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Showing papers by "Philip C. Calder published in 2014"


Journal ArticleDOI
TL;DR: An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics and the appropriate use and scope of the term probiotic.
Abstract: An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic--"live microorganisms which when administered in adequate amounts confer a health benefit on the host"--was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.

5,114 citations



Journal ArticleDOI
TL;DR: Strong evidence indicates n-3 PUFAs are beneficial as a dietary supplement in certain diseases such as rheumatoid arthritis; however for other conditions such as asthma, the data are less robust.

327 citations


Journal ArticleDOI
TL;DR: Substantial decreases in liver fat percentage can be achieved with high‐percentage erythrocyte DHA enrichment in NAFLD with evidence of contamination in the placebo group and variable adherence to the Intervention group.

267 citations


Journal ArticleDOI
TL;DR: Very long chain omega-3 (n-3) fatty acids play important roles in growth, development, optimal function, and maintenance of health and well-being right across the life course, meaning that all sectors of the population need to ensure sufficient intake of these important nutrients.
Abstract: Omega-3 (n-3) fatty acids are a family of polyunsaturated fatty acids that contribute to human health and well-being. Functionally the most important n-3 fatty acids appear to be eicosapentaenoic acid (EPA) and docosahexaenoioc acid (DHA), but roles for n-3 docosapentaenoic acid (DPA) are now emerging. Intakes of EPA and DHA are usually low, typically below recommended intakes. Increased intakes are reflected in greater incorporation into blood lipid, cell and tissue pools. Increased content of EPA and DHA modifies the structure of cell membranes and the function of membrane proteins involved as receptors, signaling proteins, transporters, and enzymes. EPA and DHA modify the production of lipid mediators and through effects on cell signaling can alter patterns of gene expression. Through these actions EPA and DHA alter cell and tissue responsiveness in a manner that seems to result in more optimal conditions for growth, development, and maintenance of health. The effects of n-3 fatty acids are evident right through the life course, meaning that there is a need for all sectors of the population to have a sufficient intake of these important nutrients. EPA and DHA have a wide range of physiological roles which are linked to certain health or clinical benefits. Practical application: Very long chain omega-3 (n-3) fatty acids are found in seafood, especially fatty fish, and in supplements. They exert a range of health benefits as a result of their molecular, cellular and physiological actions. Consequently, very long chain n-3 fatty acids play important roles in growth, development, optimal function, and maintenance of health and well-being right across the life course. Therefore, all sectors of the population need to ensure sufficient intake of these important nutrients. This can be achieved through eating fatty fish or, failing that, use of good quality supplements.

209 citations


Journal ArticleDOI
17 Oct 2014-PLOS ONE
TL;DR: Findings show that modest fatty acid supplementation can induce altered methylation of specific CpG loci in adult humans, contingent on the nature of the supplement and on sex.
Abstract: BACKGROUND: Studies in animal models and in cultured cells have shown that fatty acids can induce alterations in the DNA methylation of specific genes. There have been no studies of the effects of fatty acid supplementation on the epigenetic regulation of genes in adult humans. METHODS AND RESULTS: We investigated the effect of supplementing renal patients with 4 g daily of either n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) or olive oil (OO) for 8 weeks on the methylation status of individual CpG loci in the 5' regulatory region of genes involved in PUFA biosynthesis in peripheral blood mononuclear cells from men and women (aged 53 to 63 years). OO and n-3 LCPUFA each altered (>10% difference in methylation) 2/22 fatty acid desaturase (FADS)-2 CpGs, while n-3 LCPUFA, but not OO, altered (>10%) 1/12 ELOVL5 CpGs in men. OO altered (>6%) 8/22 FADS2 CpGs and (>3%) 3/12 elongase (ELOVL)-5 CpGs, while n-3 LCPUFA altered (>5%) 3/22 FADS2 CpGs and 2/12 (>3%) ELOVL5 CpGs in women. FADS1 or ELOVL2 methylation was unchanged. The n-3 PUFA supplementation findings were replicated in blood DNA from healthy adults (aged 23 to 30 years). The methylation status of the altered CpGs in FADS2 and ELOVL5 was associated negatively with the level of their transcripts. CONCLUSIONS: These findings show that modest fatty acid supplementation can induce altered methylation of specific CpG loci in adult humans, contingent on the nature of the supplement and on sex. This has implications for understanding the effect of fatty acids on PUFA metabolism and cell function.

