaturated fatty acids and amelioration of cardiovascular disease: possible mechanisms

Consumption of n-3 polyunsaturated fatty acids (n-3 PUFAs) is associated with a reduced incidence of coronary arterial diseases. Dietary n-3 PUFAs act via several mechanisms. They depress plasma lipids, especially triglycerides (TGs), by inhibiting hepatic TGs and possibly apoprotein synthesis. They replace arachidonic acid (AA) in phospholipid pools with eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA). EPA and DHA, when released, inhibit cyclooxygenase and lipoxygenase and reduce eicosanoid synthesis, particularly thromboxane (TXA2) and leukotriene B4 (LTB4), by platelets and macrophages. Reduction of the proaggregatory, vasoconstrictive TXA2 decreases the thrombotic tendency of platelets. This is augmented by the limited depression of the vasoactive antiaggregatory prostacyclin (PGI2) and the generation of antiaggregatory prostaglandin I3 (PGI3) from EPA. The n-3 PUFAs also depress eicosanoid metabolism in platelets, monocytes, and macrophages, and thereby may retard the initiation and progress of atherogenesis. n-3 PUFAs reduce blood pressure and blood viscosity and modulate membrane fluidity and associated enzyme and receptor functions. The collective effects of n-3 PUFAs may account for the reduction in coronary arterial disease in populations consuming foods containing n-3 PUFAs.     

Blood concentrations of individual long-chain n-3 fatty acids and risk of nonfatal myocardial infarction

BACKGROUND: Whereas dietary intake of long-chain n-3 fatty acids has been associated with risk of nonfatal myocardial infarction (MI), few studies have examined the relation for blood concentrations. OBJECTIVE: We aimed to investigate the effect of long-chain n-3 fatty acids in blood on the risk of nonfatal MI. DESIGN: Baseline blood samples were collected from 32 826 participants of the Nurses' Health Study in 1989-1990, among whom 146 incident cases of nonfatal MI were ascertained during 6 y of follow-up and matched with 288 controls. RESULTS: After multivariate adjustment, the relative risks (95% CI) comparing the highest with the lowest quartiles in plasma were 0.23 (0.09, 0.55; P for trend = 0.001) for eicosapentaenoic acid (EPA), 0.40 (0.20, 0.82; P for trend = 0.004) for docosapentaenoic acid (DPA), and 0.46 (0.18, 1.16; P for trend = 0.07) for docosahexaenoic acid (DHA). The associations for these fatty acids in erythrocytes were generally weaker and nonsignificant. In contrast to EPA and DHA, blood concentrations of DPA were not correlated with dietary consumption of n-3 fatty acids. Higher plasma concentrations of EPA, DPA, and DHA were associated with higher plasma concentrations of HDL cholesterol and lower concentrations of triacylglycerol and inflammatory markers. CONCLUSIONS: Higher plasma concentrations of EPA and DPA are associated with a lower risk of nonfatal MI among women. These findings may partly reflect dietary consumption but, particularly for DPA, may indicate important risk differences based on metabolism of long-chain n-3 fatty acids.     

Dietary omega-3 fatty acids differentially influence ova release and ovarian cyclooxygenase-1 and cyclooxygenase-2 expression in rats

Ovulation is a prostaglandin (PG)-dependent process. Although n-3 polyunsaturated fatty acids (PUFA) and conjugated linoleic acid (CLA) have differing effects in the body, both reduce PG synthesis. We hypothesized that dietary n-3 fatty acids and CLA would differentially alter ovarian PG profiles through reductions in expression of enzymes involved in PG biosynthesis resulting in enhanced ovulation. Our objectives were to determine how dietary stearidonic acid and eicosapentaenoic acid (EPA) at 0.3 g/100 g diet and mixed isomers of CLA at 0.7 g/100 g diet, human achievable levels with daily consumption of fish or beef and dairy products, respectively, would influence ovulation and ovarian cyclooxygenase-1 (COX-1) and COX-2 expression in ovulation-induced rats. After 27 days on diet and ovulation induction, ovaries were isolated and analyzed from 22 pups per diet. Eicosapentaenoic acid ingestion reduced ova release by 16% while increasing PGE₂ and PGF_2α release without altering COX-1 or COX-2 expression. Conversely, ovarian COX-1 expression was increased 135% with stearidonic acid ingestion associated with increased PGF_2α without altering PGE₂ or ova release. Conjugated linoleic acid ingestion reduced COX-2 expression to 65% of that in rats consuming control and EPA diets; however, without affecting ovulation or PGs. Although it is generally believed that the COX-2 is the primary COX involved in ovulation, these results demonstrated that the n-3 PUFA differently affect ovarian COX-1 expression and that this effect differs from CLA, which reduced COX-2 expression. Further, although ovarian PGF_2α is the primary PG altered by dietary n-3 PUFA, n-3 PUFA differentially influence ovarian PG biosynthesis and can decrease ova release, possibly induced through constitutive COX-1 enzyme expression.     

