Publications by authors named "Philip C Calder"

449 Publications

Supplementation with oil rich in eicosapentaenoic acid, but not in docosahexaenoic acid, improves global cognitive function in healthy, young adults: results from randomized controlled trials.

Am J Clin Nutr 2021 Jun 10. Epub 2021 Jun 10.

Brain Performance and Nutrition Research Centre, Northumbria University, Newcastle Upon Tyne, United Kingdom.

Background: Evidence regarding the effects of the omega-3 (ɷ-3) PUFAs (n-3 PUFAs) DHA and EPA on cognition is lacking.

Objectives: We investigated whether supplementation with oils rich in EPA or DHA improves cognition, prefrontal cortex (PFC) hemoglobin (Hb) oxygenation, and memory consolidation.

Methods: Healthy adults (n = 310; age range: 25-49 y) completed a 26-wk randomized controlled trial in which they consumed either 900 mg DHA/d and 270 mg EPA/d (DHA-rich oil), 360 mg DHA/d and 900 mg EPA/d (EPA-rich oil), or 3000 mg/d refined olive oil (placebo). Cognitive performance and memory consolidation were assessed via computerized cognitive test battery. PFC Hb oxygenation was measured using near infrared spectroscopy (NIRS).

Results: Both global accuracy and speed improved with EPA-rich oil compared with placebo and DHA-rich oil [EPA vs. placebo accuracy: estimated marginal mean (EMM) = 0.17 (95% CI: 0.09, 0.24) vs. EMM = 0.03 (95% CI = -0.04, 0.11); P = 0.044; EPA vs. placebo speed: EMM = -0.15 (95% CI: -0.22, -0.07) vs. EMM = 0.03 (95% CI: -0.05, 0.10); P = 0.003]. Accuracy of memory was improved with EPA compared with DHA [EMM = 0.66 (95% CI: 0.26, 1.06) vs. EMM = -0.08 (95% CI: -0.49, 0.33); P = 0.034]. Both EPA- and DHA-rich oils showed trends towards reduced PFC oxygenated Hb (oxy-Hb) compared with placebo [placebo: EMM = 27.36 µM (95% CI: 25.73, 28.98); DHA: EMM = 24.62 µM (95% CI: 22.75, 26.48); P = 0.060; EPA: EMM = 24.97 µM (95% CI: 23.35, 26.59); P = 0.082].

Conclusions: EPA supplementation improved global cognitive function and was superior to the oil enriched with DHA. Interpreted within a neural efficiency framework, reduced PFC oxygenated Hb suggests that n-3 PUFAs may be associated with increased efficiency.These trials were registered in the clinical trials registry (https://clinicaltrials.gov/) as NCT03158545, NCT03592251, NCT02763514.
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http://dx.doi.org/10.1093/ajcn/nqab174DOI Listing
June 2021

Response to Plat and Mensink.

Br J Nutr 2021 May 28:1-5. Epub 2021 May 28.

Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.

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http://dx.doi.org/10.1017/S0007114521001793DOI Listing
May 2021

Bronchiectasis-Could Immunonutrition Have a Role to Play in Future Management?

Front Nutr 2021 29;8:652410. Epub 2021 Apr 29.

School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.

Bronchiectasis is a chronic condition in which areas of the bronchial tubes become permanently widened predisposing the lungs to infection. Bronchiectasis is an age-associated disease with the highest prevalence in people older than 75 years. While the prevalence of bronchiectasis is higher in males, disease is more severe in females who have a poorer prognosis. The overall prevalence of the disease is thought to be rising. Its aetiology is multi-faceted, but a compromised immune system is now thought to play a central role in the pathology of this disease. Research has begun to study the role of malnutrition and certain nutrients-vitamin D and zinc-along with the role of the lung microbiome in relation to the management of bronchiectasis. Given this, the present mini review sets out to provide an overview of the state-of-the-art within the field, identify research gaps and pave the way for future developments and research investment within this field.
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http://dx.doi.org/10.3389/fnut.2021.652410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116598PMC
April 2021

Respiratory Tract Infections and Antibiotic Resistance: A Protective Role for Vitamin D?

Front Nutr 2021 25;8:652469. Epub 2021 Mar 25.

Faculty of Medicine, School of Human Development and Health, University of Southampton, Southampton, United Kingdom.

Upper and lower respiratory tract infections are among the most common infections globally, and in the United Kingdom, they account for about half of all oral antibiotics prescribed. Antibiotic overuse and the emergence of "superbugs" that are resistant to their effects is a global problem that is becoming a serious concern. Considering this, the potential role of immunonutrition as a "prehabilitation" in helping to tackle bacterial infections and reduce over-reliance on antibiotic usage is gaining interest. This narrative mini-review summarizes current knowledge on the roles of certain nutrients in helping to modulate immune function, with particular focus on vitamin D. Vitamin D supplementation appears to reduce the risk of acute respiratory tract infections and thus could have a valuable role to play in reducing over-reliance on antibiotics. Investment in high-quality trials is needed to further explore this field.
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http://dx.doi.org/10.3389/fnut.2021.652469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027331PMC
March 2021

A review of the functional effects of pine nut oil, pinolenic acid and its derivative eicosatrienoic acid and their potential health benefits.

Prog Lipid Res 2021 Apr 5;82:101097. Epub 2021 Apr 5.

School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, United Kingdom.