93 citations


Journal ArticleDOI
TL;DR: Small differences in incorporation with age and sex were identified, but these were not of sufficient magnitude to warrant a move away from population-level diet recommendations for n-3 PUFA.
Abstract: The aim of the present study was to determine whether age and sex influence both the status and incorporation of EPA and DHA into blood plasma, cells and tissues The study was a double-blind, randomised, controlled intervention trial, providing EPA plus DHA equivalent to 0, 1, 2 or 4 portions of oily fish per week for 12 months The participants were stratified by age and sex A linear regression model was used to analyse baseline outcomes, with covariates for age or sex groups and by adjusting for BMI The change in outcomes from baseline to 12 months was analysed with additional adjustment for treatment and average compliance Fatty acid profiles in plasma phosphatidylcholine, cholesteryl esters, NEFA and TAG, mononuclear cells (MNC), erythrocyte membranes, platelets, buccal cells (BU) and adipose tissue (AT) were determined At baseline, EPA concentrations in plasma NEFA and DHA concentrations in MNC, BU and AT were higher in females than in males (all P< 0·05) The concentrations of EPA in AT (P= 0·003) and those of DHA in plasma TAG (P< 0·01) and AT (P< 0·001) were higher with increasing age Following 12-month supplementation with EPA plus DHA, adjusted mean difference for change in EPA concentrations in plasma TAG was significantly higher in females than in males (P< 0·05) and was greater with increasing age (P= 0·02) Adjusted mean difference for change in DHA concentrations in AT was significantly smaller with increasing age (P= 0·02) Although small differences in incorporation with age and sex were identified, these were not of sufficient magnitude to warrant a move away from population-level diet recommendations for n-3 PUFA

73 citations


Journal ArticleDOI
TL;DR: There are significant diet/pregnancy interaction effects upon the omega-3 and omega-6 fatty acid content of liver CE, indicating that pregnant females have a different response to dietary manipulation than is seen among virgin females.
Abstract: Gas chromatography (GC) is a highly sensitive method used to identify and quantify the fatty acid content of lipids from tissues, cells, and plasma/serum, yielding results with high accuracy and high reproducibility. In metabolic and nutrition studies GC allows assessment of changes in fatty acid concentrations following interventions or during changes in physiological state such as pregnancy. Solid phase extraction (SPE) using aminopropyl silica cartridges allows separation of the major lipid classes including triacylglycerols, different phospholipids, and cholesteryl esters (CE). GC combined with SPE was used to analyze the changes in fatty acid composition of the CE fraction in the livers of virgin and pregnant rats that had been fed various high and low fat diets. There are significant diet/pregnancy interaction effects upon the omega-3 and omega-6 fatty acid content of liver CE, indicating that pregnant females have a different response to dietary manipulation than is seen among virgin females.

57 citations


Journal ArticleDOI
TL;DR: The impact of oily fish consumption during pregnancy on maternal and infant gut microbiota composition is limited, but significant differences are associated with maternal weight gain during pregnancy and mode of infant feeding.
Abstract: The gut microbiota plays an important role in the development of the immune and gastrointestinal systems of infants. In the present study, we investigated whether increased salmon consumption during pregnancy, maternal weight gain during pregnancy or mode of infant feeding alter the markers of gut immune defence and inflammation. Women (n 123) who rarely ate oily fish were randomly assigned to continue consuming their habitual diet or to consume two 150 g portions of farmed salmon per week from 20 weeks of pregnancy to delivery. Faecal samples were collected from the mothers (n 75) at 38 weeks of gestation and from their infants (n 38) on days 7, 14, 28 and 84 post-partum. Fluorescence in situ hybridisation was used to determine faecal microbiota composition and ELISA to measure faecal secretory IgA (sIgA) and calprotectin concentrations. There was no effect of salmon consumption on maternal faecal microbiota or on maternal or infant faecal sIgA and calprotectin concentrations. The degree of weight gain influenced maternal faecal microbiota, and the mode of infant feeding influenced infant faecal microbiota. Faecal samples collected from infants in the salmon group tended to have lower bacterial counts of the Atopobium cluster compared with those collected from infants in the control group (P=0·097). This difference was significant in the formula-fed infants (P< 0·05), but not in the exclusively breast-fed infants. In conclusion, the impact of oily fish consumption during pregnancy on maternal and infant gut microbiota composition is limited, but significant differences are associated with maternal weight gain during pregnancy and mode of infant feeding.

