Berry Antioxidants in Health and Disease

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Berry

Antioxidants in Health and Disease

Dorothy Klimis-Zacas ^{Edited by}

Printed Edition of the Special Issue Published in Antioxidants

antioxidants

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Berry Antioxidants in Health and Disease

Special Issue Editor

Dorothy Klimis-Zacas

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Dorothy Klimis-Zacas

Department of Food Science and Human Nutrition, School of Food and Agriculture

University of Maine USA

Editorial Office MDPI AG

St. Alban-Anlage 66 Basel, Switzerland

This edition is a reprint of the Special Issue published online in the open access journal Antioxidants (ISSN 2076-3921) in 2016 (available at:

http://www.mdpi.com/journal/antioxidants/special_issues/berry_antioxidants).

For citation purposes, cite each article independently as indicated on the article page online and as indicated below:

Author 1; Author 2; Author 3 etc. Article title. Journalname. Year. Article number/page range.

ISBN 978-3-03842-348-5 (Pbk) ISBN 978-3-03842-349-2 (PDF)

Articles in this volume are Open Access and distributed under the Creative Commons Attribution license (CC BY), which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book taken as a whole is © 2017 MDPI, Basel, Switzerland, distributed under the terms and conditions of the Creative Commons by Attribution (CC BY-NC-ND) license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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About the Guest Editor

Dorothy Klimis-Zacas, PhD. FACN is Professor of Clinical Nutrition and cooperating Graduate Faculty, School of Biomedical Sciences at the University of Maine. She is also cooperating professor of Nutrition and Dietetics at Harokopio University, Athens, Greece and at the Department of Food, Environmental and Nutritional Sciences at the University of Milan, Italy. She was awarded a senior Fulbright Fellowship to the Hellenic School of Public Health, Athens, Greece and two Fulbright Specialist awards to the University of Milan, Italy, Department of Food, Environmental and Nutritional Sciences. Additionally, she was the recipient of the Fondazione Cariplo Fellowship to direct research on the use of biosensors in exploring dietary approaches for chronic disease prevention at the University of Milan.

Dr. Klimis-Zacas has been involved in biomedical research exploring the role of trace minerals and dietary bioactives and functional foods on chronic diseases such as obesity, cardiovascular disease and the metabolic syndrome, including basic and clinical investigations. Her recent investigations examine the role of berries on attenuating co-morbidities associated with the metabolic syndrome such as obesity-induced inflammation, dyslipidemia and insulin resistance. Her applied investigations involve cross-cultural studies that utilize dietary interventions to reduce cardiovascular risk in populations both in the United States and the Mediterranean region.

Dr. Klimis-Zacas is the editor of Manganese in Health and Disease and Nutritional Concerns for Women CRC Press, and has acted as editor-in-chief of Annual Editions in Nutrition and as member of several editorial boards including the Journal of Nutritional Biochemistry and board member of the International Society of Trace Mineral Research in Humans (ISTERH). Dr. Klimis-Zacas is a member of many professional societies dedicated to promoting health and preventing disease including The American Society for Nutrition, The American College of Nutrition, The International Atherosclerosis Society, The American Academy of Nutrition and Dietetics, The Italian Society of Nutrition, The Hellenic Dietetic Association and many others.

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VII

Preface to “Berry Antioxidants in Health and Disease”

During the last decade, a high volume of work has been published on the health-promoting effects of berries (e.g., blueberries, cranberries, blackberries, etc.) that are rich in antioxidant phytochemicals, polyphenols. Consuming a diet rich in polyphenols has been documented to attenuate the risk of chronic diseases, such as cardiovascular disease, certain cancers, diabetes mellitus, and neurodegenerative disorders. Recent evidence also reveals that the biological effects of polyphenols extend beyond their traditional antioxidant role.