Pine nut oil (PNO) is rich in a variety of unusual delta-5-non-methylene-interrupted fatty acids (NMIFAs), including pinolenic acid (PLA; all cis-5,-9,-12 18:3) which typically comprises 14 to 19% of total fatty acids. PLA has been shown to be metabolised to eicosatrienoic acid (ETA; all cis-7,-11,-14 20:3) in various cells and tissues. Here we review the literature on PNO, PLA and its metabolite ETA in the context of human health applications. PNO and PLA have a range of favourable effects on body weight as well as fat deposition through increased energy expenditure (fatty acid oxidation) and decreased food energy intake (reduced appetite). PNO and PLA improve blood and hepatic lipids in animal models and insulin sensitivity in vitro and reduce inflammation and modulate immune function in vitro and in animal models. The few studies which have examined effects of ETA indicate it has anti-inflammatory properties. Another NMIFA from PNO, sciadonic acid (all cis-5,-11,-14 20:3), has generally similar properties to PLA where these have been investigated. There is potential for human health benefits from PNO, its constituent NMIFA PLA and the PLA derivative ETA. However further studies are needed to explore the effects in humans.
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http://dx.doi.org/10.1016/j.plipres.2021.101097DOI Listing
April 2021

Combination of the Probiotics GG and subsp. , BB-12 Has Limited Effect on Biomarkers of Immunity and Inflammation in Older People Resident in Care Homes: Results From the Probiotics to Reduce Infections iN CarE home reSidentS Randomized, Controlled Trial.

Front Immunol 2021 4;12:643321. Epub 2021 Mar 4.

School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.

Aging is associated with a decline in many components of the immune system (immunosenescence). Probiotics may improve the immune response in older people. The objective was to determine the effect of the combination of two probiotic organisms [ (previously known as ) GG (LGG) and subsp. , BB-12 (BB-12)] on a range of immune biomarkers measured in the blood of older people resident in care homes in the UK. In a randomized controlled trial, older people [aged 67-97 (mean 86) years] resident in care homes received the combination of LGG+BB-12 (1.3-1.6 × 10 CFU per day) or placebo for up to 12 months. Full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis, and blood culture responses to immune stimulation were all measured. Response to seasonal influenza vaccination was measured in a subset of participants. Paired samples (i.e., before and after intervention) were available for 30 participants per group. LGG and BB-12 were more likely to be present in feces in the probiotic group and were present at higher numbers. There was no significant effect of the probiotics on components of the full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis by neutrophils and monocytes, and blood culture responses to immune stimulation. There was an indication that the probiotics improved the response to seasonal influenza vaccination with significantly ( = 0.04) higher seroconversion to the A/Michigan/2015 vaccine strain in the probiotic group than in the placebo group (47 vs. 15%).
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http://dx.doi.org/10.3389/fimmu.2021.643321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969511PMC
March 2021

Efficacy of Docosahexaenoic Acid for the Prevention of Necrotizing Enterocolitis in Preterm Infants: A Randomized Clinical Trial.

Nutrients 2021 Feb 17;13(2). Epub 2021 Feb 17.

Unidad de Cuidados Intensivos Neonatales, UMAE Hospital de Gineco-Obstetricia No.3, CMN La Raza, Instituto Mexicano del Seguro Social, México City 02990, Mexico.

Necrotizing enterocolitis (NEC) is an inflammatory bowel disease and a leading cause of morbidity and mortality in preterm infants. In this study, a randomized double-blind parallel-group (1:1) trial was carried out in two neonatal intensive care units of two tertiary hospitals. Two hundred and twenty-five preterm newborns with an expected functional gastrointestinal tract were recruited and received an enteral dose of 75 mg of docosahexaenoic acid (DHA)/kg body weight or high-oleic sunflower oil daily for 14 days from the first enteral feed after birth. Confirmed NEC was evaluated with Bell's scale from stage ≥ IIa. Two hundred and fourteen randomized infants were analyzed in terms of the intent-to-treat (DHA-group: = 105; control-group: = 109); data for two hundred infants were analysed per protocol. Confirmed NEC was lower in infants from the DHA-group compared with the control-group (0/100 vs. 7/100; = 0.007), with RR = 0.93 (95% CI 0.881 to 0.981), risk difference = -7%, (95% CI -12.00 to -1.99), and number needed-to-treat = 15 (95% CI 8.3 to 50). Intent-to-treat analysis showed a lower level of treatment failure in the DHA-group compared with the control-group (6/105 (6%) vs. 16/109 (15%); = 0.03, RR = 0.905, (95% CI 0.826 to 0.991)). The results after multivariate-regression analysis remained significant. Adverse events (apart from the incidence of NEC) were not different between groups. A daily dose of DHA for 14 days starting with the first enteral feed may prevent NEC in preterm infants.
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http://dx.doi.org/10.3390/nu13020648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922869PMC
February 2021

The placental lipidome of maternal antenatal depression predicts socio-emotional problems in the offspring.

Transl Psychiatry 2021 Feb 4;11(1):107. Epub 2021 Feb 4.

Singapore Institute for Clinical Sciences (SICS), A*STAR, Brenner Centre for Molecular Medicine, Singapore, Singapore.