53 citations


Journal ArticleDOI
TL;DR: Higher AA, AA:EPA ratio, DPA and DHA and lower LA, α-LNA and EPA are seen in inflamed mucosa in UC and correlate with severity of inflammation, which suggests an alteration in fatty acid metabolism in the inflamed gut mucosa, which may offer novel targets for intervention and should be considered if nutritional strategies are used.

51 citations


Journal ArticleDOI
TL;DR: Subjects who decrease their plasma TG levels following n-3 PUFA supplementation may have a different genetic profile than individuals who do not respond, and the genetic risk score (GRS) was constructed by summing the number of risk alleles.

Journal ArticleDOI
TL;DR: The WELCOME study is testing the hypothesis that treatment with high dose purified long chain omega-3 fatty acids will have a beneficial effect on a) liver fat percentage and b) two histologically validated algorithmically-derived biomarker scores for liver fibrosis.

Journal ArticleDOI
TL;DR: Whether fish oil is a useful therapy in children with asthma receiving standard therapy is not clear from studies performed to date and this requires further exploration.
Abstract: There may be a causal relationship between intake of n-6 polyunsaturated fatty acids (PUFAs) and childhood allergic diseases. This can be explained by plausible biological mechanisms involving eicosanoid mediators produced from the n-6 PUFA arachidonic acid. Long chain n-3 PUFAs are found in fish and fish oils. These fatty acids act to oppose the actions of n-6 PUFAs. Thus, it is considered that n-3 PUFAs will lower the risk of developing allergic diseases. In support of this, protective associations have been reported between maternal fish intake during pregnancy and allergic outcomes in infants and children from those pregnancies. However, studies of fish intake during infancy and childhood and allergic outcomes in those infants or children are inconsistent, although some reported a protective association. Supplementing pregnant women with fish oil can induce immunologic changes in cord blood. This supplementation has been reported in some studies to decrease sensitisation to common food allergens and to lower the prevalence and severity of atopic dermatitis in the first year of life. The protective effect of maternal n-3 PUFAs may last until adolescence of the offspring. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, although this benefit may not persist. Whether fish oil is a useful therapy in children with asthma receiving standard therapy is not clear from studies performed to date and this requires further exploration.

Journal ArticleDOI
TL;DR: Omega-3 fatty acids (n-3 FA) exerts anti-inflammatory effects in surgical patients, without reducing the risk of postoperative complications, in conclusion.
Abstract: Omega-3 fatty acids (n-3 FA) may have beneficial clinical and immune-modulating effects in surgical patients. In a randomized, double-blind, prospective, placebo-controlled trial, 148 patients referred for elective colorectal cancer surgery received an n-3 FA-enriched oral nutritional supplement (ONS) providing 2.0 g of eicosapentaenoic acid (EPA) and 1.0 g of docosahexaenoic acid (DHA) per day or a standard ONS for seven days before surgery. On the day of operation, there was a significant increase in the production of leukotriene B5 (LTB5) (p < 0.01) and 5-hydroxyeicosapentaenoic acid (5-HEPE) (p < 0.01), a significant decrease in the production of leukotriene B4 (LTB4) (p < 0.01) and a trend for a decrease in the production of 5-hydroxyeicosatetraenoic acid (5-HETE) (p < 0.1) from stimulated neutrophils in the active group compared with controls. There was no association between LTB4 values and postoperative complications. In conclusion, oral n-3 FA exerts anti-inflammatory effects in surgical patients, without reducing the risk of postoperative complications.

Journal ArticleDOI
TL;DR: Women show a greater increase in circulating EPA than men during increased dietary ALA consumption, which could inform nutrition advice, with recommendations being specifically tailored according to habitual diet, sex, age and BMI.
Abstract: Background There is a metabolic pathway by which mammals can convert the omega-3 (n-3) essential fatty acid α-linolenic acid (ALA) into longer-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). As far as we know there are currently no studies that have specifically examined sex differences in the LC n-3 PUFA response to increased dietary ALA intake in humans, although acute studies with isotope-labelled ALA identified that women have a significantly greater capacity to synthesise EPA and DHA from ALA compared to men.

