Examination of the persistency of milk fatty acid composition responses to fish oil and sunflower oil in the diet of dairy cows

Based on the potential benefits of cis-9, trans-11 conjugated linoleic acid (CLA) for human health, there is a need to develop effective strategies for enhancing milk fat CLA concentrations. Levels of cis-9, trans-11 CLA in milk can be increased by supplements of fish oil (FO) and sunflower oil (SO), but there is considerable variation in the response. Part of this variance may reflect time-dependent ruminal adaptations to high levels of lipid in the diet, which lead to alterations in the formation of specific biohydrogenation intermediates. To test this hypothesis, 16 late lactation Holstein-British Friesian cows were used in a repeated measures randomized block design to examine milk fatty acid composition responses to FO and SO in the diet over a 28-d period. Cows were allocated at random to corn silage-based rations (8 per treatment) containing 0 (control) or 45 g of oil supplement/ kg of dry matter consisting (1:2; wt/wt) of FO and SO (FSO), and milk composition was determined on alternate days from d 1. Compared with the control, the FSO diet decreased mean dry matter intake (21.1 vs. 17.9 kg/d), milk fat (47.7 vs. 32.6 g/kg), and protein content (36.1 vs. 33.3 g/kg), but had no effect on milk yield (27.1 vs. 26.4 kg/d). Reductions in milk fat content relative to the FSO diet were associated with increases in milk trans-10 18: 1, trans-10, cis-12 CLA, and trans-9, cis-11 CLA concentrations (r(2) = 0.74, 0.57, and 0.80, respectively). Compared with the control, the FSO diet reduced milk 4: 0 to 18: 0 and cis 18:1 content and increased trans 18:1, trans 18:2, cis-9, trans-11 CLA, 20: 5 n-3, and 22: 6 n-3 concentrations. The FSO diet caused a rapid elevation in milk cis-9, trans-11 CLA content, reaching a maximum of 5.37 g/100 g of fatty acids on d 5, but these increases were transient, declining to 2.35 g/100 g of fatty acids by d 15. They remained relatively constant thereafter. Even though concentrations of trans-11 18: 1 followed the same pattern of temporal changes as cis-9, trans-11 CLA, the total trans 18:1 content of FSO milk was unchanged because of the concomitant increases in the concentration of other isomers (Delta(4-10) and Delta(12-15)), predominantely trans-10 18:1. In conclusion, supplementing diets with FSO enhances milk fat cis-9, trans-11 CLA content, but the high level of enrichment declines because of changes in ruminal biohydrogenation that result in trans-10 replacing trans-11 as the major 18:1 biohydrogenation intermediate formed in the rumen.

Fatty acids and immune function: new insights into mechanisms

Fatty acids are known to play diverse roles in immune cells. They are important as a source of energy, as structural components of cell membranes, as signaling molecules and as precursors for the synthesis of eicosanoids and similar mediators. Recent research has suggested that the localization and organisation of fatty acids into distinct cellular pools has a direct influence on the behaviour of a number of proteins involved in immune cell activation, including those associated with T cell responses, antigen presentation and fatty acid-derived inflammatory mediator production. This article reviews these studies and places them in the context of existing literature in the field. These studies indicate the existence of several novel mechanisms by which altered fatty acid availability can modulate immune responses and impact upon clinical outcomes

N-3 polyunsaturated fatty acids and inflammation in the arterial wall

Atherosclerosis, leading to cardiovascular disease, is a chronic condition involving a strong inflammatory component. There is evidence that the n-3 polyunsaturated fatty acids (PUFA) present in oily fish and fish oils protect against cardiovascular disease. While these fatty acids have well-recognised effects on plasma triacylglycerol concentrations, it is likely that they exert beneficial effects through other mechanisms in addition. A large body of evidence suggests that the n-3 PUFA have anti-inflammatory properties, some of which may be manifested in the arterial wall, either directly or indirectly, to modulate the progression of atherosclerosis. This review critically evaluates the evidence for the anti-inflammatory effects of the n-3 PUFA in cells and on pathways which have a direct influence on atherogenesis in the arterial wall.

