Antioxidants in Food, Vitamins and Supplements. Prevention and Treatment of Disease

340 Pages·2014·3.8 MB·English

by  Amitava Dasgupta and Kimberly Klein (Auth.)

Antioxidants in Food, Vitamins
and Supplements
Antioxidants in Food,
Vitamins and
Supplements
Prevention and Treatment of Disease
Amitava Dasgupta, PhD, DABCC
Professor of Pathology and Laboratory Medicine,
University of Texas Medical School at Houston
Kimberly Klein, MD
Assistant Professor of Pathology and Laboratory Medicine,
University of Texas Medical School at Houston
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Preface
We all know about antioxidants. Some of us take antioxidant vitamins and
supplements to promote health. As such, this industry is now a multibillion
dollar business. Currently, it is estimated that more than 40% men and 50%
women age 60 years or older take at least one vitamin or mineral supplement
daily. In popular health magazines, antioxidant supplements are advertised as
magic bullets capable of preventing all chronic illnesses. However, free radicals
are not villains becausethe human body requires modest amounts of them for
normal physiological functions. Therefore, scavenging all free radicals by taking
too many antioxidant supplements actually causes more harm than good. In
fact, a balanced diet rich in fruits and vegetables and a healthy lifestyle is the
best approach to combat oxidative stress. A healthy diet supplies more than
enough antioxidants. Vitamins and antioxidant supplements may be needed
only for special populations suffering from specific illnesses, and pregnant
womenmaytakefolatesupplements.
Thepurposeofthisbookistopresentcurrentmedicalknowledgeregardingthe
role of antioxidants in health and disease in a concise manner so that health
care professionals and medical students can get a balanced overview of this
broad topic. We have attempted to provide an enjoyable reading experience,
and we avoided detailed discussion of molecular pathways by which oxidative
stress triggers individual diseases. However, we provide an overview of such
molecular pathways and a long list of references in each chapter so that more
advanced readers or those interested in antioxidant research will also find this
bookhelpful.
We also deliberately avoid chemical structures and detailed discussion of the
chemistry of antioxidants, but we cover all important aspects of the chemistry
of free radicals and methods used by investigators in the field of antioxidant
research.Inordertounderstandwhatelevatedmalondialdehydeconcentration
in a disease implies, it is important to know basic chemistry of malondialde-
hyde and how it is measured in a biological matrix. We cover basic chemistry
of free radicals in Chapter 1, and in Chapter 2 we discuss various analytical
methodsusedinlipidperoxidationandfreeradicalchemistryresearch. xiii
xiv Preface
Air pollution, sunlight, cigarette smoke, and even household chemicals can
induce oxidative stress. How our environment induces oxidative stress is
addressed in Chapters 3(cid:1)5. We provide a detailed discussion of the link
betweenoxidativestressandvariousdiseasesinChapters7(cid:1)11.InChapter12,
we discuss various foods that are good sources of antioxidants and present
several tables for easy reference on the antioxidant potential of various fruits
andvegetables.Inthischapter,theglycemicindexofvariousfruitsisalsogiven
because many people throughout the world suffer from diabetes. Tea, coffee,
and chocolate are full of antioxidants, and drinking tea or coffee or both is
goodforhealth.Whereaschocolateisrichincalories,teaandcoffeearealmost
devoidofcaloriesifmilkandsugararenotadded(Chapter13).InChapter14,
the benefits of drinking alcoholic beverages in moderation are discussed.
However, consuming excessive alcohol is detrimental to health. Wine,
especially red wine, is rich in antioxidants, especially resveratrol, which is an
excellent antioxidant. In Chapter 15, antioxidant vitamins are discussed, and
herbal supplements that are antioxidants and nonherbal supplements with
antioxidantproperties are discussed in Chapter 16. However, current research
indicates that taking antioxidant supplements or antioxidant vitamins has
noaddedhealth benefits but maycauseharm.InChapter17, thebestwayto
combat oxidative stress—a healthy lifestyle—is discussed, and references are
provided that clearly indicate that daily exercise, pet ownership, interaction
with friends and family, and even yoga or mediation can significantly reduce
oxidativestress.
The purpose of this book is to provide health care professionals with an
in-depth knowledge of the current state of research in oxidative stress and
antioxidants. This book will provide clinicians, nurses, medical students,
nursing students, and pharmacists with a clear understanding of this impor-
tant aspect of health and nutrition. This is not a reference book, and it is not
intended for experts in this field because there are already excellent reference
books on antioxidants. However, students entering the field of antioxidant
researchwillfind this book useful.