This Special Issue includes 10 peer-reviewed papers, including original research papers and reviews. They present the most recent advances in the role of berry antioxidants, not only in maintaining health but also in preventing and/or reversing disease both in cell culture, animal models and in humans. Additionally, the molecular mechanisms and signaling pathways modulated by berry antioxidants are presented. Chapters include the role of berry antioxidants in whole fruit and leaves on the metabolic syndrome, obesity, diabetes and glucose intolerance, cancer, inflammation, oxidative stress and neuroprotection as well as cardiovascular disease. As a guest editor, I would like to acknowledge the authors of all chapters for their valuable contributions and reviewers for their thoughtful and constructive suggestions and time. Special thanks to the publishing team of the Antioxidants Journal for their professionalism, attention to detail and timely completion of this volume.

Dorothy Klimis-Zacas Guest Editor

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antioxidants

Review

Berry Fruit Consumption and Metabolic Syndrome

Stefano Vendrame¹, Cristian Del Bo’², Salvatore Ciappellano², Patrizia Riso²and Dorothy Klimis-Zacas^1,*

1 School of Food and Agriculture, Food Science and Human Nutrition, University of Maine, Orono, ME 04469, USA; [email protected]

2 DeFENS—Department of Food, Environmental and Nutritional Sciences, Division of Human Nutrition, Università degli Studi di Milano, 20133 Milan, Italy; [email protected] (C.D.B.);

[email protected] (S.C.); [email protected] (P.R.)

* Correspondence: [email protected]; Tel.: +1-207-581-3124 Academic Editor: Maurizio Battino

Received: 5 July 2016; Accepted: 20 September 2016; Published: 30 September 2016

Abstract: Metabolic Syndrome is a cluster of risk factors which often includes central obesity, dyslipidemia, insulin resistance, glucose intolerance, hypertension, endothelial dysfunction, as well as a pro-inflammatory, pro-oxidant, and pro-thrombotic environment. This leads to a dramatically increased risk of developing type II diabetes mellitus and cardiovascular disease, which is the leading cause of death both in the United States and worldwide. Increasing evidence suggests that berry fruit consumption has a significant potential in the prevention and treatment of most risk factors associated with Metabolic Syndrome and its cardiovascular complications in the human population. This is likely due to the presence of polyphenols with known antioxidant and anti-inflammatory effects, such as anthocyanins and/or phenolic acids. The present review summarizes the findings of recent dietary interventions with berry fruits on human subjects with or at risk of Metabolic Syndrome.

It also discusses the potential role of berries as part of a dietary strategy which could greatly reduce the need for pharmacotherapy, associated with potentially deleterious side effects and constituting a considerable ﬁnancial burden.

Keywords: berries; Metabolic Syndrome; dietary intervention studies; humans

1. Metabolic Syndrome: General Overview

Metabolic Syndrome is characterized by the simultaneous presence of multiple risk factors, which are a direct or indirect consequence of both insulin resistance and overweight/obesity [1]. Although it is not a disease in itself, this combination of health problems dramatically increases the risk of developing type II diabetes mellitus and cardiovascular disease [2].

The US National Cholesterol Education Program–Adult Treatment Panel III (ATPIII) deﬁnes Metabolic Syndrome as the combined occurrence of at least three of the following ﬁve risk factors:

abdominal obesity (waist circumference≥102 cm in males, ≥88 cm in females); high blood triglycerides (≥150 mg/dL); low HDL cholesterol (≤40 mg/dL in males, ≤50 mg/dL in females); high diastolic and/or systolic blood pressure (≥130/85 mmHg) and high fasting blood glucose (≥100 mg/L) [2].

Together with these diagnostic parameters, which were selected because of their widespread use in the clinical setting, a plethora of other dysfunctional states are often associated with Metabolic Syndrome. Although they are not used for diagnostic purposes, they signiﬁcantly contribute to the increased cardiovascular risk and the onset of type II diabetes mellitus [2]. In particular, Metabolic Syndrome is associated with a pro-oxidant, pro-inﬂammatory, and pro-thrombotic state [3,4].