Fatty acids and the immune system: from basic science to clinical applications

Over the last 25 years, the effects of fatty acids on the immune system have been characterized using in vitro, animal and human studies. Advances in fatty acid biochemistry and molecular techniques have recently suggested new mechanisms by which fatty acids could potentially modify immune responses, including modification of the organization of cellular lipids and interaction with nuclear receptors. Possibilities for the clinical applications of n-3 PUFA are now developing. The present review focuses on the hypothesis that the anti-inflammatory properties of n-3 PUFA in the arterial wall may contribute to the protective effects of n-3 PUFA in CVD, as suggested by epidemiological and secondary prevention studies. Studies are just beginning to show that dietary n-3 PUFA can be incorporated into plaque lipid in human subjects, where they may influence the morphology and stability of the atherosclerotic lesion.

Fatty acids as gatekeepers of immune cell regulation

Fatty acids have diverse roles in all cells. They are important as a source of energy, as structural components of cell membranes, as signalling molecules and as precursors for the synthesis of eicosanoids. Recent research has suggested that the organization of fatty acids into distinct cellular pools has a particularly important role in cells of the immune system and that forms of lipid trafficking exist, which are as yet poorly understood. This Review examines the nature and regulation of cellular lipid pools in the immune system, their delivery of fatty acids or fatty acid derivatives to specific locations and their potential role in health and disease.

Trans-fatty acids and cancer: the evidence reviewed

The present review comes from the authors of the recent Scientific Advisory Committee on Nutrition (SACN) review Update on Trans Fatty Acids and Health, and focuses on assessing the strength of the evidence for a link between trans-fatty acid (trans-FA) intake and cancer. It evaluates a range of human ecological, case-control and prospective studies with trans-FA exposure assessed using either dietary assessment methods or trans-FA levels in tissues. Relevant animal studies are also presented in order to elucidate potential mechanisms. It concludes that there is weak and inconsistent evidence for a relationship between trans-FA and breast or colorectal cancer. Evidence for an association between trans-FA and prostate cancer is limited, but a recent large case-control study has shown a strong interaction between risk and trans-FA intake for the RNASEL QQ/RQ genotype that is present in about 35% of the population. This potential association requires further investigation. The single study on non-Hodgkin's lymphoma reported a strong positive association, but out), used a single assessment of dietary trans-FA made at the start of the study in 1980, and the significant changes it) trans-FA intakes between then and the end Of follow-up in 1994 limit the reliability of this observation. There is insufficient evidence to allow any differentiation between the effects of trans-FA from animal or vegetable origin on cancer risk.

Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial

Background N-3 polyunsaturated fatty acids (PUFAs) from oily fish protect against death from cardiovascular disease. We aimed to assess the hypothesis that incorporation of n-3 and n-6 PUFAs into advanced atherosclerotic plaques increases and decreases plaque stability, respectively. Methods We did a randomised controlled trial of patients awaiting carotid endarterectomy. We randomly allocated patients control, sunflower oil (n-6), or fish-oil (n-3) capsules until surgery. Primary outcome was plaque morphology indicative of stability or instability, and outcome measures were concentrations of EPA, DHA, and linoleic acid in carotid plaques; plaque morphology; and presence of macrophages in plaques. Analysis was per protocol. Findings 188 patients were enrolled and randomised; 18 withdrew and eight were excluded. Duration of oil treatment was 7-189 days (median 42) and did not differ between groups. The proportions of EPA and DHA were higher in carotid plaque fractions in patients receiving fish oil compared with those receiving control (absolute difference 0.5 [95% CI 0.3-0.7], 0.4 [0.1-0.6], and 0.2 [0.1-0.4] g/100 g total fatty acids for EPA; and 0.3 [0.0-0.8], 0.4 [0.1-0.7], and 0.3 [0.1-0.6] g/100 g total fatty acids for DHA; in plaque phospholipids, cholesteryl esters, and triacylglycerols, respectively). Sunflower oil had little effect on the fatty acid composition of lipid fractions. Fewer plaques from patients being treated with fish oil had thin fibrous caps and signs of inflammation and more plaques had thick fibrous caps and no signs of inflammation, compared with plaques in patients in the control and sunflower oil groups (odds ratio 0.52 [95% CI 0.24-0.89] and 1.19 [1.02-1.57] vs control; 0.49 [0.23-0.90] and 1.16 [1.01-1.53] vs sunflower oil). The number of macrophages in plaques from patients receiving fish oil was lower than in the other two groups. Carotid plaque morphology and infiltration by macrophages did not differ between control and sunflower oil groups. Interpretation Atherosclerotic plaques readily incorporate n-3 PUFAs from fish-oil supplementation, inducing changes that can enhance stability of atherosclerotic plaques. By contrast, increased consumption of n-6 PUFAs does not affect carotid plaque fatty-acid composition or stability over the time course studied here. Stability of plaques could explain reductions in non-fatal and fatal cardiovascular events associated with increased n-3 PUFA intake.