n-3 Polyunsaturated fatty acids,fatal ischemic heart disease,and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study

BACKGROUND: Little is known about the relation of the dietary intake of n-3 polyunsaturated fatty acids, ie, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from fatty fish and alpha-linolenic acid from vegetable oils, with ischemic heart disease among older adults. OBJECTIVE: We investigated the associations of plasma phospholipid concentrations of DHA, EPA, and alpha-linolenic acid as biomarkers of intake with the risk of incident fatal ischemic heart disease and incident nonfatal myocardial infarction in older adults. DESIGN: We conducted a case-control study nested in the Cardiovascular Health Study, a cohort study of adults aged > or = 65 y. Cases experienced incident fatal myocardial infarction and other ischemic heart disease death (n = 54) and incident nonfatal myocardial infarction (n = 125). Matched controls were randomly selected (n = 179). We measured plasma phospholipid concentrations of n-3 polyunsaturated fatty acids in blood samples drawn approximately 2 y before the event. RESULTS: A higher concentration of combined DHA and EPA was associated with a lower risk of fatal ischemic heart disease, and a higher concentration of alpha-linolenic acid with a tendency to lower risk, after adjustment for risk factors [odds ratio: 0.32 (95% CI: 0.13, 0.78; P = 0.01) and 0.52 (0.24, 1.15; P = 0.1), respectively]. In contrast, n-3 polyunsaturated fatty acids were not associated with nonfatal myocardial infarction. CONCLUSIONS: Higher combined dietary intake of DHA and EPA, and possibly alpha-linolenic acid, may lower the risk of fatal ischemic heart disease in older adults. The association of n-3 polyunsaturated fatty acids with fatal ischemic heart disease, but not with nonfatal myocardial infarction, is consistent with possible antiarrhythmic effects of these fatty acids.     

Metabolism of stearidonic acid in human subjects: comparison with the metabolism of other n-3 fatty acids

BACKGROUND: For many persons who wish to obtain the health benefits provided by dietary n-3 fatty acids, daily ingestion of fish or fish oil is not a sustainable long-term approach. To increase the number of sustainable dietary options, a land-based source of n-3 fatty acids that is effective in increasing tissue concentrations of the long-chain n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is required. OBJECTIVE: The objective of the study was to examine the ability of dietary stearidonic acid (SDA) to increase tissue concentrations of EPA and DHA in healthy human subjects and to compare the effectiveness of SDA with that of the n-3 fatty acids alpha-linolenic acid (ALA) and EPA. DESIGN: Encapsulated SDA, ALA, or EPA was ingested daily in doses of 0.75 g and then 1.5 g for periods of 3 wk each by healthy male and postmenopausal female subjects (n = 15/group) in a double-blind, parallel-group design. RESULTS: Dietary SDA increased EPA and docosapentaenoic acid concentrations but not DHA concentrations in erythrocyte and in plasma phospholipids. The relative effectiveness of the tested dietary fatty acids in increasing tissue EPA was 1:0.3:0.07 for EPA:SDA:ALA. CONCLUSIONS: Vegetable oils containing SDA could be a dietary source of n-3 fatty acids that would be more effective in increasing tissue EPA concentrations than are current ALA-containing vegetable oils. The use of SDA-containing oils in food manufacture could provide a wide range of dietary alternatives for increasing tissue EPA concentrations.     

