Showing papers by "Philip C. Calder published in 2012"

Mechanisms of Action of (n-3) Fatty Acids

Abstract: (n-3) PUFA are a family of biologically active fatty acids. The simplest member of this family, α-linolenic acid, can be converted to the more biologically active very long-chain (n-3) PUFA EPA and DHA; this process occurs by a series of desaturation and elongation reactions, with stearidonic acid being an intermediate in the pathway. Biological activity of α-linolenic and stearidonic acids most likely relates to their conversion to EPA. The very long-chain (n-3) PUFA have a range of physiological roles that relate to optimal cell membrane structure and optimal cell function and responses. Thus, (n-3) PUFA play a key role in preventing, and perhaps treating, many conditions of poor health and well-being. The multiple actions of (n-3) PUFA appear to involve multiple mechanisms that connect the cell membrane, the cytosol, and the nucleus. For some actions, (n-3) PUFA appear to act via receptors or sensors, so regulating signaling processes that influence patterns of gene expression. Some effects of (n-3) PUFA seem to involve changes in cell membrane fatty acid composition. Changing membrane composition can in turn affect membrane order, formation of lipid rafts, intracellular signaling processes, gene expression, and the production of both lipid and peptide mediators. Under typical Western dietary conditions, human cells tend to have a fairly high content of the (n-6) fatty acid arachidonic acid. Increased oral intake of EPA and DHA modifies the content of arachidonic acid as well as of EPA and DHA. Arachidonic acid is the substrate for eicosanoids involved in physiology and pathophysiology. The eicosanoids produced from EPA frequently have properties that are different from those that are produced from arachidonic acid. EPA and DHA are also substrates for production of resolvins and protectins, which seem to be biologically extremely potent. Increasing the contents of EPA and DHA in membranes modifies the pattern of production of these different lipid mediators.

Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor?

Abstract: Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the population worldwide and may confer increased cardiometabolic risk with consequent adverse cardiovascular outcomes independent of traditional cardiovascular risk factors and the metabolic syndrome. It is characterized almost universally by insulin resistance and is strongly associated with type 2 diabetes and obesity. Non-alcoholic fatty liver disease is a marker of pathological ectopic fat accumulation combined with a low-grade chronic inflammatory state. This results in several deleterious pathophysiological processes including abnormal glucose, fatty acid and lipoprotein metabolism, increased oxidative stress, deranged adipokine profile, hypercoaguability, endothelial dysfunction, and accelerated progression of atherosclerosis. This ultimately leads to a dysfunctional cardiometabolic phenotype with cardiovascular mortality representing the main mode of premature death in NAFLD. This review is aimed at introducing NAFLD to the clinical cardiologist by discussing in-depth the evidence to date linking NAFLD with cardiovascular disease, reviewing the likely mechanisms underlying this association, as well as summarizing from a cardiologist's perspective, current and potential future treatment options for this increasingly prevalent disease.

Influence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis.

Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of the joints and bones. The n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (ARA) is the precursor of inflammatory eicosanoids which are involved in RA. Some therapies used in RA target ARA metabolism. Marine n-3 PUFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) found in oily fish and fish oils decrease the ARA content of cells involved in immune responses and decrease the production of inflammatory eicosanoids from ARA. EPA gives rise to eicosanoid mediators that are less inflammatory than those produced from ARA and both EPA and DHA give rise to resolvins that are anti-inflammatory and inflammation resolving, although little is known about these latter mediators in RA. Marine n-3 PUFAs can affect other aspects of immunity and inflammation relevant to RA, including dendritic cell and T cell function and production of inflammatory cytokines and reactive oxygen species, although findings for these outcomes are not consistent. Fish oil has been shown to slow the development of arthritis in animal models and to reduce disease severity. A number of randomised controlled trials of marine n-3 PUFAs have been performed in patients with RA. A systematic review included 23 studies. Evidence is seen for a fairly consistent, but modest, benefit of marine n-3 PUFAs on joint swelling and pain, duration of morning stiffness, global assessments of pain and disease activity, and use of non-steroidal anti-inflammatory drugs.

The role of marine omega-3 (n-3) fatty acids in inflammatory processes, atherosclerosis and plaque stability.

Abstract: Atherosclerosis has an important inflammatory component and acute cardiovascular events can be initiated by inflammatory processes occurring in advanced plaques. Fatty acids influence inflammation through a variety of mechanisms; many of these are mediated by, or associated with, the fatty acid composition of cell membranes. Human inflammatory cells are typically rich in the n-6 fatty acid arachidonic acid, but the contents of arachidonic acid and of the marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can be altered through oral administration of EPA and DHA. Eicosanoids produced from arachidonic acid have roles in inflammation. EPA also gives rise to eicosanoids and these are usually biologically weak. EPA and DHA give rise to resolvins which are anti-inflammatory and inflammation resolving. EPA and DHA also affect production of peptide mediators of inflammation (adhesion molecules, cytokines, etc.). Thus, the fatty acid composition of human inflammatory cells influences their function; the contents of arachidonic acid, EPA and DHA appear to be especially important. The anti-inflammatory effects of marine n-3 polyunsaturated fatty acids (PUFAs) may contribute to their protective actions towards atherosclerosis and plaque rupture.

