Table Of ContentAn Evidence-based Approach
to Phytochemicals and
Other Dietary Factors
JaneHigdon,PhD†
LinusPaulingInstitute
OregonStateUniversity
Corvallis,Oregon,USA
VictoriaJ.Drake,PhD
Manager
MicronutrientInformationCenter
LinusPaulingInstitute
OregonStateUniversity
Corvallis,Oregon,USA
2ndedition
33illustrations
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Stuttgart·NewYork
IV
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V
Foreword
AccusenotNature! tion, and interactions with one another within
Shehasdoneherpart; individualfoodsandwholediets.Itisworthnot-
Dothoubutthine! ing that research indicates that many of these
JohnMilton,ParadiseLost,1667 compounds have the potential to influence the
expressionofmammaliangenes,suggestingphy-
Archeology reveals that ancient peoples recog- tochemicals can influence fundamental aspects
nized that certain foods could promote health of our cellular function, despite their not being
and treat disease. The use of decoctions, distil- “essential”tous.Itcanappearanoverwhelming
lates,extracts,andinfusionsofplantfoods,spices challenge to document the myriad of fruits,
andrelatedbotanicalsinapothecary,Ayurvedic, grains,legumes,nuts,seeds,andvegetablesand
Chinese, Native American, and other traditional the ways in which they serve to support our
medicines reflects the early application of this physical well being and our mental state. How-
knowledge regarding their bioactive constitu- ever,thefirstpublicationofthisbookbyDr.Jane
ents. Today, exciting advances in nutrition and Higdon,nowupdatedbyDr.VictoriaDrakeinthis
medicine,aswellasnumerousreportsinpopular second edition, makes this task much easier by
booksandthemedia,havestimulatedageneral providingaconcisesynthesisofthebasic,obser-
interestinphytochemicalsandotherdietaryfac- vational,andclinicaldatanowavailableandor-
tors. New recipes emphasizing phytochemical- ganizingthematerialinapracticalfashionboth
rich dishes, common foods fortified with these byfoodsandbybioactiveconstituentsandtheir
“functional” ingredients, and dietary supple- applicationstohealthpromotionandtherapy.
ments formulated with a variety of these com- The worldwide, demographic imperative of
poundsseemtobeappearingeverymonth.How- the aging population is readily reflected in the
ever,thisprofusionofchoicesisoftenaccompa- shift during the last century from a situation
niedbyconfusionabouttheirefficacyandsafety. where most mortality resulted from communi-
Thus, the need for ready access to sound, evi- cable diseases to one where mortality is more
dence-based science by consumers and health- oftenaresultofchronicdisease.Thepromiseof
careprofessionalsismorecriticalthaneverbe- the power of nutrition lies in our being able to
fore. understand the benefits offered not only by es-
We now appreciate that our evolution in a sential macronutrients and micronutrients but
world of edible plants allowed our bodies not byotherdietaryfactors,especiallyphytochemi-
onlytoforegotheenergynecessaryforsynthe- cals like carotenoids, chlorophylls, glucosino-
sizing many critical compounds (that we now lates, organosulfurs, phytosterols, and polyphe-
call“essentialnutrients”)butalsototakeadvan- nols,aswellcompoundslikeα-lipoicacid,L-car-
tageofothernaturalconstituentsinthesefoods nitine,choline,andubiquinone(coenzymeQ ).
10
beyond their provision of basic nutritive value. Allofthesecompounds,andthefoodsthatcon-
For example, it is interesting to note how our tainthem,aredescribedinthisbook.Inaddition
retina employs the carotenoid lutein to filter to their own expertise, Drs. Higdon and Drake
phototoxicbluelightandnear-ultravioletradia- have ensured the accuracy of this material by
tion in the same way that lutein protects the havingeachchapterreviewedbyanauthorityin
plantsfromwhichweobtainit.Nutritionscien- thatfield.
tists are now working to understand the enor- Theapplicationofthisknowledgeaboutphy-
mous complexity and health implications of tochemicals and other dietary factors will pro-
thousands of phytochemicals and other dietary videasoundfoundationfornewdietaryguide-
factors, including their bioavailability, distribu- linesandalsotherequisitescientificsubstantia-
tion, metabolism, excretion, mechanisms of ac- tionforthedevelopmentofnewfoodproducts,
VI Foreword
sometimes called designer foods, functional because issues of convenience, cost, and taste
foods,pharmafoods,ornutraceuticals,aswellas mustbeconsideredbutalsobecauseourknowl-
for dietary supplements. However, a great deal edge of exactly which healthful ingredients to
moreresearchmuststillbedonetodemonstrate incorporateisstillquitelimited,includingtheir
notonlytheefficacybutalsothesafetyofthese effectivedoses,forms,combinations,andsafety.