Cardiovascular disease risk factors and n-3 fatty acid status in the adult population of James Bay Cree

BACKGROUND: Canadian native populations, which traditionally consume large amounts of fish, have lower rates of mortality from heart disease than do Canadian nonnative populations, which have low fish intakes. Fish oils rich in n-3 fatty acids may have a protective effect against cardiovascular disease (CVD) risk factors. OBJECTIVES: The purposes were to examine the profile of plasma phospholipid concentrations of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) among James Bay Cree and to verify the relation between these concentrations and CVD risk factors. DESIGN: The study population consisted of 917 subjects aged 18-74 y who participated in the 1991 Santé Québec Health Survey. Data were obtained through home interviews and clinic visits. Plasma samples were analyzed for phospholipid fatty acid composition. RESULTS: The mean fish consumption on the day before the survey was 60 g among the adult Cree population. Expressed as a percentage of total fatty acids, relative concentrations of EPA and DHA were 0.65% and 2.80%, respectively. n-3 Fatty acids were higher among coastal residents than among inland residents. A positive association was observed between plasma HDL and n-3 fatty acids. EPA and EPA+DHA were inversely associated with triacylglycerols. Among subjects aged 50-74 y, an inverse association between EPA and EPA:AA and total:HDL cholesterol was observed. CONCLUSIONS: n-3 Fatty acids may favorably influence some CVD risk factors. The Cree population must be encouraged to maintain their traditional fish-based diet, which may be one of the factors protecting them against mortality from CVD.     

n-3 Fatty acids and cardiovascular disease risk factors among the Inuit of Nunavik

BACKGROUND: Inuit traditionally consume large amounts of marine foods rich in n-3 fatty acids. Evidence exists that n-3 fatty acids have beneficial effects on key risk factors for cardiovascular disease. OBJECTIVE: Our goal was to verify the relation between plasma phospholipid concentrations of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and various cardiovascular disease risk factors among the Inuit of Nunavik, Canada. DESIGN: The study population consisted of 426 Inuit aged 18-74 y who participated in a 1992 health survey. Data were obtained through home interviews and clinical visits. Plasma samples were analyzed for phospholipid fatty acid composition. RESULTS: Expressed as the percentage of total fatty acids, geometric mean concentrations of EPA, DHA, and their combination in plasma phospholipids were 1.99%, 4.52%, and 6.83%, respectively. n-3 Fatty acids were positively associated with HDL-cholesterol concentrations and inversely associated with triacylglycerol concentrations and the ratio of total to HDL cholesterol. In contrast, concentrations of total cholesterol, LDL cholesterol, and plasma glucose increased as n-3 fatty acid concentrations increased. There were no significant associations between n-3 fatty acids and diastolic and systolic blood pressure and plasma insulin. CONCLUSIONS: Consumption of marine products, the main source of EPA and DHA, appears to beneficially affect some cardiovascular disease risk factors. The traditional Inuit diet, which is rich in n-3 fatty acids, is probably responsible for the low mortality rate from ischemic heart disease in this population.     

Dietary canola oil: effect on the accumulation of eicosapentaenoic acid in the alkenylacyl fraction of human platelet ethanolamine phosphoglyceride

Volunteers consumed a mixed-fat diet for 6 d (Pre-exp) and then either a canola-oil-based diet (CAN) containing linolenic acid (18:3n-3) or a sunflower-oil-based diet (SUN) rich in linoleic acid (18:2n-6) for 18 d, followed by the alternative diet in a crossover design. Platelet phospholipids were analyzed for changes in fatty acid composition. Eicosapentaenoic acid (EPA) (20:5n-3) was significantly higher in alkenylacyl ethanolamine phosphoglyceride (PPE) and in total phosphatidylcholine (PC) after CAN compared with SUN and Pre-exp. The 22:5n-3 was increased in PPE after CAN above concentrations found after both SUN and Pre-exp. Lower concentrations of 20:4n-6 and 22:4n-6 were observed with CAN in PC and lower concentrations of 22:4n-6 in PPE. These results indicate that the consumption of canola oil moderately increases EPA concentrations and alters the concentrations of other n-6 and n-3 fatty acids in human platelet phospholipids.     

How should patients with Barrett's esophagus be monitored?

Some patients who have been diagnosed with Barrett's esophagus will develop dysplasia and, in some cases, esophageal carcinoma (strength of recommendation [SOR]: A, based on consistent cohort studies). Endoscopic surveillance is recommended for all patients with Barrett's esophagus as it is superior to other methods for detecting esophageal cancer (SOR: B, based on systematic review). The degree of dysplasia noted on biopsy specimens correlates with the risk of esophageal carcinoma development and should guide the frequency of subsequent evaluations (SOR: B, based on consistent cohort studies). The optimal frequency of endoscopy has yet to be determined in any randomized trial. Recommendations from the 2002 American College of Gastroenterology (ACG) Practice Guideline provide guidance as to the frequency of endoscopy surveillance but were not based on an explicit systematic review of the literature (SOR: C, based on expert opinion).     