Evaluation of the immune benefits of two probiotic strains Bifidobacterium animalis ssp. lactis, BB-12® and Lactobacillus paracasei ssp. paracasei, L. casei 431® in an influenza vaccination model: a randomised, double-blind, placebo-controlled study.

Abstract: The present study investigated the ability of Bifidobacterium animalis ssp. lactis (BB-12®) and Lactobacillus paracasei ssp. paracasei (L. casei 431®) to modulate the immune system using a vaccination model in healthy subjects. A randomised, double-blind, placebo-controlled, parallel-group study was conducted in 211 subjects (56 % females, mean age 33·2 (sd 13·1) years). Subjects consumed a minimum of 10⁹ colony-forming units of BB-12® (capsule) or L. casei 431® (dairy drink) or a matching placebo once daily for 6 weeks. After 2 weeks, a seasonal influenza vaccination was given. Plasma and saliva samples were collected at baseline and after 6 weeks for the analysis of antibodies, cytokines and innate immune parameters. Changes from baseline in vaccine-specific plasma IgG, IgG1 and IgG3 were significantly greater in both probiotic groups v. the corresponding placebo group (L. casei 431®, P = 0·01 for IgG; P < 0·001 for remaining comparisons). The number of subjects obtaining a substantial increase in specific IgG (defined as ≥ 2-fold above baseline) was significantly greater in both probiotic groups v. placebo (BB-12®, P < 0·001 for IgG, IgG1 and IgG3; L. casei 431®, P < 0·001 for IgG1 and IgG3). Significantly greater mean fold increases for vaccine-specific secretory IgA in saliva were observed in both probiotic groups v. placebo (BB-12®, P = 0·017; L. casei 431®, P = 0·035). Similar results were observed for total antibody concentrations. No differences were found for plasma cytokines or innate immune parameters. Data herein show that supplementation with BB-12® or L. casei 431® may be an effective means to improve immune function by augmenting systemic and mucosal immune responses to challenge.

Long-chain fatty acids and inflammation

Abstract: Inflammation plays a key role in many common conditions and diseases. Fatty acids can influence inflammation through a variety of mechanisms acting from the membrane to the nucleus. They act through cell surface and intracellular receptors that control inflammatory cell signalling and gene expression patterns. Modifications of inflammatory cell membrane fatty acid composition can modify membrane fluidity, lipid raft formation and cell signalling leading to altered gene expression and can alter the pattern of lipid and peptide mediator production. Cells involved in the inflammatory response usually contain a relatively high proportion of the n-6 fatty acid arachidonic acid in their membrane phospholipids. Eicosanoids produced from arachidonic acid have well-recognised roles in inflammation. Oral administration of the marine n-3 fatty acids EPA and DHA increases the contents of EPA and DHA in the membranes of cells involved in inflammation. This is accompanied by a decrease in the amount of arachidonic acid present. EPA is a substrate for eicosanoid synthesis and these are often less potent than those produced from arachidonic acid. EPA gives rise to E-series resolvins and DHA gives rise to D-series resolvins and protectins. Resolvins and protectins are anti-inflammatory and inflammation resolving. Thus, the exposure of inflammatory cells to different types of fatty acids can influence their function and so has the potential to modify inflammatory processes.

Marine omega-3 fatty acids and coronary heart disease.

Abstract: Purpose of review: To provide an overview of the key earlier intervention studies with marine omega-3 fatty acids and to review and comment on recent studies reporting on mortality outcomes and on selected underlying mechanisms of action. Recent findings: Studies relating marine omega-3 fatty acid status to current or future outcomes continue to indicate benefits, for example, on incident heart failure, congestive heart failure, acute coronary syndrome, and all-cause mortality. New mechanistic insights into the actions of marine omega-3 fatty acids have been gained. Three fairly large secondary prevention trials have not confirmed the previously reported benefit of marine omega-3 fatty acids towards mortality in survivors of myocardial infarction. Studies of marine omega-3 fatty acids in atrial fibrillation and in cardiac surgery-induced atrial fibrillation have produced inconsistent findings and meta-analyses demonstrate no benefit. A study confirmed that marine omega-3 fatty acids reduce the inflammatory burden with advanced atherosclerotic plaques, so inducing greater stability. Summary: Recent studies of marine omega-3 fatty acids on morbidity of, and mortality from, coronary and cardiovascular disease have produced mixed findings. These studies raise new issues to be addressed in future research.

