Publications by authors named "Wendy L Hall"

62 Publications

Heart Rate Variability and Long Chain -3 Polyunsaturated Fatty Acids in Chronic Kidney Disease Patients on Haemodialysis: A Cross-Sectional Pilot Study.

Nutrients 2021 Jul 18;13(7). Epub 2021 Jul 18.

Department of Nutritional Sciences, School of Life Course Sciences, King's College London, 150 Stamford Street, London SE1 9NH, UK.

Low heart rate variability (HRV) is independently associated with increased risk of sudden cardiac death (SCD) and all cardiac death in haemodialysis patients. Long chain -3 polyunsaturated fatty acids (LC -3 PUFA) may exert anti-arrhythmic effects. This study aimed to investigate relationships between dialysis, sleep and 24 h HRV and LC -3 PUFA status in patients who have recently commenced haemodialysis. A cross-sectional study was conducted in adults aged 40-80 with chronic kidney disease (CKD) stage 5 (n = 45, mean age 58, SD 9, 20 females and 25 males, 39% with type 2 diabetes). Pre-dialysis blood samples were taken to measure erythrocyte and plasma fatty acid composition (wt % fatty acids). Mean erythrocyte omega-3 index was not associated with HRV following adjustment for age, BMI and use of β-blocker medication. Higher ratios of erythrocyte eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) were associated with lower 24 h vagally-mediated beat-to-beat HRV parameters. Higher plasma EPA and docosapentaenoic acid (DPA-3) were also associated with lower sleep-time and 24 h beat-to-beat variability. In contrast, higher plasma EPA was significantly related to higher overall and longer phase components of 24 h HRV. Further investigation is required to investigate whether patients commencing haemodialysis may have compromised conversion of EPA to DHA, which may impair vagally-mediated regulation of cardiac autonomic function, increasing risk of SCD.
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http://dx.doi.org/10.3390/nu13072453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308541PMC
July 2021

The effect of the a regional cardioprotective nutritional program on inflammatory biomarkers and metabolic risk factors in secondary prevention for cardiovascular disease, a randomised trial.

Clin Nutr 2021 06 28;40(6):3828-3835. Epub 2021 Apr 28.

Department of Nutrition, School of Public Health, University of São Paulo, São Paulo, Brazil. Electronic address:

Background & Aims: To evaluate the effect of the Brazilian Cardioprotective Diet Program (BALANCE Program) on inflammatory biomarkers, involved in the pathophysiology of the atherosclerosis, on inflammatory biomarkers, cardiovascular risk factors, and on plasma fatty acids in cardiovascular disease secondary prevention patients.

Methods: In this substudy of the BALANCE Program randomized clinical trial, a total of 369 patients aged 45 years or older, who have experienced cardiovascular disease in the previous 10 years, were included. These patients were randomized into two groups and followed up for six months: BALANCE Program group and control group (conventional nutrition advice). In the initial and six-month final visits, anthropometry (body weight, height and waist circumference), food intake evaluation by 24-h dietary recall, plasma inflammatory biomarkers (IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-α, adiponectin, and C-reactive protein levels), blood pressure, glycemia, insulinemia, lipid profile, and plasma fatty acids levels were evaluated.

Results: The BALANCE Program group showed increased plasma alpha-linolenic acid levels (P = 0.008), reduction in waist circumference (P = 0.049) and BMI (P = 0.032). No difference was observed among plasma inflammatory biomarkers and clinical data.

Conclusion: After six months of follow-up, BALANCE Program led to a significant reduction on BMI and waist circumference in individuals in secondary prevention for cardiovascular disease. Although plasmatic alpha-linolenic acid has increased, there was no impact on plasma inflammatory biomarkers.

Clinical Trial Registration: NCT01620398.
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http://dx.doi.org/10.1016/j.clnu.2021.04.035DOI Listing
June 2021

Meal-induced inflammation: postprandial insights from the Personalised REsponses to DIetary Composition Trial (PREDICT) study in 1000 participants.

Am J Clin Nutr 2021 09;114(3):1028-1038

Department of Nutritional Sciences, King's College London, London, United Kingdom.

Background: Meal-induced metabolic changes trigger an acute inflammatory response, contributing to chronic inflammation and associated diseases.

Objectives: We aimed to characterize variability in postprandial inflammatory responses using traditional (IL-6) and novel [glycoprotein acetylation (GlycA)] biomarkers of inflammation and dissect their biological determinants with a focus on postprandial glycemia and lipemia.

Methods: Postprandial (0-6 h) glucose, triglyceride (TG), IL-6, and GlycA responses were measured at multiple intervals after sequential mixed-nutrient meals (0 h and 4 h) in 1002 healthy adults aged 18-65 y from the PREDICT (Personalised REsponses to DIetary Composition Trial) 1 study, a single-arm dietary intervention study. Measures of habitual diet, blood biochemistry, gut microbiome composition, and visceral fat mass (VFM) were also collected.

Results: The postprandial changes in GlycA and IL-6 concentrations were highly variable between individuals. Participants eliciting an increase in GlycA and IL-6 (60% and 94% of the total participants, respectively) had mean 6-h increases of 11% and 190%, respectively. Peak postprandial TG and glucose concentrations were significantly associated with 6-h GlycA (r = 0.83 and r = 0.24, respectively; both P < 0.001) but not with 6-h IL-6 (both P > 0.26). A random forest model revealed the maximum TG concentration was the strongest postprandial TG predictor of postprandial GlycA and structural equation modeling revealed that VFM and fasting TG were most strongly associated with fasting and postprandial GlycA. Network Mendelian randomization demonstrated a causal link between VFM and fasting GlycA, mediated (28%) by fasting TG. Individuals eliciting enhanced GlycA responses had higher predicted cardiovascular disease risk (using the atherosclerotic disease risk score) than the rest of the cohort.

Conclusions: The variable postprandial increases in GlycA and their associations with TG metabolism highlight the importance of modulating TG in concert with obesity to reduce GlycA and associated low-grade inflammation-related diseases.This trial was registered at clinicaltrials.gov as NCT03479866.
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http://dx.doi.org/10.1093/ajcn/nqab132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408875PMC
September 2021

Palmitic acid-rich oils with and without interesterification lower postprandial lipemia and increase atherogenic lipoproteins compared with a MUFA-rich oil: A randomized controlled trial.

Am J Clin Nutr 2021 05;113(5):1221-1231

Department of Nutritional Sciences, School of Life Course Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.

Background: Interesterified (IE) fats are widely used in place of trans fats; however, little is known about their metabolism.

Objectives: To test the impact of a commonly consumed IE compared with a non-IE equivalent fat on in vivo postprandial and in vitro lipid metabolism, compared with a reference oil [rapeseed oil (RO)].

Methods: A double-blinded, 3-phase crossover, randomized controlled trial was performed in healthy adults (n = 20) aged 45-75 y. Postprandial plasma triacylglycerol and lipoprotein responses (including stable isotope tracing) to a test meal (50 g fat) were evaluated over 8 h. The test fats were IE 80:20 palm stearin/palm kernel fat, an identical non-IE fat, and RO (control). In vitro, mechanisms of digestion were explored using a dynamic gastric model (DGM).