Ingestion of fish oil or a derived n-3 fatty acid concentrate containing eicosapentaenoic acid (EPA) affects fatty acid compositions of individual phospholipids of rat brain, sciatic nerve and retina

The effect of feeding redfish (Sebastes marinus or mantella) oil or a derived n-3 fatty acid concentrate containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the fatty acid compositions of individual phospholipids in selected neural tissues was studied in growing male rats. Control animals were given sunflower oil in the diet for the 5-wk feeding trial. Lipid analyses revealed that EPA (20:5n-3) became significantly enriched in all phospholipid fractions (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol) in the tissues studied (brain, retina and sciatic nerve) in the two n-3 fatty acid dietary groups relative to controls. Corresponding changes were also found in the 22:5n-3 contents of these tissues, whereas little or no significant elevation in DHA (22:6n-3) was found. In contrast, the percentages by weight of the n-6 fatty acids including 18:2n-6, 20:4n-6 (arachidonic acid, AA), 22:4n-6 and 22:5n-6 were generally lower in the various phospholipids/tissues of the animals given fish oil or the n-3 fatty acid concentrate; the levels of 22:5n-6 and 22:4n-6 were markedly affected in this regard. These results indicate that dietary n-3 fatty acids (as EPA plus DHA) can greatly affect the fatty acid compositions of the various membrane phospholipids in nervous tissues within a relatively short time. These biochemical alterations may be important for functional changes including altered membrane fluidity, cellular responses, ion transport and the biosyntheses of AA- and EPA-derived prostaglandins and leukotrienes.     

Long-chain n-3 polyunsaturated fatty acids in plasma in British meat-eating, vegetarian, and vegan men

BACKGROUND: Plasma concentrations of long-chain n-3 polyunsaturated fatty acids are lower in vegetarians and in vegans than in omnivores. No data are available on whether these concentrations differ between long- and short-term vegetarians and vegans. OBJECTIVES: We compared plasma fatty acid composition in meat-eaters, vegetarians, and vegans and examined whether the proportions of eicosapentaenoic acid (20:5n-3; EPA), docosapentaenoic acid (22:5n-3; DPA), and docosahexaenoic acid (22:6n-3; DHA) were related to the subjects' duration of adherence to their diets or to the proportions of plasma linoleic acid (18:2n-6; LA) and alpha-linolenic acid (18:3n-3; ALA). DESIGN: The present cross-sectional study included 196 meat-eating, 231 vegetarian, and 232 vegan men in the United Kingdom. Information on anthropometry, diet, and smoking habits was obtained through a questionnaire. Total fatty acid composition in plasma was measured. RESULTS: The proportions of plasma EPA and DHA were lower in the vegetarians and in the vegans than in the meat-eaters, whereas only small differences were seen for DPA. Plasma EPA, DPA, and DHA proportions were not significantly associated with the duration of time since the subjects became vegetarian or vegan, which ranged from <1 y to >20 y. In the vegetarians and the vegans, plasma DHA was inversely correlated with plasma LA. CONCLUSIONS: The proportions of plasma long-chain n-3 fatty acids were not significantly affected by the duration of adherence to a vegetarian or vegan diet. This finding suggests that when animal foods are wholly excluded from the diet, the endogenous production of EPA and DHA results in low but stable plasma concentrations of these fatty acids.     

Linoleate inhibits EPA incorporation from dietary fish-oil supplements in human subjects.

Thirty healthy male subjects were randomly allocated into one of two treatment groups: group H subjects were maintained on a high-linoleic acid (LA) diet with the saturated fatty acids kept low and those in group L were kept on a low-LA, low saturate diet. After a 3-wk run-in period, subjects consumed a fish-oil supplement containing 1.6 g eicosapentaenoic acid (EPA)/d and 0.32 g docosahexaenoic acid as triglycerides for a further 4 wk. The diets alone resulted in a significant change in neutrophil phospholipid LA (H = 12.7 +/- 2.9%, L = 9.0 +/- 0.9%; P less than 0.05). Dietary supplementation with fish oil resulted in a significant increase in EPA in neutrophil phospholipids that was greater in group L (mean 2.0 +/- 0.4%) than group H (mean 1.5 +/- 0.3%; P less than 0.005). Reductions in arachidonic acid concentrations in neutrophil membranes were not different, nor could differences in leukotriene B4 production be detected. Our study indicates that the ingestion of n-6 fatty acids within the diet is an important determinant of EPA incorporation into neutrophil membranes.     