Fish Oil Supplementation Improves Neutrophil Function During Cancer Chemotherapy

Abstract: Cancer chemotherapy is associated with neutropenia and impaired neutrophil function. This study aimed to investigate whether supplementation with low dose fish oil (FO), providing n-3 polyunsaturated fatty acids, in cancer patients receiving chemotherapy after surgical tumor (mainly gastrointestinal) removal is able to improve the function of blood neutrophils. Patients (n = 38) receiving chemotherapy (5-fluorouracil and leucovorin) were randomized into two groups; one group (control) did not receive a supplement, while the other group (FO) received 2 g FO/day for 8 weeks; the FO provided 0.3 g eicosapentaenoic acid plus 0.4 g docosahexaenoic acid per day. Patients in the control group lost an average of 2.5 kg of weight over the 8 weeks of the study. The number of blood polymorphonuclear cells (PMNC), mainly neutrophils, and their functions (phagocytosis and hydrogen peroxide production) decreased in the control group (average decreases of approximately 30, 45 and 17%, respectively). FO prevented these decreases and actually increased body weight (average of 1.7 kg weight gain; p < 0.002 vs. control group), PMNC number (average 29% increase), phagocytosis (average 14% increase) and superoxide production (average 28% increase). FO may be useful in preventing chemotherapy-induced decline in neutrophil number and function.

Systematic reviews of the role of omega-3 fatty acids in the prevention and treatment of disease.

Abstract: This issue of the BJN provides a series of up to date systematic reviews on the pleiotropic effects of omega-3 fatty acids in health promotion and disease prevention. It is not yet 100 years since the studies of George and Mildred Burr provided the first evidence for the essential nature of specific types of fats. This was only made possible by the earlier pioneering work of EV McColllum who demonstrated by controlled studies that certain substances were necessary in small but measurable quantities for normal health in rats. He named these substances ‘fat-soluble A’ and ‘water-soluble B’, thus initiating the alphabetical nomenclature for vitamins. His first thoughts were that there existed one fat-soluble A and one water-soluble B, but further work in his laboratory and elsewhere soon indicated that there were numerous chemical entities involved. The prevailing view at the time was that fat represented mainly a source of energy and that its hydrophobic nature allowed energy to be concentrated better than what was possible with starches. However, prominent nutritionists indicated that animals could make fat from carbohydrates provided energy supply was in excess and ridiculed those that postulated other potential roles for fats. George Burr worked with Evans at the time and contributed in establishing that the elusive vitamin E was in the unsaponifiable fraction. Thus for a period of time Burr was drawn away from considering fatty acids as a potential novel essential dietary factor. In the process, they established that animals fed on a fat-free diet composed of casein, sugar yeast, and the unsaponifiable fraction of wheat germ and cod liver oils developed deficiency symptoms. Evans was searching for a new vitamin that could explain the observed skin changes, while Burr decided to explore the saponifiable components. This was a turning point in his path to discovery of essential fatty acids. He left Evans’ laboratory at Berkeley moving to Minnesota. Burr took two cages of Long Evans rats with him. He also took Mildred Lawson who was in charge of the rat colony. The rest is history: soon after they established a laboratory and a rat colony, they announced (in 1929) that unsaturated fat was essential, and in 1930 that linoleic acid, and possibly other fatty acids, were also active in reversing the skin changes and in restoring growth seen in rats fed fat-free diets. Work over the following 60 years conclusively determined the essential nature of both linoleic and a-linolenic acids. Yet few considered the importance of these nutrients for human health until the past decades where the full significance of dietary essential fatty acids has been realized considering their role in the synthesis of prostanoids and the myriad of pleiotropic functions that relate directly and indirectly to them. The prevailing belief was deeply rooted that fats were only a concentrated source of calories that were easily stored and served as carriers of fat-soluble vitamins. This issue of the BJN provides a glimpse of how fast this field has moved and serves to underscore the recent realization in human nutrition that the quality of the fat supply in terms of the parent n-6 and n-3 essential fatty acids as well as their longer chain, more unsaturated derivatives arachidonic, eicosapentaenoic and docosahexaenoic acids plays a vital role in human health from conception through every stage of human development, maturation and aging. In terms of health and disease the essential fatty acids and their derivatives interact at multiple levels, including cell membrane composition, metabolism, signal transduction and amplification, and gene expression. Furthermore they influence cell growth and differentiation, tissue repair, apoptosis and cell death and many physiological and pathological processes including immunity and inflammation. The observations made lead to a conclusion that long chain polyunsaturated fatty acids (arachidonic, eicosapentaenoic and docosahexaenoic acids) are conditionally essential nutrients for adequate growth, development and function in humans. Despite the impressive documentation of EPA and DHA related health benefits, the cellular and molecular mechanisms for their action are still insufficiently understood. The evidence systematically reviewed in this issue of the BJN indicates that the effects of DHA and EPA are mediated, not only by their known effects on membrane biophysical properties and the corresponding electrophysiological correlates, but also by effects on cell growth, differentiation and functional maturation, and by modulating gene expression during development and at all subsequent stages of human life. Every tissue and every cell type is influenced not only by the genetically coded DNA-proteome but also by the dietary supply of essential fatty acids that determines how tissues and animals adapt to changing environments. The plasticity given by essential fatty acids is key to biological adaptations of every type. What is also clear from the articles herein, however, is that there remain multiple unanswered questions, and specifically there is a lack of high-quality population-based effectiveness trials in many areas crucial to human development and health. With global population ageing continuing apace and a concomitant increase in the number of individuals suffering from chronic diseases British Journal of Nutrition (2012), 107, S1–S2 doi:10.1017/S0007114512001420 q The Authors 2012