Results: Plasma triacylglycerol 8-h incremental area under the curves were lower following non-IE compared with RO [-1.7 mmol/L⋅h (95% CI: -3.3, -0.0)], but there were no differences between IE and RO or IE and non-IE. LDL particles were smaller following IE and non-IE compared with RO (P = 0.005). Extra extra large, extra large, and large VLDL particle concentrations were higher following IE and non-IE compared with RO at 6-8 h (P < 0.05). No differences in the appearance of [13C]palmitic acid in plasma triacylglycerol were observed between IE and non-IE fats. DGM revealed differences in phase separation of the IE and non-IE meals and delayed release of SFAs compared with RO.

Conclusions: Interesterification did not modify fat digestion, postprandial lipemia, or lipid metabolism measured by stable isotope and DGM analysis. Despite the lower lipemia following the SFA-rich fats, increased proatherogenic large triacylglycerol-rich lipoprotein remnant and small LDL particles following the SFA-rich fats relative to RO adds a new postprandial dimension to the mechanistic evidence linking SFAs to cardiovascular disease risk.
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http://dx.doi.org/10.1093/ajcn/nqaa413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106759PMC
May 2021

Quantitative Assessment of Dietary (Poly)phenol Intake: A High-Throughput Targeted Metabolomics Method for Blood and Urine Samples.

J Agric Food Chem 2021 Jan 29;69(1):537-554. Epub 2020 Dec 29.

Department of Nutritional Sciences, School of Life Course Sciences, Faculty of Life Science and Medicine, King's College London, London SE1 9NH, U.K.

Many studies have associated the consumption of (poly)phenol-rich diets with health benefits. However, accurate high-throughput quantitative methods for estimating exposure covering a broad spectrum of (poly)phenols are lacking. We have developed and validated a high-throughput method for the simultaneous quantification of 119 (poly)phenol metabolites in plasma and urine using ultra high-performance liquid chromatography coupled with triple quadrupole mass spectrometry, with a very fast sample treatment and a single run time of 16 min. This method is highly sensitive, precise, accurate, and shows good linearity for all compounds ( > 0.992). This novel method will allow a quantitative assessment of habitual (poly)phenol intake in large epidemiological studies as well as clinical studies investigating the health benefits of dietary (poly)phenols.
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http://dx.doi.org/10.1021/acs.jafc.0c07055DOI Listing
January 2021

Apple polyphenol-rich drinks dose-dependently decrease early-phase postprandial glucose concentrations following a high-carbohydrate meal: a randomized controlled trial in healthy adults and in vitro studies.

J Nutr Biochem 2020 11 30;85:108466. Epub 2020 Jul 30.

Department of Nutritional Sciences, Faculty of Life Sciences and Medicine, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, UK. Electronic address:

Background: Previous research demonstrated that a high dose of phlorizin-rich apple extract (AE) can markedly inhibit early-phase postprandial glycemia, but efficacy of lower doses of the AE is unclear.

Objective: To determine whether lower AE doses reduce early-phase postprandial glycemia in healthy adults and investigate mechanisms.

Design: In a randomized, controlled, double-blinded, cross-over acute trial, drinks containing 1.8 g (HIGH), 1.35 g (MED), 0.9 g (LOW), or 0 g (CON) of a phlorizin-rich AE were consumed before 75 g starch/sucrose meal. Postprandial blood glucose, insulin, C-peptide, glucose-dependent insulinotropic polypeptide (GIP) and polyphenol metabolites concentrations were measured 0-240 min, acetaminophen concentrations to assess gastric emptying rate, and 24 h urinary glucose excretion. Effects of AE on intestinal glucose transport were investigated in Caco-2/TC7 cells.

Results: AE significantly reduced plasma glucose iAUC 0-30 min at all doses: mean differences (95% CI) relative to CON were -15.6 (-23.3, -7.9), -11.3 (-19.6, -3.0) and -8.99 (-17.3, -0.7) mmol/L per minute for HIGH, MEDIUM and LOW respectively, delayed T (HIGH, MEDIUM and LOW 45 min vs. CON 30 min), but did not lower C. Similar dose-dependent treatment effects were observed for insulin, C-peptide, and GIP. Gastric emptying rates and urinary glucose excretion did not differ. Serum phloretin, quercetin and epicatechin metabolites were detected postprandially. A HIGH physiological AE dose equivalent decreased total glucose uptake by 48% in Caco-2/TC7 cells.

Conclusions: Phlorizin-rich AE, even at a low dose, can slightly delay early-phase glycemia without affecting peak and total glycemic response.
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http://dx.doi.org/10.1016/j.jnutbio.2020.108466DOI Listing
November 2020

Snacking on Whole Almonds for Six Weeks Increases Heart Rate Variability during Mental Stress in Healthy Adults: A Randomized Controlled Trial.

Nutrients 2020 Jun 19;12(6). Epub 2020 Jun 19.

Department of Nutritional Sciences, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.

Cardiac autonomic regulation can be indirectly measured by heart rate variability (HRV). Low HRV, which can be induced by mental stress, is a predictor of risk of sudden cardiac death. Few studies have investigated cause-and-effect relationships between diet and HRV. Nut consumption is associated with CVD risk reduction, but the impact on HRV, particularly in response to stress, is unclear. Men and women (30-70 y) with above average risk of developing CVD were randomly assigned in a 6-week randomized, controlled, parallel arm trial to consume either whole almond or isocaloric control snacks (20% of daily estimated energy requirement). Control snacks contained the average nutrient profile of UK snacks. Five-minute periods of supine heart rate (HR) and HRV were measured at resting and during mental stress (Stroop color-word test) at baseline and six weeks. High frequency (HF) power, which reflects parasympathetic regulation of HR, was increased following almonds during the mental stress task relative to control (mean difference between groups 124 ms2; 95% CI 11, 237; = 0.031, = 105), but other indices were unaffected. Snacking on whole almonds instead of typical snacks may reduce risk of CVD partly by ameliorating the suppression of HRV during periods of mental stress.
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http://dx.doi.org/10.3390/nu12061828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353422PMC
June 2020

Whole almond consumption is associated with better diet quality and cardiovascular disease risk factors in the UK adult population: National Diet and Nutrition Survey (NDNS) 2008-2017.

Eur J Nutr 2021 Mar 16;60(2):643-654. Epub 2020 May 16.

Diet and Cardiometabolic Health Research Group, Department of Nutritional Sciences, Faculty of Life Sciences and Medicine, King's College London, London, SE1 9NH, UK.

Purpose:  This work aimed to estimate whole almond consumption in a nationally representative UK survey population and examine associations with diet quality and cardiovascular disease (CVD) risk.

Methods:  Four-day food record data from the National Diet and Nutrition Survey (NDNS) 2008-2017 (n = 6802, age ≥ 19 year) were analyzed to investigate associations between whole almond consumption and diet quality, measured by the modified Mediterranean Diet Score (MDS) and modified Healthy Diet Score (HDS), and CVD risk markers, using survey-adjusted multivariable linear regression.