While maternal mental health strongly influences neurodevelopment and health in the offspring, little is known about the determinants of inter-individual variation in the mental health of mothers. Likewise, the in utero biological pathways by which variation in maternal mental health affects offspring development remain to be defined. Previous studies implicate lipids, consistent with a known influence on cognitive and emotional function, but the relevance for maternal mental health and offspring neurodevelopment is unclear. This study characterizes the placental and circulatory lipids in antenatal depression, as well as socio-emotional outcomes in the offspring. Targeted liquid chromatography-mass spectrometry covering 470 lipid species was performed on placenta from 186 women with low (n = 70) or high (n = 116) levels of antenatal depressive symptoms assessed using the Edinburgh Postnatal Depression Scale at 26 weeks' gestation. Child socio-emotional outcomes were assessed from the Child Behavior Check List (CBCL) at 48 months. Seventeen placental lipid species showed an inverse association with antenatal EPDS scores. Specifically, lower levels of phospholipids containing LC-PUFAs: omega-3 docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and omega-6 arachidonic acid (AA) were significantly associated with depressive symptoms. Additional measurement of LC-PUFA in antenatal plasma samples at mid-gestation confirmed the reduced circulation of these specific fatty acids in mothers. Reduced concentration of the placental phospholipids also predicted poorer socio-emotional outcomes in the offspring. This study provides new insights into the role of the materno-fetal lipid cross-talk as a mechanism linking maternal mental health to that of the offspring. These findings show the potential utility of nutritional approaches among pregnant women with depressive symptoms to reduce offspring risk for later socio-emotional problems.
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http://dx.doi.org/10.1038/s41398-021-01208-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862650PMC
February 2021

Intake of n-3 polyunsaturated fatty acids in childhood, genotype, and incident asthma.

Eur Respir J 2021 Jan 28. Epub 2021 Jan 28.

Institute of Population Health Sciences, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Longitudinal evidence on the relation between dietary intake of n-3 (omega-3) very long-chain polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in mid-childhood and asthma risk is scarce. We aimed to investigate whether a higher intake of EPA and DHA from fish in childhood is associated with a lower risk of incident asthma.In the Avon Longitudinal Study of Parents and Children, dietary intakes of EPA and DHA from fish were estimated by food frequency questionnaire at 7 years of age. We used logistic regression, controlling for confounders, to analyse associations between intake of EPA and DHA (quartiles) and incidence of doctor-diagnosed asthma at age 11 or 14 years, and explored potential effect modification by a fatty acid desaturase () polymorphism (rs1535). Replication was sought in the Swedish BAMSE birth cohort.There was no evidence of association between intake of EPA plus DHA from fish and incident asthma overall (n=4543). However, when stratified by genotype, the odds ratio (95% confidence interval) comparing top bottom quartile amongst the 2025 minor G allele carriers was 0.49 (0.31-0.79) (p-trend 0.006), but no inverse association was observed in the homozygous major A allele group (odds ratio 1.43, 95% confidence interval 0.83-2.46, p-trend 0.19) (p-interaction 0.006). This gene-nutrient interaction on incident asthma was replicated in BAMSE.In children with a common variant, higher intake of EPA and DHA from fish in childhood was strongly associated with a lower risk of incident asthma up to mid-adolescence.
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http://dx.doi.org/10.1183/13993003.03633-2020DOI Listing
January 2021

An abundant biliary metabolite derived from dietary omega-3 polyunsaturated fatty acids regulates triglycerides.

J Clin Invest 2021 Mar;131(6)

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Omega-3 fatty acids from fish oil reduce triglyceride levels in mammals, yet the mechanisms underlying this effect have not been fully clarified, despite the clinical use of omega-3 ethyl esters to treat severe hypertriglyceridemia and reduce cardiovascular disease risk in humans. Here, we identified in bile a class of hypotriglyceridemic omega-3 fatty acid-derived N-acyl taurines (NATs) that, after dietary omega-3 fatty acid supplementation, increased to concentrations similar to those of steroidal bile acids. The biliary docosahexaenoic acid-containing (DHA-containing) NAT C22:6 NAT was increased in human and mouse plasma after dietary omega-3 fatty acid supplementation and potently inhibited intestinal triacylglycerol hydrolysis and lipid absorption. Supporting this observation, genetic elevation of endogenous NAT levels in mice impaired lipid absorption, whereas selective augmentation of C22:6 NAT levels protected against hypertriglyceridemia and fatty liver. When administered pharmacologically, C22:6 NAT accumulated in bile and reduced high-fat diet-induced, but not sucrose-induced, hepatic lipid accumulation in mice, suggesting that C22:6 NAT is a negative feedback mediator that limits excess intestinal lipid absorption. Thus, biliary omega-3 NATs may contribute to the hypotriglyceridemic mechanism of action of fish oil and could influence the design of more potent omega-3 fatty acid-based therapeutics.
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http://dx.doi.org/10.1172/JCI143861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954602PMC
March 2021

Optimising COVID-19 vaccine efficacy by ensuring nutritional adequacy.

Br J Nutr 2021 Jan 28:1-2. Epub 2021 Jan 28.

Faculty of Medicine, University of Southampton, Southampton, UK.

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http://dx.doi.org/10.1017/S0007114521000386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884658PMC
January 2021

Diet intervention improves cardiovascular profile in patients with rheumatoid arthritis: results from the randomized controlled cross-over trial ADIRA.

Nutr J 2021 01 23;20(1). Epub 2021 Jan 23.

Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, PO Box 459, SE-405 30, Gothenburg, Sweden.