Vascular Dysfunction Induced in Offspring by Maternal Dietary Fat Involves Altered Arterial Polyunsaturated Fatty Acid Biosynthesis

Abstract: Nutrition during development affects risk of future cardiovascular disease. Relatively little is known about whether the amount and type of fat in the maternal diet affect vascular function in the offspring. To investigate this, pregnant and lactating rats were fed either 7%(w/w) or 21%(w/w) fat enriched in either18:2n-6, trans fatty acids, saturated fatty acids, or fish oil. Their offspring were fed 4%(w/w) soybean oil from weaning until day 77. Type and amount of maternal dietary fat altered acetylcholine (ACh)-mediated vaso-relaxation in offspring aortae and mesenteric arteries, contingent on sex. Amount, but not type, of maternal dietary fat altered phenylephrine (Pe)-induced vasoconstriction in these arteries. Maternal 21% fat diet decreased 20:4n-6 concentration in offspring aortae. We investigated the role of Δ6 and Δ5 desaturases, showing that their inhibition in aortae and mesenteric arteries reduced vasoconstriction, but not vaso-relaxation, and the synthesis of specific pro-constriction eicosanoids. Removal of the aortic endothelium did not alter the effect of inhibition of Δ6 and Δ5 desaturases on Pe-mediated vasoconstriction. Thus arterial smooth muscle 20:4n-6 biosynthesis de novo appears to be important for Pe-mediated vasoconstriction. Next we studied genes encoding these desaturases, finding that maternal 21% fat reduced Fads2 mRNA expression and increased Fads1 in offspring aortae, indicating dysregulation of 20:4n-6 biosynthesis. Methylation at CpG −394 bp 5′ to the Fads2 transcription start site predicted its expression. This locus was hypermethylated in offspring of dams fed 21% fat. Pe treatment of aortae for 10 minutes increased Fads2, but not Fads1, mRNA expression (76%; P<0.05). This suggests that Fads2 may be an immediate early gene in the response of aortae to Pe. Thus both amount and type of maternal dietary fat induce altered regulation of vascular tone in offspring though differential effects on vaso-relaxation, and persistent changes in vasoconstriction via epigenetic processes controlling arterial polyunsaturated fatty acid biosynthesis.

Salmon Consumption during Pregnancy Alters Fatty Acid Composition and Secretory IgA Concentration in Human Breast Milk

Abstract: Fish oil supplementation during pregnancy alters breast milk composition, but there is little information about the impact of oily fish consumption. We determined whether increased salmon consumption during pregnancy alters breast milk fatty acid composition and immune factors. Women (n = 123) who rarely ate oily fish were randomly assigned to remain on their habitual diet or to consume 2 portions of farmed salmon per week from 20 wk of pregnancy until birth. The salmon provided 3.45 g long-chain (LC) (n-3) PUFA/wk. Breast milk fatty acid composition and immune factors [soluble CD14, transforming growth factor-b (TGFb)1, TGFb2, and secretory IgA] were analyzed at 1, 5, 14, and 28 d postpartum (PP). Breast milk from the salmon group had higher proportions of EPA (80%), docosapentaenoic acid (30%), and DHA (90%) on d 5 PP compared with controls (P , 0.01). The LC (n-6) PUFA:LC (n-3) PUFA ratio was lower for the salmon group on all days of PP sampling (P # 0.004), although individual (n-6) PUFA proportions, including arachidonic acid, did not differ. All breast milk immune factors decreased between d 1 and 28 PP (P , 0.001). Breast milk secretory IgA (sIgA) was lower in the salmon group (d 1‐28 PP; P = 0.006). Salmon consumption during pregnancy, at the current recommended intakes, increases the LC (n-3) PUFA concentration of breast milk in early lactation, thus improving the supply of these important fatty acids to the breast-fed neonate. The consequence of the lower breast milk concentration of sIgA in the salmon group is not clear. J. Nutr. doi: 10.3945/jn.112.160804.

