Limited impact of 2 g/day omega-3 fatty acid ethyl esters (Omacor®) on plasma lipids and inflammatory markers in patients awaiting carotid endarterectomy.

The objective of this study was to determine the effects of prescription omega-3 (n-3) fatty acid ethyl esters (Omacor®) on blood pressure, plasma lipids, and inflammatory marker concentrations in patients awaiting carotid endarterectomy. Patients awaiting carotid endarterectomy (n = 121) were randomised to Omacor® or olive oil as placebo (2 g/day) until surgery (median 21 days). Blood pressure, plasma lipids, and plasma inflammatory markers were determined. There were significant decreases in systolic and diastolic blood pressure and in plasma triglyceride, total cholesterol, low density lipoprotein-cholesterol, soluble vascular cellular adhesion molecule 1, and matrix metalloproteinase 2 concentrations, in both groups. The extent of triglyceride lowering was greater with Omacor® (25%) compared with placebo (9%). Soluble E-selectin concentration was significantly decreased in the Omacor® group but increased in the placebo group. At the end of the supplementation period there were no differences in blood pressure or in plasma lipid and inflammatory marker concentrations between the two groups. It is concluded that Omacor® given at 2 g/day for an average of 21 days to patients with advanced carotid atherosclerosis lowers triglycerides and soluble E-selectin concentrations, but has limited broad impact on the plasma lipid profile or on inflammatory markers. This may be because the duration of intervention was too short or the dose of n-3 fatty acids was too low.

The conditional role of inflammation in pregnancy and cancer.

Cancer growth is characterized by proliferation of tumor cells in conjunction with invasion of all different immune cells that also invade healing wounds. This inflammatory response is necessary for cell proliferation but a second purpose of the inflammatory process is so that a low Th1/Th2 ratio is present with overexpression of IL-10, TGF-ß and IFN-γ. Down regulation of NO activity also shifts the balance between M1 and M2 macrophages. Both aspects allow the antigenous nature of the tumor to escape anti-tumor effects of the host. Support for this view comes from observations in pregnancy in which the placenta exhibits identical immune responses and downregulation of NO production to allow trophoblast cells to invade the uterine tissues without being rejected. Cell proliferation requires a metabolic set-up in which the organism produces adequate substrate for growth. This also bears the characteristics of a systemic inflammatory response delivering a similar substrate mix required for cancer and fetal growth. This arrangement is clearly beneficial in pregnancy and therefore supports the view that cancer growth is facilitated by the organism: the cancerous tumor elicits an immunological response opposing anti-tumor effects and induces the host to produce building blocks for growth.

Variants in the genes encoding TNF-α, IL-10, and GSTP1 influence the effect of α-tocopherol on inflammatory cell responses in healthy men.

BACKGROUND: Despite evidence of antioxidant effects of vitamin E in vitro and in animal studies, large, randomized clinical trials have not substantiated a benefit of vitamin E in reducing inflammation in humans. An individual's genetic background may affect the response to α-tocopherol supplementation, but this has rarely been investigated. OBJECTIVE: The aim of this study was to explore the role of genetic polymorphisms on changes in LPS-stimulated inflammatory cytokine production from peripheral blood mononuclear cells (PBMCs) after α-tocopherol supplementation. DESIGN: A total of 160 healthy, middle-aged male volunteers (mean age: 52.7 y) were given dietary supplements of either 75 IU (low dose; n = 57) or 600 IU (high dose; n = 103) α-tocopherol/d for 6 wk. The production of TNF-α and IL-1ß, -6, and -10 by PBMCs after LPS stimulation was measured at baseline and after 6 wk. Polymorphisms in 15 genes involved in inflammation or responses to oxidative stress were characterized in the subjects. RESULTS: The ability of α-tocopherol to affect TNF-α production by LPS-stimulated PBMCs was influenced by the TNFA -238 polymorphism (P = 0.016). The ability of α-tocopherol to affect IL-6 production was influenced by the GSTP1 313 polymorphism (P = 0.019). The ability of α-tocopherol to affect IL-1ß production was influenced by the IL10 -592 and -1082 polymorphisms (P = 0.025 and P = 0.016, respectively). CONCLUSIONS: In healthy control subjects, the effect of α-tocopherol supplementation on the production of inflammatory cytokines appears to be dependent on an individual's genotype. These genotype-specific differences may help explain some of the discordant results in studies that used vitamin E.