Results:  Whole almond consumption was reported in 7.6% of the population. Median intake in whole almond consumers was 5.0 g/day (IQR 9.3). Consumers had higher diet quality scores relative to non-consumers; higher intakes of protein, total fat, monounsaturated, n-3 and n-6 polyunsaturated fats, fiber, folate, vitamin C, vitamin E, potassium, magnesium, phosphorus, and iron; and lower intakes of trans-fatty acids, total carbohydrate, sugar, and sodium. BMI and WC were lower in whole almond consumers compared to non-consumers: 25.5 kg/m (95% CI 24.9, 26.2) vs 26.3 kg/m (25.9, 26.7), and 88.0 cm (86.2, 89.8) vs 90.1 cm (89.1, 91.2), respectively. However, there were no dose-related fully adjusted significant associations between increasing almond intake (g per 1000 kcal energy intake) and lower CVD risk markers.

Conclusions:  Almond intake is low in the UK population, but consumption was associated with better dietary quality and lower CVD risk factors. Habitual consumption of whole almonds should be encouraged as part of a healthy diet.
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http://dx.doi.org/10.1007/s00394-020-02270-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900023PMC
March 2021

Snacking on whole almonds for 6 weeks improves endothelial function and lowers LDL cholesterol but does not affect liver fat and other cardiometabolic risk factors in healthy adults: the ATTIS study, a randomized controlled trial.

Am J Clin Nutr 2020 06;111(6):1178-1189

Diet and Cardiometabolic Health Research Group, Department of Nutritional Sciences, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.

Background: There is convincing evidence that daily whole almond consumption lowers blood LDL cholesterol concentrations, but effects on other cardiometabolic risk factors such as endothelial function and liver fat are still to be determined.

Objectives: We aimed to investigate whether isoenergetic substitution of whole almonds for control snacks with the macronutrient profile of average snack intakes, had any impact on markers of cardiometabolic health in adults aged 30-70 y at above-average risk of cardiovascular disease (CVD).

Methods: The study was a 6-wk randomized controlled, parallel-arm trial. Following a 2-wk run-in period consuming control snacks (mini-muffins), participants consumed either whole roasted almonds (n = 51) or control snacks (n = 56), providing 20% of daily estimated energy requirements. Endothelial function (flow-mediated dilation), liver fat (MRI/magnetic resonance spectroscopy), and secondary outcomes as markers of cardiometabolic disease risk were assessed at baseline and end point.

Results: Almonds, compared with control, increased endothelium-dependent vasodilation (mean difference 4.1%-units of measurement; 95% CI: 2.2, 5.9), but there were no differences in liver fat between groups. Plasma LDL cholesterol concentrations decreased in the almond group relative to control (mean difference -0.25 mmol/L; 95% CI: -0.45, -0.04), but there were no group differences in triglycerides, HDL cholesterol, glucose, insulin, insulin resistance, leptin, adiponectin, resistin, liver function enzymes, fetuin-A, body composition, pancreatic fat, intramyocellular lipids, fecal SCFAs, blood pressure, or 24-h heart rate variability. However, the long-phase heart rate variability parameter, very-low-frequency power, was increased during nighttime following the almond treatment compared with control (mean difference 337 ms2; 95% CI: 12, 661), indicating greater parasympathetic regulation.

Conclusions: Whole almonds consumed as snacks markedly improve endothelial function, in addition to lowering LDL cholesterol, in adults with above-average risk of CVD.This trial was registered at clinicaltrials.gov as NCT02907684.
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http://dx.doi.org/10.1093/ajcn/nqaa100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266688PMC
June 2020

Energy Restriction Enhances Adult Hippocampal Neurogenesis-Associated Memory after Four Weeks in an Adult Human Population with Central Obesity; a Randomized Controlled Trial.

Nutrients 2020 Feb 28;12(3). Epub 2020 Feb 28.

Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 125 Coldharbour Lane, London, SE5 9NU, UK.

Adult neurogenesis, the generation of new neurons throughout life, occurs in the subventricular zone of the dentate gyrus in the human hippocampal formation. It has been shown in rodents that adult hippocampal neurogenesis is needed for pattern separation, the ability to differentially encode small changes derived from similar inputs, and recognition memory, as well as the ability to recognize previously encountered stimuli. Improved hippocampus-dependent cognition and cellular readouts of adult hippocampal neurogenesis have been reported in daily energy restricted and intermittent fasting adult mice. Evidence that nutrition can significantly affect brain structure and function is increasing substantially. This randomized intervention study investigated the effects of intermittent and continuous energy restriction on human hippocampal neurogenesis-related cognition, which has not been reported previously. Pattern separation and recognition memory were measured in 43 individuals with central obesity aged 35-75 years, before and after a four-week dietary intervention using the mnemonic similarity task. Both groups significantly improved pattern separation ( = 0.0005), but only the intermittent energy restriction group had a significant deterioration in recognition memory. There were no significant differences in cognitive improvement between the two diets. This is the first human study to investigate the association between energy restriction with neurogenesis-associated cognitive function. Energy restriction may enhance hippocampus-dependent memory and could benefit those in an ageing population with declining cognition. This study was registered on ClinicalTrials.gov (NCT02679989) on 11 February 2016.
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http://dx.doi.org/10.3390/nu12030638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146388PMC
February 2020

Tree nut snack consumption is associated with better diet quality and CVD risk in the UK adult population: National Diet and Nutrition Survey (NDNS) 2008-2014.

Public Health Nutr 2020 12 28;23(17):3160-3169. Epub 2020 Feb 28.

Department of Nutritional Sciences, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, LondonSE1 9NH, UK.

Objectives: To examine associations of tree nut snack (TNS) consumption with diet quality and cardiovascular disease (CVD) risk in UK adults from National Diet and Nutrition Survey (NDNS) 2008-2014.

Design: Cross-sectional analysis using data from 4-d food diaries, blood samples and physical measurements for CVD risk markers. To estimate diet quality, modified Mediterranean Diet Score (MDS) and modified Healthy Diet Score (HDS) were applied. Associations of TNS consumption with diet quality and markers of CVD risk were investigated using survey-adjusted multivariable linear regression adjusted for sex, age, ethnicity, socio-economic and smoking status, region of residency and total energy and alcohol intake.

Setting: UK free-living population.

Subjects: 4738 adults (≥19 years).

Results: TNS consumers had higher modified MDS and HDS relative to non-consumers. TNS consumers also had lower BMI, WC, SBP and DBP and higher HDL compared to non-consumers, although a dose-related fully adjusted significant association between increasing nut intake (g per 4184 kJ/1000 kcal energy intake) and lower marker of CVD risk was only observed for SBP. TNS consumption was also associated with higher intake of total fat, mono-, n-3 and n-6 polyunsaturated fatty acids, fibre, vitamin A, thiamin, folate, vitamin C, vitamin E, potassium, magnesium, phosphorus, selenium and iron; and lower intake of saturated fatty acids, trans fatty acids, total carbohydrate, starch, free sugar, sodium and chloride.

Conclusions: TNS consumers report better dietary quality and consumption was associated with lower CVD risk factors. Encouraging replacement of less healthy snacks with TNS should be encouraged as part of general dietary guidelines.
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http://dx.doi.org/10.1017/S1368980019003914DOI Listing
December 2020

Intermittent energy restriction is comparable to continuous energy restriction for cardiometabolic health in adults with central obesity: A randomized controlled trial; the Met-IER study.