β2-1 Fructans have a bifidogenic effect in healthy middle-aged human subjects but do not alter immune responses examined in the absence of an in vivo immune challenge: results from a randomised controlled trial

Abstract: β2-1 fructans are considered to be prebiotics. Current literature indicates that β2-1 fructans may modulate some aspects of immune function, improve the host's ability to respond to certain intestinal infections, and modify some inflammatory outcomes in human subjects. However, there is a need to find out more about the modulation of immune markers by β2-1 fructans in humans. Healthy human subjects aged 45-65 years were randomly allocated to β2-1 fructans (Orafti® Synergy1; 8 g/d; n 22) or the digestible carbohydrate maltodextrin as placebo (n 21) for 4 weeks. Blood, saliva and faecal samples were collected at study entry and after 4 weeks. Immune parameters were measured using the blood and saliva samples and bifidobacteria were measured in the faecal samples. Faecal bifidobacteria numbers increased in the Orafti® Synergy1 group (P < 0·001) and were different at 4 weeks from numbers in the placebo group (P = 0·001). There was no significant effect of Orafti® Synergy1 on any of the immune parameters measured (blood immune cell subsets, total serum Ig, salivary IgA, neutrophil and monocyte phagocytosis of Escherichia coli and respiratory burst in response to E. coli or phorbol ester, natural killer cell activity, T cell activation and proliferation, production of six cytokines by T cells). It is concluded that, compared with maltodextrin, Orafti® Synergy1 has a bifidogenic effect in healthy middle-aged human subjects but does not alter immune responses examined in the absence of an in vivo immune challenge.

Oral Administration of Oleic or Linoleic Acids Modulates the Production of Inflammatory Mediators by Rat Macrophages

Abstract: Oleic (OLA) and linoleic (LNA) acids are commonly consumed fatty acids and they can modulate the inflammatory response, in which macrophages play an important role. The aim of this study was to investigate the effects of these two fatty acids on the production of inflammatory mediators by macrophages. Rats received oral administration of water (control), OLA or LNA (0.22 g/kg body weight) daily for 10 days and peritoneal resident macrophages were then isolated. Subsequently, they were seeded in culture plates and the production of various inflammatory mediators was assessed. Oral administration with OLA decreased the production of IL-1β, IL-6 and CINC-2αβ by resident macrophages and LNA decreased the production of IL-1β, IL-6 and VEGF in the absence of lipopolysaccharide (LPS), although it accelerated IL-1β release and decreased IL-10 synthesis when cells were stimulated with LPS. Neither fatty acid affected the production of superoxide anion, hydrogen peroxide, nitrite, TNF-α, PGE2, LTB4 or 15(S)-HETE. Thus, OLA and LNA influence the production of several inflammatory mediators by macrophages.

Lower omega-3 fatty acid intake and status are associated with poorer cognitive function in older age: A comparison of individuals with and without cognitive impairment and Alzheimer's disease.

Abstract: ObjectivesVarious strands of evidence suggest that low intake of omega-3 fatty acids increases risk of cognitive decline and dementia. The present study investigated differences in dietary intake and blood plasma content of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) in individuals with cognitive impairment no dementia (CIND), individuals with Alzheimer's disease (AD), and healthy volunteers (HV).MethodsA total of 135 individuals aged between 55 and 91 years (19 AD, 55 CIND, and 61 HV) were assessed predominantly within a hospital setting.ResultsCompared with age and sex-matched HV, individuals with AD or CIND performed poorly on a majority of tests of cognitive function. Impairment was greatest for delayed and verbal recognition memory. CIND individuals were less impaired than AD individuals. Omega-3 intake and the percentage of EPA and DHA in plasma phosphatidylcholine (PC) showed a similar pattern (AD < HV, with intermediate scores for CIND). Across the whole sa...

Maternal plasma phosphatidylcholine fatty acids and atopy and wheeze in the offspring at age of 6 years.

Abstract: Variation in exposure to polyunsaturated fatty acids (PUFAs) might influence the development of atopy, asthma, and wheeze. This study aimed to determine whether differences in PUFA concentrations in maternal plasma phosphatidylcholine are associated with the risk of childhood wheeze or atopy. For 865 term-born children, we measured phosphatidylcholine fatty acid composition in maternal plasma collected at 34 weeks' gestation. Wheezing was classified using questionnaires at 6, 12, 24, and 36 months and 6 years. At age of 6 years, the children underwent skin prick testing, fractional exhaled nitric oxide (FENO) measurement, and spirometry. Maternal n-6 fatty acids and the ratio of n-3 to n-6 fatty acids were not associated with childhood wheeze. However, higher maternal eicosapentaenoic acid, docosahexaenoic acid, and total n-3 fatty acids were associated with reduced risk of non-atopic persistent/late wheeze (RR 0.57, 0.67 and 0.69, resp. P = 0.01, 0.015, and 0.021, resp.). Maternal arachidonic acid was positively associated with FENO (P = 0.024). A higher ratio of linoleic acid to its unsaturated metabolic products was associated with reduced risk of skin sensitisation (RR 0.82, P = 0.013). These associations provide some support for the hypothesis that variation in exposure to n-6 and n-3 fatty acids during pregnancy influences the risk of childhood wheeze and atopy.