代谢综合征患者血清三酰甘油多不饱和脂肪酸谱与内脏脂肪的关系

目的 探讨血清三酰甘油中的n-6与n-3必需多不饱和脂肪酸（PUFA）各组分及其比例与代谢综合征患者核磁共振测量的腹腔内脏脂肪面积（MRI-IAF）的关系.方法 比较在体检中新发现的代谢综合征和健康人群的代谢和体脂指标的差异,探讨代谢综合征患者血清三酰甘油脂肪酸谱各组分与MRI-IAF等体脂参数的相关性,并且以相关的血清脂肪酸谱组分为被筛选变量,逐步回归分析以上变量对MRI-IAF、腰围和体质指数（BMI）的影响.结果 代谢综合征组的各项体脂及代谢指标均较对照组差,其中MRI-IAF差距较大[（108.3±13.3）cm2 vs.（63.0±7.1）cm2,t=18.28,P＜0.05）],代谢综合征组血清三酰甘油的n-6/n-3 PUFA比值高于对照组（10.1±3.3vs.7.2±2.1,t=8.564,P＜0.05）,而C18∶3 n-3[（1.4±0.4）％vs.（1.7±0.6）％,t=-3.295]、C20∶5 n-3[（0.2±0.2）％vs.（0.6±0.6）％,t=-3.611]、C22∶6n-3[（0.9±0.5）％vs.（1.2±0.6）％,t=-2.920]及n-3PUFA低于对照组[（2.5±0.6）％vs.（3.7±1.2）％,t=-7.034]（P均＜0.05）,所有n-6 PUFA及C22∶5 n-3的差异无统计学意义;n-6/n-3 PUFA、n-3 PUFA、二十二碳六烯酸和二十碳五烯酸均与MRI-IAF （r=-0.377～0.565,P=0.024）相关,n-6/n-3 PUFA还与腰围（r=0.400,P=0.016）和BMI相关（r=0.357,P=0.033）,而n-6 PUFA与各体脂参数不相关;逐步回归分析提示n-6/n-3PUFA比值与MRI-IAF、腰围、BMI的相关性较强（校正的R2=0.102～0.299,P=0.033）.结论 血清三酰甘油n-6/n-3 PUFA比值和n-3 PUFA与代谢综合征患者MRI-IAF等体脂参数相关,补充膳食n-3 PUFA的同时可能还需要考虑避免n-6 PUFA的过量摄入.     

Fish intake and serum fatty acid profiles from freshwater fish

BACKGROUND: Although high mercury concentrations in fish diets raise an alarm, fish can also be a healthy choice because it is the primary source of n-3 fatty acids (FAs). However, little information is available on the contribution of freshwater fish to serum FA concentrations. OBJECTIVE: This study examined the FA pathway from fish to serum in 243 moderate consumers of freshwater fish. DESIGN: A food-frequency questionnaire was used to determine the intakes of freshwater fish caught locally and not sold in markets and of fish purchased in markets (x +/- SD: 58 +/- 63 g/d). Locally caught freshwater fish accounted for an average of 45% of total fish intake. Fish were categorized as lean or fatty on the basis of the eicosapentaenoic acid + docosahexaenoic acid content estimated from published data. Serum FA concentrations were determined by gas chromatography. RESULTS: The results showed no relation between total fish intake or estimated n-3 FA intake from all fish and serum n-3 FA concentrations. Only fatty fish intake, particularly salmonid, and estimated EPA + DHA intake from fatty fish were significantly associated with serum EPA + DHA (R2 = 0.41 and 0.40, respectively). No relation was observed between the quantity of locally caught fish (g/d) consumed or the estimated FA intake from locally caught fish and serum n-3 FAs. Age, sex, and lipid metabolism medication were associated with serum n-3 FA concentrations. Neither blood selenium nor blood mercury was associated with serum FAs. CONCLUSION: The relation between fatty fish consumption and serum n-3 FAs cannot be generalized to all fish intakes.     