Clin Nutr 2020 06 30;39(6):1753-1763. Epub 2019 Jul 30.

Department of Nutritional Sciences, School of Life Course Sciences, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.

Background & Aims: Short bouts of severe energy restriction may have additional, beneficial cardiometabolic effects beyond that of weight loss. We aimed to assess the short-term effects of intermittent fasting on insulin sensitivity and related cardiometabolic mechanisms.

Methods: This parallel arm, randomized controlled trial compared the short-term effects of intermittent and continuous energy restriction (IER and CER) diets on markers of cardiometabolic health in individuals with central obesity, aiming for equivalent weight loss on both diets. Outcomes were assessed in non-smoking men and women (35-75 y), following 4-wk IER (48 h 600 kcal/d followed by 5-day healthy eating advice) or CER diets (-500 kcal/d healthy eating advice). The primary outcome was the revised quantitative insulin sensitivity check index (R-QUICKI), an indirect estimate of insulin sensitivity. Secondary outcomes included ambulatory blood pressure (ABP), indicators of sympathetic activity (heart rate variability (HRV) and normetanephrine), and markers of glucose homeostasis/insulin resistance, adiposity, lipids and inflammation.

Results: Forty-three participants completed the study. Reductions in body weight were equivalent in both groups: mean loss (%) -2.6; 95% CI -3.3, -1.9 and -2.9; -3.6, -2.1 for CER and IER, respectively, P = 0.464). R-QUICKI increased following IER and CER, with no between-diet differences (overall mean increase (%) 6.6; 3.6, 9.6). Fasting plasma glucose concentrations decreased after CER but not after IER (mean difference CER-IER - 4.8% (0.7, 8.9), P < 0.05) and fasting plasma non-esterified fatty acid concentrations were lower after IER compared to CER (mean difference CER-IER 0.15 mmol/L (0.06, 0.24), P < 0.005). There were no differences in lipids, adipokine/inflammatory markers, ABP or HRV between diets.

Conclusions: Short-term CER or IER diets are comparable in their effects on most markers of cardiometabolic risk, although adaptive changes in glucose and fatty acid metabolism occur. This study is registered at clinicaltrials.gov as NCT02679989.
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http://dx.doi.org/10.1016/j.clnu.2019.07.014DOI Listing
June 2020

Adherence to UK dietary guidelines is associated with higher dietary intake of total and specific polyphenols compared with a traditional UK diet: further analysis of data from the Cardiovascular risk REduction Study: Supported by an Integrated Dietary Approach (CRESSIDA) randomised controlled trial.

Br J Nutr 2019 02;121(4):402-415

Diabetes & Nutritional Sciences Division, King's College London,Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH,UK.

Adherence to dietary guidelines (DG) may result in higher intake of polyphenols via increased consumption of fruits, vegetables and whole grains. We compared polyphenol dietary intake and urinary excretion between two intervention groups in the Cardiovascular risk REduction Study: Supported by an Integrated Dietary Approach study: a 12-week parallel-arm, randomised controlled trial (n 161; sixty-four males, ninety-seven females; aged 40-70 years). One group adhered to UK DG, whereas the other group consumed a representative UK diet (control). We estimated polyphenol dietary intake, using a 4-d food diary (4-DFD) and FFQ, and analysed 24-h polyphenol urinary excretion by liquid chromatography-tandem MS on a subset of participants (n 46 control; n 45 DG). A polyphenol food composition database for 4-DFD analysis was generated using Phenol-Explorer and USDA databases. Total polyphenol intake by 4-DFD at endpoint (geometric means with 95 % CI, adjusted for baseline and sex) was significantly higher in the DG group (1279 mg/d per 10 MJ; 1158, 1412) compared with the control group (1084 mg/d per 10 MJ; 980, 1197). The greater total polyphenol intake in the DG group was attributed to higher intake of anthocyanins, proanthocyanidins and hydroxycinnamic acids, with the primary food sources being fruits, cereal products, nuts and seeds. FFQ estimates of flavonoid intake also detected greater intake in DG compared with the control group. 24-h urinary excretion showed consistency with 4-DFD in their ability to discriminate between dietary intervention groups for six out of ten selected, individual polyphenols. In conclusion, following UK DG increased total polyphenol intake by approximately 20 %, but not all polyphenol subclasses corresponded with this finding.
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http://dx.doi.org/10.1017/S0007114518003409DOI Listing
February 2019

Sleep extension is a feasible lifestyle intervention in free-living adults who are habitually short sleepers: a potential strategy for decreasing intake of free sugars? A randomized controlled pilot study.

Am J Clin Nutr 2018 01;107(1):43-53

Diabetes and Nutritional Sciences Division, King's College London, London, United Kingdom.

Background: Evidence suggests that short sleep duration may be a newly identified modifiable risk factor for obesity, yet there is a paucity of studies to investigate this.

Objective: We assessed the feasibility of a personalized sleep extension protocol in adults aged 18-64 y who are habitually short sleepers (5 to <7 h), with sleep primarily measured by wrist actigraphy. In addition, we collected pilot data to assess the effects of extended sleep on dietary intake and quality measured by 7-d food diaries, resting and total energy expenditure, physical activity, and markers of cardiometabolic health.

Design: Forty-two normal-weight healthy participants who were habitually short sleepers completed this free-living, 4-wk, parallel-design randomized controlled trial. The sleep extension group (n = 21) received a behavioral consultation session targeting sleep hygiene. The control group (n = 21) maintained habitual short sleep.

Results: Rates of participation, attrition, and compliance were 100%, 6.5%, and 85.7%, respectively. The sleep extension group significantly increased time in bed [0:55 hours:minutes (h:mm); 95% CI: 0:37, 1:12 h:mm], sleep period (0:47 h:mm; 95% CI: 0:29, 1:05 h:mm), and sleep duration (0:21 h:mm; 95% CI: 0:06, 0:36 h:mm) compared with the control group. Sleep extension led to reduced intake of free sugars (-9.6 g; 95% CI: -16.0, -3.1 g) compared with control (0.7 g; 95% CI: -5.7, 7.2 g) (P = 0.042). A sensitivity analysis in plausible reporters showed that the sleep extension group reduced intakes of fat (percentage), carbohydrates (grams), and free sugars (grams) in comparison to the control group. There were no significant differences between groups in markers of energy balance or cardiometabolic health.

Conclusions: We showed the feasibility of extending sleep in adult short sleepers. Sleep extension led to reduced free sugar intakes and may be a viable strategy to facilitate limiting excessive consumption of free sugars in an obesity-promoting environment. This trial was registered at www.clinicaltrials.gov as NCT02787577.
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http://dx.doi.org/10.1093/ajcn/nqx030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972593PMC
January 2018

Apple and blackcurrant polyphenol-rich drinks decrease postprandial glucose, insulin and incretin response to a high-carbohydrate meal in healthy men and women.

J Nutr Biochem 2017 11 27;49:53-62. Epub 2017 Jul 27.