Nutrition issues in Codex: health claims, nutrient reference values and WTO agreements: a conference report

Abstract: Background Codex documents may be used as educational and consensus materials for member governments. Also, the WTO SPS Agreement recognizes Codex as the presumptive international authority on food issues. Nutrient bioavailability is a critical factor in determining the ability of nutrients to provide beneficial effects. Bioavailability also influences the quantitative dietary requirements that are the basis of nutrient intake recommendations and NRVs.

Short-term infusion of a fish oil-based lipid emulsion modulates fatty acid status, but not immune function or (anti)oxidant balance: a randomized cross-over study.

Abstract: Background and aims: Studies suggest clinical benefits of parenteral fish oil (FO), rich in n-3 polyunsaturated fatty acids (PUFAs), over soyabean oil (SO), rich in n-6 PUFAs, in patients with pro-inflammatory conditions such as sepsis and trauma. Because the mechanisms behind these observations remain unclear, the present study explored the effects of intravenous infusion of FO and SO on fatty acid incorporation, immune functions and (anti)oxidant balance in healthy human volunteers. Methods: Saline, a SO emulsion and a FO emulsion were administered for one hour on three consecutive days at a rate of 0·2 g/kg BW/h to eight subjects in a randomized cross-over design with a 3-week interval between treatments. Plasma phospholipid and peripheral blood mononuclear cell (PBMC) fatty acid compositions, and leucocyte counts and functions were assessed prior to the first infusion (T = 0, baseline) and 1 day (T = 4, early effects) and 8 days (T = 11, late effects) after the third infusion. Results: Fish oil infusion significantly increased n-3 PUFA proportions and decreased n-6 PUFA proportions in plasma phospholipids and PBMCs. There were no differences in immune functions or (anti)oxidant balance between treatments at any time. Conclusions:?The present lipid infusion protocol appears to be safe and well tolerated and provides significant incorporation of n-3 PUFAs into plasma phospholipids and PBMCs. In the absence of overt inflammation, no direct effects of FO were observed on immune function or (anti)oxidant balance. This model may be useful to evaluate effects of parenteral lipids in other settings, for example in individuals displaying an inflammatory state.

Plasma Inflammatory and Vascular Homeostasis Biomarkers Increase During Human Pregnancy but Are Not Affected by Oily Fish Intake

Abstract: The Salmon in Pregnancy Study investigated whether the increased consumption of (n-3) long-chain PUFA (LC-PUFA) from farmed Atlantic salmon affects immune function during pregnancy and atopic disease in neonates compared with a habitual diet low in oily fish. In this context, because the ingestion of (n-3) LC-PUFA may lower the concentrations of inflammatory biomarkers, we investigated whether the consumption of oily fish affects the levels of inflammatory cytokines and vascular adhesion factors during pregnancy. Pregnant women (n = 123) were randomly assigned to continue their habitual diet (control group, n = 61), which was low in oily fish, or to consume two 150-g salmon portions/wk (salmon group, n = 62; providing 3.45 g EPA plus DHA) from 20 wk of gestation until delivery. Plasma inflammatory cytokines and vascular adhesion factors were measured in maternal plasma samples. Inflammatory biomarkers, including IL-8, hepatocyte growth factor, and monocyte chemotactic protein, increased over the course of pregnancy (P < 0.001), whereas plasma matrix metalloproteinase 9, IL-6, TNFα, and nerve growth factor concentrations were not affected. Vascular homeostasis biomarkers soluble E-selectin, soluble vascular adhesion molecule-1, soluble intercellular adhesion molecule (sICAM)-1, and total plasminogen activator inhibitor-1 increased as pregnancy progressed (P < 0.001). The plasma sICAM-1 concentration was greater in the control group than in the salmon group at wk 20 (baseline) and 38 (P = 0.007) but there was no group x time interaction, and when baseline concentration was used as a covariate, the groups did not differ (P = 0.69). The remaining biomarkers analyzed were similar in both groups. Therefore, although some inflammatory and vascular homeostasis biomarkers change during pregnancy, they are not affected by the increased intake of farmed salmon.

Documentation of functional and clinical effects of infant nutrition: setting the scene for COMMENT.