Journal ArticleDOI
TL;DR: The pattern of consumption does affect the incorporation of EPA and DHA into cells used as biomarkers of intake, and the differences identified here need to be considered in the design of studies and when extrapolating results from continuous capsule-based intervention studies to dietary guidelines for oily fish consumption.
Abstract: Consumption of oily fish is sporadic, whereas controlled intervention studies of n-3 (ω-3) fatty acids usually provide capsules containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as a daily dose. This methodologic study explored whether there are differences in the short-, medium-, and long-term incorporation of EPA and DHA into blood plasma and cells with the provision of identical amounts of EPA and DHA, equivalent to 2 oily fish servings per week (or 6.54 g/wk EPA and DHA), either intermittently (i.e., 1 portion twice per week) or continuously (i.e., divided into daily amounts). The study was part of a randomized, double-blind controlled intervention lasting 12 mo, with participants stratified by age and sex. There were 5 intervention groups, 2 of which are reported here: the 2 intermittent portions (2I) and 2 continuous portions (2C) groups. EPA and DHA were measured in plasma phosphatidylcholine, platelets, and blood mononuclear cells (MNCs) at 9 time points. Sixty-five participants completed the study (2I group, n = 30, mean age of 49.2 y; 2C group, n = 35, mean age of 50.6 y). The incorporation pattern over the 12-mo intervention was different between the 2 groups in all samples (P < 0.0001, time × treatment interaction). At the end of the 12-mo intervention, the 2C group had higher EPA, DHA, and EPA + DHA in platelets (all P < 0.01) and higher EPA and EPA + DHA in MNCs (both P < 0.05) compared with the 2I group. No significant differences were shown for plasma phosphatidylcholine EPA (P = 0.1), DHA (P = 0.15), EPA + DHA (P = 0.07), or MNC DHA (P = 0.06). In conclusion, the pattern of consumption does affect the incorporation of EPA and DHA into cells used as biomarkers of intake. The differences identified here need to be considered in the design of studies and when extrapolating results from continuous capsule-based intervention studies to dietary guidelines for oily fish consumption. This trial was registered at www.controlled-trials.com as ISRCTN48398526.

Journal ArticleDOI
TL;DR: EPA is incorporated rapidly into colonic mucosa and colonic muscular layer in patients given 3 g of ω-3 FA daily for 7 days before surgery for colorectal cancer.
Abstract: Background: The purpose of the study was to examine whether a preoperative supplement with ω-3 fatty acids (FAs) leads to their incorporation into colonic tissue in patients scheduled for colorectal cancer surgery. This would be of interest because ω-3 FAs have potential beneficial (local) immunological effects that might benefit these patients. Methods: In a randomized, double-blind, prospective, placebo-controlled, single-center intervention trial, patients referred for elective colorectal cancer surgery received either an ω-3 FA–enriched oral nutrition supplement (ONS) (200 mL twice daily) providing 2.0 g of eicosapentaenoic acid (EPA) and 1.0 g of docosahexaenoic acid (DHA) per day or a standard ONS for 7 days before surgery. Tissue samples from healthy colonic tissue (mucosa and muscular layer) were obtained during surgery, and tissue fatty acid composition was analyzed by gas chromatography. Results: EPA was significantly higher in colonic mucosa (P = .001) and in the colonic muscular layer (P = .00...

Journal ArticleDOI
TL;DR: A randomised controlled trial of a dietary intervention consisting of olive oil for cooking, an olive oil based spread, and a daily supplement drink enriched with Vitamin D and marine omega-3 fatty acids on early embryo development and the influence of the peri-implantation intra-uterine nutritional environment.
Abstract: In vitro fertilisation (IVF) treatment provides an opportunity to study early developmental responses to periconceptional dietary interventions. Retrospective studies have suggested links between preconception diet and fertility, and more recently, a "Mediterranean" diet has been reported to increase pregnancy rates by up to 40%. In addition, a prospective study examining increased intake of omega-3 polyunsaturated fats demonstrated a quickened rate of embryo development after IVF. However, up to now, few prospective randomised controlled trials have investigated the impact of periconceptional dietary interventions on fertility outcomes. The study is a randomised controlled trial of a dietary intervention consisting of olive oil for cooking, an olive oil based spread, and a daily supplement drink enriched with Vitamin D (10 microgram daily) and marine omega-3 fatty acids (2 g daily) for 6 weeks preconception versus a control diet of sunflower seed oil for cooking, a sunflower oil based spread, and a daily supplement drink without added Vitamin D or marine omega-3 fatty acids. Couples undergoing IVF will be randomised to either the intervention or control group (55 in each arm). The primary endpoint is embryo developmental competency in vitro, measured by validated morphokinetic markers. Secondary outcomes will include the effect of the dietary intervention on the nutritional content of the intrauterine environment. This approach will enable rigorous examination of the impact of the dietary intervention on early embryo development, together with the influence of the peri-implantation intra-uterine nutritional environment. ISRCTN50956936