UK Food Standards Agency workshop report: the effects of the dietary n-6 : n-3 fatty acid ratio on cardiovascular health

This report summarises a workshop convened by the UK Food Standards Agency (FSA) on 11 September 2006 to review the results of three FSA-funded studies and other recent research on effects of the dietary n-6:n-3 fatty acid ratio on cardiovascular health. The objective of this workshop was to reach a clear conclusion on whether or not it was worth funding any further research in this area. On the basis of this review of the experimental evidence and on theoretical grounds, it was concluded that the n-6:n-3 fatty acid ratio is not a useful concept and that it distracts attention away from increasing absolute intakes of long-chain n-3 fatty acids which have been shown to have beneficial effects on cardiovascular health. Other markers of fatty acid intake, that more closely relate to physiological function, may be more useful.

Long-term monounsaturated fatty acid diets reduce platelet aggregation in healthy young subjects

The aim of the present study was to compare the response of a range of atherogenic and thrombogenic risk markers to two dietary levels of saturated fatty acid (SFA) substitution with monounsaturated fatty acids (MUFA) in students living in a university hall of residence. Although the benefits of such diets have been reported for plasma lipoproteins in high-risk groups, more needs to be known about effects of more modest SFA-MUFA substitutions over the long term and in young healthy adults. In a parallel design over 16 weeks, fifty-one healthy young subjects were randomised to one of two diets: (1) a moderate-MUFA diet in which 16 g dietary SFA/100 g total fatty acids were substituted with MUFA (n 25); (2) a high-MUFA diet in which 33 g dietary SFA/100 g total fatty acids were substituted with MUFA (n 26). All subjects followed an 8-week run-in diet (reference diet), with a fatty acid composition close to the UK average values. There were no differences in plasma lipid responses between the two diets over 16 weeks of the study with similar reductions in total cholesterol (P<0.001) and LDL-cholesterol (P<0.01) in both groups; a small but significant reduction in HDL-cholesterol was also observed in both groups (P<0.01). Platelet responses to ADP (P<0.01) and arachidonic acid (P<0.05) differed with time on the two diets; at 16 weeks, platelet aggregatory response to ADP was significantly lower on the high-MUFA than the moderate-MUFA (P<0.01) diet; ADP responses were also significantly lower within this group at 8 (P< 0.05) and 16 (P< 0.01) weeks compared with baseline. There were no differences in fasting factor VII activity (factors VIII and VIIag), fibrinogen concentration or tissue-type plasminogen activator activity between the diets. There were no differences in postprandial factor VIII responses to a standard meal (area under the curve) between the diets after 16 weeks, but postprandial factor VIII response was lower than on the high-MUFA diet compared with baseline (P<0.01). In conclusion, a high-MUFA diet sustains potentially beneficial effects on platelet aggregation and postprandial activation of factor VII. Moderate or high substitution of MUFA for SFA achieves similar reductions in fasting blood lipids in young healthy subjects.