Background: The chronic inflammation in patients with rheumatoid arthritis (RA) increases the risk for cardiovascular diseases (CVD). The contribution of diet as a risk factor for CVD among these patients is however not fully understood. The aim of this study is to investigate if a proposed anti-inflammatory diet improves cardiovascular profile in weight stable patients with RA.

Methods: Patients (n = 50) with RA were included in a cross-over trial. They were randomized to either a diet rich in whole grain, fatty fish, nuts, vegetables and fruit and supplemented with probiotics, or a control diet resembling average nutritional intake in Sweden, for ten weeks. After a 4-month washout they switched diet. Participants received food bags and dietary guidelines. Primary outcome was triglyceride (TG) concentration. Secondary outcomes were total-, high density lipoprotein- (HDL) and low density lipoprotein- (LDL) cholesterol, Apolipoprotein-B100 and -A1, lipoprotein composition, plasma phospholipid fatty acids and blood pressure.

Results: Forty-seven patients completed at least one period and they remained weight stable. There was a significant between-dietary treatment effect in TG and HDL-cholesterol concentration in favor of intervention (p = 0.007 and p = 0.049, respectively). Likewise, Apolipoprotein-B100/A1 ratio shifted toward a less atherogenic profile in favor of the intervention (p = 0.007). Plasma fatty acids increased in polyunsaturated- and decreased in monounsaturated- and saturated fatty acids between diet periods in favor of the intervention period.

Conclusion: Blood lipid profile improved indicating cardioprotective effects from an anti-inflammatory dietary intervention in patients with RA.

Trial Registration: This trial is registered at ClinicalTrials.gov as NCT02941055 .
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http://dx.doi.org/10.1186/s12937-021-00663-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827982PMC
January 2021

Sex Differences in the Plasma Accumulation of Oxylipins in Response to Supplemental n-3 Fatty Acids.

Authors:
Philip C Calder

J Nutr 2021 03;151(3):462-464

School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.

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http://dx.doi.org/10.1093/jn/nxaa421DOI Listing
March 2021

Omega-3 Polyunsaturated Fatty Acids and the Intestinal Epithelium-A Review.

Foods 2021 Jan 19;10(1). Epub 2021 Jan 19.

School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.

Epithelial cells (enterocytes) form part of the intestinal barrier, the largest human interface between the internal and external environments, and responsible for maintaining regulated intestinal absorption and immunological control. Under inflammatory conditions, the intestinal barrier and its component enterocytes become inflamed, leading to changes in barrier histology, permeability, and chemical mediator production. Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) can influence the inflammatory state of a range of cell types, including endothelial cells, monocytes, and macrophages. This review aims to assess the current literature detailing the effects of ω-3 PUFAs on epithelial cells. Marine-derived ω-3 PUFAs, eicosapentaenoic acid and docosahexaenoic acid, as well as plant-derived alpha-linolenic acid, are incorporated into intestinal epithelial cell membranes, prevent changes to epithelial permeability, inhibit the production of pro-inflammatory cytokines and eicosanoids and induce the production of anti-inflammatory eicosanoids and docosanoids. Altered inflammatory markers have been attributed to changes in activity and/or expression of proteins involved in inflammatory signalling including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator activated receptor (PPAR) α and γ, G-protein coupled receptor (GPR) 120 and cyclooxygenase (COX)-2. Effective doses for each ω-3 PUFA are difficult to determine due to inconsistencies in dose and time of exposure between different in vitro models and between in vivo and in vitro models. Further research is needed to determine the anti-inflammatory potential of less-studied ω-3 PUFAs, including docosapentaenoic acid and stearidonic acid.
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http://dx.doi.org/10.3390/foods10010199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835870PMC
January 2021

Differential Effects of DHA- and EPA-Rich Oils on Sleep in Healthy Young Adults: A Randomized Controlled Trial.

Nutrients 2021 Jan 16;13(1). Epub 2021 Jan 16.

Brain, Performance and Nutrition Research Centre, Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK.

Emerging evidence suggests that adequate intake of omega-3 polyunsaturated fatty acids (-3 PUFAs), which include docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), might be associated with better sleep quality. N-3 PUFAs, which must be acquired from dietary sources, are typically consumed at suboptimal levels in Western diets. Therefore, the current placebo-controlled, double-blind, randomized trial, investigated the effects of an oil rich in either DHA or EPA on sleep quality in healthy adults who habitually consumed low amounts of oily fish. Eighty-four participants aged 25-49 years completed the 26-week intervention trial. Compared to placebo, improvements in actigraphy sleep efficiency ( = 0.030) and latency ( = 0.026) were observed following the DHA-rich oil. However, these participants also reported feeling less energetic compared to the placebo ( = 0.041), and less rested ( = 0.017), and there was a trend towards feeling less ready to perform ( = 0.075) than those given EPA-rich oil. A trend towards improved sleep efficiency was identified in the EPA-rich group compared to placebo ( = 0.087), along with a significant decrease in both total time in bed ( = 0.032) and total sleep time ( = 0.019) compared to the DHA-rich oil. No significant effects of either treatment were identified for urinary excretion of the major melatonin metabolite 6-sulfatoxymelatonin. This study was the first to demonstrate some positive effects of dietary supplementation with -3 PUFAs in healthy adult normal sleepers, and provides novel evidence showing the differential effects of -3 PUFA supplements rich in either DHA or EPA. Further investigation into the mechanisms underpinning these observations including the effects of -3 PUFAs on sleep architecture are required.
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http://dx.doi.org/10.3390/nu13010248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830450PMC
January 2021

Long-Chain Polyunsaturated Fatty Acids (LCPUFAs) and the Developing Immune System: A Narrative Review.