Docosahexaenoic acid inhibits the adhesion of flowing neutrophils to cytokine stimulated human umbilical vein endothelial cells.

The (n-3) PUFA, DHA, is widely thought to posses the ability to modulate the inflammatory response. However, its modes of interaction with inflammatory cells are poorly understood. In particular, there are limited data on the interactions of DHA with vascular endothelium, the cells that regulate the traffic of leukocytes from the blood into inflamed tissue. Using human umbilical vein endothelial cells (EC) cultured in a flow-based adhesion assay and activated with TNFα, we tested whether supplementing human umbilical vein EC with physiologically achievable concentrations of DHA would inhibit the recruitment of flowing neutrophils. DHA caused a dose-dependent reduction in neutrophil recruitment to the EC surface, although cells that became adherent were activated and could migrate across the human umbilical vein EC monolayer normally. Using EPA as an alternative supplement had no effect on the levels of neutrophil adhesion in this assay. Analysis of adhesion receptor expression by qPCR demonstrated that DHA did not alter the transcriptional activity of human umbilical vein EC. However, DHA did significantly reduce E-selectin expression at the human umbilical vein EC surface without altering the total cellular pool of this adhesion receptor. Thus, we have identified a novel mechanism by which DHA alters the trafficking of leukocytes during inflammation and demonstrate that this involves disruption of intracellular transport mechanisms used to present adhesion molecules on the surface of cytokine-stimulated EC.

The true cost of in-patient obesity: impact of obesity on inflammatory stress and morbidity.

The objective of the present review is to provide an overview of the metabolic effects of pro-inflammatory cytokine production during infection and injury; to highlight the disadvantages of pro-inflammatory cytokine production and inflammatory stress on morbidity and mortality of patients; to identify the influence of genetics and adiposity on inflammatory stress in patients and to indicate how nutrients may modulate the inflammatory response in patients. Recent research has shown clearly that adipose tissue actively secretes a wide range of pro- and anti-inflammatory cytokines. Paradoxically, although inflammation is an essential part of the response of the body to infection, surgery and trauma, it can adversely affect patient outcome. The metabolic effects of inflammation are mediated by pro-inflammatory cytokines. Metabolic effects include insulin insensitivity, hyperlipidaemia, muscle protein loss and oxidant stress. These effects, as well as being present during infective disease, are also present in diseases with a covert inflammatory basis. These latter diseases include obesity and type 2 diabetes mellitus. Inflammatory stress also increases during aging. The level of cytokine production, within individuals, is influenced by single nucleotide polymorphisms (SNP) in cytokine genes. The combination of SNP controls the relative level of inflammatory stress in both overt and covert inflammatory diseases. The impact of cytokine genotype on the intensity of inflammatory stress derived from an obese state is unknown. While studies remain to be done in the latter context, evidence shows that these genomic characteristics influence morbidity and mortality in infectious disease and diseases with an underlying inflammatory basis and thereby influence the cost of in-patient obesity. Antioxidants and n-3 PUFA alter the intensity of the inflammatory process. Recent studies show that genotypic factors influence the effectiveness of immunonutrients. A better understanding of this aspect of nutrient-gene interactions and of the genomic factors that influence the intensity of inflammation during disease will help in the more effective targeting of nutritional therapy.

Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability.

OBJECTIVE: To examine n-3 polyunsaturated fatty acid (PUFA) incorporation into atherosclerotic plaques and the association with plaque inflammation and stability. METHODS AND RESULTS: Patients awaiting carotid endarterectomy (n=121) were randomised to consume control capsules or n-3 PUFA ethyl ester capsules until surgery (median 21 days). The fatty acid compositions of plasma and carotid plaque phospholipids, plaque features, and expression of inflammatory genes were determined. The proportion of eicosapentaenoic acid (EPA) was higher (P<0.0001) in carotid plaque phospholipids in patients in the n-3 PUFA group. Plaques from patients in the n-3 PUFA group had fewer foam cells (P=0.0390). There were no other differences between plaques in the two groups with regard to histological characteristics or morphology. Plaque stability was not different between the two groups. However, the EPA content of plaque phospholipids was inversely associated with plaque instability (P=0.0209), plaque inflammation (P=0.0108), the number of T cells in the plaque (P=0.0097) and a summary score considering a range of plaque features (P=0.0425). Plaques from patients who received n-3 PUFAs had significantly lower levels of mRNA for matrix metalloproteinases (MMP)-7 (P=0.0055), -9 (P=0.0048) and -12 (P=0.0044) and for interleukin-6 (P=0.0395) and intercellular adhesion molecule 1 (P=0.0142). CONCLUSIONS: Atherosclerotic plaques readily incorporate EPA. A higher plaque EPA content is associated with a reduced number of foam cells and T cells, less inflammation and increased stability.