Antioxidants 2016, 5, 34 1 www.mdpi.com/journal/antioxidants

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Chronic, low-grade, systemic inﬂammation is one of the landmark characteristics of Metabolic Syndrome, leading to unnecessary tissue damage, endothelial dysfunction, thrombosis, insulin resistance, high blood pressure, and all the pathologies related to such risk factors, including cardiovascular disease, diabetes, some forms of cancer, arthritis, neurodegenerative diseases, and many others [3,4].

Fat accumulation and obesity are major underlying causes of chronic inﬂammation, due to the inherent ability of adipocytes to secrete inﬂammatory mediators: mainly adipocyte-derived cytokines (called adipokines), but also hormones like leptin [5].

Inflammation and fat accumulation both lead to impairment in glucose metabolism and insulin resistance, and in turn, impaired glucose metabolism exacerbates inflammation and tissue damage, thus sustaining a pro-inflammatory state and endothelial dysfunction [6,7].

Indeed, another landmark characteristic of Metabolic Syndrome is the development of endothelial dysfunction, which is strictly related to oxidative stress and inﬂammation via the nuclear factor kappa-b pathway [1].

Endothelial dysfunction is characterized by an imbalance between vasoconstrictor and vasodilator responses leading to impaired vascular tone, peripheral vascular resistance, and organ perfusion, and is one of the earliest events in the development of atherosclerotic lesions. Metabolic Syndrome is often associated with impaired endothelium-dependent vasodilation, likely due to insufﬁcient NO production or bioavailability, [8] and with exaggerated vasoconstriction, due to an increased production of vasoconstricting mediators [9].

2. The Role of Berries in the Modulation of Metabolic Syndrome

Berries represent a variety of small fruits characterized by the red, purple, and blue color. The most common berries are: blueberry, bilberry, cranberry, blackberry, raspberry, black, white or red currant, and strawberry. Minor berries include: lingonberry, cloudberry, elderberry, honeyberry, whortleberry, and chokeberry.

Berries are consumed both as fresh product as well as processed foods (i.e., juices, beverages, jams, freeze-dried). They contain high levels of polyphenols including flavonoids (anthocyanins, flavonols, and flavanols), condensed tannins (proanthocyanidins), hydrolyzable tannins (ellagitannins and gallotannins), phenolic acids (hydroxybenzoic and hydroxycinnamic acids, chlorogenic acid), stilbenoids and lignans [10,11]. Their concentration varies according to species, genotype, growing and post-harvesting conditions [12].

Anthocyanins (ACNs) are probably the main bioactive compounds that characterize berries with pelargonidin, cyanidin, delphinidin, petunidin, peonidin, and malvidin the most predominant ACN compounds. They are found mainly in the external layer of the pericarp. ACNs include aglycones–anthocyanidins and their glycosides–anthocyanins. They differ with regard to the position and number of hydroxyl groups, degree of methylation, type and number of sugar molecules (mono-, di- or tri-glycosides), type of sugars (the most common sugars include glucose, galactose and arabinose) and type and number of aliphatic or aromatic acids (i.e., p-coumaric, caffeic, ferulic acid). Among berries, blackcurrants, black elderberries, blackberries and blueberries are particularly rich in ACNs (400 to 500 mg/100 g) [13]. Phenolic acids are represented by hydroxycinnamic acids (i.e., ferulic, caffeic, p-cumaric acids. and caffeoylquinic esters) and benzoic acid derivatives (i.e., gallic acid, salicylic, p-hydroxybenzoic. and ellagic acids). They occur mainly in bound forms as esters or glycosides. Gallic acid and chlorogenic acids are abundant in blueberry (~200 mg/100 g) and blackberry (~300 mg/100 g).

Ellagic acid is the main phenolic acid in strawberries (from 300 mg to 600 mg/100 g) where it is present in free form or esteriﬁed to glucose in hydrolysable ellagitannins. Blueberries and cranberries are also important sources of ferulic acid, bilberries and blackcurrants of p-coumaric and caffeic acid, while chokeberries are rich sources of caffeic, chlorogenic, and neochlorogenic acids [13].