Nutrients 2021 Jan 16;13(1). Epub 2021 Jan 16.

Faculty of Medicine, School of Human Development and Health, University of Southampton, Southampton SO16 6YD, UK.

The immune system is complex: it involves many cell types and numerous chemical mediators. An immature immune response increases susceptibility to infection, whilst imbalances amongst immune components leading to loss of tolerance can result in immune-mediated diseases including food allergies. Babies are born with an immature immune response. The immune system develops in early life and breast feeding promotes immune maturation and protects against infections and may protect against allergies. The long-chain polyunsaturated fatty acids (LCPUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA) are considered to be important components of breast milk. AA, eicosapentaenoic acid (EPA) and DHA are also present in the membranes of cells of the immune system and act through multiple interacting mechanisms to influence immune function. The effects of AA and of mediators derived from AA are often different from the effects of the n-3 LCPUFAs (i.e., EPA and DHA) and of mediators derived from them. Studies of supplemental n-3 LCPUFAs in pregnant women show some effects on cord blood immune cells and their responses. These studies also demonstrate reduced sensitisation of infants to egg, reduced risk and severity of atopic dermatitis in the first year of life, and reduced persistent wheeze and asthma at ages 3 to 5 years, especially in children of mothers with low habitual intake of n-3 LCPUFAs. Immune markers in preterm and term infants fed formula with AA and DHA were similar to those in infants fed human milk, whereas those in infants fed formula without LCPUFAs were not. Infants who received formula plus LCPUFAs (both AA and DHA) showed a reduced risk of allergic disease and respiratory illness than infants who received standard formula. Studies in which infants received n-3 LCPUFAs report immune differences from controls that suggest better immune maturation and they show lower risk of allergic disease and respiratory illness over the first years of life. Taken together, these findings suggest that LCPUFAs play a role in immune development that is of clinical significance, particularly with regard to allergic sensitisation and allergic manifestations including wheeze and asthma.
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http://dx.doi.org/10.3390/nu13010247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830895PMC
January 2021

Editorial: Omega-3 fatty acids: new studies, new data, new questions.

Curr Opin Clin Nutr Metab Care 2021 Mar;24(2):109-113

Department of Pediatrics, Institute of Human Nutrition, Columbia University Irving Medical Center, New York, New York, USA.

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http://dx.doi.org/10.1097/MCO.0000000000000726DOI Listing
March 2021

Dysregulation of endocannabinoid concentrations in human subcutaneous adipose tissue in obesity and modulation by omega-3 polyunsaturated fatty acids.

Clin Sci (Lond) 2021 Jan;135(1):185-200

School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.

Obesity is believed to be associated with a dysregulated endocannabinoid system which may reflect enhanced inflammation. However, reports of this in human white adipose tissue (WAT) are limited and inconclusive. Marine long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have anti-inflammatory actions and therefore may improve obesity-associated adipose tissue inflammation. Therefore, fatty acid (FA) concentrations, endocannabinoid concentrations, and gene expression were assessed in subcutaneous WAT (scWAT) biopsies from healthy normal weight individuals (BMI 18.5-25 kg/m2) and individuals living with metabolically healthy obesity (BMI 30-40 kg/m2) prior to and following a 12-week intervention with 3 g fish oil/day (1.1 g eicosapentaenoic acid (EPA) + 0.8 g DHA) or 3 g corn oil/day (placebo). WAT from individuals living with metabolically healthy obesity had higher n-6 PUFAs and EPA, higher concentrations of two endocannabinoids (anandamide (AEA) and eicosapentaenoyl ethanolamide (EPEA)), higher expression of phospholipase A2 Group IID (PLA2G2D) and phospholipase A2 Group IVA (PLA2G4A), and lower expression of CNR1. In response to fish oil intervention, WAT EPA increased to a similar extent in both BMI groups, and WAT DHA increased by a greater extent in normal weight individuals. WAT EPEA and docosahexaenoyl ethanolamide (DHEA) increased in normal weight individuals only and WAT 2-arachidonyl glycerol (2-AG) decreased in individuals living with metabolically healthy obesity only. Altered WAT fatty acid, endocannabinoid, and gene expression profiles in metabolically healthy obesity at baseline may be linked. WAT incorporates n-3 PUFAs when their intake is increased which affects the endocannabinoid system; however, effects appear greater in normal weight individuals than in those living with metabolically healthy obesity.
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http://dx.doi.org/10.1042/CS20201060DOI Listing
January 2021

In Vitro Bioassay-Guided Identification of Anticancer Properties from Lam. Leaf against the MDA-MB-231 Cell Line.

Pharmaceuticals (Basel) 2020 Dec 15;13(12). Epub 2020 Dec 15.

Cellular and Molecular Immunology Research Unit (CMIRU), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand.