We thank Professor Robert Hunter, our department chair, for encouraging us
to write the book and for his support during preparation of the manuscript.
Furthermore, we thank our loving spouses, Alice and Chad, respectively.
Preparation of the manuscript required an exorbitant amount of time and
energy; without theirloveandsupport,this workwouldnot havebeen possi-
ble. Wehope you,the readers,willfind this bookuseful;ifyoudo,our effort
will be duly rewarded.
Amitava Dasgupta
Kimberley Klein
CHAPTER 1
Introduction to Free Radicals and the
’
Body s Antioxidant Defense
1.1 INTRODUCTION
CONTENTS
The “oxygen paradox” is defined by the fact that aerobic organisms require
1.1 Introduction
oxygen for survival but oxygen is also inherently toxic to these organisms
...............................1
due to its association with free radical generation and oxidative stress.
Various freeradicalsare commonproducts ofrespiration andother biochem- 1.2 Free Radicals
...............................1
icalreactionsincellsthatarenormalphysiologicalprocessesessential forsur-
1.2.1 VariousSources
vival. To survive in an unfriendly oxygen environment, living organisms
ofFreeRadicals.........2
generate water- and lipid-soluble antioxidants that can neutralize these 1.2.2 Damageof
highly reactive free radicals [1]. For healthy living, a delicate balance must be BiomoleculesbyFree
maintained between oxidative stress and antioxidant defense of the body. If Radicals......................8
the body’s antioxidant mechanism does not operate optimally, excess free 1.2.3 Physiological
RoleofFree
radicals can damage various biomolecules, including lipids, proteins, carbo-
Radicals....................10
hydrates, andnucleic acids.
1.3 The Body’s
Antioxidant
Defense..............11
1.2 FREE RADICALS
1.3.1 Enzymesas
A free radical is defined as an atom or molecule containing one or more Antioxidants............11
1.3.2 Chain-Breaking
unpaired electrons that are capable of free existence. Free radicals can be gen-
Antioxidants............13
erated as products of homolytic, heterolytic, or redox reaction, and they usu- 1.3.3 Exerciseand
ally consist of reactive oxygen species or reactive nitrogen species. Reactive AntioxidantStatusof
oxygen species include oxygen-carrying free radicals as well as other reactive Blood.........................14
1.3.4 Markersfor
oxygen species such as hydrogen peroxide, which is not a free radical.
OxidativeStressin
Similarly, reactive nitrogen species include both nitrogen-containing free
HumanBlood...........15
radicalsandotherreactive moleculesinwhichthereactivitycenterisnitrogen
1.4 Conclusion..16
[2]. Common free radicals and oxidantsare summarized in Box 1.1.
References.........16
Free radicals are generated during normal respiration and cellular functions.
Under normal physiological conditions, approximately 2% of oxygen con-
sumed by the human body during respiration is converted into superoxide
1
A.DasguptaandK.Klein:AntioxidantsinFood,VitaminsandSupplements.DOI:http://dx.doi.org/10.1016/B978-0-12-405872-9.00001-X
©2014ElsevierInc.Allrightsreserved.
2 CHAPTER 1: Introduction to Free Radicals and Antioxidant Defense
Box 1.1 COMMON FREE RADICALS AND OXIDANTS
ENCOUNTERED IN HUMAN
PHYSIOLOGY
FreeRadicals (cid:3) Thiylradical
(cid:3) Superoxideanionradical (cid:3) Proteinradical
(cid:3) Hydroxylradical
Oxidants
(cid:3) Hydroperoxylradical
(cid:3) Singletoxygen
(cid:3) Peroxylradical
(cid:3) Ozone
(cid:3) Lipidradical
(cid:3) Hydrogenperoxide
(cid:3) Lipidperoxylradical
(cid:3) Hypochlorite
(cid:3) Lipidalkoxylradical
(cid:3) Nitrousacid
(cid:3) Nitricoxide
(cid:3) Peroxynitrousacid
(cid:3) Nitrosylcation
(cid:3) Nitrousoxide
anion free radical, which is negatively charged (O (cid:1)2) [3]. The human body
2
also contains approximately4.5mg ofiron,most ofwhichis found in hemo-
globin and other proteins. However, a small amount of iron that is found
formingcomplexes with avariety ofsmall molecules can react with hydrogen
peroxide, producing the hydroxyl radical (Fenton reaction). In general,
oxygen-centered free radicals (reactive oxygen species), such as superoxide,
the hydroxyl radical, peroxyl radical, and alkoxy radical, and nitrogen oxide,
play animportant role in inducing oxidativestress [4].