ingredients and how they are formulated into Nonetheless,manyelementsarenowconverging
newproductsthatoffertoenhanceourbiological to ensure these challenges will be met: the re-
defense mechanisms, promote optimal physio- quirementofboththeprivateandpublicsector
logicalresponses,reducetheriskofspecificdis- toreducehealth-carecosts,thedemandsofcon-
eases, and even slow the processes associated sumersfor“natural”solutionstolivelongerand
with aging. While regulations concerning label- betterlives,andthedriveoffoodcompaniesand
ingandclaimsofbenefitmadeforfoodproducts thestoresthatselltheirproductstorespondto
seemoftentobecontroversial,thereisnodoubt their customers’ needs. Drs. Higdon and Drake
thatevaluatingtheemergingscientificinforma- have given us a book that is authoritative but
tion with sound judgment, as is done in this easytoreadandprovidesasolidbackgroundfor
book,willhelphealth-careproviders,especially those wanting to understand how phytochemi-
dietitians,nurses,andphysicians,applyittoday calsandotherdietaryfactorsmayoffersomeso-
andallowpolicymakersandresearcherstoplan lutionstothisproblem.
forthefutureinarationalmanner.
Whethercounselingpatientsabouttheirdiets JeffreyBlumberg,PhD,FASN,FACN,CNS
or developing more healthful food products, a FriedmanSchoolofNutritionScienceandPolicy
two-prongedapproachisrequired:reducingin- JeanMayerUSDAHumanNutritionResearch
gredients with negative attributes, such as re- CenteronAging
finedsugars,saturatedandtrans-fattyacids,and TuftsUniversity
sodium,andincreasingingredientswithpositive Boston,Massachusetts
attributes, including phytochemicals and other USA
dietaryfactors.However,thisisdifficult,notonly
VII
Preface to the Second Edition
IamhonoredtoreviseandupdateDr.JaneHig- safetyprofiles,includingpotentialdrugandnu-
don’s book, An Evidence-based Approach to Di- trient interactions. This extensively referenced
etaryPhytochemicals.Sincethefirsteditionwas bookconciselysynthesizesalargeamountofex-
published in 2007, the literature on the role of perimental, epidemiological, and clinical re-
plant foods and phytochemicals (literally, plant searchonthehealtheffectsofplantfoods,phyto-
chemicals)inhealthanddiseasehasgreatlyex- chemicals, and other dietary factors, and also
panded.Inthissecondedition,all20chaptersof provides the reader with practical information
thefirsteditionhaveincorporatednewinforma- onsources(dietaryandsupplemental),nutrient
tionfromtherelevant,morerecentlypublished and drug interactions, and possible adverse ef-
peer-reviewed studies, especially studies with fects.
humansubjects.Moreover,thiseditionhasbeen
expanded to include new chapters on other di-
etary factors, including choline, coenzyme Q , Acknowledgments
10
L-carnitine,andlipoicacid.Thefirstpartofthis
bookdiscussestheevidenceforthehealtheffects Iwishtothankthefaculty,staff,andstudentsof
ofvariousplantfoodsandbeverages:fruitsand theLinusPaulingInstitutefortheireditorialad-
vegetables, cruciferous vegetables, legumes, viceandsupportintherevisionofthisbook,es-
nuts, whole grains, coffee, and tea. The second pecially Balz Frei, PhD, director and endowed
section focuses on individual phytochemicals chair; Stephen Lawson, administrative officer;
andclassesofphytochemicals,andthethirdsec- andBarbaraMcVicar,assistanttothedirector.I
tion covers key nutrients (essential fatty acids am very appreciative to all of the distinguished
andcholine),aswellasotherdietaryfactors(co- scientistslistedastheEditorialAdvisoryBoard,
enzymeQ ,L-carnitine,andlipoicacid)thatthe whoreviewedthecontentsofeachchapterand
10
body synthesizes but that are also found in di- providedhelpfulcomments.Iwouldalsoliketo
etaryandsupplementarysources. thankJamesW.Anderson,MD,andMartijnB.Ka-
Theimportanceofaplant-baseddietinmain- tan,PhD,forreviewingtheinformationpresent-
tainingoptimumhealthandpreventingchronic edonlegumesandcoffee,respectively.Finally,I
disease is now well recognized. Plant foods not am extremely grateful for the careful and com-
onlyprovideessentialvitaminsandmineralsbut prehensive work by Dr. Higdon in writing the
alsocontaincountlessphytochemicals,aswellas firsteditionofthisbook.Ihopethatreadersfind
dietaryfiber,thatbenefithealth.Itiscriticalthat thisneweditionaddssuccessfullytoherlegacy.