Chylomicron particle size and number, factor VII activation and dietary monounsaturated fatty acids

This study evaluated the effects of substituting dietary saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) on postprandial chylomicron (triacylglycerol (TAG), apolipoprotein B-48 (apo B-48) and retinyl ester (RE)), chylomicron particle size and factor VII (FVII) response when subjects were given a standard meal. In a controlled sequential design, 51 healthy young subjects followed an SFA-rich diet (Reference diet) for 8 weeks after which half of the subjects followed a moderate MUFA diet (n = 25) and half followed a high MUFA diet (n = 26) for 16 weeks. Fasting lipoprotein and lipid measurements were evaluated at baseline and at 8-week intervals during the Reference and MUFA diets. In 25 of the subjects (n = 12 moderate MUFA, n = 13 high MUFA), postprandial responses to a standard test meal containing RE and 13 C-tripalmitin were investigated at the end of the Reference and the MUFA diet periods. Although there were no differences in the postprandial lipid markers (TAG, RE, C-13-TAG) on the two diets, the postprandial apo B-48 response (incremental area under the curve (IAUC) was reduced by 21% on the moderate MUFA diet (NS) and by 54% on the high MUFA diet (P < 0.01). The postprandial peak concentrations of apo B-48 were reduced by 33% on the moderate MUFA diet (P < 0.01) and 48% on the high MUFA diet (P < 0.001). Fasting values for factor VII activity (FVIIc), activated factor VII (FVIIa) or factor VII antigen (FVIIag) did not differ significantly when subjects were transferred from Reference to MUFA diets. However, the postprandial increases in coagulation FVII activity (FVIIc) were 18% lower and of activated FVII (FVIIa) were 17% lower on the moderate MUFA diet (NS). Postprandial increases in FVIIc and FVIIa were 50% (P < 0.05) and 29% (P < 0.07) lower on the high MUFA diet and the area under the postprandial FVIIc response curve (AUC) was also lower on the high MUFA diet (P < 0.05). Significantly higher ratios of RE:apo B-48 (P < 0.001) and 13 C-palmitic acid:apo B-48 (P < 0.01) during both MUFA diets suggest that the CMs formed carry larger amounts of dietary lipids per particle, reflecting an adaptation to form larger lipid droplets in the enterocyte when increased amounts of dietary MUFAs are fed. Smaller numbers of larger chylomicrons may explain attenuated activation of factor VII during the postprandial state when the background diet is rich in MUFA. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Effect of forage type and proportion of concentrate in the diet on milk fatty acid composition in cows given sunflower oil and fish oil

Based on the potential benefits of cis-9, trans- 11 conjugated linoleic acid (CLA) for human health there is a need to develop effective strategies for enhancing milk fat CLA concentrations. In this experiment, the effect of forage type and level of concentrate in the diet on milk fatty acid composition was examined in cows given a mixture of fish oil and sunflower oil. Four late lactation Holstein-British Friesian cows were used in a 4 x 4 Latin-square experiment with a 2 x 2 factorial arrangement of treatments and 21-day experimental periods. Treatments consisted of grass (G) or maize (M) silage supplemented with low (L) or high (H) levels of concentrates (65: 35 and 35: 65; forage: concentrate ratio, on a dry matter (DM) basis, respectively) offered as a total mixed ration at a restricted level of intake (20 kg DM per day). Lipid supplements (30 g/kg DM) containing fish oil and sunflower oil (2: 3 w/w) were offered during the last 14 days of each experimental period. Treatments had no effect on total DM intake, milk yield, milk constituent output or milk fat content, but milk protein concentrations were lower (P<0.05) for G than M diets (mean 43.0 and 47.3 g/kg, respectively). Compared with grass silage, milk fat contained higher (P<0.05) amounts Of C-12: 0, C-14: 0, trans C-18:1 and long chain >= C20 (n-3) polyunsaturated fatty acids (PUFA) and lower (P<0.05) levels Of C-18:0 and trans C-18:2 when maize silage was offered. Increases in the proportion of concentrate in the diet elevated (P<0.05) C-18:2 (n-6) and long chain >= C20 (n-3) PUFA content, but reduced (P<0.05) the amount Of C-18:3 (n-3). Concentrations of trans-11 C-18:1 in milk were independent of forage type, but tended (P<0.10) to be lower for high concentrate diets (mean 7.2 and 4.0 g/100 g fatty acids, for L and H respectively). Concentrations of trans-10 C-18:1 were higher (P<0.05) in milk from maize compared with grass silage (mean 10.3 and 4.1 g/100 g fatty acids, respectively) and increased in response to high levels of concentrates in the diet (mean 4.1 and 10.3 g/100 g fatty acids, for L and H, respectively). Forage type had no effect (P>0.05) on total milk conjugated linoleic acid (CLA) (2.7 and 2.8 g/100 g fatty acids, for M and G, respectively) or cis-9, trans-11 CLA content (2.2 and 2.4 g/100 g fatty acids). Feeding high concentrate diets tended (P<0.10) to decrease total CLA (3.3 and 2.2 g/100 g fatty acids, for L and H, respectively) and cis-9, trans-11 CLA (2.9 and 1/7 g/100 g fatty acids) concentrations and increase milk trans-9, cis-11 CLA and trans-10, cis-12 CLA content. In conclusion, the basal diet is an important determinant of milk fatty acid composition when a supplement of fish oil and sunflower oil is given.