Diabetes & Nutritional Sciences Division, Faculty of Life Sciences and Medicine, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. Electronic address:

Postprandial glycemic responses to meals are inhibited by polyphenol-rich plant foods. Combinations of polyphenols may be particularly effective through complementary mechanisms. A randomized, controlled, double-blinded cross-over trial was conducted in healthy volunteers to test the hypothesis that apple and blackcurrant polyphenol-rich drinks would reduce postprandial blood glucose concentrations. Secondary outcomes included insulin and glucose-dependent insulinotropic polypeptide (GIP) secretion. Twenty men (mean age 26 y, SD 8) and 5 postmenopausal women (mean age 57 y, SD 3) consumed a placebo drink (CON) and 2 polyphenol-rich drinks containing fruit extracts: either 1200 mg apple polyphenols (AE), or 600 mg apple polyphenols+600 mg blackcurrant anthocyanins (AE+BE), in random order with a starch and sucrose meal. Incremental areas under the curve (iAUC) for plasma glucose concentrations were lower following AE+BE over 0-30 and 0-120 min compared with CON; mean differences (95% CI) -32 mmol/L·min (-41, -22, P<.0005) and -52 mmol/L min (-94, -9, P<.05), respectively. AE significantly reduced iAUC 0-30 min (mean difference -26 mmol/L min, -35, -18, P<.0005) compared with CON, but the difference over 120 min was not significant. Postprandial insulin, C-peptide and GIP concentrations were significantly reduced relative to CON. A dose response inhibition of glucose transport was demonstrated in Caco-2 cells, including total and GLUT-mediated transport, and SGLT1-mediated glucose transport was strongly inhibited at all doses in Xenopus oocytes, following 10 min incubation with 0.125-4 mg apple polyphenols/ml. In conclusion, ingestion of apple and blackcurrant polyphenols decreased postprandial glycemia, which may be partly related to inhibition of intestinal glucose transport.
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http://dx.doi.org/10.1016/j.jnutbio.2017.07.013DOI Listing
November 2017

A comparison of heart rate variability, n-3 PUFA status and lipid mediator profile in age- and BMI-matched middle-aged vegans and omnivores.

Br J Nutr 2017 Mar 3;117(5):669-685. Epub 2017 Apr 3.

1Diabetes & Nutritional Sciences Division,King's College London, Faculty of Life Sciences & Medicine,Franklin-Wilkins Building,150 Stamford Street,London SE1 9NH,UK.

Low heart rate variability (HRV) predicts sudden cardiac death. Long-chain (LC) n-3 PUFA (C20-C22) status is positively associated with HRV. This cross-sectional study investigated whether vegans aged 40-70 years (n 23), whose diets are naturally free from EPA (20 : 5n-3) and DHA (22 : 6n-3), have lower HRV compared with omnivores (n 24). Proportions of LC n-3 PUFA in erythrocyte membranes, plasma fatty acids and concentrations of plasma LC n-3 PUFA-derived lipid mediators were significantly lower in vegans. Day-time interbeat intervals (IBI), adjusted for physical activity, age, BMI and sex, were significantly shorter in vegans compared with omnivores (mean difference -67 ms; 95 % CI -130, -3·4, P50 % and high-frequency power) were similarly lower in vegans, with no differences during sleep. In conclusion, vegans have higher 24 h SDNN, but lower day-time HRV and shorter day-time IBI relative to comparable omnivores. Vegans may have reduced availability of precursor markers for pro-resolving lipid mediators; it remains to be determined whether there is a direct link with impaired cardiac function in populations with low-n-3 status.
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http://dx.doi.org/10.1017/S0007114517000629DOI Listing
March 2017

Does Intragastric Balloon Treatment for Obesity in Chronic Kidney Disease Heighten Acute Kidney Injury Risk?

Am J Nephrol 2016 27;44(6):411-418. Epub 2016 Oct 27.

Department of Nutrition and Dietetics, King's College Hospital NHS Foundation Trust, London, UK.

Background: The outcomes of intragastric balloon (IGB) placement to achieve weight loss in obese patients with chronic kidney disease (CKD) have not been reported to date. This study aimed to assess the safety and efficacy of the IGB as a weight-loss treatment among this patient population.

Methods: A prospective, single-arm, 'first in CKD' interventional study was conducted in patients with a body mass index >35 kg/m2 and CKD stages 3-4, referred for weight loss. After clinical assessment, the IGB was endoscopically inserted into the stomach and kept in place for 6 months. Complications, adverse events, acceptability, weight loss and metabolic responses were monitored over 6 months.

Results: Eleven participants were recruited over 18 months. Two patients withdrew (1 prior to IGB insertion and 1 early removal after 3 days due to persistent vomiting) from the study; 9 patients completed the study. There were 5 episodes of acute kidney injury (AKI), occurring in 3 patients. After 6 months, the mean body mass decreased by 9.6% (SD ±6.8). Median waist circumference and total cholesterol decreased significantly (-7.7 cm; interquartile range (IQR) -15.3 to -3.9; and -0.2 mmol/l; IQR -0.6 to -0.05, respectively), with no changes in estimated glomerular filtration rate, blood pressure, triglycerides, adipokines, inflammation, or arterial stiffness measured by carotid-femoral pulse wave velocity. At IGB removal, there was 1 new case each of gastritis and esophagitis.

Conclusions: Treatment with IGB has only moderate efficacy on weight loss; yet it results in a high rate of complications in obese patients with established CKD. The risk of AKI may be raised due to increased risk of dehydration secondary to gastrointestinal symptoms associated with IGB placement and reduced baseline kidney function.
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http://dx.doi.org/10.1159/000450765DOI Listing
January 2018

Drinks containing anthocyanin-rich blackcurrant extract decrease postprandial blood glucose, insulin and incretin concentrations.

J Nutr Biochem 2016 12 14;38:154-161. Epub 2016 Sep 14.

Diabetes & Nutritional Sciences Division, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. Electronic address:

Blackcurrants are rich in polyphenolic glycosides called anthocyanins, which may inhibit postprandial glycemia. The aim was to determine the dose-dependent effects of blackcurrant extract on postprandial glycemia. Men and postmenopausal women (14M, 9W, mean age 46 years, S.D.=14) were enrolled into a randomized, double-blind, crossover trial. Low sugar fruit drinks containing blackcurrant extract providing 150-mg (L-BE), 300-mg (M-BE) and 600-mg (H-BE) total anthocyanins or no blackcurrant extract (CON) were administered immediately before a high-carbohydrate meal. Plasma glucose, insulin and incretins (GIP and GLP-1) were measured 0-120min, and plasma 8-isoprostane F, together with arterial stiffness by digital volume pulse (DVP) was measured at 0 and 120min. Early plasma glucose response was significantly reduced following H-BE (n=22), relative to CON, with a mean difference (95% CI) in area over baseline (AOB) 0-30min of -0.34mmol/l.h (-0.56, -0.11, P<.005); there were no differences between the intermediate doses and placebo. Plasma insulin concentrations (AOB 0-30min) were similarly reduced. Plasma GIP concentrations (AOB 0-120min) were significantly reduced following H-BE, with a mean difference of -46.6ng/l.h (-66.7, -26.5, P<.0001) compared to CON. Plasma GLP-1 concentrations were reduced following H-BE at 90min. There were no effects on 8-isoprostane F or vascular function. Consumption of blackcurrant extract in amounts roughly equivalent to 100-g blackcurrants reduced postprandial glycemia, insulinemia and incretin secretion, which suggests that inclusion of blackcurrant polyphenols in foods may provide cardio-metabolic health benefits. This trial was registered at clinicaltrials.gov as NCT01706653.
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http://dx.doi.org/10.1016/j.jnutbio.2016.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5170886PMC
December 2016

Modulation of postprandial lipaemia by a single meal containing a commonly consumed interesterified palmitic acid-rich fat blend compared to a non-interesterified equivalent.