Abstract: The Early Nutrition Academy and the Child Health Foundation, in collaboration with the Committee on Nutrition, European Society for Paediatric Gastroenterology, Hepatology and Nutrition, held a workshop in March 2011 to explore guidance on acquiring evidence on the effects of nutritional interventions in infants and young children. The four objectives were to (1) provide guidance on the quality and quantity of evidence needed to justify conclusions on functional and clinical effects of nutrition in infants and young children aged <3 years; (2) agree on a range of outcome measures relevant to nutrition trials in this age group for which agreed criteria are needed; (3) agree on an updated 'core data set' that should generally be recorded in nutrition trials in infants and young children, and (4) provide guidance on the use of surrogate markers in paediatric nutrition research. The participants discussed these objectives and agreed to set up six first working groups under the auspices of the Consensus Group on Outcome Measures Made in Paediatric Enteral Nutrition Clinical Trials (COMMENT). Five groups will aim to identify and define criteria for assessing key outcomes, i.e. growth, acute diarrhoea, atopic dermatitis and cows' milk protein allergy, infections and 'gut comfort'. The sixth group will review and update the 'core data set'. The COMMENT Steering Committee will discuss and decide upon a method for reaching consensus which will be used by all working groups and plan to meet again within 2 years and to report and publish their conclusions.

Different outcomes for omega-3 heart trials: why?

Abstract: DOI:10.1097/MCO.0b013e32834ec9e5 Over the past decade, there has been considerable enthusiasm for using the long-chain omega-3 (n–3) fatty acids (FAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) to lower the risk of coronary heart disease and for secondary prevention of myocardial infarction. This makes sense given the multiple biological pathways that are affected by these n–3 FAs. Impacting these pathways seems to be beneficial in preventing dyslipidemia, lowering blood pressure, improving vascular function, inhibiting inflammatory responses, decreasing platelet aggregation, and diminishing (at least in animal models) pathways associated with LDL uptake in the aorta [1–4]. Furthermore, effects of n–3 FAs on cardiac arrhythmias [5], heart rate variability [6], and inflammation within advanced atherosclerotic plaques [7,8] are expected to benefit secondary prevention. The landmark GISSI-Prevenzione and JELIS (Japan EPA Lipid Intervention Study) studies, both secondary prevention randomized controlled trials with cohort sizes of over 11 000 and 18 000, respectively, showed decreases in cardiovascular morbidities and mortality after an initial cardiac event [9,10]. GISSI-Prevenzione provided approximately 900 mg EPAþDHA per day, whereas JELIS provided 1.8 g EPA per day. Meta-analyses of n–3 FAs and cardiovascular mortality in patients with coronary heart disease demonstrated significant reductions [11–13]. Wang et al. [14] in a review of 46 published articles that met strict criteria in terms of study design and EPA and DHA intakes, provided evidence that increased consumption of n–3 FAs, either through fish or supplements, or both, reduced the rates of all-cause mortality and fatal myocardial infarction through reduced sudden cardiac death, with evidence strongest in secondary prevention trials, but also with some positive effects in primary prevention studies. Of these favorable reviews and meta-analyses, only one [13] included the results from JELIS. In contrast to these reports favoring n–3 FAs with respect to cardiovascular mortality, Hooper et al. [15] concluded in a meta-analysis that there were no benefits of n–3 FAs in terms of cardiovascular events or total mortality. Of interest, this latter analysis by Hooper et al. combined interventions with a-linolenic acid and those with EPA and DHA, included a trial with

Does maternal long chain polyunsaturated fatty acid status in pregnancy influence the bone health of children? The Southampton Women's Survey.

Abstract: In this large, population-based, prospective, mother–offspring cohort study, maternal long chain polyunsaturated fatty acid (LCPUFA) status during pregnancy was found to be positively associated with bone mass in the offspring at age 4 years. The findings suggest that variation in intrauterine exposure to n-3 and n-6 LCPUFAs may have potential consequences for skeletal development. Maternal diet in pregnancy has been linked to childhood bone mass, but the mechanisms and nutrients involved are uncertain. Long-chain polyunsaturated fatty acids (LCPUFAs) have been shown to affect bone metabolism, but the relationship between maternal fatty acid status and bone mass in the offspring remains unknown. We evaluated the association between maternal LCPUFA status in late pregnancy (34 weeks gestation) and bone density in their children at age 4 years within 727 mother–child pairs taking part in the Southampton Women’s Survey. Concentrations of the n-3 LCPUFA component of maternal plasma phosphatidylcholine were positively associated with a number of bone mineral measures at the age of 4 years; these associations persisted after adjustment for maternal body build, walking speed and infant feeding. Relationships were most evident for eicosapentaenoic acid (r = 0.09, p = 0.02 for whole body areal bone mineral density [aBMD] and r = 0.1, p = 0.008 for lumbar spine aBMD) and for docosapentaenoic acid (r = 0.09, p = 0.02 for whole body aBMD and r = 0.12, p = 0.002 for lumbar spine aBMD). These findings suggest that variation in early exposure to n-3 and n-6 LCPUFA may have potential consequences for bone development and that the effects appear to persist into early childhood.