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Antioxidants 2016, 5, 34

Flavonols, 3-hydroxyﬂavones and tannins are also widespread in berries. Flavan-3-ols are a complex subclass of polyphenols without glycoside residues and with different levels of polymerization ranging from monomeric, oligomeric, and polymeric forms. Tannins include both condensed non-hydrolysable tannins known as proanthocyanidins, and esters of gallic and ellagic acids called hydrolysable tannins. Tannins play an essential role in deﬁning the sensory properties of fresh fruit and fruit-derived products. They are responsible for the taste and changes in the color of fruit and fruit juice.

Moreover, tannins stabilize ACNs by binding to form co-polymers. The amount of ﬂavan-3-ols and proanthocyanidins in chokeberries, blueberries, and strawberries varies from 150 mg to 700 mg/100 g, while in blackberries and raspberries the amount is about 300 mg/100 g [13].

Blackberries, blueberries, and strawberries are rich sources of ellagitannins (up to 600 mg/100 g), followed by chokeberries, cloudberries and red raspberries (~260 mg/100 g), while small quantities of tannins are found in honeyberries [13].

During recent years, a multitude of clinical research studies have focused on the health properties of berries. In particular, increasing attention has been devoted to the role of berries and their components in the modulation of oxidative stress [14], vascular function [15], inﬂammation, and lipid metabolism [16]. In addition, research studies have explored the role of berries on chronic diseases such as cardiovascular diseases, diabetes, and obesity with promising, albeit preliminary, results. Several studies have also investigated the effect of berry consumption on their ability to modulate/attenuate risk factors associated with Metabolic Syndrome.

A search of the literature on intervention studies investigating the effect of berry consumption in the modulation of Metabolic Syndrome and/or related risk factors was carried out. Abstracts and full texts from human acute and chronic intervention studies were screened. PUBMED, ScienceDirect, and ScholarGoogle databases were searched to identify articles published later than 1 January 2000.

The searches used the following terms and text words alone and in combination: “berry”, “Metabolic Syndrome”, “overweight”, “obesity”, “hypertension”, “hypercholesterolemia”, “hyperlipemia”,

“Type II diabetes”, and ”humans”. Interventions conducted in healthy subjects (not presenting any of the risk factors characterizing Metabolic Syndrome) were excluded. Reference lists of the obtained articles were also searched for related articles. The search was limited to English-language articles. A total of 45 articles were obtained from the database searches and from their reference lists.

Four papers were excluded because studies were performed with a mix of fruits and vegetables and other foods in which berries did not constitute the main food [17–20]. Therefore after exclusions, a total of 41 studies were included in the review (Figure 1). Thirty-four explored a medium-long term intervention, four were post-prandial while three investigated both or performed a chronic intervention followed by an acute study. Here, we summarize the main results of the human studies.

The results obtained are also reported in Table 1, describing the type of food or supplement, number of intervention days, number of subjects and their characteristics, dose/day of test food, the use of control/placebo food, and the signiﬁcant ﬁndings.

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Table1.EffectofberryconsumptiononMetabolicSyndromeandassociatedriskfactors. BerryInterventionParticipantsDoseMainﬁndingsReferences Blueberry

8-week,randomized, double-blind, placebo-controlled,parallel intervention Forty-eightpostmenopausalwomen (Blueberrygroup:BMI30.1±5.94kg/m2; age59.7±4.58year;Controlgroup: BMI32.7±6.79kg/m2; age57.3±4.76year)withpre-andstage 1-hypertension

Blueberrygroup:480mLblueberrydrink (22gfreeze-driedblueberrypowder correspondingto1freshcupblueberries) Controlgroup:480mLplacebodrink

↓systolic,diastolicbloodpressureand brachial-anklepulsewavevelocity ↑NOplasmalevels ↑superoxidedismutaseactivityafter blueberryandcontrolgroup =weight,waistcircumference,CRP Johnsonetal.[21] 6-weekrandomized, double-blind, placebo-controlled,parallel intervention