Journal ArticleDOI
TL;DR: Investigation of the effect of environmental oxygen tension on the amino acid metabolism of human embryonic stem cells suggests that amino acid turnover could be used as a measure of the self-renewal capacity of hESCs.
Abstract: Background/Aims: Human embryonic stem cells (hESCs) are a potential source of cells for treatment of many degenerative diseases, but in culture have a propensity to spontaneously differentiate, possibly due to suboptimal conditions. Culture at low oxygen tensions improves hESC maintenance and regulates carbohydrate metabolism. Hence, a greater understanding of the nutrient requirements of hESCs will allow production of more appropriate culture media. This study aims to investigate the effect of environmental oxygen tension on the amino acid metabolism of hESCs. Methods: The production or depletion of amino acids by hESCs cultured at 5% or 20% oxygen in the presence or absence of FGF2 was measured by reversephase HPLC. Results: Atmospheric oxygen, or removal of FGF2 from hESCs cultured at 5% oxygen, perturbed the uptake or release of individual amino acids and the total amino acid turnover compared to hESCs cultured at 5% oxygen. In particular, serine uptake was reduced at 20% oxygen and by removal of FGF2. Conclusions: Highly pluripotent hESCs, cultured at 5% oxygen, demonstrate a greater amino acid turnover than hESCs cultured at 20% oxygen, or without FGF2. These data suggest that amino acid turnover could be used as a measure of the self-renewal capacity of hESCs.

Journal ArticleDOI
TL;DR: Short-term IV FLE modulates some inflammatory markers in critically ill elderly patients receiving enteral nutrition (EN), suggesting an anti-inflammatory effect and suggests a role for FLE administration as a supplement in elderly ICU patients receiving standard EN.
Abstract: Background: enteral supply of ?-3 polyunsaturated fatty acids has been used in an attempt to modulate inflammation and improve outcome in critically ill patients. However, enteral administration may be slow to change membrane composition and therefore may not be the best route to supply these fatty acids in patients with acute conditions. This study evaluated the effects of short-term intravenous (IV) administration of fish oil–based lipid emulsion (FLE) as pharmaconutrition on cytokine levels in critically ill elderly patients. Methods: enterally fed patients (n = 40; aged 60–80 years) were recruited in the first 48 hours of intensive care unit (ICU) admission. Fifteen patients received IV FLE (0.2 g/kg body weight) over 6 hours for 3 consecutive days, and 25 patients did not receive IV lipid (control). Samples were collected before and 24 hours and 72 hours after the third FLE infusion. Nutrient intakes, clinical parameters, and serum cytokine concentrations were measured. Results: compared with the control, FLE resulted in higher energy intake, lower serum tumor necrosis factor–? and interleukin (IL)–8 concentrations, and higher serum IL-10. These differences occurred around 7–9 days of ICU stay at the time of the patient’s extubation. ICU stay, mortality, and markers of coagulation and liver function did not differ between groups. Conclusions: short-term IV FLE modulates some inflammatory markers in critically ill elderly patients receiving enteral nutrition (EN), suggesting an anti-inflammatory effect. This may be a benefit and suggests a role for FLE administration as a supplement in elderly ICU patients receiving standard EN