Effect of dietary fish oil on biohydrogenation of fatty acids and milk fatty acid content in cows

Mechanisms underlying milk fat conjugated linoleic acid (CLA) responses to supplements of fish oil were investigated using five lactating cows each fitted with a rumen cannula in a simple experiment consisting of two consecutive 14-day experimental periods. During the first period cows were offered 18 kg dry matter (DM) per day of a basal (B) diet formulated from grass silage and a cereal based-concentrate (0.6 : 0.4; forage : concentrate ratio, on a DM basis) followed by the same diet supplemented with 250 g fish oil per day (FO) in the second period. The flow of non-esterified fatty acids leaving the rumen was measured using the omasal sampling technique in combination with a triple indigestible marker method based on Li-Co-EDTA, Yb-acetate and Cr-mordanted straw. Fish oil decreased DM intake and milk yield, but had no effect on milk constituent content. Milk fat trans-11C(18:1), total trans-C-18:1, cis-9 trans-11 CLA, total CLA, C-18 :2 (n- 6) and total C-18:2 content were increased in response to fish oil from 1.80, 4.51, 0.39, 0. 56, 0.90 and 1.41 to 9.39, 14.39, 1.66, 1.85, 1.25 and 4.00 g/100 g total fatty acids, respectively. Increases in the cis-9, trans-11 isomer accounted for proportionately 0.89 of the CLA response to fish oil. Furthermore, fish oil decreased the flow of C-18:0 (283 and 47 g/day for B and FO, respectively) and increased that of trans-C-18:1 fatty acids entering the omasal canal (38 and 182 g/day). Omasal flows of trans-C-18:1 acids with double bonds in positions from delta-4 to -15 inclusive were enhanced, but the effects were isomer dependent and primarily associated with an increase in trans-11C(18:1) leaving the rumen (17.1 and 121.1 g/day for B and FO, respectively). Fish oil had no effect on total (4.36 and 3.50 g/day) or cis-9, trans-11 CLA (2.86 and 2.08 g/day) entering the omasal canal. Flows of cis-9, trans-11 CLA were lower than the secretion of this isomer in milk. Comparison with the transfer of the trans-9, trans-11 isomer synthesized in the rumen suggested that proportionately 0.66 and 0.97 of cis-9, trans-11 CLA was derived from endogenous conversion of trans-11 C-18:1 in the mammary gland for B and FO, respectively. It is concluded that fish oil enhances milk fat cis-9, trans-11 CLA content in response to increased supply of trans-11 C-18:1 that arises from an inhibition of trans C-18:1 reduction in the rumen.