Forty-foursubjectswithmetabolic syndrome(Blueberrygroup:BMI35.2± 0.8kg/m2;age55±2year;Controlgroup: BMI36.0±1.1kg/m2;age59±2year) Blueberrygroup:Smoothiepreparedwith 45gblueberrypowder Controlgroup:identicalsmoothiewithout blueberrybioactives

↑endothelialfunction =bloodpressureandinsulinsensitivityStulletal.[22] 6-week,randomized, placebo-controlled, crossoverintervention

Eighteenmale(BMI24.8±2.6kg/m2; age47.8±9.7year)withCVDriskfactors Wildblueberrygroup:250mLblueberry drink(25gWBpowder,equivalentto148g freshWB) Controlgroup:250mLwaterwithsensory characteristicssimilartotheWBdrink

↓Endogenousandoxidatively-induced DNAdamageinPBMCs =lipidproﬁle,weight,markersof inﬂammationandendothelialfunction, dietarymarkers,DNArepairactivity

Risoetal.[23] 6-week,randomized, double-blinded, placebo-controlled,parallel intervention

Twenty-seven(BMIbetween32and45 kg/m2;age>20year)obese, insulin-resistantsubjects Blueberrygroup:smoothiepreparedwith 45gofblueberrypowder(22.5gtwicea day)(equivalentto2cupsoffresh blueberries) Controlgroup:identicalsmoothiewithout blueberrybioactives

↑insulinsensitivity =markersofinﬂammation,lipidproﬁleand bloodpressureStulletal.[24] 8-week,randomized, single-blinded,controlled parallelintervention

Forty-eightsubjectswithmetabolic syndrome(4malesand44females;BMI 37.8±2.3kg/m2;age50.0±3.0year) Blueberrygroup:480mLblueberrydrink (50gfreeze-driedblueberries correspondingto350gfreshberries) Controlgroup:480mLwater

↓systolicanddiastolicbloodpressure ↓plasmaox-LDL,MDAandHNElevels =lipidproﬁle,weight,waistcircumference, inﬂammationmarkers

Basuetal.[25] Bilberry8-week,randomized, controlled,parallel intervention

Twenty-sevensubjects(Bilberrygroup: BMI31.4±4.7kg/m2;age53±6year; Controlgroup:32.9±3.4year;age50±7 year)withmetabolicsyndrome Bilberrygroup:200gofbilberrypuréeand 40gofdriedbilberries(eq.200goffresh bilberries) Controlgroup:habitualdiet.Theuseof berrieswasallowedatmaximumof 1dL/day(correspondingto80g/day).

↓serumlevelsofhs-CRP,IL-6,IL-12and inﬂammationscore. ↓expressionofMMDandCCR2transcripts associatedwithmonocyteandmacrophage functionassociatedgenes =bodyweight,glucose,andlipidproﬁle Kolehmainenetal.[26] 5-week,randomized, cross-overintervention

Eightyoverweightandobesewomen (BMI29.6±2.1kg/m2;age44.2±6.2year; 21subjectsmeetingmetabolicsyndrome criteria) Bilberrygroup:100gfreshbilberries Seabuckthorngroup:Seabuckthorn(SB), SBfractionsorSBoils(equivalentto 100gofberries) Controlgroup:none

↓bodyweight,waistcircumference, VCAM-1,TNF-α,adiponectin ↑insulin,GHbA1C =fatpercent,bloodpressure,fastingplasma cholesterol,triacylglycerol,ALATandIL-6 serumlevels Lehtonenetal.[27] 4-week,randomized, controlled,parallel intervention

Sixty-twosubjects(Bilberrygroup:BMI range19.9–31.7kg/m2;agerange34–68 year;Controlgroup:BMIrange17.8–31.5 kg/m2;agerange30–68year)withCVD riskfactors Bilberrygroup:330mLbilberryjuice/day (dilutedto1Lusingtapwater) Controlgroup:1Lofwater