The effect of n - 3 PUFA/gamma-cyclodextrin complex on serum lipids in healthy volunteers--a randomized, placebo-controlled, double-blind trial

OBJECTIVES: This study was carried out to examine whether serum triglyceride concentrations were decreased by administration of n-3 polyunsaturated fatty acid (PUFA)/gamma-cyclodextrin (gamma-CD) complex-containing capsules as reported previously with n-3PUFA without gamma-CD. STUDY DESIGN: A placebo-controlled double-blind study with healthy subjects (n=35) and hypertriglyceridemic subjects (n=7) of 35-66 years of age was performed. The subjects were randomized to a group (n-3 group) supplemented with n-3PUFA/gamma-CD-containing capsules (660 mg EPA + 280 mg DHA/day) or a control group supplemented with capsules containing essentially no n-3 PUFA for 8 weeks with stratification by sex, age, and serum triglyceride levels in a double blind manner. Fasting blood samples were obtained at the start of administration and 4 and 8 weeks afterward. RESULTS: EPA concentrations in the total phospholipid fraction of red blood cells increased significantly in all subjects in the n-3 group, whereas no changes were seen in the control group. Triglyceride levels were significantly decreased (-17%) in the n-3 group compared with the control group at week 8. The following serum lipids did not significantly change over time: total-cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol. Only two subjects in the n-3 group guessed at the end of the study that their capsules were active. CONCLUSION: n-3 PUFA/gamma-CD complex lowered triglyceride levels in normal and slightly hypertriglyceridemic subjects. There was a possibility that gamma-CD might at least partly cover the smell and aftertaste of fish oil.     

Dietary ratio of (n-6)/(n-3) polyunsaturated fatty acids alters the fatty acid composition of bone compartments and biomarkers of bone formation in rats

The effects of dietary polyunsaturated fatty acids (PUFA) on ex vivo bone prostaglandin E(2) (PGE(2)) production and bone formation rate were evaluated in rats. Weanling male Sprague-Dawley rats were fed AIN-93G diet containing 70 g/kg of added fat for 42 d. The dietary lipid treatments were formulated with safflower oil and menhaden oil to provide the following ratios of (n-6)/(n-3) fatty acids: 23.8 (SMI), 9.8 (SMII), 2.6 (SMIII), and 1.2 (SMIV). Ex vivo PGE(2) production in liver homogenates and bone organ cultures (right femur and tibia) were significantly lower in rats fed diets with a lower dietary ratio of (n-6)/(n-3) fatty acids than in those fed diets with a higher dietary ratio. Regression analysis revealed a significant positive correlation between bone PGE(2) and the ratio of arachidonic acid (AA)/eicosapentaenoic acid (EPA), but significant negative correlations between bone formation rate and either the ratio of AA/EPA or PGE(2) in bone. Activities of serum alkaline phosphatase isoenzymes, including the bone-specific isoenzyme (BALP), were greater in rats fed a diet high in (n-3) or a low ratio of (n-6)/(n-3), further supporting the positive action of (n-3) fatty acids on bone formation. These results demonstrated that the dietary ratio of (n-6)/(n-3) modulates bone PGE(2) production and the activity of serum BALP in growing rats.     

Peripheral blood mononuclear cell fatty acid composition and inflammatory mediator production in adult Crohn's disease

BACKGROUND & AIMS: Crohn's disease (CD) is associated with nutritional deficiencies, altered plasma concentrations of polyunsaturated fatty acids (PUFA) and an anti-inflammatory response to fish oil that contains n-3 PUFA. This suggests that, in CD, immune cells may have altered n-3 PUFA composition with functional consequences. The aim of this study is to investigate n-3 and n-6 PUFA composition and synthetic function of peripheral blood mononuclear cells (PBMC) in the basal state. METHODS: A case control study of 52 adult CD patients and healthy, age- and sex-matched controls. Composition of PBMC and plasma phospholipids were measured by gas chromatography and production of tumour necrosis factor-alpha, prostaglandin E2 (PGE2) and interferon-gamma (IFN-gamma) by PBMC were measured by ELISA. RESULTS: CD was associated with higher concentrations of eicosapentaenoic acid and other n-3 PUFA, and lower arachidonic acid (AA) (n-6 PUFA) in PBMC. This was not explained by differences in dietary fat intake. Lower rates of production of PGE2 and IFN-gamma by PBMC were noted in quiescent and active CD, respectively, compared to controls. CONCLUSIONS: CD is associated with a greater availability, and not a deficiency, of n-3 PUFA in PBMC, but lower concentrations of AA, and lower rates of production of PGE2 and IFN-gamma, compared to healthy controls.