n-3 fatty acids in psoriasis

Increased concentrations of free arachidonic acid (AA) and its proinflammatory metabolites have been observed in psoriatic lesions. Replacement of arachidonic acid by alternative precursor polyunsaturated fatty acids (PUFA), especially eicosapentaenoic acid (EPA), which can be metabolized via the same enzymatic pathways as AA, might be a therapeutic option in psoriasis. However the results of studies evaluating the therapeutic benefit of dietary fish oil have been conflicting and not clearly dose-dependent. To overcome the slow kinetics and limited availability of oral supplementation, we have performed three studies to assess the efficacy and safety of an intravenously administered fish oil derived lipid emulsion on different forms of psoriasis. Patients received daily infusions of either an n-3 fatty acid-based lipid emulsion (Omegaven) or a conventional n-6 lipid emulsion (Lipoven) in different time and dose regimens. In addition to an overall assessment of the clinical course of psoriasis, EPA- and AA-derived neutrophil 5-lipoxygenase (LO)--products, thromboxane (TX) B2/B3, PAF and plasma free fatty acids were investigated. Treatment with n-3 fatty acids resulted in a considerably higher response rate than infusion of n-6 lipids. A more than 10-fold increase in neutrophil EPA-derived 5-LO product formation was noted in the n-3 group, accompanied by a rapid increase in plasma-free EPA within the first days. In conclusion, intravenous n-3-fatty acid administration causes reduction of psoriasis, which may be related to changes in inflammatory eicosanoid generation. The rapidity of the response to intravenous n-3 lipids exceeds by orders of magnitude the hitherto reported kinetics of improvement of psoriatic lesions upon use of oral supplementation.     

n-3 fatty acids of marine origin lower systolic blood pressure and triglycerides but raise LDL cholesterol compared with n-3 and n-6 fatty acids from plants

We compared the cardiovascular risk-reduction potential of three major polyunsaturated fatty acids in a double-blind study. Thirty-three normotensive and mildly hypercholesterolemic men were randomly allocated to one of three diets supplemented with linoleic acid (14.3 g/d), alpha-linolenic acid (9.2 g/d), or eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) (3.4 g/d). Diets were matched to provide similar amounts of the major classes of fatty acids and cholesterol. Blood pressure and plasma lipids were measured for 6 wk after a 3-wk run-in period on the linoleic acid supplement. For the diet supplemented with EPA plus DHA compared with the linoleic acid diet systolic blood pressure fell 5.1 mm Hg (p = 0.01); plasma triglyceride and VLDL cholesterol fell by 39% (p = 0.001) and 49% (p = 0.01), respectively; and LDL cholesterol rose by 9% (p = 0.01). There were no significant changes with the diet supplemented with alpha-linolenic acid. The net effect on cardiovascular risk therefore is complex and the systolic blood pressure reduction was substantial.     

Comparative cholesterol lowering properties of vegetable oils: beyond fatty acids

OBJECTIVE: Our laboratory has previously reported that the hypolipidemic effect of rice bran oil (RBO) is not entirely explained by its fatty acid composition. Although RBO has up to three times more serum cholesterol-raising saturated fatty acids (SATS) than some unsaturated vegetable oils, we hypothesized that its greater content of the unsaponifiables would compensate for its high SATS and yield comparable cholesterol-lowering properties to other vegetable oils with less SATS. METHODS: To study the comparative effects of different unsaturated vegetable oils on serum lipoprotein levels, nine cynomologus monkeys (Macaca fascicularis) were fed diets, for four weeks, in a Latin square design, containing rice bran, canola or corn oils (as 20% of energy) in a basal mixture of other fats to yield a final dietary fat concentration of 30% of energy. All animals were fed a baseline diet containing 36% of energy as fat with 15% SATS, 15% monounsaturated fatty acids (MONOS) and 6% polyunsaturated fatty acids (POLYS). RESULTS: Despite the lower SATS and higher MONOS content of canola oil and the higher POLYS content of corn oil, RBO produced similar reductions in serum total cholesterol (TC) (-25%) and low density lipoprotein cholesterol (LDL-C) (-30%). In addition, as compared to the baseline diet, the reduction in serum TC and LDL-C cholesterol with RBO was not accompanied by reductions in high density lipoprotein cholesterol (HDL-C) which occurred with the other two dietary oils. Using predictive equations developed from data gathered from several studies with non-human primates, we noted that the observed serum TC and LDL-C lowering capabilities of the RBO diet were in excess of those predicted based on the fatty acid composition of RBO. CONCLUSIONS: These studies suggest that non-fatty acid components (unsaponifiables) of RBO can contribute significantly to its cholesterol-lowering capability.     