Journal ArticleDOI
25 May 2014-Lipids
TL;DR: A dual effect of fish oil on oxidative stress and inflammation in asthma is suggested, since the supplement lowered oxidative stress in the lungs of asthmatic rats, presenting an antioxidant effect, but did not affect PAF bioactivity.
Abstract: Dietary fish oil supplementation increases the content of n-3 polyunsaturated fatty acids (PUFA) in cellular membranes. The highly unsaturated nature of n-3 PUFA could result in an enhanced lipid peroxidation in the oxidative environment characteristic of asthma. The oxidative reaction cascade culminates in an increased production of components associated to oxidative stress and of an important proinflammatory mediator platelet-activating factor (PAF)-like lipid. We evaluated the effect of fish oil supplementation in asthmatic rats upon the PAF bioactivity and parameters related to oxidative stress in the lung. Fish oil supplementation of asthmatic rats resulted in lower concentrations of nitrite (1.719 ± 0.137 vs. 2.454 ± 0.163 nmol/mL) and lipid hydroperoxide (72.190 ± 7.327 vs. 120.200 ± 11.270 nmol/mg protein). In asthmatic animals, fish oil increased the activities of superoxide dismutase (EC 1.15.1.1) (33.910 ± 2.325 vs. 24.110 ± 0.618 U/mg protein) and glutathione peroxidase (EC 1.11.1.9) (164.100 ± 31.250 vs. 12.590 ± 5.234 U/mg protein). However, fish oil did not affect PAF bioactivity in lung tissue of asthmatic rats (0.545 ± 0.098 340/380 vs. 0.669 ± 0.101 340/380 nm ratio). Considering the two-step process—oxidative stress and PAF bioactivity—fish oil exhibited a divergent action on these aspects of asthmatic inflammation, since the supplement lowered oxidative stress in the lungs of asthmatic rats, presenting an antioxidant effect, but did not affect PAF bioactivity. This suggests a dual effect of fish oil on oxidative stress and inflammation in asthma.

Journal ArticleDOI
TL;DR: Two portions/wk of oily fish increased plasma essential AA concentrations during pregnancy and could contribute to a maternal health benefit and did not affect plasma AA concentrations in the newborn.

Journal ArticleDOI
TL;DR: The dietary strategy achieved the aims of inducing insulin resistance and dyslipidemia, especially hypertriglyceridemia in marine n–3 PUFAs in rhesus monkeys fed a high-carbohydrate, high-fructose diet.
Abstract: Rates of obesity, insulin resistance, and metabolic syndrome are increasing in many countries. Diet is an obvious factor that can contribute to the risk of these metabolic conditions, which, in turn, predispose one to type 2 diabetes and cardiovascular disease, major sources of morbidity, mortality, and health expenditure. The key dietary components involved in increasing metabolic risk are subject to much conjecture, but there is a view that increased intake of fructose as dietary sucrose and from high-fructose syrups is a major culprit (1). Recent work in rhesus monkeys demonstrated that a high-carbohydrate, high-fructose diet induced several features of human metabolic syndrome, including obesity, hypertriglyceridemia, and insulin resistance (2). In this issue of The Journal of Nutrition, an article reports on the effects of marine n–3 (v-3) PUFAs in rhesus monkeys fed a high-carbohydrate, high-fructose diet (3). Marine n–3 PUFAs were shown to prevent the hypertriglyceridemia and insulin resistance induced by the high-carbohydrate, high-fructose diet. The animals were adult males aged 12 to 20 y and weighed an average of 15.6 kg at study entry. They were fed a grain-based primate diet providing 11% of energy as fat (>90% as n–6 FAs), 30% of energy as protein, and 59% of energy as carbohydrate, and additionally received 75 g of fructose daily in a 500-mL beverage. The intention of this dietary strategy was to induce metabolic syndrome, in particular obesity, insulin resistance, and dyslipidemia, as previously demonstrated (2). Half of the animals received a treat that included 4 g of fish oil (FO), whereas the treat given to the remaining animals, the control group, contained 4 g of safflower oil, which is rich in the n–6 essential FA linoleic acid. The treats used, which weighed 44 g, also provided unspecified amounts of fat and carbohydrate. The FO provided ;0.64 g EPA and 0.44 g DHA daily. The feeding period was 6 mo. The intention of supplementing the FO was to prevent the development of metabolic syndrome. Over the 6-mo feeding period, the control group demonstrated increases in body weight (13%), total insulin AUC during a 60-min intravenous-glucose-tolerance test (89%), and concentrations of fasting plasma TGs (64%), apoC3 (25%), apoE (29%), fasting insulin (104%), and leptin (30%), and a decrease in concentrations of adiponectin (221%). Thus, the dietary strategy achieved the aims of inducing insulin resistance and dyslipidemia, especially hypertriglyceridemia. Data on body composition are not presented, but the increase in leptin concentration might suggest increased fat mass in the control group. What, then, was the effect of supplementation with FO? The animals that received marine n–3 PUFAs showed an average 9% increase in body weight, less than in the control group, although the increase in body weight was not significantly different between the 2 groups of animals. However, this lack of significant difference between weight gains of 13% and 9% may be due to the small number of animals in each group (9 in the control group and 10 in the FO group) rather than a lack of effect. Also, the difference in weight gain may have becomemore pronounced with a longer duration of feeding. In the FO-supplemented animals, plasma TGs declined by 8.5%, and this change (i.e., the effect of treatment) was different from that in the control group. Likewise, apoC3 decreased in the FO group, and the change from study entry was different from that seen in the control group, whereas the increase in apoE in the FO group was less than that in the control group. Thus, including marine n–3 PUFAs in a high-carbohydrate, high-fructose diet prevented the hypertriglyceridemic effect of that diet. Plasma insulin concentration and the total insulin AUC during a 60-min intravenous-glucose-tolerance test were not significantly altered in the FO group, indicating that FO prevented the diet-induced decline in insulin sensitivity seen in the control group. Plasma leptin was not significantly increased from study entry in the FO group, although there was a small elevation of ;6.5%. Comparison of data for change in leptin concentration from study entry showed that this was significantly less in the FO group than that in the control group, suggesting that FO reduces the development of adiposity induced by the high-carbohydrate, high-fructose diet. Curiously, FO did not affect the diet-induced decrease in plasma adiponectin. This study provides sound evidence to support that marine n–3 PUFAs have effects that can prevent the deleterious metabolic consequences of a diet high in carbohydrates, including a substantial amount of fructose. That these effects were observed in nonhuman primates is a significant advance, because much of the existing data of this type come from studies in rodents and rabbits; many of these small animals have significant differences in diet, metabolic rate, and lipid metabolism compared with humans, limiting the ability to translate the findings. Nevertheless, the diet of the rhesus monkeys studied here was rather different from a typical human diet. Dietary protein was higher than in most human diets, whereas fat, at 11% of energy, was lower than in most Western diets. It would be interesting to study the effect of n–3 FAs in this sort of high-carbohydrate, 1 Author disclosures: P. C. Calder serves on the Danone Scientific Advisory Board on Immunity and Allergy, on the Clinical Advisory Board of Pronova BioPharma, and on the scientific advisory boards of Aker Biomarine and of Smartfish; he acts as a consultant to the Danone Research Centre for Specialised Nutrition, Vifor Pharma, Pfizer, Enzymotec, and Amarin Corporation, and has received speaking honoraria from Fresenius Kabi, B. Braun, Abbott Nutrition, Baxter Healthcare, Nestlé, Unilever, and DSM. * To whom correspondence should be addressed. E-mail: pcc@soton.ac.uk.