people—health professionals and the general
public alike—have access to scientifically accu- VictoriaJ.Drake,PhD
rate and peer-reviewed information regarding Manager,MicronutrientInformationCenter
how plant foods and their constituents affect LinusPaulingInstitute
health.Additionally,astheavailabilityandpopu- OregonStateUniversity
larity of functional foods and dietary supple- Corvallis,Oregon
mentsincreases,itisnecessarytoconsidertheir USA
VIII PrefacetotheFirstEdition
Preface to the First Edition
Plantfoods,includingfruits,vegetables,legumes, pected effects, the available evidence regarding
wholegrains,andnuts,areprominentfeaturesof thesafetyoftheseCompoundsisalsoreviewed.
healthydietarypatterns.Inadditiontoproviding My goal in writing this book was to synthe-
energy and essential micronutrients (vitamins sizeandorganizetheresultsofthousandsofex-
andminerals),plantfoodscontributethousands perimental,clinical,andepidemiologicalstudies
of phytochemicals to the human diet. Although toprovideanoverviewofcurrentscientificand
theterm“phytochemicals”literallymeansplant clinical knowledge regarding the role of plant
chemicals,itisoftenusedtodescribeplant-de- foodsandphytochemicalsinhumanhealthand
rivedcompoundsthatmayaffecthealthbutare disease. An expert in the field covered in each
notessentialnutrients.Althoughthereisample chapterhasreviewedthetexttoensureitsaccu-
evidencetosupportthehealthbenefitsofdiets racy. The names and affiliations of these scien-
richinplantfoods,evidencethatthesebenefits tists are listed in the Editorial Advisory Board.
areduetospecificphytochemicalsismorelimit- Throughoutthisbook,humanresearchpublished
ed.Becauseplantfoodsarecomplexpackagesof inpeerreviewedjournaisisemphasized.Where
biologicallyactivecompounds,thehealthbene- relevant, the results of experimental studies in
fits of individual phytochemicals cannot always cell culture or animal models are included. Al-
beseparatedfromthoseofthefoodsthatcontain thoughrandomizedcontrolledtrialsprovidethe
them.Consequently,thefirstsectionofthebook strongest support for the efficacy of phyto
discussestheevidenceforthehealthbenefitsof chemicals,itisnotalwaysethicalorpracticalto
plant foods and beverages, including fruits and perform a randomized, double-blind, placebo-
vegetables, legumes, nuts, whole grains, coffee, controlled trial. Observational studies also pro-
andtea. vide important information about relationships
Scientificresearchonthepotentialforspecific between plant food and phytochemical intakes
dietaryphytochemicalsorclassesofdietaryphy- andhumanhealthanddisease.Inreviewingthe
tochemicalstopreventandtreatchronicdiseases epidemiological research, more weight is given
has expanded rapidly over the past decade. In totheresultsoflargeprospectivecohortstudies,
some cases, the results of preclinical research suchastheNurses’HealthStudyandHealthPro-
havebeenpromisingenoughtowarrantclinical fessionals Follow-up Study, than retrospective
trials designed to examine the bioavailability, case-control or cross-sectional studies. When
safety,andefficacyofhighdosesofisolatedphy- available, the results of systematic reviews and
tochemicalsinhumans.IntheUnitedStatesand meta-analyses,whichsummarizeinformationon
other countries, supplements and extracts con- thefindingsofmanysimilarstudies,arealsoin-
taining concentrated doses of isolated phyto- cluded.
chemicals are available to the public as dietary Thisbookcouldnothavebeenwrittenwith-
supplementswithoutaprescription.Themarket out the collaboration and support of the scien-
for functional foods, such as phytosterol-en- tists and staff of the Linus Pauling Institute at
richedmargarines,isalsorapidlyexpanding.As OregonStateUniversity.TheInstitutewasfound-
thepopularityoftheseproductsincreases,health edin1973byLinusPauling,Ph.D.,theonlyindi-
andnutritionprofessionalsneedaccurateinfor- vidual ever to win two, unshared Nobel Prizes
mationaboutpotentialhealthbenefits,risks,and (Chemistry, 1954; Peace, 1962). In 1996, the
interactions associated with these phytochemi- Linus Pauling Institute moved to the campus of
cals.Thesecondsectionofthisbookreviewsthe OregonStateUniversity(Dr.Pauling’sundergrad-
scientific and clinical evidence for the health uatealmamater)andnowoperatesasoneofthe
benefits of individual dietary phytochemicals University’s Research Centers and Institutes.
andclassesofphytochemicals.Becausehighdos- More than 35 years ago, Dr. Pauling proposed
es of isolated phytochemicals may have unex- thatdietaryfactors,suchasvitaminC,couldplay