Sex difference in composition of plaques of patients undergoing carotid endarterectomy.

Our study aimed to examine the hypothesis that women have more stable plaques (a lower proportion of lipid component and a higher proportion of fibrous tissue) compared to men. Plaque specimens of 141 consecutive carotid endarterectomy patients (60 females and 81 males) were studied. Medical histories were recorded and the plasma concentrations of cholesterol and inflammatory markers were measured. We found that plaques from females had significantly less lipid than those from males (p = .01): the mean percentage of plaque lipid for women and men was 47.8% and 58.2%, respectively. Plaques from females had more fibrous tissue than those from men (p = .02): the mean percentage of fibrous tissue for women and men was 38.8% and 29.8%, respectively. This study concluded that the histology of carotid artery plaques from women appears to be more stable than that of those from men.

Hsp70 expression in monocytes from patients with peripheral arterial disease and healthy controls: monocyte Hsp70 in PAD.

BACKGROUND: Heat shock proteins (HSP) are induced during cellular stress. Their role is to chaperone cellular proteins giving protection from denaturation and ultimately preventing cell death. Monocytes are key cells involved in atherosclerosis and are highly responsive to HSP induction. Therefore, we wished to examine monocyte Hsp70 expression and induction in patients with peripheral arterial disease (PAD) and in healthy controls. METHODS: We measured cellular Hsp70 levels in freshly isolated monocytes and released Hsp70 levels in plasma and monocyte culture supernatants, obtained from patients with PAD and from healthy controls. We assessed the effect of statin therapy on Hsp70 levels and examined monocyte cell survival in culture with and without immunological stress. RESULTS: Monocyte cellular Hsp70 was lower in patients with PAD compared to healthy controls (11.3 +/- 7.4 ng/10(6) cells vs 20.7 +/- 16.0 ng/10(6) cells; p < 0.001). Individuals on statin therapy from both PAD and control groups had lower monocyte Hsp70 compared to those not treated with statins. Concentrations of Hsp70 released into culture supernatants were not dependent on PAD or statin therapy. Cell survival was inversely associated with Hsp70 concentrations in culture supernatants but had no association with cellular concentrations of Hsp70. CONCLUSIONS: Cellular Hsp70 and released Hsp70 may play different roles in monocyte health. Whilst induced Hsp70 destined for release appears to be unaffected in PAD, mechanisms responsible for cellular retention of Hsp70 may provide an area for future therapeutic targets in vascular disease.

Omega-3 Fatty acids and inflammation: novel interactions reveal a new step in neutrophil recruitment.