Journal ArticleDOI
TL;DR: The background to several expert groups' work, findings and recommendations on the assessment and interpretation of immune markers, and one focussed on chronic low-grade inflammation in relation to overweight and obesity are described.
Abstract: In order to gain better insight into meaningful effects of nutrition on immune function, there is a need for guidance on the assessment and interpretation of immune markers. However, there is no consensus as to which markers best represent the various aspects of immunity, including acute, chronic or low-grade inflammation. International Life Sciences Institute European Branch has commissioned several expert groups comprising individuals from different backgrounds including academia, government and the food industry to prepare descriptive and guidance documents on this topic. Two of these considered the markers of the immune response mainly in the context of host defence against pathogens, two considered general markers of inflammation, and one focussed on chronic low-grade inflammation in relation to overweight and obesity. This article describes the background to these documents and will summarise the work, findings and recommendations of the expert groups.

Journal ArticleDOI
TL;DR: This paper presents the results of a two-year research project aimed at determining the phytochemical properties of fruit juice and its role in human development and health.
Abstract: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK; Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology ‘‘José Mataix,’’ Biomedical Research Center, University of Granada, Granada, Spain; National Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton National Health Service Foundation Trust and University of Southampton, Southampton, UK; and Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia

Book
01 Nov 2014
TL;DR: In this article, the authors bring together articles written by leading international authorities in the area of intravenous lipids and discuss the latest findings in the field, ranging from pre-clinical research to the most recent clinical trials.
Abstract: Lipids have been in clinical use as components of intravenous nutrition for over 50 years. Over the last 15 years, new and improved lipids that include olive oil and/or fish oil have replaced the more traditional ones. These new lipids offer the opportunity to deliver high amounts of fatty acids and possess different functional properties: in particular, they can influence inflammatory processes, immune responses and hepatic metabolism. This book brings together articles written by leading international authorities in the area of intravenous lipids. Contributions discuss the latest findings in the field, ranging from pre-clinical research to the most recent clinical trials. Lipid functionality and utility in pediatric, adult surgical and critically ill patients are covered, as is the use of lipids in long-term home parenteral nutrition. Addressing a broad spectrum of topics, this publication provides a wealth of information for basic scientists, clinical researchers and clinical practitioners alike.