↓serumlevelsofCRP,IL-6,IL-15, TNF-α,MIG =markersofantioxidantsstatusand oxidativestress

Karlsenetal.[28]

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Table1.Cont. BerryInterventionParticipantsDoseMainﬁndingsReferences Cranberry4-week,placebo-controlled double-blind,crossover intervention

Thirty-ﬁveabdominallyobesemen (age45±10year,BMI28.3±2.4kg/m2 andawaistcircumference≥90cm)with metabolic(n=13)andwithoutmetabolic syndrome(n=22) Cranberrygroup:500mL/dayofeither low-caloriejuice(27%juice) Controlgroup:500mL/dayplacebojuice

↓arterialstiffnessandglobalendothelial function =bloodpressure,markersofendothelial function Rueletal.[29] 60days,parallel intervention

Fifty-sixsubjects(cranberrygroup:BMI 30.9kg/m2median,age51.0yearmedian; controlgroup:BMI34.0kg/m2median, age48.5yearmedian)with metabolicsyndrome Cranberrygroup:700mL/day reduced-energycranberryjuice Controlgroup:usualdiet

↓serumhomocysteinelevels, lipoperoxidation,proteinoxidation ↑serumfolicacidlevels =metabolicandinﬂammatorybiomarkers C-reactiveprotein,TNF-α,IL-1andIL-6 Simãoetal.[30] 12-week,randomized, double-blind,parallel intervention

Fifty-eight(BMI28.8±3.6kg/m2, age54.8±9.1year)TypeII diabeticsubjects Cranberrygroup:240mL/day cranberryjuice Controlgroup:240mL/dayplacebojuice

↓glucose,ApoB ↑ApoA-1,PON-1activity =lipoprotein(a)Shidfaretal.[31] Post-prandial4-week, randomized, placebo-controlled, cross-overintervention

Fifteen(BMInotreported,age62±8year, 13%female)subjectswithcoronary arterydiseases Forty-sevensubjectswithcoronaryartery diseases(cranberrygroup:BMI 30±5kg/m2,age61±11year; Controlgroup:BMI29±4kg/m2, age63±9year) Cranberrygroup:480mLcranberryjuice Controlgroup:None Cranberrygroup:480mL/daycranberry juice Controlgroup:480mL/dayplacebojuice

↑flowmediateddilationandlnPATscoreas markersofendothelialfunction =bloodpressure,heartrate,brachial diameter,hyperemicflow ↓carotid-femoralpulsewavevelocity (ameasureofcentralaorticstiffness).and HDL-cholesterolaftercranberryjuice =lipidprofile,glucose,insulin,HOMA-IR, C-reactiveprotein,ICAM-1serumlevels, brachialarteryflow-mediateddilation, digitalpulseamplitudetonometry,blood pressure,andcarotid-radialpulsewave velocity Dohadwalaetal.[32] 8-week,randomized double-blind, placebo-controlled,parallel intervention

Thirty-one(BMI40.0±7.7kg/m2, age52.0±8.0year)femalewith metabolicsyndrome Cranberrygroup:480mL/day cranberryjuice Controlgroup:480mL/dayplacebodrink

↓ox-LDL,MDA&HNEplasma/serum levels ↑Totalplasmaantioxidantcapacity =bloodpressure,glucose,plasma lipoprotein-lipid,markersofinﬂammation

Basuetal.[33] Post-prandialcross-over intervention

Thirteen(6femaleand7male) noninsulin-dependentsubjects (age61.6±2.3year,BMI33.25± 1.22kg/m2) Cranberrygroup: Group1:rawcranberry(55g,21cal, 1gfiber) Group2:sweeteneddriedcranberry(40g, 138cal;2.1gfiber) Group3:sweeteneddriedcranberries-less sugarsgroup(40g;113cal;1.8gfiber+ 10gpolydextrose) Controlgroup:whitebread(57g,160cal; 1gfiber)

↓glycemicandinsulinemicresponse followingSDC-LSWilsonetal.[34]