Does consumption of two portions of salmon per week enhance the antioxidant defense system in pregnant women

Abstract: Salmon is a rich source of marine n-3 fatty acids, which may increase oxidative stress and, in turn, could affect the antioxidant defense system in blood plasma and erythrocytes of pregnant women. The Salmon in Pregnancy Study provided two meals of salmon per week to pregnant women from week 20 of gestation; the control group maintained their habitual diet low in oily fish. Higher selenium and retinol plasma concentrations were observed after dietary salmon supplementation. Besides, a concomitant increase in selenium and glutathione concentration as well as glutathione peroxidase and reductase activities were detected as pregnancy progressed. However, tocopherols, retinol, β-carotene, and coenzyme Q(10) decreased in late pregnancy. Collectively, our findings lead to the hypothesis that increased farmed salmon intake may increase antioxidant defenses during pregnancy. Clinical trials identifier NCT00801502.

Conclusions and Recommendations from the Symposium, Heart Healthy Omega-3s for Food: Stearidonic Acid (SDA) as a Sustainable Choice

Abstract: Faculty who had presented at the symposium "Heart Healthy Omega-3s (n-3 fatty acids) for Food: Stearidonic Acid (SDA) as a Sustainable Choice" met and agreed upon conclusions and recommendations that could be made on the basis of evidence provided at the symposium. The participants also submitted manuscripts relating to their topics and these are presented in this supplement. These manuscripts were reviewed and also contributed to the conclusions and recommendations presented herein. The three major objectives of the symposium were to: 1) increase understanding of the current and emerging knowledge regarding the health benefits of (n-3) fatty acids (FA) including a focus on stearidonic acid (SDA) and EPA; 2) evaluate the importance of increasing (n-3) FA consumption in the US and the current challenge of doing so via mainstream foods; and 3) consider the health and food application benefits of SDA as a precursor to EPA and a plant-based sustainable source of highly unsaturated (n-3) FA for mainstream foods. Specific areas for future research were defined and included in the summary and conclusions herein. Overall evidence-based conclusions included: the current evidence provides a strong rationale for increasing (n-3) FA intakes in the US and other populations; current consumption of (n-3) FA in most populations is either insufficient or not efficient at providing adequate tissue levels of the long-chain (n-3) FA EPA and DHA; SDA in soybean oil appears to be a cost-effective and sustainable plant-based source that could contribute to reaching recommended levels of (n-3) FA intake, but more research and surveillance is needed; and adding SDA-enriched soybean oil to foods should be considered as a natural fortification approach to improving (n-3) FA status in the US and other populations. References for these conclusions and recommendations can be found in the articles included in the supplement.

The Nutrition Society fully engages with the Open Access model of publishing: Journal of Nutritional Science.

Abstract: In the context of scientific publishing, Open Access is the model through which an article is made freely available to all, the costs typically being offset by a one-off payment from the author's funding body or institution. Open Access in one form or another is increasingly required by funders of research. The Nutrition Society wishes to make more papers available to readers through Open Access, which is available in its flagship journal the British Journal of Nutrition (BJN). However, only a minority of articles published in the BJN are Open Access. Therefore, in collaboration with the publishers of the BJN, Cambridge University Press, the Society has launched a new journal, Journal of Nutritional Science (JNS) (http://www.nutritionsociety.org/journal-nutritional-science). JNS will be published only online and will be fully Open Access. Under Open Access, upon acceptance of a paper the authors pay a one-off processing fee. This fee, which can often be covered by a funding body or host institution, covers the cost of reviewing, producing, hosting and archiving the article (in the existing publishing model, these costs are covered by the subscribers). Immediately upon publication, articles in JNS will be made freely accessible online in perpetuity and will automatically be deposited in PubMed Central on the authors' behalf, ensuring visibility and citability throughout the community. JNS shares its scope with BJN and the two journals will be closely linked, initially sharing Editorial Boards. Articles published in JNS will have been fully peer-reviewed. JNS will publish high-quality research articles across the full spectrum of nutritional science including public health nutrition, nutritional epidemiology, dietary surveys, nutritional requirements, metabolic studies, body composition, energetics, appetite, obesity, and nutritional aspects of ageing, endocrinology, immunology, neuroscience, microbiology, genetics and molecular and cell biology. The underlying aim of all work should be, as far as possible, to develop nutritional concepts. Articles may be submitted to JNS at http://jnutsci.msubmit.net/cgi-bin/main.plex. The launch of JNS represents an exciting development for the Nutrition Society, authors and researchers in nutritional science. I am certain that JNS will be welcomed by all and I wish it success. Some of the content of this editorial is shared with the editorial ‘BJN gets a new sister!’ published in the British Journal of Nutrition(, 1 ).