Inflammation is a physiological response to tissue trauma or infection, but leukocytes, which are the effector cells of the inflammatory process, have powerful tissue remodelling capabilities. Thus, to ensure their precise localisation, passage of leukocytes from the blood into inflamed tissue is tightly regulated. Recruitment of blood borne neutrophils to the tissue stroma occurs during early inflammation. In this process, peptide agonists of the chemokine family are assumed to provide a chemotactic stimulus capable of supporting the migration of neutrophils across vascular endothelial cells, through the basement membrane of the vessel wall, and out into the tissue stroma. Here, we show that, although an initial chemokine stimulus is essential for the recruitment of flowing neutrophils by endothelial cells stimulated with the inflammatory cytokine tumour necrosis factor-alpha, transit of the endothelial monolayer is regulated by an additional and downstream stimulus. This signal is supplied by the metabolism of the omega-6-polyunsaturated fatty acid (n-6-PUFA), arachidonic acid, into the eicosanoid prostaglandin-D(2) (PGD(2)) by cyclooxygenase (COX) enzymes. This new step in the neutrophil recruitment process was revealed when the dietary n-3-PUFA, eicosapentaenoic acid (EPA), was utilised as an alternative substrate for COX enzymes, leading to the generation of PGD(3). This alternative series eicosanoid inhibited the migration of neutrophils across endothelial cells by antagonising the PGD(2) receptor. Here, we describe a new step in the neutrophil recruitment process that relies upon a lipid-mediated signal to regulate the migration of neutrophils across endothelial cells. PGD(2) signalling is subordinate to the chemokine-mediated activation of neutrophils, but without the sequential delivery of this signal, neutrophils fail to penetrate the endothelial cell monolayer. Importantly, the ability of the dietary n-3-PUFA, EPA, to inhibit this process not only revealed an unsuspected level of regulation in the migration of inflammatory leukocytes, it also contributes to our understanding of the interactions of this bioactive lipid with the inflammatory system. Moreover, it indicates the potential for novel therapeutics that target the inflammatory system with greater affinity and/or specificity than supplementing the diet with n-3-PUFAs.

Dangers, and benefits of the cytokine mediated response to injury and infection.

The inflammatory response is essential for survival in an environment where continuous exposure to noxious events threaten the integrity of the organism. However, the beneficial effects of the response are influenced by factors, which disadvantage individuals within a population. These factors include malnutrition, infection, genotype, gender, pre-existing inflammation, and chronic intoxication. Although the inflammatory response is generally successful in dealing with noxious events, life-long exposure to these events takes its toll on the integrity of the body and becomes apparent as chronic disease, atherosclerosis, organ failure, and frailty. Progress in ameliorating the consequences of lifetime exposure to inflammatory events can only occur if a fuller understanding can be obtained of the factors, which influence the persistence and outcome of the inflammatory response at an individual level. A multitude of studies has shown that specific nutrients, diets, and dietary restriction are able to modulate the inflammatory response in the population as a whole. To advance in this area, precise knowledge is needed of how the disadvantageous factors, mentioned above, affect the individual's response to anti-inflammatory nutrients.

Cancer cachexia is associated with the IL10 -1082 gene promoter polymorphism in patients with gastroesophageal malignancy.

BACKGROUND: The genetic predisposition of the host to local or systemic inflammation may contribute to the effect of cancer cachexia. OBJECTIVE: We investigated the relation between cytokine polymorphisms (IL1B -511, IL6 -174, IL10 -1082, TNFA -308, and LTA +252) and markers of nutritional status among patients with gastroesophageal cancer to determine whether any such association was reflected by cytokine concentrations in the tumor or plasma compartments. DESIGN: Patients (n = 203) with a diagnosis of gastroesophageal cancer underwent nutritional assessment (body mass index, anthropometric measures, dysphagia scoring, and estimation of dietary intake). Single nucleotide polymorphism genotyping was performed by TaqMan allelic discrimination genotyping. Serum cytokine and C-reactive protein concentrations were determined by enzyme-linked immunosorbent assay. Tumor tissue cytokine protein concentrations (n = 56) were determined by using the Cytometric Bead Array System. RESULTS: IL10 GG and IL6 CC polymorphisms were associated with elevated serum C-reactive protein concentrations, and the IL6 CC genotype was also associated with elevated tumor tissue cytokine concentrations. At diagnosis, the IL10 GG, but not the IL6, genotype was linked with increased total weight loss: 4.9% for AA, 7.1% for AG, and 12.0% for GG (P = 0.007). Serum C-reactive protein concentrations correlated with increased weight loss (r = 0.24, P < 0.001). Compared with other genotypes, the IL10 GG genotype retained an independent association in determining the extent of weight loss on multivariate analysis (95% CI: 0.52, 3.43; P = 0.008). Possession of the GG allele was associated with a 2.3 times increased risk of developing cachexia (95% CI: 1.2, 4.3; P = 0.014). CONCLUSION: These data suggest that the IL10 genotype of the host can influence the development of cachexia among patients with gastroesophageal malignancy.

Polymorphisms in the CD36 gene modulate the ability of fish oil supplements to lower fasting plasma triacyl glycerol and raise HDL cholesterol concentrations in healthy middle-aged men.