Eur J Nutr 2017 Dec 10;56(8):2487-2495. Epub 2016 Aug 10.

Diabetes and Nutritional Sciences Division, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.

Purpose: Interesterification of palm stearin and palm kernal (PSt/PK) is widely used by the food industry to create fats with desirable functional characteristics for applications in spreads and bakery products, negating the need for trans fatty acids. Previous studies have reported reduced postprandial lipaemia, an independent risk factor for CVD, following interesterified (IE) palmitic and stearic acid-rich fats that are not currently widely used by the food industry. The current study investigates the effect of the most commonly consumed PSt/PK IE blend on postprandial lipaemia.

Methods: A randomised, controlled, crossover (1 week washout) double-blind design study (n = 12 healthy males, 18-45 years), compared the postprandial (0-4 h) effects of meals containing 50 g fat [PSt/PK (80:20); IE vs. non-IE] on changes in plasma triacylglycerol (TAG), glucose, glucose-dependent insulinotropic polypeptide (GIP), peptide YY (PYY), insulin, gastric emptying (paracetamol concentrations) and satiety (visual analogue scales).

Results: The postprandial increase in plasma TAG was higher following the IE PSt/PK versus the non-IE PSt/PK, with a 51 % greater incremental area under the curve [mean difference with 95 % CI 41 (23, 58) mmol/L min P = 0.001]. The pattern of lipaemia was different between meals; at 4-h plasma TAG concentrations declined following the IE fat but continued to rise following the non-IE fat. Insulin, glucose, paracetamol, PYY and GIP concentrations increased significantly after the test meals (time effect; P < 0.001 for all), but did not differ between test meals. Feelings of fullness were higher following the non-IE PSt/PK meal (diet effect; P = 0.034). No other significant differences were noted.

Conclusions: Interesterification of PSt/PK increases early phase postprandial lipaemia (0-4 h); however, further investigation during the late postprandial phase (4-8 h) is warranted to determine the rate of return to baseline values.

Trial Registration Number: Clinicaltrials.gov as NCT02365987.
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http://dx.doi.org/10.1007/s00394-016-1284-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682848PMC
December 2017

Berries and anthocyanins: promising functional food ingredients with postprandial glycaemia-lowering effects.

Proc Nutr Soc 2016 08 12;75(3):342-55. Epub 2016 May 12.

Diabetes & Nutritional Sciences Division,King's College London,Franklin-Wilkins Building,150 Stamford Street,London SE1 9NH,UK.

The prevalence of type 2 diabetes (T2D) is predicted to reach unprecedented levels in the next few decades. In addition to excess body weight, there may be other overlapping dietary drivers of impaired glucose homeostasis that are associated with an obesogenic diet, such as regular exposure to postprandial spikes in blood glucose arising from diets dominated by highly refined starches and added sugars. Strategies to reduce postprandial hyperglycaemia by optimising the functionality of foods would strengthen efforts to reduce the risk of T2D. Berry bioactives, including anthocyanins, are recognised for their inhibitory effects on carbohydrate digestion and glucose absorption. Regular consumption of berries has been associated with a reduction in the risk of T2D. This review aims to examine the evidence from in vitro, animal and human studies, showing that berries and berry anthocyanins may act in the gut to modulate postprandial glycaemia. Specifically, berry extracts and anthocyanins inhibit the activities of pancreatic α-amylase and α-glucosidase in the gut lumen, and interact with intestinal sugar transporters, sodium-dependent glucose transporter 1 and GLUT2, to reduce the rate of glucose uptake into the circulation. Growing evidence from randomised controlled trials suggests that berry extracts, purées and nectars acutely inhibit postprandial glycaemia and insulinaemia following oral carbohydrate loads. Evidence to date presents a sound basis for exploring the potential for using berries/berry extracts as an additional stratagem to weight loss, adherence to dietary guidelines and increasing physical exercise, for the prevention of T2D.
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http://dx.doi.org/10.1017/S0029665116000240DOI Listing
August 2016

Compliance with dietary guidelines affects capillary recruitment in healthy middle-aged men and women.

Eur J Nutr 2017 Apr 8;56(3):1037-1044. Epub 2016 Jan 8.

Diabetes and Nutritional Sciences Division, Faculty of Life Sciences and Medicine, King's College London, 4.108 Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.

Purpose: Healthy microcirculation is important to maintain the health of tissues and organs, most notably the heart, kidney and retina. Single components of the diet such as salt, lipids and polyphenols may influence microcirculation, but the effects of dietary patterns that are consistent with current dietary guidelines are uncertain. It was hypothesized that compliance to UK dietary guidelines would have a favourable effect on skin capillary density/recruitment compared with a traditional British diet (control diet).

Methods: A 12-week randomized controlled trial in men and women aged 40-70 years was used to test whether skin microcirculation, measured by skin video-capillaroscopy on the dorsum of the finger, influenced functional capillary density (number of capillaries perfused under basal conditions), structural capillary density (number of anatomical capillaries perfused during finger cuff inflation) and capillary recruitment (percentage difference between structural and functional capillary density).

Results: Microvascular measures were available for 137 subjects out of the 165 participants randomized to treatment. There was evidence of compliance to the dietary intervention, and participants randomized to follow dietary guidelines showed significant falls in resting supine systolic, diastolic and mean arterial pressure of 3.5, 2.6 and 2.9 mmHg compared to the control diet. There was no evidence of differences in capillary density, but capillary recruitment was 3.5 % (95 % CI 0.2, 6.9) greater (P = 0.04) on dietary guidelines compared with control.

Conclusions: Adherence to dietary guidelines may help maintain a healthy microcirculation in middle-aged men and women. This study is registered at www.isrctn.com as ISRCTN92382106.
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http://dx.doi.org/10.1007/s00394-015-1151-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346414PMC
April 2017

Differential acute effects of carbohydrate- and protein-rich drinks compared with water on cardiac output during rest and exercise in healthy young men.

Appl Physiol Nutr Metab 2015 Aug;40(8):803-10

Diabetes and Nutritional Sciences Division, School of Medicine, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.