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Table1.Cont. BerryInterventionParticipantsDoseMainﬁndingsReferences 12-weekintervention(three 4-weekinterventionwith 125,250and500mL/day cranberryjuice)

Thirty(BMI27.8±3.2kg/m2,age51±10 year;9subjectswithmetabolicsyndrome and21withoutmetabolicsyndrome) abdominallyobesemen Cranberrygroup:125,250and500mL/day cranberryjuice Controlgroup:none

↓ox-LDLfollowing250and500mL cranberryjuice ↓systolicbloodpressure,s-VCAM,ICAM plasmalevelsfollowing500mL cranberryjuice ↓ox-LDL,ICAMplasmalevelsinsubjects withmetabolicsyndromefollowing 12-weekintervention ↑HDLcholesterolfollowing250and 500mLcranberryjuice =Total,LDLApoBcholesterol, triglycerides,diastolicbloodpressure, heartbeat,E-selectinplasmalevels

Rueletal.[35] 12-week,randomized, placebo-controlled, double-blind,parallel intervention

Thirty(16malesand14females)TypeII diabeticsubjects(Cranberrygroup:9/6 male/female,BMI26.2±0.7kg/m2,age65 ±2year;Controlgroup:7/8male/female, BMI25.9±1.0kg/m2,age66±2year) Cranberrygroup:500mg/capsule cranberry powderextract,threetimesaday Controlgroup:500mg/capsuleplacebo

↓Totalcholesterol,Total:HDLcholesterol ratio,LDLcholesterol =waistcircumference,BMI,fastingserum glucose,insulin,HbA1c,HOMAinsulin resistance,C-reactiveprotein,blood pressure,ox-LDL,triglyceride, HDL-cholesterollevels,uricacid

Leeetal.[36] Post-prandialinterventionTwelve(6maleand6female)typeII diabeticsubjects(age65.3±2.3year,BMI 34.7±1.6kg/m2

Cranberrygroup: Group1:normalcaloriecranberryjuice (NCCBJ;27%cranberryjuice,v/v; 130Cal/240mL) Group2:unsweetenedlow-calorie cranberryjuice(LCCBJ;27%,v/vCBJ;19 Cal/240mL) Controlgroup:Group1:normalcalorie control(NCC;140Cal/240mL)madewith dextrose Group2:low-caloriecontrol(LCC; 19Cal/240mL)

↓plasmainsulinandglycemicresponse followingLCCBJWilsonetal.[37] 12-weekintervention(three 4-weekinterventionwith 125,250,and500mL/day cranberryjuice)

Thirty(BMI27.8±3.3kg/m2,age51±10 year)abdominallyobesemen Cranberrygroup:125,250and500mL/day cranberryjuice Controlgroup:none

↓bodyweight,BMI,waistcircumference, waist-to-hipratio,total:HDLcholesterol apoB,afterinterventionwith250and500 mLcranberryjuice ↑plasmanitrite/nitratefollowing interventionwith500mL ↑plasmaantioxidantcapacityfollowing 250and500mLcranberryjuice ↑HDLcholesterolfollowing250mL cranberryjuice =Total,LDLandVLDLcholesterol

Rueletal.[38]

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Table1.Cont. BerryInterventionParticipantsDoseMainﬁndingsReferences 2-weekinterventionTwenty-one(BMI26.9±3.8kg/m2, age38±8year)abdominally obese-dyslipidemicmen Cranberrygroup:7mL/kgBW(range 460–760mL/daycranberryjuice) Controlgroup:none

↓BMI,plasmaox-LDLlevels ↑Totalplasmaantioxidantcapacity =waistandhipcircumference,waist/hip ratio,bloodpressure,plasma lipoprotein-lipid,inﬂammationmarkers Rueletal.[39] 12-weekrandomized, controlled,parallelintervention