Antiarrhythmic effects of n-3 polyunsaturated fatty acids

The n-3 or omega 3 polyunsaturated fatty acids are a promising dietary preventive therapy for cardiovascular disease. The main dietary source of n-3 polyunsaturated fatty acids comes from sea fish. During recent years, the subject of antiarrhythmic role of n-3 polyunsaturated fatty acids has been investigated extensively. A great deal of evidence has shown that the antiarrhythmic effect of n-3 polyunsaturated fatty acids is exerted by altering the electrophysiology of myocytes. This article is intended to review specifically this role of n-3 polyunsaturated fatty acids as demonstrated by both basic and clinical evidence in animal and human studies, including current concepts on the antiarrhythmic mechanism of this class of polyunsaturated fatty acids.     

n-3 polyunsaturated fatty acids and immune function

n-3 PUFA have been shown to reduce the risk of cardiovascular and inflammatory diseases. However, they have also been shown to suppress T-cell-mediated immune function, an undesirable effect, especially in immuno-suppressed individuals. Studies have thus far suggested that this immuno-suppression may be in part attributable to increased lipid peroxidation and decreased antioxidant (especially vitamin E) levels, which can be prevented by appropriate vitamin E supplementation. Further well-designed human studies are needed to determine the appropriate levels of n-3 PUFA and vitamin E supplementation to optimize the beneficial anti-inflammatory effect of n-3 PUFA and minimize their suppressive effect on T-cell function.     

Lack of dose response by dietary n-3 fatty acids at a constant ratio of n-3 to n-6 fatty acids in suppressing eicosanoid biosynthesis from arachidonic acid

This study evaluated whether it is the ratio of n-3 to n-6 fatty acids or the absolute amount of n-3 fatty acids in diets that determines the degree of inhibition of eicosanoid biosynthesis from arachidonic acid (AA). Rats were fed diets containing different doses of linolenic acid or menhaden oil for 3 mo. Constant ratios of n-3 to n-6 fatty acids were maintained by concomitant increases in safflower oil as the n-6 fatty acid source. Results showed that AA concentrations in liver, platelet, and lung phospholipids and concentrations of eicosanoids synthesized in tissues were significantly (P less than 0.05) suppressed both by linolenic acid and menhaden oil; however, there was a lack of a dose response within groups fed different amounts of the same dietary fat. These results indicate that the ratio of n-3 to n-6 fatty acids in the diets, rather than the absolute amount of n-3 fatty acids, is the determining factor in inhibiting eicosanoid biosynthesis from AA.     

Dietary n-3 and n-6 fatty acids alter avian pituitary sensitivity

The effects of dietary saturated and polyunsaturated fatty acids (PUFAs) of the n-3 and n-6 series on avian pituitary sensitivity were investigated by infusing human growth hormone (GH) releasing hormone--fragment 1-29--and chicken luteinising hormone releasing hormone (LHRH) into catheterized broiler chickens. At 3 weeks of age three groups (n = 18; six birds per group) were fed for 6 weeks isonitrogenous and isoenergetic experimental diets containing 80 g/kg of edible tallow (saturated fatty acids), fish oil (n-3 PUFAs) or sunflower oil (n-6 PUFAs). Jugular catheterisation was performed under general anaesthesia during week four of the dietary treatments and the birds allowed 7 days post surgery to recover. A bolus of LHRH (20 microg/bird) and a GH releasing hormone (12.5 microg/kg) infusion was given on different days to each chicken and serial blood samples taken over a 1 h period. Plasma luteinising hormone and GH concentrations were measured by radioimmunoassay. Pre-infusion GH concentrations were similar for the tallow, fish and sunflower oil dietary groups (5.2 +/- 3.9, 5.2 +/- 1.0 and 6.1 +/- 3.1 ng/ml, respectively), however, GH concentration in response to the GH releasing hormone infusion was elevated in the sunflower oil group (44.7 +/- 5.7 ng/ml) when compared to chicken fed tallow (33.7 +/- 9.7ng/ml) or fish oil (21.3 +/- 5.0 ng/ml). There was a significant decrease (P < 0.05) in the clearance rate of plasma GH for the birds fed the fish oil compared with those fed sunflower oil with an intermediate value being observed in the tallow fed group. Pre-infusion plasma luteinising hormone concentrations for the birds fed tallow (3.2 +/- 0.7 ng/ml) were significantly elevated (P < 0.05) when compared to birds fed either the sunflower oil (0.84 +/- 0.25 ng.ml) or fish oil (0.93 +/- 0.22 ng/ml) diets. There were no significant differences between the dietary groups in either the maximal plasma luteinising concentration or its disappearance rate following the LHRH infusion. The data demonstrate that dietary fatty acids alter avian pituitary sensitivity and this modulation is determined by the nature of the dietary fat rather than the degree of saturation per se. In addition, this study also shows that dietary fats have a differential effect on pituitary cell activity and are specific to certain pituitary cell types.     