Lam. (MO) is a medicinal plant distributed across the Middle East, Asia, and Africa. MO has been used in the traditional treatment of various diseases including cancer. This study aimed to perform bioassay-guided fractionation and identification of bioactive compounds from MO leaf against MDA-MB-231 breast cancer cells. MO leaf was sequentially extracted with hexane, ethyl acetate (EtOAc), and ethanol. The most effective extract was subjected to fractionation. MO extract and its derived fractions were continuously screened for anti-cancer activities. The strongest fraction was selected for re-fractionation and identification of bioactive compounds using LC-ESI-QTOF-MS/MS analysis. The best anticancer activities were related to the fraction no. 7-derived crude EtOAc extract. This fraction significantly reduced cell viability and clonogenic growth and increased cells apoptosis. Moreover, sub-fraction no. 7.7-derived fraction no. 7 was selected for the identification of bioactive compounds. There were 10 candidate compounds tentatively identified by LC-ESI-QTOF-MS. Three of identified compounds (7-octenoic acid, oleamide, and 1-phenyl-2-pentanol) showed anticancer activities by inducing cell cycle arrest and triggering apoptosis through suppressed Bcl-2 expression which subsequently promotes activation of caspase 3, indicators for the apoptosis pathway. This study identified 10 candidate compounds that may have potential in the field of anticancer substances.
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http://dx.doi.org/10.3390/ph13120464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765196PMC
December 2020

Assessing the cognitive status of older adults attending primary healthcare centers in Saudi Arabia using the Mini-Mental State Examination.

Saudi Med J 2020 Dec;41(12):1315-1323

Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia. E-mail.

Objectives:  To assess the cognitive status of older adults in Saudi Arabia.

Methods:  This was a cross-sectional, multistage, stratified study of older individuals (≥60 years of age) attending primary healthcare centres in Riyadh, Saudi Arabia between January 2015 and April 2017. We collected data using a structured questionnaire, which incorporated questions regarding demographic and anthropometric variables, the Arabic version of Mini-Mental State Examination, the Mini-Nutritional Assessment tool, and the Modified Katz Index of Independence in activities of daily living.

Results:  Of the 1299 participants, 914 (70.4%) were male, with a mean age of 66.2 ± 5.9 years. Approximately 79.1% of the participants had intact cognitive function, 17.1 had mild cognitive impairment, and 3.8% had severe cognitive impairment. Impaired cognitive function was associated with increased age, female gender, low education, unmarried status, and unemployed (p less than 0.001). Reduced cognitive impairment was significantly associated with functional impairment and malnutrition (p less than 0.001).

Conclusion:  Cognitive impairment affected around 21% of the participants. The reduced cognitive function was associated with increased age, female gender, low education level, unmarried, low income, dependency on others, functional impairment, and malnutrition. Such information could motivate health-policy makers to introduce appropriate measures to improve older adults' existing healthcare services in primary care, including cognitive function assessment.
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http://dx.doi.org/10.15537/smj.2020.12.25576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841595PMC
December 2020

Lipidomic Analysis of Plasma from Healthy Men and Women Shows Phospholipid Class and Molecular Species Differences between Sexes.

Lipids 2021 03 7;56(2):229-242. Epub 2020 Dec 7.

School of Human Development and Health, Faculty of Medicine, Southampton General Hospital, University of Southampton, Tremona Road, Southampton, SO16 6YD, UK.

The phospholipid composition of lipoproteins is determined by the specificity of hepatic phospholipid biosynthesis. Plasma phospholipid 20:4n-6 and 22:6n-3 concentrations are higher in women than in men. We used this sex difference in a lipidomics analysis of the impact of endocrine factors on the phospholipid class and molecular species composition of fasting plasma from young men and women. Diester species predominated in all lipid classes measured. 20/54 Phosphatidylcholine (PtdCho) species were alkyl ester, 15/48 phosphatidylethanolamine (PtdEtn) species were alkyl ester, and 12/48 PtdEtn species were alkenyl ester. There were no significant differences between sexes in the proportions of alkyl PtdCho species. The proportion of alkyl ester PtdEtn species was greater in women than men, while the proportion of alkenyl ester PtdEtn species was greater in men than women. None of the phosphatidylinositol (PtdIns) or phosphatidylserine (PtdSer) molecular species contained ether-linked fatty acids. The proportion of PtdCho16:0_22:6, and the proportions of PtdEtn O-16:0_20:4 and PtdEtn O-18:2_20:4 were greater in women than men. There were no sex differences in PtdIns and PtdSer molecular species compositions. These findings show that plasma phospholipids can be modified by sex. Such differences in lipoprotein phospholipid composition could contribute to sexual dimorphism in patterns of health and disease.
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http://dx.doi.org/10.1002/lipd.12293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048887PMC
March 2021

Maternal high fat diet in mice alters immune regulation and lung function in the offspring.

Br J Nutr 2020 Nov 27:1-24. Epub 2020 Nov 27.

Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.