Journal ArticleDOI
TL;DR: Advice to specifically increase n-6 polyunsaturated fatty acid intake is unlikely to provide the intended benefits and may actually increase the risks of coronary heart disease and death.
Abstract: DOI:10.1097/MCO.0000000000000038 Until relatively recently, understandings about dietary fatty acids and human health were fairly straightforward. First, saturated fatty acids raise serum cholesterol concentration and so would be associated with increased cardiovascular risk and have therefore been considered to be unhealthy [1]. Secondly, the n-6 fatty acid linoleic acid lowers serum cholesterol concentration and so would be associated with lower cardiovascular risk, and has therefore been considered to be healthy [1]. Finally, the marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) favourably modify cardiovascular risk factors, lowering cardiovascular morbidity and mortality and have therefore been considered to be healthy [2,3]. These anticipated effects on cardiovascular disease risk are uniformly reflected in dietary recommendations that are in place across the globe. Further support for a key role for marine n-3 fatty acids in human health comes from observations of benefits in inflammatory conditions [4,5], cancer [6,7], and mental health [8,9]. However, in 2010 Ramsden et al. [10] produced a new meta-analysis that questioned the traditionally accepted roles of saturated fatty acids and linoleic acid in determining cardiovascular risk, as discussed elsewhere [11,12]. Ramsden et al. [10] evaluated the findings of studies specifically addressing the impact of increased linoleic acid intake separately from those that included linoleic acid in combination with n-3 fatty acids. They concluded that ‘[current] advice to specifically increase n-6 polyunsaturated fatty acid intake is unlikely to provide the intended benefits and may actually increase the risks of coronary heart disease and death’ [10]. Furthermore, in the same year, three large intervention trials with marine n-3 fatty acids failed to replicate earlier findings of reduced cardiovascular mortality in at-risk patients [13–15]; these trials are discussed elsewhere [16,17]. Over the past 2 years, a series of diverse publications have further rocked the formerly sound foundations on which advice to consume linoleic acid and marine n-3 fatty acids has been built. Early in 2013, Ramsden et al. [18] published new data from an old intervention study, the Sydney



Journal ArticleDOI
TL;DR: Clinical trials in patients following myocardial infarction or with heart failure demonstrated significantly lowered mortality with pharmaceutical grade omega-3 ethyl esters at a dose of approximately 850 mg/day suggesting a therapeutic effect in at-risk patients.
Abstract: Commentary on: Roncaglioni MC, Tombesi M, et al. Risk and Prevention Study Collaborative Group. n-3 fatty acids in patients with multiple cardiovascular risk factors. N Engl J Med 2013;368:1800–8[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Ecological, case–control and prospective studies consistently demonstrate reduced cardiovascular morbidity and mortality associated with higher intake of fish and their constituent omega-3 fatty acids and with higher omega-3 fatty acid status.1 This effect has been ascribed to improvement of the cardiovascular risk profile resulting in disease prevention.1 Trials in patients following myocardial infarction (MI) or with heart failure demonstrated significantly lowered mortality with pharmaceutical grade omega-3 ethyl esters at a dose of approximately 850 mg/day,2 ,3 suggesting a therapeutic effect in at-risk patients. This may be due to a reduction in cardiac arrhythmias, although this effect has not been demonstrated unequivocally, … [1]: {openurl}?query=rft.jtitle%253DN%2BEngl%2BJ%2BMed%26rft.issn%253D0028-4793%26rft.volume%253D368%26rft.spage%253D1800%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa1205409%26rft_id%253Dinfo%253Apmid%252F23656645%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa1205409&link_type=DOI [3]: /lookup/external-ref?access_num=23656645&link_type=MED&atom=%2Febmed%2F19%2F1%2F18.atom [4]: /lookup/external-ref?access_num=000318540000008&link_type=ISI