n-3及n-6多不饱和脂肪酸与乳腺癌关系的Meta分析

目的 系统评价n-3多不饱和脂肪酸(n-3PUFAs)、n-6多不饱和脂肪酸(n-6PUFAs)及其比例与乳腺癌发病风险的关系。方法 系统检索Pubmed、Embase、Web of Science、知网、万方等数据库截止至2022年1月1日有关n-3及n-6多不饱和脂肪酸与乳腺癌关系的研究,对最终纳入的文献进行数据提取与质量评价,采用Stata 15.1软件进行Meta分析。结果 共纳入33项针对n-3及n-6PUFAs和乳腺癌发病风险关联的观察性流行病学研究,其中队列研究14项,病例对照研究20项,共纳入研究对象1 077 178例,患者19 207例。Meta分析结果显示:n-3多不饱和脂肪酸(OR=0.933,95%CI:0.858～1.014)、n-6多不饱和脂肪酸(OR=1.018,95%CI:0.914～1.133)与乳腺癌发病风险无统计学关联(P>0.05),而较高的n-6/n-3PUFAs比值会显著增加乳腺癌的发病风险(OR=1.166,95%CI:1.047～1.299,P=0.005)。结论 n-6/n-3多不饱和脂肪酸的比值与乳腺癌的发病风险呈正相关,提示合理的膳食脂肪摄入比可能会降低乳腺癌的患病风险。而n-3及n-6多不饱和脂肪酸与乳腺癌发病风险的单独效应关系尚不明确,仍需更多前瞻性实验流行病学证据进行支持。     

n-3 polyunsaturated fatty acids and the cardiovascular system

n-3 Polyunsaturated fatty acids, mainly those contained in fish oils, are candidates for inclusion in secondary prevention programmes for coronary heart disease, based on the results of recent randomized trials in humans. Marine n-3 polyunsaturated fatty acids retard coronary atherosclerosis and appear to prevent fatal arrhythmias; and they decrease mortality subsequent to myocardial infarction.     

Effects of n-3 fatty acids on cartilage metabolism

Although the clinical benefits of dietary supplementation with n-3 polyunsaturated fatty acids (PUFA) has been recognised for a number of years, the molecular mechanisms by which particular PUFA affect metabolism of cells within the synovial joint tissues are not understood. This study set out to investigate how n-3 PUFA and other classes of fatty acids affect both degradative and inflammatory aspects of metabolism of articular cartilage chondrocytes using an in vitro model of cartilage degradation. Using well-established culture models, cartilage explants from normal bovine and human osteoarthritic cartilage were supplemented with either n-3 or n-6 PUFA, and cultures were subsequently treated with interleukin 1 to initiate catabolic processes that mimic cartilage degradation in arthritis. Results show that supplementation specifically with n-3 PUFA, but not n-6 PUFA, causes a decrease in both degradative and inflammatory aspects of chondrocyte metabolism, whilst having no effect on the normal tissue homeostasis. Collectively, our data provide evidence supporting dietary supplementation of n-3 PUFA, which in turn may have a beneficial effect of slowing and reducing inflammation in the pathogenesis of degenerative joint diseases in man.     

n-3 polyunsaturated fatty acids and colon cancer prevention

The incidence of colon cancer in industrialised countries has increased since the early 1970s. It is estimated that more than one-third of cases are associated with factors related to a Western diet. Both the type and amount of dietary fats consumed have been implicated in colon cancer aetiology. Recent studies have demonstrated that n-3 polyunsaturated fatty acids (PUFAs), commonly found in fish oil (FO), could prevent colon cancer development. Evidences show that n-3 PUFAs act at different stages of cancer development and through several mechanisms including the modulation of arachidonic acid-derived prostaglandin synthesis, and Ras protein and protein kinase C expression and activity. As a result, n-3 PUFAs limit tumour cell proliferation, increase apoptotic potential along the crypt axis, promote cell differentiation and possibly limit angiogenesis. The modulatory actions of n-3 PUFAs on the immune system and their anti-inflammatory effects might also play a role in reducing colon carcinogenesis. There remains, nevertheless, some ambiguity over the safety of n-3 PUFAs with respect to secondary tumour formation. However, it appears that n-3 PUFAs may be of use in colon cancer prevention.     

n-3 fatty acids and periodontitis in US adults

Background

Periodontitis is a common, chronic inflammatory disease. Although n-3 fatty acids have anti-inflammatory properties, it is unclear whether n-3 fatty acids can treat or prevent periodontitis.

Method

We studied 9,182 adults aged 20 years and older who participated in the National Health and Nutrition Examination Survey between 1999 and 2004. Periodontitis was assessed by dental exam and was defined as >4 mm pocket depth and >3 mm attachment loss in any one tooth. Intake of n-3 fatty acids was assessed by 24-hour dietary recall. We used multivariable logistic regression to estimate the associations between periodontitis and intakes of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and linolenic acid (LNA).