Polyunsaturated fatty acids (PUFA) modulate immune function and have been associated with risk of childhood atopy and asthma. We investigated the effect of maternal fat intake in mice on PUFA status, elongase and desaturase gene expression, inflammatory markers and lung function in the offspring. C57BL/6J mice (n=32) were fed either standard chow (C, 21% kcal fat) or a high fat diet (HFD, 45% kcal fat) for 4 weeks prior to conception and during gestation and lactation. At 21 days of age, offspring were weaned onto either the HFD or C, generating four experimental groups: C/C, C/HF, HF/C and HF/HF. Plasma and liver fatty acid composition were measured by gas chromatography and gene expression by qPCR. Lung resistance to methacholine was assessed. Arachidonic acid concentrations in offspring plasma and liver phospholipids were increased by HFD; this effect was greater in the post-natal HFD group. Docosahexaenoic acid concentration in offspring liver phospholipids was increased in response to HFD and was higher in the post-natal HFD group. Post-natal HFD increased hepatic FADS2 and ELOVL5 expression in male offspring, whereas maternal HFD elevated expression of FADS1 and FADS2 in female offspring comparing to males. Post-natal HFD increased expression of IL-6 and CCL2 in perivascular adipose tissue. The HFD lowered lung resistance to methacholine. Excessive maternal fat intake during development modifies hepatic PUFA status in offspring through regulation of gene expression of enzymes that are involved in PUFA biosynthesis and modifies the development of the offspring lungs leading to respiratory dysfunction.
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http://dx.doi.org/10.1017/S0007114520004742DOI Listing
November 2020

Nutrition, immunity and COVID-19.

Authors:
Philip C Calder

BMJ Nutr Prev Health 2020 20;3(1):74-92. Epub 2020 May 20.

School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.

The immune system protects the host from pathogenic organisms (bacteria, viruses, fungi, parasites). To deal with this array of threats, the immune system has evolved to include a myriad of specialised cell types, communicating molecules and functional responses. The immune system is always active, carrying out surveillance, but its activity is enhanced if an individual becomes infected. This heightened activity is accompanied by an increased rate of metabolism, requiring energy sources, substrates for biosynthesis and regulatory molecules, which are all ultimately derived from the diet. A number of vitamins (A, B, B, folate, C, D and E) and trace elements (zinc, copper, selenium, iron) have been demonstrated to have key roles in supporting the human immune system and reducing risk of infections. Other essential nutrients including other vitamins and trace elements, amino acids and fatty acids are also important. Each of the nutrients named above has roles in supporting antibacterial and antiviral defence, but zinc and selenium seem to be particularly important for the latter. It would seem prudent for individuals to consume sufficient amounts of essential nutrients to support their immune system to help them deal with pathogens should they become infected. The gut microbiota plays a role in educating and regulating the immune system. Gut dysbiosis is a feature of disease including many infectious diseases and has been described in COVID-19. Dietary approaches to achieve a healthy microbiota can also benefit the immune system. Severe infection of the respiratory epithelium can lead to acute respiratory distress syndrome (ARDS), characterised by excessive and damaging host inflammation, termed a cytokine storm. This is seen in cases of severe COVID-19. There is evidence from ARDS in other settings that the cytokine storm can be controlled by n-3 fatty acids, possibly through their metabolism to specialised pro-resolving mediators.
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http://dx.doi.org/10.1136/bmjnph-2020-000085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295866PMC
May 2020

Marine n-3 Fatty Acids, Sudden Cardiac Death, and Ischemic Heart Disease: Fish or Supplements?

J Nutr 2020 12;150(12):3055-3057

School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.

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http://dx.doi.org/10.1093/jn/nxaa319DOI Listing
December 2020

The effect of a duodenal-jejunal bypass liner on lipid profile and blood concentrations of long chain polyunsaturated fatty acids.

Clin Nutr 2021 Apr 22;40(4):2343-2354. Epub 2020 Oct 22.

Imperial College London, London, UK.

Background & Aims: Duodenal-jejunal bypass liners (DJBLs) prevent absorption in the proximal small intestine, the site of fatty acid absorption. We sought to investigate the effects of a DJBL on blood concentrations of essential fatty acids (EFAs) and bioactive polyunsaturated fatty acids (PUFAs).

Methods: Sub-study of a multicentre, randomised, controlled trial with two treatment groups. Patients aged 18-65 years with type-2 diabetes mellitus and body mass index 30-50 kg/m were randomised to receive a DJBL for 12 months or best medical therapy, diet and exercise. Whole plasma PUFA concentrations were determined at baseline, 10 days, 6 and 11.5 months; data were available for n = 70 patients per group.

Results: Weight loss was significantly greater in the DJBL group compared to controls after 11.5 months: total body weight loss 11.3 ± 5.3% versus 6.0 ± 5.7% (mean difference [95% CI] = 5.27% [3.75, 6.80], p < 0.001). Absolute concentrations of both EFAs, linoleic acid and α-linolenic acid, and their bioactive derivatives, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, were significantly lower in the DJBL group than in the control group at 6 and 11.5 months follow-up. Total serum cholesterol, LDL-cholesterol and HDL-cholesterol were also significantly lower in the DJBL group.

Conclusion: One year of DJBL therapy is associated with superior weight loss and greater reductions in total serum cholesterol and LDL-cholesterol, but also depletion of EFAs and their longer chain derivatives. DJBL therapy may need to be offset by maintaining an adequate dietary intake of PUFAs or by supplementation.

Trial Registration: ClinicalTrials.gov Identifier NCT02459561.
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http://dx.doi.org/10.1016/j.clnu.2020.10.026DOI Listing
April 2021

Is There an Advantage in Enriching Parenteral Lipid Emulsions Containing Fatty Acids From Fish Oil With Medium-Chain Triglycerides? A Study on Body Pool Concentrations of ω-3 Fatty Acids in Lewis Rats.

JPEN J Parenter Enteral Nutr 2020 Oct 27. Epub 2020 Oct 27.