Twenty-sevenTypeIIdiabeticsubjects (cranberrygroup:14subjects,6women and8men,BMInotreported,age57.9± 10.6year;placebogroup:13subjects6 womenand7men,BMInotreported,age 52.6±13.7year) Cranberrygroup:6capsules(equivalentto 240mLcranberryjuice)containing cranberryjuiceconcentratepowder Controlgroup:6capsulescontaining placebopowder

↑insulinlevelsafterplacebotreatment =fastingserumglucose,HbA1c, fructosamine,triglyceride,HDL, LDL-cholesterollevels

Chambers&Camire [40] Raspberry

14-day(4-dayblack-raspberry intake,post-prandial, randomized,cross-over intervention,wash-outand 4-dayblack-raspberryintake) Tenolderoverweightandobese(BMI, 31.4±2.7kg/m2,age64.7±6.9year) males Berrygroup:45g/dayoflyophilizedblack raspberrypowderfor4days+highfat mealpostprandial Controlgroup:Noblackraspberry+high fatmealpostprandial

↓serumIL-6levels =TNF-α,CRPSardoetal.[41] 12-week,randomized, controlled,parallelintervention

Seventy-sevensubjects(berrygroup:BMI, 26.3±4.3kg/m2,age58.0±9.2year; controlgroup:BMI,25.1±4.0kg/m2,age 60.1±9.5year)withmetabolicsyndrome Berrygroup:750mg/dayofblack raspberry powderascapsules Controlgroup:750mg/dayofcellulose, isomalto,andcornpowderascapsules

↓totalcholesterolleveltotalcholesterol/HDL ratioIL-6,TNF-α ↑ﬂowmediateddilation,adiponectin =serumlipidproﬁle,CRP,ICAMandVCAM

Jeongetal.[42] Chokeberry4-weekinterventionTwenty-threesubjects(BMI,notreported, age47.5±10.4year)withhypertension

Berrygroup:200mL/dayof polyphenol-richorganicchokeberryjuice Controlgroup:none

↓systolicanddiastolicbloodpressure,heart ratehigh-frequencypower,heartratevery lowfrequency,standarddeviationofnormal RRintervalsHolterECG =lipidproﬁle,glucose,CRP,urea,creatinine, Ac.uricum,AST,ALT,markersrelatedto shorttermheartrateandHolterECG

Kardumetal.[43] 4-weekinterventionTwentywomen(BMI,36.1±4.4kg/m2; age53.0±5.4year)withabdominal obesity

Berrygroup:100mL/day glucomannan-enriched(2g),chokeberry juice-based Controlgroup:none

↓BMI,waistcircumference,systolicblood pressure,serumHDLcholesterol, erythrocytesmonounsaturatedfattyacids, n6/n3ratio ↑erythrocytesn3polyunsaturatedfattyacids =erythrocytessaturatedandn6 polyunsaturatedfattyacids,unsaturation index,diastolicbloodpressure,lipidproﬁle, glucoseandenzymaticactivity (SOD,CAT,GPx)

Kardumetal.[44] 8-weekintervention

Fifty-twosubjects(42–65yearsold;berry group:38subjects,BMI31.1±3.3kg/m2; controlgroup:14healthysubjects;BMI24.4 ±1.5kg/m2)withmetabolicsyndrome Berrygroup:300mg/daychokeberry extract Controlgroup:Nointervention

↓serumtotalandLDLcholesterol, triglycerides,coagulationandplatelet aggregationparameters =BMI,waistcircumference,serum HDLcholesterol

Sikoraetal.[45]

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Berry Antioxidants in Health and Disease

Berry

Antioxidants in Health and Disease

Dorothy Klimis-Zacas Edited by

Printed Edition of the Special Issue Published in Antioxidants

antioxidants

Berry Antioxidants in Health and Disease

Special Issue Editor

Dorothy Klimis-Zacas

Table of Contents

About the Guest Editor

Preface to “Berry Antioxidants in Health and Disease”

antioxidants

Berry Fruit Consumption and Metabolic Syndrome

Dorothy Klimis-Zacas ^{Edited by}