The acute effects of drinks rich in protein (PRO) versus carbohydrate (CHO) on cardiovascular hemodynamics and reactivity are uncertain. A randomized crossover design was used to compare 400-mL isoenergetic (1.1 MJ) drinks containing whey protein (PRO; 44 g) or carbohydrate (CHO; 57 g) versus 400 mL of water in 14 healthy men. The primary and secondary outcomes were changes in cardiac output, blood pressure, systemic vascular resistance (SVR) and digital volume pulse measured prior to and 30 min following consumption at rest, during 12 min of multi-stage bicycle ergometry, and 15 min postexercise. The mean change (95% confidence interval (CI)) in resting cardiac output at 30 min was greater for CHO than for PRO or water: 0.7 (0.4 to 1.0), 0.1 (-0.2 to 0.40), and 0.0 (-0.3 to 0.3) L/min (P < 0.001), respectively; the higher cardiac output following CHO was accompanied by an increase in stroke volume and a lower SVR. The mean increments (95% CI) in cardiac output during exercise were CHO 4.7 (4.4 to 5.0), PRO 4.9 (4.6 to 5.2), and water 4.6 (4.3 to 4.9) L/min with the difference between PRO versus water being significant (P < 0.025). There were no other statistically significant differences. In summary, a CHO-rich drink increased cardiac output and lowered SVR in the resting state compared with a PRO-rich drink or water but the effect size of changes in these variables did not differ during or after exercise between CHO and PRO. Neither protein nor carbohydrate affected blood pressure reactivity to exercise.
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http://dx.doi.org/10.1139/apnm-2014-0358DOI Listing
August 2015

Participation in a Structured Weight Loss Program and All-Cause Mortality and Cardiovascular Morbidity in Obese Patients With Chronic Kidney Disease.

J Ren Nutr 2015 Nov 2;25(6):472-9. Epub 2015 Jul 2.

School of Medicine, King's College London, London, UK; Department of Renal Medicine, King's College Hospital, London, UK.

Objective: To determine if participation in a weight loss program impacted upon a composite end point of all-cause mortality and cardiovascular morbidity in obese patients with chronic kidney disease (CKD).

Design: Retrospective cohort study.

Subjects: All patients with a body mass index (BMI) >30 kg/m(2) or >28 kg/m(2) with at least 1 comorbidity (hypertension, diabetes, or dyslipidemia) referred to an established weight management program (WMP) from 2005 to 2009 at a metropolitan tertiary teaching hospital were eligible for inclusion in the study cohort.

Intervention: Twelve-month structured weight loss program.

Main Outcome Measures: Combined outcome of all-cause mortality, myocardial infarction, stroke, and hospitalization for congestive heart failure; kidney transplantation waitlisting.

Results: A total of 169 obese patients with CKD commenced the WMP and 169 did not-becoming the observational control group (CON). There were no significant differences between groups for age, BMI, sex, ethnicity, smoking, hypertension, or kidney function at baseline, although CON included more patients with diabetes than WMP (49% vs. 38%, P = .03). Kaplan-Meier survival analysis with log-rank test differed between groups for the combined outcome (P = .03). Cox regression analysis with adjustment for age, sex, ethnicity, hypertension, diabetes, kidney function, baseline BMI, and smoking status, indicated that patients in WMP had a significantly longer event-free period for the combined outcome, than those in CON (adjusted hazard ratio 0.53; 95% confidence interval [CI] 0.29-0.97; P = .04). Participation in the WMP did not increase the likelihood of kidney transplantation waitlisting (odds ratio [OR] 1.06; 95% CI 0.39-2.87; P = .9). Lower baseline BMI and greater weight loss over 12 months were the only factors related to kidney transplantation waitlisting (adjusted R(2) = 0.426).

Conclusions: Participation in a structured weight loss program may be associated with improved outcomes in obese patients with CKD.
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http://dx.doi.org/10.1053/j.jrn.2015.05.001DOI Listing
November 2015

How effective are current dietary guidelines for cardiovascular disease prevention in healthy middle-aged and older men and women? A randomized controlled trial.

Am J Clin Nutr 2015 May 18;101(5):922-30. Epub 2015 Mar 18.

From the Diabetes and Nutritional Sciences Division, King's College London, Franklin-Wilkins Building, London, United Kingdom (DPR, JD, WLH, and TABS), and Women's Health Division (PTS) and British Heart Foundation Centre, School of Medicine (PJC), King's College London, St Thomas' Hospital, London, United Kingdom.

Background: Controversy surrounds the effectiveness of dietary guidelines for cardiovascular disease (CVD) prevention in healthy middle-aged and older men and women.

Objective: The objective was to compare effects on vascular and lipid CVD risk factors of following the United Kingdom dietary guidelines with a traditional British diet (control).

Design: With the use of a parallel-designed randomized controlled trial in 165 healthy nonsmoking men and women (aged 40-70 y), we measured ambulatory blood pressure (BP) on 5 occasions, vascular function, and CVD risk factors at baseline and during 12 wk after random assignment to treatment. The primary outcomes were differences between treatments in daytime ambulatory systolic BP, flow-mediated dilation, and total cholesterol/HDL cholesterol. Secondary outcomes were differences between treatment in carotid-to-femoral pulse wave velocity, high-sensitivity C-reactive protein, and a measure of insulin sensitivity (Revised Quantitative Insulin Sensitivity Check Index).

Results: Data were available on 162 participants, and adherence to the dietary advice was confirmed from dietary records and biomarkers of compliance. In the dietary guidelines group (n = 80) compared with control (n = 82), daytime systolic BP was 4.2 mm Hg (95% CI: 1.7, 6.6 mm Hg; P < 0.001) lower, the treatment effect on flow-mediated dilation [-0.62% (95% CI: -1.48%, 0.24%)] was not significant, the total cholesterol:HDL cholesterol ratio was 0.13 (95% CI: 0, 0.26; P = 0.044) lower, pulse wave velocity was 0.29 m/s (95% CI: 0.07, 0.52 m/s; P = 0.011) lower, high-sensitivity C-reactive protein was 36% (95% CI: 7%, 48%; P = 0.017) lower, the treatment effect on the Revised Quantitative Insulin Sensitivity Check Index [2% (95% CI: -2%, 5%)] was not significant, and body weight was 1.9 kg (95% CI: 1.3, 2.5 kg; P < 0.001) lower. Causal mediated effects analysis based on urinary sodium excretion indicated that sodium reduction explained 2.4 mm Hg (95% CI: 1.0, 3.9 mm Hg) of the fall in blood pressure.

Conclusion: Selecting a diet consistent with current dietary guidelines lowers BP and lipids, which would be expected to reduce the risk of CVD by one-third in healthy middle-aged and older men and women. This study is registered at www.isrctn.com as 92382106.
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http://dx.doi.org/10.3945/ajcn.114.097352DOI Listing
May 2015

Risk for chronic kidney disease increases with obesity: Health Survey for England 2010.

Public Health Nutr 2015 Dec 6;18(18):3349-54. Epub 2015 Mar 6.

1Department of Nutrition and Dietetics,King's College Hospital,Denmark Hill,London SE5 9RS,UK.

Objective: Studies of the relationship between obesity and chronic kidney disease (CKD) in nationally representative population samples are limited. Our study aimed to determine if overweight and obesity were independently associated with the risk for CKD in the 2010 Health Survey for England (HSE).

Design: The HSE is an annually conducted cross-sectional study. In 2010 serum creatinine was included to determine the incidence of CKD in the population. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Multivariable logistic regression models were developed to calculate odds ratios and 95% confidence intervals for CKD risk by BMI (reference category: BMI=18.5-24.9 kg/m2) and adjusted for age, gender, ethnicity, smoking, diabetes and hypertension.