Nitric oxide (NO(cid:1)) is synthesized from L-arginine by many cell types through
nitric oxide synthesis. Nitric oxide and superoxide are the major reactive spe-
cies produced in cells. Both superoxide and nitric oxide can react with other
species, producing reactive oxygen species and reactive nitrogen species,
respectively. Nitric oxide can also bind to transition metals such as ferrous
ions, and it plays an important role in the formation of cyclic guanosine
monophosphate, a second messenger [5]. In general, superoxide anion radi-
cals and nitric oxide are primary free radicals generated by cells during nor-
mal physiological functions.
1.2.1 Various Sources of Free Radicals
There are two sources of free radicals: endogenous sources and exogenous
sources. Major endogenous sources of free radicals are summarized in
Table 1.1. The most common reactive oxygen species are superoxide anion,
hydrogen peroxide, hydroxyl radicals, peroxyl radicals, singlet oxygen, and
ozone. The production of superoxide occurs mostly within mitochondria.
The mitochondrial electron transport chain is the main source of energy that
is stored in adenosine triphosphate (ATP) molecules. Movement of electrons
1.2Free Radicals 3
Table1.1 EndogenousSourcesofFreeRadicals
PhysiologicalProcess Comment
Mitochondrialrespiration Essentialprocessoflifethatgeneratessuperoxideanion
radical.
Autoxidation Autoxidationofmanybiologicalmolecules(hemoglobin,
myoglobin,catecholamines,etc.)inthehumanbodycan
producefreeradicals.Superoxideistheprimaryfreeradical
formed.
Enzymaticreaction Manyenzymaticreactionsinvolvingxanthineoxidase,
lipoxygenase,aldehydeoxidase,etc.cangeneratefree
radicals.
Respiratoryburst Thisisaprocessinwhichphagocytesconsumealarge
amountofoxygenduringphagocytosis.
Metalions Metalionssuchascopperionandferrousion,whichare
essentialforthebody,canreactwithhydrogenperoxideto
producefreeradicals.
Strenuousexercise Mayactivatexanthineoxidase,producingfreeradicals.
Infection Mayproducefreeradicalsbecausetheimmunesystemmay
trytoneutralizeinvadingmicroorganismswithaburstoffree
radicals.
Ischemia/reperfusion Mayactivatexanthineoxidase,causingfreeradical
generation.
from oxidizable organic molecules to molecular oxygen is responsible for
ATP production by the mitochondrial electron transport system. During this
process, superoxide anions are generated due to leaking of electrons to oxy-
gen. Superoxide is also formed enzymatically in the process of reduction of
molecular oxygen mediated by nicotinamide adenine dinucleotide phos-
phate oxidase (NADPH oxidase) and xanthine oxidase in mitochondria.
Superoxide has a relatively longer half-life than that of other free radicals,
but it is less reactive than the hydroxyl radical. Inflammatory cells also
produce relatively large amounts of superoxide. Superoxide is membrane
impermeable but can diffuse within cells [5].
Peroxisomes are another significant source for free radicals. Peroxisomes are
specialized cytoplasmic organelles that carry out important physiological
functions such as β-oxidation of long-chain and very-long-chain fatty acids
and degradation of uric acid. Peroxisomal oxidase is capable of generating
hydrogen peroxide. The reaction of xanthine and xanthine oxidase produces
the superoxide anion and hydrogen peroxide through one-electron and two-
electron reduction of molecular oxygen, respectively, to form uric acid.
Hydrogen peroxide is a relatively stable agent that is permeable to cell
membranes.Hydrogenperoxide can generatefreeradicals such as the hydroxyl
radical but cannot directly oxidize lipid or DNA. Therefore, cytotoxicity of
4 CHAPTER 1: Introduction to Free Radicals and Antioxidant Defense
hydrogen peroxide is due to its ability to produce hydroxyl radicals through
metal-catalyzed reactions such as the Fenton reaction. However, hydroxyl
radicals are highly reactive and can damage any biomolecules close to
their site of generation. These radicals are some of the most dangerous free
radicals encountered in physiology [6]. Singlet oxygen is an electronically
excited form of oxygen, but it is not a free radical. However, singlet oxygen is
a reactive oxygen species generated during dismutation of superoxide anion
in water.
Another endogenously produced oxygen free radical is the peroxyl radical
(ROO(cid:1)), the simplest form of which is HOO(cid:1), which is the protonated form
of superoxide. Hydroperoxy radical is known to initiate lipid peroxidation.