Laboratory of Nutrition and Metabolic Surgery (LIM-35), Department of Gastroenterology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Background: The addition of medium-chain triglycerides (MCTs) into parenteral lipid emulsions rich in fatty acids from fish oil (FOLEs) has been shown to improve their clearance and extrahepatic uptake. We assessed whether this effect could favor the leukocyte uptake of ω-3 polyunsaturated fatty acids (PUFAs) for immunomodulatory purposes METHODS: Following 5-day adaptation in metabolic cages, 42 male Lewis rats fed with AIN-93M chow were killed (baseline control group [BC]) or submitted to central venous catheterization and distributed into (1) surgical control group without parenteral infusion (chow group), (2) test emulsion (MCT/LCT/FO) group with the parenteral infusion of a FOLE containing 40% MCT, and (3) control emulsion group (LCT/FO) with the parenteral infusion of an FOLE without MCT. The 2 FOLEs had similar ω-3 PUFA contents and ω-6/ω-3 PUFA ratios and were infused during 48 and 72 hours. Concentrations of ω-3 and ω-6 PUFAs in plasma, liver, and blood mononuclear and polymorphonuclear leukocytes were assessed by gas chromatography RESULTS: In both FOLE groups, leukocyte concentrations of ω-3 PUFAs peaked after 48 hours' infusion (vs BC). At this time point, plasma concentrations of ω-3 PUFAs were higher in MCT/LCT/FO group than in LCT/FO group and the opposite was found in the liver (P<.05), but no differences in PUFA concentrations were observed between these groups in leukocytes (P>.05) CONCLUSION: The ω-3 PUFAs provided by FOLEs rich in MCT were less incorporated by liver and remained more available for extrahepatic cell delivery, but this did not result in a clear benefit in increasing their incorporation by peripheral leukocytes.
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http://dx.doi.org/10.1002/jpen.2041DOI Listing
October 2020

The Fatty Acid Composition of Human Follicular Fluid Is Altered by a 6-Week Dietary Intervention That Includes Marine Omega-3 Fatty Acids.

Lipids 2021 03 12;56(2):201-209. Epub 2020 Oct 12.

NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK.

The fatty acid composition of human follicular fluid is important for oocyte development and for pregnancy following in vitro fertilization (IVF). This study investigated whether a dietary intervention that included an increase in marine omega-3 fatty acids, olive oil and vitamin D alters the fatty acid composition of human follicular fluid. The association of lifestyle factors with follicular fluid fatty acid composition was also investigated. Fifty-five couples awaiting IVF were randomized to receive the 6-week treatment intervention of olive oil for cooking, an olive oil-based spread, and a daily supplement drink enriched with vitamin D and the marine omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and 56 couples were randomized to receive placebo equivalents. Dietary questionnaires were completed, and samples of blood were taken before and after the intervention. Follicular fluid was collected at oocyte retrieval and the fatty acid profile assessed using gas chromatography. In the control group, individual fatty acids in red blood cells and follicular fluid were significantly correlated. Furthermore, a healthier diet was associated with a lower percentage of follicular fluid arachidonic acid. The follicular fluid of women in the treatment group contained significantly higher amounts of EPA and DHA compared to the control group, while the omega-6 fatty acids linoleic, γ-linolenic, dihomo-γ-linolenic, and arachidonic were lower. This is the first report of a dietary intervention altering the fatty acid composition of follicular fluid in humans. Further research is required to determine whether this intervention improves oocyte quality.
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http://dx.doi.org/10.1002/lipd.12288DOI Listing
March 2021

A novel -3 glyceride mixture enhances enrichment of EPA and DHA after single dosing in healthy older adults: results from a double-blind crossover trial.

Br J Nutr 2021 Jul 13;126(2):244-252. Epub 2020 Oct 13.

School of Human Development and Health, Faculty of Medicine, University of Southampton, SouthamptonSO16 6YD, UK.

A glyceride mixture of monoglyceride, diglyceride and TAG increases solubilisation and enhances emulsification of n-3 fatty acid (FA)-containing lipids in the stomach. This allows for better access of digestive enzymes, pivotal for the release of bioactive n-3 FA. The objective was to compare the effect of a glyceride formulation and an ethyl ester formulation of EPA + DHA on concentrations of EPA and DHA in plasma following single dosing. We conducted a double-blind crossover trial in which twenty healthy adults aged 50-70 years consumed a single dose (2·8 g EPA + DHA) of each EPA + DHA formulation without a meal in random order separated by a 2-week washout period. EPA and DHA were measured in plasma total lipid over the following 12 h. EPA and DHA in plasma total lipid increased over 12 h with both formulations. A 10-fold greater Δ concentration of EPA, 3-fold greater Δ concentration of DHA and 5-fold greater Δ concentration of EPA + DHA were seen with the glyceride-EPA + DHA. The time at which the maximal concentrations of n-3 FA occurred was 4 h earlier for EPA, 1 h earlier for DHA and 2 h earlier for EPA + DHA when consuming glyceride-EPA + DHA. A mixture of monoglyceride, diglyceride and TAG results in greater and faster incorporation of EPA and DHA into blood plasma lipid in the absence of a fatty meal. This may provide benefit to individuals on a low-fat diet or with digestive impairments and could result in greater efficacy in clinical trials using n-3 FA.
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http://dx.doi.org/10.1017/S0007114520004031DOI Listing
July 2021