Five SNPs in the CD36 gene, 25444G>A, 27645del>ins, 30294G>C, -31118G>A and -33137A>G in haplotypic combinations, link to fasting plasma NEFA concentrations. Fish oil lowers TAG concentrations. The influence of CD36 SNPs on hypotriglyceridemic effects is unknown. The study examines how four of the SNPs modify the effects of fish oil on fasting plasma TAG, NEFA, glucose LDL and HDL cholesterol concentrations in 111 healthy, middle-aged, Caucasian men. Subjects consumed habitual diets while taking 6g MaxEPA daily for 12 weeks. TAG decreased from 1.48 mol/l to 0.11 mmol/l, and glucose and HDL rose from 5.92 to 0.15 mmol/l and from 1.27 to 0.04 mmol/l, respectively, irrespective of genotype. NEFA was unaffected. Significant falls in TAG only occurred in individuals with the GG variant of the 25444, 30294, -31118 or -33137 SNPs. The TAG-lowering effects may be via stimulation of CD36 activity in extrahepatic tissue in individuals with the GG variants of these SNPs.

Managing hypercholesterolemia and its correlation with carotid plaque morphology in patients undergoing carotid endarterectomy.

PURPOSE: Hypercholesterolemia is a critical problem in patients with carotid atherosclerosis. The adequacy of attention to lipid risk factors in patients with carotid stenosis awaiting carotid endarterectomy (CEA) has rarely been studied. We also assessed patient awareness of hypercholesterolemia and carotid plaque morphology. METHODS: A prospective study was conducted of 141 consecutive patients admitted electively for CEA. Each patient's medical history was taken. Plasma cholesterol concentrations were determined. Plaque histology was scored according to American Heart Association criteria and their modification. RESULTS: Of patients who were aware of their hypercholesterolemia and who were receiving treatment, 28.6% had total cholesterol levels > or =5 mmol/L. Among those patients who had been told that they had no problem with hypercholesterolemia, 32.5% had plasma cholesterol concentrations > or =5 mmol/L. Among those patients who had never had their plasma cholesterol measured, 48.4% had total cholesterol levels > or =5 mmol/L. Patients in this last group tended to have more severe types of plaque pathology than those in other groups (12.9% plaque rupture). CONCLUSIONS: Hypercholesterolemia does not seem to be well managed in patients awaiting CEA.

Dietary supplementation with fish oil modifies the ability of human monocytes to induce an inflammatory response.

Monocytes/macrophages are key orchestrators of inflammation and are involved in the pathogenesis of chronic inflammatory disorders, including atherosclerosis. (n-3) Fatty acids, found in fish oil, have been shown to have protective effects in such disorders. To investigate possible modes of action, we used a monocyte:endothelial cell (EC) coculture model to investigate the pro-inflammatory potential of monocytes. Monocytes were isolated from the blood of donors with peripheral arterial disease (PAD) or control donors, before and after a 12-wk supplementation of their diet with fish oil. The monocytes were cultured with human umbilical vein EC (HUVEC) for 24 h, after which the ability of the HUVEC to recruit flowing neutrophils was tested. Monocytes from either group of donors stimulated the EC to support the adhesion and migration of neutrophils. Fish oil supplementation reduced the potency of monocytes from normal subjects, but not those from patients with PAD, to induce recruitment. Concurrent medication may have acted as a complicating factor. On subgroup analysis, only those free of medication showed a significant effect of fish oil. Responses before or after supplementation were not closely linked to patterns of secretion of cytokines by cultured monocytes, tested in parallel monocultures. These results suggest that fish oil can modulate the ability of monocytes to stimulate EC and that this might contribute to their protective effects against chronic inflammatory disorders. Benefits, however, may depend on existing medical status and on other treatments being received.

Fish oil induced increase in walking distance, but not ankle brachial pressure index, in peripheral arterial disease is dependent on both body mass index and inflammatory genotype.