As mentioned previously, nitric oxide (NO(cid:1)) is synthesized from L-arginine
through nitric oxide synthases (NOS) in many cell types. Nitric oxide is a
water-soluble,short-lived free radicalthat plays an important role as asignal-
ing molecule in the body. Mammalian cells contain three genes encoding
NOS (NOS1, NOS2, and NOS3), with 51(cid:1)57% homology between isomers.
NOS1, also known as nNOS (isoform first purified from neuronal tissue),
and NOS3, also known as eNOS (isoform first found in endothelial cells),
are also termed constitutive because they are expressed continuously in neu-
rons and endothelial cells, respectively. These enzymes also require an
increase in calcium concentration in tissues for their activity, thus producing
low transient concentration of nitric oxide. In contrast, NOS2 is an inducible
calcium-independent form also known as iNOS [7]. The reaction of superox-
ide with nitric oxide producesperoxynitrite, whichis a strong oxidizing agent
capable ofdamaging proteinand DNA.
Respiratory burst, a process by which phagocytic cells such as white blood
cells consume a large amount of oxygen during phagocytosis, is another
source of endogenous free radicals. Phagocytosis is an important function of
immune defense that produces free radicals, mostly superoxide, and also
hydrogen peroxide (respiratory burst). In addition, myeloperoxidase is also
secreted. Myeloperoxidase, which is highly expressed in neutrophils, catalyti-
cally reacts with hydrogen peroxide in the presence of physiological concen-
tration of chloride, producing hypochlorous acid (HOCl). This short-lived
and diffusible oxidant plays an important role in killing invading microor-
ganisms [8]. During ischemia, xanthine oxidase enzymes may be activated,
causing oxidative stress by generating free radicals. In addition, the concen-
tration of antioxidant enzymes may be reduced. During reperfusion, oxida-
tive stress is also increased. Strenuous exercise also increases oxidative stress
due to production of free radicals, but the body has the capability to neutral-
ize these excess free radicals. Therefore, regular exercise has health benefits.
Wagner et al. [9] reported that in 42 male subjects who participated in
Ironman triathletes, markers of oxidative stress in blood increased
1.2Free Radicals 5
moderately after the race and returned to normal levels after 5 days. They
concluded that despite a temporary increase in oxidative stress, because there
was appropriate antioxidant intake and protective alteration in antioxidant
defenseof the body, there was no DNAdamage.
There are also external sources of free radicals. For example, breathing pol-
luted air may expose people to free radicals. These external sources are sum-
marized in Table 1.2. Epidemiological studies indicate that fine particulates
found in polluted air that are less than 10 μm in diameter (PM 10) can
increase the risk of asthma attack and chronic obstructive pulmonary disease.
These small particulates in polluted air have free radical activities causing
lung inflammation and damage to lung cells [10]. Organic compounds and
metal ions, which are major components of these particulates, may originate
from industrial source. Air pollution due to automobile exhaust may also
contain harmful polycyclic aromatic hydrocarbons that are not only capable
of generating free radicals but also act as carcinogens. Reducing exposure to
air pollution by using face masks is recommended for patients who are more
susceptible to the harmful effects of air pollution, such as patients with coro-
nary heart diseases [11]. If possible, it is preferable to stay indoors as much
as possible, especially when air quality is poor on hot days, when free radi-
cals containing particulates may be at the ground level. In general, air quality
is superiorin rural areas compared tourbanareas (see Chapter 3).
Table1.2 ExternalSourcesofOxidativeStress
ExternalSource Comment
Airpollution Exposuretoparticulatemattersinpollutedaircan
producesignificantoxidativestress,increasingtheriskfor
asthma,cardiovasculardiseases,chronicpulmonary
obstructivedisease(COPD),andlungcancer.
Inorganicparticlesinair Ingestionofmineralparticlesfromdustinindividuals
workinginindustrymaycauseoxidativestress,
particularlyifaircontainsfinemineraldust(quartz,silica,
andasbestos).
Tobaccosmoking Oxidantspresentintobaccosmokecandamagelungs,
causingCOPDandevenraisingriskoflungcancer.
Somemedications Medicationssuchasbleomycin,adriamycin,and
sulfasalazinemayproduceoxidativestress.
Industrialsolvents Someindustrialsolvents,suchaschloroformandcarbon
tetrachloride,ifinhaledmaycauseoxidativedamage.
Exposuretoradiation Exposuretoexcessiveultravioletlight,prolonged
exposuretothesun(sunbathing),andtreatmentwith
radiationaspartofcancertherapyincreaseoxidative
stress.