Results

The weighted prevalence and 95% confidence interval (CI) of periodontitis was 8.2% (95% CI 7.0 to 9.4). Compared with the lowest tertiles, the adjusted odds ratios for periodontitis associated with the highest tertiles of dietary n-3 intake were 0.78 (95% CI 0.61 to 1.00; P=0.009) for DHA, 0.85 (95% CI 0.67 to 1.08; P=0.10) for EPA, and 0.86 (95% CI 0.60 to 1.23; P=0.28) for LNA. The associations were little changed by multivariable adjustment or exclusion of individuals reporting use of dietary supplements containing DHA, EPA, or LNA.

Conclusions

In this nationally representative sample, higher dietary intakes of DHA and, to a lesser degree, EPA, were associated with lower prevalence of periodontitis. Interventional studies are needed to confirm the potential protective effects of n-3 fatty acids on periodontitis.     

Dietary n-6 and n-3 fatty acids in immunity and autoimmune disease

Clearly there is much evidence to show that under well-controlled laboratory and dietary conditions fatty acid intake can have profound effects on animal models of autoimmune disease. Studies in human autoimmune disease have been less dramatic; however, human trials have been subject to uncontrolled dietary and genetic backgrounds, infection and other environmental influences, and basic trial designs have been inadequate. The impact of dietary fatty acids on animal autoimmune disease models appears to depend on the animal model and the type and amount of fatty acids fed. Diets low in fat, essential fatty acid-deficient, or high in n-3 fatty acids from fish oils increase the survival and reduce disease severity in spontaneous autoantibody-mediated disease, whilst linoleic acid-rich diets appear to increase disease severity. In experimentally-induced T-cell-mediated autoimmune disease, essential fatty acid-deficient diets or diets supplemented with n-3 fatty acids appear to augment disease, whereas n-6 fatty acids prevent or reduce the severity. In contrast, in both T-cell and antibody-mediated auto-immune disease the desaturated and elongated metabolites of linoleic acid are protective. Suppression of autoantibody and T lymphocyte proliferation, apoptosis of autoreactive lymphocytes, and reduced pro-inflammatory cytokine production by high-dose fish oils are all likely mechanisms by which n-3 fatty acids ameliorate autoimmune disease. However, these could be undesirable long-term effects of high-dose fish oil which may compromise host immunity. The protective mechanism(s) of n-6 fatty acids in T-cell- mediated autoimmune disease are less clear, but may include dihomo-gamma-linolenic acid- and arachidonic acid-sensitive immunoregulatory circuits such as Th1 responses, TGF beta 1-mediated effects and Th3-like responses. It is often claimed that n-6 fatty acids promote autoimmune and inflammatory disease based on results obtained with linoleic acid only. It should be appreciated that linoleic acid does not reflect the functions of dihomo-gamma-linolenic and arachidonic acid, and that the endogenous rate of conversion of linoleic to arachidonic acid is slow (Hassam et al. 1975, 1977; Phylactos et al. 1994; Harbige et al. 1995). In addition to effects of dietary fatty acids on immunoregulation, inflammation as a consequence of immune activation in autoimmune disease may also be an important mechanism of action whereby dietary fatty acids modulate disease activity. In conclusion, regulation of gene expression, signal transduction pathways, production of eicosanoids and cytokines, and the action of antioxidant enzymes are all mechanisms by which dietary n-6 and n-3 fatty acids may exert effects on the immune system and autoimmune disease. Probably the most significant of these mechanisms in relation to our current understanding of immunoregulation and inflammation would appear to be via fatty acid effects on cytokines. The amount, type and balance of dietary fatty acids and associated antioxidant nutrients appear to impact on the immune system to produce immune-deviation or immunosuppressive effects, and to reduce immune-mediated inflammation which will in turn affect the susceptibility to, or severity of, autoimmune disease.     

德阳市市售植物油中反式脂肪酸含量调查

目的 了解德阳市市售植物油中反式脂肪酸的含量范围。方法 利用分层随机抽样抽取12类德阳市市售植物油共计121份样品,应用气相色谱法对样品中反式脂肪酸进行分离检测,采用归一化法进行结果计算。结果 德阳市市售植物油中12种反式脂肪酸的含量范围为未检出至3.19%,以反式亚麻酸（C18:3T）为主,其中橄榄油未检测出反式脂肪酸,最常见的菜籽油、玉米油、调和油、大豆油的反式脂肪酸平均含量分别为1.64%、2.20%、1.75%、2.58%。结论 德阳市市售植物油中普遍存在反式脂肪酸且含量各不相同。