Peripheral arterial disease (PAD) is an atherosclerotic disease. Evidence suggests that atherosclerosis is an inflammatory condition and long chain n-3 fatty acids, found in oily fish and fish oils, have been shown to reduce inflammation. Genetic and lifestyle factors such as body mass index (BMI) also influence inflammation. In this study we have examined the effect of fish oil in patients with claudication secondary to PAD. Fish oil supplementation, providing 1g EPA and 0.7 g DHA per day for 12 weeks, increased walking distance on a treadmill set at 3.2 km/h with a 7% incline. Walking distance to first pain increased from 76.2+/-8.5 m before fish oil to 140.6+/-25.5 m after fish oil (mean+/-SEM, p=0.004) and total distance walked increased from 160.0+/-21.5 m before fish oil to 242.1+/-34.5 m after fish oil (p=0.002). Fish oil supplementation also improved ankle brachial pressure index (ABPI) from 0.599+/-0.017 before fish oil to 0.776+/-0.030 after fish oil (p<0.001). The increase in walking distance was dependent on both BMI and genotype for single nucleotide polymorphisms in the genes encoding the pro-inflammatory cytokines tumour necrosis factor-alpha and interleukin (IL)-1beta and the anti-inflammatory cytokine IL-10 (detected using amplification refractory mutation system polymerase chain reaction). Neither BMI nor any of the genotypes examined affected the ability of fish oil to increase ABPI. The mechanisms by which fish oil affects walking distance and ABPI do not appear to be the same.

Long-chain n-3 fatty acid supplementation in men increases resistance to activated protein C.

It has recently and controversially been demonstrated that fish oil supplementation may not be beneficial for everyone, but to date there have been no biological explanations. We suggest that resistance to the anticoagulant, activated protein C (APC), be considered as a potential mechanism, because it has been demonstrated that the type of fatty acids on phospholipids modulates function of the APC pathway. The APC ratio in plasma was decreased by 7% after fish oil supplementation in healthy men (P<.005; n=35). The decrease in APC ratio equates to an increase in APC resistance. Fish oil lowered the APC ratio by (1) increasing low-density lipoprotein (LDL) cholesterol (P<.01) and apolipoprotein B (P<.05) and (2) increasing platelet microparticles (P<.05). In vitro, purified LDL decreased the APC ratio and increased microparticle formation. These changes affecting the anticoagulant APC could contribute toward a prothrombotic state, potentially explaining the recent observation that fish oil supplementation may not always be of benefit. These findings will need to be repeated in different disease states.

The effects of sulfur amino acid intake on immune function in humans.

No direct data exist on the influence of supranormal intakes of sulfur amino acids on immune function in humans. However 3 major products of sulfur amino acids, glutathione (GSH), homocysteine (Hcy), and taurine (Tau), influence, mainly, inflammatory aspects of the immune response in vitro and in vivo. Methionine intakes above approximately 1 g/d transiently raise plasma Tau, Hcy, and GSH. Tau and GSH ameliorate inflammation. Hcy has the opposite effect. A biphasic relation, between cellular GSH and CD4+ and CD8+ numbers occurs in healthy men. How changes in sulfur amino acid intake influence this phenomenon is unknown. In animals, high Tau intakes are antiinflammatory. How immune function in humans is affected is unknown. A positive relation between plasma neopterin (a marker of a Th-1-type immune response) and Hcy indicates that Hcy may play a part in inflammatory aspects of Parkinson's disease and aging. In vitro, Hcy, at concentrations seen following consumption of approximately 6 g L-methionine/d in adults, increases the interactions among T lymphocytes, monocytes, and endothelium. Whether a similar phenomenon occurs in vivo is unknown. Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with raised plasma Hcy in young but not old subjects. The relation of this observation to immune function is unknown. The relationships among Hcy, inflammatory aspects of disease, and in vitro alterations in immune cell behavior create a cautionary note about supplementation of diets with l-methionine to raise intake above approximately 1 g/d. Studies directly linking methionine intake, genetics, plasma Hcy, Tau, and GSH and immune function are needed.

Effects of dairy products naturally enriched with cis-9,trans-11 conjugated linoleic acid on the blood lipid profile in healthy middle-aged men.