Setting: A random sample of nationally representative households in England.

Subjects: Adults (n 3463) with calculable eGFR and BMI were included.

Results: The prevalence of CKD was 5.9%. The risk of CKD was over 2.5 times higher in obese participants compared with normal-weight participants in the fully adjusted model (BMI=30.0-39.9 kg/m2: adjusted OR=2.78 (95% CI 1.75, 4.43); BMI ≥ 40.0 kg/m2: adjusted OR=2.68 (95% CI 1.05, 6.85)).

Conclusions: Obesity is associated with an increased risk of CKD in a national sample of the UK population, even after adjustment for known CKD risk factors, which may have implications for CKD screening and future national health service planning and delivery.
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http://dx.doi.org/10.1017/S1368980015000488DOI Listing
December 2015

A thin layer angiogenesis assay: a modified basement matrix assay for assessment of endothelial cell differentiation.

BMC Cell Biol 2014 Dec 5;15:41. Epub 2014 Dec 5.

Comparative Biomedical Sciences, Royal Veterinary College, University of London Royal College Street, London, NW1 0TU, UK.

Background: Basement matrices such as Matrigel™ and Geltrex™ are used in a variety of cell culture assays of anchorage-dependent differentiation including endothelial cell tube formation assays. The volumes of matrix recommended for these assays (approximately 150 μl/cm(2)) are costly, limit working distances for microscopy, and require cell detachment for subsequent molecular analysis. Here we describe the development and validation of a thin-layer angiogenesis (TLA) assay for assessing the angiogenic potential of endothelial cells that overcomes these limitations.

Results: Geltrex™ basement matrix at 5 μl/cm(2) in 24-well (10 μl) or 96-well (2 μl) plates supports endothelial cell differentiation into tube-like structures in a comparable manner to the standard larger volumes of matrix. Since working distances are reduced, high-resolution single cell microscopy, including DIC and confocal imaging, can be used readily. Using MitoTracker dye we now demonstrate, for the first time, live mitochondrial dynamics and visualise the 3-dimensional network of mitochondria present in differentiated endothelial cells. Using a standard commercial total RNA extraction kit (Qiagen) we also show direct RNA extraction and RT-qPCR from differentiated endothelial cells without the need to initially detach cells from their supporting matrix.

Conclusions: We present here a new thin-layer assay (TLA) for measuring the anchorage-dependent differentiation of endothelial cells into tube-like structures which retains all the characteristics of the traditional approach but with the added benefit of a greatly lowered cost and better compatibility with other techniques, including RT-qPCR and high-resolution microscopy.
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http://dx.doi.org/10.1186/s12860-014-0041-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263020PMC
December 2014

An interesterified palm olein test meal decreases early-phase postprandial lipemia compared to palm olein: a randomized controlled trial.

Lipids 2014 Sep 8;49(9):895-904. Epub 2014 Aug 8.

Diabetes & Nutritional Sciences Division, School of Medicine, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK,

Palm oil that has been interesterified to produce a higher proportion of palmitic acid (16:0) in the sn-2 position reduces postprandial lipemia in young, normolipidemic men and women, but effects in older subjects with higher fasting triacylglycerol (TAG) concentrations are unknown. We tested the hypothesis that high-fat meals rich in interesterified palm olein (IPO) decrease lipemia and alter plasma lipoprotein fraction composition compared to native palm olein (NPO) in men aged 40-70 years with fasting TAG concentrations ≥1.2 mmol/L. Postprandial changes in plasma lipids following meals containing 75 g fat (NPO and IPO) were compared using a randomized, double-blind crossover design (n = 11). Although there were no significant differences in plasma TAG concentrations between meals over the total 6-h postprandial measurement period, IPO resulted in a decreased plasma TAG response during the first 4 h of the postprandial period (iAUC 1.65 mmol/L h, 95% CI 1.01-2.29) compared to NPO (iAUC 2.33 mmol/L h, 95% CI 1.58-3.07); meal effect P = 0.024. Chylomicron fraction TAG concentrations at 4-6 h were slightly reduced following IPO compared to NPO [NPO-IPO mean difference 0.29 mmol/L (95% CI -0.01-0.59), P = 0.055]. There were no differences in IDL fraction TAG, cholesterol or apolipoprotein B48 concentrations following IPO compared with NPO. In conclusion, consuming a meal containing palm olein with a higher proportion of 16:0 in the sn-2 position decreases postprandial lipemia compared to native palm olein during the early phase of the postprandial period in men with higher than optimal fasting triacylglycerol concentrations.
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http://dx.doi.org/10.1007/s11745-014-3936-1DOI Listing
September 2014

High-fat meals rich in EPA plus DHA compared with DHA only have differential effects on postprandial lipemia and plasma 8-isoprostane F2α concentrations relative to a control high-oleic acid meal: a randomized controlled trial.

Am J Clin Nutr 2014 Oct 6;100(4):1019-28. Epub 2014 Aug 6.

From Comparative Biomedical Sciences, Royal Veterinary College (RP, SHL, KMB, and CPDW-J) and Diabetes & Nutritional Sciences Division (WLH), King's College London, London, United Kingdom.

Background: Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation has beneficial cardiovascular effects, but postprandial influences of these individual fatty acids are unclear.

Objectives: The primary objective was to determine the vascular effects of EPA + DHA compared with DHA only during postprandial lipemia relative to control high-oleic acid meals; the secondary objective was to characterize the effects of linoleic acid-enriched high-fat meals relative to the control meal.

Design: We conducted a randomized, controlled, double-blind crossover trial of 4 high-fat (75-g) meals containing 1) high-oleic acid sunflower oil (HOS; control), 2) HOS + fish oil (FO; 5 g EPA and DHA), 3) HOS + algal oil (AO; 5 g DHA), and 4) high-linoleic acid sunflower oil (HLS) in 16 healthy men (aged 35-70 y) with higher than optimal fasting triacylglycerol concentrations (mean ± SD triacylglycerol, 1.9 ± 0.5 mmol/L).

Results: Elevations in triacylglycerol concentration relative to baseline were slightly reduced after FO and HLS compared with the HOS control (P < 0.05). The characteristic decrease from baseline in plasma nonesterified fatty acids after a mixed meal was inhibited after AO (Δ 0-3 h, P < 0.05). HLS increased the augmentation index compared with the other test meals (P < 0.05), although the digital volume pulse-reflection index was not significantly different. Plasma 8-isoprostane F2α analysis revealed opposing effects of FO (increased) and AO (reduced) compared with the control (P < 0.05). No differences in nitric oxide metabolites were observed.

Conclusions: These data show differential postprandial 8-isoprostane F2α responses to high-fat meals containing EPA + DHA-rich fish oil compared with DHA-rich AO, but these differences were not associated with consistent effects on postprandial vascular function or lipemia. More detailed analyses of polyunsaturated fatty acid-derived lipid mediators are required to determine possible divergent functional effects of single meals rich in either DHA or EPA. This trial was registered at clinicaltrials.gov as NCT01618071.
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http://dx.doi.org/10.3945/ajcn.114.091223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163792PMC
October 2014
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