BACKGROUND: Interest in the development of dairy products naturally enriched in conjugated linoleic acid (CLA) exists. However, feeding regimens that enhance the CLA content of milk also increase concentrations of trans-18:1 fatty acids. The implications for human health are not yet known. OBJECTIVE: This study investigated the effects of consuming dairy products naturally enriched in cis-9,trans-11 CLA (and trans-11 18:1) on the blood lipid profile, the atherogenicity of LDL, and markers of inflammation and insulin resistance in healthy middle-aged men. DESIGN: Healthy middle-aged men (n = 32) consumed ultra-heat-treated milk, butter, and cheese that provided 0.151 g/d (control) or 1.421 g/d (modified) cis-9,trans-11 CLA for 6 wk. This was followed by a 7-wk washout and a crossover to the other treatment. RESULTS: Consumption of dairy products enriched with cis-9,trans-11 CLA and trans-11 18:1 did not significantly affect body weight, inflammatory markers, insulin, glucose, triacylglycerols, or total, LDL, and HDL cholesterol but resulted in a small increase in the ratio of LDL to HDL cholesterol. The modified dairy products changed LDL fatty acid composition but had no significant effect on LDL particle size or the susceptibility of LDL to oxidation. Overall, increased consumption of full-fat dairy products and naturally derived trans fatty acids did not cause significant changes in cardiovascular disease risk variables, as may be expected on the basis of current health recommendations. CONCLUSION: Dairy products naturally enriched with cis-9,trans-11 CLA and trans-11 18:1 do not appear to have a significant effect on the blood lipid profile.

Does nutrition have a role in peripheral vascular disease?

Peripheral vascular disease (PVD) is a manifestation of systemic atherosclerosis in the lower limbs, and PVD patients have a 3- to 5-fold increased risk of cardiovascular mortality compared with age-matched controls. Nevertheless, recent reports show how PVD patients are undertreated with regard to CVD risk-factor reduction and the use of lipid-lowering or antiplatelet drugs. There is appreciable evidence that demonstrates the beneficial effects of certain nutrients and dietary habits in the prevention of CVD, but there has been little attention paid to the role of nutrients in PVD. The purpose of the present review is to provide an overview of our understanding of how foods could possibly benefit PVD. In the last few decades, several nutrients have arisen as potentially health-promoting in PVD. While nutritional interventions in PVD show positive clinical effects for fish oil, carnitine or vitamin E, others such as olive oil or vitamin C seem to interact only at a biochemical level by decreasing risk factors. Moreover, only epidemiological associations exist for the potential role of fibre, folates or vitamin B6 in this disease. In all cases, the limited data available provide no clear-cut evidence in favour of the clinical benefit of nutritional interventions aimed at reducing risk factors and ameliorating symptoms in PVD patients. No practical recommendations can be given at this stage, and further studies are clearly needed.

Pulmonary cachexia, systemic inflammatory profile, and the interleukin 1beta -511 single nucleotide polymorphism.

BACKGROUND: Cachexia is common in chronic obstructive pulmonary disease (COPD) and is thought to be linked to an enhanced systemic inflammatory response. OBJECTIVE: We investigated differences in the systemic inflammatory profile and polymorphisms in related inflammatory genes in COPD patients. DESIGN: A cross-sectional study was performed in 99 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stages II-IV), who were stratified by cachexia based on fat-free mass index (FFMI; in kg/m2: <16 for men and <15 for women) and compared with healthy control subjects (HCs). Body composition was determined by bioelectrical impedance analysis. Plasma concentrations and gene polymorphisms of interleukin 1beta (IL-1beta -511), IL-6 (IL-6 -174), and the tumor necrosis factor system (TNF-alpha -308 and lymphotoxin-alpha +252) were determined. Plasma C-reactive protein, leptin, and urinary pseudouridine (as a marker of cellular protein breakdown) were measured. RESULTS: Fat mass, leptin, and pseudouridine were significantly different (P < 0.001) between noncachectic patients (NCPs) and cachectic patients (CPs: n = 35); the systemic inflammatory cytokine profile was not. NCPs had a body compositional shift toward a lower fat-free mass and a higher fat mass compared with HCs. CPs and NCPs had a greater systemic inflammatory response (P < 0.05) than did HCs, as reflected in C-reactive protein, soluble TNF-R75, and IL-6 concentrations. The overall distribution of the IL-1beta -511 polymorphism was significantly different between the groups (P < 0.05). CONCLUSIONS: In COPD patients, who are characterized by an elevated systemic inflammatory response, cachexia is not discriminatory for the extent of increase in inflammatory status. This study, however, indicates a potential influence of genetic predisposition on the cachexia process.